Predictive modeling for breast cancer classification in the context of Bangladeshi patients by use of machine learning approach with explainable AI.

Breast cancer has rapidly increased in prevalence in recent years, making it one of the leading causes of mortality worldwide. Among all cancers, it is by far the most common. Diagnosing this illness manually requires significant time and expertise. Since detecting breast cancer is a time-consuming process, preventing its further spread can be aided by creating machine-based forecasts. Machine learning and Explainable AI are crucial in classification as they not only provide accurate predictions but also offer insights into how the model arrives at its decisions, aiding in the understanding and trustworthiness of the classification results. In this study, we evaluate and compare the classification accuracy, precision, recall, and F1 scores of five different machine learning methods using a primary dataset (500 patients from Dhaka Medical College Hospital). Five different supervised machine learning techniques, including decision tree, random forest, logistic regression, naive bayes, and XGBoost, have been used to achieve optimal results on our dataset. Additionally, this study applied SHAP analysis to the XGBoost model to interpret the model's predictions and understand the impact of each feature on the model's output. We compared the accuracy with which several algorithms classified the data, as well as contrasted with other literature in this field. After final evaluation, this study found that XGBoost achieved the best model accuracy, which is 97%.

Unveiling Therapeutic Avenues for Crohn's Disease Management: Exploring Inhibitors for Adherent-Invasive Escherichia coli Propanediol Dehydratase.

INTRODUCTION: Inflammatory Bowel Disease (IBD) encompasses a group of chronic disorders distinguished by inflammation of the gastrointestinal tract. Among these, Crohn's Disease (CD) stands out as a complex and impactful condition due to challenges for both diagnosis and management, making it a cynosure of research. METHOD: In CD, there is the predominance of proinflammatory bacteria, including the Adherentinvasive Escherichia coli (AIEC) with virulence-associated metabolic enzyme Propanediol Dehydratase (pduC), which has been identified as a therapeutic target for the management of CD. Herein, molecular modeling techniques, including molecular docking, Molecular Mechanics with Generalized Born and Surface Area (MMGBSA), drug-likeness, and pharmacokinetics profiling, were utilized to probe the potentials of eighty antibacterial compounds to serve as inhibitors of pduC. RESULT: The results of this study led to the identification of five compounds with promising potentials; the results of the molecular docking simulation revealed the compounds as possessing better binding affinities for the target compared to the standard drug (sulfasalazine), while Lipinski's rule of five-based assessment of their drug-likeness properties revealed them as potential oral drugs. MMGBSA free energy calculation and Molecular Dynamics (MD) simulation of the complexes formed a sequel to molecular docking, revealing the compounds as stable binders in the active site of the protein. CONCLUSION: Ultimately, the results of this study have revealed five compounds to possess the potential to serve as inhibitors of pduC of AIEC. However, experimental studies are still needed to validate the findings of this study.

Revisiting methotrexate and phototrexate Zinc15 library-based derivatives using deep learning in-silico drug design approach.

Introduction: Cancer is the second most prevalent cause of mortality in the world, despite the availability of several medications for cancer treatment. Therefore, the cancer research community emphasized on computational techniques to speed up the discovery of novel anticancer drugs. Methods: In the current study, QSAR-based virtual screening was performed on the Zinc15 compound library (271 derivatives of methotrexate (MTX) and phototrexate (PTX)) to predict their inhibitory activity against dihydrofolate reductase (DHFR), a potential anticancer drug target. The deep learning-based ADMET parameters were employed to generate a 2D QSAR model using the multiple linear regression (MPL) methods with Leave-one-out cross-validated (LOO-CV) Q2 and correlation coefficient R2 values as high as 0.77 and 0.81, respectively. Results: From the QSAR model and virtual screening analysis, the top hits (09, 27, 41, 68, 74, 85, 99, 180) exhibited pIC50 ranging from 5.85 to 7.20 with a minimum binding score of -11.6 to -11.0 kcal/mol and were subjected to further investigation. The ADMET attributes using the message-passing neural network (MPNN) model demonstrated the potential of selected hits as an oral medication based on lipophilic profile Log P (0.19-2.69) and bioavailability (76.30% to 78.46%). The clinical toxicity score was 31.24% to 35.30%, with the least toxicity score (8.30%) observed with compound 180. The DFT calculations were carried out to determine the stability, physicochemical parameters and chemical reactivity of selected compounds. The docking results were further validated by 100 ns molecular dynamic simulation analysis. Conclusion: The promising lead compounds found endorsed compared to standard reference drugs MTX and PTX that are best for anticancer activity and can lead to novel therapies after experimental validations. Furthermore, it is suggested to unveil the inhibitory potential of identified hits via in-vitro and in-vivo approaches.

