Integrating 16S rRNA profiling and in-silico analysis for an epitope-based vaccine strategy against Achromobacter xylosoxidans infection.

Achromobacter xylosoxidans is an aerobic, catalase-positive, non-pigment-forming, Gram-negative, and motile bacterium. It potentially causes a wide range of human infections in cystic fibrosis and non-cystic fibrosis patients. However, developing a safe preventive or therapeutic solution against A. xylosoxidans remains challenging. This study aimed to construct an epitope-based vaccine candidate using immunoinformatic techniques. A. xylosoxidans was isolated from an auto workshop in Lahore, and its identification was confirmed through 16S rRNA amplification and bioinformatic analysis. Two protein targets with GenBank accession numbers AKP90890.1 and AKP90355.1 were selected for the vaccine construct. Both proteins exhibited antigenicity, with scores of 0.757 and 0.580, respectively and the epitopes were selected based on the IC50 value using the ANN 4.0 and NN-align 2.3 epitope prediction method for MHC I and MHC II epitopes respectively and predicted epitopes were analyzed for antigenicity, allergenicity and pathogenicity. The vaccine construct demonstrated structural stability, thermostability, solubility, and hydrophilicity. The vaccine produced 250 B-memory cells per mm3 and approximately 16,000 IgM + IgG counts, indicating an effective immune response against A. xylosoxidans. Moreover, the vaccine candidate interacted stably with toll-like receptor 5, a pattern recognition receptor, with a confidence score of 0.98. These results highlight the potency of the designed vaccine candidate, suggesting its potential to withstand rigorous in vitro and in vivo clinical trials. This epitope-based vaccine could serve as the first preventive immunotherapy against A. xylosoxidans infections, addressing this bacterium's health and financial burdens. The findings demonstrate the value of employing immunoinformatic tools in vaccine development, paving the way for more precise and tailored approaches to combating microbial threats.

Investigation of the insecticidal potential of curcumin derivatives that target the Helicoverpa armigera sterol carrier protein-2.

Cotton bollworm (Helicoverpa armigera) is a highly polyphagous, widely prevalent, and persistent Old World insect pest that affects numerous important crops that are directly consumed by people, including tomato, cotton, pigeon pea, chickpea, rice, sorghum, and cowpea. Insects do not synthesize steroids but obtain them from their diet. Inhibition of dietary uptake of steroids by insects is a potentially effective insecticidal mechanism that should not be toxic to humans and other mammals, who synthesize their steroids. Ten curcumin derivatives were tested against H. armigera sterol carrier protein-2 (HaSCP-2) for their potential as insecticidal agents. Curcumin derivatives were initially docked at the binding site of HaSCP-2 to determine their binding affinities and plausible binding modes. The binding modes predominantly show hydrophobic interactions of derivatives with Phe53, Phe110, and Phe89 as core interacting residues in the active site. Validation of in silico results was carried out by performing a fluorescence binding and displacement assay to determine the binding affinities of curcumin derivatives. Among a collection of curcumin derivatives tested, Cur10 showed the lowest IC50 value of 9.64 µM, while Cur07 was 19.86 µM, and Cur06 was 20.79 µM. There was a significant negative correlation between the ability of the curcumin derivatives tested to displace the fluorescent probe from the sterol binding site of HaSCP-2 and to inhibit Sf9 insect cell growth in culture, which is consistent with the curcumin derivatives acting by the novel mechanism of blocking sterol uptake. Then molecular dynamics simulation studies validated the predicted binding modes and the interactions of curcumin derivatives with HaSCP-2 protein. In conclusion, these studies support the potential use of curcumin derivatives as insecticidal agents.

Development of nanoemulgel of 5-Fluorouracil for skin melanoma using glycyrrhizin as a penetration enhancer.

