Clinical profile of functional constipation in Saudi children.

BACKGROUND: Functional constipation (FC) is a common condition in children, and information on the clinical characteristics of FC in Saudi children is scarce. OBJECTIVE: Describe the clinical profile of FC in Saudi children. DESIGN: Retrospective. SETTING: Hospital that provides primary, intermediate and tertiary care. PATIENTS AND METHODS: All children diagnosed with FC according to the Rome IV criteria were included and had at least one follow-up clinic visit. Demographic and clinical data collected from medical records included the age at onset, duration of constipation, clinical features, treatment modalities, and factors associated with clinical response. Descriptive statistics and Pearson's chi-squared test were used in the statistical analysis to see how categorical study variables were linked to clinical response. A P value of ≤.05 was used to report statistical significance. MAIN OUTCOME MEASURE: Compliance and clinical response to polyethylene glycol (PEG) compared with lactulose. SAMPLE SIZE: 370 children from 0.1 to 13 years of age. RESULTS: The median (IQR) age of onset was 4 (5) years and less than one year in 14%. The median (IQR) duration of constipation was 4 months (11) and less than two months in 93/370 (25%). Abdominal pain was the most commonly associated feature (44%). Screening for celiac disease and hypothyroidism was negative. A Fleet enema was the most common disimpaction method (54%) and PEG was the most common maintenance medication (63.4%). PEG was significantly better tolerated (P=.0008) and more effective than lactulose (P<.0001). Compliance was the only variable significantly associated with clinical response. CONCLUSIONS: PEG was better tolerated and more effective than lactulose in our study, a finding in agreement with the literature. Therefore, PEG should be the drug of choice in the initial management of FC in Saudi children. Prospective studies on the causes of noncompliance are needed to improve the response to treatment. LIMITATIONS: The limitations of retrospective design are missing data, recall bias, and hospital-based limitation, such as missing milder cases treated at the outpatient level. However, the sample size of 370 may have minimized these limitations.

Fungus-mediated synthesis of Se-BiO-CuO multimetallic nanoparticles as a potential alternative antimicrobial against ESBL-producing Escherichia coli of veterinary origin.

Bacterial infections emerge as a significant contributor to mortality and morbidity worldwide. Emerging extended-spectrum ß-lactamase (ESBL) Escherichia coli strains provide a greater risk of bacteremia and mortality, are increasingly resistant to antibiotics, and are a major producer of ESBLs. E. coli bacteremia-linked mastitis is one of the most common bacterial diseases in animals, which can affect the quality of the milk and damage organ functions. There is an elevated menace of treatment failure and recurrence of E. coli bacteremia necessitating the adoption of rigorous alternative treatment approaches. In this study, Se-Boil-CuO multimetallic nanoparticles (MMNPs) were synthesized as an alternate treatment from Talaromyces haitouensis extract, and their efficiency in treating ESBL E. coli was confirmed using standard antimicrobial assays. Scanning electron microscopy, UV-visible spectroscopy, and dynamic light scattering were used to validate and characterize the mycosynthesized Se-BiO-CuO MMNPs. UV-visible spectra of Se-BiO-CuO MMNPs showed absorption peak bands at 570, 376, and 290 nm, respectively. The average diameters of the amorphous-shaped Se-BiO-CuO MMNPs synthesized by T. haitouensis extract were approximately 66-80 nm, respectively. Se-BiO-CuO MMNPs (100 µg/mL) showed a maximal inhibition zone of 18.33 ± 0.57 mm against E. coli. Se-BiO-CuO MMNPs also exhibited a deleterious impact on E. coli killing kinetics, biofilm formation, swimming motility, efflux of cellular components, and membrane integrity. The hemolysis assay also confirms the biocompatibility of Se-BiO-CuO MMNPs at the minimum inhibitory concentration (MIC) range. Our findings suggest that Se-BiO-CuO MMNPs may serve as a potential substitute for ESBL E. coli bacteremia.

Corrigendum: Exploring the antibacterial and dermatitis-mitigating properties of chicken egg white-synthesized zinc oxide nano whiskers.

[This corrects the article DOI: 10.3389/fcimb.2023.1295593.].

Phytochemical profiling, antioxidant, cytotoxic, and anti-inflammatory activities of Plectranthus rugosus extract and fractions: in vitro, in vivo, and in silico approaches.

