A mechanistic review of the pharmacological potential of narirutin: a dietary flavonoid.

Flavanones, a type of polyphenol, are found in substantial amounts in citrus fruits. When high- or moderate-dose orange juice consumption occurs, flavanones make up a significant portion of the total polyphenols in plasma. Disaccharide derivative narirutin, mainly dihydroxy flavanone, is found in citrus fruits. The substantial chemotherapeutic potential of narirutin has been amply demonstrated by numerous experimental studies. Consequently, the purpose of this study is to compile the research that has already been done showing narirutin to be a promising anticancer drug, with its mechanism of action being documented in treatment plans for various cancer forms. Narirutin functions in a variety of cancer cells by regulating several pathways that include cell cycle arrest, apoptosis, antiangiogenic, antimetastatic, and DNA repair. Narirutin has been shown to modify many molecular targets linked to the development of cancer, including drug transporters, cell cycle mediators, transcription factors, reactive oxygen species, reactive nitrogen species, and inflammatory cytokines. Taken together, these reviews offer important new information about narirutin's potential as a potent and promising drug candidate for use in medicines, functional foods, dietary supplements, nutraceuticals, and other products targeted at improving the treatment of cancer.

Pb uptake, accumulation, and translocation in plants: Plant physiological, biochemical, and molecular response: A review.

Lead (Pb) is a highly toxic contaminant that is ubiquitously present in the ecosystem and poses severe environmental issues, including hazards to soil-plant systems. This review focuses on the uptake, accumulation, and translocation of Pb metallic ions and their toxicological effects on plant morpho-physiological and biochemical attributes. We highlight that the uptake of Pb metal is controlled by cation exchange capacity, pH, size of soil particles, root nature, and other physio-chemical limitations. Pb toxicity obstructs seed germination, root/shoot length, plant growth, and final crop-yield. Pb disrupts the nutrient uptake through roots, alters plasma membrane permeability, and disturbs chloroplast ultrastructure that triggers changes in respiration as well as transpiration activities, creates the reactive oxygen species (ROS), and activates some enzymatic and non-enzymatic antioxidants. Pb also impairs photosynthesis, disrupts water balance and mineral nutrients, changes hormonal status, and alters membrane structure and permeability. This review provides consolidated information concentrating on the current studies associated with Pb-induced oxidative stress and toxic conditions in various plants, highlighting the roles of different antioxidants in plants mitigating Pb-stress. Additionally, we discussed detoxification and tolerance responses in plants by regulating different gene expressions, protein, and glutathione metabolisms to resist Pb-induced phytotoxicity. Overall, various approaches to tackle Pb toxicity have been addressed; the phytoremediation techniques and biochar amendments are economical and eco-friendly remedies for improving Pb-contaminated soils.

Anti-proliferative, Pro-apoptotic, and Chemosensitizing Potential of 3-Acetyl-11-keto-ß-boswellic Acid (AKBA) Against Prostate Cancer Cells.

Prostate cancer incidences are rising worldwide at an alarming rate. Drug resistance and relapse are two major challenges in the treatment of prostate cancer. Therefore, new multimodal, safe, and effective therapeutic agents are urgently required which could effectively mitigate the menace of tumor recurrence and chemo-resistance. Plant-derived products are increasingly being utilized due to their antioxidant, antibacterial, and anti-tumor potential. In the current study, 3-acetyl-11-keto-ß-boswellic acid, a triterpenoid isolated from plant Boswellia, was utilized to ascertain its chemotherapeutic potential against human prostate cancer cells. Various in vitro assays including cell viability, nuclear staining, mitochondria potential, reactive oxygen species (ROS) generation, and quantification of apoptosis, were performed for the evaluation of the cytotoxic potential of AKBA. We observed that AKBA (10-50 µM) dose-dependently suppressed cell proliferation and caused programmed cell death in PC3 cells via both intrinsic and extrinsic pathway. Intriguingly, AKBA was also found to chemosensitize PC3 cells in synergistic combination with doxorubicin. To the best of our knowledge, this is the first study to document the synergistic chemosensitizing impact of AKBA when combined with doxorubicin in prostate cancer cells.This showcases the potential of AKBA in combinatorial therapy or adjuvant therapy for the management of prostate cancer. In sum, our results suggested that AKBA is a promising drug-like molecule against prostate cancer. Our investigation introduces a novel perspective, elucidating a previously unexplored dimension, and uncovering a compelling chemosensitizing phenomenon along with a strong synergistic effect arising from the concurrent application of these two agents.

