Diabetes and TB: Confluence of Two Epidemic and Its Effect on Clinical Presentation.

BACKGROUND: Tuberculosis (TB) has become a rising concern in low-income countries, particularly in those with Human Immuno Deficiency Virus (HIV) epidemics, and type 2 diabetes has emerged as a significant global chronic health problem, owing to increases in obesity, lifestyle changes, and ageing populations. Diabetes has been identified as a major risk factor for the development of TB. Despite the fact that diabetes imparts a substantially lower risk of TB (3-fold) as compared to HIV (>20-fold), in communities where the number of DM patients is high, the contribution of diabetes to TB might be bigger than HIV. METHODS: This review will focus on the link between TB and diabetes, which is now one of the most important topics for physicians since diabetes impacts the clinical presentation and outcome of TB and vice versa. RESULTS: Though TB is more common in type 1 diabetes, the extent of the problem in type 2 diabetes should be taken into account with equal care, as type 2 diabetes affects a substantially higher number of individuals. CONCLUSIONS: Diabetes patients are more vulnerable to infections because of their impaired immune systems. Increased glucose level leads to a rise in the infection status among TB patients and also leads to a rise in various complications. Extensive and increased screening for both TB and DM over years can help diagnose disease priorly and help in better management. TB, when diagnosed in its early stages, can be easily eradicated.

Prevalence of Depression and Anxiety Disorders Among Cancer Patients: An Insight From a Single Institute.

Objective This cross-sectional, observational study aimed at finding the prevalence of anxiety and depression in cancer patients and the correlation of anxiety and depression with various factors, such as age, sex, marital status, educational status, occupation, financial support, duration, type of care, sort of carcinoma, and stages of malignancy, among cancer patients attending the G. Kuppuswamy Naidu Memorial Hospital, Coimbatore, Tamil Nadu, India from July 2022 to December 2022, using the Hospital Anxiety and Depression Scale (HADS). Methods A total of 162 cancer patients referred for various cancer therapies (chemo/surgery/combination therapies) were included. All patients were administered the HADS. The association between anxiety scores and various factors such as age, site, and sex was found using the chi-square test. Results Thirty-nine (24.1%) patients had severe anxiety, 60 (37%) patients had borderline anxiety, and 63 (38.9%) patients were found to be normal. Fifty-three (32.7%) patients had severe depression, 47 (29%) patients had borderline depression, and 62 (38.3%) patients were found to be normal. The findings of this study indicate that educational status and occupational status are the significant factors (p < 0.05) responsible for increasing the risk of prevalence of anxiety and depression in cancer patients. Another interesting observation in this study was that patients with breast and gastrointestinal cancer had the highest prevalence of depression among other cancer types. Conclusions The present study contributed to the prevalence of anxiety and depression in cancer patients in Tamil Nadu, India. While the study population is small, which is a limitation of the present study, it has provided an overview that educational status and occupation contribute significantly to anxiety and depression, which has not been explored much in the past. To efficiently manage this, patients should be made aware of the financial support available from various philanthropic groups, government policies, and insurance so that they can improve their quality of life and manage their clinical condition in a more confident manner. These findings call for the need for early psychiatric interventions in cancer care to improve the quality of life of patients by focusing on improving patients' mental stability and adherence to the medications for providing positive outcomes from the cancer treatments.

A Computational Study of Famciclovir Derivatives Against Thymidine Kinase as a Molecular Target for the Development of Novel Anticancer Drugs via Suicide Gene Therapy Concepts.

