Analysis of E2F1 single-nucleotide polymorphisms reveals deleterious non-synonymous substitutions that disrupt E2F1-RB protein interaction in cancer.

Cancer is a medical condition that is caused by the abnormal growth and division of cells, leading to the formation of tumors. The E2F1 and RB pathways are critical in regulating cell cycle, and their dysregulation can contribute to the development of cancer. In this study, we analyzed experimentally reported SNPs in E2F1 and assessed their effects on the binding affinity with RB. Out of 46, nine mutations were predicted as deleterious, and further analysis revealed four highly destabilizing mutations (L206W, R232C, I254T, A267T) that significantly altered the protein structure. Molecular docking of wild-type and mutant E2F1 with RB revealed a docking score of -242 kcal/mol for wild-type, while the mutant complexes had scores ranging from -217 to -220 kcal/mol. Molecular simulation analysis revealed variations in the dynamics features of both mutant and wild-type complexes due to the acquired mutations. Furthermore, the total binding free energy for the wild-type E2F1-RB complex was -64.89 kcal/mol, while those of the L206W, R232C, I254T, and A267T E2F1-RB mutants were -45.90 kcal/mol, -53.52 kcal/mol, -55.67 kcal/mol, and -61.22 kcal/mol, respectively. Our study is the first to extensively analyze E2F1 gene mutations and identifies candidate mutations for further validation and potential targeting for cancer therapeutics.

Exploring the antibacterial, antidiabetic, and anticancer potential of Mentha arvensis extract through in-silico and in-vitro analysis.

BACKGROUND: Mentha arvensis has been utilized in diverse traditional medicines as an antidiabetic, anticarcinogenic, antiallergic, antifungal, and antibacterial agent. In this work, we have explored the phytochemical analyses and pharmacological potential of Mentha arvensis using both in silico and in vitro approaches for drug discovery. METHODS: To determine the extract with the highest potential for powerful bioactivity, ethanol was used as the solvent. The phytochemical components of the extracts were quantified using liquid chromatography-mass spectrometry analysis. The potential bioactivities of extracts and lead phytocompounds, including their antibacterial, cytotoxic, and anti-diabetic effects, were evaluated. RESULTS: The compounds oleanolic acid, rosmarinic acid, luteolin, isoorientin, and ursolic acid have been identified through liquid chromatography mass spectrometry analysis. Based on antimicrobial research, it has been found that the Mentha arvensis extract shows potential activity against K. pneumoniae which was 13.39 ± 0.16. Mentha arvensis has demonstrated a greater degree of efficacy in inhibiting α-glucosidase, with an inhibition rate of 58.36 ± 0.12, and in inhibiting α-amylase, with an inhibition rate of 42.18 ± 0.83. The growth of HepG2 cells was observed to be significantly suppressed upon treatment with extracts obtained from Mentha arvensis. Finally, In-silico methods demonstrated that the Luteolin and Rosmarinic acid exhibit acceptable drug-like characteristics. Furthermore, Molecular docking studies further demonstrated that both compounds have strong potential to inhibit the active sites of therapeutically relevant enzymes involved in Diabetes, Bacterial infections, and Cancer. CONCLUSIONS: The results of this study suggest that the Mentha arvensis extract possesses potent pharmacological potentials, particularly in terms of antibacterial, anti-diabetic, and cytotoxic effects. Particularly, Luteolin and Rosmarinic acid were identified as the top contenders for potential bioactivity with acceptable drug-like properties.

Paraclostridium benzoelyticum Bacterium-Mediated Zinc Oxide Nanoparticles and Their In Vivo Multiple Biological Applications.

We presented a low-cost, eco-friendly, and efficient bacterium-mediated synthesis of zinc oxide nanoparticles (ZnO-NPs) utilizing Paraclostridium benzoelyticum strain 5610 as a capping and reducing agent. Scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, energy-dispersive X-ray, and UV-vis spectroscopy were used to physiochemically characterize the biosynthesized ZnO-NPs. A major narrow peak at 441 nm was observed using UV-visible spectroscopy, verifying the presence of nanoparticles. According to SEM and TEM studies, the average dimensions of ZnO-NPs was 50 nm. The crystal size of 48.22 nm was determined by XRD analysis. FTIR analysis confirmed the presence of various reducing metabolites on the surface of ZnO-NPs. The synthesized nanoparticles were investigated for biological activity against Helicobacter suis, Helicobacter bizzozeronii, Helicobacter felis, and Helicobacter salomonis. Helicobacter suis was the most vulnerable strain, with an inhibitory zone of 19.53 ± 0.62 mm at 5 mg/mL dosage. The anti-inflammatory and the findings of the rat paw edema experiments revealed that the bacterium-mediated ZnO-NPs had a strong inhibitory action. In the arthritis model, the solution of ZnO-NPs showed 87.62 ± 0.12% inhibitory effect of edema after 21 days when linked with that of the standard drug. In the antidiabetic assay, ZnO-NPs sharply reduced glucose level in STZ-induced diabetic mice. In this study, the particle biocompatibility by human red blood cells was also determined. Keeping in view the biological importance of ZnO-NPs, we may readily get the conclusion that Paraclostridium benzoelyticum strain 5610-mediated ZnO-NPs will be a prospective antidiabetic, antibacterial, antiarthritic, and anti-inflammatory agent in vivo experimental models and can be used as a potent antidiabetic drug.

