Type 2 diabetes mellitus (T2DM) is a prevalent chronic condition, accounting for over 90% of diabetes cases globally, characterized by insulin resistance and chronic hyperglycemia. Beyond metabolic dysfunction, T2DM is associated with significant immune system alterations, including impaired macrophage, neutrophil, and natural killer cell functions. These immune dysfunctions contribute to increased susceptibility to infections, inflammation, and complications in diabetic individuals. Chronic hyperglycemia triggers an inflammatory response that weakens the body's immune defenses, further complicating disease management. This review delves into the intricate interplay between T2DM and the immune system, emphasizing how immune cell dysfunction exacerbates insulin resistance and impacts infection control. It also explores the role of pro-inflammatory markers and cellular responses in T2DM pathophysiology. Additionally, the article examines innovative strategies for managing T2DM, such as personalized medicine, telemedicine, and artificial intelligence. Personalized medicine tailors treatment to individual genetic, environmental, and lifestyle factors, while telemedicine facilitates remote monitoring and care. Artificial intelligence aids in early detection, personalized treatment plans, and enhanced patient management. By addressing both immune system alterations and advanced management strategies, this article provides a comprehensive understanding of T2DM and advocates for a more integrated approach to improve outcomes and patient care.

Herein, a novel series of natural product alkaloid 'Cephalandole A' analogues 19a -y, and 20a -d were rapidly synthesised under microwave irradiation conditions using PTSA in catalytic amount dissolved in acetonitrile at 90 degrees C for 15 min. The developed one-pot protocol is operationally simple, rapid (15 min) and furnished the target analogues in up to 90 % yield. All the synthesised analogues of Cephalandole A were evaluated for their in vitro antioxidant activity using DPPH free-radical scavenging and FRAP assays. The in vitro studies of DPPH radical scavenging assay provided 19a (IC50 = 11.87 +/- 0.14 mu g/mL), 19f (IC50 = 16.34 +/- 0.27 mu g/mL), 19n (IC50 = 15.37 +/- 0.11 mu g/mL) and 20a (IC50 = 14.54 +/- 0.31 mu g/mL) respectively, as the most active compounds of the series. In addition, the analogous 19d (556.3 +/- 13.1 mu M) and 19v (551.9 +/- 14.2 mu M) showed promising activity in FRAP assay. However, the standard reference drug ascorbic acid showed an IC50 value of 4.57 mu g/mL in the DPPH assay, and BHT showed C-0.5FRAP = 546.0 +/- 13.6 mu M in the FRAP assay. In silico studies were performed to validate the wet results. To the best of our knowledge, this is the first report demonstrating 'Cephalandole A' analogues as a new class of antioxidant agents.

Genetic control is vital for the growth of cells and tissues, and it also helps living things, from single-celled organisms to complex creatures, maintain a stable internal environment. Within cells, structures called mitochondria act like tiny power plants, producing energy and keeping the cell balanced. The two primary categories of RNA are messenger RNA (mRNA) and non-coding RNA (ncRNA). mRNA carries the instructions for building proteins, while ncRNA does various jobs at the RNA level. There are different kinds of ncRNA, each with a specific role. Some help put RNA molecules together correctly, while others modify other RNAs or cut them into smaller pieces. Still others control how much protein is made from a gene. Scientists have recently discovered many more ncRNAs than previously known, and their functions are still being explored. This article analyzes the RNA molecules present within mitochondria, which have a crucial purpose in the operation of mitochondria. We’ll also discuss how genes can be turned on and off without changing their DNA code, and how this process might be linked to mitochondrial RNA. Finally, we’ll explore how scientists are using engineered particles to silence genes and develop new treatments based on manipulating ncRNA.