The purpose of this study was to enhance the topical delivery of 5-Fluorouracil (5-FU), a cancer treatment, by developing a nanoemulgel formulation. Glycyrrhizin (GLY), a natural penetration enhancer has been investigated to exhibit synergistic effects with 5-FU in inhibiting melanoma cell proliferation and inducing apoptosis, Hence, GLY, along with suitable lipids was utilized to create an optimized nanoemulsion (NE) based gel. Solubility studies and ternary phase diagram revealed isopropyl myristate (IPM), Span 80, Tween 80 as Smix and Transcutol P as co-surfactant. IPM demonstrates excellent solubilizing properties facilitates higher drug loading, ensuring efficient delivery to the target site.,The optimized formulation consisting of 40 % IPM, 30 % of mixture of Tween80: Span80 (Smix) and 15 % Transcutol P provides with a nanometric size of 64.1 ± 5.13 nm and drug loading of 97.3 ± 5.83 %. The optimized formulation observed with no creaming and breakeing of NE and found thermodynamically stable during different stress conditions (temperatures of 4.0 °C and 45.0 °C) and physical thawing (-21.0 ± 0.50 °C to 20.0 ± 0.50 °C). The NE was then transformed into a nanoemulgel (NEG) using 1.5 % w/w Carbopol base and 0.1 % w/w glycyrrhizin. The ex vivo permeability studies showed significant enhancements in drug permeability with the GLY-based 5-FU-NEG formulation compared to pure 5-FU gel in excised pig skin upto1440 min in PBS 7.4 as receptor media. The IC50 values for Plain 5-FU gel, 5-FU-NEG, and GLY-based 5-FU-NEG were found to be 20 µg/mL, 1.1 µg/mL, and 0.1 µg/mL, respectively in B16F10 cell lines. The percentage intracellular uptake of GLY-5-FU-NEG and 5-FU-NEG was found to be 44.3 % and 53.6 %, respectively. GLY-based 5-FU-NEG formulation showed alterations in cell cycle distribution, in compared to 5-FU-NE gel. The overall findings suggest that the GLY-based 5-FU-NEG holds promise for improving anti-melanoma activity.

Structural vaccinology, molecular simulation and immune simulation approaches to design multi-epitopes vaccine against John Cunningham virus.

The JCV (John Cunningham Virus) is known to cause progressive multifocal leukoencephalopathy, a condition that results in the formation of tumors. Symptoms of this condition such as sensory defects, cognitive dysfunction, muscle weakness, homonosapobia, difficulties with coordination, and aphasia. To date, there is no specific and effective treatment to completely cure or prevent John Cunningham polyomavirus infections. Since the best way to control the disease is vaccination. In this study, the immunoinformatic tools were used to predict the high immunogenic and non-allergenic B cells, helper T cells (HTL), and cytotoxic T cells (CTL) epitopes from capsid, major capsid, and T antigen proteins of JC virus to design the highly efficient subunit vaccines. The specific immunogenic linkers were used to link together the predicted epitopes and subjected to 3D modeling by using the Robetta server. MD simulation was used to confirm that the newly constructed vaccines are stable and properly fold. Additionally, the molecular docking approach revealed that the vaccines have a strong binding affinity with human TLR-7. The codon adaptation index (CAI) and GC content values verified that the constructed vaccines would be highly expressed in E. coli pET28a (+) plasmid. The immune simulation analysis indicated that the human immune system would have a strong response to the vaccines, with a high titer of IgM and IgG antibodies being produced. In conclusion, this study will provide a pre-clinical concept to construct an effective, highly antigenic, non-allergenic, and thermostable vaccine to combat the infection of the John Cunningham virus.

GC-MS profiling of Bacillus spp. metabolites with an in vitro biological activity assessment and computational analysis of their impact on epithelial glioblastoma cancer genes.

Background: Bacterial metabolites play a crucial role in human health and have proven effective in treating various diseases. In this study, the 16S rRNA method and streaking were employed to isolate and molecularly identify a bacterial strain, with the goal of characterizing bioactive volatile metabolites extracted using nonpolar and polar solvents. Methods: Gas chromatography-mass spectrometry (GC-MS) analysis was conducted to identify 29 compounds in the bacterial metabolites, including key compounds associated with Bacillus spp. The main compounds identified included 2-propanone, 4,4-ethylenedioxy-1-pentylamine, 1,2-benzenedicarboxylic acid, 1,1-butoxy-1-isobutoxy-butane, and 3,3-ethoxycarbonyl-5-hydroxytetrahydropyran-2-one. Results: The literature indicates the diverse biological and pharmacological applications of these compounds. Different concentrations of the metabolites from Bacillus species were tested for biological activities, revealing significant inhibitory effects on anti-diabetic activity (84.66%), anti-inflammatory activity (99%), antioxidant activity (99.8%), and anti-hemolytic activity (90%). Disc diffusion method testing also demonstrated a noteworthy inhibitory effect against tested strains. Conclusion: In silico screening revealed that 1,2-benzenedicarboxylic acid exhibited anticancer activity and promising drug-designing properties against epithelial glioblastoma cancer genes. The study highlights the potential of Bacillus spp. as a valuable target for drug research, emphasizing the significance of bacterial metabolites in the production of biological antibacterial agents.

