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This study introduces a sustainable method for producing silver nanoparticles (AgNPs), focusing on sustainability and environmental protection. The technique includes the use of Salvia elegans aqueous leaf extract as a reducing agent. In addition, the research investigates the dose-dependent degradation of pUC19 DNA by silver nanoparticles, which is facilitated by the generation of singlet oxygen. The presence of S. elegans extract results in significant color changes, going from a colorless state to a dark brown hue, serving as an indication of the synthesis of AgNPs. A range of experimental methods were employed to analyze the biogenic AgNPs, such as UV–visible absorption spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The meticulously produced AgNPs demonstrate a high level of uniformity, featuring a spherical shape and a particle size of 60 nm. DNA photo-cleavage studies show that singlet oxygen plays a crucial role in triggering DNA damage caused by AgNPs, indicating their potential as powerful cytotoxic agents specifically aimed at cancer cells. Additional studies are required to clarify the effectiveness and specificity of AgNPs against various cancer cell types to assess their therapeutic potential. The cytotoxic effects of AgNPs, particularly in relation to DNA photocleavage, are of considerable interest in cancer research. This research holds promise for developing novel and sustainable cancer therapies based on the unique properties of biogenic silver nanoparticles.

This study focuses on gene cloning, expression, biochemical and analytical characterization along with structural and functional characterization of collagenase followed with molecular docking, dynamics study and Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA). The collagenase gene identified from the genome of the novel collagenase Bacillus siamensis strain Z1 is introduced into E.coli DH5α, subsequently expressed in E.coli BL21 (DE3) withisopropyl β −d – 1 − thiogalactopyranoside(IPTG) induction and further affinity purified yielding in ∼ 89.4 kDa recombinant collagenase which demonstrated alkali characteristics and thermostability determined by thermodynamic parameters. Recombinant collagenase revealed good stability when exposed to diverse biochemical components. The recombinant collagenase identity was confirmed through matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) showing specific mass peaks and via N-terminal sequence analysis as MTAVNQTISK. Moreover, the concluded N-terminal amino acid sequence from Edman degradation displayed significant resemblance. The structural and functional analysisof recombinant collagenase was analysed by Circular dichroism (CD), Proton nuclear magnetic resonance (1H NMR) spectrometry and Thermogravimetric analysis (TGA). The recombinant collagenase also showed gelatin liquefaction ability. The collagenase gene sequence is also assessed for structural and functional characterizations by using various computational tools and revealed its classification in U32 family peptidase. A Grand average of hydropathicity index (GRAVY) score of −0.295 and instability index of 37.22 was obtained. Homology model of collagenase gene was generated by employing SWISS-MODEL and structure analysis by Ramachandran plot. Molecular docking of modelled collagenase with four different substrates was carried out by PyRx and Autodocking. Highest docking score of −12.7 kcal/mol was obtained for Alaska pollock hydroxyproline containing marine collagen peptide (APHCP). Subsequently, Molecular dynamics and simulations for highest score docked complex was assessed using GROningenMAchine for Chemical Simulations (GROMACS).

This study focuses on the synthesis, characterization, and use of zinc oxide nanoparticles (ZnONPs) derived from W. bifurcata fruit peel extract. ZnONPs are frequently synthesized utilizing a green technique that is both cost-effective and ecologically friendly. ZnONPs were characterized utilizing analytical techniques. Ultra Violet visible (UV-Vis) spectra showed peaks at 364 nm, confirming the production of ZnONPs. Scanning Electron Microscope analysis indicated that the nanoparticles generated were spherical/agglomerated, with diameters ranging from 11 to 25 nm. FTIR spectroscopy was used to identify the particular functional groups responsible for the nanoparticles’ reduction, stabilization, and capping. Phytochemical analysis of the extract revealed that flavonoids, saponins, steroids, triterpenoids, and resins were present. The antibacterial activity of W. bifurcata synthesised nanoparticles was evaluated against pathogenic bacteria. The ZnONPs antioxidant activity was assessed using DPPH assay. The in vitro cytotoxicity was assessed against prostate cancer PC3 cells. The wound healing potential was assessed by employing in vitro scratch assay and in vivo excision model in Wistar rats. Because of its environmentally benign production, low toxicity, and biocompatibility, ZnONPs exhibited potential antibacterial, antioxidant, anticancer, and wound healing activities, indicating that they could be used in cancer treatment and wound management. Further study is required to examine the fundamental mechanisms and evaluate the safety and effectiveness of the test sample in clinical situations.

L-glutaminase is a unique enzyme with catalytic activity and the ability to modulate glutamine levels, making it a valuable enzyme with numerous potential applications. L-glutaminase triggers a distinctive reaction by converting L-glutamine into glutamic acid while releasing ammonia concurrently. This enzymatic process holds potential applications across diverse industries, notably in food and pharmaceuticals. The primary objective of the present research was to identify and isolate a fungal strain proficient in L-glutaminase production from soil found in maritime environments. The physical and nutritional conditions were optimized for maximum synthesis of L-glutaminase under solid state fermentation (SSF) and submerged fermentation conditions (SmF). The isolated organism was identified as Fusarium solani-melongenae strain CRI 24 by morphological and 18S rRNA analysis. The optimum carbon source under SmF and SSF was found to be starch (0.2% w/v). Wheat bran as solid substrate among others showed optimum enzyme activity. On the seventh day of incubation, at pH 8.0 and 0.7% L-glutamine concentration under SSF and SmF, the highest enzyme activity was detected. The greatest enzyme activity in SSF was seen at a moisture content of 10%. Fusarium solani-melongenae species produced the enzyme under optimal conditions and 4.20 and 4.73-fold increase (from 0.8 U/mL to 3.61 U/mL and from 0.781 U/mL to 3.69 U/mL) was achieved after optimization in submerged and in solid state fermentation, respectively. The selective isolation and optimization processes described in this work are a promising technique for the industrial production of L-glutaminase and can be applied in the pharmaceutical and food industries.

Since ancient times, bioactive phytocompounds from different parts of medicinal plants have been used to heal various disease ailments and they are now regarded as a valuable source of disease prevention globally. Kalanchoe pinnata is a member of the Crassulaceae family; it has a long history of usage in traditional ayurvedic treatment. Analysis of bioactive compounds for their potential anti-type-2 diabetes mellitus (T2DM) mechanism along with in-vitro and in-silico approaches was studied in the present research. The alpha-amylase and alpha-glucosidase inhibitory activity of methanolic extract of Kalanchoe pinnata (α-amylase: IC50 29.50 ± 0.04 μg/ml; α-glucosidase IC50 32.04 ± 0.35 μg/ml) exhibit a high degree of similarity to the standard drug acarbose (IC50 35.82 ± 0.14 μg/ml). Different biological databases were used to list phytocompounds from the plant, and ADME analysis using swissADME was carried out to screen compounds that obeyed the Lipinski rule of 5 and were employed further. STRING and KEGG pathway analysis was performed for gene enrichment analysis followed by network pharmacology to identify key target proteins involved in DM. AMY2A, NOX4, RPS6KA3, ADRA2A, CHRM5, and IL2 were identified as core targets for luteolin, kaempferol, alpha amyrin, stigmasterol compounds by modulating neuroactive ligand interaction, P13-AKT, MAPK, and PPAR signaling pathways. Molecular docking was performed to study the binding affinity among bioactive compounds of K. pinnata against aldose reductase, alpha-amylase, alpha-glucosidase, and dipeptidyl peptidase IV. Alpha-amylase-friedelin [FRI] and alpha-amylase-acarbose [STD] complexes were subjected to molecular simulation for a 200 ns duration that depicted the stability of the compounds and proteins. In the current study, employing dual approach in-silico and in-vitro enzyme assays has yielded a comprehensive and strong understanding of its potential therapeutic properties, making a significant step towards the development of novel anti-diabetic treatment.

The Indian Clove (Syzygium aromaticum) is a naturally occurring spice with significant biological properties. It is primarily found in India and Indonesia, but can also be cultivated in other coastal areas. Clove is commonly used as a natural preservative and in the production of natural medicines. One of the notable benefits of clove is its ability to help treat diseases caused by various bacteria and fungi, including E. coli, P. aeruginosa, S. aureus, Z. mobilis, and C. albicans. Additionally, clove possesses antioxidant properties that can help reduce cell damage caused by free radicals. Clove has also shown potential in inhibiting the growth of cancer cells and reducing the activity of enzymes such as amylase, glucosidase, and lipase, which can be beneficial for managing diabetes. The study demonstrated that Silver nanoparticles (AgNPs) synthesized from Indian clove leaf extract exhibited promising antimicrobial, anticancer, antidiabetic, and antioxidant activities. This suggests that these nanoparticles could have versatile applications in antimicrobial therapy, cancer treatment, diabetes management, and antioxidant supplementation. However, further research is needed to understand the underlying mechanisms of these activities and to evaluate the safety and efficacy of these nanoparticles in more complex biological systems. In summary, clove possesses diverse biological properties and has potential applications in various therapeutic areas. The synthesis of AgNPs from clove leaf extract shows promise in multiple fields, but more research is required for a deeper understanding of its mechanisms and broader applications.

