Identification of a Single Nucleotide Polymorphism of Vitamin D Receptor (VDR) and Vitamin D Binding Protein (VDBP) Gene and Its Dysregulated Pathway Through VDR-VDBP Interaction Network Analysis in Vitamin D-Deficient Infertile Females.

INTRODUCTION: The prevalence of female infertility in Pakistan is currently estimated at 22%, and emerging research suggests that vitamin D (VD) deficiency (VDD) may play a significant role in influencing female fertility. The focus of this study was to investigate the single nucleotide polymorphism (SNP) patterns within the VD binding protein (VDBP). The study aimed to explore dysregulated pathways and gene enrichment through an interaction network analysis, specifically focusing on the interplay between the VD receptor (VDR) and VDBP in females experiencing unexplained infertility (UI) coupled with VDD. METHODS: A cross-sectional study was conducted on VD-deficient, fertile, and UI female subjects. VDBP and VDR were assessed by enzyme-linked immunoassay and genotyping performed. FunRich (version 3.1.3; http://funrich.org/index.html) was employed for analysis of the identified proteins: VDR and VDBP and with their mapped gene datasets, gene enrichment, and protein-protein interaction (PPI) network. RESULTS: The mean VD and VDR values of infertile females were significantly lower than those of fertile females. VDBP in infertile females (median (IQR)): 296.05 (232.58-420.23)) was lower than that of fertile females (469.9 (269.57-875.55), (p=0.01)). On sequence analysis, a mutation rs 4588 SNP (Thr 436 Lys) was found in exon 11 of the VDBP gene of UI females, but no mutation in exons 8 and 9 of the VDR gene, with some insignificant intronic variants, was observed. The proteins such as plasma membrane estrogen receptor signaling pathway (p < 0.001), VDR, SMAD3, NCOR1, CREBBP, NCOA1, STAT1, GRB2, PPP2CA, TP53, and NCOA2 were enriched after biological pathway grouping when VDR was made the focused gene and directly interacting with VDBP. CONCLUSION: The females with UI exhibited significantly low VD, VDBP, and VDR. The plasma membrane estrogen receptor signaling pathway was enriched in VDD infertile females.

Design and development of new inhibitors against breast cancer, Monkeypox and Marburg virus by modification of natural Fisetin via in silico and SAR studies.

The natural Fisetin and its derivatives have been shown to have effective bioactivity and strong pharmacological profile, which is continuously drawing the interest of therapeutic applications to the development of new biomolecules against Breast cancer and Monkeypox, and Marburg viral infection, while computational approaches and the study of their structure-activity relationship (SAR) are the most eloquent and reliable platform for performing their hypothetical profile renovation. So, the main perspective of this investigation is to evaluate dual function of Fisetin and its derivatives against both virus and cancerous target. First and foremost, the prediction of activity spectra for materials (PASS) valuation has provided preliminary data on the antiviral, antibacterial, antiparasitic, and anti-cancer possibilities of the mentioned compounds. According to the evidence, PASS predicted scores were shown to perform better in antineoplastic and antiviral than antibacterial, and antiparasitic efficiency; as evidenced by their higher PASS scores in antineoplastic and antiviral drug tests. Breast cancer, Monkeypox, and Marburg virus have been selected as targeted pathogens, and different in silico studies were conducted to determine the dual function of mention derivatives. The "Lipinski five rules," on the other hand, has been subjected to extensive testing for drug-like characteristics. Molecular docking against Breast cancer, Monkeypox, and Marburg virus have been accomplished after confirmation of their bioactivity. The molecular docking evaluation against targeted disease displayed re-markable binding affinity and non-bonding engagement, with most of the results indicating that derivatives are more effective than the FDA approved standard antiviral, and antineoplastic drugs. Finally, the ADMET characteristics have been computed, and they indicate that the substance is suitable to use and did not have any chance to produce adverse effects on aquatic or non-aquatic environment, as well as having a highly soluble capacity in water medium, high G.I absorption rate, with outstanding bioavailability index. Therefore, these mentioned Fisetin derivatives could be suggested as potential medication against Breast cancer and newly reported Monkeypox, and Marburg virus, and may further proceed for laboratory experiment, synthesis, and clinical trials to evaluate their practical value.