Phytochemical-Based Study of Ethanolic Extract of Saraca asoca in Letrozole-Induced Polycystic Ovarian Syndrome in Female Adult Rats.

Polycystic ovarian syndrome (PCOS) is a complex metabolic and endocrine disorder which affects women of reproductive age. It is a condition in which ovaries produce an excessive amount of androgen (the male sex hormone). Saraca asoca (Roxb.) Willd. is a plant of the Fabaceae family. This plant has been traditionally used as a uterine tonic in leucorrhea and dysmenorrhea due to its various pharmacological activities. In this study, the ethanolic extract of S. asoca (EESA) was evaluated for its potential to be used for the management of PCOS. HPLC analysis revealed the presence of various phytoconstituents: kaempferol, rutin, (-)-epicatechin, salicylic acid, and gallic acid. For PCOS induction, 30 adult female rats were randomly divided into two groups: the control group (n = 5) and the PCOS group (n = 25). Letrozole (1 mg/kg/day) was administered per orally (p.o.) for a period of 7 weeks for the induction of disease. Weekly body weight measurements and daily vaginal cytology examinations were performed for disease confirmation. After disease induction, the PCOS group was further divided into five groups (n = 5), that is, disease control, metformin, and EESA (200, 400, and 600 mg/kg) groups, respectively, and given treatment doses for next 5 weeks. After the treatment period, all animals were weighed and euthanized humanly. Blood samples were collected for hormonal assays, lipid profiles, and liver function tests. For histological assessment of ovarian cysts, ovaries were dissected. Livers were preserved to evaluate EESA's antioxidant properties. Histopathology analysis revealed that EESA reduced body weight and the number of cystic follicles. Furthermore, it also lowered the elevated levels of serum testosterone, luteinizing hormone, insulin, and malonaldehyde in PCOS rats while increasing the levels of follicle-stimulating hormone, estradiol, progesterone, prolactin, and other antioxidant enzymes such as superoxide dismutase, glutathione, and catalase. It can be concluded that EESA exhibited beneficial effects in normalizing the perturbed hormonal profile and improved the ovary status by decreasing the cystic follicle and improving the ovulation status in a dose-dependent manner.

ESOMIR: a curated database of biomarker genes and miRNAs associated with esophageal cancer.

'Esophageal cancer' (EC) is a highly aggressive and deadly complex disease. It comprises two types, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), with Barrett's esophagus (BE) being the only known precursor. Recent research has revealed that microRNAs (miRNAs) play a crucial role in the development, prognosis and treatment of EC and are involved in various human diseases. Biological databases have become essential for cancer research as they provide information on genes, proteins, pathways and their interactions. These databases collect, store and manage large amounts of molecular data, which can be used to identify patterns, predict outcomes and generate hypotheses. However, no comprehensive database exists for EC and miRNA relationships. To address this gap, we developed a dynamic database named 'ESOMIR (miRNA in esophageal cancer) (https://esomir.dqweilab-sjtu.com)', which includes information about targeted genes and miRNAs associated with EC. The database uses analysis and prediction methods, including experimentally endorsed miRNA(s) information. ESOMIR is a user-friendly interface that allows easy access to EC-associated data by searching for miRNAs, target genes, sequences, chromosomal positions and associated signaling pathways. The search modules are designed to provide specific data access to users based on their requirements. Additionally, the database provides information about network interactions, signaling pathways and region information of chromosomes associated with the 3'untranslated region (3'UTR) or 5'UTR and exon sites. Users can also access energy levels of specific miRNAs with targeted genes. A fuzzy term search is included in each module to enhance the ease of use for researchers. ESOMIR can be a valuable tool for researchers and clinicians to gain insight into EC, including identifying biomarkers and treatments for this aggressive tumor. Database URL https://esomir.dqweilab-sjtu.com.

Mutational analysis of FOLR1 and FOLR2 genes in children with Myelomeningocele.