BACKGROUND: The viral thymidine kinase (TK) phosphorylates the antiviral medication famciclovir (FCV), which treats herpes simplex virus (HSV-TK). The phosphorylated FCV destroys the infected cells by preventing cellular DNA synthesis. OBJECTIVE: We hypothesize that FCV impurity, which is a related substance to FCV, should be efficient in killing cells independent of HSV-TK and is currently the most widely used suicide agent for gene therapy of cancer. METHODS: This study proposes the binding affinity of these derivatives for the active site of TK through molecular docking to a protein (PDB ID: 1W4R). The derivatives' reliability was ensured through the in-silico preliminary drug designing model by screening their Lipinski rule of five violations, if any, ADMET prediction for their profile using online tools. Using MOE 2009.10 computational software, we performed molecular docking of approximately 22 famciclovir derivatives alongside the famciclovir drug. RESULTS: Our results suggest that these derivatives are indicative of possible chemical stability irrespective of all the parameters used to evaluate the selected derivatives as a possible drug candidates for their cytotoxicity. FC20 (i.e., 2-(2-(2-((1-(9-(4-Acetoxy-3-(acetoxymethyl)butyl)-2-amino-9Hpurin- 8-yl)ethyl)amino)-9H-purin-9-yl)ethyl)propane-1,3-diyl diacetate) and FC21 (i.e., 2-Amino-1,9- dihydro-9-(4-hydroxybutyl)-6H-purin-6-one), showed maximum and minimum scores of -26.95 and - 7.21 kcal/mol, respectively when compared to famciclovir (-15.4122 kcal/mol). CONCLUSION: Considering that there might be a cytotoxicity effect due to competition between protein TK and the suicidal gene of famciclovir derivatives. The outcome of the study proved that the FCV impurity could successfully modify an HSV-TK-dependent antiviral drug into an anti-tumor drug. Further, it can be used for the design and development of novel compounds of FCV impurity that could be cytotoxic agents if properly delivered to cancer cells.

A Recent Update on the Impact of Nano-Selenium on Plant Growth, Metabolism, and Stress Tolerance.

Selenium (Se) is a microelement that plays an important nutrient role by influencing various physiological and biochemical traits in plants. It has been shown to stimulate plant metabolism, enhancing secondary metabolites and lowering abiotic and biotic stress in plants. Globally, the enormous applications of nanotechnology in the food and agricultural sectors have vastly expanded. Nanoselenium is more active than bulk materials, and various routes of synthesis of Se nanoparticles (Se-NPs) have been reported in which green synthesis using plants is more attractive due to a reduction in ecological issues and an increase in biological activities. The Se-NP-based biofortification is more significant because it increases plant stress tolerance and positively impacts their metabolism. Se-NPs can enhance plant resistance to various oxidative stresses, promote growth, enhance soil nutrient status, enhance plant antioxidant levels, and participate in the transpiration process. Additionally, they use a readily available, biodegradable reducing agent and are ecologically friendly. This review concentrates on notable information on the different modes of Se-NPs' synthesis and characterization, their applications in plant growth, yield, and stress tolerance, and their influence on the metabolic process.

Critical Clinical Evaluation of COVID-19 Patients with Tuberculosis in the Indian Sub-Continent.

BACKGROUND: COVID-19 and tuberculosis (TB) are infectious diseases that predominantly affect the respiratory system with common symptoms, such as cough, fever, and shortness of breath, making them dual burdens. METHODS: This review will discuss the characteristics of the coexistence of TB and new infectious illnesses to provide a framework for addressing the current epidemic. Currently, there are no clear and significant data on COVID-19 infection in TB patients, they may not respond appropriately to drug therapy and may have worse treatment outcomes, especially if their TB treatment is interrupted. Due to emergence, measurements should be taken to minimize TB and COVID-19 transmission in communal settings and health care institutions were created. For both TB and COVID-19, accurate diagnostic testing and well-designed, and established therapeutic strategies are required for effective treatment. RESULTS: Several health care organizations and networks have specimen transit methods that can be utilized to diagnose and monitor the etiology and progression of COVID 19 and perform contact tracing in developed and underdeveloped nations. Furthermore, patients and health care programs could benefit from increased use of digital health technology, which could improve communication, counseling, treatment, and information management, along with other capabilities to improve health care. CONCLUSION: Patients with COVID-19 pulmonary/respiratory problems may seek treatment from respiratory physicians, pulmonologists, TB experts, and even primary health care workers. To have prophylactic and therapeutic strategies against COVID-19, TB patients should take the appropriate health care measures recommended by health care professionals/government officials and maintain their TB therapy as indicated.