BACKGROUND: Inflammation is a key biological reaction that comprises a complex network of signals that both initiate and stop the inflammation process. PURPOSE: This study targets to evaluate the anti-inflammatory potential of the leaves of the Plectranthus rugosus (P. rugosus) plant involving both in vitro and in vivo measures. The current available drugs exhibit serious side effects. Traditional medicines impart an essential role in drug development. P. rugosus is a plant used in traditional medicine of Tropical Africa, China, and Australia to treat various diseases. METHODS: Lipopolysaccharide (LPS), an endotoxin, kindles macrophages to discharge huge quantities of pro-inflammatory cytokines like TNF-α and IL-6. So, clampdown of macrophage stimulation may have a beneficial potential to treat various inflammatory disorders. The leaves of the P. rugosus are used for swelling purpose by local population; however, its use as an anti-inflammatory agent and associated disorders has no scientific evidence. RESULTS: The extracts of the plant Plectranthus rugosus ethanolic extract (PREE), Plectranthus rugosus ethyl acetate extract (PREAF), and the compound isolated (oleanolic acid) suppress the pro-inflammatory cytokines (IL-6 and TNF-α) and nitric oxide (NO), confirming its importance in traditional medicine. CONCLUSION: The pro-inflammatory cytokines are inhibited by P. rugosus extracts, as well as an isolated compound oleanolic acid without compromising cell viability.

Natural sapogenins as potential inhibitors of aquaporins for targeted cancer therapy: computational insights into binding and inhibition mechanism.

Aquaporins (AQPs) are membrane proteins that facilitate the transport of water and other small molecules across biological membranes. AQPs are involved in various physiological processes and pathological conditions, including cancer, making them as potential targets for anticancer therapy. However, the development of selective and effective inhibitors of AQPs remains a challenge. In this study, we explored the possibility of using natural sapogenins, a class of plant-derived aglycones of saponins with diverse biological activities, as potential inhibitors of AQPs. We performed molecular docking, dynamics simulation and binding energy calculation to investigate the binding and inhibition mechanism of 19 sapogenins against 13 AQPs (AQP0-AQP13) that are overexpressed in various cancers. Our results showed that out of 19 sapogenins, 8 (Diosgenin, Gitogenin, Tigogenin, Ruscogenin, Yamogenin, Hecogenin, Sarsasapogenin and Smilagenin) exhibited acceptable drug-like characteristics. These sapogenin also exhibited favourable binding affinities in the range of -7.6 to -13.4 kcal/mol, and interactions within the AQP binding sites. Furthermore, MD simulations provided insights into stability and dynamics of the sapogenin-AQP complexes. Most of the fluctuations in binding pocket were observed for AQP0-Gitogenin and AQP4-Diosgenin. However, remaining protein-ligand complex showed stable root mean square deviation (RMSD) plots, strong hydrogen bonding interactions, stable solvent-accessible surface area (SASA) values and minimum distance to the receptor. These observations suggest that natural sapogenin hold promise as novel inhibitors of AQPs, offering a basis for the development of innovative therapeutic agents for cancer treatment. However, further validation of the identified compounds through experiments is essential for translating these findings into therapeutic applications.Communicated by Ramaswamy H. Sarma.

Discovering potential inhibitors of Raf proto-oncogene serine/threonine kinase 1: a virtual screening approach towards anticancer drug development.

Raf proto-oncogene serine/threonine kinase 1 (RAF1 or c-Raf) is a serine/threonine protein kinase crucial in regulating cell growth, differentiation, and survival. Any disruption or overexpression of RAF1 can result in neoplastic transformation and other disorders such as cardiomyopathy, Noonan syndrome, leopard syndrome, etc. RAF1 has been identified as a potential therapeutic target in drug development against various complex diseases, including cancer, due to its remarkable role in disease progression. Here, we carried out a multitier virtual screening study involving different in-silico approaches to discover potential inhibitors of RAF1. After applying the Lipinski rule of five, we retrieved all phytocompounds from the IMPPAT database based on their physicochemical properties. We performed a molecular docking-based virtual screening and got top hits with the best binding affinity and ligand efficiency. Then we screened out the selected hits using the PAINS filter, ADMET properties, and other druglike features. Eventually, PASS evaluation identifies two phytocompounds, Moracin C and Tectochrysin, with appreciable anti-cancerous properties. Finally, all-atom molecular dynamics simulation (MDS) followed by interaction analysis was performed on the elucidated compounds in complex with RAF1 for 200 ns to investigate their time-evolution dynamics and interaction mechanism. Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and Dynamical Cross-Correlation Matrix (DCCM) analyses then followed these results from the simulated trajectories. According to the results, the elucidated compounds stabilize the RAF1 structure and lead to fewer conformational alterations. The results of the current study indicated that Moracin C and Tectochrysin could serve as potential inhibitors of RAF1 after required validation.Communicated by Ramaswamy H. Sarma.