Background:The most frequent lesion in the blood vessels feeding the myocardium is vascular stenosis, a condition that develops slowly but can prove to be deadly in a long run. Non-invasive biomarkers could play a significant role in timely diagnosis, detection and management for vascular stenosis events associated with cardiovascular disorders.Aims:The study aimed to investigate high sensitivity troponin I (hs-TnI), cardiac troponin I (c-TnI) and high sensitivity C-reactive protein (hs-CRP) that may be used solely or in combination in detecting the extent of vascular stenosis in CVD patients.Methodology:274 patients with dyspnea/orthopnea complaints visiting the cardiologists were enrolled in this study. Angiographic study was conducted on the enrolled patients to examine the extent of stenosis in the five prominent vessels (LDA, LCX, PDA/PLV, RCA, and OM) connected to the myocardium. Samples from all the cases suspected to be having coronary artery stenosis were collected, and subjected to biochemical evaluation of certain cardiac inflammatory biomarkers (c-TnI, hsTn-I and hs-CRP) to check their sensitivity with the level of vascular stenosis. The extent of mild and culprit stenosis was detected during angiographic examination and the same was reported in the form significant (≥50% stenosis in the vessels) and non-significant (<50% stenosis in the vessels) Carotid Stenosis. Ethical Clearance for the study was provided by Dr. Ram Manohar Lohia Institute of Medical Sciences Institutional Ethical Committee. Informed consent was obtained from all the participants enrolled in the study.Results:We observed that 85% of the total population enrolled in this study was suffering from hypertension followed by 62.40% detected with sporadic episodes of chest pain. Most of the subjects (42% of the total population) had stenosis in their LAD followed by 38% who had stenosis in their RCA. Almost 23% patients were reported to have stenosis in their LCX followed by OM (18% patients), PDA/PLV (13%) and only 10% patients had blockage problem in their diagonal. 24% of the subjects were found to have stenosis in a single vessel and hence were categorized in the Single Vessel Disease (SVD) group while 76% were having stenosis in two or more than two arteries (Multiple Vessel Disease). hs-TnI level was found to be correlated with the levels of stenosis and was higher in the MVD group as compared to the SVD group.Conclusion:hs-TnI could be used as a novel marker as it shows prominence in detecting the level of stenosis quite earlier as compared to c-TnI which gets detected only after a long duration in the CVD patients admitted for angiography. hs- CRP gets readily detected as inflammation marker in these patients and hence could be used in combination with hs-TnI to detect the risk of developing coronary artery disease.

The biggest receptor family in the genome, G-protein coupled receptors (GPCRs), are of tremendous interest for the development of innovative medications for a wide range of illnesses, including neurologic disorders, obesity, and type 2 diabetes mellitus. The latter is a chronic condition that affects more than 400 million people globally and is characterized by insulin resistance and decreased insulin secretion. Here, we give an overview of: a) The molecular underpinnings of GPCR signaling, including its role in the control of insulin secretion and glucose homeostasis; and b) the function of GPCRs in the pathogenesis of type 2 diabetes and as potential therapeutic targets for new and existing glucose-lowering medications.

The recent epidemics and pandemics caused by different viruses such as SARS-CoV-2, monkey pox, H1N1, ebola virus etc. have been a cause of mass destruction in the human race, the biggest decline slope in the global economy and mental trauma. A number of viruses have been discovered that may cause serious problems and to overcome this problem, early diagnosis of the viruses and understanding their infection pattern is a must. Early detection of viruses inside the host provides timely management in a strategic manner. Scientists have developed some effective and efficient methods to detect the viruses. In this review, we have explained a few types of diagnostic techniques: Biosensor based, immunological-based, and molecular-based diagnostic techniques that are prominent methodologies to identify and detect the course of infection related to the medical viruses. In biosensor-based diagnostic technique, an analytical device consisting of biological elements and physicochemical component gives a signal upon detection of viral antigen. In immunological-based diagnostic techniques, enzyme-linked antibodies are utilized to find the particular antiviral antibody or viral antigen in human specimens, and nucleic acid-based diagnostic techniques are based on the principle of amplification of the viral genome.

Noncoding ribonucleic acids (RNAs) regulate gene expression at the transcriptional and posttranscriptional levels. Noncoding RNAs are involved in epigenetic processes and play crucial roles in histone modification, deoxyribonucleic acid (DNA) methylation, and gene silencing. Here, we have described the synthesis and functions of noncoding RNAs for example microRNAs, siRNAs, PIWI-RNAs, long noncoding RNAs, circular RNAs and enhancer RNAs in health and disease. Moreover, alterations in the expression levels of noncoding RNAs lead to phenotypes of many life-threatening diseases such as diabetes and cancer. These roles of noncoding RNAs could be utilized to target genes or pathways causing diseases. Targeting noncoding RNAs can be one of the future safe strategies in the management of diabetes mellitus that could be utilized in drug development and pharma industries in near future. In this chapter, the authors have focused on the biology of various types of ncRNAs in health and disease.