Bioactive Compounds in Oxidative Stress-Mediated Diseases: Targeting the NRF2/ARE Signaling Pathway and Epigenetic Regulation.

Oxidative stress is a pathological condition occurring due to an imbalance between the oxidants and antioxidant defense systems in the body. Nuclear factor E2-related factor 2 (NRF2), encoded by the gene NFE2L2, is the master regulator of phase II antioxidant enzymes that protect against oxidative stress and inflammation. NRF2/ARE signaling has been considered as a promising target against oxidative stress-mediated diseases like diabetes, fibrosis, neurotoxicity, and cancer. The consumption of dietary phytochemicals acts as an effective modulator of NRF2/ARE in various acute and chronic diseases. In the present review, we discussed the role of NRF2 in diabetes, Alzheimer's disease (AD), Parkinson's disease (PD), cancer, and atherosclerosis. Additionally, we discussed the phytochemicals like curcumin, quercetin, resveratrol, epigallocatechin gallate, apigenin, sulforaphane, and ursolic acid that have effectively modified NRF2 signaling and prevented various diseases in both in vitro and in vivo models. Based on the literature, it is clear that dietary phytochemicals can prevent diseases by (1) blocking oxidative stress-inhibiting inflammatory mediators through inhibiting Keap1 or activating Nrf2 expression and its downstream targets in the nucleus, including HO-1, SOD, and CAT; (2) regulating NRF2 signaling by various kinases like GSK3beta, PI3/AKT, and MAPK; and (3) modifying epigenetic modulation, such as methylation, at the NRF2 promoter region; however, further investigation into other upstream signaling molecules like NRF2 and the effect of phytochemicals on them still need to be investigated in the near future.

Ameliorative effect of silymarin against linezolid-induced hepatotoxicity in methicillin-resistant Staphylococcus aureus (MRSA) infected Wistar rats.

Linezolid has a better choice for eradication of methicillin-resistant Staphylococcus aureus (MRSA) infections, but its use is limited because of linezolid-induced hepatotoxicity, myelosuppression, and lactic acidosis. This research elucidated the role of silymarin against hepatoxicity of linezolid therapy in MRSA infected Wistar rats. The rats were rendered neutropenic by an intraperitoneal injection of cyclophosphamide injection. The neutropenic rats were injected subcutaneously with 106 CFU/ml of MRSA. The rats were divided into 6 groups. Normal control, Infected, Infected animals treated with linezolid 50 mg/kg/twice/day and Infected animals treated with linezolid and different dose of silymarin 25, 50, and 100 mg/kg/twice/day for 14 days. On the 15th day, the blood, liver, kidney, and bone marrow were collected for biochemical and histopathological examination. The MRSA was confirmed by PCR assay. The minimum inhibitory concentration of linezolid was 0.5-2 µg/ml. The linezolid induced liver damage was confirmed by elevation of marker enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), Lactate dehydrogenase (LDH) levels, serum bilirubin, lactate, and histopathological studies of the liver. The linezolid treated rats also showed myelosuppression, lactic acidosis, oxidative stress and decreased intestinal alkaline phosphatase (IAP). The silymarin administration exhibited marked hepatoprotective effect by significantly lowering the liver marker enzymes, serum parameters, and cytological findings reflect the hepatoprotection. Additionally, Silymarin showed protection against myelosuppression and lactic acidosis evidenced by bone marrow smear and serum lactate estimation. Antioxidant effect of silymarin was confirmed by decreased levels of lipid peroxidation, restored the enzymatic and non-enzymatic antioxidants of the liver nearer to normal. The present study indicates that the silymarin could be a better herbal therapeutic agent which protects against the linezolid induced hepatotoxicity in MRSA infected rats.