Computational antigenic insights into the novel NADC-34-like Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) isolate YC-2020.

In this computational study, we advanced the understanding of the antigenic properties of the NADC-34-like isolate of the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), named YC-2020, relevant in veterinary pathology. We utilized sequence comparison analyses of the M and N proteins, comparing them with those of NADC34, identifying substantial amino acid homology that allowed us to highlight conserved epitopes and crucial variants. Through the application of Clustal Omega for multiple sequence alignment and platforms like Vaxijen and AllerTOP for predicting antigenic and allergenic potential, our analyses revealed important insights into the conservation and variation of epitopes essential for the development of effective diagnostic tools and vaccines. Our findings, aligned with initial experimental studies, underscore the importance of these epitopes in the development of targeted immunodiagnostic platforms and significantly contribute to the management and control of PRRSV. However, further studies are required to validate the computational predictions of antigenicity for this new viral isolate. This approach underscores the potential of computational models to enable ongoing monitoring and control of PRRSV evolution in swine. While this study provides valuable insights into the antigenic properties of the novel PRRSV isolate YC-2020 through computational analysis, it is important to acknowledge the limitations inherent to in silico predictions, specifically, the absence of laboratory validation.

Molecular characterization of plasma virome of hepatocellular carcinoma (HCC) patients.

Hepatocellular carcinoma (HCC) stands as the most common cancer type, arising from various causes, and responsible for a substantial number of cancer-related fatalities. Recent advancements in viral metagenomics have empowered scientists to delve into the intricate diversity of the virosphere, viral evolution, interactions between viruses and their hosts, and the identification of viral causes behind disease outbreaks, the development of specific symptoms, and their potential role in altering the host's physiology. The present study had the objective of "Molecular Characterization of HBV, HCV, anelloviruses, CMV, SENV-D, SENV-H, HEV, and HPV viruses among individuals suffering from HCC." A total of 381 HCC patients contributed 10 cc of blood each for this study. The research encompassed the assessment of tumor markers, followed by molecular characterization of HBV, HCV, Anelloviruses (TTV, TTMV, and TTMDV), SENV-H and SENV-D viruses, HEV, CMV, and HPV, as well as histopathological examinations. The outcomes of this study revealed that majority of the HCC patients 72.4% (276/381) were male as compared to females. HCV infection, at 76.4% (291 out of 381), exhibited a significant association (p < 0.05) with HCC. Most patients displayed singular lesions in the liver, with Child Pugh Score Type B being the predominant finding in 45.2% of cases. Plasma virome analysis indicated the prevalence of TTMDV (75%), followed by TTMV (70%) and TTV (42.1%) among anelloviruses in HCC patients. Similarly, SENV-H (52%) was followed by SENV-D (20%), with co-infections at 15%. The presence of CMV and HEV among the HCC patients was recorded 5% each however 3.5% of the patients showed the presence of HPV. In conclusion, this study underscores that HCC patients serve as reservoirs for various pathogenic and non-pathogenic viruses, potentially contributing to the development, progression, and severity of the disease.

Ligand-based drug design against Herpes Simplex Virus-1 capsid protein by modification of limonene through in silico approaches.

