Category Archives: Integrative Medicine

While the ideal amount of water varies for each person depending on your geographic location, body type, and more, according to Dana Cohen, M.D., integrative medicine physician and co-author of Quench, you should aim to drink about half of your body weight in ounces of water each day to ensure youre staying adequately hydrated.

However, while it would take a lot to reach the point of "overhydrating," it is, in fact, possible to drink too much water. "In overhydration an excess of water dilutes the electrolyte concentrations in the blood, causing imbalance throughout the body's many systems," physician Catherine Waldrop, M.D., previously told mbg.

In fact, drinking too much water can even lead to an electrolyte imbalance called hyponatremia, that can have some fairly gnarly side effects on the body. "Mild hyponatremia is characterized by gastrointestinal tract symptoms, nausea, vomiting, loss of appetite," one study revealed. In short, hyponatremia is essentially low sodium in the blood.

Continue reading here:
Can You Really Drink Too Much Water? We Investigated - mindbodygreen

One simple breathing technique that takes just over a minute to complete could help you fall asleep faster and get a better night's rest overall, according to experts.

The technique, known as 4-7-8 breathing, was developed by Dr. Andrew Weila trained medical doctor and founder of the Arizona Center for Integrative Medicine.

Weil developed the technique, which is based on breathing exercises found in yoga, for the purposes of managing stress and anxiety.

But experts told Newsweek the technique can also be useful for people who are having trouble sleeping.

Sleep is crucial to our physical and mental health, enabling our body to recover and wake up feeling refreshed.

But large portions of the population don't get sufficient sleep, have poor sleep quality, or have trouble falling asleep as a result of sleep disorders, medical conditions or mental health issues.

According to the American Sleep Association, 50 to 70 million adults in the United States have a sleep disorder, with insomnia being the most common one.

Around 10 percent of adults suffer from chronic insomnia, while many more suffer short-term issues. Meanwhile around 25 million U.S. adults have obstructive sleep apneaa sleep disorder characterized by repeated obstruction to the airway during sleep.

In addition, 35 percent of adults report getting less than seven hours of sleep during a typical 24-hour periodless than the minimum recommend amount.

"The 4-7-8 breath that I teach is the most powerful relaxation method that I've discovered," Weil said in a video demonstration of the technique. "It's very simple, requires no equipment, takes very little time, costs nothing."

This is how to practise the technique correctly:

The speed with which you do the technique is not necessarily important. What is important is maintaining the 4-7-8 ratio between the counts.

According to Weil, this is a technique that you have to practise regularlyat least twice a dayto benefit from fully.

"You can do it more frequently than twice a day but never more than four breath cycles at one time," Weil said in the video.

According to Weil, it may take four to six weeks before you notice any physiological changes from the practise.

Over time he said it could help to lower heart rate, lower blood pressure, improve digestion, improve circulation, and to help people fall asleep.

"It is the most effective anti-anxiety techniques that I've found," he said. "I've taught it to patients with the most extreme forms of panic disorder, who eventually brought that under control, just relying on this breathing technique."

According to Patrick McKeown, a leading international expert on breathing and sleep, and author of bestselling books like The Oxygen Advantage, changing our breathing can have a profound impact on our physical and mental states.

"With breathing exercises one can down-regulate and up-regulate, giving us control over how our minds and bodies react to external stimuli," McKeown told Newsweek. "For sleep, breathing and mental health, functional breathing is instrumental.

"Knowing what exercises to practise can be life changing as we learn to change states. It's not about taking the deep breath. It's much more than that!"

According to McKeown, how a person breathes during the day will influence our breathing patterns during sleep.

"If our breathing patterns mean we are breathing through the mouth, with a faster rate and from the upper chest, (rather than from the diaphragm) this will increase the risk of sleep issues including insomnia, snoring and sleep apnea."

McKeown said that for people with functional breathing who are able to slow down their respiratory rate to around three breaths per minutelike during 4-7-8 exerciseextended exhalation will help activate the bodies relaxation response.

"When the rest and digest response is activated, one feels sleepy and experience increased watery saliva in the mouth," he said. "Slowing breathing rate also enables a better gas exchange to take place from the lungs to the blood.

"Practising this breathing technique before going to bed will not only help people fall asleep but will noticeably improve quality of sleep and when practiced regularly, will lead to a better quality of life all around."

Michael Breus, a clinical psychologist who is a diplomate of the American Board of Sleep Medicine and a fellow of the American Academy of Sleep Medicine, told Newsweek he is a "huge fan" of the 4-7-8 breathing technique.

According to Breus, the technique lowers the heart rate to the point it needs to be at night when some is trying to fall asleep.

"I have adopted this method, as both a 'help you fall asleep' but more of a 'help you get back to sleep' method," Breus told Newsweek. "Most people do not know this metric, but in order to get to a state of unconsciousness you need a heart rate of 60 or below, to get there. So, when you wake up in the middle of the night and your anxiety is high because you looked at the clock, this can help you get back to sleep."

In addition, Breus said there is plenty of data to show that diaphragmatic breathing helps to lower anxiety, which has been linked to difficulties falling and staying asleep.

"Most people are what we call 'shallow breathers' meaning that they do not use their full lung capacity, unless during full-on physical activity," Breus said. "This type of breathing requires more breaths per minute to get the required volume of air to live. More breaths per minute equals increased heart rateand we know we need to get to 60, which is usually down from where people tend to sit naturally (unless you are an athlete)."

Breathing for four counts in will slowly fill the lungs, holding for seven enables oxygen exchange to the fullest, and breathing out for eight pushes all the excess carbon dioxide out of the lungs and allows more fresh, highly oxygenated air to enter the system, and so the heart does not have to work as hard, according to Breus. This leads to a lowering of the heart rate.

McKeown said it is important to note that not everyone will be able to practise 4-7-8 breathing.

"People with poor breathing already experience a breathlessness that we call 'air hunger'. Slowing down the respiratory rate to three breaths per minute will be impossible for them to practise. It could even cause a disruption to their breathing," he said.

Read this article:
The Breathing Trick That Could Help You Fall Asleep Almost Instantly - Newsweek

In a recently published report, Northwestern Health Sciences University (NWHSU) has identified seven domains of knowledge, skills, and behaviors that clinicians need to provide the best integrative care.

Integrative care has many elements. At NWHSU, the concept of integrative care extends beyond multi-disciplinary care, including team-based and holistic care, interprofessional collaboration, and partnerships between patients and communities. Integrative care also includes interdependent considerations such as genetics, social determinants of health, community support and resources, and beliefs and habits that influence health.

Domain 1, values, ethics, culture, and diversity: In integrative care, clinicians work with colleagues in other professions in a climate of mutual respect and shared values, with the recognition that there is diversity in and between disciplines as well as diversity in patient populations.

Values, ethics, culture, and diversity are the connective tissue of integrative care and a transdisciplinary approach to healthcare, says Michele Renee, DC, director of integrative care at NWHSU. "It is the shared mindset that unifies diverse paradigms of healing, creating a dynamic approach in which each point of view is honored and yet not sufficient in and of itself. We are also acknowledging the importance of social factors, from socio-economic status to religion to cultural norms, and professional diversity, from indigenous healing to mainstream medicine to complementary and integrative healthcare approaches. All these differences are important considerations in providing robust, multifaceted, and individualized approaches to care."

Domain 2, patient-centered care: Clinicians should seek out, integrate, and value contributions and engagement of the patient, family, and community in designing and providing care.

Patient-centered care acknowledges the pivotal role of patients in their care, Renee says. "Patient-centered care calls out the importance of acknowledging the bio-psycho-social-spiritual nature of whole person care. It is vital that healthcare providers are not doing to the patient, but rather with the patient. Our patients are active participants in care and the most important person in a healthcare team."

Domain 3, roles and responsibilities: Clinicians should use knowledge of their role and the role of other professions to identify and address the healthcare needs of patients, families, and communities.

"For team-based care to work, we must each understand the part we play, the unique skills others bring, and how we all fit into the larger picture. This is a dynamic process, created uniquely for each person we serve. These skills are essential to ensure care is complete and wraps around our patients and communities," Renee says.