The limitations of the current vaccination strategy for the Kyasanur Forest Disease virus (KFDV) underscore the critical need for effective antiviral treatments, highlighting the crucial importance of exploring novel therapeutic approaches through in silico drug design. Kyasanur Forest Disease, caused by KFDV, is a tick-borne disease with a mortality of 3–5% and an annual incidence of 400 to 500 cases. In the early stage of infection, the envelope protein plays a crucial role by facilitating host–virus interactions. The objective of this research is to develop effective antivirals targeting the envelope protein to disrupt the virus–host interaction. In line with this, the 3D structure of the envelope protein was modeled and refined through molecular modeling techniques, and subsequently, ligands were designed via de novo design and pharmacophore screening, yielding 12 potential hits followed by ADMET analysis. The top five candidates underwent geometry optimization and molecular docking. Notably, compounds L4 (SA28) and L3 (CNP0247967) are predicted to have significant binding affinities of −8.91 and −7.58 kcal/mol, respectively, toward the envelope protein, based on computational models. Both compounds demonstrated stability during 200 ns molecular dynamics simulations, and the MM-GBSA binding free-energy values were −85.26 ± 4.63 kcal/mol and −66.60 ± 2.92 kcal/mol for the envelope protein L3 and L4 complexes, respectively. Based on the computational prediction, it is suggested that both compounds have potential as drug candidates for controlling host–virus interactions by targeting the envelope protein. Further validation through in-vitro assays would complement the findings of the present in silico investigations.

In this study, new series of N'-(2-(substitutedphenoxy)acetyl)-4-(1H-pyrrol-1-yl)benzohydrazides (3a-j) 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N'-(2-(substitutedphenoxy)acetyl)benzohydrazides (5a-j) were synthesized, characterized and assessed as inhibitors of enoyl ACP reductase and DHFR. Most of the compounds exhibited dual inhibition against the enzymes enoyl ACP reductase and DHFR. Several synthesized substances also demonstrated significant antibacterial and antitubercular properties. A molecular docking analysis was conducted in order to determine the potential mechanism of action of the synthesized compounds. The results indicated that there were binding interactions seen with the active sites of dihydrofolate reductase and enoyl ACP reductase. Additionally, important structural details were identified that play a critical role in sustaining the dual inhibitory activity. These findings were useful for the development of future dual inhibitors. Therefore, this study provided strong evidence that several synthesized molecules could exert their antitubercular properties at the cellular level through multi-target inhibition. By shedding light on the mechanisms through which these compounds exert their inhibitory effects, this research opens up promising avenues for the future development of dual inhibitors with enhanced antibacterial and antitubercular properties. The study's findings underscore the importance of multi-target approaches in drug design, providing a strong foundation for the design and optimization of novel compounds that can effectively target bacterial infections at the cellular level.

Zinc oxide nanoparticles (ZnO NPs) are establishing themselves as an important class of nanomaterials due to their exceptional physicochemical properties and wide range of applications. Due to their affordability, lack of toxicity, and strong biocompatibility, ZnO NPs find extensive use in the field of biomedicine. ZnO NPs are promising in biomedicine, especially for their ability as anticancer and antimicrobial agents. The ecologically sustainable preparation of metallic NPs using different plant extracts is a viable alternative to more conventional synthesis methods. The present study investigates the effects of changing the physical conditions on ZnO NPs synthesis from Bixa orellana (B. orellana) extract using the precipitation method. Confirmation and characterization of the ZnO NPs were achieved by analytical techniques. EDS results verified that highly pure ZnO NPs were synthesized. X-ray diffraction analysis verified the crystal nature of the synthesized NPs and their crystalline particle size of 82.66 nm. The XRD graphs strongly indicate the formation of wurtzite ZnO due to the presence of the (100), (002), and (101) planes. The antibacterial activity was assessed through the utilization of agar disc diffusion. The findings revealed that ZnO NPs exhibited significant efficacy in inhibiting the growth of both Gram-positive and Gram-negative bacteria. The zone of inhibition with the greatest diameter (22 mm) was reported for the bacterial strain B. cereus. The present investigation provides evidence that B. orellana leaves extract is capable of producing ZnO NPs, which play a crucial role in its antibacterial action. Additional investigation is necessary to validate the role of diverse phytochemicals in the synthesis of ZnO NPs and their applications in diverse fields such as agriculture, cosmetics, food, and healthcare.

Bixa orellana (B. Orellana) is a frequently utilized plant that has grown in significance in pharmaceutical applications. The leaves extract of B. orellana was used in the current study for preliminary phytochemical analysis in terms of both quantitative and qualitative, which indicates the presence of phenols, alkaloids, and flavonoids. Furthermore, the extract demonstrated antifungal activity at 30 mm zone of clearance against Candida albicans and antibacterial activity at 16 mm zone of clearance against Bacillus nakamuria by well diffusion method against different strains. The plant extract showed a MIC of 20 µg/mL and MBC of 157.11 µg/mL against E. coli by ELISA and broth dilution method, respectively. To evaluate the phytochemicals in the extract, further purification of the extract by TLC, column chromatography, and component analysis by GC–MS, which reported 18 components, and UV spectrum were performed. A number of therapeutic applications for the extract were observed, including antidiabetic activity (anti-glucosidase) of 98.34% inhibition at 100 µg/mL, anti-lipase of 100% inhibition at 100 µg/mL, and anti-amylase activity of 100% inhibition at 100 µg/mL, antioxidant activity (anti-DPPH activity) of 59.74% inhibition at 100 µg/mL, anthelmintic at 1 min by 1000 µg/mL, antifibrinolytic at 20 secs by 1000 µg/mL and cytotoxic activity against A549 lung cell lines, wherein, the cell viability was below 40 % at the highest dose (100 µg/mL), with an IC50 value of 39.9 µg/mL.

The main objective of this research was to perform Gymnema sylvestre (Asclepiadaceae) extract’s phytochemical screening and identify its therapeutic potential. Using a Soxhlet apparatus, the powdered plant material was extracted using ethyl acetate. The preliminary phytochemical analysis confirmed the presence of alkaloids, flavonoids, phenols, glycosides, and steroids. Gas chromatography–mass spectroscopy analysis of the extract was performed and confirmed the presence of 11 compounds. As per the quantitative analysis, the extract exhibited a phenolic content of 948 µg gallic acid equivalent/g dry weight, a total flavonoid content of 398 µg quercetin equivalent/g dry weight, and an alkaloid content of 487 µg atropine equivalent/g dry weight. As per the in vitro cytotoxicity test using A549 cells, the IC50 (half-maximal inhibitory concentration) value for the extract was found to be 76.06 ± 1.26 µg/mL, indicating its cytotoxic effect on the cells. The ethyl acetate extract showed significant antibacterial efficacy, as evidenced by a zone of clearance measuring 3 mm against Escherichia coli and 6 mm against Bacillus subtilis. For anthelmintic activity, the earthworm paralysis time induced by G. sylvestre extract (10 mg/mL) was 28.13 ± 0.8 min, and the time of death was 68.21 ± 1.72 min. In comparison, the reference drug, piperazine citrate (10 mg/mL), caused paralysis in 22.18 ± 1.02 min and resulted in death at 66.22 ± 2.35 min. Similarly, the coagulation time was notably prolonged, with blood clot formation observed at 1 min and 40 s, at a concentration of 1 mg/mL, which underscores the potential anticoagulant or hemostatic modulation properties of G. sylvestre extract. The test extract showed good inhibition of alpha-amylase activity and exhibited an IC50 value of 15.59 µg/mL. The IC50 value for DPPH (2,2-diphenyl-1-picrylhydrazyl)-scavenging activity for the extract was 19.19 µg/mL. Based on the GCMS results, the compound 2,7-dimethyl-undecane was selected for its anticancer potential. Docking studies were conducted with the epidermal growth factor receptor (EGFR) protein, specifically the 5WB7 variant associated with lung cancer. The docking score was −4.5, indicating a potential interaction. Key interaction residues such as ASN328, VAL350, and THR358 were identified. Overall, this research provides valuable insights into the phytochemical composition and diverse biological activities of G. sylvestre extract, offering a foundation for further exploration of its medicinal and pharmacological potential.

Introduction: Pharmacovigilance (PV) is critical in determining the risk–benefit ratio of medicines and encouraging their safe, rational, and effective use, hence enhancing patient safety and care. Pharmacists, as drug experts, share responsibility for ensuring that medicines remain safe. Objective: The study aimed to assess the knowledge, attitude, and practice of hospital pharmacists towards PV and adverse drug reaction (ADR) reporting and to know factors that discourage them from reporting ADRs in Najran, Saudi Arabia. Methods: A pre-tested self-administered questionnaire was distributed to all the pharmacists working in government hospitals who consented to participate in the study. Data was collected over three months, from 01 June 2018 to 31 Aug 2018. Data were analyzed using Statistical Package for Social Science (SPSS) software for Windows, version 23. Descriptive statistics such as frequency and percentages, mean ± standard deviation (SD) were calculated, and the Pearson's Chi-square test was used to examine the relationship between different variables. Results: A total of 145 questionnaires were distributed, and the response rate obtained was 70.3%. The definition of PV and ADR were correctly identified by 42% and 68.3% of participants, respectively. A noteworthy finding is that 95% of participants were aware of the existence of the ADR reporting system, and 88.9% knew the responsible regulatory agency. Participants showed a positive attitude towards PV and ADR reporting; 90.1% considered ADR reporting a part of professional obligation, and 94.1% believed that there should be collaboration between pharmacists and other healthcare professionals. A majority of participants (86.1%) had identified an ADR during their practice, and 71.3% had reported an ADR. The unavailability of a professional environment to discuss ADR and insufficient pharmacotherapy/clinical knowledge was cited as the main factors discouraging from reporting ADRs. Conclusions: Overall, the pharmacists had an average to good knowledge of and positive attitude towards PV and ADR reporting and a good ADR reporting practice. The concept of PV and ADR reporting should be further strengthened, and there is a vast potential for the same.