The pharmacological effects of limonene, especially their derivatives, are currently at the forefront of research for drug development and discovery as well and structure-based drug design using huge chemical libraries are already widespread in the early stages of therapeutic and drug development. Here, various limonene derivatives are studied computationally for their potential utilization against the capsid protein of Herpes Simplex Virus-1. Firstly, limonene derivatives were designed by structural modification followed by conducting a molecular docking experiment against the capsid protein of Herpes Simplex Virus-1. In this research, the obtained molecular docking score exhibited better efficiency against the capsid protein of Herpes Simplex Virus-1 and hence we conducted further in silico investigation including molecular dynamic simulation, quantum calculation, and ADMET analysis. Molecular docking experiment has documented that Ligands 02 and 03 had much better binding affinities (- 7.4 kcal/mol and - 7.1 kcal/mol) to capsid protein of Herpes Simplex Virus-1 than Standard Acyclovir (- 6.5 kcal/mol). Upon further investigation, the binding affinities of primary limonene were observed to be slightly poor. But including the various functional groups also increases the affinities and capacity to prevent viral infection of the capsid protein of Herpes Simplex Virus-1. Then, the molecular dynamic simulation confirmed that the mentioned ligands might be stable during the formation of drug-protein complexes. Finally, the analysis of ADMET was essential in establishing them as safe and human-useable prospective chemicals. According to the present findings, limonene derivatives might be a promising candidate against the capsid protein of Herpes Simplex Virus-1 which ultimately inhibits Herpes Simplex Virus-induced encephalitis that causes interventions in brain inflammation. Our findings suggested further experimental screening to determine their practical value and utility.

Evaluation of Plant-Based Silver Nanoparticles for Antioxidant Activity and Promising Wound-Healing Applications.

The current research focuses on the green synthesis of silver nanoparticles (AgNPs) using a polar extract of taro corms and the evaluation of its antioxidant properties and wound-healing applications. Taro corm extract (100 mL) was treated with a 5 mM AgNO3 solution (100 mL) at room temperature for the formation of AgNPs, and a color change was observed. The surface plasmon resonance (SPR) peaks in their UV-visible spectra appeared at a range of 438-445 nm. Fourier transform infrared, scanning electron microscopy, energy-dispersive X-ray, dynamic light scattering, and X-ray diffraction were used for the characterization of the taro corms extract-mediated AgNPs (TCE-AgNPs). The synthesized AgNPs were crystalline and spherical, with an average size of 244.9-272.2 nm with a polydispersity index of 0.530 and zeta potential of -18.8 mV, respectively. The antibacterial potential of TCE-AgNPs was tested, and the inhibition zones detected against Cronobacter sakazakii, Pseudomonas aeruginosa, Listeria monocytogenes, and Enterococcus faecalis were 28, 26, 18, and 13 mm, respectively. Furthermore, the antioxidant activity of TCE-AgNPs showed significant radical-scavenging activity compared to the standard used. Collagen content data collected from regenerated tissue and higher collagen content indicated rapid wound healing compared to others, which was seen in a group treated with TCE-AgNP film bandages.

Targeting human progesterone receptor (PR), through pharmacophore-based screening and molecular simulation revealed potent inhibitors against breast cancer.

Breast cancer, the prevailing malignant tumor among women, is linked to progesterone and its receptor (PR) in both tumorigenesis and treatment responsiveness. Despite thorough investigation, the precise molecular mechanisms of progesterone in breast cancer remain unclear. The human progesterone receptor (PR) serves as an essential therapeutic target for breast cancer treatment, warranting the rapid design of small molecule therapeutics that can effectively inhibit HPR. By employing cutting-edge computational techniques like molecular screening, simulation, and free energy calculation, the process of identifying potential lead molecules from natural products has been significantly expedited. In this study, we employed pharmacophore-based virtual screening and molecular simulations to identify natural product-based inhibitors of human progesterone receptor (PR) in breast cancer treatment. High-throughput molecular screening of traditional Chinese medicine (TCM) and zinc databases was performed, leading to the identification of potential lead compounds. The analysis of binding modes for the top five compounds from both database provides valuable structural insights into the inhibition of HPR for breast cancer treatment. The top five hits exhibited enhanced stability and compactness compared to the reference compound. In conclusion, our study provides valuable insights for identifying and refining lead compounds as HPR inhibitors.

Anti-ulcerative colitis effects of chemically characterized extracts from Calliandra haematocephala in acetic acid-induced ulcerative colitis.

