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Lin Zhao, 1 Omer Mustapha, 2 Shumaila Shafique, 2 Talha Jamshaid, 3 Fakhar ud Din, 4 Yasir Mehmood, 5 Khaleeq Anwer, 6 Qurrat ul Ain Yousafi, 7 Talib Hussain, 8 Ikram Ullah Khan, 5 Muhammad Usman Ghori, 9 Yasser Shahzad, 8 Abid Mehmood Yousaf 8 1Department of Rheumatology of Traditional Chinese and Western Medicine, Xinxiang Central Hospital, Xinxiang 453000, People’s Republic of China; 2Faculty of Pharmaceutical Sciences, Dow College of Pharmacy, Dow University of Health Sciences, Karachi 74200, Pakistan; 3Faculty of Pharmacy and Alternative Medicine, Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan; 4Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan; 5Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38040, Pakistan; 6Office of Chief Executive Officer, District Health Authority, Pakpattan 57400, Pakistan; 7Department of Neurosurgery, District Headquarters Hospital, Rawalpindi 46000, Pakistan; 8Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, Lahore 54000, Pakistan; 9Department of Pharmacy, School of Applied Science, University of Huddersfield, Huddersfield HD1 3DH, UKCorrespondence: Abid Mehmood Yousaf Tel +92-300-477-4147; +92-345-722-0536Email abid.ucp@hotmail.com Email talib.hussain@cuilahore.edu.pkBackground: Piroxicam exhibits low oral bioavailability, due to its meager solubility in water. The intent of this study was to ameliorate the bioavailability of the drug by employing a solubility-enhancing encapsulation technique.Methods: Seven samples were formulated with piroxicam and gelatin using both solvent evaporation and electrospraying together. Evaluation of solubility and release rate in water and assessment of bioavailability in rats were carried out in comparison with piroxicam plain drug powder (PPDP). Other in vitro explorations were accomplished using powder X-ray diffraction analysis, differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, and Fourier-transform infrared spectroscopy.Results: All piroxicam-loaded gelatinnanocontainers (PLGNs) enhanced solubility and release of the payload in water. In particular, a PLGN formulation consisting of piroxicam and gelatin at a 1:8 (w:w) ratio presented about 600-fold the drug solubility of that shown by PPDP. Moreover, 85.12%± 10.96% of the payload was released from this formulation in 10 minutes which was significantly higher than that dissolved from PPDP in 10 minutes (11.81%± 5.34%). Drug content, drug loading, and encapsulation efficiency of this formulation were 93.41%± 0.56%, 10.45%± 0.06%, and 66.74%± 6.87%, respectively. The drug loaded in PLGNs existed in the amorphous state, as confirmed by X-ray diffraction and differential scanning–calorimetry analyses, and was more stable when analyzed by thermogravimetric analysis. Moreover, Fourier-transform infrared spectroscopy analysis suggested nonexistence of any piroxicam–gelatin interaction in the formulation. In the scanning electron–microscopy image, PLGNs appeared as round, smooth particles, with particle size of < 1,000 nm. Amelioration in bioavailability of piroxicam with the aforementioned PLGN formulation was fourfold that of PPDP.Conclusion: The PLGN formulation fabricated with piroxicam and gelatin at 1:8 (w:w) might be a promising system for enhanced biopharmaceutical performance of the drug.Keywords: aqueous solubility, electrospraying, gelatin encapsulation, nanocontainers, oral bioavailability, piroxicam

