Effect of Calebin-A on Critical Genes Related to NAFLD: A Protein-Protein Interaction Network and Molecular Docking Study.

Background: Calebin-A is a minor phytoconstituent of turmeric known for its activity against inflammation, oxidative stress, cancerous, and metabolic disorders like Non-alcoholic fatty liver disease(NAFLD). Based on bioinformatic tools. Subsequently, the details of the interaction of critical proteins with Calebin-A were investigated using the molecular docking technique. Methods: We first probed the intersection of genes/ proteins between NAFLD and Calebin-A through online databases. Besides, we performed an enrichment analysis using the ClueGO plugin to investigate signaling pathways and gene ontology. Next, we evaluate the possible interaction of Calebin-A with significant hub proteins involved in NAFLD through a molecular docking study. Results: We identified 87 intersection genes Calebin-A targets associated with NAFLD. PPI network analysis introduced 10 hub genes (TP53, TNF, STAT3, HSP90AA1, PTGS2, HDAC6, ABCB1, CCT2, NR1I2, and GUSB). In KEGG enrichment, most were associated with Sphingolipid, vascular endothelial growth factor A (VEGFA), C-type lectin receptor, and mitogen-activated protein kinase (MAPK) signaling pathways. The biological processes described in 87 intersection genes are mostly concerned with regulating the apoptotic process, cytokine production, and intracellular signal transduction. Molecular docking results also directed that Calebin-A had a high affinity to bind hub proteins linked to NAFLD. Conclusion: Here, we showed that Calebin-A, through its effect on several critical genes/ proteins and pathways, might repress the progression of NAFLD.

Exploration of the Key Genes Involved in Non-alcoholic Fatty Liver Disease and Possible MicroRNA Therapeutic Targets.

Background: MicroRNAs (miRNAs) are promising therapeutic agents for non-alcoholic fatty liver disease (NAFLD). This study aimed to identify key genes/proteins involved in NAFLD pathogenesis and progression and to evaluate miRNAs influencing their expression. Methods: Gene expression profiles from datasets GSE151158, GSE163211, GSE135251, GSE167523, GSE46300, and online databases were analyzed to identify significant NAFLD-related genes. Then, protein-protein interaction networks and module analysis identified hub genes/proteins, which were validated using real-time PCR in oleic acid-treated HepG2 cells. Functional enrichment analysis evaluated signaling pathways and biological processes. Gene-miRNA interaction networks identified miRNAs targeting critical NAFLD genes. Results: The most critical overexpressed hub genes/proteins included: TNF, VEGFA, TLR4, CYP2E1, ACE, SCD, FASN, SREBF2, and TGFB1 based on PPI network analysis, of which TNF, TLR4, SCD, FASN, SREBF2, and TGFB1 were up-regulated in oleic acid-treated HepG2 cells. Functional enrichment analysis for biological processes highlighted programmed necrotic cell death, lipid metabolic process response to reactive oxygen species, and inflammation. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the highest adjusted P-value signaling pathways encompassed AGE-RAGE in diabetic complications, TNF, and HIF-1 signaling pathways. In gene-miRNA network analysis, miR-16 and miR-124 were highlighted as the miRNAs exerting the most influence on important NAFLD-related genes. Conclusion: In silico analyses identified NAFLD therapeutic targets and miRNA candidates to guide further experimental investigation.

Analysis of the therapeutic potential of miR-124 and miR-16 in non-alcoholic fatty liver disease.