Identification of mitogen-activated protein kinase 7 inhibitors from natural products: Combined virtual screening and dynamic simulation studies.

Mitogen-activated protein kinase 7 (MAPK7) is a serine/threonine protein kinase that belongs to the MAPK family and plays a vital role in various cellular processes such as cell proliferation, differentiation, gene transcription, apoptosis, metabolism, and cell survival. The elevated expression of MAPK7 has been associated with the onset and progression of multiple aggressive tumors in humans, underscoring the potential of targeting MAPK7 pathways in therapeutic research. This pursuit holds promise for the advancement of anticancer drug development by developing potential MAPK7 inhibitors. To look for potential MAPK7 inhibitors, we exploited structure-based virtual screening of natural products from the ZINC database. First, the Lipinski rule of five criteria was used to filter a large library of ~90,000 natural compounds, followed by ADMET and pan-assay interference compounds (PAINS) filters. Then, top hits were chosen based on their strong binding affinity as determined by molecular docking. Further, interaction analysis was performed to find effective and specific compounds that can precisely bind to the binding pocket of MAPK7. Consequently, two compounds, ZINC12296700 and ZINC02123081, exhibited significant binding affinity and demonstrated excellent drug-like properties. All-atom molecular dynamics simulations for 200 ns confirmed the stability of MAPK7-ZINC12296700 and MAPK7-ZINC02123081 docked complexes. According to the molecular mechanics Poisson-Boltzmann surface area investigation, the binding affinities of both complexes were considerable. Overall, the result suggests that ZINC12296700 and ZINC02123081 might be used as promising leads to develop novel MAPK7 inhibitors. Since these compounds would interfere with the kinase activity of MAPK7, therefore, may be implemented to control cell growth and proliferation in cancer after required validations.

Exploring the potential of phytochemicals as inhibitors of 3'-phosphoadenosine 5'-phosphosulfate synthase 1 targeting cancer therapy.

3'-phosphoadenosine 5'-phosphosulfate synthase 1 (PAPSS1) is an enzyme that critically synthesises the biologically active form of sulfate (PAPS) for all sulfation reactions. The discovery of PAPSS1 as a possible drug target for cancer therapy, specifically in non-small cell lung cancer, has prompted us to investigate potential small-molecule inhibitors of PAPSS1. Here, a structure-based virtual screening method was used to search for phytochemicals in the IMPPAT database to find potential inhibitors of PAPSS1. The primary hits were selected based on their physicochemical, ADMET, and drug-like properties. Then, the binding affinities were calculated and analyzed the interactions to identify safer and more effective hits. The research identified two phytochemicals, Guggulsterone and Corylin, that exhibited significant affinity and specific interaction with the ATP-binding pocket of PAPSS1. Structural observations made by molecular docking were further accompanied by molecular dynamics (MD) simulations and principal component analysis (PCA) to examine the conformational changes and stability of PAPSS1 with the elucidated compounds Guggulsterone and Corylin. MD simulation results suggested that the binding of Guggulsterone and Corylin stabilizes the PAPSS1 structure, leading to fewer conformational changes. This implies that these compounds may be useful in developing PAPSS1 inhibitors for the therapeutic development against non-small cell lung cancer (NSCLC). This study highlights the potential of phytochemicals as PAPSS1 inhibitors and the utility of computational approaches in drug discovery.Communicated by Ramaswamy H. Sarma.

Network Pharmacology Combined with Molecular Docking, Molecular Dynamics, and In Vitro Experimental Validation Reveals the Therapeutic Potential of Thymus vulgaris L. Essential Oil (Thyme Oil) against Human Breast Cancer.