Flavone Analogues as Antimicrobial Agents.

BACKGROUND: Most of the available antimicrobial drugs have developed resistance, some of them suffer from severe toxicity and side effects. So, there is a need to discover novel compound(s) which should not only be potent, but also less toxic and cost effective. OBJECTIVES: The aim of the study is to develop new synthetic antimicrobial agents (Anti-bacterial and anti-fungal) such as 3-substituted flavone/flavanone derivatives, which should be significantly potent with low toxicity. METHOD: An attempt was made to synthesize a newer series of 3-methyl flavanone derivatives together with the synthesis of a series of 3- hydroxyl flavone analogues. The structures of the test compounds were elucidated and established by UV, IR, 1H-NMR, 13C-NMR and mass spectrometry. The synthesized compounds were subjected for in vitro antimicrobial screening using cup plate methods, followed by the determination of zone of inhibitions. RESULT: Two series (each 10) of 3-methyl flavanone and 3-hydroxy flavone derivatives were synthesized. The structures of the test compounds were characterized and established by various spectroscopic methods. The synthesized compounds were screened for in vitro antibacterial and antifungal activity against different strains (3-Gram positive, 3-Gram negative and 2- fungal strains). CONCLUSION: Some of the 3- hydroxyl flavones derivatives (1b, 3b, 4b, and 5b) and 3- methyl flavanone derivatives (3a, 1a, 2a and 4a) were found to elicit potent antimicrobial activity. The study revealed that 3-hydroxy flavone derivatives were found to be most active against Gram negative, while 3-methyl flavanone derivatives were active against Gram positive bacteria.

Cytotoxicity and Anti-inflammatory Activity of Flavonoid Derivatives Targeting NF-kappaB.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) has been reported to regulate various genes involved in cancer and inflammation. Accordingly, drugs inhibiting NF-kappaB may possess both anti-inflammatory and anticancer properties. So there is a need to discover novel compounds which should not only be a potential lead but also less toxic and cost effective. OBJECTIVES: The aim of the study was to develop new synthetic anti-inflammatory and cytotoxic agents targeting NF-kappaB. METHODS: Test compounds were synthesized and characterized by UV, IR, 1H-NMR, 13C-NMR and mass spectrometry. The synthesized compounds were evaluated for in vitro cytotoxicity by MTT assay against various cancer cell lines and in vivo anti-inflammatory in carrageenan-induced paw edema model. Selected compounds were subjected to cell cycle analysis using propidium iodide. Docking study was done into an active site of NF-kappaB using Auto Dock 4.2. RESULT: Three series of compounds were synthesized and characterized by various spectroscopic techniques. The test compounds (10b), (1c) and (2c) were found to be the most potent anti-inflammatory agents, whereas compounds such as (10b), (6b), (4b), (2b), (6a), (4a), (5c) and (3c) have shown promising cytotoxicity in different cancer cell lines, followed by cell cycle analysis of selected compounds ((10b) and (4b)). The free energy of binding of ligands was in the range between -6.47 to -12.50.Kcal/ mole. CONCLUSION: compound (10b) was found to be the most potent as both anti-inflammatory and cytotoxic agents. In silico approach was in good tune with the wet lab experiments. The promising compounds have shown to induce cell cycle arrest at G2/M Phase.

Nanocapsules: the weapons for novel drug delivery systems.