BACKGROUNDS: Non-alcoholic fatty liver disease (NAFLD) is a common condition affecting >25 % of the population worldwide. This disorder ranges in severity from simple steatosis (fat accumulation) to severe steatohepatitis (inflammation), fibrosis and, at its end-stage, liver cancer. A number of studies have identified overexpression of several key genes that are critical in the initiation and progression of NAFLD. MiRNAs are potential therapeutic agents that can regulate several genes simultaneously. Therefore, we transfected cell lines with two key miRNAs involved in targeting NAFLD-related genes. METHODS: The suppression effects of the investigated miRNAs (miR-124 and miR-16) and genes (TNF, TLR4, SCD, FASN, SREBF2, and TGFß-1) from our previous study were investigated by real-time PCR in Huh7 and HepG2 cells treated with oleic acid. Oil red O staining and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay were utilized to assess cell lipid accumulation and cytotoxic effects of the miRNAs, respectively. The pro-oxidant-antioxidant balance (PAB) assay was undertaken for miR-16 and miR-124 after cell transfection. RESULTS: Following transfection of miRNAs into HepG2, oil red O staining showed miR-124 and miR-16 reduced oleic acid-induced lipid accumulation by 35.2 % and 28.6 % respectively (p < 0.05). In Huh7, miR-124 and miR-16 reduced accumulation by 23.5 % and 31.3 % respectively (p < 0.05) but without impacting anti-oxidant activity. Real-time PCR in HepG2 revealed miR-124 decreased expression of TNF by 0.13-fold, TLR4 by 0.12-fold and SREBF2 by 0.127-fold (p < 0.05). miR-16 decreased TLR4 by 0.66-fold and FASN by 0.3-fold (p < 0.05). In Huh7, miR-124 decreased TNF by 0.12-fold and FASN by 0.09-fold (p < 0.05). miR-16 decreased SCD by 0.28-fold and FASN by 0.64-fold (p < 0.05). MTT assays showed, in HepG2, viability was decreased 24.7 % by miR-124 and decreased 33 % by miR-16 at 72 h (p < 0.05). In Huh7, miR-124 decreased viability 42 % at 48 h and 29.33 % at 72 h (p < 0.05), while miR-16 decreased viability by 32.3 % (p < 0.05). CONCLUSION: These results demonstrate the ability of miR-124 and miR-16 to significantly reduce lipid accumulation and expression of key pathogenic genes associated with NAFLD through direct targeting. Though this requires further in vivo investigation.

Diffraction of light from a long rectangular phase slit.

The phenomenon of light diffraction from an opaque screen containing a long rectangular slit has a closed-form solution in the Fraunhofer regime, which is covered in the undergraduate physics curriculum and experimentally verified. Here, we examine the more general situation of a semi-transparent plane that contains a long rectangular slit. Our analysis reveals that the diffraction patterns differ significantly between two specific cases: diffraction from an opaque screen containing a slit, and diffraction from a transparent plane featuring a slit (phase slit or a phase strip). The calculations demonstrate that the diffraction pattern resulting from the phase slit comprises two distinct sets of fringes with different spatial frequencies, and the width (size) of the phase slit (or strip) can be determined by examining the lower-frequency fringes. To verify these calculations, we fabricated appropriate phase slits and phase strips and analyzed their diffraction patterns. Our experimental findings showed excellent agreement with the theoretical predictions.

Identification and analysis of the molecular targets of statins in colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer in the world. According to several types of research, statins may impact the development and treatment of CRC. This work aimed to use bioinformatics to discover the relationship between statin targets and differentially expressed genes (DEGs) in CRC patients and determine the possible molecular effect of statins on CRC suppression. We used CRC datasets from the GEO database to select CRC-related DEGs. DGIdb and STITCH databases were used to identify gene targets of subtypes of statin. Further, we identified the statin target of CRC DEGs hub genes by using a Venn diagram of CRC DEGs and statin targets. Funrich and enrichr databases were carried out for the KEGG pathway and gene ontology (GO) enrichment analysis, respectively. GSE74604 and GSE10950 were used to identify CRC DEGs. After analyzing datasets,1370 genes were identified as CRC DEGs, and 345 targets were found for statins. We found that 35 genes are CRC DEGs statin targets. We found that statin targets in CRC were enriched in the receptor and metallopeptidase activity for molecular function, cytoplasm and plasma membrane for cellular component, signal transduction, and cell communication for biological process genes were substantially enriched based on FunRich enrichment. Analysis of the KEGG pathways revealed that the overexpressed DEGs were enriched in the IL-17, PPAR, and Toll-like receptor signaling pathways. Finally, CCNB1, DNMT1, AURKB, RAC1, PPARGC1A, CDKN1A, CAV1, IL1B, and HSPD1 were identified as hub CRC DEGs statin targets. The genetic and molecular aspects of our findings reveal that statins might have a therapeutic effect on CRC.