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.].

Genomic Insight of Leishmania Parasite: In-Depth Review of Drug Resistance Mechanisms and Genetic Mutations.

Leishmaniasis, which is caused by a parasitic protozoan of the genus Leishmania, is still a major threat to global health, impacting millions of individuals worldwide in endemic areas. Chemotherapy has been the principal method for managing leishmaniasis; nevertheless, the evolution of drug resistance offers a significant obstacle to therapeutic success. Drug-resistant behavior in these parasites is a complex phenomenon including both innate and acquired mechanisms. Resistance is frequently related to changes in drug transportation, drug target alterations, and enhanced efflux of the drug from the pathogen. This review has revealed specific genetic mutations in Leishmania parasites that are associated with resistance to commonly used antileishmanial drugs such as pentavalent antimonials, miltefosine, amphotericin B, and paromomycin, resulting in changes in gene expression along with the functioning of various proteins involved in drug uptake, metabolism, and efflux. Understanding the genetic changes linked to drug resistance in Leishmania parasites is essential for creating approaches for tackling and avoiding the spread of drug-resistant variants. Based on which specific treatments focus on mutations and pathways could potentially improve treatment efficacy and help long-term leishmaniasis control. More study is needed to uncover the complete range of genetic changes generating medication resistance and to develop new therapies based on available information.

In-vivo anti-hyperglycemic effect of herbal extracts Tribulus terrestris (L) and Curcuma amada (R) on streptozotocin-induced diabetic rats and its associated histopathological studies.

Dia/betes is a serious health concern in many countries with high blood glucose, obesity, and multiple organ failures in late stages. Treating diabetes with effective drugs is still a challenging issue since most of the available diabetic drugs are not effective in combating diabetes, especially in secondary disease complications like obesity, retinopathy, and nephropathy associated with diabetes. Hence search for effective antidiabetic medication, especially from natural sources is mandatory with no adverse side effects. In the present study, a combined herbal aqueous extract of Tribulus terrestris and Curcuma amada was administered to diabetic-induced rats for 37 days. During experimentation, the mean blood glucose level was estimated and at the end of the experiment on the 37th day, the animal was sacrificed and observed for weight gain, plasma insulin, glycogen, glycated hemoglobin, urea, and creatinine level. The results revealed that TT and CA extract-treated diabetic groups significantly lowered the mean blood glucose level followed by increased glycogen and insulin level. Urea, creatinine, and HbA1c levels were considerably reduced in TT and CA-treated diabetic animals as compared to that of antidiabetic drug Glibenclamide-treated groups. TT and CA-treated diabetic animals showed considerable net body weight gain at the end of the experimental day. A concluding remark of the study shows that TT and CA herbal extract is effective against diabetes and it can be considered as an antidiabetic agent in ayurvedic medicine practice.

Targeting GluR3 in Depression and Alzheimer's Disease: Novel Compounds and Therapeutic Prospects.

