Coadministration of Melatonin and Insulin Improves Diabetes-Induced Impairment of Rat Kidney Function.

INTRODUCTION: The present study was designed to evaluate the therapeutic efficacy of melatonin and insulin coadministration in diabetes-induced renal injury in rats. RESEARCH DESIGN AND METHODS: Diabetes was achieved by giving streptozotocin (15 mg/kg) for 6 consecutive days. The diabetic condition was confirmed by assessing the blood glucose level; animals having blood glucose levels above 250 mg were considered as diabetic. Following the confirmation, animals were randomly divided into different experimental groups, viz group I served as the control (CON), group II diabetic (D), group III D+melatonin (MEL), group IV D+insulin (INS), group V D+MEL+INS, group VI D+glibenclamide (GB), group VII CON+MEL, group VIII CON+INS, and group IX CON+GB. Following the completion of the experimental period, animals were sacrificed, blood was collected via a retro-orbital puncture, and kidneys were harvested. Diabetic rats exhibited a significant increment in blood glucose and biochemical indexes of renal injury (tubular disruption, swollen glomeruli with loss of glomerular spaces, and distortion of the endothelial lining) including augmented levels of serum creatinine, urea, uric acid, Na+, and K+, and inhibition/suppression of the activity of glutathione (GSH) peroxidase, GSH reductase, glucose-6-phosphate dehydrogenase, and GSH-S-transferase in the renal cortex. RESULTS: By examining thiobarbiturate reactive substances, reduced GSH, superoxide dismutase activity, and catalase activity in the renal cortex of control and diabetic rats, it was documented that treatment with melatonin or insulin alone or in combination showed a significant ad integrum recovery of GSH-dependent antioxidative enzymatic activities. Melatonin and insulin coadministration caused greater reductions in circulating tumor necrosis factor-α, tumor growth factor-ß1, interleukin (IL)-1ß, and IL-6 levels in diabetic rats, whereas IL-10 levels increased, as compared to each treatment alone. Diabetic rats showed a significant increase in the expression of both MT1 and MT2 melatonin receptor genes. Melatonin or insulin treatment alone or in combination resulted in significant restoration of the relative expression of both melatonin receptors in the renal cortex. CONCLUSION: The coadministration of exogenous melatonin and insulin abolished many of the deleterious effects of type 1 diabetes on rat renal function.

CRISPR/Cas9 system: a reliable and facile genome editing tool in modern biology.

Genome engineering has always been a versatile technique in biological research and medicine, with several applications. In the last several years, the discovery of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 technology has swept the scientific community and revolutionised the speed of modern biology, heralding a new era of disease detection and rapid biotechnology discoveries. It enables successful gene editing by producing targeted double-strand breaks in virtually any organism or cell type. So, this review presents a comprehensive knowledge about the mechanism and structure of Cas9-mediated RNA-guided DNA targeting and cleavage. In addition, genome editing via CRISPR-Cas9 technology in various animals which are being used as models in scientific research including Non-Human Primates Pigs, Dogs, Zebra, fish and Drosophila has been discussed in this review. This review also aims to understand the applications, serious concerns and future perspective of CRISPR/Cas9-mediated genome editing.

Honey infused with herbs: A boon to cure pathological diseases.

Healing with herbs has been a common practice for ages. Nowadays, various infectious diseases like malaria, flu, hepatitis B; COVID-19, etc. are commonly spreading around the world as a consequence of environmental pollution and related consequences. These diseases are not well controlled by the present drug treatment. Antibiotics are failing because of bacterial resistance. Although people believe that herbal medicines are more effective and safer. Therefore, traditional herbal remedies have been recommended for treatment purposes throughout the world. They are often used in combination, fused with honey, or alone for curing different types of ailments. Today, modern formulations of these medicines exist in the form of capsules, tablets, powders, and granules. In several traditional systems, 'Honey' is recommended as a natural medicine that improves several health conditions. In 'Ayurveda', honey is considered a most precious and miraculous product of nature and is used to treat various diseases either alone or after its infusion with herbs. It is a natural, antioxidant-rich, and highly nutritious food that is widely used as a natural sweetener without any side effects. It has antibacterial, antiviral, antifungal, and antioxidant properties. It also proves fruitful in managing/curing various disorders like colds, coughs, cancer, diabetes, wound healing, and cardiovascular disorders. Honey infused with herbs is also used to repair wounds, diabetes, lymphedema, and the prevention of chronic venomous diseases as a part of the folk medicinal system. The current article aims to analyse the medicinal efficiency of honey infused with herbs for curing/managing/treating various types of ailments.

Arsenic toxicity: sources, pathophysiology and mechanism.