Efferocytosis: a double-edged sword in microbial immunity.

Efferocytosis is characterized as the rapid and efficient process by which dying or dead cells are removed. This type of clearance is initiated via "find-me" signals, and then, carries on by "eat-me" and "don't-eat-me" ones. Efferocytosis has a critical role to play in tissue homeostasis and innate immunity. However, some evidence suggests it as a double-edged sword in microbial immunity. In other words, some pathogens have degraded efferocytosis by employing efferocytic mechanisms to bypass innate immune detection and promote infection, despite the function of this process for the control and clearance of pathogens. In this review, the efferocytosis mechanisms from the recognition of dying cells to phagocytic engulfment are initially presented, and then, its diverse roles in inflammation and immunity are highlighted. In this case, much focus is also laid on some bacterial, viral, and parasitic infections caused by Mycobacterium tuberculosis (M. tb), Mycobacterium marinum (M. marinum), Listeria monocytogenes (L. monocytogenes), Chlamydia pneumoniae (CP), Klebsiella pneumoniae (KP), Influenza A virus (IAV), human immunodeficiency virus (HIV), and Leishmania, respectively.

How does the Immunological System Change during the SARS-COV-2 Attack? A Clue for the New Immunotherapy Discovery.

The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) is one of the biggest unsolved global problems of the 21st century for which there has been no definitive cure yet. Like other respiratory viruses, SARS-COV-2 triggers the host immunity dramatically, causing dysfunction in the immune system, both innate and adaptive, which is a common feature of COVID-19 patients. Evidence shows that in the early stages of COVID-19, the immune system is suppressed while it is overactive in severe patients characterized by excessive and prolonged inflammatory responses called "Cytokine Storm". There are many elements in the immune system that undergo alterations as the disease progresses. Some significant changes in the innate immune system following infection with SARS-COV-2 include delayed or inhibited interferon type 1 production by the infected cells leading to elevated virus replication, excessive recruitment of activated monocytes and macrophages, decrease in eosinophil population (eosinopenia), consequent decrease in CD8+T lymphocyte proliferation, natural killer (NK) cell dysfunction, and increase in neutrophil infiltration (neutrophilia) and neutrophil extracellular trap (NET) formation. Moreover, hallmark alterations in the adaptive immune system in this process cause an overall decrease in the T lymphocyte number (lymphopenia) and changes in the activity of some lymphocyte subsets and a number of B cells. This review delves into the mentioned changes in the immune system following SARS-COV-2 infection and the implications thereof to guide the development of immunotherapies for patients with COVID-19.

Statins as a Potential Treatment for Non-Alcoholic Fatty Liver Disease: Target Deconvolution using Protein-protein Interaction Network Analysis.