Breast cancer is a major global health issue for women. Thyme oil, extracted from Thymus vulgaris L., has shown promising anticancer effects. In the present study, we investigated how Thyme oil can influence breast cancer treatment using a multimethod approach. We used network pharmacology to identify the active compounds of Thyme oil, their molecular targets, and the pathways involved in breast cancer. We found that Thyme oil can modulate several key proteins (EGFR, AKT1, ESR1, HSP90AA1, STAT-3, SRC, IL-6, HIF1A, JUN, and BCL2) and pathways (EGFR tyrosine kinase inhibitor resistance, prolactin signaling pathway, HIF-1 signaling pathway, estrogen signaling pathway, ERBB signaling pathway, AGE-RAGE signaling pathway, JAK-STAT signaling pathway, FoxO signaling pathway, and PI3K-AKT signaling pathway) related to breast cancer progression. We then used molecular docking and dynamics to study the interactions and stability of the Thyme oil-compound complexes. We discovered three potent compounds (aromadendrene, α-humulene, and viridiflorene) that can bind strongly to important breast cancer proteins. We also performed in vitro experiments on MCF-7 cells to confirm the cytotoxicity and antiproliferative effects of Thyme oil. We observed that Thyme oil can inhibit cancer cell growth and proliferation at a concentration of 365.37 µg/mL. Overall, our results provide a comprehensive understanding of the pharmacological mechanism of Thyme oil in breast cancer treatment and suggest its potential as a new or adjuvant therapy. Further studies are needed to validate and optimize the therapeutic efficacy of Thyme oil and its active compounds.

Exploring the antibacterial and dermatitis-mitigating properties of chicken egg white-synthesized zinc oxide nano whiskers.

Introduction: Zinc oxide nanoparticles (ZnO-NPs) have garnered considerable interest in biomedical research primarily owing to their prospective therapeutic implications in combatting pathogenic diseases and microbial infections. The primary objective of this study was to examine the biosynthesis of zinc oxide nanowhiskers (ZnO-NWs) using chicken egg white (albumin) as a bio-template. Furthermore, this study aimed to explore the potential biomedical applications of ZnO NWs in the context of infectious diseases. Methods: The NWs synthesized through biological processes were observed using electron microscopy, which allowed for detailed examination of their characteristics. The results of these investigations indicated that the NWs exhibited a size distribution ranging from approximately 10 to 100 nm. Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) mapping analyses successfully corroborated the size, dimensions, and presence of biological constituents during their formation. In this study, XTT assay and confocal imaging were employed to provide evidence of the efficacy of ZnO-NWs in the eradication of bacterial biofilms. The target bacterial strains were Staphylococcus aureus and Escherichia coli. Furthermore, we sought to address pertinent concerns regarding the biocompatibility of the ZnO-NWs. This was achieved through comprehensive evaluation of the absence of cytotoxicity in normal HEK-293T and erythrocytes. Results: The findings of this investigation unequivocally confirmed the biocompatibility of the ZnO-NWs. The biosynthesized ZnO-NWs demonstrated a noteworthy capacity to mitigate the dermatitis-induced consequences induced by Staphylococcus aureus in murine models after a therapeutic intervention lasting for one week. Discussion: This study presents a comprehensive examination of the biosynthesis of zinc oxide nanowhiskers (ZnO-NWs) derived from chicken egg whites. These findings highlight the considerable potential of biosynthesized ZnO-NWs as a viable option for the development of therapeutic agents targeting infectious diseases. The antibacterial efficacy of ZnO-NWs against both susceptible and antibiotic-resistant bacterial strains, as well as their ability to eradicate biofilms, suggests their promising role in combating infectious diseases. Furthermore, the confirmed biocompatibility of ZnO-NWs opens avenues for their safe use in biomedical applications. Overall, this research underscores the therapeutic promise of ZnO-NWs and their potential significance in future biomedical advancements.

Resistance Modulation of Individual and Polymicrobial Culture of S. aureus and E. coli through Nanoparticle-Coupled Antibiotics.