Background: Ulcerative colitis is a chronic immune-mediated inflammatory bowel disease that involves inflammation and ulcers of the colon and rectum. To date, no definite cure for this disease is available. Objective: The objective of the current study was to assess the effect of Calliandra haematocephala on inflammatory mediators and oxidative stress markers for the exploration of its anti-ulcerative colitis activity in rat models of acetic acid-induced ulcerative colitis. Methods: Methanolic and n-hexane extracts of areal parts of the plant were prepared by cold extraction method. Phytochemical analysis of both extracts was performed by qualitative analysis, quantitative methods, and high-performance liquid chromatography (HPLC). Prednisone at 2 mg/kg dose and plant extracts at 250, 500, and 750 mg/kg doses were given to Wistar rats for 11 days, which were given acetic acid on 8th day through the trans-rectal route for the induction of ulcerative colitis. A comparison of treatment groups was done with a normal control group and a colitis control group. To evaluate the anti-ulcerative colitis activity of Calliandra haematocephala, different parameters such as colon macroscopic damage, ulcer index, oxidative stress markers, histopathological examination, and mRNA expression of pro and anti-inflammatory mediators were evaluated. mRNA expression analysis was carried out by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Results: The phytochemical evaluation revealed polyphenols, flavonoids, tannins, alkaloids, and sterols in both extracts of the plant. Results of the present study exhibited that both extracts attenuated the large bowel inflammation and prevented colon ulceration at all tested doses. Macroscopic damage and ulcer scoreswere significantly decreased by both extracts. Malondialdehyde (MDA) levels and nitrite/nitrate concentrations in colon tissues were returned to normal levels while superoxide dismutase (SOD) activity was significantly improved by all doses. Histopathological examination exhibited that both extracts prevented the inflammatory changes, cellular infiltration, and colon thickening. Gene expression analysis by RT-qPCR revealed the downregulation of pro-inflammatory markers such as tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) whereas the anti-inflammatory cytokines including Interleukin-4 (IL-4) and Interleukin-10 (IL-10) were found to be upregulated in treated rats. Conclusion: It was concluded based on study outcomes that methanolic and n-hexane extracts of Calliandra haematocephala exhibited anti-ulcerative colitis activity through modulation of antioxidant defense mechanisms and the immune system. In this context, C. haematocephala can be considered as a potential therapeutic approach for cure of ulcerative colitis after bioassay-directed isolation of bioactive phytochemicals and clinical evaluation.

Chemical profiling of volatile compounds of the essential oil of grey-leaved rockrose (Cistus albidus L.) and its antioxidant, anti-inflammatory, antibacterial, antifungal, and anticancer activity in vitro and in silico.

Cistus albidus: L., also known as Grey-leaved rockrose and locally addressed as stab or tûzzâla lbîda, is a plant species with a well-established reputation for its health-promoting properties and traditional use for the treatment of various diseases. This research delves into exploring the essential oil extracted from the aerial components of Cistus albidus (referred to as CAEO), aiming to comprehend its properties concerning antioxidation, anti-inflammation, antimicrobial efficacy, and cytotoxicity. Firstly, a comprehensive analysis of CAEO's chemical composition was performed through Gas Chromatography-Mass Spectrometry (GC-MS). Subsequently, four complementary assays were conducted to assess its antioxidant potential, including DPPH scavenging, ß-carotene bleaching, ABTS scavenging, and total antioxidant capacity assays. The investigation delved into the anti-inflammatory properties via the 5-lipoxygenase assay and the antimicrobial effects of CAEO against various bacterial and fungal strains. Additionally, the research investigated the cytotoxic effects of CAEO on two human breast cancer subtypes, namely, MCF-7 and MDA-MB-231. Chemical analysis revealed camphene as the major compound, comprising 39.21% of the composition, followed by α-pinene (19.01%), bornyl acetate (18.32%), tricyclene (6.86%), and melonal (5.44%). Notably, CAEO exhibited robust antioxidant activity, as demonstrated by the low IC50 values in DPPH (153.92 ± 4.30 µg/mL) and ß-carotene (95.25 ± 3.75 µg/mL) assays, indicating its ability to counteract oxidative damage. The ABTS assay and the total antioxidant capacity assay also confirmed the potent antioxidant potential with IC50 values of 120.51 ± 3.33 TE µmol/mL and 458.25 ± 3.67 µg AAE/mg, respectively. In terms of anti-inflammatory activity, CAEO displayed a substantial lipoxygenase inhibition at 0.5 mg/mL. Its antimicrobial properties were broad-spectrum, although some resistance was observed in the case of Escherichia coli and Staphylococcus aureus. CAEO exhibited significant dose-dependent inhibitory effects on tumor cell lines in vitro. Additionally, computational analyses were carried out to appraise the physicochemical characteristics, drug-likeness, and pharmacokinetic properties of CAEO's constituent molecules, while the toxicity was assessed using the Protox II web server.