Poor circulation, unresolved inflammation, neuropathy, and infection make wound care difficult. Manilkara zapota (M. zapota) antibacterial and antioxidant properties may help speed up the healing process. The present investigation aimed to evaluate the wound healing activity of M. zapota bark ethanolic extract (MZE) by employing in-vitro migration scratch assay and in-vivo animal models. Wistar albino rats were used for the in-vivo wound healing models. No treatment was given to Group I; Group II received povidone-iodine (5% W/W); Group III received MZE (5% W/W); and Group IV received MZE (10% W/W). Linear incision models and excision wound models were used to induce injury. The ointments were applied immediately to the wounds after causing the injury. The percentage of wound contraction, the length of the epithelization period, and the wound’s tensile strength were all calculated. The scratch assay assessed the test drug’s potential for wound healing in-vitro. H2O2 and DPPH scavenging assays were used to measure antioxidant activity. A p < 0.05 was used to define statistical significance. On days 4, 8, 12, 16, and 20, the wound contraction potential of animals treated with MZE ointment was significantly higher (p < 0.001) than that of the control group. On day 20, the proportion of wound contraction in MZE-treated animals was 99.88%, compared to 83.86% in untreated animals. The test group had a significantly (p < 0.01) faster time to full epithelization than the control group. In the incision model, the control group had considerably lower mechanical strength (p < 0.001) than animals treated with MZE. In addition, MZE caused a significant increase (p < 0.001) in total protein and hydroxyproline levels. In the scratch experiment, test drug-treated cells showed a higher rate of cell migration than untreated cells. Furthermore, animals treated with MZE showed increased levels of epithelial tissue, collagen proliferation, and keratinization. To summarize, the current study found that M. zapota improved wound healing activity both in vitro and in vivo, as evidenced by the study results. M. zapota extract has significant wound-healing potential and could be a viable source of wound-healing nutraceuticals.

The major goal of the study was to isolate bacteria synthesizing protease enzyme from a soil sample taken in Dandeli, Karnataka, India. Furthermore, screening, production, and optimization of medium components for maximum protease activity, partial purification of crude enzymes, and application of protease produced by Bacillus nakamurai were carried out. At 72 hrs and pH 6, the optimum incubation time, pH, and temperature were evaluated (acidic and thermophilic). As a substrate, casein was employed. Plackett-Burman screening was performed, and KH2PO4, xylose, MnCl2, and peptone were discovered to be essential components in protease production media. Following the production and optimization processes, partial purification was performed using ammonium sulfate precipitation, with the maximum protease activity at 60% ammonium sulfate, and further dialysis was performed using precipitated enzyme, yielding enzyme activity of 0.747 U/mL. The protease enzyme proved effective at removing egg yolk stains as well as degrading (dehairing) chicken feathers and hairs from goat skin. Bacillus nakamurai PL4 can be utilized for the industrial-scale production of proteases to fulfill current demands. Thus, such optimized parameters can optimize protease production and their application across various industries.

Objectives: The main objective of the present research is to provide GC–MS and LC-MS phytochemcial profiling of Corchorus olitorius along with Flow cytometry based mechanistic investigation of cytotoxic activity of its extracts against breast and lung cancer cell lines. Methods: The Soxhlet extraction method was used in the sequential extraction of C. olitorius. The phytochemical profiling was done using LC-MS and GC–MS techniques, and total phenolic and flavonoid content was determined. The cytotoxicity was studied against non-cancerous L929 cells and cancerous MCF-7 and A549 cell lines using MTT assay, followed by flow cytometry based molecular mechanisms study through anti-Bcl-2 assay, Caspase-3, and DNA fragmentation (TUNEL assay). Results: The C. olitorius methanolic extract showed the phenolic compounds and flavonoids as a major constituents with 699 µg GAE/g of dw and 1361.50 µg QE/g of dw, respectively. The GC–MS and LC-MS results confirmed the presence of active phytochemicals. Toxicity study against L929 cell line revealed that methanol extract proved to be less toxic with a higher IC50 value i.e. 227.84 µg/ml. Cell viability MTT assay for methanol extract against MCF-7 and A549 cell lines revealed significant results with IC50 values of 20 µg/ml and 12.45 µg/ml, respectively. The flow cytometry based molecular marker studies showed that the extract successively induced early and late apoptosis in tested breast and lung cancer cells through activation of Caspase-3 with inhibition of Bcl-2 protein and induced cell death through DNA damage. Conclusion: Collectively, these findings show that the methanol extract of C. olitorius inhibits breast cancer and lung cancer cell lines with significant cytotoxic activity. Thus, C. olitorius would be a promising source of chemopreventive agents that warrant further investigation to find lead compounds with cancer chemotherapeutic potential.

Various protein/receptor targets have been discovered through in-silico research. They are expanding rapidly due to their extensive advantage of delivering new drug candidates more quickly, efficiently, and at a lower cost. The automation of organic synthesis and biochemical screening will lead to a revolution in the entire research arena in drug discovery. In this research article, a few fungal metabolites were examined through an in-silico approach which involves major steps such as (a) Molecular Docking Analysis, (b) Drug likeness and ADMET studies, and (c) Molecular Dynamics Simulation. Fungal metabolites were taken from Antibiotic Database which showed antiviral effects on severe viral diseases such as HIV. Docking, Lipinski's, and ADMET analyses investigated the binding affinity and toxicity of five metabolites: Chromophilone I, iso; F13459; Stachyflin, acetyl; A-108836; Integracide A (A-108835). Chromophilone I, iso was subjected to additional analysis, including a 50 ns MD simulation of the protein to assess the occurring alterations. This molecule's docking data shows that it had the highest binding affinity. ADMET research revealed that the ligand might be employed as an oral medication. MD simulation revealed that the ligand–protein interaction was stable. Finally, this ligand can be exploited to develop SARS-CoV-2 therapeutic options. Fungal metabolites that have been studied could be a potential source for future lead candidates. Further study of these molecules may result in creating an antiviral drug to battle the SARS-CoV-2 virus.

In this study, a new series of 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N’-(2-(substituted)acetyl) benzohydrazides (5a–n) were prepared and new heterocycles underwent thorough characterization and evaluation for antibacterial activity; some of them underwent further testing for in vitro inhibition of enoyl ACP reductase and DHFR enzymes. The majority of the synthesized molecules exhibited appreciable action against DHFR and enoyl ACP reductase enzymes. Some of the synthesized compounds also showed strong antibacterial and antitubercular properties. In order to determine the potential mode of action of the synthesized compounds, a molecular docking investigation was conducted. The results revealed binding interactions with both the dihydrofolate reductase and enoyl ACP reductase active sites. These molecules represent excellent future therapeutic possibilities with potential uses in the biological and medical sciences due to the compounds’ pronounced docking properties and biological activity.

Communities play an important and active role in preventing and controlling the spread of coronavirus disease (COVID-19). Reduction of COVID-19-related barriers and threats perceived by the public should be the top priority in promoting positive preventive behaviors among people. This cross-sectional study aimed at identifying the barriers and threats perceived by public university students in the southwestern part of Saudi Arabia during the COVID-19 pandemic. The students were recruited through a snowball sampling technique, and data were collected using a web-based questionnaire. Data on socio-demographic aspects, perceived barriers, and perceived threats were collected. Perceived barriers were estimated using the Health Belief Model (HBM) questionnaire, and perceived threats were estimated using the patient threat perceptions in the emergency department scale. This study was conducted between March and June 2020. Approximately 50% of the study participants had a high level of perceived barriers and a moderate level of total perceived threats. Notable factors associated with participants’ perceived barriers and threats were age, college type, and monthly income. Perceived barriers, participants’ residence location, and sex were also significantly related to each other. Moreover, perceived barriers were significantly correlated with perceived threats. COVID-19-related perceived barriers and threats ranged from a moderate level to a high level among most of the participating students. Perceived barriers were associated with some of the demographic variables. The findings from this study may help the government in formulating strategies for planning interventions to reduce COVID-19 pandemic propagation.

The COVID-19 pandemic has imposed various stresses on individuals and communities. Coping with sudden, tense, demanding situations during an infectious disease outbreak requires self-efficacy. Increasing the public’s self-efficacy for preventive and control measures is important in the management of the COVID-19 pandemic. This research was aimed at evaluating the self-efficacy and associated factors of students at a public university in the southwest region of Saudi Arabia during the COVID-19 pandemic. This was a cross-sectional study, and a snowball sampling method was used to recruit participants. Data were collected from the beginning of April to the end of June 2020 using an online questionnaire. A total of 761 students were included in the study. The participants’ demographic data were collected, and self-efficacy was analyzed using the General Self-efficacy Scale. The results showed that self-efficacy for dealing with the COVID-19 pandemic was moderate in almost half of the students but was low in approximately 25% of the participants. There were statistically significant associations between self-efficacy regarding the COVID-19 pandemic and gender, college type, marital status, and family income (p < 0.05). However, the participants’ self-efficacy was not associated with age, residence, or history of chronic illness. In dealing with the COVID-19 pandemic, most students had either moderate or low self-efficacy. Certain demographic variables were positively associated with self-efficacy as perceived by the students. These findings provide data central to the development of self-efficacy initiatives. They may also be useful for the effective implementation of public health preventive behavior programs during the COVID-19 pandemic.

The present study aimed to determine the susceptibility of Pseudomonas aeruginosa strains isolated from patients with nosocomial infections to standard synthetic chemical antibiotics and organic ethanoic acids derived from local produce. The minimum inhibitory concentrations (MIC) of the standard synthetic antibiotics determined from standard e-test results and antibiotic sensitivity tests showed many multidrug-resistant strains among the isolates. We compared the susceptibility of these strains to organic ethanoic acids derived from different sources using standard microbiological assays. All strains of P. aeruginosa isolated from the patients were susceptible to the organic ethanoic acids with a satisfactory MIC and minimum bactericidal concentrations. Therefore, organic ethanoic acids were more effective against P. aeruginosa than standard synthetic antibiotics.