Background: Arsenic is a naturally occurring element that poses a significant threat to human health due to its widespread presence in the environment, affecting millions worldwide. Sources of arsenic exposure are diverse, stemming from mining activities, manufacturing processes, and natural geological formations. Arsenic manifests in both organic and inorganic forms, with trivalent meta-arsenite (As3+) and pentavalent arsenate (As5+) being the most common inorganic forms. The trivalent state, in particular, holds toxicological significance due to its potent interactions with sulfur-containing proteins. Objective: The primary objective of this review is to consolidate current knowledge on arsenic toxicity, addressing its sources, chemical forms, and the diverse pathways through which it affects human health. It also focuses on the impact of arsenic toxicity on various organs and systems, as well as potential molecular and cellular mechanisms involved in arsenic-induced pathogenesis. Methods: A systematic literature review was conducted, encompassing studies from diverse fields such as environmental science, toxicology, and epidemiology. Key databases like PubMed, Scopus, Google Scholar, and Science Direct were searched using predetermined criteria to select relevant articles, with a focus on recent research and comprehensive reviews to unravel the toxicological manifestations of arsenic, employing various animal models to discern the underlying mechanisms of arsenic toxicity. Results: The review outlines the multifaceted aspects of arsenic toxicity, including its association with chronic diseases such as cancer, cardiovascular disorders, and neurotoxicity. The emphasis is placed on elucidating the role of oxidative stress, genotoxicity, and epigenetic modifications in arsenic-induced cellular damage. Additionally, the impact of arsenic on vulnerable populations and potential interventions are discussed. Conclusions: Arsenic toxicity represents a complex and pervasive public health issue with far-reaching implications. Understanding the diverse pathways through which arsenic exerts its toxic effects is crucial to developing effective mitigation strategies and interventions. Further research is needed to fill gaps in our understanding of arsenic toxicity and to inform public health policies aimed at minimising exposure.Arsenic toxicity is a crucial public health problem influencing millions of people around the world. The possible sources of arsenic toxicity includes mining, manufacturing processes and natural geological sources. Arsenic exists in organic as well as in inorganic forms. Trivalent meta-arsenite (As3+) and pentavalent arsenate (As5+) are two most common inorganic forms of arsenic. Trivalent oxidation state is toxicologically more potent due to its potential to interact with sulfur containing proteins. Humans are exposed to arsenic in many ways such as environment and consumption of arsenic containing foods. Drinking of arsenic-contaminated groundwater is an unavoidable source of poisoning, especially in India, Bangladesh, China, and some Central and South American countries. Plenty of research has been carried out on toxicological manifestation of arsenic in different animal models to identify the actual mechanism of aresenic toxicity. Therefore, we have made an effort to summarize the toxicology of arsenic, its pathophysiological impacts on various organs and its molecular mechanism of action.

Melatonin: a modulator in metabolic rewiring in T-cell malignancies.

Melatonin, (N-acetyl-5-methoxytryptamine) an indoleamine exerts multifaced effects and regulates numerous cellular pathways and molecular targets associated with circadian rhythm, immune modulation, and seasonal reproduction including metabolic rewiring during T cell malignancy. T-cell malignancies encompass a group of hematological cancers characterized by the uncontrolled growth and proliferation of malignant T-cells. These cancer cells exhibit a distinct metabolic adaptation, a hallmark of cancer in general, as they rewire their metabolic pathways to meet the heightened energy requirements and biosynthesis necessary for malignancies is the Warburg effect, characterized by a shift towards glycolysis, even when oxygen is available. In addition, T-cell malignancies cause metabolic shift by inhibiting the enzyme pyruvate Dehydrogenase Kinase (PDK) which in turn results in increased acetyl CoA enzyme production and cellular glycolytic activity. Further, melatonin plays a modulatory role in the expression of essential transporters (Glut1, Glut2) responsible for nutrient uptake and metabolic rewiring, such as glucose and amino acid transporters in T-cells. This modulation significantly impacts the metabolic profile of T-cells, consequently affecting their differentiation. Furthermore, melatonin has been found to regulate the expression of critical signaling molecules involved in T-cell activations, such as CD38, and CD69. These molecules are integral to T-cell adhesion, signaling, and activation. This review aims to provide insights into the mechanism of melatonin's anticancer properties concerning metabolic rewiring during T-cell malignancy. The present review encompasses the involvement of oncogenic factors, the tumor microenvironment and metabolic alteration, hallmarks, metabolic reprogramming, and the anti-oncogenic/oncostatic impact of melatonin on various cancer cells.

Management of stored grain pest with special reference to Callosobruchus maculatus, a major pest of cowpea: A review.