Investigating the Impact of Carbon Nanotube Nanoparticle Exposure on Testicular Oxidative Stress and Histopathological Changes in Swiss albino Mice.

Carbon nanotubes (CNTs) possess remarkable properties that make them valuable for various industrial applications. However, concerns have arisen regarding their potential adverse health effects, particularly in occupational settings. The main aim of this research was to examine the effects of short-term exposure to multiwalled carbon nanotube nanoparticles (MWCNT-NPs) on testicular oxidative stress in Swiss albino mice, taking into account various factors such as dosage, duration of exposure, and particle size of MWCNT-NP. In this study, 20 mice were used and placed into six different groups randomly. Four of these groups comprised four repetitions each, while the two groups served as the vehicle control with two repetitions each. The experimental groups received MWCNT-NP treatment, whereas the control group remained untreated. The mice in the experimental groups were exposed to MWCNT-NP for either 7 days or 14 days. Through oral administration, the MWCNT-NP solution was introduced at two distinct dosages: 0.45 and 0.90 µg, whereas the control group was subjected to distilled water rather than the MWCNT-NP solution. The investigation evaluated primary oxidative balance indicators-glutathione (GSH) and glutathione disulfide (GSSG)-in response to MWCNT-NP exposure. Significantly, a noticeable reduction in GSH levels and a concurrent increase in GSSG concentrations were observed in comparison to the control group. To better understand and explore the assessment of the redox status, the Nernst equation was used to calculate the redox potential. Intriguingly, the calculated redox potential exhibited a negative value, signifying an imbalance in the oxidative state in the testes. These findings suggest that short-term exposure to MWCNT-NP can lead to the initiation of testicular oxidative stress and may disrupt the male reproductive system. This is evident from the alterations observed in the levels of GSH and GSSG, as well as the negative redox potential. The research offers significant insights into the reproductive effects of exposure to MWCNTs and emphasizes the necessity of assessing oxidative stress in nanomaterial toxicity studies.

Machine learning and molecular simulation-based protocols to identify novel potential inhibitors for reverse transcriptase against HIV infections.

Acquired immunodeficiency syndrome (AIDS) is a potentially fatal condition affecting the human immune system, which is attributed to the human immunodeficiency virus (HIV). The suppression of reverse transcriptase activity is a promising and feasible strategy for the therapeutic management of AIDS. In this study, we employed machine learning algorithms, such as support vector machines (SVM), k-nearest neighbor (k-NN), random forest (RF), and Gaussian naive base (GNB), which are fast and effective tools commonly used in drug design. For model training, we initially obtained a dataset of 5,159 compounds from BindingDB. The models were assessed using tenfold cross-validation to ensure their accuracy and reliability. Among these compounds, 1,645 compounds were labeled as active, having an IC50 below 0.49 µM, while 3,514 compounds were labeled "inactive against reverse transcriptase. Random forest achieved 86% accuracy on the train and test set among the different machine learning algorithms. Random forest model was then applied to an external ZINC dataset. Subsequently, only three hits-ZINC1359750464, ZINC1435357562, and ZINC1545719422-were selected based on the Lipinski Rule, docking score, and good interaction. The stability of these molecules was further evaluated by deploying molecular dynamics simulation and MM/GBSA, which were found to be -38.6013 ± 0.1103 kcal/mol for the Zidovudine/RT complex, -59.1761 ± 2.2926 kcal/mol for the ZINC1359750464/RT complex, -47.6292 ± 2.4206 kcal/mol for the ZINC1435357562/RT complex, and -50.7334 ± 2.5713 kcal/mol for the ZINC1545719422/RT complex.Communicated by Ramaswamy H. Sarma.

Fabrication, organoleptic evaluation and in vitro characterization of cream loaded with Carica papaya seed extract.