Irrational Self-Medication (SM) practice leads to incorrect diagnosis and is a risk factor for disease exacerbation and serious health consequences. Hence Responsible SM is vital for better health outcomes. In the present community-based study we explored the SM practice during the last 3 months, frequency, outcome, medications used, reasons influencing SM, source of the drug, and information. Data were analyzed using SPSS; chi-square test was performed to indicate significance, Odds ratio, Pearson correlation, univariant and multivariant regression analysis were performed to find out factors and predictors of SM. A total of 611 residents completed the survey. SM was practiced by 52.9% of participants during the last 3 months, with a frequency of one to two times. Headache (64.8%), pain (35.4%), fever/flu (31.4%), cold & cough (21.9%) and dysmenorrhea (20.9%) were illnesses managed using pain killers (75.9%), multivitamins (25.5%), anti-pyretic (24.7%) and herbal medicines (18.5%). Minor illness (67.9%), earlier experience (33.9%) and shortness of time to attend healthcare facilities (18.8%) were the reasons for practicing SM. Distance to healthcare and routine physical activity have significantly influenced the SM practice. Residents stated that inappropriate SM would lead to negative outcomes, including drug side effects (70%), Interaction (34.2%), poor treatment outcome (32.6%) and return of symptoms (26.5%). Interestingly, two-thirds of participants (68.9%) have recommended SM in case of minor illnesses only, 85.3% of respondents have expressed their desire to learn more about appropriate SM, and 76.6% are willing to return their leftover or unused medications to drug take-back centers.

Finding structurally similar compounds in compound databases is highly efficient and is widely used in present-day drug discovery methodology. The most-trusted and -followed similarity indexing method is Tanimoto similarity indexing. Epigenetic proteins like histone deacetylases (HDACs) inhibitors are traditionally used to target cancer, but have only been investigated very recently for their possible effectiveness against rheumatoid arthritis (RA). The synthetic drugs that have been identified and used for the inhibition of HDACs include SAHA, which is being used to inhibit the activity of HDACs of different classes. SAHA was chosen as a compound of high importance as it is reported to inhibit the activity of many HDAC types. Similarity searching using the UNPD database as a reference identified aglaithioduline from the Aglaia leptantha compound as having a ~70% similarity of molecular fingerprints with SAHA, based on the Tanimoto indexing method using ChemmineR. Aglaithioduline is abundantly present in the shell and fruits of A. leptantha. In silico studies with aglaithioduline were carried out against the HDAC8 protein target and showed a binding affinity of −8.5 kcal mol. The complex was further subjected to molecular dynamics simulation using Gromacs. The RMSD, RMSF, compactness and SASA plots of the target with aglaithioduline, in comparison with the co-crystallized ligand (SAHA) system, showed a very stable configuration. The results of the study are supportive of the usage of A. leptantha and A. edulis in Indian traditional medicine for the treatment of pain-related ailments similar to RA. Our study therefore calls for further investigation of A. leptantha and A. edulis for their potential use against RA by targeting epigenetic changes, using in vivo and in vitro studies.

Aim: The objective of this research is to present a phytochemical profile of Fagonia arabica and to investigate the cytotoxic potential of its extracts against breast, oral, and lung cancer cell lines using MTT assay and dual staining-based mechanistic analysis. Methods: The progressive extraction of F. arabica was carried out using the Soxhlet extraction technique. The total phenolic and flavonoid content was calculated as part of the phytochemical profiling performed using GCMS and LCMS methods. The MTT assay was utilized to assess the cytotoxicity against normal L929 cells, as well as malignant A549, MCF-7, and KB-3-1cell lines. Results: The phenolic compounds and flavonoids were the two main elements of the F. arabica methanolic extract, with 1323 µg GAE/g of dry weight and 523.07 µg QE/g of dry weight, respectively. The presence of the functional phytochemicals was verified by GCMS and LCMS analyses. Toxicity testing on the L929 cell line found that the F. arabica methanol extract was the least harmful, with the highest IC50 (296.11 µg/mL). The MTT assay for cell viability against MCF-7 and KB-3-1 yielded significant results, with IC50 values of 135.02 µg/mL and 195.21 µg/mL, respectively. The aqueous extract exhibited significant cytotoxicity against the A549 cell lines (IC50 116.06 µg/mL). The molecular marker analyses using dual staining revealed that the methanolic extract successfully triggered apoptosis in the different cancer cells tested. Conclusion: The present data suggest that the methanol extract of F. arabica has substantial cytotoxic action against lung, breast, and oral cancer cell lines. Thus, F. Arabica would be a promising source of anticancer medicines, warranting more research to identify the lead molecules with anticancer properties.

Cancer is characterized by the abnormal development of cells that divide in an uncontrolled manner and further take over the body and destroy the normal cells of the body. Although several therapies are practiced, the demand and need for new therapeutic agents are ever-increasing because of issues with the safety, efficacy and efficiency of old drugs. Several plant-based therapeutics are being used for treatment, either as conjugates with existing drugs or as standalone formulations. Withania somnifera (L.) Dunal is a highly studied medicinal plant which is known to possess immunomodulatory activity as well as anticancer properties. The pivotal role of KAT6A in major cellular pathways and its oncogenic nature make it an important target in cancer treatment. Based on the literature and curated datasets, twenty-six compounds from the root of W. somnifera and a standard inhibitor were docked with the target KAT6A using Autodock vina. The compounds and the inhibitor complexes were subjected to molecular dynamics simulation (50 ns) using Desmond to understand the stability and interactions. The top compounds (based on the docking score of less than −8.5 kcal/mol) were evaluated in comparison to the inhibitor. Based on interactions at ARG655, LEU686, GLN760, ARG660, LEU689 and LYS763 amino acids with the inhibitor WM-8014, the compounds from W. somnifera were evaluated. Withanolide D, Withasomniferol C, Withanolide E, 27-Hydroxywithanone, Withanolide G, Withasomniferol B and Sitoindoside IX showed high stability with the residues of interest. The cell viability of human breast cancer MCF-7 cells was evaluated by treating them with W. Somnifera root extract using an MTT assay, which showed inhibitory activity with an IC50 value of 45 µg/mL. The data from the study support the traditional practice of W. somnifera as an anticancer herb.

These days an extensive amount of the attention of researchers is focused towards exploring bioactive compounds of natural or herbal origin for therapeutic intervention in different ailments of significant importance. One such novel bioactive compound that has a variety of biological properties, including anti-inflammatory and antioxidant activities, is piperine. However, until today, piperine has not been explored for its potential to improve inflammation and enhance healing in acute and chronic wounds. Therefore, the present study aimed to investigate the wound healing potential of piperine hydrogel formulation after topical application. Hydrogels fit the need for a depot system at the wound bed, where they ensure a consistent supply of therapeutic agents enclosed in their cross-linked network matrices. In the present study, piperine-containing carbopol 934 hydrogels mixed with Aloe vera gels of different gel strengths were prepared and characterized for rheological behavior, spreadability, extrudability, and percent (%) content uniformity. Furthermore, the wound healing potential of the developed formulation system was explored utilizing the excision wound healing model. The results of an in vivo study and histopathological examination revealed early and intrinsic healing of wounds with the piperine-containing bioactive hydrogel system compared to the bioactive hydrogel system without piperine. Therefore, the study’s findings establish that the piperine-containing bioactive hydrogel system is a promising therapeutic approach for wound healing application that should be diligently considered for clinical transferability.

The objectives of this study are to investigate the cytotoxic effect of different Citrullus colocynthis extracts on breast and lung cancer cell lines using flow cytometry to gain mechanistic insights. C. colocynthis was extracted sequentially using the Soxhlet method. We first tested the plant extracts’ cytotoxicity on non-malignant L929 cells and cancerous breast (MCF-7) and lung (A549) cell lines. We observed that the IC50 of the methanol extract on the viability of MCF-7 and A549 cell lines was 81.08 µg/mL and 17.84 µg/mL, respectively, using the MTT assay. The aqueous and methanol extracts were less toxic when tested against the non-cancerous L929 cell line, with IC50 values of 235.48 µg/mL and 222.29 µg/mL, respectively. Then, using flow cytometry, we investigated the underlying molecular pathways with Annexin-V, Anti-Bcl-2, Caspase-3, and DNA fragmentation (TUNEL) assays. Flow cytometric and molecular marker analyses revealed that the methanol extract activated caspase-3 and inhibited Bcl-2 protein, causing early and late apoptosis, as well as cell death via DNA damage in breast and lung cancer cells. These findings indicate that the methanol extract of C. colocynthis is cytotoxic to breast and lung cancer cell lines. The total phenolic and flavonoid content analysis results showed the methanolic extract of C. colocynthis has a concentration of 326.25 μg GAE/g dwt and 274.61 μg QE/g dwt, respectively. GC-MS analysis of the methanol extract revealed phytochemicals relevant to its cytotoxicity.

The demand for microbial pectinase has increased due to its vast applications in different industries. The current study dealt with the synthesis of pectinase by a novel native strain Aspergillus cervinus ARS2 using agro-industrial waste. Comparative studies conducted on pectinase production by submerged fermentation (SmF) and solid-state fermentation (SSF) showed that pectinase activity was more increased in SSF (44.51 ± 1.33 IU/mL) than in SmF (40.60 ± 1.15 IU/mL) when using orange peel as a substrate. Using SSF, one-factor-at-a-time (OFAT) studies were conducted, considering different process variables such as inoculum size, initial pH, incubation time, moisture content, incubation temperature, and substrate particle size, all of which affected the pectinase activity. OFAT results showed the highest pectinase activity at an inoculum size of 106 spores/mL (43.11 ± 1.06 U/mL), an incubation time of 6 days (43.81 ± 1.21 U/mL), a moisture content of 100% (44.30 ± 1.69 U/mL), a substrate particle size of 1.7 mm (42.06 ± 1.20 U/mL), an incubation temperature of 37 °C (45.90 ± 1.33 U/mL), and an initial pH of 4 (43.31 ± 0.89 U/mL). The identified significant process variables were then optimized by response surface methodology (RSM)-central composite design (CCD). The results showed optimum pectinase activity of 107.14 ± 0.71 IU/mL for a substrate particle size of 2 mm, an incubation temperature of 31.5 °C, an initial pH of 4.9, and a moisture content of 107%, which was obtained from the Minitab optimizer. By using statistical optimization, the pectinase production from the isolated novel fungal strain A. cervinus ARS2 was increased 2.38-fold. Therefore, the A. cervinus ARS2 strain can be further explored for large-scale pectinase production which could meet the growing industrial demands.