Bruchids are most pernicious pest of stored grain pulses, especially in the tropical and subtropical areas. They penetrate into the fully grown matured pods, grains in fields and also during post-harvest storage. Among bruchids, Callosobruchus maculatus is the prominent pest having ubiquitous distribution. Chemical/synthetic insecticides provides adequate control against the C. maculatus on the pulses. However, the use of synthetic insecticides induces adverse health outcomes in agricultural workers and many causes various diseases such as cancers, genomic damage, oxidative stress, neurological disorders and respiratory, metabolic and thyroid effects. Therefore, alternative effective, safe and sustainable pest control, integration of different compatible methods should be taken into considerations. One of the possible managements might be use of traditional as well modern pest management practices. Traditional techniques include sealed containers, inert materials, harvesting time, alternate host, intercropping, storing un-threshed pulses, cleanliness, vegetable oil etc. Modern techniques such as temperature, freezing and heating, radiation treatments, resistance varieties, natural control, botanical extracts, chemical and microbial, transgenic approach, cold plasma treatments etc. thus integrated pest management might be alternative approach to combat the effect of pest. Therefore, present review aims to considers various measures for the handling of bruchids with special reference to Callosobruchus maculatus and integrated molecular inventions to decrease bruchids populations and enhance pulse productivity in pulses.

Mechanisms and treatment strategies of organophosphate pesticide induced neurotoxicity in humans: A critical appraisal.

Organophosphates (OPs) are commonly used pesticides worldwide. Humans are exposed to OPs via different routes viz., the respiratory tract, gastrointestinal tract, and dermal integuments. OPs induce neuropathy by either phosphorylating acetyl cholinesterase or neuropathy target esterase, or by binding specifically to nicotinic or muscarinic receptors of nervous system. Other than neurobehavioral effects in humans, OPs cause cholinergic crisis, intermediate syndrome, OP-induced delayed neuropathy, and Chronic organophosphate-induced neuropsychiatric disorders in time and dosage dependent manner. Biomonitoring of OP markers from body fluids minimizes or measures the severity of the impact, allowing for timely control of the exposure. The standard treatments for OPs poisoning which avoid secondary organ damage are atropine administration, acetylcholine esterase restoration therapy with oximes, and general intensive care. This review summarizes the toxic manifestation data available on humans and discusses potential therapeutic modalities, with the aim to highlight the importance of increasing awareness about its potential risk and reevaluation of exposure level.

Oxidative Stress in Human Pathology and Aging: Molecular Mechanisms and Perspectives.

Reactive oxygen and nitrogen species (RONS) are generated through various endogenous and exogenous processes; however, they are neutralized by enzymatic and non-enzymatic antioxidants. An imbalance between the generation and neutralization of oxidants results in the progression to oxidative stress (OS), which in turn gives rise to various diseases, disorders and aging. The characteristics of aging include the progressive loss of function in tissues and organs. The theory of aging explains that age-related functional losses are due to accumulation of reactive oxygen species (ROS), their subsequent damages and tissue deformities. Moreover, the diseases and disorders caused by OS include cardiovascular diseases [CVDs], chronic obstructive pulmonary disease, chronic kidney disease, neurodegenerative diseases and cancer. OS, induced by ROS, is neutralized by different enzymatic and non-enzymatic antioxidants and prevents cells, tissues and organs from damage. However, prolonged OS decreases the content of antioxidant status of cells by reducing the activities of reductants and antioxidative enzymes and gives rise to different pathological conditions. Therefore, the aim of the present review is to discuss the mechanism of ROS-induced OS signaling and their age-associated complications mediated through their toxic manifestations in order to devise effective preventive and curative natural therapeutic remedies.

Honeybee nutrition and pollen substitutes: A review.

Like other invertebrates, honey bees too are poikilothermic animals; they cannot regulate their body temperature and they have to undergo a period of inactivation when atmospheric temperature is un-tolerable. During this period, their nutritional requirements and metabolic activities are minimized due to highly restricted foraging activities. The egg-laying by queen and rearing of unsealed and sealed brood are decreased, however their extent is governed by the quantum of stored food available. The problems of deleterious influence of adverse weather conditions and non-availability of bee flora all round the year, in a particular locality, have been realized by the researchers/beekeepers and migration concept has been developed to solve this problem. But again, migration itself is not an easy task. The provision of artificial feeding as an alternate of migration. Scientists all over the world have formulated different artificial food recepies for bees on the basis of nutrient composition of honey and pollen, acceptability, palatability, digestibility and affordability of ingredients. This may help to maintain all colony parameters enough to derive maximum advantage of forthcoming floral rich season. However, a standard balanced diet for commercial beekeeping that is accepted worldwide is still awaited.

Melatonin supplementation revives diabetic induced biochemical, histological and hematological impairments in rats.