BACKGROUND: The hallmark of non-alcoholic fatty liver disease (NAFLD) is aberrant buildup of triglycerides (TGs) in hepatocytes. Many genes promote NAFLD development. Using bioinformatics tools, we investigated the possible effect of statins on genes involved in NAFLD progression. METHODS: Protein interactions of statins and NAFLD were searched in gene-drug and gene-disease databases. A Protein-Protein interaction (PPI) network was constructed to find hub genes and Molecular Complex Detection (MCODE) of NAFLD-related genes. Shared protein targets between protein targets of statins and NAFLD-associated genes were identified. Next, targets of each statin were assayed with all modular clusters in the MCODEs related to NAFLD. Biological process and pathway enrichment analysis for shared proteins was performed. RESULTS: Screening protein targets for conventional statins and curated NAFLD-related genes identified 343 protein targets and 70 genes, respectively. A Venn diagram of NAFLD-related genes and protein targets of statins showed 24 shared proteins. The biological pathways on KEGG enrichment associated with the 24 shared protein sets were evaluated and included cytokine-cytokine receptor interaction, adipocytokine, PPAR, TNF and AMPK signaling pathways. Gene Ontology analysis showed major involvement in lipid metabolic process regulation and inflammatory response. PPI network analysis of 70 protein targets indicated 13 hub genes (PPARA, IL4, CAT, LEP, SREBF1, PRKCA, CYP2E1, NFE2L2, PTEN, NR1H4, ADIPOQ, GSTP1 and TGFB1). Comparing all seven statins with the three MCODE clusterings and 13 hub genes revealed that simvastatin as the most associated statin with NAFLD. CONCLUSIONS: Simvastatin has the most impact on NAFLD-related genes versus other statins.

Harnessing aptamers against COVID-19: A therapeutic strategy.

The novel coronavirus crisis caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was a global pandemic. Although various therapeutic approaches were developed over the past 2 years, novel strategies with more efficient applicability are required to target new variants. Aptamers are single-stranded (ss)RNA or DNA oligonucleotides capable of folding into unique 3D structures with robust binding affinity to a wide variety of targets following structural recognition. Aptamer-based theranostics have proven excellent capability for diagnosing and treating various viral infections. Herein, we review the current status and future perspective of the potential of aptamers as COVID-19 therapies.

On the Characteristics of Fatigue Fracture with Rapid Frequency Change.

The effect of sudden variations in working modes and fatigue behavior of CS 1018 is studied. A general model based on the framework of the fracture fatigue entropy (FFE) concept is developed to capture such changes. Fully reversed bending tests are performed on flat dog bone specimens with a series of variable frequency tests without turning the machine off to simulate fluctuating working conditions. The results are then post-processed and analyzed to assess how fatigue life changes when a component is subjected to sudden changes in multiple frequencies. It is demonstrated that regardless of the frequency changes, FFE remains constant and stays within a narrow band range, similar to that of a constant frequency.

Microarray-Based Detection of Critical Overexpressed Genes in the Progression of Hepatic Fibrosis in Non-Alcoholic Fatty Liver Disease: A Protein-Protein Interaction Network Analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a prevalent cause of chronic liver disease and encompasses a broad spectrum of disorders, including simple steatosis, steatohepatitis, fibrosis, cirrhosis, and liver cancer. However, due to the global epidemic of NAFLD, where invasive liver biopsy is the gold standard for diagnosis, it is necessary to identify a more practical method for early NAFLD diagnosis with useful therapeutic targets; as such, molecular biomarkers could most readily serve these aims. To this end, we explored the hub genes and biological pathways in fibrosis progression in NAFLD patients. METHODS: Raw data from microarray chips with GEO accession GSE49541 were downloaded from the Gene Expression Omnibus database, and the R package (Affy and Limma) was applied to investigate differentially expressed genes (DEGs) involved in the progress of low- (mild 0-1 fibrosis score) to high- (severe 3-4 fibrosis score) fibrosis stage NAFLD patients. Subsequently, significant DEGs with pathway enrichment were analyzed, including gene ontology (GO), KEGG and Wikipathway. In order to then explore critical genes, the protein-protein interaction network (PPI) was established and visualized using the STRING database, with further analysis undertaken using Cytoscape and Gephi software. Survival analysis was undertaken to determine the overall survival of the hub genes in the progression of NAFLD to hepatocellular carcinoma. RESULTS: A total of 311 significant genes were identified, with an expression of 278 being upregulated and 33 downregulated in the high vs. low group. Gene functional enrichment analysis of these significant genes demonstrated major involvement in extracellular matrix (ECM)-receptor interaction, protein digestion and absorption, and the AGE-RAGE signaling pathway. The PPI network was constructed with 196 nodes and 572 edges with PPI enrichment using a p-value < 1.0 e-16. Based on this cut-off, we identified 12 genes with the highest score in four centralities: Degree, Betweenness, Closeness, and Eigenvector. Those twelve hub genes were CD34, THY1, CFTR, COL3A1, COL1A1, COL1A2, SPP1, THBS1, THBS2, LUM, VCAN, and VWF. Four of these hub genes, namely CD34, VWF, SPP1, and VCAN, showed significant association with the development of hepatocellular carcinoma. CONCLUSIONS: This PPI network analysis of DEGs identified critical hub genes involved in the progression of fibrosis and the biological pathways through which they exert their effects in NAFLD patients. Those 12 genes offer an excellent opportunity for further focused research to determine potential targets for therapeutic applications.