OBJECTIVE: The current study aimed to provide preliminary insights into potential biopharmaceutical applications of Carica papaya seed extract by evaluating its phytochemical and biological profiles. Furthermore, the study aimed to develop a stable oil-in-water (O/W) emulsion for the effective delivery of antioxidant-rich biologicals for cosmetic purposes. METHODS: The hydroethanolic (ethanol 80%: 20% water) extract of C. papaya seeds was prepared via maceration technique. The chemical composition was carried out through preliminary phytochemical screening and estimation of total phenolic contents (TPC) and total flavonoid contents (TFC). The biological profile of the extract was explored using various in-vitro antioxidant methods. The homogenization procedure was used to create a cream of O/W and various tests were applied to assess the stability of the emulsion. By keeping the emulsion at different storage conditions (8 ± 0.5°C, 25 ± 0.5°C, 40 ± 0.5°C, and 40 ± 0.5°C ± 75% relative humidity [RH]) for a period of 28 days), the physical stability parameters of the emulsion, including pH, viscosity, centrifugation, phase separation, and conductivity, as well as rheological parameters and organoleptic parameters (odor, color, liquefaction, and creaming), were assessed. RESULTS: The preliminary phytochemical screening assay revealed the presence of various plant secondary metabolites including alkaloids, phenolics, flavonoids, tannins, saponins, and quinones. The extract was found to be rich in TPC and TFC. The in vitro antioxidant study gave maximum activity in the DPPH method. The plant extract containing cosmetic cream exhibited remarkable stability during the entire research. Data gathered indicated that no phase separation or liquefaction was seen after the experimental period. Throughout the experimental period, a small variation in the pH and conductivity values of the base and formulation was seen. CONCLUSION: The findings suggest that the seed extract of C. papaya is a rich source of polyphenols with antioxidant potential and can be a promising alternative for the treatment of various ailments. The stability of emulsion paves the way for its utilization as a carrier for the delivery of 3% C. papaya seed extract and applications in cosmetics products.

Diuretic Potential of Fenchyl Acetate with Its Mechanism of Action: Toxicity Study.

Hypertension has become a global threat and is one of the greatest risk factors for chronic kidney disease. Fenchyl acetate is a monoterpene that has been assessed for its various pharmacological activities in the past, but no study has evaluated its diuretic potential and the mechanism involved in the diuretic activity after prolonged administration in rats. Therefore, this study aimed to measure the safety and diuretic profile of fenchyl acetate in rats. For evaluating the acute toxicity, a single dose of 2000 mg/kg was administered as per the OECD guideline no. 425, and the rats were observed for 14 days. After 14 days, blood samples were assessed for biochemical, hematological, and oxidative stress parameters. For the acute diuretic study, fenchyl acetate was given in doses of 100, 200, and 400 mg/kg, and urine samples after 8 h were assessed for sodium, potassium, creatinine, uric acid excretion, and urinary output. A single dose of fenchyl acetate (F.A) was selected for prolonged diuretic activity, and furosemide was taken as the standard drug in a repeated dose administration for 7 days. Rats' urine was assessed for pH, sodium, potassium, creatinine, and uric acid excretion along with urinary volume excretion. Furthermore, blood was withdrawn by cardiac puncture, and selected organs like the heart, liver, kidney, and spleen were analyzed for oxidative stress biomarkers. Using pharmacological antagonists or inhibitors, the involvement of L-NAME, acetylcholine, or prostaglandin in F.A.-induced diuresis was determined. Mitochondrial respiratory chain enzyme complexes were also assessed in the kidney homogenates. The acute toxicity results showed F.A to be safe as its LD50 was greater than 2000 mg/kg and there were no signs of mortality or toxicity. The acute diuretic study showed that F.A resulted in a significant and dose-dependent increase in sodium, potassium, creatinine, and uric acid excretion along with urinary output, and these results were comparable to the standard drug furosemide. Prolonged administration with F.A (400 mg/kg) resulted in a comparable excretion of sodium, potassium, creatinine, uric acid, and urine output with furosemide (15 mg/kg). The oxidative stress parameters revealed that F.A (400 mg/kg) resulted in reducing the formation of free radicals. The results from the mechanism-based studies showed the involvement of NO in inducing diuresis. Furthermore, F.A (400 mg/kg) significantly increased the mitochondrial complexes I, II, III, IV, I + III, and II + III in the kidney homogenates, thus restoring the mitochondrial enzymes and improving the renal function. The current study suggests that F.A is safe with a significant diuretic potential with the involvement of NO in its mechanism of action.