Diabetes is an age-dependent health issue prevalent worldwide and specially seen in those families with prevalent history of the disorder. Insufficient insulin production by the defective pancreas that leads to high blood glucose levels in the systemic circulation makes the patients more prone to an infection that exaggerates with time as compared to their counterparts. This increased prevalence of infections in diabetics may be due to defects in the immune functionality of the diabetes patients. High blood glucose level evokes inflammatory responses due to provoked inflammatory immune response against hyperglycemic condition in adipocytes and macrophages. The inflammatory mediators attack the pancreatic beta cells thus affecting the insulin production, which in-turn again results in hyperglycemia. Dysfunction of the immune response could not control the invasion of pathogens thereby, increasing the incidence of infectious diseases and related co- morbidities. This chapter discusses about immune dysfunction and suppression in T2DM and the underlying inflammation and infections in diabetics. An elaborate and in-depth understanding of the immune dysfunction in T2DM patients can help in the management and development of better targeted therapeutics to cure the disorder. It may also provide an insight in how to take care of one’s health as a precautionary measure to avoid the complications leading to diabetes and vice versa.

Japanese encephalitis (JE) is a vector-borne neurotropic disease caused by Japanese encephalitis virus (JEV) associated with high mortality rate distributed from Eastern and Southern Asia to Northern Queensland (Australia). The challenges in early detection and lack of point-of-care biomarkers make it the most important Flavivirus causing encephalitis. There is no specific treatment for the disease, although vaccines are licenced. In this review, we focussed on point-of-care biomarkers as early detection tools and developing the effective therapeutic agents that could halt JE. We have also provided molecular details of JEV, disease progression, and its pathogenesis with recent findings which might bring insights to overcome the disease burden.

Diindolylmethane (DIM) is a key metabolite of indole-3-carbinol found in cruciferous vegetables such as broccoli, cauliflower, and cabbage. DIM has been known for its anti-cancerous activity through various mechanisms. Most cancer cells, including triple-negative breast cancer (TNBC), adapt distinct metabolic reprogramming for rapid growth and proliferation. Hence, targeting metabolic dysregulation may provide a favorable therapeutic condition for the treatment of TNBC. Earlier, we found that DIM increases the intracellular accumulation of Centchroman (CC), a potential anticancer agent, thereby enhancing the therapeutic potential of CC against breast cancer. However, the role of DIM in regulating TNBC cellular metabolism remains unknown. In the current study, we investigated the potential therapeutic interventions of DIM in TNBC and its metabolic reprogramming in enhancing the efficacy of CC. We found that DIM induced metabolic catastrophe in TNBC cells by regulating aerobic glycolysis and intermediate metabolism. Further, the DIM and CC combination significantly inhibited the TNBC tumor growth in the 4T1-syngeneic model. The inhibition of tumor growth was associated with the downregulation of key aerobic glycolysis mediators such as PKM2, GLUT1, and hypoxia-inducible factor 1α (HIF-1α). This is a first-of-a-kind investigation linking DIM with aerobic glycolysis regulation and enhancing the treatment efficacy of CC against TNBC. Therefore, these findings suggest that DIM-based nutraceuticals and functional foods can be developed as adjuvant therapy for treating metabolically dysregulated TNBC.

Background: Genotyping of Human PapillomaVirus (HPV) has become a necessary criterion to establish a clear connection between the efficiency of HPV vaccine clinical trials and HPV prevalence worldwide. HPV infections contribute to 40%-60% of all known cancers and its screening and vaccination is an important aspect for a healthy life in females. Studies in North India Population have not been conducted yet in this regard. Materials & Methods: In this study, overall HPV prevalence and type specific prevalence were assessed in cervical smear of 2700 samples, using real time polymerase chain reaction for screening and linear array assay for genotyping. HPV status was studied in relation to age and other lifestyle factors. Results: Twenty per cent of samples were HPV positive. HPV type diversity was broad, and multiple strains of HPV infections occurred in half of the HPV positive samples. Younger women were significantly more likely to harbor multiple high risk HPV (HR-HPV) infections. Infections with high risk HPV types were found to be 41% of positive tested samples followed by 35% of moderate risk HPV types. The 41% infections were contributed by HPV type 16 and 18 alone. Conclusion: HR-HPV infections were most prevalent in North Indian women population due to multiple factors related to the marital and sexual life style of the subjects. Extensive cross-cultural study needs to be conducted to reach some scientific conclusion that will help the medical community in developing targeted therapeutics against HPV and thus will help in mitigating the burden of cervical cancer in the society.