Domain 4, interprofessional communication: Clinicians should be responsive and responsible in their communication with patients, families, communities, and other healthcare professionals, which helps establishing a team approach to health and the treatment of disease.

Communication is often where healthcare fails, so shared communication competencies are essential, Renee says. "This includes understanding ourselves, acknowledging biases, identifying and resolving conflict when it arises, and documenting care in a way that is universally understood. Multilayered communication is key to building trusting relationships."

Domain 5, team and teamwork: Clinicians should practice relationship-building values and embrace team dynamics to perform effectively in different team roles to plan, deliver, and evaluate patient-centered care that is safe, timely, efficient, effective, and equitable.

Patients and communities rely upon their healthcare teams knowing how to evaluate, plan, and deliver care, Renee says. "This involves designing and implementing evidence-informed systems that support effective teamwork, and creating accountability for each care team member to focus on all aspects of patient and population focused problem solving. Team-based care goes beyond what happens in the treatment room or hospital to include social determinants of health and health equity."

Domain 6, collaborative leadership: Clinicians should foster shared leadership and collaborative practice of care.

Healthcare professionals need to cultivate the skill of passing the baton as needed, Renee says. "One provider may be providing the primary intervention at one moment in time and complementary care at another. The needs of the patient change over time and the care team needs to be prepared to collaborate and share leadership accordingly, leaning on one another's unique insights and expertise as needed."

Domain 7, well-being and resilience: Clinicians need to recognize that the health of an individual has positive and negative effects on their ability to make change around them and adopt sustainable strategies to address challenges, while remaining committed to their sense of purpose.

Building a resilient healthcare system starts with the well-being of healthcare professionals, Renee says. "Health creation begins with prioritizing self-care, which in turn reduces burnout and improves job performance and satisfaction. Learning the skills to identify one's circle of influence, develop a growth mindset, and cultivate grit prepare providers to better support patients in their own health creation by putting the focus on well-being and resilience instead of disease management."

Christopher Cheney is the senior clinical care editor at HealthLeaders.

More here:
Qualities Clinicians Need to Have to Deliver Integrative Care - HealthLeaders Media

ReportLinker

Global Nutrigenomics Market 2022-2026 The analyst has been monitoring the nutrigenomics market and it is poised to grow by $ 690. 14 mn during 2022-2026, accelerating at a CAGR of 12.

New York, Aug. 17, 2022 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Global Nutrigenomics Market 2022-2026" - https://www.reportlinker.com/p06314557/?utm_source=GNW 4% during the forecast period. Our report on the nutrigenomics market provides a holistic analysis, market size and forecast, trends, growth drivers, and challenges, as well as vendor analysis covering around 25 vendors.The report offers an up-to-date analysis of the current global market scenario, the latest trends and drivers, and the overall market environment. The market is driven by the increasing cost of medical treatment, growing investments by government and private stakeholders, and the rising number of health-conscious people.The nutrigenomics market analysis includes the application segment and geographic landscape.

The nutrigenomics market is segmented as below:By Application Obesity Cardiovascular diseases Cancer research

By Geographical Landscape North America Europe Asia Rest of World (ROW)

This study identifies the rising demand for training in and awareness of nutrigenomics technologies as one of the prime reasons driving the nutrigenomics market growth during the next few years. Also, increasing approval of grants and increasing prevalence of obesity will lead to sizable demand in the market.

The analyst presents a detailed picture of the market by the way of study, synthesis, and summation of data from multiple sources by an analysis of key parameters. Our report on nutrigenomics market covers the following areas: Nutrigenomics market sizing Nutrigenomics market forecast Nutrigenomics market industry analysis

This robust vendor analysis is designed to help clients improve their market position, and in line with this, this report provides a detailed analysis of several leading nutrigenomics market vendors that include BASF SE, Cell Logic Pty Ltd, Cura Integrative Medicine, DNA Life, Fagron NV, geneOmbio Technologies Pvt Ltd., Genetic Healing, Genova Diagnostics Inc., Greenarray, Holistic Health International LLC, Koninklijke DSM NV, Metagenics Inc., My DNA Health Ltd., NutriFit Canada, Nutrigenomix Inc., ORIG3N Inc., Preventine Life Care, The Gene Box, and Xcode Life Sciences Pvt. Ltd. Also, the nutrigenomics market analysis report includes information on upcoming trends and challenges that will influence market growth. This is to help companies strategize and leverage all forthcoming growth opportunities.The study was conducted using an objective combination of primary and secondary information including inputs from key participants in the industry. The report contains a comprehensive market and vendor landscape in addition to an analysis of the key vendors.

The analyst presents a detailed picture of the market by the way of study, synthesis, and summation of data from multiple sources by an analysis of key parameters such as profit, pricing, competition, and promotions. It presents various market facets by identifying the key industry influencers. The data presented is comprehensive, reliable, and a result of extensive primary and secondary research. Technavios market research reports provide a complete competitive landscape and an in-depth vendor selection methodology and analysis using qualitative and quantitative research to forecast accurate market growth.Read the full report: https://www.reportlinker.com/p06314557/?utm_source=GNW

About ReportlinkerReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.

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The Global Nutrigenomics Market is expected to grow by $ 690.14 mn during 2022-2026, accelerating at a CAGR of 12.4% during the forecast period -...

Introduction

Type 2 diabetes mellitus (T2DM) and obesity are major public health problems affecting millions of people worldwide. T2DM is a metabolic disorder characterized by long-term hyperglycemia and is one of the leading causes of morbidity and mortality.1 Obesity is an important exo-promoting factor of T2DM. Accumulating evidence demonstrates that obesity is not only strongly related to the etiology and pathogenesis of T2DM but also to the development of diabetic complications.2 Hyperglycemia and glucose toxicity can induce oxidative stress, worsening the outcome of AMI (acute myocardial infarction) in patients with diabetes.3 In addition, both hypertension and diabetes are critical risk factors for stroke in patients with atherosclerotic cardiovascular impairment.4 Capability of entering the CNS is an effective way for drug development to improve metabolism, alleviate diabetes, and obesity. CNS is an important target for improving obesity and many obesity-improving drugs exert effect through the CNS.5 Therefore, whether it can cross the BBB determines the effect of the drug. GLP-1 is secreted during mealtime and reduces blood glucose levels by enhancing insulin secretion and inhibiting glucagon release. A growing number of GLP-1RAs have been produced, which can be classified into short-acting or long-acting compounds. The net effects of the former reduce postprandial blood glucose, while the latter affects both fasting and postprandial blood glucose.6 In rodents, the anorexigenic effect of GLP-1RA administration peripherally requires central GLP-1R, for it is not inhibited in mice with central specific GLP-1R deletion.7

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are a novel class of oral drugs for the treatment of T2DM. These drugs block SGLT-2 in proximal tubules, through which 90% of glucose is reabsorbed, thus decreasing the reabsorption of glucose and lowering the blood glucose levels.8 In addition to the anti-diabetic effects, weight loss has also been observed in patients receiving SGLT-2i monotherapy.911 This drug class affects multiple systems, including the nervous, cardiovascular and endocrine systems, resulting in exceedingly complex metabolic effects beyond glycemic control.

Clinical studies have shown that both SGLT-2is and GLP-1RAs reduce body weight and lower the risk of hospitalization and mortality of cardiovascular disease such as AMI in patients with type 2 diabetes.1214 These two agents possibly share similar CNS routes, but their modes of action might be very distinct.15,16 The blood-brain barrier (BBB) is a dynamic barrier that maintains the regular physiological state and metabolism of the central nervous system (CNS), but it also inhibits peripheral drugs from entering the CNS.17 Both the lipid-soluble GLP-1RAs and small-molecule SGLT-2is were considered to be able to cross the BBB in numerous preclinical trials.