Myelomeningocele (MMC) is a congenital disease. For a long time, molecular mechanism of MMC, the role of folate receptor and transporter proteins remain unclear. Folate from maternal lumen to developing embryo is carried out with the help of folate transporters (SLC46A1, SLC19A1, FOLH1 and SLC25A32) and folate receptor (FOLR1, FOLR2 and FOLR3). Due to the loss of function of these important genes, complications can facilitate the risk of MMC. This study focused on the mutational analysis of FOLR1 and FOLR2 genes in children suffering from MMC. Myelomeningocele is a rare disorder so twenty blood samples from the children were collected. Primers of selected exons for FOLR1 and FOLR2 genes were designed with the help of PrimerFox software. Extracted DNA was amplified, and PCR based mutational analysis was done to check any type of mutation/SNPs in these genes. Sanger sequencing method was performed to confirm mutation in FOLR1 and FOLR2 genes. The results showed that certain environmental factors (smoking, low socio-economic status of mother bearing MMC fetus) were found to be significantly (P<0.05) associated with MMC but no mutation in the selected exons of FOLR1 and FOLR2 genes was detected. Thus, genetic variations in the folate transporter gene may have no role in the progression of MMC in the studied population.

Influence of lip position on esthetics perception with respect to profile divergence using silhouette images.

BACKGROUND: The aim of the study was to determine the facial divergence and lip position combinations that are most and least preferred, and to investigate whether age or gender has an impact on these preferences. METHODS: The current investigation was carried out on a sample of 1077 individuals who were not experts in the field (253 men and 824 females). The research employed black silhouette photographs of profiles featuring different lip locations and profile divergences. The recruitment of participants was conducted in order to assess the attractiveness of the profiles, employing a Likert scale. The various positions of the lips and variations in facial profiles were thoroughly categorized. Results were analyzed using the Chi-square test. RESULTS: The findings of the research demonstrated that aesthetic perceptions displayed diversity when considering different lip locations and profile divergences. It was shown that neutral lip positions were predominantly favored, accounting for approximately 40.2% of the total frequencies in the anterior diverging group. It is noteworthy to highlight the aesthetically pleasing features exhibited by those with the most prominent lip position, occurring at a frequency of 10.9% in straight-diverging group. In the posterior divergent group, the most protruded lip position, showed very attractive aesthetics with frequency (7.1%). Gender, age, region, and level of education had significant influence on aesthetic perception. CONCLUSIONS: The variety of aesthetic preferences is influenced by the location of the lips and the divergence of the facial profile, resulting in different outcomes within the categories of anterior, straight, and posterior divergence. Clinicians are advised to customize the treatment regimen in order to correspond with the unique desires and preferences of the patient.

Integrated omics and machine learning-assisted profiling of cysteine-rich-receptor-like kinases from three peanut spp. revealed their role in multiple stresses.

Arachis hypogaea (peanut) is a leading oil and protein-providing crop with a major food source in many countries. It is mostly grown in tropical regions and is largely affected by abiotic and biotic stresses. Cysteine-rich receptor-like kinases (CRKs) is a family of transmembrane proteins that play important roles in regulating stress-signaling and defense mechanisms, enabling plants to tolerate stress conditions. However, almost no information is available regarding this gene family in Arachis hypogaea and its progenitors. This study conducts a pangenome-wide investigation of A. hypogaea and its two progenitors, A. duranensis and A. ipaensis CRK genes (AhCRKs, AdCRKs, and AiCRKs). The gene structure, conserved motif patterns, phylogenetic history, chromosomal distribution, and duplication were studied in detail, showing the intraspecies structural conservation and evolutionary patterns. Promoter cis-elements, protein-protein interactions, GO enrichment, and miRNA targets were also predicted, showing their potential functional conservation. Their expression in salt and drought stresses was also comprehensively studied. The CRKs identified were divided into three groups, phylogenetically. The expansion of this gene family in peanuts was caused by both types of duplication: tandem and segmental. Furthermore, positive as well as negative selection pressure directed the duplication process. The peanut CRK genes were also enriched in hormones, light, development, and stress-related elements. MicroRNA (miRNA) also targeted the AhCRK genes, which suggests the regulatory association of miRNAs in the expression of these genes. Transcriptome datasets showed that AhCRKs have varying expression levels under different abiotic stress conditions. Furthermore, the multi-stress responsiveness of the AhCRK genes was evaluated using a machine learning-based method, Random Forest (RF) classifier. The 3D structures of AhCRKs were also predicted. Our study can be utilized in developing a detailed understanding of the stress regulatory mechanisms of the CRK gene family in peanuts and its further studies to improve the genetic makeup of peanuts to thrive better under stress conditions.

Investigation of VEGF (rs 699947) polymorphism in the progression of Rheumatoid Arthritis (RA) and in-silico nanoparticle drug delivery of potential phytochemicals to cure RA.