BACKGROUND: The present study investigates the interrelated pathophysiology of depression and Alzheimer's disease (AD), with the objective of elucidating common underlying mechanisms. OBJECTIVE: Our objective is to identify previously undiscovered biogenic compounds from the NuBBE database that specifically interact with GluR3. This study examines the bidirectional association between depression and AD, specifically focusing on the role of depression as a risk factor in the onset and progression of the disease. METHODS: In this study, we utilize pharmacokinetics, homology modeling, and molecular docking-based virtual screening techniques to examine the GluR3 AMPA receptor subunit. RESULTS: The compounds, namely ZINC000002558953, ZINC000001228056, ZINC000000187911, ZINC000003954487, and ZINC000002040988, exhibited favorable pharmacokinetic profiles and drug-like characteristics, displaying high binding affinities to the GluR3 binding pocket. CONCLUSIONS: These findings suggest that targeting GluR3 could hold promise for the development of therapies for depression and AD. Further validation through in vitro, in vivo, and clinical studies is necessary to explore the potential of these compounds as lead candidates for potent and selective GluR3 inhibitors. The shared molecular mechanisms between depression and AD provide an opportunity for novel treatment approaches that address both conditions simultaneously.

GC-MS screening of the phytochemical composition of Ziziphus honey: ADME properties and in vitro/in silico study of its antimicrobial activity.

A revival interest has been given to natural products as sources of phytocompounds to be used as alternative treatment against infectious diseases. In this context, we aimed to investigate the antimicrobial potential of Ziziphus honey (ZH) against twelve clinical bacterial strains and several yeasts and molds using in vitro and computational approaches. The well-diffusion assay revealed that ZH was able to induce growth inhibition of most Gram-positive and Gram-negative bacteria. The high mean growth inhibition zone (mGIZ) was recorded in E. coli (Clinical strain, 217), S. aureus followed by E. coli ATCC 10536 (mGIZ values: 41.00 ± 1 mm, 40.67 ± 0.57 mm, and 34.67 ± 0.57 mm, respectively). The minimal bactericidal concentrations (MBCs) and minimal fungicidal concentration values (MFCs) from approximately 266.33 mg/mL to over 532.65 mg/mL. Molecular docking results revealed that the identified compounds maltose, 2-furoic acid, isopropyl ester, 2,4-imidazolidinedione, 5-(2-methylpropyl)-(S)- and 3,4,5-trihydroxytoluene, S-Methyl-L-Cysteine, 2-Furancarboxylic acid, L-Valine-N-ethoxycarbonyl, Hexanoic acid, 3,5,5-trimethyl-, Methyl-beta-D-thiogalactoside, gamma-Sitosterol, d-Mannose, 4-O-Methylmannose, 2,4-Imidazolidinedione, 5-(2-methylpropyl)- (S) were found to have good affinity for targeted receptor, respectively. Through a 100-ns dynamic simulation research, binding interactions and stability between promising phytochemicals and the active residues of the studied enzymes were confirmed. The ADMET profiling of all identified compounds revealed that most of them could be qualified as biologically active with good absorption and permeation. Overall, the results highlighted the efficiency of ZH against the tested clinical pathogenic strains. The antimicrobial potential and the potency displayed by the identified compounds could imply their further pharmacological applications.Communicated by Ramaswamy H. Sarma.

The role of Aedes aegypti in inducing/aggravating IgE-mediated allergic airway disease: extensive computational studies for identification of allergenic proteins.

Respiratory allergies have become a major public health concern and affect one-third of the world's population. Several factors like environmental changes, industrialization, and immunologic interactions are reported to contribute to allergic respiratory diseases. Immunological reactions because of mosquito bite (allergic proteins) have been reported to have a high contribution to IgE-mediated allergic airway disease but they are largely ignored. In this study, we aim to predict the potential allergens (proteins) from Aedes aegypti that might play a role in the reactions of IgE-mediated allergic airway diseases. The allergens are identified from an extensive literature search and the 3D structures were prepared using the SwissDock server. Computational studies were performed to identify the potential allergens that might be responsible for IgE-mediated allergies. Our docking and molecular dynamics (MD) simulation results suggest that ADE-3, an allergen from Aedes aegypti, has the highest docking score and is predicted to be responsible for IgE-mediated allergic reaction(s). Overall, this study highlights the importance of immunoinformatics, and the obtained information can be used for designing prophylactic peptide vaccine candidates and inhibitors for controlling IgE-mediated inflammations.Communicated by Ramaswamy H. Sarma.

