Environmental Factors as Diabetic Mediators–A Mechanistic Approach

Abstract: Despite substantial investment in research and treatment options, diabetes mellitus remains a pressing public health concern with potential epidemic proportions globally. There are reports that by the end of 2040, 642 million people will be suffering from diabetes. Also, according to an estimation, 1.6 million deaths were caused directly by diabetes in 2016. Diabetes is a metabolic disorder characterized by impaired glucose regulation in the body due to the destruction of pancreatic β-cells or insulin resistance. Genetic propensity, unhealthy and imbalanced diet, obesity and increasing urbanization are the common risk factors for diabetes. Besides this, it has been reported that environmental pollutants like organic pesticides, heavy metals, and air pollutants act as strong predisposing factors for diabetes owing to their highly bio-accumulative nature. These pollutants disturb glucose homeostasis either by up-regulating or down-regulating the expression of diabetic marker genes like insulin (INS), glucokinase (GCK). Unfortunately, the molecular mechanism about the role of pollutants in causing diabetes is not very clear. This mechanistic review provides evidence of different environmental determinants including persistent organic pollutants (POPs), air pollutants, toxic metals, etc. in inducing diabetes and proposes a framework for the possible mechanisms involved. It also illuminates the current status and future challenges which will not only broaden our understanding but can also be a reasonable platform for further investigation.

Download Full-text

Clostridial Spores for Cancer Therapy: Targeting Solid Tumour Microenvironment

Journal of Toxicology ◽

10.1155/2012/862764 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 14

Author(s):

Brittany Umer ◽

David Good ◽

Jozef Anné ◽

Wei Duan ◽

Ming Q. Wei

Keyword(s):

Cancer Therapy ◽

Solid Tumour ◽

Early Stage ◽

Treatment Options ◽

Anaerobic Bacteria ◽

Past Research ◽

Tumour Microenvironment ◽

The Body ◽

Solid Tumours ◽

Current Status

Solid tumour accounts for 90% of all cancers. The current treatment approach for most solid tumours is surgery, however it is limited to early stage tumours. Other treatment options such as chemotherapy and radiotherapy are non-selective, thus causing damage to both healthy and cancerous tissue. Past research has focused on understanding tumour cells themselves, and conventional wisdom has aimed at targeting these cells directly. Recent research has shifted towards understanding the tumour microenvironment and it’s differences from that of healthy cells/tissues in the body and then to exploit these differences for treatmeat of the tumour. One such approach is utilizing anaerobic bacteria. Several strains of bacteria have been shown to selectively colonize in solid tumours, making them valuable tools for selective tumour targeting and destruction. Amongst them, the anaerobicClostridiumhas shown great potential in penetration and colonization of the hypoxic and necrotic areas of the tumour microenvironment, causing significant oncolysis as well as enabling the delivery of therapeutics directly to the tumourin situ. Various strategies utilizingClostridiumare currently being investigated, and represent a novel area of emerging cancer therapy. This review provides an update review of tumour microenvironment as well as summary of the progresses and current status of Clostridial spore-based cancer therapies.

Download Full-text

Excretion of Heavy Metals and Glyphosate in Urine and Hair Before and After Long-Term Fasting in Humans

Frontiers in Nutrition ◽

10.3389/fnut.2021.708069 ◽

2021 ◽

Vol 8 ◽

Author(s):

Franziska Grundler ◽

Gilles-Eric Séralini ◽

Robin Mesnage ◽

Vincent Peynet ◽

Françoise Wilhelmi de Toledo

Keyword(s):

Heavy Metals ◽

Environmental Pollutants ◽

Dietary Exposure ◽

The Body ◽

Health Concern ◽

Obese People ◽

Clinical Trial Registration ◽

Reduced Body ◽

Before And After

Background: Dietary exposure to environmental pollutants in humans is an important public health concern. While long-term fasting interrupts the dietary exposure to these substances, fat mobilization as an energy source may also release bioaccumulated substances. This was, to our knowledge, only investigated in obese people decades ago. This study explored the effects of 10-days fasting on the excretion of heavy metals and glyphosate.Methods: Urinary levels of arsenic, chromium, cobalt, lead, nickel, mercury and glyphosate were measured before and after 10 fasting days in 109 healthy subjects. Additionally, hair analysis was done before and ten weeks after fasting in 22 subjects.Results: Fasting caused a decrease in body weight, and in urinary arsenic (by 72%) and nickel (by 15%) concentrations. A decrease in lead hair concentrations (by 30%) was documented. Urinary mercury levels were unchanged for chromium, cobalt and glyphosate, which were undetectable in most of the subjects. Additionally, fatigue, sleep disorders, headache and hunger were reduced. Body discomfort symptoms diminished four weeks after food reintroduction.Conclusions: The results of this study provide the first insights into the changes in heavy metal excretion caused by long-term fasting. Further studies focusing on the kinetics of efflux between different compartments of the body are needed.Clinical Trial Registration:https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016657, identifier: DRKS00016657.