Mutation in the VEGF gene disturbs the production of chondrocytes and angiogenesis which are essential for cartilage health. Cytokines and chemokines produced by auto-activation of B-cells degrade cartilage. Bruton's Tyrosine Kinase (BTK) plays a crucial role in the activation of these B-cells. VEGF has a central part in angiogenesis, in the recruitment of endothelial cells, and is involved in mechanisms that result in tumour formation. The objective of this research is to investigate the potential role of VEGF polymorphism in the development of Rheumatoid Arthritis (RA) and the screening of potential natural, synthetic BTK inhibitor compounds as possible in-silico chemotherapeutic agents to control auto-activation of B-cells and cartilage degrading cytokines. In this study, it had been shown that allele A frequency was significantly higher than that of allele C in RA-positive patients as compared to controls. Hence it depicts that allele A of VEGF (rs699947) can increase the risk of RA while allele C has a protective role. The phytochemicals which showed maximum binding affinity at the inhibitory site of BTK include beta boswellic acid, tanshinone, and baicalin. These phytochemicals as BTK inhibitor give insights to use them as anti-arthritic compounds by nanoparticle drug delivery mechanism.

Design and development of new inhibitors against breast cancer, Monkeypox and Marburg virus by modification of natural Fisetin via in silico and SAR studies.

The natural Fisetin and its derivatives have been shown to have effective bioactivity and strong pharmacological profile, which is continuously drawing the interest of therapeutic applications to the development of new biomolecules against Breast cancer and Monkeypox, and Marburg viral infection, while computational approaches and the study of their structure-activity relationship (SAR) are the most eloquent and reliable platform for performing their hypothetical profile renovation. So, the main perspective of this investigation is to evaluate dual function of Fisetin and its derivatives against both virus and cancerous target. First and foremost, the prediction of activity spectra for materials (PASS) valuation has provided preliminary data on the antiviral, antibacterial, antiparasitic, and anti-cancer possibilities of the mentioned compounds. According to the evidence, PASS predicted scores were shown to perform better in antineoplastic and antiviral than antibacterial, and antiparasitic efficiency; as evidenced by their higher PASS scores in antineoplastic and antiviral drug tests. Breast cancer, Monkeypox, and Marburg virus have been selected as targeted pathogens, and different in silico studies were conducted to determine the dual function of mention derivatives. The "Lipinski five rules," on the other hand, has been subjected to extensive testing for drug-like characteristics. Molecular docking against Breast cancer, Monkeypox, and Marburg virus have been accomplished after confirmation of their bioactivity. The molecular docking evaluation against targeted disease displayed re-markable binding affinity and non-bonding engagement, with most of the results indicating that derivatives are more effective than the FDA approved standard antiviral, and antineoplastic drugs. Finally, the ADMET characteristics have been computed, and they indicate that the substance is suitable to use and did not have any chance to produce adverse effects on aquatic or non-aquatic environment, as well as having a highly soluble capacity in water medium, high G.I absorption rate, with outstanding bioavailability index. Therefore, these mentioned Fisetin derivatives could be suggested as potential medication against Breast cancer and newly reported Monkeypox, and Marburg virus, and may further proceed for laboratory experiment, synthesis, and clinical trials to evaluate their practical value.

Inhibition of cMYC-MAX transcription factors hetero-dimerization with structurally engineered omoMYC to downregulate oncogenic pathways in renal carcinoma.

In the current study, we employed, structural informatics, and molecular simulation-based methods to engineer OmoMyc, a c-Myc dominant negative protein, to design novel mutants that could abrogate the c-MYC-MAX complex in Renal Carcinoma (RC). Among the total 472 mutations, only six mutations A61Q, Q64E, Q64K, N77R, Q64E-N77R, and Q64K-N77R were reported to increase the binding affinity and subjected to subsequent analysis such as protein-protein docking. The docking results revealed that the predicted mutants improve the functionality of the OmoMyc by not only increasing the binding affinity but also vdW and electrostatic energy in each complex that consequently increase the binding of the engineered OmoMyc by establishing extra hydrogen bonds, salt-bridges, and non-bonded contacts. Molecular simulation revealed a more stable behavior by the mutant complexes in contrast to the native OmoMyc however structural perturbations were reported in the regions, DBD (DNA-binding domain), loop region, and minor deviations at CTD (C terminal domain). Moreover, the hydrogen bonding and binding free energy results further validated the promising activity of our predicted mutants of OmoMyc. The results for TBE (total binding energy) revealed that the for each complex the TBE was calculated to be -87.88 ± 0.16 kcal/mol (WT OmoMyc-MAX), -91.89 ± 0.21 kcal/mol (A61Q OmoMyc-MAX), -91.55 ± 0.20 kcal/mol (Q64E OmoMyc-MAX), -95.17 ± 0.24 kcal/mol (Q64K OmoMyc-MAX), -96.49 ± 0.22 kcal/mol (N77R OmoMyc-MAX), -97.76 ± 0.22 kcal/mol (Q64E-N77R OmoMyc-MAX), and -95.31 ± 0.20 kcal/mol (Q64K-N77R OmoMyc-MAX) respectively. The results for TBE revealed promising results that allow the mutants to competitively inhibit the c-Myc-MAX complex more swiftly. Additionally, the internal motion and energy landscape were altered. These findings provide important insights into the potential of the mutants of OmoMyc as a therapeutic candidate for cancer treatment, particularly renal carcinoma, and could pave the way for the development of more effective clinical versions of OmoMyc.