Age-induced aortic modifications are accompanied by alterations in the antioxidant defense system in female rats.

Introduction: Aging leads to significant structural and functional changes in blood vessels, which disrupt their normal function and impact cardiovascular health. Current research is actively exploring the NRF2 antioxidative pathway, recognizing its role in protecting cells by preserving their antioxidant defenses against damage. However, there has been limited exploration into the role of the NRF2 pathway in vascular aging. The primary objective of this study was to determine whether age-related changes in the aorta are associated with variations in the baseline levels of antioxidant enzymes, with a particular emphasis on how the NRF2 pathway operates in the aortic wall. Methods: A group of healthy aging female SD rats was compared with their younger counterparts. Various assessments were conducted, including measuring blood pressure, analyzing serum lipid profiles, examining aortic tissue, and assessing the expression of antioxidant enzymes. Results: The results revealed significant differences in both blood pressure and serum lipid levels between the aged and younger rats. The examination of the aorta in older rats showed structural alterations, increased apoptosis, and the accumulation of fatty deposits. In the older rats, levels of SOD-1 (superoxide dismutase) and GSS (glutathione synthetase) were lower, whereas NRF2, KEAP-1 (Kelch-like ECH-associated protein 1), and HO-1 (Heme oxygenase 1) were higher. Discussion: This study advances our understanding of how aging affects the antioxidant system in blood vessels, particularly in relation to the regulation of the NRF2/HO-1 pathway in the aorta. These findings suggest that targeting the NRF2/HO-1 pathway could present anovel therapeutic approach for addressing age-related vascular issues.

Microwave-Assisted Formation of Ternary Inclusion Complex of Pterostilbene.

Pterostilbene (PTS) is a naturally occurring phytoalexin. PTS displays limited water solubility, which consequently results in its diminished oral bioavailability. Therefore, a ternary inclusion complex (TIC) of PTS with ß-cyclodextrin (ßCD) in the presence of ternary substance Pluronic® F-127 (PLF) was prepared using microwave technology. The PTS-TIC was characterized by dissolution performance. Further, the prepared TIC was characterized by DSC, FTIR, NMR, XRD, and SEM analysis. Additionally, the antioxidant activity of PTS and PTS-TIC was also evaluated. Phase-solubility studies revealed that PTS's solubility in water was increased by 6.72 times when ßCD/PLF was present. In comparison with PTS, prepared PTS-TIC produced a considerable improvement in PTS release. After 1 h, 74.03 ± 4.47% of PTS was released from PTS-TIC. Outcomes of DSC, FTIR, NMR, XRD, and SEM analysis revealed that the PTS was enclosed in the ßCD cavity. In terms of antioxidant properties, the PTS-TIC formulation demonstrated superior activity compared to PTS, possibly attributed to the improved solubility of PTS resulting from the formation of TIC using microwave technology. It was concluded that microwave technology proved to be an extremely beneficial means of interacting PTS with ßCD. In addition to increasing the solubility of PTS, the findings are also expected to improve its bioavailability by increasing its solubility. As a result, this study could provide insight into potential methods for enhancing the solubility of polyphenolic substances like PTS.

Napthyridine-derived compounds as promising inhibitors for Staphylococcus aureus CrtM: a primer for the discovery of potential anti-Staphylococcus aureus agents.

The disease-free existence of humans is constantly under attack by a variety of infections caused by a variety of organisms including bacteria. Notable among the bacteria is Staphylococcus aureus which is an etiological organism for infections including impetigo, folliculitis, and furuncles. The response of the human immune system against this disease is often neutralized by the production of a pigment called Staphyloxanthin (STX) via a series of reactions mediated by several enzymes. Among these enzymes, dehydrosqualene synthase, also known as CrtM, has emerged as a viable drug target due to its role in mediating the first step of the pathway. Consequently, this study employs molecular modeling approaches including molecular docking, quantum mechanical calculations, and molecular dynamics (MD) simulations among others to investigate the potential of napthyridine derivatives to serve as inhibitors of the CrtM. The results of the study revealed the high binding affinities of the compounds for the target as demonstrated by their docking scores, while further subjection to screening pipeline aimed at determining their fitness for development into drugs revealed just one compound namely 6-[[1-[(2-fluorophenyl) methyl]triazol-4-yl]methoxy]-4-oxo-1H-1,5-naphthyridine-3-carboxylic acid as the compound with good drug-like, pharmacokinetics, and toxicity properties profiles. A 100 ns-long MD simulation of the complexes formed after molecular docking revealed the stable interaction of the compound with the target. Ultimately, this study can be a promising outlet to discover a weapon to fight against clinically resistant bacteria, however, further experimental studies are suggested to carry out in the wet lab, pre-clinical, and clinical levels.