Doxorubicin (DOXO) is an antineoplastic drug that is used extensively in managing multiple cancer types. However, DOXO-induced cardiotoxicity is a limiting factor for its widespread use and considerably affects patients’ quality of life. Farnesol (FSN) is a sesquiterpene with antioxidant, anti-inflammatory, and anti-tumor properties. Thus, the current study explored the cardioprotective effect of FSN against DOXO-induced cardiotoxicity. In this study, male Wistar rats were randomly divided into five groups (n = 7) and treated for 14 days. Group I (Control): normal saline, p.o. daily for 14 days; Group II (TOXIC): DOXO 2.4 mg/kg, i.p, thrice weekly for 14 days; Group III: FSN 100 mg/kg, p.o. daily for 14 days + DOXO similar to Group II; Group IV: FSN 200 mg/kg, p.o. daily for 14 days + DOXO similar to Group II; Group V (Standard): nifedipine 10 mg/kg, p.o. daily for 14 days + DOXO similar to Group II. At the end of the study, animals were weighed, blood was collected, and heart-weight was measured. The cardiac tissue was used to estimate biochemical markers and for histopathological studies. The observed results revealed that the FSN-treated group rats showed decrease in heart weight and heart weight/body weight ratio, reversed the oxidative stress, cardiac-specific injury markers, proinflammatory and proapoptotic markers and histopathological aberrations towards normal, and showed cardioprotection. In summary, the FSN reduces cardiac injuries caused by DOXO via its antioxidant, anti-inflammatory, and anti-apoptotic potential. However, more detailed mechanism-based studies are needed to bring this drug into clinical use.

To manage the COVID-19 outbreak, the WHO recommends adult and child vaccination. Vaccine skepticism has been a major worldwide health concern for decades, and the situation is worsening. The primary purpose of this study was to investigate parental willingness to vaccinate their children (aged 5 to 11 years) against COVID-19 and to describe its relationship with attitude, barriers, facilitators, and sources of knowledge regarding the vaccine. Methods: From February to March 2022, a community-based cross-sectional survey was undertaken among the parents of Riyadh city, Saudi Arabia. We employed a convenient sampling procedure to gather the required sample. Using the Raosoft sample size calculator, a minimum sample size of 385 was determined based on a 95% confidence level, a 5% margin of error, and a 5% precision level. The data were analyzed using version 26 of SPSS. A p-value less than 0.05 was judged statistically significant. The Chi-square test and likelihood ratio were utilized to describe the relationship between socio-demographic characteristics, driving factors, and COVID-19 vaccine hesitancy. Vaccine hesitancy associated factors were identified using multivariate binary logistic regression. A total of 528 replies were received. The majority of respondents were mothers (77.7%), aged 26 to 40 years (67.8%), married (91.5%), Saudi nationals (96.2%), college graduates (70.6%), with a monthly family income of more than SAR 10,000 (46.4%), non-healthcare professionals (84.7%), employed in the government sector (33.7%), with three children (23.3%), and children aged 5 to 11 years (88.7%). A little more than half of the parents (55.7%) exhibited considerable vaccination hesitancy. About 16.28% of parents were willing to vaccinate their children as soon as possible, compared to 38.44% who had no interest whatsoever in vaccination. A greater proportion of mothers and unemployed parents were unwilling to vaccinate their children. Parents with a higher monthly income (above SAR 10,000), who worked as healthcare professionals, and whose children suffered from chronic conditions were significantly more ready to vaccinate their children against COVID-19. Parents who were aware of anti-vaccination campaigns and who vaccinated their children with required childhood vaccines were also much more likely to vaccinate their children against COVID-19. Most parents (66.9%) obtained information on COVID-19 via the Saudi Ministry of Health website, followed by social media (48.1%). The vaccine’s novelty and the dearth of reliable information about its safety (65%) and insufficient information about its effectiveness (36.2%) were the primary reasons for not vaccinating children against COVID-19, whereas preventing children from contracting COVID-19 (55.9%) and government mandate (38.8%) were the primary reasons for vaccinating children against COVID-19. Conclusions: There was significant parental hesitancy to immunize their children against COVID-19. To involve and educate parents, multi-component interventions must be developed and implemented.

The primary objective of this research was to use flow cytometry to gain mechanistic insights into the cytotoxic effects of Tribulus terrestris extracts on breast cancer (MCF7) and lung cancer (A549) cell lines. T. terrestris was extracted using a Soxhlet apparatus in a progressive process. GC–MS was used to establish the phytochemical constituents. The amounts of phenolic compounds and flavonoids in the plant extracts were calculated using spectrophotometric analysis. The cytotoxicity of plant extracts was initially evaluated in non-malignant L929 cells, then in carcinogenic MCF-7 and A549 cell lines. Then, we performed an Annexin V assay, an anti-Bcl-2 assay, a Caspase-3 assay, and a DNA fragmentation (TUNEL) assay, using flow cytometry to investigate the underlying molecular processes. Based on the data, the methanolic extract of T. terrestris contained the highest amounts of phenolic compounds and flavonoids, with values of 169.87 µg GAE/g dwt and 160.12 µg QE/g dwt, respectively. Analysis by GC–MS revealed the presence of bioactive phytochemicals with proven cytotoxicity. Based on the MTT experiment, we determined that the IC50 values for the methanol extract’s effect on the viability of the MCF-7 and A549 cell lines were 218.19 and 179.62 µg/mL, respectively. The aqueous and methanol extracts were less cytotoxic when tested against the cancer-free L929 cell line (IC50 = 224.35 µg/mL). In both breast and lung cancer cells, the methanolic extract was found to activate caspase-3 and inhibit the Bcl-2 protein, resulting in early and late apoptosis and cell death via DNA damage. These findings point to cytotoxic effects of T. terrestris methanol extract against breast and lung cancer cell lines. Due to its potential as a source of anti-cancer chemotherapeutic medicines, T. terrestris warrants further investigation.

Areca catechu seeds and their extract/s are currently used to treat various ailments and infections including snakebites. The purpose of this investigation was to assess the inhibiting/neutralizing effect of ethyl acetate and aqueous ethanolic seed extracts of A. catechu on Bungarus caeruleus (krait) venom. The enzyme activities and their inhibition were evaluated using standard procedures (in vitro). In vivo studies were conducted using chick embryos and murine models. The extracts inhibited hyaluronidase and phospholipase A2 activities. Protease activity was neutralized by the aqueous ethanolic extract only. The IC50 value of aqueous ethanolic extract for hyaluronidase was 0.001 g/mL, while that for the ethyl acetate extract for phospholipase A2 was 0.006 g/mL. In addition, both the extracts neutralized the indirect hemolysis and fibrinogenolytic activity induced by B. caeruleus venom. The LD50 for the chick embryos was 4.9 µg/egg. The 50 and 100 µg aqueous ethanolic extracts neutralized the LD50 and the challenging dose (3LD50) of venom effectively in the chick embryo model. The LD50 of B. caeruleus venom in mice was 0.1927 µg/kg; the extract extended the survival time of the mice from 25 min to 30 and 35 min in 1:10 and 1:20 ((w/w) venom:extract) ratios, respectively. The extract also neutralized myotoxic activity. The A. catechu seed extract showed promising inhibitory properties against B. caeruleus venom. In this regard, academia and industries should work collaboratively to develop and formulate a cost-effective first-aid drug.

The main objective of the proposed work was the development of a thermosensitive gel (containing clove and tea tree oil) for the management of vaginal candidiasis. Both oils have been recommended to be used separately in a topical formulation for vaginal candidiasis. Incorporating two natural ingredients (clove and tea tree oil) into a product give it a broad antimicrobial spectrum and analgesic properties. The two oils were mixed together at a 3:1 ratio and converted into o/w nanoemulsion using the aqueous titration method and plotting pseudo ternary phase diagrams. Further transformations resulted in a gel with thermosensitive properties. To determine the final formulation’s potential for further clinical investigation, in vitro analyses (viscosity measurement, MTT assay, mucoadhesion, ex vivo permeation) and in vivo studies (fungal clearance kinetics in an animal model) were conducted. The current effort leveraged the potential of tea tree and clove oils as formulation ingredients and natural therapeutic agents for vaginal infections. Its synergy generated a stable and effective thermosensitive gel that can be utilized for recurrent candidiasis and other infections.