Polymicrobial mastitis is now becoming very common in dairy animals, resulting in exaggerated resistance to multiple antibiotics. The current study was executed to find drug responses in individual and mixed Culture of Staphylococcus aureus and Escherichia coli isolated from milk samples, as well as to evaluate the antibacterial potential of tungsten oxide nanoparticles. These isolates (alone and in mixed culture) were further processed for their responses to antibiotics using the disc diffusion method. On the other hand, tungsten oxide WO3 (W) nanoparticles coupled with antibiotics (ampicillin, A, and oxytetracycline, O) were prepared through the chemical method and characterized by X-ray diffraction, scanning electron microscopy (SEM), and UV-visible techniques. The preparations consisting of nanoparticles alone (W) and coupled with ampicillin (WA) and oxytetracycline (WO) were tested against individual and mixed Culture through the well diffusion and broth microdilution methods. The findings of the current study showed the highest resistance in E. coli was against penicillin (60%) and ampicillin (50%), while amikacin, erythromycin, ciprofloxacin, and oxytetracycline were the most effective antibiotics. S. aureus showed the highest resistance against penicillin (50%), oxytetracycline (40%), and ciprofloxacin (40%), while, except for ampicillin, the sensitive strains of S. aureus were in the range of 40-60% against the rest of antibiotics. The highest zones of inhibition (ZOI) against mixed Culture were shown by imipenem and ampicillin, whereas the highest percentage decrease in ZOI was noted in cases of ciprofloxacin (-240%) and gentamicin (-119.4%) in comparison to individual Culture of S. aureus and E. coli. It was noteworthy that the increase in ZOI was not more than 38% against mixed Culture as compared to the individual Culture. On the other hand, there was a significant reduction in the minimum inhibitory concentration (MIC) of nanoparticle-coupled antibiotics compared to nanoparticles alone for individual and mixed-culture bacteria, while MICs in the case of mixed Culture remained consistently high throughout the trial. This study therefore concluded that diverse drug resistance was present in both individual and mixed-culture bacteria, whereas the application of tungsten oxide nanoparticle-coupled antibiotics proved to be an effective candidate in reversing the drug resistance in bacterial strains.

Methotrexate-conjugated zinc oxide nanoparticles exert a substantially improved cytotoxic effect on lung cancer cells by inducing apoptosis.

In the current study, we report the synthesis of methotrexate-conjugated zinc oxide nanoparticles (MTX-ZnONPs) and their high efficacy against lung cancer cells. Conjugation of MTX with ZnONPs was authenticated by UV-vis spectroscopy, dynamic light scattering (DLS), Fourier-transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). This drug-nanoconjugate also showed high drug-loading efficiency. The therapeutic efficacy of MTX-ZnONPs was further tested in vitro against A549 cells, and the results of MTT and LDH release assays showed that MTX-ZnONPs, in addition to free MTX, were efficient in exerting cytotoxic effect on A549 cells; however, the effectiveness of MTX-ZnONPs was found to be considerably enhanced at very low doses compared to that of free MTX. Moreover, ZnONPs alone significantly inhibited the cell viability of A549 cells at a much higher concentration compared to MTX-ZnONPs and MTX. Furthermore, the cytomorphology of A549 cells was characterized by cellular shrinkage and detachment from the surface in all the treatment groups. Similarly, A549 cells, in all the treatment groups, showed fragmented and condensed nuclei, indicating the initiation of apoptosis. Mitochondrial membrane potential (ψm) in A549 cells showed a gradual loss in all the treatment groups. Results of the qualitative and quantitative analyses depicted increased reactive oxygen species (ROS) levels in A549 cells. The results of the caspase activity assay showed that MTX-ZnONPs andfree MTX caused significant activation of caspase-9, -8, and -3 in A549 cells; however, the effect of MTX-ZnONPs was more profound at very low doses compared to that of free MTX. Thus, our results showed high efficacy of MTX-ZnONPs, suggesting efficient intracellular delivery of the drug by ZnONPs as nanocarriers.

Molecular interactions of cucurbitacins A and B with anaplastic lymphoma kinase for lung cancer treatment.

Lung cancer is a major global public health issue and the leading cause of cancer-related deaths. Several medications are commonly used to treat lung cancer, either alone or in combination with other treatments. The anaplastic lymphoma kinase (ALK) protein is one of several target proteins that are thought to be potential therapeutic targets in the context of lung cancer. Several ALK inhibitors have been identified, but many of these have been associated with side effects and toxicity concerns. In this study, we intend to computationally predict the binding potential of cucurbitacins (CBNs), A and B to the active pockets of ALK, in order to estimate their potential ALK inhibitors. Compared to CBN-A, which has a binding energy of -7.9 kcal/mol, CBN B exhibits significantly better binding efficacy with a binding energy of -8.1 kcal/mol. This is closely comparable to the binding energy of Crizotinib, which is -8.2 kcal/mol. The results of the molecular dynamics simulation indicated that the docked complexes remained stable for the duration of the 100 ns simulation period. CBN inhibited the proliferation of both non-small cell lung cancer cell lines, H1299 and A549, in a dose-dependent manner. CBN-B inhibited the proliferation of lung cancer cells, showing IC50 values of 0.08 µM for H1299 cells and 0.10 µM for A549 cells. The computational analyses provide strong evidence that CBN-B has the potential to act as a potent natural inhibitor against ALK, and could prove to be a valuable treatment option for lung cancer.Communicated by Ramaswamy H. Sarma.