Furthermore, increased levels of circulating free fatty acids, inflammatory cytokines (TNF-, IL-1, IL-6) and chemokines increase BBB permeability. These effects are compounded by the apoptosis of BBB microvascular endothelial cells caused by hyperglycemia and obesity.1821 BBB impairment has also been reported in a variety of neurological disorders, including Parkinsons disease and Alzheimers disease.22 Interestingly, oxidative stress is a common feature of all these cases. Elevated levels of reactive oxygen species (ROS) are observed during pathological processes, and ROS is considered to contribute to the increased permeability of the BBB. Mitochondria are the main source of ROS production in cells. The destruction of the mitochondrial electron transport chain (ETC) leads to an increase in ROS production, which triggers matrix metalloproteinases (MMP) induction, ultimately disrupting tight junctions and increasing BBB permeability.23 The integrity of the BBB is compromised in certain pathological states, and its temporary disruption allows drugs in the peripheral circulation to enter the CNS. Consequently, GLP-1RAs and SGLT-2is are able to cross the BBB. Terami et al revealed that diabetes-induced disruption of the BBB allowed SGLT-2is to pass through in a dose-dependent manner.24

This review introduces the basic structure and permeation mechanism of the BBB, discussing the relationship between the structural and/or chemical properties of SGLT-2is/GLP-1RAs and their permeability through the BBB.

The bloodbrain barrier (BBB) is composed of capillary endothelial cells linked by tight junctions, basal lamina, pericytes, and astrocytes. It acts as a regulatory interface between capillaries and nerve tissues in the brain and spinal cord that restricts the transfer of most drug substances from the bloodstream into the brain and serves as an important barrier to maintaining the brains homeostasis (Figure 1).17,25 However, some structures, such as circumventricular organs (CVOs), lack a complete BBB. CVOs are composed of malformed ependymal cells and many leaky capillaries that lack a full blood-brain barrier, allowing chemicals to enter the brain. CVOs include the pineal gland, the organum vasculosum of the lamina terminalis (OVLTs), the subfornical organ (SFO), the choroid plexus, the region postrema (AP), the pituitary glands posterior lobe, the subcommissural organ, and the median eminence (ME) of the mediobasal hypothalamus.26,27

Figure 1 Structure of the BBB: capillary endothelial cell, tight junction, basal lamina, astrocyte, pericyte, interneuron.

The semipermeable nature of BBB restricts the movement of large molecules, such as drugs or proteins >500 kDa. Compounds having logPoct2.0 have optimal brain penetration. The parameters used for predicting drug penetrability by modified Lipinskis rules for CNS penetration include hydrogen bond donors (HBD) 3; hydrogen bond acceptors (HBA) 7; logPoct 5.0; 7.5 < pKa < 10.5; molecular weight 400Da.28

Substances can cross the blood-brain barrier via paracellular transport and intercellular transport. Although most macromolecules in the blood are physically prevented from entering the brain due to the presence of the blood-brain barrier and tight junctions, specific and non-specific transcellular mechanisms transport various macromolecules and complexes across the blood-brain barrier. Figure 2 illustrates several primary routes across the BBB: positively charged macromolecules cross the BBB via adsorptive-mediated transcytosis (AMT); non-polar solutes and lipid-soluble drugs pass via passive diffusion; c) carrier-mediated transport (CMT) is responsible for the transport of a variety of essential polar molecules into the CNS; and receptor-mediated transcytosis (RMT), which requires specific ligands29 (Figure 2).

Figure 2 Mechanism of BBB transportation: a) Carrier-mediated influx, in which polar molecules are transported; b) Adsorptive-mediated transcytosis, in which positively charged macromolecules bind to receptors and are transported across the endothelial cell; c) Passive diffusion, in which most lipid-soluble molecules are transported; d) Receptor-mediated transcytosis, in which macromolecules bind to receptors and are transported to the CNS; e) Tight junction model (partially or completely open). Arrows indicate the direction of transportation.

Jensen et al conducted a study in the CNS by isolating and purifying a novel specific monoclonal GLP-1R antibody and detecting the location of GLP-1R using an in situ hybridization technique.30,31 The results confirmed that GLP-1 receptors (GLP-1R) are widely distributed throughout the cerebral cortex, hypothalamus, hippocampus, thalamus, caudate nucleus, and globus pallidus. Numerous studies focusing on diverse brain illnesses such as Alzheimers disease (AD) and ischemic brain injury have corroborated the localization of GLP-1R in the CNS.3234 In addition, a study reported GLP-1R expression on pericytes, which are multi-functional mural cells located at the center of the neurovascular unit (NVU).35 Other studies have mapped the action of GLP-1RAs, demonstrating that GABA neurons in the NTS express GLP-1 receptors and mediate the anorectic effects of liraglutide in rats.36 However, a study of single-cell RNA sequencing in the brain shows that the presence of GLP-1R on BBB endothelial cells is negligible.37

Exenatide,38 lixisenatide,39,40 beinaglutide,41 liraglutide,42 dulagutide43 and semaglutide44 are now commercially accessible as GLP-1 receptor agonists (Table 1). The GLP-1 receptor agonists can be classified into two groups based on their chemical structure. Exenatide is based on the exendin-4 structure and has a low amino acid sequence homology with human GLP-1, whereas natural GLP-1RAs, such as liraglutide, have a higher amino acid sequence homology of 95% with human GLP-1.45 According to the different molecular conformations (natural GLP-1 or long-acting GLP-1 analogs) and drug administration pathways, GLP-1 and its analogs transmit food reduction signals directly or indirectly to the central nervous system (CNS) through different signal pathways.

Table 1 The Physicochemical Properties of GLP-1 Receptor Agonists

Numerous studies have discovered the expression of native GLP-1 in CNS, implying that natural GLP-1 could cross the BBB from the peripheral circulation via passive transport due to their physiological, molecular biology, pharmacokinetic, and pharmacodynamic properties. Kastin et al observed and analyzed the influx rate following intravenous injection of 125I-[Ser8] GLP-1. The blood-brain flow of GLP-1 via passive diffusion may be determined by its physicochemical properties rather than lipophilicity, demonstrating the BBBs permeability to GLP-1.46 Several preclinical and clinical studies on ischemia-induced brain injury, Alzheimers disease (AD), Parkinsons disease (PD), and other neurodegenerative disorders have established that GLP-1RAs can cross the BBB and exert a significant neuroprotective effect.3234 Furthermore, various studies have examined the anorexia-promoting properties of GLP-1RAs. The studies have demonstrated that GLP-1R is also expressed in nuclei controlling food intake, such as the arcuate nucleus (ARC) and paraventricular thalamic nucleus (PVN). Previous studies also demonstrated that GLP-1RAs might cross the BBB and promote bodyweight loss by acting on these nuclei.4750 The effect of intravenous infusion of GLP-1 on food intake disappeared after vagotomy in humans, which suggested that the vagus afferent pathway is involved in the effect of GLP-1 on appetite.51 However, subdiaphragmatic vagotomy had no effect on GLP-1-induced acute activation of PKA in the brain, indicating that the vagus nerve is not involved in GLP-1RAs entering the brain.52 Interestingly, subphrenic vagus afferents can also attenuate the short-term appetite inhibitory effects of liraglutide and exendin-4, but their long-term effects on food intake do not depend entirely on vagus afferents.53 The above findings indicate that GLP-1RAs inhibit food intake and cause weight loss mainly by acting on different brain regions, which also supports the evidence of long-acting GLP-1RAs penetrating incomplete BBB in certain areas. GLP-1Rmediated transport occurs through circumventricular organs (CVOs) and maybe other parts of the hypothalamus via fenestrated capillaries and is partially dependent on tanycytemediated transport through certain localized compartments of the cerebrospinal fluid (CSF).54,55 Central administration of GLP-1RAs suppressed appetite, accompanied by increased expression of c-Fos in neurons within the PVN, amygdala, NTS, AP, LPB and ARC, which was consistent with the results of GLP-1R expression studies in the CNS.56 Decreased food intake and weight loss were observed with peripheral administration of GLP-1RAs, but inactivation of intestinal GLP-1 production did not interfere with food intake or weight control, suggesting that the GLP-1R-dependent signaling regulating appetite and body weight occurs in the CNS.50,57