Gastric cancer predominantly adenocarcinoma, accounts for over 85% of gastric cancer diagnoses. Current therapeutic options are limited, necessitating the discovery of novel drug targets and effective treatments. The Affymetrix gene expression microarray dataset (GSE64951) was retrieved from NCBI-GEO data normalization and DEGs identification was done by using R-Bioconductor package. Gene Ontology (GO) analysis of DEGs was performed using DAVID. The protein-protein interaction network was constructed by STRING database plugin in Cytoscape. Subclusters/modules of important interacting genes in main network were extracted by using MCODE. The hub genes from in the network were identified by using Cytohubba. The miRNet tool built a hub gene/mRNA-miRNA network and Kaplan-Meier-Plotter conducted survival analysis. AutoDock Vina and GROMACS MD simulations were used for docking and stability analysis of marine compounds against the 5CNN protein. Total 734 DEGs (507 up-regulated and 228 down-regulated) were identified. Differentially expressed genes (DEGs) were enriched in processes like cell-cell adhesion and ATP binding. Eight hub genes (EGFR, HSPA90AA1, MAPK1, HSPA4, PPP2CA, CDKN2A, CDC20, and ATM) were selected for further analysis. A total of 23 miRNAs associated with hub genes were identified, with 12 of them targeting PPP2CA. EGFR displayed the highest expression and hazard rate in survival analyses. The kinase domain of EGFR (PDBID: 5CNN) was chosen as the drug target. Adociaquinone A from Petrosia alfiani, docked with 5CNN, showed the lowest binding energy with stable interactions across a 50 ns MD simulation, highlighting its potential as a lead molecule against EGFR. This study has identified crucial DEGs and hub genes in gastric cancer, proposing novel therapeutic targets. Specifically, Adociaquinone A demonstrates promising potential as a bioactive drug against EGFR in gastric cancer, warranting further investigation. The predicted miRNA against the hub gene/proteins can also be used as potential therapeutic targets., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Laboratory and field assays of three sets of experiments were conducted to evaluate the impact of different phagostimulants alone and in combination with other phagostimulant lure sources, such as ammonium acetate, DAP, and acetic acid, on the attractancy of both sexes of B. zonata . In the first experiment, the laboratory olfactometer study revealed that out of eleven phagostimulants, banana, mulberry, mango, guava, molasses, and protein hydrolysate exhibited moderate attractancy (15.2-60.2%) to B. zonata . Unexpectedly, banana and protein hydrolysate were demonstrated to be highly attractive phagostimulants for starved female B. zonata (53.6% and 60.2%, respectively). In the field study, none of the tested phagostimulants exhibited high attractancy; however, banana, mulberry, protein hydrolysate, guava, mango, and molasses demonstrated moderate attractancy (5.6-35.6%) to B. zonata . In the second experiment, out of five phagostimulant-mixtures, phagostimulant-mixture-4 proved highly attractive (40.5-68.6% and 45.5-51.2%), followed by phagostimulant-mixture-3, which proved to be moderately attractive (17.0-22.5% and 28.4-36.1%) to B. zonata in olfactometer and field studies, respectively. In the third experiment, out of five phagostimulant-AdMixtures, phagostimulant-AdMixture-4 demonstrated strong attractiveness in the olfactometer (41.6-68.7%) and field studies (52.7-58.7%) for B. zonata , while the rest of the AdMixtures demonstrated moderate to no attractiveness for B. zonata . So, phagostimulant-AdMixture-4 with GF-120 could be used in the development of a phagostimulant bait station which attracts the maximum B. zonata population and ultimately provides pest-free fruits to the farmers.

An evaluation of the expression and predictive significance of the MDM2 gene in brain lower-grade glioma (LGG) cancer was carried out using onco-informatics pipelines. Several transcriptome servers were used to measure the differential expression of the targeted MDM2 gene and search mutations and copy number variations. GENT2, Gene Expression Profiling Interactive Analysis, Onco-Lnc, and PrognoScan were used to figure out the survival rate of LGG cancer patients. The protein-protein interaction networks between MDM2 gene and its co-expressed genes were constructed by Gene-MANIA tool. Identified bioactive phytochemicals were evaluated through molecular docking using Schrödinger Suite Software, with the MDM2 (PDB ID: 1RV1) target. Protein-ligand interactions were observed with key residues of the macromolecular target. A molecular dynamics simulation of the novel bioactive compounds with the targeted protein was performed. Phytochemicals targeting MDM2 protein, such as Taxifolin and (-)-Epicatechin, have been shown with more highly stable results as compared to the control drug, and hence, concluded that phytochemicals with bioactive potential might be alternative therapeutic options for the management of LGG patients. Our once informatics-based designed pipeline has indicated that the MDM2 gene may have been a predictive biomarker for LGG cancer and selected phytochemicals possessed outstanding interaction results within the macromolecular target's active site after utilizing in silico approaches. In vitro and in vivo experiments are recommended to confirm these outcomes.