Synthesis, Antioxidant, Molecular Docking and DNA Interaction Studies of Metal-Based Imine Derivatives.

Currently, numerous ongoing studies are investigating the interaction of free radicals with biological systems, such as lipids, DNA and protein. In the present work, synthesis, characterization, antioxidant, DNA binding and molecular docking studies of Schiff base ligand and its Ni(II), Co(II), Cu(II) and Zn(II) were evaluated. The metal complexes have shown significant dose-dependent antioxidant activities higher than those of the free ligand but lesser than those of the standard antioxidant, ascorbic acid. The DNA binding constants (Kb) were found in the order Zn(pimp)2 {9.118 × 105 M-1} > H-pimp {3.487 × 105 M-1} > Co(pimp)2 {3.090 × 105 M-1} > Ni(pimp)2 {1.858 × 105 M-1} > Cu(pimp)2 {1.367 × 105 M-1}. Binding constants (Kb) values calculated from the molecular docking analysis were found to be in close agreement with the experimental results. The obtained results indicate the importance of synthesis complexes as a source of synthetic antioxidants and anticancer drugs.

Evaluating the influence of Aloe barbadensis extracts on edema induced changes in C-reactive protein and interleukin-6 in albino rats through in vivo and in silico approaches.

The current study investigated the in-vivo and in-silico anti-inflammatory effect of Aloe barbadensis in edema induced rat and its blood biomarkers. 60 albino rats (160-200 g) were divided into 4 groups. The 1st group (control) comprised of 6 rats that were treated with saline. The 2nd group (standard) comprised of 6 rats that were treated with diclofenac. The 3rd and 4th experimental groups consisted of 48 rats, treated with A. barbadensis gel ethanolic and aqueous extracts respectively at doses of 50, 100, 200 and 400 mg/kg. According to paw sizes, groups III and IV showed 51% and 46% inhibition respectively at the 5th hour, as compared to group II with 61% inhibition. Correlation was negative between biomarkers in group III, while, positive in group IV. Blood samples were collected; C-reactive protein and interleukin-6 were measured using commercially available ELISA kits. Similarly, biomarkers showed significant effect in dose-dependent manner. In molecular docking, for CRP both ligands aloe emodin and emodin showed -7.5 kcal/mol binding energy as compared to diclofenac with -7.0 kcal/mol. For IL-1beta, both ligands showed -4.7 kcal/mol binding energy as compared to diclofenac -4.4 kcal/mol. Hence, we concluded that A. barbadensis extracts can be used as an effective drug for managing inflammation.

2-Substituted-3-(5-Substituted-1,3,4-oxadiazol/thiadiazol-2-yl) Thiazolidin-4-one Derivatives: Synthesis, Anticancer, Antimicrobial, and Antioxidant Potential.