Download Full-text

An Overview of Dementias

Perspectives on Swallowing and Swallowing Disorders (Dysphagia) ◽

10.1044/sasd21.3.75 ◽

2012 ◽

Vol 21 (3) ◽

pp. 75-84

Author(s):

Venkata Vijaya K. Dalai ◽

Jason E. Childress ◽

Paul E Schulz

Keyword(s):

Clinical Presentation ◽

Treatment Options ◽

Current Treatment ◽

Great Variability ◽

Health Concern ◽

Public Health Concern ◽

Life Threatening ◽

The Common ◽

Neurodegenerative Dementias ◽

Made In

Dementia is a major public health concern that afflicts an estimated 24.3 million people worldwide. Great strides are being made in order to better diagnose, prevent, and treat these disorders. Dementia is associated with multiple complications, some of which can be life-threatening, such as dysphagia. There is great variability between dementias in terms of when dysphagia and other swallowing disorders occur. In order to prepare the reader for the other articles in this publication discussing swallowing issues in depth, the authors of this article will provide a brief overview of the prevalence, risk factors, pathogenesis, clinical presentation, diagnosis, current treatment options, and implications for eating for the common forms of neurodegenerative dementias.

Download Full-text

Novel Approaches for Oral Delivery of Insulin and Current Status of Oral Insulin Products

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2010.3.3.3 ◽

2010 ◽

Vol 3 (3) ◽

pp. 1057-1064 ◽

Cited By ~ 2

Author(s):

Kinesh V P ◽

Neelam D P ◽

Punit B ◽

Bhavesh S.B ◽

Pragna K. S

Keyword(s):

Diabetes Mellitus ◽

Oral Delivery ◽

Proteolytic Enzymes ◽

Oral Route ◽

The Body ◽

Current Status ◽

Intestinal Lumen ◽

Insulin Administration ◽

Novel Approaches ◽

Dose Dependent

Diabetes mellitus is a serious pathologic condition that is responsible for major healthcare problems worldwide and costing billions of dollars annually. Insulin replacement therapy has been used in the clinical management of diabetes mellitus for more than 84 years. The present mode of insulin administration is by the subcutaneous route through which insulin is presented to the body in a non-physiological manner having many challenges. Hence novel approaches for insulin delivery are being explored. Challenges to oral route of insulin administration are: rapid enzymatic degradation in the stomach, inactivation and digestion by proteolytic enzymes in the intestinal lumen and poor permeability across intestinal epithelium because of its high molecular weight and lack of lipophilicity. Liposomes, microemulsions, nanocubicles, and so forth have been prepared for the oral delivery of insulin. Chitosan-coated microparticles protected insulin from the gastric environment of the body and released intestinal pH. Limitations to the delivery of insulin have not resulted in fruitful results to date and there is still a need to prepare newer delivery systems, which can produce dose-dependent and reproducible effects, in addition to increased bioavailability.

Download Full-text

Immunotherapy and potential predictive biomarkers in the treatment of neuroendocrine neoplasia

Future Oncology ◽

10.2217/fon-2020-0703 ◽

2020 ◽

Author(s):

Guanghui Xu ◽

Yuhao Wang ◽

Hushan Zhang ◽

Xueke She ◽

Jianjun Yang

Keyword(s):

Current Knowledge ◽

Checkpoint Inhibitors ◽

Treatment Options ◽

Predictive Biomarkers ◽

The Body ◽

Low Grade ◽

Ablative Therapies ◽

Cancer Types ◽

New Treatment ◽

Well Differentiated

Neuroendocrine neoplasias (NENs) are a heterogeneous group of rare tumors scattered throughout the body. Surgery, locoregional or ablative therapies as well as maintenance treatments are applied in well-differentiated, low-grade NENs, whereas cytotoxic chemotherapy is usually applied in high-grade neuroendocrine carcinomas. However, treatment options for patients with advanced or metastatic NENs are limited. Immunotherapy has provided new treatment approaches for many cancer types, including neuroendocrine tumors, but predictive biomarkers of immune checkpoint inhibitors (ICIs) in the treatment of NENs have not been fully reported. By reviewing the literature and international congress abstracts, we summarize the current knowledge of ICIs, potential predicative biomarkers in the treatment of NENs, implications and efficacy of ICIs as well as biomarkers for NENs of gastroenteropancreatic system, lung NENs and Merkel cell carcinoma in clinical practice.