Phytopathogenic fungi are serious threats in the agriculture sector especially in fruit and vegetable production. The use of plant essential oil as antifungal agents has been in practice from many years. Plant essential oils (PEOs) of Cuminum cyminum , Trachyspermum ammi , Azadirachta indica , Syzygium aromaticum , Moringa oleifera , Mentha spicata , Eucalyptus grandis , Allium sativum , and Citrus sinensis were tested against Fusarium oxysporum . Three phase trials consist of lab testing (MIC and MFC), field testing (seed treatment and foliar spray), and computer-aided fungicide design (CAFD). Two concentrations (25 and 50  μ l/ml) have been used to asses MIC while MFC was assessed at four concentrations (25, 50, 75, and 100  μ l/ml). C. sinensis showed the largest inhibition zone (47.5 and 46.3 m 2 ) for both concentrations. The lowest disease incidence and disease severity were recorded in treatments with C. sinensis PEO . Citrus sinensis that qualified in laboratory and field trials was selected for CAFD. The chemical compounds of C. sinensis PEO were docked with polyketide synthase beta-ketoacyl synthase domain of F. oxysporum by AutoDock Vina. The best docked complex was formed by nootkatone with -6.0 kcal/mol binding affinity. Pharmacophore of the top seven C. sinensis PEO compounds was used for merged pharmacophore generation. The best pharmacophore model with 0.8492 score was screened against the CMNP database. Top hit compounds from screening were selected and docked with polyketide synthase beta-ketoacyl synthase domain. Four compounds with the highest binding affinity and hydrogen bonding were selected for confirmation of lead molecule by doing MD simulation. The polyketide synthase-CMNPD24498 showed the highest stability throughout 80 ns run of MD simulation. CMNPD24498 (FW054-1) from Verrucosispora was selected as the lead compound against F. oxysporum ., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Qudsia Yousafi et al.)

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a more severe strain of coronavirus (CoV) that was first emerged in China in 2019. Available antiviral drugs could be repurposed and natural compounds with antiviral activity could be safer and cheaper source of medicine for SARS-CoV-2. 78 natural antiviral compounds database was identified from literature and virtual screening technique was applied to identify potential 3-chymotrypsin-like protease (3CLpro) inhibitors. Molecular docking studies were conducted to analyze the main protease (3CLpro) and inhibitors interactions with key residues of active site of target protein (PDB ID: 6LU7), active site constitute the part of active domain I and II of 3CLpro. 10 compounds with highest dock score were subjected to calculate ADMET parameters to figure out drug-likeness. Molecular dynamic (MD) simulation of the selected lead was performed by Amber simulation package to understand the conformational changes in docked complex. MD simulations analysis (RMSD, RMSF, Rg, BF, HBs, and SASA plots) of lead bounded with 3CLpro, hence revealed the important structural turns and twists during MD simulations from 0 to 100 ns. MM-PBSA/GBSA methods has also been applied for the estimation binding free energy (BFE) of the selected lead-complex. The present study has identified lead compound "Forsythoside A" an active extract of Forsythia suspense as SARS-CoV-2 3CLpro inhibitor that can block the viral replication and translation. Structural analysis of target protein and lead compound performed in this study could contribute to the development of potential drug against SARS-CoV-2 infection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier B.V. on behalf of King Saud University.)

Diabetes mellitus (DM) is a very common metabolic disorder/disease. The deterioration of β -cells by autoimmune system is the hallmark of this disease. Thioredoxin-Interacting Protein (TXNIP) is responsible for β -cells degradation by T-cells in the pancreas. This protein had been declared a good drug target for controlling DM. Lots of side effects have been reported as a result of long-time consumption of conventional antidiabetic drugs. The development of new and effective drugs with the minimal side effects needs time. TXNIP was selected as a target for Computer-Aided Drug Design. The antidiabetic fungal metabolite compounds were selected from the literature. The compounds were screened for their drug-likeness properties by DruLiTo and DataWarior tools. Twenty-two drug-like fungal compounds were subjected to Quantitative Structure-Activity Relationship (QSAR) analysis by using CheS-Mapper 2.0. The lowest (0.01) activity cliff was found for three compounds: Pinazaphilone A, Pinazaphilone B, and Chermesinone A. The highest value for apol (81.76) was shown by Asperphenamate, while Albonoursin and Sterenin L showed highest score (40.66) for bpol. The lowest value (0.46) for fractional molecular frame (FMF) was calculated for Pinazaphilone A and Pinazaphilone B. TPSA for Pinazaphilone A and Pinazaphilone B was 130.51 Å 2 . log   P < 5 was observed for all the twenty-two compounds. Molecular docking of fungal compounds with TXNIP was done by AutoDock Vina. The binding energy for complexes ranged between -9.2 and -4.6 kcal/mol. Four complexes, TXNIP-Pinazaphilone A, TXNIP-Pinazaphilone B, TXNIP-Asperphenamate, and TXNIP-Sterenin L, were selected for MD simulation to find out the best lead molecule. Only one complex, TXNIP-Pinazaphilone B, showed a stable conformation throughout the 80 ns run of MD simulation. Pinazaphilone B derived from the Penicillium species fungi was selected as the lead molecule for development of antidiabetic drug having the least side effects., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Shahzad Saleem et al.)