Identification of key upregulated genes involved in foam cell formation and the modulatory role of statin therapy.

BACKGROUND: We aimed to investigate the possible effect of statins on important genes/proteins involved in foam cell formation. METHODS: The gene expression profile of the GSE9874, GSE54666, and GSE7138from the Omnibus database were usedto identify genes involved in foam cell formation. The protein-protein interaction (PPI) network and MCODE analysis of the intersection of three databases were analyzed. We used molecular docking analysis to investigate the possible interaction of different statins with the overexpressed hub genes obtained from PPI analysis. RESULTS: The intersection among the three datasets showed 54 upregulated and 26 down-regulated genes. The most critical overexpressed genes/proteins obtained as hub genes included: G6PD, NPC1, ABCA1, ABCG1, PGD, PLIN2, PPAP2B, and TXNRD1 based on PPI analysis. Functional enrichment analysis of 81 intersection DEGs at the biological process level focusing on the cholesterol metabolic process, secondary alcohol biosynthetic process and the cholesterol biosynthetic process. Under cellular components, the analysis confirmed that these 81 intersection DEGs were mainly applied in endoplasmic reticulum membrane, lysosome and lytic vacuole. The molecular functions were identified as sterol binding, oxidoreductase activity and NADP binding. The molecular docking showed that all statins appear to affect important protein targets overexpressed in foam cell formation. However, lipophilic statins, especially pitavastatin and lovastatin, had a greater effect than hydrophilic statins. The most significant protein target of all the overexpressed genes interacting with all statin types was ABCA1. CONCLUSION: The effect of lipophilic statins was shown for several critical proteins in foam cell formation.

The development of a novel copper-loaded mesoporous silica nanoparticle as a peroxidase mimetic for colorimetric biosensing and its application in H2O2 and GSH assay.

In recent years, the development of nanomaterials-based peroxidase mimics as enzyme sensors has been attracting considerable interest due to their outstanding features, including potent stability, and cost-effectiveness toward natural enzymes. In this work, mesoporous silica nanoparticles functionalized by copper (Cu-MSN) were prepared as a new artificial enzyme for the first time through the sol-gel procedure. A comprehensive investigation of the catalytic activity of Cu-MSN was done through the oxidation of chromogenic peroxidase substrates, 3,3',5,5'-tetramethylbenzidine (TMB), and (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), in the presence of H2O2. The results indicate that the peroxidase-like activity of the as-prepared sample is significantly higher than other nanoparticles. Additionally, for the study, a facile and rapid sensing method based on the enzyme-like activity of Cu-MSN to detect H2O2 and glutathione (GSH) was developed to examine the potency of the proposed biosensor. Preliminary analysis revealed that the limit of detection (LOD) of H2O2 and GSH is 0.2 and 0.0126 µM, in the range of 0.9-100 and 0.042-1 µM, respectively. These findings support the claims for the efficiency of the sensor in detection fields. Also, human serum was utilized as the real sample to obtain additional evidence.

Application of nanotechnology in air purifiers as a viable approach to protect against Corona virus.