A Comprehensive Review on the Medicinal Importance; Biological and Therapeutic Efficacy of Lagenaria siceraria (Mol.) (Bottle Gourd) Standley Fruit.

Herbal remedies have been employed for the treatment and management of different diseases for ages. Herbal medicines are a promising choice over modern synthetic drugs because of their low side effects and are thus considered to be safe and effective in treating human diseases. Lagenaria siceraria (Mol.) Standley fruit (Bottle gourd) belongs to the Cucurbitaceae family that has been used in a different system of traditional medication to treat various diseases. This is a domestic plant that provides food as well as medication. This vegetable have low caloric values and high water contents. The edible portion of it contains phytochemicals like vitamins, proteins, choline, minerals, terpenoids, flavonoids, etc. Several bioactive compounds have been isolated from L. siceraria, including triterpenoids, sterols, cucurbitacins, flavones, C-glycosides and ß-glycosides. Researchers have evaluated various parts of this plant viz. fruit, root, flowers, and leaves for pharmacological activities like antianxiety, antidepressant, diuretic, antimicrobial, cytotoxic, antihyperlipidemic, cardio protective, analgesic, anti-inflammatory, anthelmintic, anti-hyperglycemic, antihepatotoxic, anti-urolithiatic, antistress, antiulcer, anticancer, hepatoprotective, anthelmintic, immunomodulatory, and antioxidant. In this review, an attempt has been made to explore its phytochemical constituents, traditional, medicinal, and pharmacological uses to highlight the therapeutic importance of this well-known plant. This would be helpful in reviving its importance and will highlight its several promising aspects to encourage researchers for further research on L. siceraria.

Dose-Dependent Internalization and Externalization Integrity Study of Newly Synthesized 99mTc-Thymoquinone Radiopharmaceutical as Cancer Theranostic Agent.

Thymoquinone (TQ) is a bioactive phytochemical isolated from Nigella sativa and has been investigated for biochemical and biological activities in both in vitro and in vivo models. It is best known for its anticancer activities. Thymoquinone accomplishes anticancer activities through targeting multiple cancer markers including PPAR-γ, PTEN, P53, P73, STAT3, and generation of reactive oxygen species at the cancer cell surface. The radiolabeling of TQ with γ- and ß-emitter radionuclide could be used as cancer diagnostic or therapeutic radiopharmaceutical, respectively. In this study, we are reporting the radiolabeling of TQ with technetium-99m (99mTc), stability in saline and blood serum, internalization and externalization of 99mTc-TQ using rhabdomyosarcoma cancer cells line. The quality control study revealed more than 95% labeling yield and stable in blood serum up to 4 hours. In vitro internalization rate was recorded 27.08% ± 0.95% at 1 hour post 2 hours internalization period and comparatively slow externalization. The results of this study are quite encourging and could be investigated for further key preclinical parameters to enter phase I clinical trials.

Isolation of Quercetin from Rubus fruticosus, Their Concentration through NF/RO Membranes, and Recovery through Carbon Nanocomposite. A Pilot Plant Study.

In this study, an attempt has been made to devise a method for a large-scale production of quercetin from a medicinal plant. The natural products are first isolated from plants and then synthesized commercially. During their synthesis, a number of impurities or side products are also formed, most of which are carcinogenic. Plant products have limited side effects. Therefore, they are considered safe to be used for systemic uses. In the Rubus fruticosus fruit, the ethyl acetate extract was loaded to 50 optimized silica gel columns. The effluents of columns were passed through the membrane system for concentration. A 100% recovery was achieved from the drain pipe in case of reverse osmosis membrane when the specified rely of the pilot plant was set on 25% rejection. About 95% recovery was achieved through the NF membrane while the 5% loss in permeate was recovered through magnetic carbon nanocomposite (characterized through a bar magnet, SEM, XRD, and EDX). The equilibrium time of adsorption was 83 min and followed by pseudo-first-order kinetics. The adsorption equilibrium data fitted well to the Langmuir isotherm model. Through the devised method, quercetin was successfully concentrated with high efficiencies; however, further studies are needed to validate the method.