Isolation of anticancer bioactive secondary metabolites from the sponge-derived endophytic fungi Penicillium sp. and in-silico computational docking approach.

Introduction: Fungus-derived secondary metabolites are fascinating with biomedical potential and chemical diversity. Mining endophytic fungi for drug candidates is an ongoing process in the field of drug discovery and medicinal chemistry. Endophytic fungal symbionts from terrestrial plants, marine flora, and fauna tend to produce interesting types of secondary metabolites with biomedical importance of anticancer, antiviral, and anti-tuberculosis properties. Methods: An organic ethyl acetate extract of Penicillium verruculosum sponge-derived endophytic fungi from Spongia officinalis yielded seven different secondary metabolites which are purified through HPLC. The isolated compounds are of averufin (1), aspergilol-A (2), sulochrin (3), monomethyl sulochrin (4), methyl emodin (5), citreorosein (6), and diorcinol (7). All the seven isolated compounds were characterized by high-resolution NMR spectral studies. All isolated compounds', such as anticancer, antimicrobial, anti-tuberculosis, and antiviral, were subjected to bioactivity screening. Results: Out of seven tested compounds, compound (1) exhibits strong anticancer activity toward myeloid leukemia. HL60 cell lines have an IC50 concentration of 1.00µm, which is nearly significant to that of the standard anticancer drug taxol. A virtual computational molecular docking approach of averufin with HL60 antigens revealed that averufin binds strongly with the protein target alpha, beta-tubulin (1JFF), with a -10.98 binding score. Consecutive OSIRIS and Lipinski ADME pharmacokinetic validation of averufin with HL60 antigens revealed that averufin has good pharmacokinetic properties such as drug score, solubility, and mutagenic nature. Furthermore, aspergilol-A (2) is the first report on the Penicillium verruculosum fungal strain. Discussion: We concluded that averufin (1) isolated from Penicillium verruculosum can be taken for further preliminary clinical trials like animal model in-vivo studies and pharmacodynamic studies. A future prospect of in-vivo anticancer screening of averufin can be validated through the present experimental findings.

GC-MS-based profiling and ameliorative potential of Carissa opaca Stapf ex Haines fruit against cardiac and testicular toxicity: An In vivo study.

Fruit of Carissa opaca Stapf ex Haines (C. opaca) is a feed additive and is commonly used against cardiac dysfunction, fever, asthma, diarrhea, gastrointestinal ailments, and skin diseases. In this study, we aimed to evaluate the metabolic profile and antioxidant potential of C. opaca fruit against carbon tetrachloride (CCl4)-induced cardiotoxicity and testicular toxicity in rats. Gas Chromatoghraphy-Mass Spectrometry (GC-MS) analysis of C. opaca fruit for the identification of potential metabolic profile, followed by methanolic extract of C. opaca and its derived fractions including n-hexane, ethyl acetate, chloroform, butanol, and aqueous were used to assess the antioxidant potential of fruits. Ten groups of rats received different treatments and got evaluated for cardiac and testicular antioxidant enzymes, histological architecture, and serum hormonal levels. GC-MS analysis of methanolic extract of C. opaca fruit showed the presence of some bioactive metabolites like cyclodecane, diethyl 2,6-pyridine dicarboxylate, tetrahydro-geraniol, S-[2-[N, N-Dimethylamino]ethyl]morpoline, 2,3-Methylenedioxyphenol, alpha-d-Glucopyranoside, 5,10-Diethoxy-2,3,7,8-tetrahydro-1H, 6H-dipyrrolo [1,2-a; 1',2'-d] pyrazine and 1,3-Benzothiazol-2(3H)-one,3-(3,3-dimethyl-1-oxobutyl) that corresponds the medicinal properties of C. opaca fruit. Prepared fractions of C. opaca fruits mitigated the toxicity induced by CCl4 in the heart and testicular tissues of rats. Oxidative stress was caused by the inhibition of activities of glutathione and other antioxidant enzymes of the body, while on the other hand elevating the levels of nitrite and hydrogen peroxide. Treatment with C. opaca fruit extract normalized the levels of enzymes, reproductive hormones, and free radicals thus restoring the histopathological and enzymatic biomarkers towards the normal group. The study supports the indigenous use of fruits as an alternative medicine against cardiac dysfunction by providing scientific evidence of protection against CCl4-induced injuries, and it also concludes the antioxidant defensive role in testicular tissues.