The outbreak of COVID-19 disease, the cause of severe acute respiratory syndrome, is considered a worldwide public health concern. Although studies indicated that the virus could spread through respiratory particles or droplets in close contact, current research have revealed that the virus stays viable in aerosols for several hours. Numerous investigations have highlighted the protective role of air purifiers in the management of COVID-19 transmission, however, there are still some doubts regarding the efficiency and safety of these technologies. According to those observations, using a proper ventilation system can extensively decrease the spread of COVID-19. However, most of those strategies are currently in the experimental stages. This review aimed at summarising the safety and effectiveness of the recent approaches in this field including using nanofibres that prevent the spread of airborne viruses like SARS-CoV-2. Here, the efficacy of controlling COVID-19 by means of combining multiple strategies is comprehensively discussed.

Porphyrin-based ligand interaction with G-quadruplex: Metal cation effects.

The G-quadruplex planar-ligand complex is used to detect heavy metal cations such as Ag+ , Cu2+ , Pb2+ , Hg2+ , organic molecules, nucleic acids, and proteins. The interaction of the three planar porphyrins (L1), 5,10,15,20-tetrakis (1-ethyl-1-λ4 -pyridine-4-yl) porphyrin (L2), and 5,10,15,20-tetrakis (1-methyl-1-λ4 -pyridine-4-yl) porphyrin (L3), coming from the porphyrin family, with G-quadruplex obtained from human DNA telomeres in the presence of lithium, sodium, potassium, rubidium, cesium, magnesium, and calcium ions was studied by molecular dynamics simulation. When G-quadruplex containing divalent ions of magnesium and calcium interacts with L1, L2, and L3 ligands, the hydrogen bonds of the lower G-quadruplex sheet are more affected by ligands and the distance between guanines in the lower tetrad increases. In the case of G-quadruplex interactions containing monovalent ions with ligands, the hydrogen bond between the sheets does not follow a specific trend. For example, in the presence of lithium ions, the upper and middle sheets are more affected by ligands, while they are less affected by ligands in the presence of sodium. The binding pocket and the binding energy of the three ligands to the G-quadruplex were also obtained in the various systems. The results show that ligands make the G-quadruplex more stable through the penetration between the sheets and the interaction with the loops. Among the ligands mentioned, the interaction level of the ligand L2 is greater than the others. Our calculations are consistent with the previous experimental observations so that it can help to understand the molecular mechanism of porphyrin interaction and its derivatives with the G-quadruplex.

Dysregulated balance in Th17/Treg axis of Pristane-induced lupus mouse model, are mesenchymal stem cells therapeutic?

BACKGROUND: Despite advances in general and targeted immunosuppressive therapies, limiting all mainstay treatment options in refractory systemic lupus erythematosus (SLE) cases has necessitated the development of new therapeutic strategies. Mesenchymal stem cells (MSCs) have recently emerged with unique properties, including a solid propensity to reduce inflammation, exert immunomodulatory effects, and repair injured tissues. METHODS: An animal model of acquired SLE mice was induced via intraperitoneal immunization with Pristane and affirmed by measuring specific biomarkers. Bone marrow (BM) MSCs were isolated from healthy BALB/c mice and cultured in vitro, then were identified and confirmed by flow cytometry and cytodifferentiation. Systemic MSCs transplantation was performed and then several parameters were analyzed and compared, including specific cytokines (IL-17, IL-4, IFN-É£, TGF-ß) at the serum level, the percentage of Th cell subsets (Treg/Th17, Th1/Th2) in splenocytes, and also the relief of lupus nephritis, respectively by enzyme-linked immunosorbent assay (ELISA), flow cytometry analysis and by hematoxylin & eosin staining and also immunofluorescence assessment. Experiments were carried out with different initiation treatment time points (early and late stages of disease). Analysis of variance (ANOVA) followed by post hoc Tukey's test was used for multiple comparisons. RESULTS: The rate of proteinuria, anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibodies, and serum creatinine levels decreased with BM-MSCs transplantation. These results were associated with attenuated lupus renal pathology in terms of reducing IgG and C3 deposition and lymphocyte infiltration. Our findings suggested that TGF-ß (associated with lupus microenvironment) can contribute to MSC-based immunotherapy by modulating the population of TCD4+ cell subsets. Obtained results indicated that MSCs-based cytotherapy could negatively affect the progression of induced SLE by recovering the function of Treg cells, suppressing Th1, Th2, and Th17 lymphocyte function, and downregulating their pro-inflammatory cytokines. CONCLUSION: MSC-based immunotherapy showed a delayed effect on the progression of acquired SLE in a lupus microenvironment-dependent manner. Allogenic MSCs transplantation revealed the ability to re-establish the balance of Th17/Treg, Th1/Th2 and restore the plasma cytokines network in a pattern dependent on disease conditions. The conflicting results of early versus advanced therapy suggest that MSCs may produce different effects depending on when they are administered and their activation status.