Investigation of Chemopreventive and Antiproliferative Potential of Dicliptera roxburghiana.

CONTEXT: Carcinogenesis causes much human misery. It is a process involving multistage alterations. Medicinal plants are candidates for beneficial anticancer agents. OBJECTIVES: Investigation of anticancer proficiencies of the plant Dicliptera roxburghiana. MATERIAL AND METHODS: Crude extract and derived fractions were inspected for their inhibitory potential against nuclear factor KB (NFκB), nitric oxide synthase inhibition, aromatase inhibition and induction of quinone reductase 1 (QR 1). Antiproliferative activity was determined by using various cancer cell lines for example hormone responsive breast cancer cell line MCF-7, estrogen receptor negative breast cancer cell line MDA-MB-231, murine hepatoma cells Hepa 1c1c7, human neuroblastoma cells SK-N-SH and neuroblastoma cells MYCN-2. RESULTS: Ethyl acetate and n-butanol fractions of D. roxburghiana were strongly active against NFκB with IC50 of 16.6 ± 1.3 and 8.4 ± 0.7 µg/ml respectively with 100% survival. Chloroform fraction of the plant exhibited an induction ratio of 2.4 ± 0.09 with CD value of 17.7 µg/ml. Regarding the nitrite assay, the n-hexane fraction exhibited significant inhibition of NO activity with IC50 of 17.8 ± 1.25 µg/ml. The n-butanol fraction exhibited strong antiproliferative activity against IcIc-7 cell lines with IC50 values of 13.6 ± 1.91 µg/ml; against MYCN-2 a cytotoxic effect developed with dose dependence, with IC50 of 12.6 ± 1.24 µg/ml. In antiproliferative activity against SK-N-SH cell lines, chloroform, ethyl acetate and n-butanol fractions were efficiently active with IC50 values of 11.2 ± 0.84, 14.6 ± 1.71 and 16.3 ± 1.57 respectively. DISCUSSION AND CONCLUSION: It was demonstrated that various fractions of D. roxburghiana displayed appreciable anticancer characteristics and could be a potent source for the development of anticancer leads.

Development of Iron Nanoparticles (FeNPs) Using Biomass of Enterobacter: Its Characterization, Antimicrobial, Anti-Alzheimer's, and Enzyme Inhibition Potential.

Nanotechnology is a new field that has gained considerable importance due to its potential uses in the field of biosciences, medicine, engineering, etc. In the present study, bio-inspired metallic iron nanoparticles (FeNPs) were prepared using biomass of Enterobacter train G52. The prepared particles were characterized by UV-spectroscopy, TGA, XRD, SEM, EDX, and FTIR techniques. The crystalline nature of the prepared FeNPs was confirmed by XRD. The SEM techniques revealed the particles size to be 23 nm, whereas in FTIR spectra the peaks in the functional group region indicated the involvement of bioactive compounds of selected bacterial strains in the capping of FeNPs. The EDX confirmed the presence of iron in the engineered FeNPs. The FeNPs were then evaluated for its antibacterial, antifungal, antioxidant, anti-inflammatory, anti-Alzheimer's, anti-larvicidal, protein kinase inhibition, anti-diabetic, and biocompatibility potentials using standard protocols. Substantial activities were observed in almost all biological assays used. The antioxidant, anti-cholinesterase, and anti-diabetic potential of the prepared nanoparticles were high in comparison to other areas of biological potential, indicating that the FeNPs are capable of targeting meditators of oxidative stress leading to diabetes and Alzheimer's disease. However, the claim made needs some further experimentation to confirm the observed potential in in vivo animal models.

Plant-Based Synthesis of Zinc Oxide Nanoparticles (ZnO-NPs) Using Aqueous Leaf Extract of Aquilegia pubiflora: Their Antiproliferative Activity against HepG2 Cells Inducing Reactive Oxygen Species and Other In Vitro Properties.