An estimated 35% of the world’s population depends on wheat as their primary crop. One fifth of the world’s wheat is utilized as animal feed, while more than two thirds are used for human consumption. Each year, 17–18% of the world’s wheat is consumed by China and India. In wheat, spot blotch caused by Bipolaris sorokiniana is one of the major diseases which affects the wheat crop growth and yield in warmer and humid regions of the world. The present work was conducted to evaluate the effect of green synthesized silver nanoparticles on the biochemical constituents of wheat crops infected with spot blotch disease. Silver nanoparticles (AgNPs) were synthesized using Mangifera indica leaf extract and their characterization was performed using UV-visible spectroscopy, SEM, XRD, and PSA. Characterization techniques confirm the presence of crystalline, spherical silver nanoparticles with an average size of 52 nm. The effect of green synthesized nanoparticles on antioxidative enzymes, e.g., Superoxide dismutase (SOD), Catalase (CAT), Glutathione Reductase (GR), Peroxidase (POX), and phytochemical precursor enzyme Phenylalanine Ammonia-Lyase (PAL), and on primary and secondary metabolites, e.g., reducing sugar and total phenol, in Bipolaris sorokiniana infected wheat crop were studied. Inoculation of fungal spores was conducted after 40 days of sowing. Subsequently, diseased plants were treated with silver nanoparticles at different concentrations. Elevation in all biochemical constituents was recorded under silver nanoparticle application. The treatment with a concentration of nanoparticles at 50 pp min diseased plants showed the highest resistance towards the pathogen. The efficacy of the green synthesized AgNPs as antibacterial agents was evaluated against multi drug resistant (MDR) bacteria comprising Gram-negative bacteria Escherichia coli (n = 6) and Klebsiella pneumoniae (n = 7) and Gram-positive bacteria Methicillin resistant Staphylococcus aureus (n = 2). The results show promising antibacterial activity with significant inhibition zones observed with the disc diffusion method, thus indicating green synthesized M. indica AgNPs as an active antibacterial agent against MDR pathogens.

Rice is the most important staple food crop feeding more than 50% of the world’s population. Rice blast is the most devastating fungal disease, caused by Magnaporthe oryzae (M. oryzae) which is widespread in rice growing fields causing a significant reduction in the yield. The present study was initiated to evaluate the effect of green synthesized silver nanoparticles (AgNPs) on the biochemical constituents of rice plants infected with blast. AgNPs were synthesized by using Azadirachta indica leaf extract and their characterization was performed using UV-visible spectroscopy, particle size analyser (PSA), scanning electron microscope (SEM), and X-ray diffraction (XRD) which confirmed the presence of crystalline, spherical shaped silver nanoparticles with an average size of 58.9 nm. After 45 days of sowing, artificial inoculation of rice blast disease was performed. After the onset of disease symptoms, the plants were treated with AgNPs with different concentrations. Application of nanoparticles elevated the activity of antioxidative enzymes such as superoxide dismutase, catalase, peroxidase, glutathione reductase, and phenylalanine ammonia-lyase compared to control plants, and total phenol and reducing sugars were also elevated. The outcome of this study showed that an increase in all biochemical constituents was recorded for A. indica silver nanoparticles-treated plants. The highest values were recorded in 30 ppm and 50 ppm AgNPs-treated plants, which showed the highest resistance towards the pathogen. Green synthesized AgNPs can be used in future for disease control in susceptible varieties of rice. The synthesized AgNPs using A. indica leaf extract have shown promising antibacterial activity when tested against 14 multidrug-resistant (MDR) bacteria comprising Gram-negative bacteria Escherichia coli (n = 6) and Klebsiella pneumoniae (n = 7) with a good zone of inhibition diameter, tested with the disc diffusion method. Based on these findings, it appears that A. indica AgNPs have promise as an antibacterial agent effective against MDR pathogens.

The objectives of this research were to carry out GC–MS and LC–MS-based phytochemical profiling of Barleria hochstetteri, as well as flow cytometry-based mechanistic investigations of the cytotoxic effect of its extracts against breast and lung cancer cell lines. This preclinical in vitro study was carried out in Saudi Arabia and India, from 11 August to 15 January 2022. Barleria hochstetteri was sequentially extracted using the Soxhlet extraction technique. Utilizing LC–MS and GC–MS methods, the phytochemical profiling was performed. Additionally, the total phenolic compounds and flavonoids were quantified in the plant extract using spectrophotometric techniques. In this study, we first examined the cytotoxicity of the plant extract on non-malignant L929 cells and on the carcinogenic MCF-7 and A549 cell lines. Then, we studied the underlying molecular pathways by means of Anti-Bcl-2, caspase-3, and DNA fragmentation (TUNEL) assays, using flow cytometry. The results revealed phenolic compounds and flavonoids to be the two major components in the methanolic extract of B. hochstetteri, with concentrations of 3210 µg GAE/g dwt and 1863 µg QE/g dwt, respectively. Results from GC–MS and LC–MS analyses revealed the presence of bioactive phytochemicals with known cytotoxicity. From the MTT assay on cell viability, the IC50 of the methanol extract for the MCF-7 and A549 cell lines were 219.67 and 144.30 µg/mL, respectively. With IC50 values of 324.24 and 266.66 µg/mL, respectively, the aqueous and methanol extracts were less toxic when tested against the non-cancerous L929 cell line. The extract caused early and late apoptosis in the tested breast and lung cancer cells by activating caspase-3 and inhibiting Bcl-2 protein, and it also caused cell death via DNA damage, based on flow cytometric and molecular marker analyses. These findings indicate that the methanol extract of B. hochstetteri was cytotoxic on breast cancer and lung cancer cell lines. To uncover cancer-fighting chemicals, there is a need for further research on B. hochstetteri, as it is a promising source of anti-cancer chemotherapeutic drugs.

Oral cancer has a high mortality rate, which is mostly determined by the stage of the disease at the time of admission. Around half of all patients with oral cancer report with advanced illness. Hitherto, chemotherapy is preferred to treat oral cancer, but the emergence of resistance to anti-cancer drugs is likely to occur after a sequence of treatments. Curcumin is renowned for its anticancer potential but its marred water solubility and poor bioavailability limit its use in treating multidrug-resistant cancers. As part of this investigation, we prepared and characterized Curcumin nanomicelles (CUR-NMs) using DSPE-PEG-2000 and evaluated the anticancer properties of cisplatin-resistant cancer cell lines. The prepared CUR-NMs were sphere-shaped and unilamellar in structure, with a size of 32.60 ± 4.2 nm. CUR-NMs exhibited high entrapment efficiency (82.2%), entrapment content (147.96 µg/mL), and a mean zeta potential of −17.5ζ which is considered moderately stable. The cellular uptake and cytotoxicity studies revealed that CUR-NMs had significantly higher cytotoxicity and cellular uptake in cisplatin drug-resistant oral cancer cell lines and parental oral cancer cells compared to plain curcumin (CUR). The DAPI and FACS analysis corroborated a high percentage of apoptotic cells with CUR-NMs (31.14%) compared to neat CUR (19.72%) treatment. Conclusively, CUR-NMs can potentially be used as an alternative carrier system to improve the therapeutic effects of curcumin in the treatment of cisplatin-resistant human oral cancer.

Pectinolytic enzymes are related enzymes that hydrolyze pectic substances. Pectinolytic enzymes are of great interest in industrial applications for softening fruits, extracting and clarifying juices, extracting olive oil, retting textile fibers, preparing gel, and isolating protoplasts. The current work presents acidic extracellular pectinase production using low-cost agro-industrial waste with the indigenously isolated novel strain Aspergillus cervinus. Two fungal isolates, ARS2 and ARS8, with maximum pectinase activity, 41.88 ± 1.57 IU/mL and 39.27 ± 1.14 IU/mL, respectively, were screened out of 27 isolates from decayed fruit peels (orange, banana, and lemon) and soil containing decomposed vegetables. The isolate ARS2, identified as Aspergillus cervinus by molecular characterization, showed the highest pectinase activity of 43.05 ± 1.38IU/mL during screening and was further used for media component screening and optimization studies. To understand their effect on pectinase activity, one-factor-at-a-time (OFAT) studies were conducted on carbon sources, nitrogen sources, and mineral salts. The OFAT results showed the highest pectinase activity for orange peel (carbon source) at 44.51 ± 1.33 IU/mL, peptone (nitrogen source) at 45.05 ± 1.04 IU/mL, and NaH2PO4 (mineral salts) at 43.21 ± 1.12 IU/mL. The most significant media components screened by the Plackett–Burman (PB) design based on the p-value, Pareto chart, and main effect plot, were orange peel (p < 0.001), peptone (p < 0.001), NaH2PO4 (p < 0.001), and KH2PO4 (p < 0.001), which were further optimized using Response Surface Methodology (RSM) and Central Composite Design (CCD). The optimization results for the media components showed a maximum pectinase activity of 105.65 ± 0.31 IU/mL for 10.63 g orange peel, 3.96 g/L peptone, 2.07 g/L KH2PO4, and 2.10 g/L NaH2PO4. Thus, it was discovered that the indigenously isolated novel strain Aspergillus cervinus ARS2 was able to successfully produce a significant amount of pectinase using agro-industrial waste. Therefore, it can be considered for the large-scale optimized production of pectinase to meet industrial demands.