Exendin-4, a bioactive peptide produced from Heloderma suspectum venom, is a 39-amino-acid peptide.58 Exendin-4 improved cognitive behavioral tests in Alzheimers disease patients by protecting the brain against abnormal insulin signaling.59 Kastin and Akerstrom established in a landmark study that peripherally injected Exendin-4 passed readily through the BBB, facilitated by its lipophilicity, rather than becoming trapped in the endothelial cell.60 According to multiple time regression analyses, exendin-4 passes directly through the BBB. Exendin-4 has been shown to easily cross the BBB, which is critical for Parkinsons disease treatment.61 In addition, Exendin-4 quickly enters the brain and brain microvascular endothelial cells via active ligands that bind to and activate GLP-1 receptors.52 Exenatide is based on exendin-4 structure.62 Numerous clinical trials established exenatides efficacy in individuals with Parkinsons disease, demonstrating that it entered the CNS via the BBB and exerted neuroprotective and neurorestorative effects.6365 Additionally, it was demonstrated that exendin-4 is also mediated by the adsorptive transcytosis across brain endothelial cells.66

On the other hand, Salamehs research indicates that lixisenatide can penetrate the BBB via adsorptive transcytosis.66 Lixisenatide has been demonstrated to pass the blood-brain barrier and exert neuroprotective effects in Alzheimers disease.67 Hunter and Holscher reported increased cAMP levels in the CNS at all dosages after 30 minutes and 3 hours of lixisenatide injection, which indicated the activation of the GLP-1 receptor, and presented persuasive evidence that lixisenatide crossed the BBB.68

Liraglutide is a GLP-1 agonist with neuroprotective properties in Alzheimers disease.69 It has demonstrated the ability to cross the BBB. The pharmacological concentration of GLP-1RA in the brain was proportional to the intraperitoneal injections, with 2.5, 25, or 250 nmol per kg of body weight protecting against impairment of recognition memory synaptic loss and degradation in the hippocampus of patients.68,70 Despite its varied ability to cross the BBB, liraglutide was more effective than exendin-4 in repairing the damage induced by 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MTPT).71 While these findings suggest that GLP-1RAs can reach brain tissue by passive diffusion across the BBB, other research has shown that liraglutide could only enter the brain by binding to the central GLP-1 receptor.

Dulaglutide is a GLP-1RA with a larger molecular weight, which may potentially cross a compromised BBB.72 However, there is no direct evidence proving that dulaglutide crosses the BBB.

In 2017, the US Food and Drug Administration (FDA) authorized semaglutide as the seventh clinically available GLP-1RA.44 The longer aliphatic chain in semaglutide, a long-acting formulation based on the structure of liraglutide, enhances hydrophobicity by altering the DPP-4 enzyme hydrolysis site with polyethylene glycol (PEG), allowing it to strongly bind to albumin. Semaglutide was detected within vascular endothelial cells and could not cross the BBB. According to the research by Gabery et al, semaglutide could bind to albumin and directly reach the brainstem, septal nucleus, and hypothalamus via CVOs, but showed no interaction with endothelial cells and could not cross the BBB. Interestingly, semaglutide seems to be able to pass through the tanycytes that line the ventricular wall or areas lacking a BBB.73

SGLT-2 is mainly expressed in the apical membranes of kidney segments 1 and 2 of the proximal convoluted tubules.74 A previous study has demonstrated that SGLT-2 is present in the central nervous system, including the brain parenchymal and the BBB.7577 SGLT-2 was shown to be expressed in ependymal cells and choroid plexus epithelial cells (CPE) in the brainstem, hypothalamus, periaqueductal grey (PAG), amygdala, and solitary nucleus of mice and humans.78

SGLT-2is are a novel class of diabetes medications and are well-known for their efficacy in the treatment of chronic heart failure in both diabetic and non-diabetic patients. RAAS is one of the most important arterial blood pressure regulators and plays a key role in cardiovascular and renal diseases. A study by Shin et al reported that dapagliflozin attenuated inflammatory and fibrotic markers.79 In addition to their anti-diabetic effects, SGLT-2is play a role in cardio-nephroprotection due to RAAS activation from their diuretic and sympathoinhibition effects.80 Phlorizin, the first SGLT-2i, is a naturally occurring chalcone compound discovered in apple bark in the 1850s by French researchers. It is a non-specific SGLT-1 and SGLT-2i that was not used as an anti-hyperglycemic medication due to gastrointestinal side effects until the chemical structure was modified in this decade. SGLT-2is are lipid soluble drugs with low molecular weight, as indicated by their chemical structures (Figure 3).

Figure 3 Chemical structure and molecule weight of SGLT-2 inhibitors. Dapagliflozin(2013) MF:C21H25ClO6 MW:408.88; Empagliflozin(2014) MF:C23H27ClO7, MW:450.91; Sotagliflozin(2019) MF:C21H25ClO5S MW:424.94; Ertugliflozin(2017) MF:C22H25ClO7 MW:436.88; Luseogliflozin(2014) MF:C23H30O6S MW:434.55; Tofogliflozin(2014) MF:C22H26O6 MW:386.44; Ipragliflozin(2014) MF:C21H21FO5S MW:404.45; Canagliflozin(2013) MF:C24H25FO5S MW:444.52.

Abbreviations: MF, molecular formula; MW, molecular weight.

Physicochemical properties, including molecular weight, pKa, LogPoct, HBA and HBD, are critical parameters related to the ability of drugs to cross the BBB. These properties can be obtained from the ChEMBL database, which is an open database that contains information on a large number of drug-like bioactive compounds: https://www.ebi.ac.uk/chembldb(Table 2).

Table 2 Physicochemical propertiesrelated to penetration capacity of the BBB of SGLT-2is.

Notably, given that SGLT-2 is expressed in the brain, which is consistent located with enhanced cFos expression induced by SGLT-2is, we hypothesize that SGLT-2is may cross the BBB via receptor-mediated transcytosis.76,81 In a recent study, we discovered that the SGLT-2i dapagliflozin might cross the BBB and interact with SGLT-2 in the brain.81 In addition to its hypoglycemic effect, the neuroprotective effect of SGLT-2is may be another evidence that it can cross the BBB. Dapagliflozin may enter the brain through impaired BBB, irrespective of its lipid-soluble properties, as evidenced by dramatically increased BBB permeability and disruption of tight junction between endothelial cells in Parkinsons disease.82 Empagliflozin improved cognitive performance in diabetic rats by lowering brain oxidative stress. In this context, the increase in cognitive function associated with empagliflozin and canagliflozin may also support the notion that these medicines are capable of penetrating the damaged BBB.83 Inflammation in the CNS of patients with diabetes or other chronic diseases may increase the permeability of the BBB, allowing SGLT-2is to pass through. El-Sahar et al examined dapagliflozins neuroprotective effect in rats with Huntingtons disease and discovered that it was capable of modulating aberrant neurotransmission. Other abnormal conditions in the rat striatum, such as apoptosis, glycolysis, and autophagy, may allow SGLT-2is to cross the BBB.84 On the other hand, some research shows that the neuroprotective effect of SGLT-2is is most likely caused by the increased native GLP-1 concentration and decreased corticosterone concentration following SGLT-2is administration.85

Dapagliflozin was the first SGLT-2i to be licensed as a commercially accessible drug by the US Food and Drug Administration in 2000. Our previous study found that dapagliflozin may act on the rostral ventrolateral medulla (RVLM) and affect the sympathetic outflow of sympathetic preganglionic neurons to the intermediolateral nucleus of the spinal cord (IML), thereby promoting parasympathetic activity. Dapagliflozin also inhibits SGLT-2 in mice and regulates central autonomic activity by stimulating neurons in the central nervous system and controls cardiovascular functions. SGLT-2 was localized to specific regions involved in autonomic control. Expression of c-Fos was significantly higher in major critical nuclei in the aforementioned regions in the mice group treated with dapagliflozin.81 Shaikh et al reported that dapagliflozin is a potent dual inhibitor of SGLT-2 and acetylcholinesterase, which could be used as the basis for future dual therapy for patients with diabetes and diabetes-related neurological disorders.86

In 2014, the drug empagliflozin (EMPA) was approved for the treatment of T2DM. Extensive investigation revealed that EMPA had been shown to have a neuroprotective impact on illnesses like Alzheimers disease and Parkinsons disease. In a recent study, EMPA was shown to traverse the damaged BBB and to improve ultrastructural remodeling of the neurovascular unit (NVU) and neuroglia in female diabetic mice.87 Entesar et al also confirmed that EMPA exerted neuroprotective effects in hyperglycemic rats.88 Increased expression of cerebral caspase-3 was observed in ischemia/reperfusion(I/R)-injured rats administered with oral EMPA, whereas apoptotic cells decreased, indicating that EMPA may help protect neurons. The researchers speculated that EMPA could cross through a compromised BBB and exert neuroprotective benefits. The above findings suggest that EMPA can enter areas with compromised BBB integrity (Figure 3).