INTRODUCTION: Nanocapsules, existing in miniscule size, range from 10 nm to 1000 nm. They consist of a liquid/solid core in which the drug is placed into a cavity, which is surrounded by a distinctive polymer membrane made up of natural or synthetic polymers. They have attracted great interest, because of the protective coating, which are usually pyrophoric and easily oxidized and delay the release of active ingredients. METHODS: Various technical approaches are utilized for obtaining the nanocapsules; however, the methods of interfacial polymerization for monomer and the nano-deposition for preformed polymer are chiefly preferred. Most important characteristics in their preparation is particle size and size distribution which can be evaluated by using various techniques like X-ray diffraction, scanning electron microscopy, transmission electron microscopy, high-resolu¬tion transmission electron microscopy, X-ray photoelectron spectroscopy, superconducting quantum interference device, multi angle laser light scattering and other spectroscopic techniques. RESULTS: Nanocapsules possessing extremely high reproducibility have a broad range of life science applications. They may be applied in agrochemicals, genetic engineering, cosmetics, cleansing products, wastewater treatments, adhesive component applications, strategic delivery of the drug in tumors, nanocapsule bandages to fight infec¬tion, in radiotherapy and as liposomal nanocapsules in food science and agriculture. In addition, they can act as self-healing materials. CONCLUSION: The enhanced delivery of bio¬active molecules through the targeted delivery by means of a nanocapsule opens numerous challenges and opportunities for the research and future development of novel improved therapies.

Antineoplastic and antibacterial activity of some mononuclear Ru(II) complexes.

These ligands (L) show a bidentate behavior, forming octahedral ruthenium complexes. The title complexes were subjected to in-vivo anticancer activity tests against a transplantable murine tumor cell line, Ehrlich's Ascitic Carcinoma (EAC) and in-vitro antibacterial activity against several Gram positive and Gram negative bacterial strains. [Ru(bpy)2(ihqs)]Cl2 and [Ru(bpy)2 (hc)]Cl2 (where bpy = 2,2'-bipyridine, ihqs = 7-iodo-8hydroxy quinoline-5-sulphonic acid and hc = 3-hydroxy coumarin) showed promising antitumor activity. Treatment with these complexes prolonged the life span of EAC bearing mice as well as decreased their tumor volume and viable ascitic cell count. All the tested complexes exhibited mild to moderate antibacterial activity.

Synthesis, anticancer and antibacterial activity of some novel mononuclear Ru(II) complexes.

In search of potential anticancer drug candidates in ruthenium complexes, a series of mononuclear ruthenium complexes of the type [Ru(phen)(2)(nmit)]Cl(2) (Ru1), [Ru(bpy)(2)(nmit)]Cl(2) (Ru2), [Ru(phen)(2)(icpl)]Cl(2) (Ru3), Ru(bpy)(2)(icpl)]Cl(2) (Ru4) (phen=1,10-phenanthroline; bpy=2,2'-bipyridine; nmit=N-methyl-isatin-3-thiosemicarbazone, icpl=isatin-3-(4-Cl-phenyl)thiosemicarbazone) and [Ru(phen)(2)(aze)]Cl(2) (Ru5), [Ru(bpy)(2)(aze)]Cl(2) (Ru6) (aze=acetazolamide) and [Ru(phen)(2)(R-tsc)](ClO(4))(2) (R=methyl (Ru7), ethyl (Ru8), cyclohexyl (Ru9), 4-Cl-phenyl (10), 4-Br-phenyl (Ru11), and 4-EtO-phenyl (Ru12), tsc=thiosemicarbazone) were prepared and characterized by elemental analysis, FTIR, (1)H-NMR and FAB-MS. Effect of these complexes on the growth of a transplantable murine tumor cell line (Ehrlich Ascites Carcinoma) and their antibacterial activity were studied. In cancer study the effect of hematological profile of the tumor hosts have also been studied. In the cancer study, the complexes Ru1-Ru4, Ru10 and Ru11 have remarkably decreased the tumor volume and viable ascitic cell count as indicated by trypan blue dye exclusion test (p<0.05). Treatment with the ruthenium complexes prolonged the lifespan of Ehrlich Ascites Carcinoma (EAC) bearing mice. Tumor inhibition by the ruthenium chelates was followed by improvements in hemoglobin, RBC and WBC values. All the complexes showed antibacterial activity, except Ru5 and Ru6. Thus, the results suggest that these ruthenium complexes have significant antitumor property and antibacterial activity. The results also reflect that the drug does not adversely affect the hematological profiles as compared to that of cisplatin on the host.