Current advancements in nanotechnology and nanoscience have resulted in new nanomaterials, which may pose health and environmental risks. Furthermore, several researchers are working to optimize ecologically friendly procedures for creating metal and metal oxide nanoparticles. The primary goal is to decrease the adverse effects of synthetic processes, their accompanying chemicals, and the resulting complexes. Utilizing various biomaterials for nanoparticle preparation is a beneficial approach in green nanotechnology. Furthermore, using the biological qualities of nature through a variety of activities is an excellent way to achieve this goal. Algae, plants, bacteria, and fungus have been employed to make energy-efficient, low-cost, and nontoxic metallic nanoparticles in the last few decades. Despite the environmental advantages of using green chemistry-based biological synthesis over traditional methods as discussed in this article, there are some unresolved issues such as particle size and shape consistency, reproducibility of the synthesis process, and understanding of the mechanisms involved in producing metallic nanoparticles via biological entities. Consequently, there is a need for further research to analyze and comprehend the real biological synthesis-dependent processes. This is currently an untapped hot research topic that required more investment to properly leverage the green manufacturing of metallic nanoparticles through living entities. The review covers such green methods of synthesizing nanoparticles and their utilization in the scientific world., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chopra, Bibi, Singh, Hasan, Khan, Yousafi, Baig, Rahman, Islam, Emran and Cavalu.)

Glucose-regulated protein 78 (GRP78) might be a receptor for SARS-CoV-2 to bind and enter the host cell. Recently reported mutations in the spike glycoprotein unique to the receptor-binding domain (RBD) of different variants might increase the binding and pathogenesis. However, it is still not known how these mutations affect the binding of RBD to GRP78. The current study provides a structural basis for the binding of GRP78 to the different variants, i.e., B.1.1.7, B.1.351, B.1.617, and P.1 (spike RBD), of SARS-CoV-2 using a biomolecular simulation approach. Docking results showed that the new variants bound stronger than the wild-type, which was further confirmed through the free energy calculation results. All-atom simulation confirmed structural stability, which was consistent with previous results by following the global stability trend. We concluded that the increased binding affinity of the B.1.1.7, B.1.351, and P.1 variants was due to a variation in the bonding network that helped the virus induce a higher infectivity and disease severity. Consequently, we reported that the aforementioned new variants use GRP78 as an alternate receptor to enhance their seriousness.

Lepidoptera is the second most diverse insect order outnumbered only by the Coeleptera. Acetylcholinesterase (AChE) is the major target site for insecticides. Extensive use of insecticides, to inhibit the function of this enzyme, have resulted in the development of insecticide resistance. Complete knowledge of the target proteins is very important to know the cause of resistance. Computational annotation of insect acetylcholinesterase can be helpful for the characterization of this important protein. Acetylcholinesterase of fourteen lepidopteran insect pest species was annotated by using different bioinformatics tools. AChE in all the species was hydrophilic and thermostable. All the species showed lower values for instability index except L. orbonalis, S. exigua and T. absoluta . Highest percentage of Arg, Asp, Asn, Gln and Cys were recorded in P. rapae . High percentage of Cys and Gln might be reason for insecticide resistance development in P. rapae. Phylogenetic analysis revealed the AChE in T. absoluta , L. orbonalis and S. exigua are closely related and emerged from same primary branch. Three functional motifs were predicted in eleven species while only two were found in L. orbonalis, S. exigua and T. absoluta. AChE in eleven species followed secretory pathway and have signal peptides. No signal peptides were predicted for S. exigua , L. orbonalis and T. absoluta and follow non secretory pathway. Arginine methylation and cysteine palmotylation was found in all species except S. exigua , L. orbonalis and T. absoluta . Glycosylphosphatidylinositol (GPI) anchor was predicted in only nine species., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