High-throughput screening and in vitro evaluation of CSB-0914; a novel small molecule NF-κB inhibitor attenuating inflammatory responses through NF-κB, Nrf2 and HO-1 cross-talk.

Unpleasant side effects of standard inflammatory drugs urges search for novel therapeutic candidates. This study aims in identifying novel anti-inflammatory NF-κB inhibitor by high-throughput computational and in-vitro pre-clinical approaches. Lead candidate selection was conducted by the use of computational docking molecular-dynamic simulations. The RBL-2H3 cell line, derived from rat basophils, was used to evaluate the release of cytokines and degranulation. The study focused on the study of neutrophil elastase and its role in cellular motility. Flow cytometry was utilized to evaluate the activation of basophils and the expression of critical signaling proteins. High throughput screening identified CSB-0914 to stably bind NF-κB-p50 subunit. Dose based loss in T NF-α and IL-2 release were observed in RBL-2H3 cells in addition to degranulation inhibition by CSB-0914. The compound demonstrated significant efficacy in reducing basophil activation assay induced by FcεRI receptors, with an IC50 value of 98.41 nM.. A dose dependent decrease in neutrophil migration and elastase were observed when treated with CSB- 0914. The compound was effective in decreasing. Upon stimulation, RBL-2H3 cells exhibited phosphorylation of NF-κB p-65 as well as upregulation of the Nrf2 and HO-1 signaling pathways. Collectively, our study has successfully identified a novel inhibitor called CSB-0914 that effectively regulates inflammatory responses. These reactions are primarily mediated by the interplay between NF-κB, Nrf2, and HO-1. The findings of this study provide support for the need to conduct more research on CSB-0914 with the aim of its development as a pharmaceutical agent for anti-inflammatory purposes.Communicated by Ramaswamy H. Sarma.

Potential honey bee (Apis mellifera) allergens associated with IgE-mediated allergy- An In-silico study.

Allergies due to honeybee venom (HBV) are reported to be the second most common form of allergy to Hymenoptera venom that occurs after being stung. Indeed, 15-20% of people test IgE positive after being stung. However, accurate data on the incidence of honey bee allergens is missing and estimated to be less than 0.001%. Beekeeping is an ancient and widely practiced activity across the Kingdom of Saudi Arabia. Still, studies on the allergenic effect of the different subspecies of honey bees are very rare in Saudi Arabia. Hence, in this study, using the In-silico approach, we aimed to study and evaluate the effect of allergens from honey bees in Ha'il City, Saudi Arabia on IgE-mediated allergies. A list of potential allergens from Apis mellifera was prepared, and the 3D structure was prepared using the SWISS-MODEL web server and the PDB database was used for retrieving the structure of the immunoglobulin E- fragment antigen-binding (IgE-Fab) region. Molecular docking (clusPro webserver) and molecular dynamics (Schrödinger) results revealed that the B2D0J5 protein from Apis mellifera might be the key protein associated with IgE-mediated allergic response. Overall, the identified knowledge can be used for exploring prophylactic vaccine candidates and improving the diagnosis of allergic reactions to honey bees in the Ha'il region of Saudi Arabia.

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.

Unlocking the Anticancer Potential of Frankincense Essential Oils (FEOs) Through Nanotechnology: A Review.

Cancer is a group of heterogeneous diseases that occur when cells in the body proliferate and divide uncontrollably. As the current treatment modalities have pros and cons, the discovery of new chemotherapeutic agents with the least side effects is one of the most investigated research areas. In this context, plant-based natural products are a rich source of drugs and have served humanity for ages. Frankincense essential oils (FEOs) are among the most promising plant-based oils in Gulf countries. In addition to their high cultural value, FEOs are also famous for their engaging biological activities, including anti-cancerous. However, the practical application of FEOs is often hindered/by their low water solubility, limited bioavailability, high volatility, and sensitivity toward heat, humidity, light, or oxygen. Thus, a significant demand for technological advancement would improve their ability to target particular cells and tissues. Nanotechnology emerged as an exciting approach in this context. Through suitable nano-formulation (functionalization or encapsulation into a nanostructure), issues arising due to solubility, targeting capability, and delivery can be controlled.