Silver nanoparticles (AgNPs) have recently gained interest in the medical field because of their biological features. The present study aimed at screening Rhizophora apiculata secondary metabolites, quantifying their flavonoids and total phenolics content, green synthesis and characterization of R. apiculata silver nanoparticles. In addition, an assessment of in vitro cytotoxic, antioxidant, anti-inflammatory and wound healing activity of R. apiculata and its synthesized AgNPs was carried out. The powdered plant material (leaves) was subjected to Soxhlet extraction to obtain R. apiculata aqueous extract. The R. apiculata extract was used as a reducing agent in synthesizing AgNPs from silver nitrate. The synthesized AgNPs were characterized by UV-Vis, SEM-EDX, XRD, FTIR, particle size analyzer and zeta potential. Further aqueous leaf extract of R. apiculata and AgNPs was subjected for in vitro antioxidant, anti-inflammatory, wound healing and cytotoxic activity against A375 (Skin cancer), A549 (Lung cancer), and KB-3-1 (Oral cancer) cell lines. All experiments were repeated three times (n = 3), and the results were given as the mean ± SEM. The flavonoids and total phenolics content in R. apiculata extract were 44.18 ± 0.086 mg/g of quercetin and 53.24 ± 0.028 mg/g of gallic acid, respectively. SEM analysis revealed R. apiculata AgNPs with diameters ranging from 35 to 100 nm. XRD confirmed that the synthesized silver nanoparticles were crystalline in nature. The cytotoxicity cell viability assay revealed that the AgNPs were less toxic (IC50 105.5 µg/mL) compared to the R. apiculata extract (IC50 47.47 µg/mL) against the non-cancerous fibroblast L929 cell line. Antioxidant, anti-inflammatory, and cytotoxicity tests revealed that AgNPs had significantly more activity than the plant extract. The AgNPs inhibited protein denaturation by a mean percentage of 71.65%, which was equivalent to the standard anti-inflammatory medication diclofenac (94.24%). The AgNPs showed considerable cytotoxic effect, and the percentage of cell viability against skin cancer, lung cancer, and oral cancer cell lines was 31.84%, 56.09% and 22.59%, respectively. R. apiculata AgNPs demonstrated stronger cell migration and percentage of wound closure (82.79%) compared to the plant extract (75.23%). The overall results revealed that R. apiculata AgNPs exhibited potential antioxidant, anti-inflammatory, wound healing, and cytotoxic properties. In future, R. apiculata should be further explored to unmask its therapeutic potential and the mechanistic pathways of AgNPs should be studied in detail in in vivo animal models.

Zinc Oxide Nanoparticles (ZnONPs) are one of the most widely used metal oxide nanoparticles in biological applications because of their outstanding biocompatibility, affordability, and low toxicity. In biomedicine, ZnONPs have shown promise, particularly in the disciplines of anticancer and antibacterial fields. In comparison to other standard synthesis methods, the environmentally-friendly synthesis of metallic nanoparticles utilizing various plant extracts is a good option. The current research focuses on the synthesis of zinc oxide nanoparticles (ZnONPs) from R. sativus leaf extract under various physical conditions (Precipitation method). Analytical methods were used to confirm and characterize the produced ZnONPs. The spherical nature of the produced nanoparticles was established by SEM analysis. The generation of very pure ZnONPs was confirmed by EDS data. The crystalline nature of the produced nanoparticles, with a particle size of 66.47 nm, was confirmed by XRD. The XRD graphs’ presence of the (100), (002), and (101) planes strongly suggest the production of wurtzite ZnO. The visual and infrared area exhibits transmissions of 84 percent in the pH 10 nanoparticles. The band gap of the nanoparticles increases from 3.34 to 3.38 eV when the pH increases. These nanoparticles were effective against both Gram-positive and Gram-negative bacteria. The effect of several process parameters such as pH and temperature were investigated, and the best conditions were discovered to be pH 12 and 80 °C, respectively. The effect of ZnONPs was tested with human breast cancer cells (MCF-7), and they showed significant cytotoxic results. Collectively, our data suggest that ZnONPs of R. sativus leaf extract inhibit breast cancer cell lines. The ZnONPs are, therefore, a prospective source of chemopreventive drugs that merit additional exploration in order to uncover lead compounds with cancer chemotherapeutic potential.

The present study aims to design and develop a nanoemulgel formulation of Tamoxifen citrate (TAM), a water-insoluble, potent anticancer drug, using the spontaneous emulsification method to improve topical delivery, achieve high accumulation at the tumour site, and spare the healthy tissues. The oil-based selection was related to the TAM solubility, while the surfactant and co-surfactant were chosen based on the droplets’ thermodynamic stability and size. Afterwards, a pseudo-ternary phase diagram was built for the most promising formulation using two oils, olive and sesame, with a varied mix of Tween 40 as the surfactant and Trascutol HP as the co-surfactant (Smix), by the optimisation of experiments. The nanoemulsion (NE) formulations that were prepared were found to have an average droplet size of 41.77 ± 1.23 nm and 188.37 ± 3.53 nm, with suitable thermodynamic stability and physicochemical properties. Both olive and sesame oils are natural food additives due to their associated antioxidant effects; therefore, they showed no toxicity profile on breast cell lines (MCF-7, ATCC number HTB-22). The TAM-NE preparations revealed a prolonged and doublings superior cumulative percentage of in vitro release of TAM compared to TAM plain gel suspension over 24 h. The release data suggested that the Higuchi model was the best fitting kinetical model for the developed formulations of NE1, NE9, and NE18. The extended release of the drug as well as an acceptable amount of the drug permeated TAM via nanogel preparations suggested that nanoemulgel (NEG) is suitable for the topical delivery of TAM in breast cancer management. Thus, this work suggests that a nanogel of TAM can improve anticancer properties and reduce systemic adverse effects compared to a suspension preparation of TAM when applied in the treatment of breast cancer.

The cold extraction method was used to obtain the aqueous extract of Vitex leucoxylon leaves in a ratio of 1:10. Iron nanoparticles (FeNPs) were synthesized using aqueous leaf extract of V. leucoxylon as a reducing agent. The phytoreducing approach was used to make FeNPs by mixing 1 mL of plant extract with 1 mM of ferric sulfate. Scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), Ultraviolet–visible spectroscopy (UV-Vis), and energy-dispersive X-ray spectroscopy were used to examine the synthesized FeNPs. The reducing reaction was shown by a change in the color of the solution, and the formation of black color confirms that FeNPs have been formed. The greatest absorption peak (max) was found at 395 nm in UV-Vis spectral analysis. The FTIR spectra of V. leucoxylon aqueous leaf extract showed shifts in some peaks, namely 923.96 cm−1 and 1709.89 cm−1, with functional groups carboxylic acids, unsaturated aldehydes, and ketones, which were lacking in the FTIR spectra of FeNPs and are responsible for FeNPs formation. FeNPs with diameters between 45 and 100 nm were observed in SEM images. The creation of FeNPs was confirmed by EDX, which shows a strong signal in the metallic iron region at 6–8 Kev. XRD revealed a crystalline nature and an average diameter of 136.43 nm. Antioxidant, anti-inflammatory, cytotoxic, and wound healing in vitro tests reported significant activity of the FeNPs. The cumulative findings of the present study indicate that the green synthesis of FeNPs boosts its biological activity and may serve as a possible dermal wound-healing agent and cytotoxic agent against cancer. Future study is needed on the identification of mechanisms involved in the synthesis of FeNPs by V. leucoxylon and its biomedical applications.

Objective: There is a growing demand for colourants of natural origin in the food, pharmaceutical, cosmetic and textile sectors. Previously, our group has screened a fungal species from forest soil, identified as Penicillium europium. The isolated fungus transformed the longifolene into various metabolites, of which 12 were isolated in pure form, with potential to be utilized in the perfumery industry. This study aimed to isolate and identify novel fungal pigments from Penicillium europium. Methods: The current study showcases the extraction and identification of fungal pigment from Penicillium europium using different spectral studies. The strain was isolated from forest soil, Western Ghats, India, and was found to be capable of using longifolene as the sole carbon source. The yellowish pink coloured pigment-producing fungal strain was identified as Penicillium europium. Further, the pinkish pigment was extracted, purified, and using spectral studies like UV, IR, NMR and Mass, the structure of the pure pigment was identified. Results: The pure pigment structure was analyzed and tentatively confirmed as 2-(1,5, dimethyl hexyl)-3,5-dimethyl-6-hydro-1,4-benzoquinone having the molecular formula C16H24O3. Toxicity study using LD50 on Albino rats revealed that the pigment had no toxic effect on rats. Conclusion: Penicillium europium synthesized pigments could contribute to biotechnology and add value to the food, feed, and pharmaceutical industries. They can be used for various industrial applications, for example, as dyes for textile and non-textile substrates such as paper, leather, coatings and paints, in cosmetics, and food additives. Negative cytotoxicity result inferred that the pigment could be a potential replacement for hazardous synthetic dyes.

Enzymes that degrade pectin are called pectinases. Pectinases of microbial origin are used in juice clarification as the process is cost-effective. This study screened a pectinase-producing bacterium isolated from soil and identified as Bacillus subtilis 15A B-92 based on the 16S rRNA molecular technique. The purified pectinase from the isolate showed 99.6 U/mg specific activity and 11.6-fold purity. The molecular weight of the purified bacterial pectinase was 14.41 ± 1 kD. Optimum pectinase activity was found at pH 4.5 and 50 °C, and the enzyme was 100% stable for 3.5 h in these conditions. No enzymatic inhibition or activation effect was seen with Fe2+, Ca2+, or Mg2+. However, a slight inhibition was seen with Cu2+, Mn2+, and Zn2+. Tween 20 and 80 slightly inhibited the pectinase, whereas iodoacetic acid (IAA), ethylenediaminetetraacetate (EDTA), urea, and sodium dodecyl sulfate (SDS) showed potent inhibition. The bacterial pectinase degraded citrus pectin (100%); however, it was inactive in the presence of galactose. With citrus pectin as the substrate, the Km and Vmax were calculated as 1.72 mg/mL and 1609 U/g, respectively. The high affinity of pectinase for its substrate makes the process cost-effective when utilized in food industries. The obtained pectinase was able to clarify orange and apple juices, justifying its application in the food industry.