Background: Failure to conceive following regular or frequent unprotected intercourse for a year or more has been defined as infertility. In-Vitro Fertilization (IVF) is the most recommended treatment for unresolved infertility issues worldwide. There are various factors associated with the risk of infertility and if left intreated these may lead to an exaggerated damage that further results into recurrent IVF failure in these patients. Materials & Methods: This study was conducted at Krishna Medical Centre, Lucknow, Uttar Pradesh, from September 2012 to December 2019 in 800 patients experiencing infertility problem. The study includes females with valid indication for IVF treatment age between 20 years to 50 years. Various pathological, environmental and anatomical factors associated with infertility have been investigated in the patients. The surgical interventions used to modify the anatomical barriers leading to infertility in the patients have also been mentioned in the manuscript. Result: In this study it was found that there are various physical, physiological, environmental and anatomical risk factors that pose threat to successful pregnancy in the infertile couples. These factors also create restrictions in successful conception through in vitro ferlilization in these subjects. If left untreated these factors may lead to permanent sterility and infertility in these couples. Hence timely treatment and proper medical care along with surgical intervention can help the patients overcome their fertility issues via IVF. Conclusion: This study contains the data of 800 female patients suffering from various types of infertility issues. The investigators have studied the factors associated with infertility and have also tied to treat the anatomical barriers posing threat to fertility in these subjects. The article is being produced with the hope to generate awareness to the infertile couple with knowledge and information of the medical advancements that can benefit them in overcoming their infertility issue and lead a successful life.

Cervical cancer is the most common cancer associated with women in developing countries with 80% cases reported every year and could be prevented by proper screening and vaccination. The objective of this study was to explore the knowledge, attitudes, and practices of North Indian women visiting Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow for cervical cancer screening. This was a cross-sectional study of 300 women attending the Out-patient department (OPD) at Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow. We used a validated questionnaire tool comprised of 24 items to collect data through face-to-face interviews between January 2018 and October, 2019. Results are expressed in percentage form for each question in this article. The mean age ± SD of the participants was 34 ± 10.34 years, they were mostly married (198; 66%), and had a high school or higher education (235; 78.3%). Over 66% (198 participants) were aware of cervical cancer as a disease and had heard about it from various sources like their family, friends, television, print media, radio etc. Most of these participants (66%) who were aware of Cervical cancer (CX CA) had been able to identify the various established risk factors, signs and symptoms of the disease but only 20% were aware with Pap smear procedure while almost 70% didn’t know that early detection of this disease is possible. Nearly 53% (158 participants) believed that CX CA vaccination will protect them against cervical cancer. After explaining all the signs, symptoms, possible modes of transmission and dangers related to the ignorance of cervical cancer screening, 68.3 percent of the women participants agreed to allow their female relatives for CX CA screening and vaccination while 32% still had certain hesitations related to the screening and vaccination program. The need of the hour is a better-planned program to generate awareness and allow the women candidates to explore the CX CA issue and get themselves and their relatives prepared for screening and vaccination from the deadly disease.

The study was aimed to assess the relation between high sensitivity C-reactive protein (hs-CRP) and obesity in Indian population. Obesity is increasing to epidemic proportions in India to such an extent that the prevalence of obesity has also been found to be rising in children and adolescents leading to various coronary events and inflammatory conditions like cardiac disorders, atherosclerosis etc. in young adults. Obesity is associated with the release of many inflammatory cytokines from adipose tissue among which IL-6, one of the proinflammatory cytokines produced from adipose tissue, plays a major role in stimulating the release of CRP-a novel inflammatory marker released from the liver. In this study, we tried to study the role of hs-CRP and the trend of its increase in Indian population with various levels of obesity. The subjects in the study were participants from voluntary health check-up in MedicineOPD at Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India. The study population was matched for age, BMI, WC, and WHR. Subjects with BMI >30 waist circumference/hip circumference ratio were considered as obese for this study. Baseline characters such as blood pressure, cholesterol levels and glucose level were measured along with the changes in the hs-CRP level in the subjects and the same was compared with those with BMI > 30, serving as control. It was found that the level of hs-CRP increases with obesity and may lead to various medical complications if left unattended as obesity have been found to be linked with number of atherogenic, hypertensive and metabolic disorders known till date.

Dyslipidemia is a common finding in patients with thyroid disease, explained by the adverse effects of thyroid hormones in almost all steps of lipid metabolism. Clinical hypothyroidism, through different mechanisms, are associated with lipid alterations, mainly concerning total and LDL cholesterol and less often HDL cholesterol, triglycerides, lipoprotein (a), apolipoprotein A1, and apolipoprotein B. In addition to quantitative, qualitative alterations of lipids have been also reported, including atherogenic and oxidized LDL and HDL particles. In thyroid disease, dyslipidemia coexists with various metabolic abnormalities and induce insulin resistance and oxidative stress via a vice-vicious cycle. The above associations in combination with the thyroid hormone induced hemodynamic alterations, might explain the increased risk of coronary artery disease, cerebral ischemia risk, and angina pectoris in older, and possibly ischemic stroke in younger patients with overt or subclinical hyperthyroidism. This article presents a correlation study between hypothyroidism, Apo B and Apo A. It has been found that the 55 subjects enrolled in this study show a significant correlation between TSH and Apo B.