The cytoplasmic dynein light chain 1 (DYNLL1) is an important constituent of motor proteins complex. In human it is encoded by DYNLL1 gene. It is involved in cargo transport functions and interacts with many viral proteins with the help of short linear consensus motif sequence (K/R) XTQT. Viral proteins bind to DYNLL1 through its consensus short linear motif (SLiM) sequence to reach the target site in the cell and cause different infections in the host. It is still unknown if bacterial proteins also contain the same conserved SLiMs sequence through which they bind to this motor protein and cause infections. So, it is important to investigate the role of DYNLL1 in human bacterial infections. The interaction partner proteins of DYNLL1 against conserved viral motif sequences were predicted through PDBSum. Pairwise sequence alignment, between viral motif sequence and that of predicted proteins, was performed to identify conserved region in predicted interaction partners. Docking between the DYNLL1 and new pathogenic interaction partners was performed, by using PatchDock, to explore the protein-protein binding quality. Interactions of docked complexes were visualized by DimPlot. Three pathogenic bacterial proteins i.e ., enterochelin esterase (3MGA), protective antigen (3J9C) and putative lipoprotein (4KT3) were selected as candidate interaction partners of DYNLL1. The putative lipoprotein (4KT3) showed low quality binding with DYNLL1. So, enterochelin esterase (3MGA) and protective antigen (3J9C) were speculated to be involved in human bacterial infections by using DYNLL1 to reach their target sites., Competing Interests: The authors declare no conflict of interest, (© 2019 Published by Elsevier B.V. on behalf of King Saud University.)

Objective: Phosphorous is an essential micronutrient of plants and involved in critical biological functions. In nature, phosphorous is mostly present in immobilized inorganic mineral and in the fixed organic form including phytic acid and phosphoesteric compounds. However, the bioavailability of bound phosphorous could be enhanced by the use of phosphate solubilizing microorganisms such as bacteria and fungi. The phytases are widespread in an environment and have been isolated from different sources comprising bacteria and fungi., Methodology: In current studies, we show the successful use of gamma rays and EMS (Ethyl Methane Sulphonate) mutagenesis for enhanced activity of phytases in a fungal strain Sporotrichum thermophile ., Results: We report an improved strain ST2 that could produce a clear halo zone around the colony, up to 24 mm. The maximum enzymatic activity was found of 382 U/mL on pH 5.5. However, the phytase activity was improved to 387 U/ml at 45 °C. We also report that the mutants produced through EMS showed the greater potential for phytase production., Conclusion: The current study highlights the potential of EMS mutagenesis for strain improvement over physical mutagens., (© 2019 King Saud University.)

Background: Breast cancer is a multifactorial disease with the highest frequency in females. Genetic and environmental factors can cause mutation in several genes like tyrosine kinase, JAK2 gene which may initiate cancer. Molecular analysis of mutations in the JAK2 gene along with determination of environmental, clinical and haematological risk factors associated with breast cancer patients is need of hour to improve patient's healthcare. Somatic JAK2 valine-to-phenylalanine (617 codon) mutation is one of the widely prevalent mutations., Methods: Blood was collected from seventy breast cancer patients after their consent. The questionnaire included risk factors, age group, locality, number of children, tumor type, family history, time of initial diagnosis, no of cycles/month, water conditions and exposure to radiations. Molecular analysis were carried out from genomic DNA using Sanger sequencing and allele-specific PCR to check the V617F point mutation., Results: The breast cancer risk factors includes unfiltered water (68.57%), urban (58.57%), menopause (55.71%), family history of cancer (18.57%), tumor grades (II, 37.14% and III, 35.71%), consanguineous marriages (44.28%) and having more than 3-4 children (45.71%). Prevalence of breast cancer was higher after the age of 35 and maximum at 35-50. In allele-specific PCR of 70 patients, 25 patients were wild type (229 bp), 25 patients were with partially deleted gene (200 bp), and 20 patient had shown no or less than 40 bp size fragments. In Sanger's sequencing of 70 BC cases, 18% were found to be positive for V617F point mutation, including 6 homozygous (T/T) and 7 heterozygous (G/T) mutations at nucleotide position 1849 in exon 14 of the JAK2 gene., Conclusions: Environmental and clinical risk factors were associated with breast cancer which can be overcome by improving awareness of associated risks, health facilities and reducing stress., Competing Interests: The authors declare that there is no conflict of interest.