Unleashing the Potential of Benincasa hispida Peel Extract: Synthesizing Selenium Nanoparticles with Remarkable Antibacterial and Anticancer Properties.

In this study, we successfully synthesized selenium nanoparticles (P-SeNPs) using an environment-friendly approach. This method involves utilizing the aqueous peel extract of Benincasa hispida (ash gourd) in combination with selenium salt. Through our innovative procedure, we harnessed the impressive bio-reduction capabilities, therapeutic potential, and stabilizing attributes inherent in B. hispida. This results in the formation of P-SeNPs with distinct and noteworthy qualities. Our findings were thoroughly substantiated through comprehensive characterizations employing various techniques, including ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, and Fourier transform infrared spectroscopy (FTIR). The nanoparticles exhibited a spherical shape, considerable size (22.32 ± 2 nm), uniform distribution, and remarkable stability (-24 mV), all of which signify the effective integration of the phytoconstituents of B. hispida. Furthermore, P-SeNPs displayed robust antibacterial efficacy against pathogenic bacterial strains, as indicated by their low minimum inhibitory concentration values. Our research also revealed the remarkable ability of P-SeNPs to fight cancer, as demonstrated by their impressive IC50 value of 0.19 µg/mL against HeLa cells, while showing no harm to primary human osteoblasts, while simultaneously demonstrating no toxicity toward primary human osteoblasts. These pivotal findings underscore the transformative nature of P-SeNPs, which holds promise for targeted antibacterial treatment and advancements in cancer therapeutics. The implications of these nanoparticles extend to their potential applications in therapies, diagnostics, and various biomedical contexts. Notably, the environmentally sustainable synthesis process and exceptional properties established this study as a significant milestone in the field of nanomedicine, paving the way for a more promising and health-enhancing future.

Synthesis and Photophysical, Electrochemical, and DFT Studies of Piperidyl and Pyrrolidinyl Chalcones.

Small organic molecules with interesting optical and electrochemical properties find applications as organic luminescent materials. In this work, we report the synthesis of novel chalcones with D-A-D and D-A-D-A architecture, followed by their optical, electrochemical, and computational studies. The absorption band of these compounds occurs at 360-480 nm with emission maxima appearing around 513-552 nm. The large Stokes shifts (Δλ) for all compounds (90-132 nm) suggest intramolecular charge transfer (ICT) in the excited states. The molar absorptivity and fluorescence quantum yields were found to be in the range of 1.7-4.26 × 104 M-1 cm-1 and 0.29-0.39, respectively. The electrochemical parameters were determined by using cyclic voltammetry (CV). Density functional theory (DFT) calculations of all compounds were made by using B3LYP/G (d,p) functionals in chloroform and were found to have a good correlation with experimental results. Preliminary studies of absorption, photoluminescence, CV, and their theoretical correlation suggest that these compounds may be optimized for their applications in optoelectronics, sensing, and bioimaging.

Identification of potential Escherichia coli DNA gyrase B inhibitors targeting antibacterial therapy: an integrated docking and molecular dynamics simulation study.

The alarming rise in the rate of antibiotic resistance is a matter of significant concern. DNA gyrase B (GyrB), a critical bacterial enzyme involved in DNA replication, transcription, and recombination, has emerged as a promising target for antibacterial agents. Inhibition of GyrB disrupts bacterial DNA replication, leading to cell death, making it an attractive candidate for antibiotic development. Although several classes of antibiotics targeting GyrB are currently in clinical use, the emergence of antibiotic resistance necessitates the exploration of novel inhibitors. In this study, we aimed to identify potential Escherichia coli GyrB inhibitors from a database of phytoconstituents sourced from Indian medicinal plants. Utilizing virtual screening, we performed a rigorous search to identify compounds with the most promising inhibitory properties against GyrB. Two compounds, namely Zizogenin and Cucurbitacin S, were identified based on their favorable drug likeliness and pharmacokinetic profiles. Employing advanced computational techniques, we analyzed the binding interactions of Zizogenin and Cucurbitacin S with the ATP-binding site of GyrB through molecular docking simulations. Both compounds exhibited robust binding interactions, evidenced by their high docking energy scores. To assess the stability of these interactions, we conducted extensive 100 ns molecular dynamics (MD) simulations, which confirmed the stability of Zizogenin and Cucurbitacin S when bound to GyrB. In conclusion, our study highlights Zizogenin and Cucurbitacin S as promising candidates for potential antibacterial agents targeting GyrB. Experimental validation of these compounds is warranted to further explore their efficacy and potential as novel antibiotics to combat antibiotic-resistant bacteria.Communicated by Ramaswamy H. Sarma.