Sotagliflozin, often known as a dual SGLT-1/SGLT-2 inhibitor, has the highest affinity for SGLT1 receptors but is not yet commonly used in diabetic patients as it is the newest SGLT-2is.89 In theory, sotagliflozin may have a greater neuroprotective effect than other SGLT-2is due to increased SGLT1 expression in the brain.90 Sotagliflozin should be able to penetrate the BBB via passive diffusion based on its lipid-soluble molecular structure. However, no current investigations have examined this concept.

Ertugliflozin was licensed for clinical usage in 2017 after it was demonstrated to decrease the risk of heart failure hospitalization (HHF).91 However, minimal research has been conducted on its BBB permeability. Based on physicochemical and polypharmacological data, ertugliflozin is likely unable to cross the BBB.92

Luseogliflozin is a selective SGLT-2 inhibitor that received marketing approval on March 24, 2014, for the treatment of T2DM.93 Many studies have shown that luseogliflozon could reverse cerebrovascular dysfunction and cognitive impairments in diabetic animals and elderly diabetics.94,95

The FDA authorized tofogliflozin for diabetic therapy in 2014. Takeda et al discovered that tofogliflozin could enhance food intake. They hypothesized that delivering tofogliflozin intracerebroventricularly (ICV) could stimulate food intake by acting directly on the CNS, whereas intraperitoneal administration showed no such effects.96 Tofogliflozin administered via ICV enhanced food intake, indicating the presence of SGLT-2 in the brain. However, the BBB permeability of tofogliflozin remains unknown (Figure 4). Additionally, c-fos (a neuronal activation indicator) was significantly enhanced in the arcuate nucleus (ARC) within 23 hours after tofogliflozin treatment, suggesting that tofogliflozin could permeate these regions and bind to receptors on the ARC.

Figure 4 Factors influencing the blood-brain barrier permeability and possible treatment strategy. Increased oxidative stress, decreased VEGF levels and increased matrix metalloproteinase (MMP) activity result in basement membrane expansion, pericyte disintegration, increased paracellular diffusion, and decreased tight junction protein expression. In addition, fatty acids induce inflammatory responses, which reduce protein expression in BBB microvessels and increase BBB apoptosis, resulting in increased BBB permeability. Evidence shows that modification of the gut microbiota with prebiotics or probiotics and high-fiber diets improve systemic inflammation, restoring BBB integrity. In addition, treatment with GLP-1RAs and SGLT-2is inhibit the activation of inflammatory factors and attenuate oxidative stress via blood glucose and fatty acids reduction.

Ipraglifozin has a five-membered ring structure with low selectivity for SGLT-2 and was first approved in Japan in 2014. Destruction of mitochondrial ETC leads to increased ROS production, which triggers matrix metalloproteinases (MMP) induction, ultimately leading to compromised BBB integrity. Studies have shown that ipragliflozin can reduce body fat mass and alleviate mitochondrial dysfunction.97,98 Therefore, it has the effect of both anti-obesity, and anti-oxidant to improve BBB permeability. However, there are no adequate studies revealing the mechanism of ipragliflozin and its ability to cross the BBB.

In 2013, the FDA approved canagliflozin as an anti-diabetic medicine. Canagliflozin (CAN) has been demonstrated to bind to both AChE and SGLT-2, inhibiting both enzymes simultaneously.99 Its effects on neurotransmitters may also be linked to the activation of its receptors. Therefore, canagliflozin may potentially exert direct effects on CNS SGLT-2. Although a study found that canagliflozin had a cognitive protective effect in high-fat diet mice by decreasing obesity-related neuroinflammation,100 there is no conclusive evidence that it can cross the BBB. Due to its lipophilicity and low molecular weight, CAN could partially cross the blood-brain barrier via passive diffusion.101

DM and obesity influence BBB integrity through a number of mechanisms (Figure 4). In our previous studies, hyperglycemia and inflammation were shown to lead to pathological capillary changes in the retina.102 The current findings in the diabetic brain suggest a striking similarity, indicating a common pathophysiological mechanism between the retina and the brain microvessels. Magnetic resonance (MR) brain imaging with intravenous gadolinium (Gd) diethylenetriamine pentaacetic acid revealed increased BBB permeability in diabetic patients (Gd-DTPA). IgG has been demonstrated to leak into the brain interstitium of DMHC pigs via the permeable BBB.18,19 According to recent research, chronic hyperglycemic exposure resulted in compromised BBB integrity, characterized by altered tight junctions, thickened basement membrane, capillary density changes, and pericyte deterioration. In addition, pericyte loss caused by the Krebs cycle processing of excessive glucose resulted in increased oxidative stress. Furthermore, advanced glycation end products activate vascular endothelial growth factor (VEGF), which increases matrix metalloproteinase synthesis and alters tight junction proteins. In diabetic patients and rodents, elevated plasma matrix metalloproteinase (MMP) activity lowered BBB tight junction protein synthesis and increased BBB permeability.103105 Microvascular diseases may lead to BBB decomposition, allowing serum-derived components to flow into the brain parenchyma.106 Hyperglycemia also induces the production of reactive oxygen species107 and increases pro-inflammatory cytokines and chemokines in many cells.108,109

Obesity is considered a low-grade chronic inflammation and has already been associated with functional alterations in the BBB (Figure 4). Dietary components such as fatty acids stimulate lipopolysaccharide (LPS) receptors and toll-like receptor 4(TLR4), triggering an inflammatory cascade that releases inflammatory mediators(TNF-, IL-1, IL-6). Studies have shown a decrease in energy consumption in BBB microvessels and a suppression of expression of 47 types of BBB proteins in diet-induced obesity (DIO) mice. Additionally, the activities of enzymes, transporters, and cytoskeleton proteins on BBB microvessels are preferentially suppressed in these DIO animals.110,111 Moreover, a study indicated that a high-energy (HE) diet is related to increased BBB permeability as elevations in peripheral proinflammatory cytokines compromise BBB function in specific areas of the brain.112

Decreased BBB permeability and upregulated expression of tight junction proteins were observed in germ-free adult mice.113 Intestinal flora disorders may compromise the BBB integrity due to the decreased expression of tight junction proteins.114 Disorders of the gut-microbial flora may cause systemic inflammation by destroying the intestinal epithelial barrier and introducing toxic by-products in the blood circulation.115 In humans, changes in the composition of gut-microbial flora are associated with obesity and T2DM.116,117 Furthermore, increasing evidence indicates that modifying the microbiota with prebiotics or probiotics benefits the host, while high-fiber diets also induce faster resolution of inflammatory responses.118,119

Temporary disruption of BBB has been widely studied as a prevalent approach for delivering drugs into the CNS from the circulatory system.120 BBB malfunction is a hallmark of a variety of neurological disorders, including Alzheimers disease, Parkinsons disease, cerebral ischemia, stroke, hyperlipidemia, and diabetes.121 GLP-1RAs and SGLT-2is could cross the temporarily disrupted BBB in the brains of experimental animals and individuals with neurological disorders, diabetes, and obesity via a variety of transmembrane routes. GLP-1RAs and SGLT-2is both have the ability to penetrate damaged basement membranes and tight junctions (Figure 5).