Outbreak investigation of NDM-producing Burkholderia cepacia causing neonatal sepsis in Pakistan.

Aim: To investigate the outbreak of Burkholderia cepacia complex (BCC), mortality, antimicrobial resistance and associated risk factors in the neonatal intensive care unit. Method: Eighteen blood culture samples from neonates and twenty swab samples from different neonatal intensive care unit surfaces were collected. The VITEK 2 was used to confirm the isolates and generate the antibiogram. PCR was used to identify blaNDM. Results: Eighteen samples tested positive for BCC, and 10/18 (55.5%) of the neonates died. 13/18 (72%) of the neonates had late-onset neonatal sepsis, and 10/18 (55%) had low birth weight. Resistance to minocycline and chloramphenicol was 100%, 72.2% to meropenem; 72.2% NDM gene was found in neonates and was 20% from the environment. Conclusion: Outbreak of NDM-producing BCC resulting in high neonatal mortality in NICU.

Neonatal septicemia, or blood poisoning, is a dangerous illness in newborns. It is caused by bacteria or other infections entering the blood and spreading. Pregnancy, labor, delivery and exposure after birth can result in infection of the newborn. Neonatal septicemia kills 700,000 babies worldwide, mostly in low- and middle-income countries. Burkholderia cepacia complex bacteria can cause infections in people with weaker immune systems or other disorders. They are particularly dangerous in hospitals, as they can cause chronic lung problems. This study collected blood samples from newborns with blood poisoning. Most samples that contained Burkholderia cepacia complex were not susceptible to drugs. Four of the newborns carried the same bacteria, indicating that hospital staff should practice hand washing and equipment and environmental cleaning to prevent the spread of the bacteria.

Novel computational and drug design strategies for inhibition of human papillomavirus-associated cervical cancer and DNA polymerase theta receptor by Apigenin derivatives.

The present study deals with the advanced in-silico analyses of several Apigenin derivatives to explore human papillomavirus-associated cervical cancer and DNA polymerase theta inhibitor properties by molecular docking, molecular dynamics, QSAR, drug-likeness, PCA, a dynamic cross-correlation matrix and quantum calculation properties. The initial literature study revealed the potent antimicrobial and anticancer properties of Apigenin, prompting the selection of its potential derivatives to investigate their abilities as inhibitors of human papillomavirus-associated cervical cancer and DNA polymerase theta. In silico molecular docking was employed to streamline the findings, revealing promising energy-binding interactions between all Apigenin derivatives and the targeted proteins. Notably, Apigenin 4'-O-Rhamnoside and Apigenin-4'-Alpha-L-Rhamnoside demonstrated higher potency against the HPV45 oncoprotein E7 (PDB ID 2EWL), while Apigenin and Apigenin 5-O-Beta-D-Glucopyranoside exhibited significant binding energy against the L1 protein in humans. Similarly, a binding affinity range of - 7.5 kcal/mol to - 8.8 kcal/mol was achieved against DNA polymerase theta, indicating the potential of Apigenin derivatives to inhibit this enzyme (PDB ID 8E23). This finding was further validated through molecular dynamic simulation for 100 ns, analyzing parameters such as RMSD, RMSF, SASA, H-bond, and RoG profiles. The results demonstrated the stability of the selected compounds during the simulation. After passing the stability testing, the compounds underwent screening for ADMET, pharmacokinetics, and drug-likeness properties, fulfilling all the necessary criteria. QSAR, PCA, dynamic cross-correlation matrix, and quantum calculations were conducted, yielding satisfactory outcomes. Since this study utilized in silico computational approaches and obtained outstanding results, further validation is crucial. Therefore, additional wet-lab experiments should be conducted under in vivo and in vitro conditions to confirm the findings.