The anti-cancer, anti-aging, anti-inflammatory, antioxidant, and anti-diabetic effects of zinc oxide nanoparticles (ZnO-NPs) produced from aqueous leaf extract of Aquilegia pubiflora were evaluated in this study. Several methods were used to characterize ZnO-NPs, including SEM, FTIR, XRD, DLS, PL, Raman, and HPLC. The nanoparticles that had a size of 34.23 nm as well as a strong aqueous dispersion potential were highly pure, spherical or elliptical in form, and had a mean size of 34.23 nm. According to FTIR and HPLC studies, the flavonoids and hydroxycinnamic acid derivatives were successfully capped. Synthesized ZnO-NPs in water have a zeta potential of -18.4 mV, showing that they are stable solutions. The ZnO-NPs proved to be highly toxic for the HepG2 cell line and showed a reduced cell viability of 23.68 ± 2.1% after 24 hours of ZnO-NP treatment. ZnO-NPs also showed excellent inhibitory potential against the enzymes acetylcholinesterase (IC50: 102 µg/mL) and butyrylcholinesterase (IC50: 125 µg/mL) which are involved in Alzheimer's disease. Overall, the enzymes involved in aging, diabetes, and inflammation showed a moderate inhibitory response to ZnO-NPs. Given these findings, these biosynthesized ZnO-NPs could be a good option for the cure of deadly diseases such as cancer, diabetes, Alzheimer's, and other inflammatory diseases due to their strong anticancer potential and efficient antioxidant properties.

Seroepidemiology and associated risk factors of hepatitis B and C virus infections among pregnant women attending maternity wards at two hospitals in Swabi, Khyber Pakhtunkhwa, Pakistan.

BACKGROUND & AIM: Hepatitis B and C infections are global issues that are associated with a massive financial burden in developing countries where vertical transmission is the major mode and remains high. This cross-sectional study was designed to investigate the seroepidemiology and associated risk factors of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among 375 pregnant women attending antenatal care health facilities at Bacha Khan Medical Complex (BKMC) Shahmansoor and District Head Quarter (DHQ) Hospital Swabi, Khyber Pakhtunkhwa, Pakistan. METHODOLOGY: From a total of 375 pregnant women selected using systematic random sampling from both hospitals, 10 ml of blood samples were collected and alienated serum was examined for indicators identification through the Immuno-Chromatographic Test (ICT) and 3rd Generation Enzyme-Linked Immunosorbent Assay (ELISA). A pre-structured questionnaire was used to collect the socio-demographic data and possible risk factors. The data was analyzed via SPSS 23.0 statistical software. A chi-square analysis was performed to determine the association between variables. P-value < 0.05 was set statistically significant. RESULTS: The overall frequency of HBV and HCV among 375 pregnant women involved in the study was 3.7% and 2.1% respectively. None of the pregnant women were co-infected with HBV and HCV. Dental extraction (P = 0.001) and blood transfusion (P = 0.0005) were significantly allied with HBV infection while surgical procedure (P = 0.0001) was significantly associated with HCV infection. Moreover the sociodemographic characteristics: residential status (P = 0.017) and educational level (P = 0.048) were found significant risk factors of HBsAg and maternal age (P = 0.033) of anti-HCV, respectively. CONCLUSION & RECOMMENDATION: HBV and HCV infections are intermediary endemic in the study area. A higher prevalence of HBV was detected among pregnant mothers with a history of dental extraction, history of blood transfusion, resident to the urban area and low educational level. The age and surgical procedures were the potential risk factors found significantly associated with HCV positivity among pregnant mothers in our setup. Future negotiations to control vertical transmission should include routine antenatal screening for these infections early in pregnancy and the requirement of efficient preventive tools including the birth dose of the hepatitis B vaccine in combination with hepatitis B immune globulins to the neonate.

Health risk assessment of heavy metals via consumption of dietary vegetables using wastewater for irrigation in Swabi, Khyber Pakhtunkhwa, Pakistan.