Figure 5 (A) Normal BBB: GLP-1RAs can cross the normal BBB by receptor-mediated transport and passive diffusion, but whether SGLT-2is may cross the compromised BBB via passive diffusion is still being investigated. (B) Impaired BBB.

Although providing a first glimpse at the capacity of GLP-1RAs and SGLT-2is to traverse the BBB, the current review has not disclosed the specific signaling mechanisms, particularly for SGLT-2is. In addition, it is yet unknown how the physical and chemical features of SGLT-2is regulate their transportation in the CNS. The interaction of GLP-1RAs and SGLT-2is with the blood-brain barrier (BBB) requires additional research and direct evidence at the molecular or cellular level.

In conclusion, the preclinical and clinical studies demonstrated that GLP-1RAs and SGLT-2is act directly or indirectly on their receptors by crossing the BBB. Thus, they can not only lower glucose levels but also be applied in the treatment of CNS diseases. Central administration of GLP-1RAs or SGLT-2is could increase the expression of c-Fos in neurons within the PVN, amygdala, NTS, AP, and ARC,56,96 which was consistent with the expression of GLP-1R/SGLT-2 in the whole CNS.30,31,7577 This may be considered evidence that these drugs could pass through the BBB and activate the neurons in these nuclei. Some of the GLP-1RAs have been proven to cross through the BBB via passive diffusion.34,46,48,68 In addition, GLP-1RAs could cross the BBB via the GLP-1 receptor-mediated uptake mechanism.52 Liraglutide has access to specific areas of the brain associated with appetite regulation and was measured in selected CVOs and specific hypothalamic regions, of which the signal was GLP-1R-dependent.54 Adsorption transcytosis could be another mechanism involved in exendin-4 and lixisenatide crossing the BBB.66 Semaglutide may be unable to cross the regular BBB directly but could bind to serum albumin and pass through the tanycytes lining the ventricle wall.73 In summary, peripheral administration of GLP-1RAs either acts directly on the hypothalamus and hindbrain, which lack BBB, or directly crosses the BBB into CNS, which are then projected to other key feeding areas of the brain (Figure 6). Notably, SGLT-2is are medications of small molecular weight, with lower LogPoct than the permeation prediction index of BBB (listed in Table 2). SGLT-2is activated c-Fos expression in the CNS, and the relationship between the chemical structure/properties of SGLT-2is and BBB could be interpreted as evidence for penetrating the BBB.81 Due to the increased permeability of the BBB in hyperglycemia and obesity, SGLT-2is and GLP-1RAs are likely to pass through the compromised BBB.18 As such, the prospects of comprehensively elucidating the mechanism of SGLT-2is and GLP-1RAs interacting with BBB are promising, through which corresponding strategies for the prevention and treatment of DM, AD, PD and CVD can be developed.

Figure 6 The arcuate nucleus (ARC) in the hypothalamus, the area postrema (AP) and the Nucleus of Solitary (NTS) in the brainstem are 3 examples of CVOs that are not protected by an effective blood-brain barrier. Once GLP-1RAs enter the bloodstream by subcutaneous injection, they can activate ARC hypothalamic POMC/CART neurons, which subsequently stimulate sympathetic efferent output, controlling insulin secretion. It is unclear if GLP-1-RAs stimulate the pre-vertebral ganglia directly. GLP-1RAs also activate GLP-1 receptors on the surface of pancreatic cells, resulting in the conversion of adenosine to cyclic adenosine phosphate (cAMP) in islet cells through conjugation of active G protein with adenosine cyclase. As cAMP levels rise, the pancreatic beta cell membrane depolarizes, which promotes insulin secretion. Further work is required to determine whether SGLT-2is may cross the BBB and exert similar effects on the brain.

This work was supported by the Project of Key Medical Discipline of Pudong Hospital of Fudan University (Zdxk2020-11), Project of Key Medical Specialty and Treatment Center of Pudong Hospital of Fudan University (Zdzk2020-24), Integrative Medicine special fund of Shanghai Municipal Health Planning Committee (ZHYY- ZXYJHZX-2-201712), Special Department Fund of the Pudong New Area Health Planning Commission (PWZzk2017-03), Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai (PWR12014-06), Pudong New Area Clinical Plateau Discipline Project (PWYgy-2021-03), the Natural Science Foundation of China (21675034), National Natural Science Foundation of China (81370932), Shanghai Natural Science Foundation (19ZR1447500) and Education Funding in Wenzhou Medical University (JG2021197).

The authors report no conflicts of interest in this work.

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The Relationship Between the Blood-Brain-Barrier and the Central Effec | DMSO - Dove Medical Press

Zinc is an essential mineral for your health. It plays a role in:

Of all the trace minerals, only iron is found in higher concentrations in the body.

Yet even though zinc is important for your health, you can still get too much of it.

"The tolerable upper intake level (UL) for zinc, meaning the highest recommended daily amount, is 40 mg per day," says Dr. Jeffrey Gladd, an integrative medicine physician and chief medical officer at Fullscript.

Read on to learn the signs of a zinc overdose, how to get treatment, and what you can do to get the recommended daily amount of zinc.

A zinc overdose can involve different symptoms, depending on whether it's acute or chronic.

An acute overdose means you ingest a large amount of zinc in a short period of time.

Symptoms of an acute overdose usually won't appear until you ingest one to two grams of zinc, and Gladd says you don't need to worry about getting too much zinc from your diet.

A zinc overdose typically happens as a result of:

Symptoms of acute zinc overdose might include:

A zinc overdose can be life threatening. If you suspect you may have consumed too much zinc and have symptoms of an overdose, you'll want to contact 911 or a poison control center for emergency medical support, Gladd says.

The treatment for oral zinc overdose may include:

A chronic overdose means you've regularly consumed too much zinc over a longer period of time.

Chronic zinc overdose can occur when you ingest anywhere from 150-450 milligrams (mg) of zinc per day.

This generally happens as a result of taking too many zinc supplements, but using large amounts of zinc-containing denture creams can also expose you to excess zinc.

The symptoms of chronic excess zinc can affect your whole body and may include:

If you've taken more than the daily recommended amount of zinc for more than a few days and notice any of the above signs and symptoms, you should stop taking any supplemental zinc and check in with your doctor. Depending on how much zinc you've taken, and for how long, they may recommend treatment.

If you eat a balanced diet that includes a variety of zinc-containing foods, you likely don't need to supplement with extra zinc, Gladd says. This means, of course, you won't run the risk of getting too much zinc.

Foods that contain plenty of zinc include:

However, certain groups of people are more likely to have a zinc deficiency, including:

"If you're concerned about zinc levels, the best option is to get a zinc blood test. They are relatively inexpensive and allow you to get quick, accurate results," says Daniel Powers, herbal medicine expert and founder of the Botanical Institute.

Keep in mind it's always important to ask a healthcare professional before taking any supplement especially zinc, which you can easily overconsume.

The FDA doesn't regulate supplements, so it's important to check with your doctor if you're unsure about how much of any supplement to take. Opting for supplements that have undergone third-party testing can also help you ensure you get the supplement you want, in the advertised amount.

If you choose to supplement, keep in mind that experts recommend consuming no more than the recommended daily allowance (RDA) of zinc:

Zinc requirements for children and teens range from 2 mg to 11 mg per day, depending on age. If you think your child may not get enough zinc from their diet, it's best to ask your pediatrician about the correct dose.

Although you need zinc to maintain good health, you can take too much and excess zinc can have serious health consequences. If you've taken more than the daily recommended dose of zinc, you should get medical attention right away.

In most cases, a varied diet will provide enough zinc, and many people don't need to supplement. However, if you eat a limited diet, are pregnant or lactating, or have a health condition that affects zinc absorption, you may have a higher risk of zinc deficiency.

Your doctor or another healthcare professional can offer more guidance on how much zinc you should take for optimal health.