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.

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.

Phytocompound identification of aqueous Zingiber officinale rhizome (ZOME) extract reveals antiproliferative and reactive oxygen species mediated apoptotic induction within cervical cancer cells: an in vitro and in silico approach.

The prevalence of cervical cancer in women is in the fourth position among various other types of cancer globally. Many established therapies, including surgery, chemotherapy, and immunomodulation, are present, but high levels of side effects cause mortality and morbidity among the patients. Zingiber officinale rhizome (ZOME) has been potentially used to cure a variety of ailments and diseases. The aqueous ZOME extract also contains ample phytochemical constituents having anticancer effects on different cancers. The cell viability of HeLa cells was evaluated using MTT assay with IC50 at 97 µg/mL. Furthermore, a significant level of ROS generation causes the apoptosis of the cells. Nuclear staining dye DAPI and Hoechst 33342 showed DNA's fragmented and condensed form. Propidium Iodide staining showed necrotic or late-apoptotic cells. While acidic organelle dye LysoTracker and MitoTracker dye along with dual staining showed significant results. In silico studies were carried out using identified phytochemicals from GC-MS analysis with pharmacokinetics properties (ADMET), and targeted toward receptor proteins for molecular docking. Ligands with high docked scores were subjected to molecular dynamics simulations at 310 K for 100 ns. In vitro and in silico investigations in our studies showed that aqueous ZOME extract can be used as an efficient therapy against cervical cancer treatment as it showed significant cytotoxic and antiproliferative effects toward the HeLa cell line.Communicated by Ramaswamy H. Sarma.

Revealing novel cytb and nad5 genes-based population diversity and benzimidazole resistance in Echinococcus granulosus of bovine origin.

Cystic echinococcosis (CE) is a neglected zoonotic disease caused by Echinococcus granulosus (sensu stricto). The parasite affects a wide range of livestock and wild animals. In this study, the population diversity of the Echinococcus species was investigated based on mitochondrial cytochrome b (cytb) and NADH dehydrogenase subunit 5 (nad5) genes. In addition to this, ß-tubulin gene isoforms of Echinococcus granulosus were amplified to determine the resistance against benzimidazoles. For this purpose, 40 cyst samples from cattle (n = 20) and buffaloes (n = 20) were collected from the main abattoir of Sialkot. DNA extraction was performed using Qiagen Blood and Tissue Kits. Amplification was performed through PCR. Each amplicon was confirmed by GelRed™ stained agarose gel (2%). Samples were sequenced in a DNA analyzer and viewed for any misread nucleotide by using MEGA (v.11). Corrections in nucleotide sequence and multiple sequence alignment were made through the same software. NCBI-BLAST was used for sample specific sequences to identify them as belonging to a particular species. Diversity indices were estimated using DnaSP (v.6) while phylogenetic analysis was inferred using the Bayesian method using MrBayes (v.1.1). ß-tubulin gene isoforms sequence analysis was performed to find out the candidate gene causing benzimidazole resistance. All 40 isolates were found positive for E. granulosus. BLAST-based searches of sequences of each isolate for each gene (nad5 and cytb) confirmed their maximum similarity with the G1 genotype. Overall, high haplotype diversity (Hd nad5 = 1.00; Hd cytb = 0.833) and low nucleotide diversity (π nad5 = 0.00560; π = cytb = 0.00763) was identified based on diversity indices. For both the genes, non-significant values of Tajima's D (nad5 = -0.81734; cytb = -0.80861) and Fu's Fs (nad5 = -1.012; cytb = 0.731) indicate recent population expansion. Bayesian phylogeny-based results of nad5 and cytb sequences confirmed their genotypic status as distinct from other Echinococcus species. This study shed light on the status of benzimidazole resistance in Echinococcus granulosus for the very first time from Pakistan. The findings of this study will significantly add in the information available on genetic diversity of Echinoccous granulosus based on cytb and nad5 genes sequences.