Health assumptions to the population due to the utilization of contaminated vegetables have been a great concern all over the world. In this study, an investigation has been conducted to ascertain metal concentrations in the wastewater, soil and commonly consumed vegetables from the vicinity of Gadoon Industrial Estate Swabi, Khyber Pakhtunkhwa Pakistan. Physicochemical parameters such as pH, electrical conductivity (EC), total dissolved solids (TDS), total suspended solids (TSS) and total solids (TS) and heavy metals such as Pb, Cr, Cd, Ni, Zn, Cu, Fe, Mn were determined using Atomic Absorption Spectrophotometer (AAS). Moreover, possible health risks due to the consumption of vegetables have also been estimated. pH and TSS in wastewater were found to be higher than the permissible limit set by WHO (1996). These results revealed that Cr concentration in the wastewater was above the permissible limits of United States Environmental Protection Agency (USEPA) which may lead to a detrimental effect on soil quality deterioration, ultimately leading to food contamination. ANOVA analysis demonstrated a significant difference in soil samples for Pb, Cr, Cd, Ni, Zn and Cu at p ≤ 0.001, for Mn at p ≤ 0.05 while no significant difference was observed for Fe respectively. ANOVA analysis also exhibited the highest mean value for Pb, Cr, Cd and Zn in vegetables. A substantial positive correlation was found among the soil and vegetable contamination. The transfer factor for Cr, Pb, Zn, Mn, Ni, Cd and Cu was greater than 0.5 due to contamination caused by domestic discharges and industrial effluents. Health assessment via consumption of dietary vegetables revealed a higher level than the permissible limit (HRI > 1) for Pb and Cd in children and adults. Enrichment factor (EF) due to consumption of vegetables was found higher for Pb and Cr respectively. Based on the findings of this study, there would be a significant risk to the consumers associated with consumptions of vegetables being cultivated in Gadoon Industrial Estate area of district Swabi. Therefore, strict regulatory control measures are highly recommended for the safety of vegetables originated from the study area.

Green Synthesis of Zinc Oxide (ZnO) Nanoparticles Using Aqueous Fruit Extracts of Myristica fragrans: Their Characterizations and Biological and Environmental Applications.

In the present work, bioaugmented zinc oxide nanoparticles (ZnO-NPs) were prepared from aqueous fruit extracts of Myristica fragrans. The ZnO-NPs were characterized by different techniques such as X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, ultraviolet (UV) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and thermogravimetric analysis (TGA). The crystallites exhibited a mean size of 41.23 nm measured via XRD and were highly pure, while SEM and TEM analyses of synthesized NPs confirmed their spherical or elliptical shape. The functional groups responsible for stabilizing and capping of ZnO-NPs were confirmed using FTIR analysis. The ζ-size and ζ-potential of synthesized ZnO-NPs were reported as 66 nm and -22.1 mV, respectively, via the DLS technique can be considered as moderate stable colloidal solution. Synthesized NPs were used to evaluate for their possible antibacterial, antidiabetic, antioxidant, antiparasitic, and larvicidal properties. The NPs were found to be highly active against bacterial strains both coated with antibiotics and alone. Klebsiella pneumoniae was found to be the most sensitive strain against NPs (27 ± 1.73) and against NPs coated with imipinem (26 ± 1.5). ZnO-NPs displayed outstanding inhibitory potential against enzymes protein kinase (12.23 ± 0.42), α-amylase (73.23 ± 0.42), and α-glucosidase (65.21 ± 0.49). Overall, the synthesized NPs have shown significant larvicidal activity (77.3 ± 1.8) against Aedes aegypti, the mosquitoes involved in the transmission of dengue fever. Similarly, tremendous leishmanicidal activity was also observed against both the promastigote (71.50 ± 0.70) and amastigote (61.41 ± 0.71) forms of the parasite. The biosynthesized NPs were found to be excellent antioxidant and biocompatible nanomaterials. Biosynthesized ZnO-NPs were also used as photocatalytic agents, resulting in 88% degradation of methylene blue dye in 140 min. Owing to their eco-friendly synthesis, nontoxicity, and biocompatible nature, ZnO-NPs synthesized from M. fragrans can be exploited as potential candidates for biomedical and environmental applications.

Green synthesis, characterisation and biological evaluation of plant-based silver nanoparticles using Quercus semecarpifolia Smith aqueous leaf extract.

The development of reliable and green methods for the fabrication of metallic nanoparticles (NPs) has many advantages in the field of nanotechnology. In this direction, the present work describes an eco-friendly and cost-effective protocol for the production of silver NPs (AgNPs) using an aqueous extract of Quercus semecarpifolia leaves. Different techniques were carried out for the characterisation of the synthesised AgNPs. The ultraviolet-visible spectroscopic analysis showed the highest absorbance peak at 430 nm. The particle size and structure were confirmed by scanning electron microscopy as well as transmission electron microscopy (TEM) analysis. From TEM imaging, it was revealed that the formed particles were spherical with an average size of 20-50 nm. The crystalline nature of the NPs was determined by X-ray powder diffraction patterns. Thermogravimetry and differential thermal analysis were also evaluated by a temperature increment from 100 to 1000°C. Bio-inspired synthesis of AgNPs was performed for their pharmacological evaluation in relation to the activities of the crude methanolic, n-hexane, chloroform, ethyl acetate, and aqueous extracts. Good cytotoxic activity was exhibited by the green-synthesised AgNPs (77%). Furthermore, the AgNPs were found to exhibit significant antioxidant activity at 300 µg/ml (82%). The AgNPs also exhibited good phytotoxic potential (75%).