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Zinc side effects: Signs of overdose and how to treat it - Insider

The Indian Institute of Chemical Technology (IICT)s 10th director D. Srinivasa Reddys career reads like a fairy tale.

The Shanti Swarup Bhatnagar award winner hails from Shobhanadripuram village in Nalgonda district, studied in a Telugu medium school till his graduation, did his post-graduation from Osmania University and Ph.D. from University of Hyderabad (UoH) under the tutelage of eminent academic-scientist Prof. Goverdhan Mehta.

He is currently holding the additional charge of CSIR-Institute of Integrative Medicine (Jammu) and CSIR-Drug Research Institute (Lucknow). In this interview, Dr. Reddy talks about his life and plans for the premier chemical research institute.

a) You have been a project assistant here and have returned as the director!

A: My father was a farmer and I never thought of becoming a scientist. I came to Hyderabad for my Intermediate in Mahabub College and B.Sc (BZC) in S.P. College when I used to distribute newspapers, give home tuitions and worked in a timber depot loading logs to earn money. With a lot of difficulty I joined as a project associate in IICT. Later, I cleared my CSIR-NET exam and joined Prof. Mehta. From then on, it has been growing upwards though hard work and perseverance.

b) How did your switch from private sector to research in public labs happen?

A: After my post-doctoral studies in United States and seriously considering settling there, I was offered a job with Dr. Reddys Labs. Later, I moved to Advinus Therapeutics (Pune) after which I joined CSIR-National Chemical Laboratory (Pune) as I wanted to pursue my passion for organic chemistry research, taking a huge pay cut. My wife, Vidya Ramdas, has been my co-researcher from UoH days and she continues to work in the pharma field. We have done some great work at NCL and I continue to have my lab with six research students. Soon, I will have a lab here and take in student researchers.

c) What are the areas of research you have been working on?

A: We developed the Silicon-switch approach for developing drug strategies for diseases affecting the central nervous system as most patents do not claim silicon derivatives. This has huge potential in discovering drugs in a short time. Our group has identified a few novel compounds that can protect from vector spreading diseases like dengue or zika virus and also kill the mosquitoes. We have filed a patent and talks are on with a private firm to develop this further for daily use. We have collaborated with different labs including CSIR-CCMB to authenticate the anti-cancer drug for use in Sickle Cell Anaemia.

d) What will be the areas of focus here in IICT?

A: We will be actively involved in the Anti-Virus Mission in association with other CSIR labs studying available molecules and re-purposing of existing anti-viral drugs to deal with SARS-COVID, Monkey Pox and several other viruses. We will soon have a BSL-3 facility here. We are actively assisting pharma and vaccine companies in their research. Our aim is to make the country self-reliant in APIs active pharmaceutical ingredients, KSMs- key starting materials and others with public, private partnerships. I am still trying to understand the various projects here.

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IICT to be involved in anti-virus mission & public, private partnerships for developing APIs - The Hindu

image:Joseph D. Buxbaum, PhD, Director of the Seaver Autism Center for Research and Treatment at Mount Sinai view more

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A new study of genes underlying neurodevelopmental differences has uncovered more than 70 that are very strongly associated with autism and more than 250 with strong links to the condition. The analysis is the largest of its kind to date and includes more than 150,000 participants, 20,000 of whom have been diagnosed with autism.

The results offer the most comprehensive look yet at diverse forms of genetic variation in autism and in more broadly defined neurodevelopmental conditions. The insights shed light on the molecular roots of brain development and neurodiversity, and provide new avenues for future research on the biology of autism.

The findings result from a collaboration involving scientists and datasets from the Autism Sequencing Consortium, the Simons Foundation Powering Autism Research initiative, the Lundbeck Foundation Initiative for Integrative Psychiatric Research, the Population-Based Autism Genetics and Environmental Study, and the Center for Common Disease Genomics at the Broad Institute of the Massachusetts Institute of Technology and Harvard. The work is the culmination of an investment several years ago by these consortia to conduct large-scale genetic analysis for neurodevelopmental conditions and share these datasets on autism.

The new work appears in Nature Genetics, alongside three related studies that use some of the same data to advance the understanding of the genetic basis of autism.

We know that many genes, when mutated, contribute to autism and in this unprecedented study, we were able to bring together multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions. This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment, said co-senior author Joseph D. Buxbaum, PhD, Director of theSeaver Autism Center for Research and Treatmentat Mount Sinai, and Professor of Psychiatry, Neuroscience, and Genetics and Genomic Sciences, at the Icahn School of Medicine at Mount Sinai.

In an analysis led by co-first author Minshi Peng, then a graduate student in the lab of co-senior author Kathryn Roeder, PhD, a professor of statistics and life sciences at Carnegie Mellon University, the scientists examined the expression, or activity levels, of the genes they uncovered in developing human neurons. They learned that genes linked predominantly to developmental delay tend to be active in early neuronal development, whereas autism-related genes tend to play a role in more mature neurons. Furthermore, in an analysis of more than 20,000 samples from individuals with schizophrenia, the researchers found that genes that are strongly associated with autism were also more likely to be associated with genes that increase risk for schizophrenia.

These analyses indicatethat there are shared genetic risk factors between autism and other neurological and psychiatric disorders, Dr. Buxbaum said.

Our discoveries were enabled not only by very large-scale, rich data collections in autism research and population genetic studies, but also by newly developed analysis methods, allowing us to explore the genetic roots of neurodevelopmental variability in new ways. In addition to the massive gene discovery efforts in the field, we are beginning to make inroads into understanding where, when, and how these genes exert their effects during neurodevelopment, said co-senior author Michael Talkowski, PhD, institute member at the Broad and director of the Center for Genomic Medicine at Massachusetts General Hospital.

Based on the study findings, Dr. Buxbaum said a precision medicine approach to autism would benefit patients, as treatments that work for individuals carrying a mutation in one gene may not work in other individuals carrying a mutation in a different gene.

A critical takeaway is that autism has many genetic mutations driving it and thus genetic testing is warranted, not just for the benefit of families and individuals at risk for autism spectrum disorder, but also to drive development of therapeutics, said Dr. Buxbaum. The more we can advance therapeutics, based on the targets identified in these genetic findings, the more people we have the potential to help, which could have a significant impact in addressing autism and developmental delay worldwide.

Additional co-senior authors on the study include Mark Daly, PhD (Broad and Center for Genomic Medicine at Massachusetts General Hospital), Bernie Devlin, PhD (University of Pittsburgh School of Medicine), and Stephan Sanders,PhD (University of California, San Francisco).Additional co-first authors include Harrison Brand, PhD, an assistant professor in neurology at Massachusetts General Hospital and Harvard Medical School; Jack Fu, a postdoctoral fellow in the Talkowski lab; and Kyle Satterstrom, a computational biologist in the Daly lab.

About Mount Sinai Health SystemThe Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, over 400 outpatient practices, over 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.

Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients medical and emotional needs at the center of all treatment.

About Seaver Autism Center for Research and Treatment at Mount SinaiThe Seaver Autism Center for Research and Treatment at Mount Sinai conducts progressive research studies to enhance the diagnosis of autism and related disorders, discover the biological causes of those disorders, and develop and disseminate breakthrough treatments. With a vision to be the international leaders for precision medicine in autism and related disorders, the Center bridges the gap between new discoveries in basic science and enhanced care, while ensuring the community is aware of new and improved approaches to caring for people with autism. The Seaver Autism Center was founded through the generous support of the Beatrice and Samuel A. Seaver Foundation.

For more information, visitwww.seaverautismcenter.org, or find us on Facebook, Twitter and Instagram.

The Autism Sequencing ConsortiumCo-founded by Dr. Buxbaum in 2010, the ASC was first funded by the Beatrice and Samuel A. Seaver Foundation and the Seaver Autism for Research and Treatment at Mount Sinai and subsequently continuously funded by the National Institute of Mental Health for almost a decade. The groups research has gained additional support over the past decade from the Simons Foundation for Autism Research Initiative, the National Human Genome Research Institute, sand the National Institute of Child Health and Human Development.