Harnessing the Therapeutic Potential of Antimicrobial Peptides for Cancers: State of the Art.

Despite significant breakthroughs in cancer treatment, cancer remains a serious global health concern that takes thousands of lives each year. Still, drug resistance and adverse effects are the main problems in conventional cancer therapeutic approaches. Thus, the discovery of new anticancer agents with distinct mechanisms of action is a critical requirement that offers significant obstacles. Antimicrobial peptides (AMPs), which can be found in various forms of life, are recognized as defensive weapons against infections of microbial pathogens. Surprisingly, they are also capable of killing a variety of cancer cells. These powerful peptides can cause cell death in the gastrointestinal, urinary tract, and reproductive cancer cell lines. To emphasize the anti-cancer properties of AMPs, we summarize the research that examined their impact on cancer cell lines in this review.

Identification of Potent Small-Molecule PCSK9 Inhibitors Based on Quantitative Structure-Activity Relationship, Pharmacophore Modeling, and Molecular Docking Procedure.

The leading cause of atherosclerotic cardiovascular disease (ASCVD) is elevated low-density lipoprotein cholesterol (LDL-C). Proprotein convertase subtilisin/kexin type 9 (PCSK9) attaches to the domain of LDL receptor (LDLR), diminishing LDL-C influx and LDLR cell surface presentation in hepatocytes, resulting in higher circulating LDL-C levels. PCSK9 dysfunction has been linked to lower levels of plasma LDLC and a decreased risk of coronary heart disease (CHD). Herein, using virtual screening tools, we aimed to identify a potent small-molecule PCSK9 inhibitor in compounds that are currently being studied in clinical trials. We first performed chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) filtering of 9800 clinical trial compounds obtained from the ZINC 15 database using Lipinski's rule of 5 and achieved 3853 compounds. Two-dimensional (2D) quantitative structure-activity relationship (QSAR) was initiated by computing molecular descriptors and selecting important descriptors of 23 PCSK9 inhibitors. Multivariate calibration was performed with the partial least square regression (PLS) method with 18 compounds for training to design the QSAR model and 5 compounds for the test set to assess the model. The best latent variables (LV) (LV=6) with the lowest value of Root-Mean-Square Error of Cross-Validation (RMSECV) of 0.48 and leave-one-out cross-validation correlation coefficient (R2CV) = 0.83 were obtained for the QSAR model. The low RMSEC (0.21) with high R²cal (0.966) indicates the probability of fit between the experimental data and the calibration model. Using QSAR analysis of 3853 compounds, 2635 had a pIC50<1 and were considered for pharmacophore screening. The PHASE module (a complete package for pharmacophore modeling) designed the pharmacophore hypothesis through multiple ligands. The top 14 compounds (pIC50>1) were defined as active, whereas 9 (pIC50<1) were considered as an inactive set. Three five-point pharmacophore hypotheses achieved the highest score: DHHRR1, DHHRR2, and DHRRR1. The highest and best model with survival scores (5.365) was DHHRR1, comprising 1 hydrogen donor (D), 2 hydrophobic groups (H), and 2 rings of aromatic (R) features. We selected the molecules with a higher 1.5 fitness score (257 compounds) in pharmacophore screening (DHHRR1) for molecular docking screening. Molecular docking indicates that ZINC000051951669, with a binding affinity: of -13.2 kcal/mol and 2 H-bonds, has the highest binding to the PCSK9 protein. ZINC000011726230 with energy binding: -11.4 kcal/mol and 3 H-bonds, ZINC000068248147 with binding affinity: -10.7 kcal/mol and 1 H-bond, ZINC000029134440 with a binding affinity: -10.6 kcal/mol and 4 H-bonds were ranked next, respectively. To conclude, the archived molecules identified as inhibitory PCSK9 candidates, and especially ZINC000051951669 may therefore significantly inhibit PCSK9 and should be considered in the newly designed trials.