Background: Cancer is a dangerous threat that creates extremely high rates of death and morbidity in various regions of the world. Finding suitable therapeutics to improve cancer therapy while avoiding side effects is critical. The most appropriate innovative therapeutics, which combine natural ingredients and nanomaterials, can improve the biological activity of cancer chemotherapeutics. Methods: Phenolic profiling using high-resolution mass spectrometry and the synthesis of zinc oxide nanoparticles was achieved through the reaction of zinc acetate with Euphorbia retusa extract. The characterization of ZnONPs was performed by UV, IR, Zeta potential, XRD, SEM, and TEM. The cytotoxic activity of the ZnONPs was evaluated using a SRB assay against lung, liver, and breast cancer cell lines. Moreover, the mechanism of cytotoxic activity was evaluated in the form of caspase-8 promoters and anti-inflammatory mechanisms using the Western blot method. Results: The high-resolution LC/MS/MS of the E. retusa led to the identification of 22 compounds in the plant for the first time. The Er-ZnONPs had hexagonal shapes, were approximately 100 nm in size, and consisted of aggregated particles of about 10 nm. The E. retusa ZnONPs exhibited cytotoxic activity against HA-549 (IC50 = 22.3 µg/mL), HepG2 (IC50 = 25.6), Huh-7 (IC50 = 25.7), MCF-7 (IC50 = 37.7), and MDA-MB-231 (IC50 = 37). Conclusions: E. retusa are rich in phenolics that are capable of synthesizing ZnONPs, which possess cytotoxic activity, via caspase-8 promotion and anti-inflammatory mechanisms.

The applications of bioactive compounds from medicinal plants as therapeutic drugs are largely increasing. The present study selected the bioactive compounds from Acacia concinna (A. concinna) and Citrus limon (C. limon) to assess their phytochemicals, proteins, and biological activity. The plant material was collected, and extraction performed as per the standard procedure. Qualitative analysis was undertaken, and identification of functional organic groups was performed by FTIR and HPLC. Antibacterial, anticancer, antioxidant, antihyperglycemic, antihyperlipidemic, and inhibition kinetics studies for enzymes were performed to assess the different biological activities. Flavonoids and phenols were present in a significant amount in both the selected plants. A. concinna showed significant antimicrobial activity against Z. mobilis, E. coli, and S. aureus, with minimum inhibition zones (MIZ) of 24, 22, and 20 mm, respectively. C. limon strongly inhibited all the tested pathogenic bacteria with maximum and minimum MIZ of 32 and 17 mm. A. concinna silver nanoparticles also exhibited potent antimicrobial activity. Both extracts showed substantial antioxidant, antihyperlipidemic, antidiabetic, anticancer (MCF-7), and anti-urease (antiulcer) properties. To conclude, these plants can be used to treat hyperlipidemia, diabetes, cancer, and gastrointestinal ulcers. They can also serve as antimicrobial and antioxidant agents. Thus, the studied plants must be exploited cost-effectively to generate therapeutic drugs for various diseases.

Bionanotechnology is a branch of science that has revolutionized modern science and technology. Nanomaterials, especially noble metals, have attracted researchers due to their size and application in different branches of sciences that benefit humanity. Metal nanoparticles can be synthesized using green methods, which are good for the environment, economically viable, and facilitate synthesis. Due to their size and form, gold nanoparticles have become significant. Plant materials are of particular interest in the synthesis and manufacture of theranostic gold nanoparticles (NPs), which have been generated using various materials. On the other hand, chemically produced nanoparticles have several drawbacks in terms of cost, toxicity, and effectiveness. A plant-mediated integration of metallic nanoparticles has been developed in the field of nanotechnology to overcome the drawbacks of traditional synthesis, such as physical and synthetic strategies. Nanomaterials′ tunable features make them sophisticated tools in the biomedical platform, especially for developing new diagnostics and therapeutics for malignancy, neurodegenerative, and other chronic disorders. Therefore, this review outlines the theranostic approach, the different plant materials utilized in theranostic applications, and future directions based on current breakthroughs in these fields.

Current drug discovery involves finding leading drug candidates for further development. New scientific approaches include molecular docking, ADMET studies, and molecular dynamic simulation to determine targets and lead compounds. Hepatitis B is a disease of concern that is a life-threatening liver infection. The protein considered for the study was HBx. The hepatitis B X-interacting protein crystal structure was obtained from the PDB database (PDB ID-3MSH). Twenty ligands were chosen from the PubChem database for further in silico studies. The present study focused on in silico molecular docking studies using iGEMDOCK. The triethylene glycol monoethyl ether derivative showed an optimum binding affinity with the molecular target HBx, with a high negative affinity binding energy of −59.02 kcal/mol. Lipinski’s rule of five, Veber, and Ghose were followed in subsequent ADMET studies. Molecular dynamic simulation was performed to confirm the docking studies and to analyze the stability of the structure. In these respects, the triethylene glycol monoethyl ether derivative may be a promising molecule to prepare future hepatitis B drug candidates. Substantial research effort to find a promising drug for hepatitis B is warranted in the future.

Thymoquinone is a natural bioactive with significant therapeutic activity against multiple ailments including wound healing. The poor aqueous solubility and low skin permeability limit its therapeutic efficacy. The present investigation aimed to improve the biopharmaceutical attributes of thymoquinone to enhance its topical efficacy in wound healing. A nanoemulsion-based hydrogel system was designed and characterized as a nanotechnology-mediated drug delivery approach to improve the therapeutic efficacy of thymoquinone, utilizing a high-energy emulsification technique. The black seed oil, as a natural home of thymoquinone, was utilized to improve the drug loading capacity of the developed nanoemulsion system and reduced the oil droplet size to p < 0.05) influence on the mean droplet size and polydispersity index of the generated nanoemulsion. The developed nanoemulgel system of thymoquinone demonstrated the pseudoplastic behavior with thixotropic properties, and this behavior is desirable for topical application. The nanoemulgel system of thymoquinone exhibited significant enhancement (p < 0.05) in skin penetrability and deposition characteristics after topical administration compared to the conventional hydrogel system. The developed nanoemulgel system of thymoquinone exhibited quicker and early healing in wounded Wistar rats compared to the conventional hydrogel of thymoquinone, while showing comparable healing efficacy with respect to marketed silver sulfadiazine (1%) cream. Furthermore, histopathology analysis of animals treated with a developed formulation system demonstrated the formation of the thick epidermal layer, papillary dermis along with the presence of extensive and organized collagen fibers in newly healed tissues. The outcome of this investigation signifies that topical delivery of thymoquinone through nanoemulgel system is a promising candidate which accelerates the process of wound healing in preclinical study.

Breast cancer (BRCA) remains the leading cause of cancer morbidity and mortality worldwide. In the present study, we identified novel biomarkers expressed during estradiol and tamoxifen treatment of BRCA. The microarray dataset of E-MTAB-4975 from Array Express database was downloaded, and the differential expressed genes (DEGs) between estradiol-treated BRCA sample and tamoxifen-treated BRCA sample were identified by limma package. The pathway and gene ontology (GO) enrichment analysis, construction of protein-protein interaction (PPI) network, module analysis, construction of target genes—miRNA interaction network and target genes-transcription factor (TF) interaction network were performed using bioinformatics tools. The expression, prognostic values, and mutation of hub genes were validated by SurvExpress database, cBioPortal, and human protein atlas (HPA) database. A total of 856 genes (421 up-regulated genes and 435 down-regulated genes) were identified in T47D (overexpressing Split Ends (SPEN) + estradiol) samples compared to T47D (overexpressing Split Ends (SPEN) + tamoxifen) samples. Pathway and GO enrichment analysis revealed that the DEGs were mainly enriched in response to lysine degradation II (pipecolate pathway), cholesterol biosynthesis pathway, cell cycle pathway, and response to cytokine pathway. DEGs (MCM2, TCF4, OLR1, HSPA5, MAP1LC3B, SQSTM1, NEU1, HIST1H1B, RAD51, RFC3, MCM10, ISG15, TNFRSF10B, GBP2, IGFBP5, SOD2, DHF and MT1H), which were significantly up- and down-regulated in estradiol and tamoxifen-treated BRCA samples, were selected as hub genes according to the results of protein-protein interaction (PPI) network, module analysis, target genes—miRNA interaction network and target genes-TF interaction network analysis. The SurvExpress database, cBioPortal, and Human Protein Atlas (HPA) database further confirmed that patients with higher expression levels of these hub genes experienced a shorter overall survival. A comprehensive bioinformatics analysis was performed, and potential therapeutic applications of estradiol and tamoxifen were predicted in BRCA samples. The data may unravel the future molecular mechanisms of BRCA.

The present study aimed to investigate the molecular mechanisms underlying glioblastoma multiform (GBM) and its biomarkers. The differentially expressed genes (DEGs) were diagnosed using the limma software package. The ToppGene (ToppFun) was used to perform pathway and Gene Ontology (GO) enrichment analysis of the DEGs. Protein-protein interaction (PPI) networks, extracted modules, miRNA-target genes regulatory network and TF-target genes regulatory network were used to obtain insight into the actions of DEGs. Survival analysis for DEGs was carried out. A total of 590 DEGs, including 243 up regulated and 347 down regulated genes, were diagnosed between scrambled shRNA expression and Lin7A knock down. The up-regulated genes were enriched in ribosome, mitochondrial translation termination, translation, and peptide biosynthetic process. The down-regulated genes were enriched in focal adhesion, VEGFR3 signaling in lymphatic endothelium, extracellular matrix organization, and extracellular matrix. The current study screened the genes in the PPI network, extracted modules, miRNA-target genes regulatory network, and TF-target genes regulatory network with higher degrees as hub genes, which included NPM1, CUL4A, YIPF1, SHC1, AKT1, VLDLR, RPL14, P3H2, DTNA, FAM126B, RPL34, and MYL5. Survival analysis indicated that the high expression of RPL36A and MRPL35 were predicting longer survival of GBM, while high expression of AP1S1 and AKAP12 were predicting shorter survival of GBM. High expression of RPL36A and AP1S1 were associated with pathogenesis of GBM, while low expression of ALPL was associated with pathogenesis of GBM. In conclusion, the current study diagnosed DEGs between scrambled shRNA expression and Lin7A knock down samples, which could improve our understanding of the molecular mechanisms in the progression of GBM, and these crucial as well as new diagnostic markers might be used as therapeutic targets for GBM.