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Data/statistical analysis

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'Rare coding variation provides insight into the genetic architecture and phenotypic context of autism

18-Aug-2022

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Study of more than 150,000 people identifies - EurekAlert

A rare genetic mutation may help explain why some families are more susceptible to diabetes and kidney failure, according to a new study led by University of Utah health scientists. They say the discovery, made within several generations of the same family, could eventually lead to better treatments for these conditions among a range of patients, whether they have inherited the mutation or not.

In the past, we have seen sporadic cases here and there, but this is the first family to demonstrate that this mutation may be inherited. Marcus Pezolesi, PhD, MPH, corresponding author of the study and U of U Health associate professor of internal medicine in the department of nephrology, says. What is exciting is that treatments are being developed that can improve this condition not only within this family but in the vast spectrum of patients with diabetes at risk of kidney disease.

The study, conducted in collaboration with the Joslin Diabetes Center and Harvard Medical School in Boston, appears in NPJ Genomic Medicine,

Scientists have long known that people who are overweight or obese produce less adiponectin, a hormone that promotes insulin sensitivity, inhibits cell death, and reduces inflammation. As a result, these individuals have a higher risk of developing insulin resistance, type 2 diabetes, kidney disease, and other life-threatening conditions.

To determine whether there may be a genetic cause for diabetic kidney disease, Pezolsi and his colleagues analyzed DNA samples from 14 members of a family collected at the Joslin Diabetes Center. In all, six family members over three generations had diabetes and end-stage kidney disease.

Digging deeper, the researchers used whole-genome sequencing to isolate a defect in a gene called ADIPOQ, which encodes the adiponectin protein. The mutation shortens the gene, disrupting its ability to produce the hormone, which breaks down ceramides, a fatty substance similar to cholesterol. As a result, people with the mutation have higher levels of ceramides. Previous studies suggest that ceramides are a driving force behind the onset of type 2 diabetes and may contribute to diabetic kidney disease.

In laboratory studies of human embryonic kidney cells, researchers found that just one copy of this mutation was able to reduce adiponectin production. Researchers determined that this mutation occurs in about one out of every 57,000 people.

Overall, carriers of the genetic mutation had approximately 85% less adiponectin and 30% higher levels of ceramides circulating in their blood relative to non-carriers within the same family, who were used as a control group.

Whats most exciting to me is that this discovery allows us to confirm decades of research in animals, says William Holland, PhD, study co-corresponding author and U Health Associate Professor of Nutrition and Integrative Medicine. physiology. The biological effects of adiponectin in regulating insulin sensitivity, glucose tolerance and ceramide levels are well established in rats, and the present study demonstrates that loss of adiponectin impairs metabolic health in humans.

Although the study was conducted in the same family, Holland says, its findings could have broad implications for the diagnosis and treatment of these conditions in many people. We can use these findings as a starting point for the development of personalized drugs that mimic the beneficial effects of adiponectin and reduce the risk of diabetes and kidney disease, he says.

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material provided by University of Utah Health, Note: Content can be edited for style and length.

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Detection Of Rare Genetic Mutation In A Family Could Lead To Better Diabetes Treatment - Nation World News

Inflammation. You've no doubt come across this nutrition buzzword. And like a lot of folks, you may not fully understand what it means or why it's such a hot topic. So, before getting into the worst eating habits that cause inflammation and may speed up aging, let's get solid on what inflammation really is.

Whether you're stung by a bee or burn your hand on the stove, your body has an immune response that fends off toxins, pathogens, and infections, causing short-term inflammation in the process.

The dark side of inflammation is when it becomes chronic and simmers in the background, the swelling and heat never abating because your body keeps sending out inflammatory cells to fight even when there's no invader.

This type of long-term, low-grade inflammation can damage tissues and joints. "You may even notice that your skin ages faster when you're constantly inflamed as inflammation can break down collagen and elastin, which are responsible for keeping your skin looking young and supple," says Dr. Rene Armenta, a surgeon with Renew Bariatrics.

Months and years of chronic inflammation may initiate such inflammatory diseases as cardiovascular disease, cancer, type 2 diabetes, kidney disease, autoimmune disorders, and non-alcoholic fatty liver disease, according to research published in Nature Medicine. These inflammatory diseases and disorders are associated with aging.

Eating foods with anti-inflammation properties is part of a two-prong approach to avoiding aging-associated diseases. The other is ditching the following worst types of eating habits that may trigger inflammation and accelerate aging.

This is an unhealthy habit you'll want to break to avoid chronic inflammation. "Fruits like berries and oranges and green leafy vegetables like spinach and kale provide the vitamins, minerals, and antioxidants we need to help keep our immune systems healthy and strong, which is essential especially as you age," says medical review board member Amy Goodson, MS, RD, a registered dietitian and the author of The Sports Nutrition Playbook. "Only 1 in 10 people eat the recommended amounts, which means 90% of us can do a better job."

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The high temperatures needed to fry foods can create harmful compounds called Advanced Glycation End Products (AGEs) that accumulate in the body as we age.

"Foods such as cooked red meat and refined carbohydrates like white bread contain AGEs," says Johna Burdeos, RD, owner of Dietitian Johna. "Consuming too much of these foods can result in cellular damage and inflammation, which can speed up the aging process and increase the risk of insulin resistance and type 2 diabetes. The inflammatory response in the skin is seen in visible signs of weakened skin elasticity, like wrinkles, puffiness, and acne."

RELATED:The 11 Worst Foods Damaging Your Skin, Say Dermatologists

Processed meats like cold cuts, bacon, hot dogs, and junk foods like candy bars, cookies, sugary drinks, potato chips, ice cream, and fast foods are not the healthiest things to eat. Research suggests these ultra-processed foods, the hallmark of what's known as the Western Diet, can disrupt the delicate balance of healthy and unhealthy microbes in the gut or microbiome.

"When processed foods alter the bacteria that live in our gut, this triggers an altered immune response leading to chronic inflammation," says Kathryn Piper, RDN, LD, of The Age-Defying Dietitian. "Diabetes, heart disease, and dementia have been linked to chronic inflammation."

The remedy for an unhealthy microbiome is avoiding ultra-processed foods and making a habit of getting more dietary fiber, ideally 25 to 38 grams per day from foods like whole grains, fruits, vegetables, nuts, seeds, beans, lentils, and legumes, says Goodson.

"Very few people eat enough fiber, but if you want to age gracefully with positive gut health and a healthy cholesterol, fiber is the key," says Goodson. "Make your goal to get 4 to 6 grams of fiber at every meal and snack throughout the day."

Drinking any alcohol may increase inflammation in your body, and excessive alcohol intake definitely increases your risk of chronic low-grade inflammation among other health hazards, says Piper.

"If you drink, limit your consumption to the recommended less than 1 alcoholic beverage per day for women and less than 2 drinks per day for men," she says.

RELATED:The Lifestyle Habits That Slow Down Aging, From a 100-Year-old Neurologist

Gluten is a protein found in wheat and other grains, which means it shows up in bread, pizza crust, pasta, baked goods, and cereals. Although many people digest gluten without issue, people who are sensitive to gluten (a condition called nonceliac gluten sensitivity) experience a different type of immune response that causes an inflammatory effect, according to a 2020 study in Gastroenterology.6254a4d1642c605c54bf1cab17d50f1e

"If someone experiences gut issues, has been diagnosed with an autoimmune disease, or has had unexplained chronic symptoms that put them on the path to an autoimmune disease or another serious diagnosis, then going gluten-free will likely help," says Jenny Levine Finke, a Certified Integrative Nutrition Coach, and author of Dear Gluten, It's Not Me, It's You.

In a 2022 study published in Nutrition Reviews, researchers found that a gluten-free diet can "ameliorate" autoimmune-related symptoms in 64.7% of those with a nonceliac autoimmune disease. For clues to where you stand with gluten, ask your doctor or dietitian to know what's good for you as an individual.

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6 Worst Eating Habits Causing Inflammation and Aging You Faster - Eat This, Not That