In this innovative research, a novel series of thiazolidin-4-one analogues having a 1,3,4-oxadiazole/thiadiazole moiety were derived and the structures of all the newly obtained molecules were established using different physicochemical and analytical means (1H-NMR, FTIR, mass spectra, and elemental analyses). The synthesized molecules were then investigated for their antiproliferative, antimicrobial, and antioxidant potential. The cytotoxicity screening studies revealed that analogues D-1, D-6, D-15, and D-16 possessed comparable efficacy, within the IC50 range (1 to 7 µM), when taking doxorubicin as a reference drug (IC50 = 0.5 µM). The antimicrobial activity was assessed using different Gram-(+) and Gram-(-) bacterial and fungal strains and the results revealed that molecules D-2, D-4, D-6, D-19, and D-20 possessed potent activity against selective strains of microbes with MIC ranges of 3.58 to 8.74 µM. The antioxidant evaluation was performed using the DPPH assay and the screening results revealed that analogue D-16 was the most potent derivative (IC50 = 22.3 µM) when compared with the positive control, ascorbic acid (IC50 = 111.6 µM). Structure-activity relationship (SAR) studies of the synthesized novel derivatives revealed that para-substituted halogen and hydroxy derivatives have remarkable potential against the MCF-7 cancer cell line and antioxidant potential. Similarly, electron-withdrawing groups (Cl/NO2) and -donating groups at the para position possess moderate to promising antimicrobial potential.

Evaluating the in-vivo effects of olive oil, soya bean oil, and vitamins against oxidized ghee toxicity.

The aim of this study was to examine the protective role of various lipids (olive and soya oil) and vitamin (E and C) against the toxicity of thermally oxidized ghee in rabbits. Vanaspati ghee was thermally oxidized on a hot plate at 100°C for ten consecutive hours, and the oxidized ghee was stored in a refrigerator at -20°C until administration. Thirty male rabbits were purchased as experimental animals at a local market and were divided into ten corresponding groups of three based on their body weight. The blood samples of 5 ml were collected on day 0, 7, and 14 of the experiment for the analysis of hematological and biochemical serum parameters. We observed that oxidized ghee significantly elevated ALT level by affecting liver hepatocytes. Furthermore, vitamin E rapidly decreased the ALT levels compared to vitamin C and other oils. The oxidized ghee caused a significant increase in cholesterol compared to the other groups. Vitamin E and C showed the best antioxidant activity and decreased cholesterol levels to normal. Histopathological examinations of the normal rabbits' liver sections revealed no significant histological abnormality. The liver of the rabbits fed with oxidized ghee had an intact lobular architecture but the portal tracts showed inflammation and mild fibrosis, the bile ducts showed proliferation, and the hepatocytes showed feathery degeneration. In the liver sections from the groups fed with oxidized ghee and different doses of olive oil inflammation in portal tracts and large vacuoles in the hepatocytes were observed. The group fed with oxidized ghee and vitamin E had intact lobular architecture with no significant histological abnormality in portal tracts but fatty changes were present in the hepatocytes. These findings support the antioxidant activity of vitamins C and E as they reduced liver infection caused by oxidized ghee. It was concluded that oxidized ghee was highly toxic and not safe for consumption. The present study indicated that soya bean oil and vitamin E were more effective in protecting against the toxicity of thermally oxidized ghee than olive oil and vitamin C.

Design, physicochemical characterisation, and in vitro cytotoxicity of cisplatin-loaded PEGylated chitosan injectable nano / sub-micron crystals.

The study aimed to develop cisplatin-loaded PEGylated chitosan nanoparticles. The optimal batch of cisplatin-loaded PEGylated chitosan nanoparticles had a + 49.9 mV zeta potential, PDI of 0.347, and % PDI of 58.9. Nanoparticle zeta size was 741.4 z. d.nm, the size in diameter was 866.7 ± 470.5 nm, and nanoparticle conductivity in colloidal solution was 0.739 mS/cm. Differential scanning calorimetry (DSC) revealed that cisplatin-loaded PEGylated chitosan nanoparticles had sharp endothermic peaks at temperatures at 168.6 °C. The thermogravimetric analysis (TGA) showed the weight loss of cisplatin-loaded PEGylated chitosan nanoparticles, which was observed as 95% at 262.76 °C. XRD investigation on cisplatin-loaded PEGylated chitosan nanoparticles exhibited distinct peaks at 2θ as 9.7°, 20.4°, 22.1°, 25.3°, 36.1°, 38.1°, 39.5°, 44.3°, and 64.5°, confirming crystalline structure. The 1H NMR analysis showed the fingerprint region of cisplatin-loaded PEGylated chitosan nanoparticles as 0.85, 1.73, and 1.00 ppm in the proton dimension and de-shielded proton peaks appeared at 3.57, 3.58, 3.58, 3.59, 3.65, 3.67, 3,67, 3,67, 3.70, 3.71, 3.77, 3.78 and 4.71 ppm. The 13C NMR spectrum showed specified peaks at 63.18, 69.20, and 70.77 ppm. The FT-IR spectra of cisplatin loaded PEGylated nanoparticles show the existence of many fingerprint regions at 3186.52, 2931.68, 1453.19, 1333.98, 1253.71, 1085.19, 1019.60, 969.98, 929.53, 888.80, 706.13, and 623.67 cm-1. The drug release kinetics of cisplatin loaded PEGylated chitosan nanoparticles showed zero order kinetics with 48% of drug release linearity fashion which has R2 value of 0.9778. Studies on the MCF-7 ATCC human breast cancer cell line in vitro revealed that the IC50 value 82.08 µg /mL. Injectable nanoparticles had good physicochemical and cytotoxic properties. This method is novel since the application of the PEGylation processes leads to an increased solubility of chitosan nanoparticles at near neutral pH.