Cholesterol and triglyceride fats are transported as part of lipoprotein particles in the bloodstream. The various lipoprotein classes Low Density Lipoprotein (LDL) that carry most part of the blood cholesterol, Very Low Density Lipoprotein (VLDL), which carry most of the blood triglycerides, High Density Lipoprotein (HDL) and Chylomicrons. LDL also found as serum cholesterol plays a significant role in coronary heart diseases. The role of these lipoproteins is quite independent of other risk factors and is quite predictive that could be easily assessed. The present article is focused on the estimation of plasma lipoprotein (a) [Lp(a)] level in AMI patients along with their cardiac Troponin-I levels to study the correlation between the two and to look into the possibility of dual marker approach to deal with complications associated with acute myocardial infarction. Lp(a) is a major risk factor of several cardiovascular diseases, namely atherosclerotic vascular diseases, aortic calcification, and perhaps also venous thromboembolic diseases and hence could be a prominent therapeutic target for primary and secondary prevention. This calls for the development of a safe and effective means of lowering Lp(a) that will provide an opportunity to conduct intervention trials to further decipher its contribution in the etiology of CHD.

Endothelium is a highly efficient part of the vasculature that plays a very important role in fulfilling the metabolic requirements of the body. Endothelium dysfunction signified by the impaired activities of the endothelium leads to various acute diseases and symptomatic problems. One major role of the endothelial cells is angiogenesis, which either gets impaired or exaggerated in conditions like cardiovascular disorders and cancer, to name a few. Various genetic factors and signalling molecules also contribute to these impairments in the vasculature. Homocysteine is one such molecule which is the precursor of methionine generation pathway in the body. But it has been found that this molecule when tends to accumulate in the body due to certain inhibitions in its pathway, results into various problems associated with the endothelium and angiogenesis. In this article the author has reviewed the functions of endothelium, the role of angiogenesis in vasculature, its role in the cardiovascular disorder especially atherosclerosis and the various consequences of hyper homocystenemia on the endothelium. The author also proposes the role of folic acid in mitigating the problems that arise due to homocysteine accumulation in the body, leading to various complications. Keywords: Angiogenesis; Atherosclerosis; Endothelium; Folic acid; Homocysteine; Vasculature

Markedly or mildly elevated circulating homocysteine concentrations are associated with increased risk of vascular occlusion. Here we review possible mechanisms that mediate these effects. Inborn errors of homocysteine metabolism result in markedly elevated plasma homocysteine (200–300 μmol/L) and thromboembolic (mainly venous) disease which is easily normalized with oral folate and ongoing trials are assessing the effect of folate treatment on outcomes. Some people have a common genetic variant (called methylenetetrahydrofolate reductase, abbreviated MTHFR) that also impairs their ability to process folate. Indeed, there are evidences suggesting an acute antioxidant effect of folic acid on homocysteine concentrations. This antioxidant mechanism may oppose an oxidant effect of homocysteine and be relevant to treatment of patients with vascular disease, especially those with chronic renal insufficiency. Such patients have moderately elevated plasma homocysteine and greatly increased cardiovascular risk that is largely unexplained.

Markedly or mildly elevated circulating homocysteine concentrations are associated with increased risk of vascular occlusion. Here we review possible mechanisms that mediate these effects. Inborn errors of homocysteine metabolism result in markedly elevated plasma homocysteine (200-300 μmol/L) and thromboembolic (mainly venous) disease which is easily normalized with oral folate and ongoing trials are assessing the effect of folate treatment on outcomes. Some people have a common genetic variant (called methylenetetrahydrofolate reductase, abbreviated MTHFR) that also impairs their ability to process folate. Indeed, there are evidences suggesting an acute antioxidant effect of folic acid on homocysteine concentrations. This antioxidant mechanism may oppose an oxidant effect of homocysteine and be relevant to treatment of patients with vascular disease, especially those with chronic renal insufficiency. Such patients have moderately elevated plasma homocysteine and greatly increased cardiovascular risk that is largely unexplained.