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.

Reconciling the Gap between Medications and their Potential Leads: The Role of Marine Metabolites in the Discovery of New Anticancer Drugs: A Comprehensive Review.

One-third of people will be diagnosed with cancer at some point in their lives, making it the second leading cause of death globally each year after cardiovascular disease. The complex anticancer molecular mechanisms have been understood clearly with the advent of improved genomic, proteomic, and bioinformatics. Our understanding of the complex interplay between numerous genes and regulatory genetic components within cells explaining how this might lead to malignant phenotypes has greatly expanded. It was discovered that epigenetic resistance and a lack of multitargeting drugs were highlighted as major barriers to cancer treatment, spurring the search for innovative anticancer treatments. It was discovered that epigenetic resistance and a lack of multitargeting drugs were highlighted as major barriers to cancer treatment, spurring the search for innovative anticancer treatments. Many popular anticancer drugs, including irinotecan, vincristine, etoposide, and paclitaxel, have botanical origins. Actinomycin D and mitomycin C come from bacteria, while bleomycin and curacin come from marine creatures. However, there is a lack of research evaluating the potential of algae-based anticancer treatments, especially in terms of their molecular mechanisms. Despite increasing interest in the former, and the promise of the compounds to treat tumours that have been resistant to existing treatment, pharmaceutical development of these compounds has lagged. Thus, the current review focuses on the key algal sources that have been exploited as anticancer therapeutic leads, including their biological origins, phytochemistry, and the challenges involved in converting such leads into effective anticancer drugs.

Effect of Calcitriol in Inhibiting the Cancer Cell Growth and Promoting Apoptosis in ErbB2-positive Breast Cancer Cells.

BACKGROUND: Targeted therapies, specifically ErbB family tyrosine kinase inhibitors, have demonstrated potential for improving outcomes in patients with ErbB2-positive breast cancer. Despite their effectiveness, these therapies are associated with limitations, including high costs, side effects, drug resistance, lack of specificity, and toxicity. To overcome these challenges, drug repurposing has emerged as a promising strategy in breast cancer treatment. OBJECTIVE: The aim of this investigation was to assess the influence of calcitriol on breast cancer cell lines expressing ErbB2 and comparing its effects with the conventional treatment, neratinib. METHODS: We employed an MTT test to determine cell viability and utilized staining techniques to assess cell apoptosis. Flow cytometry was used to evaluate cell cycle arrest, while a scratch wound healing test was performed to examine cancer cell migration ability. Additionally, gene expression studies were conducted for calcitriol and neratinib to support our hypothesis regarding the ErbB2 gene. RESULTS: The repurposing of calcitriol demonstrated enhanced efficacy in suppressing cancer cell growth in ErbB2- positive breast cancer. Proportionally, calcitriol significantly reduced the viability of SK-BR-3 cells, similar to neratinib. Furthermore, calcitriol exhibited significant cytotoxicity against neratinib and substantially reduced breast cancer cell growth. These findings were corroborated by the wound healing assay, cell cycle arrest analysis, and gene expression studies, demonstrating comparable efficacy to the standard treatment, neratinib. CONCLUSION: The findings from this investigation offer compelling proof that highlights the promising role of calcitriol as an adjuvant drug with antiproliferative and antitumoral effects in the management of ErbB2-positive breast carcinoma patients. Therefore, we recommend further evaluation of calcitriol in clinical settings, particularly for the treatment of ErbB2-positive breast cancer, as it shows promise as a valuable therapeutic option.

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.

Phytochemical and in-vitro Biological Investigation of Indian Traditional Medicinal Plants for their Cytotoxicity and Hepatoprotective Potential.

OBJECTIVE: This study aimed to select 16 medicinal plants based on their folklore remedy for treating various diseases like inflammation, cancer, etc., and scientifically validate their potency. METHODS: Five among them, namely Centella asiatica (CA), Myristica fragrans (MF), Trichosanthes palmata (TP), Woodfordia fruticosa (WF), and Curculigo orchioides (CO), were scientifically confirmed through the extraction and in-vitro cytotoxic and hepatoprotective evaluation. Based on the cytotoxic and hepatoprotective results, the various fractions of CO were chosen for an in-depth phytochemical study to isolate and characterize active compounds by GC-MS. RESULTS: The results showed promising cytotoxic activity (i.e., IC50=<100 µg/ml) against HeLa cell lines and significant hepatoprotective activity in a dose-dependent manner on CCl4 intoxicated isolated hepatocyte cells. CONCLUSION: The present study confirmed the scientific evidence regarding the effectiveness of selected medicinal plants in HeLa and hepatocyte cells. Furthermore, a detailed study on their mechanism of action and clinical application is suggested.