Modulation of Mesenchymal Stem Cells-Mediated Adaptive Immune Effectors' Repertoire in the Recovery of Systemic Lupus Erythematosus.

The breakdown of self-tolerance of the immune response can lead to autoimmune conditions in which chronic inflammation induces tissue damage. Systemic lupus erythematosus (SLE) is a debilitating multisystemic autoimmune disorder with a high prevalence in women of childbearing age; however, SLE incidence, prevalence, and severity are strongly influenced by ethnicity. Although the mystery of autoimmune diseases remains unsolved, disturbance in the proportion and function of B cell subsets has a major role in SLE's pathogenesis. Additionally, colocalizing hyperactive T helper cell subgroups within inflammatory niches are indispensable. Despite significant advances in standard treatments, nonspecific immunosuppression, the risk of serious infections, and resistance to conventional therapies in some cases have raised the urgent need for new treatment strategies. Without the need to suppress the immune system, mesenchymal stem cells (MSCs), as ''smart" immune modulators, are able to control cellular and humoral auto-aggression responses by participating in precursor cell development. In lupus, due to autologous MSCs disorder, the ability of allogenic engrafted MSCs in tissue regeneration and resetting immune homeostasis with the provision of a new immunocyte repertoire has been considered simultaneously. In Brief The bone marrow mesenchymal stem cells (BM-MSCs) lineage plays a critical role in maintaining the hematopoietic stem-cell microstructure and modulating immunocytes. The impairment of BM-MSCs and their niche partially contribute to the pathogenesis of SLE-like diseases. Allogenic MSC transplantation can reconstruct BM microstructure, possibly contributing to the recovery of immunocyte phenotype restoration of immune homeostasis. In terms of future prospects of MSCs, artificially gained by ex vivo isolation and culture adaptation, the wide variety of potential mediators and mechanisms might be linked to the promotion of the immunomodulatory function of MSCs.

An experimental study on a cylindrical-conical cavity receiver for the parabolic dish collector.

Solar thermal energy is a promising solution to the environmental and energy demands issues which the world is faced with them. Among all the solar thermal collectors and solar towers used in this field, parabolic dish collectors are one of the preferable options for researchers due to their high working temperature range and high thermal performance. It has been proved that cavity receivers in solar dish collectors are the best way to achieve the best thermal performance. The main concern in the cavity receivers is their thermal efficiency enhancement by employing different geometries. The hybrid geometry of cylindrical-conical can be used to achieve the high pressure drop and low thermal efficiency of conventional cylindrical and conical cavity receivers, respectively. Furthermore, using proper insulation for the cavity receiver helps to performance enhancement of the dish collector. Ceramic fiber insulation can be suitable for this purpose due to its good thermal properties and fewer environmental issues. Hence, in this study, the objective of efficiency enhancement of parabolic dish collector is followed by utilizing a cylindrical-conical cavity receiver equipped with the fiber ceramic insulation. The results show that ceramic fiber is better insulation than the common mineral wool insulation and can enhance thermal performance by 5.03% on average. In addition, the maximum, average, and minimum thermal efficiencies of the cylindrical-conical cavity receiver by using the ceramic fiber insulation and water as the working fluid were obtained up to 38.77%, 35.19%, and 32.66%, respectively.