Download Full-text

PSIX-33 Docosahexaenoic Acid (DHA) but not Eicosapentaenoic Acid (EPA) induces the trans-differentiation of C2C12 into white-like adipocytes phenotype

Journal of Animal Science ◽

10.1093/jas/skaa278.552 ◽

2020 ◽

Vol 98 (Supplement_4) ◽

pp. 309-310

Author(s):

Yan Huang ◽

Saeed Ghnaimawi ◽

Yongjie Wang ◽

Shilei Zhang ◽

Jamie Baum

Keyword(s):

Mitochondrial Biogenesis ◽

Cultured Cells ◽

Adipogenic Differentiation ◽

The Body ◽

C2c12 Cells ◽

Brown Adipocyte ◽

Marker Genes ◽

Induction Medium ◽

Spare Capacity ◽

Epa And Dha

Abstract Muscle-derived stem cells (MDSCs, or myoblasts) play an important role in myotubes regeneration. However, these cells can differentiate into adipocytes once exposed to EPA and DHA, which are highly suggested during pregnancy. The objective of this study aims at determining the effect of isolated EPA and DHA on C2C12 cells undergoing white and brown adipogenic differentiation. Confluent cultured cells were treated with white and brown adipocyte induction medium (WIM and BIM respectively) with 50µM EPA and 50µM DHA separately. DHA treated groups differentiated into white-like adipocyte by down-regulating the expression of myogenic genes such as MyoD, MyoG, and Mrf4; but promoted white adipocyte marker genes(P < 0.05). Moreover, cells treated with WIM and DHA exhibited a decrease in mitochondrial biogenesis through suppressing PGC1a and TFAM expression (P < 0.05). Also, DHA promoted the expression of lipolysis regulating genes. DHA impaired C2C12 cells browning through reducing the mitochondrial biogenesis by significantly suppressing the expression of COX7a1, PGC1a, and UCP3 genes (P < 0.05). DHA treated groups showed an increased accumulation of lipid droplets and suppressed maximal mitochondrial respiration and spare capacity. EPA treatment reduced myogenesis regulating genes (P < 0.05) but did not affect adipogenic genes (P >0.05). Likewise, EPA suppressed the expression of WAT signature genes (P < 0.05), indicating its antagonism to DHA. EPA and WIM treatment suppressed the expression of TFAM and PGC1a, but did not affect PGC1a protein level. Although mitochondrial biogenic gene expression was reduced in EPA and BIDM treated group, no changes in mitochondrial function were observed. EPA supplementation did not affect the differential route of C2C12 into brown adipocytes. To conclude, EPA and DHA may similarly affect the integrity of muscle tissue, but DHA is a potent adipogenic and lipogenic factor that can change the metabolic profile of the body by increasing intramuscular fat.

Download Full-text

Technologies for Water Reuse: Current Status and Future Challenges

Water ◽

10.3390/w13060832 ◽

2021 ◽

Vol 13 (6) ◽

pp. 832

Author(s):

Mauro Capocelli ◽

Vincenzo Piemonte

Keyword(s):

Sustainable Development ◽

Water Reuse ◽

Food Production ◽

Current Status ◽

The Sustainable Development ◽

Future Challenges

Water is fundamental for the quality of both ecosystems and society, and plays a key role for energy and food production, a prerequisite for the sustainable development [...]

Download Full-text

Pharmacotherapy of 1,044 inpatients with posttraumatic stress disorder: current status and trends in German-speaking countries

European Archives of Psychiatry and Clinical Neuroscience ◽

10.1007/s00406-020-01223-x ◽

2020 ◽

Author(s):

Matthias A. Reinhard ◽

Johanna Seifert ◽

Timo Greiner ◽

Sermin Toto ◽

Stefan Bleich ◽

...

Keyword(s):

Posttraumatic Stress Disorder ◽

Posttraumatic Stress ◽

Stress Disorder ◽

Treatment Options ◽

Psychiatric Inpatient ◽

Primary Diagnosis ◽

Current Status ◽

German Speaking ◽

Inpatient Settings ◽

Prescription Rates

AbstractPosttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder with limited approved pharmacological treatment options and high symptom burden. Therefore, real-life prescription patterns may differ from guideline recommendations, especially in psychiatric inpatient settings. The European Drug Safety Program in Psychiatry (“Arzneimittelsicherheit in der Psychiatrie”, AMSP) collects inpatients’ prescription rates cross-sectionally twice a year in German-speaking psychiatric hospitals. For this study, the AMSP database was screened for psychiatric inpatients with a primary diagnosis of PTSD between 2001 and 2017. N = 1,044 patients with a primary diagnosis of PTSD were identified with 89.9% taking psychotropics. The average prescription rate was 2.4 (standard deviation: 1.5) psychotropics per patient with high rates of antidepressant drugs (72.0%), antipsychotics drugs (58.4%) and tranquilizing drugs (29.3%). The presence of psychiatric comorbidities was associated with higher rates of psychotropic drug use. The most often prescribed substances were quetiapine (24.1% of all patients), lorazepam (18.1%) and mirtazapine (15.0%). The use of drugs approved for PTSD was low (sertraline 11.1%; paroxetine 3.7%). Prescription rates of second-generation antipsychotic drugs increased, while the use of tranquilizing drugs declined over the years. High prescription rates and extensive use of sedative medication suggest a symptom-driven prescription (e.g., hyperarousal, insomnia) that can only be explained to a minor extent by existing comorbidities. The observed discrepancy with existing guidelines underlines the need for effective pharmacological and psychological treatment options in psychiatric inpatient settings.

Download Full-text