Evidence from genetic studies among rs2107538 variant in the CCL5 gene and Saudi patients diagnosed with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic and metabolic disorder that affects the adult population. Chemokines are proinflammatory cytokines that play a role in the development of chronic diseases such as obesity, gestational diabetes, and T2DM. The C-C Motif Chemokine Ligand 5 (CCL5) gene plays a role in antiviral immunity, tumor development, obesity, impaired glucose tolerance, and T2DM. This study aimed to investigate the genetic role of the rs2107538 variant in the CCL5 gene in Saudi patients with T2DM. Sixty subjects with T2DM patients and 60 healthy controls participated in this prospective case-control study. Prior to Sanger sequencing, genomic DNA was extracted and amplified with Polymerase chain reaction (PCR), after which the PCR products were purified. The collected data were used to conduct various statistical analyses to determine the relationship between T2DM and control subjects. The findings of the current study revealed a positive association for most parameters between T2DM and control subjects (p < 0.05). The frequency of genotypes (p = 0.002, AA vs.GG: p = 0.008, GA + AA vs. GG: p = 0.0002) and alleles (A vs. G: p = 0.0007) revealed a strong risk association. Multiple logistic regression with individual effects revealed a link between SBP and HDLc levels (p = 0.03). In patients with T2DM, waist (p = 0.001), TG (p = 0.0007), and LDLc (p = 0.0004) levels were all associated with the ANOVA. Finally, the rs2107538 variant was linked to an increased risk of T2DM in the Saudi Population. The GA and AA genotypes were strongly connected to the T2DM subjects. In order to rule out disease-causing variants in the global population, future research should use a large sample size.

Biosynthesis and Mathematical Interpretation of Zero-Valent Iron NPs Using Nigella sativa Seed Tincture for Indemnification of Carcinogenic Metals Present in Industrial Effluents.

Zero-valent iron nanoparticles (ZVI-NPs) are utilized for the indemnification of a wide range of environmental pollutants. Among the pollutants, heavy metal contamination is the major environmental concern due to their increasing prevalence and durability. In this study, heavy metal remediation capabilities are determined by the green synthesis of ZVI-NPs using aqueous seed extract of Nigella sativa which is a convenient, environmentally friendly, efficient, and cost-effective technique. The seed extract of Nigella sativa was utilized as a capping and reducing agent for the generation of ZVI-NPs. UV-visible spectrophotometry (UV-vis), scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDX), and Fourier transform infrared spectroscopy (FTIR) was used to investigate the ZVI-NP composition, shape, elemental constitution, and perspective functional groups, respectively. The biosynthesized ZVI-NPs displayed a peak of plasmon resonance spectra at 340 nm. The synthesized NPs were cylindrical in shape, with a size of 2 nm and (-OH) hydroxyl, (C-H) alkanes and alkynes N-C, N=C, C-O, =CH functional groups attached to the surface of ZVI-NPs. Heavy metals were successfully remediated from industrial wastewater collected from the various tanneries of Kasur. During the reaction duration of 24 h, different concentrations of ZVI-NPs (10 µg, 20 µg and 30 µg) per 100 mL were utilized for the removal of heavy metals from industrial wastewater. The 30 µg/100 mL of ZVI-NPs proved the pre-eminent concentration of NPs as it removed >90% of heavy metals. The synthesized ZVI-NPs were analyzed for compatibility with the biological system resulting in 87.7% free radical scavenging, 96.16% inhibition of protein denaturation, 60.29% and 46.13% anti-cancerism against U87-MG and HEK 293 cell lines, respectively. The physiochemical and exposure mathematical models of ZVI-NPs represented them as stable and ecofriendly NPs. It proved that biologically synthesized NPs from a seed tincture of Nigella sativa have a strong potential to indemnify heavy metals found in industrial effluent samples.