Diabetes is very common all over the world, but still not curable and controlled; it causes alteration in all over body. It needs serious concern for the scientific community to find out some control measures. The current work was planned to explore the possible defensive effect of melatonin against the diabetes induced changes in whole blood profile. For this study albino rats were treated with streptozotocin [(STZ) (15 mg/kg for 6 days)] to induce diabetes. Induction was confirmed by blood glucose and serum sugar assessment. Total 36 rats were randomly selected for the experimental purpose and were divided into two major groups. Major group-1 consisting eighteen (18) and were further sub-divided into three (3) different groups viz. group-I served as normal control, group-II served as melatonin treated, group-III served as glibenclamide treated. Major group-2 consisting eighteen (18) rats were given streptozotocin (STZ) injection (15 mg/kg) for 6 days. After confirmation of diabetes by measuring blood glucose level, animals having blood glucose level above 250 mg/dl) confirmed as diabetic. Eighteen (18) Diabetic rats were three subdivided into following sub-groups and were given different therapeutic treatments, Viz group-IV served as Diabetic control, group-V treated with melatonin, group-VI treated with glibenclamide, respectively. Diabetic rats demonstrated inflection in all hematological variables. Diabetic animals revealed considerable reduction in RBCs count, HB content and its associated indices (HCT, RDW, MCV, MCH and MCHC). Decrease in WBCs and its related indices (polymorphs and lymphocytes). Platelet count showed significant increase, but platelet distribution width (PDW %) was found decreased. However administration of melatonin restored all the alterations in hematological parameters. Therefore, it can be concluded that melatonin will be better therapeutic molecule to revive hematological alterations during diabetes.

Combined administration of exogenous melatonin and insulin ameliorates streptozotocin induced toxic alteration on hematological parameters in diabetic male Wistar rats.

The aim of the present was to ameliorate the protective effect of exogenous melatonin and insulin against the diabetes induced alterations in the different hematological variables. Albino rats were administrated streptozotocin at the dose of 15 mg/kg for 6 days. Total 54 rats were randomly selected for the experimental purpose and were divided into two major groups. Group-1 consisting twenty four (24) and were further sub-divided into four (4) different groups viz. group-I served as normal control, group-II served as melatonin treated, group-III served as insulin treated and group-IV served as glibenclamide treated. Group-2 consisting thirty (30) rats were given streptozotocin (STZ) injection (15 mg/kg) for 6 days. After confirmation of diabetes by measuring blood glucose level, animals having blood glucose level above 250 mg/dl) confirmed as diabetic. Thirty (30) Diabetic rats were further subdivided into following sub-groups and were given different therapeutic treatments, Viz group-I served as Diabetic control, group-II treated with melatonin, group-III treated with insulin, group-IV given treatment of melatonin and insulin and group-V were given treatment of glibenclamide respectively. Diabetic rats showed modulation in all the studied hematological variables. Diabetic rats displayed significant decline in RBCs count, HB level and its associated indices (HCT, RDW, MCV, MCH, MCHC), WBCs and its related indices (polymorphs and lymphocytes) and platelet distribution width (PDW %) whereas platelet count showed significant increase. Nonetheless alone as well as combined treatment of exogenous melatonin and insulin restored all altered hematological parameters. However, significant recovery was found in the group in which combined dose of melatonin and insulin was administrated. Therefore, it might be concluded that combined administration of melatonin and insulin will be better remedy to normalize the altered blood profile during the diabetic condition.

Melatonin and insulin modulates the cellular biochemistry, histoarchitecture and receptor expression during hepatic injury in diabetic rats.

Aims; The present study was designed to ameliorate the integrated efficacy of exogenous melatonin and insulin on tissue biochemical, serological, histopathological architecture and receptor expression of melatonin (MT1, MT2) and insulin receptor (IR) expression against the hepatic injury in diabetic rats. Materials and Method; the rats were randomly allocated into nine different experimental groups. Diabetes was induced by streptozotocin (15 mg/kg) for 6 days. Rats having blood glucose level above 250 mg/dl were considered as diabetic. Animals euthanized after 4 weeks, blood and liver samples were collected to perform various biochemical, serological, histopathological and receptor expression of melatonin (MT1, MT2) and insulin receptor (IR). Key findings; Diabetic rats revealed significant increase in lipid peroxidation (LPO) of liver tissue, liver function tests (ALT, AST and ALP), increase in serum cholesterol, LDL, VLD, but decrease in HDL level. Further, diabetic rats exhibited significant decrement in antioxidative enzymatic system (GSH, SOD, CAT, GR, GPX, G6PDH and GST), total tissue protein and glycogen content. Histomicrograph of liver of diabetic rats resulted in vacuolization indicating cellular damages as well as upregulation in liver MT1, MT2 and IR protein expression. However, the combined therapy (Melatonin and insulin treatment) revealed significant recovery and restoration in biochemical, cellular architecture of liver cells and receptor expression pattern of MT1, MT2 and IR. Significance; It may establish a synergistic action of melatonin and insulin, which might be a novel evidence for clinicians to combat the hepatic complication along with controlling diabetes.