Sodium Alginate-Based MgO Nanoparticles Coupled Antibiotics as Safe and Effective Antimicrobial Candidates against Staphylococcus aureus of Houbara Bustard Birds.

Alternative and modified therapeutic approaches are key elements in culminating antibiotic resistance. To this end, an experimental trial was conducted to determine the cytotoxicity and antibacterial potential of composites of magnesium oxide (MgO) nanoparticles and antibiotics stabilized in sodium alginate gel against multi-drug-resistant Staphylococcus aureus isolated from a houbara bustard. The characterization of preparations was carried out using X-ray diffraction (XRD), scanning transmissible electron microscopy (STEM), and Fourier-transform infrared spectroscopy (FTIR). The preparations used in this trial consisted of gel-stabilized MgO nanoparticles (MG), gel-stabilized tylosin (GT), gel-stabilized ampicillin (GA), gel-stabilized cefoxitin (GC), gel-stabilized MgO and tylosin (GMT), gel-stabilized MgO and cefoxitin (GMC), and gel-stabilized MgO and ampicillin (GMA). The study presents composites that cause a lesser extent of damage to DNA while significantly enhancing mitotic indices/phases compared to the other single component preparations with respect to the positive control (methyl methanesulphonate). It was also noted that there was a non-significant difference (p > 0.05) between the concentrations of composites and the negative control in the toxicity trial. Studying in parallel trials showed an increased prevalence, potential risk factors, and antibiotic resistance in S. aureus. The composites in a well diffusion trial showed the highest percentage increase in the zone of inhibition in the case of GT (58.42%), followed by GMT (46.15%), GC (40.65%), GMC (40%), GMA (28.72%), and GA (21.75%) compared to the antibiotics alone. A broth microdilution assay showed the lowest minimum inhibitory concentration (MIC) in the case of GMA (9.766 ± 00 µg/mL), followed by that of GT (13.02 ± 5.64 µg/mL), GMC (19.53 ± 0.00 µg/mL), GA (26.04 ± 11.28 µg/mL), GMT (26.04 ± 11.28 µg/mL), MG (39.06 ± 0.00 µg/mL), and GC (39.06 ± 0.00 µg/mL). The study thus concludes the effective tackling of multiple-drug-resistant S. aureus with sodium-alginate-stabilized MgO nanoparticles and antibiotics, whereas toxicity proved to be negligible for these composites.

Pleurospermum candollei Methanolic Extract Ameliorates CCl4-Induced Liver Injury by Modulating Oxidative Stress, Inflammatory, and Apoptotic Markers in Rats.

The main objective of this study was to investigate the hepatoprotective potency of the Pleurospermum candollei methanol extract against CCl4-induced liver damage in rats. HPLC technique was used to estimate the presence of polyphenols in the methanol extract of P. candollei (PCM), while proximate analysis revealed the presence of carbohydrates, lipids, and moisture in the extract. The antioxidant potential of PCM was evaluated by 2,2-diphenylpicrylhydrazyl (DPPH) and reducing power assay, which showed a high percentage of inhibition against free radicals. Hepatotoxicity was induced by carbon tetrachloride (CCl4). CCl4 administration reduced the activity of endogenous antioxidants, whereas it increased the production of nitrites and hydrogen peroxide (H2O2) in rats. Furthermore, the level of hepatic markers in serum was also elevated after CCl4 administration. Moreover, the expression of stress-related markers, proinflammatory mediators, and apoptotic genes was enhanced in CCl4-treated rats. Coadministration of PCM along with CCl4 in rats reduced the levels of free radicals and the above genes to normal levels. CCl4 administration caused histopathological alterations in liver tissues, while cotreatment with PCM mitigated liver injuries. These findings suggest that the methanol extract of P. candollei possesses antioxidant and anti-inflammatory properties and can prevent liver injury. Further pharmacological research will be helpful in determining the effectiveness of P. candollei in humans. Development of FDA-approved plant-based anti-inflammatory drugs can help treat patients and reduce the chances of toxicity.