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Abdominal aortic aneurysm (AAA) has been recognized as a serious chronic inflammatory degenerative aortic disease in recent years. At present, there is no other effective intervention except surgical treatment for AAA. With the aging of the human population, its incidence is increasing year by year, posing a serious threat to human health. Modern studies suggest that vascular chronic inflammatory response is the core process in AAA occurrence and development. Inflammasome, a multiprotein complex located in the cytoplasm, mediates the expression of various inflammatory cytokines like interleukin (IL)-1β and IL-18, and thus plays a pivotal role in inflammation regulation. Therefore, inflammasome may exert a crucial influence on the progression of AAA. This article reviews some mechanism studies to investigate the role of inflammasome in AAA and then summarizes several potential drugs targeting inflammasome for the treatment of AAA, aiming to provide new ideas for the clinical prevention and treatment of AAA beyond surgical methods. [ABSTRACT FROM AUTHOR]

Background: Dysfunction in myocardial energy metabolism plays a vital role in the pathological process of Dilated Cardiomyopathy (DCM). However, the precise mechanisms remain unclear. This study aims to investigate the key molecular mechanisms of energy metabolism and potential therapeutic agents in the progression of dilated cardiomyopathy with heart failure. Methods: Gene expression profiles and clinical data for patients with dilated cardiomyopathy complicated by heart failure, as well as healthy controls, were sourced from the Gene Expression Omnibus (GEO) database. Gene sets associated with energy metabolism were downloaded from the Molecular Signatures Database (MSigDB) for subsequent analysis. Weighted Gene Coexpression Network Analysis (WGCNA) and differential expression analysis were employed to identify key modules and genes related to heart failure. Potential biological mechanisms were investigated through Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and the construction of a competing endogenous RNA (ceRNA) network. Molecular docking simulations were then conducted to explore the binding affinity and conformation of potential therapeutic drugs with hub genes. Results: Analysis of the left ventricular tissue expression profiles revealed that, compared to healthy controls, patients with dilated cardiomyopathy exhibited 234 differentially expressed genes and 2 genes related to myocardial energy metabolism. Additionally, Benzoylaconine may serve as a potential therapeutic agent for the treatment of dilated cardiomyopathy. Conclusion: The study findings highlight the crucial role of myocardial energy metabolism in the progression of Dilated Cardiomyopathy. Notably, Benzoylaconine emerges as a potential candidate for treating Dilated Cardiomyopathy, potentially exerting its therapeutic effects by targeted modulation of myocardial energy metabolism through NRK and NT5. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDs) are a diverse group of disorders characterized by the progressive degeneration and death of neurons, leading to a range of neurological symptoms. Despite the heterogeneity of these conditions, a common denominator is the implication of mitochondrial dysfunction in their pathogenesis. Mitochondria play a crucial role in creating biomolecules, providing energy through adenosine triphosphate (ATP) generated by oxidative phosphorylation (OXPHOS), and producing reactive oxygen species (ROS). When they're not functioning correctly, becoming fragmented and losing their membrane potential, they contribute to these diseases. In this review, we explore how mitochondria fuse and undergo fission, especially in the context of NDs. We discuss the genetic and protein mutations linked to these diseases and how they impact mitochondrial dynamics. We also look at the key regulatory proteins in fusion (MFN1, MFN2, and OPA1) and fission (DRP1 and FIS1), including their post-translational modifications. Furthermore, we highlight potential drugs that can influence mitochondrial dynamics. By unpacking these complex processes, we aim to direct research towards treatments that can improve life quality for people with these challenging conditions. [ABSTRACT FROM AUTHOR]

Tumor microenvironment (TME) is closely correlated to the occurrence and progression of breast cancer, however its potentiality in assisting diagnosis and therapeutic decision remains unclear. Therefore, the major aim of this study is to explore the prognostic value of TME related gene in breast cancer. Expression matrices and clinical data of breast cancer obtained from public databases were divided into TME relevant clusters according to immune characterization. A 12-gene molecular classifier was generated through the utilization of differentially expressed genes identified between distinct Tumor Microenvironment (TME) clusters, coupled with correlative regression analysis. The performance of this TME-driven prognostic signature (TPS) were examined across both the training and validation cohorts. Furthermore, our study revealed that breast cancer cases classified as high-risk based on the TPS exhibited the phenotype with elevated immune cell infiltration, higher tumor mutational burden, and a notably worse overall prognostic outcome. To conclude, the novel TME-based TPS was able to serve as a superior prognosis indicator for breast cancer, alone or jointly with other clinical factors. Also, breast cancer patients belong to different risk subgroups of TPS were found potentially suitable for distinguished therapeutic agents, which might improve personalized treatment for breast cancer in the future.

As an essential nutrient, copper's redox properties are both beneficial and toxic to cells. Therefore, leveraging the characteristics of copper-dependent diseases or using copper toxicity to treat copper-sensitive diseases may offer new strategies for specific disease treatments. In particular, copper concentration is typically higher in cancer cells, making copper a critical limiting nutrient for cancer cell growth and proliferation. Hence, intervening in copper metabolism specific to cancer cells may become a potential tumor treatment strategy, directly impacting tumor growth and metastasis. In this review, we discuss the metabolism of copper in the body and summarize research progress on the role of copper in promoting tumor cell growth or inducing programmed cell death in tumor cells. Additionally, we elucidate the role of copper-related drugs in cancer treatment, intending to provide new perspectives for cancer treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Preeclampsia is a pregnancy-related condition that causes high blood pressure and proteinuria after 20 weeks of pregnancy. It is linked to increased maternal mortality, organ malfunction, and foetal development limitation. In this view, there is a need critical to identify biomarkers for the early detection of preeclampsia. The objective of this study is to discover critical genes and explore medications for preeclampsia treatment that may influence these genes. Methods Four datasets, including GSE10588, GSE25906, GSE48424 and GSE60438 were retrieved from the Gene Expression Omnibus database. The GSE10588, GSE25906, and GSE48424 datasets were then removed the batch effect using the “sva” R package and merged into a complete dataset. The differentially expressed genes (DEGs) were identified using the “limma” R package. The potential small-molecule agents for the treatment of PE was further screened using the Connective Map (CMAP) drug database based on the DEGs. Further, Weight gene Co-expression network (WGNCA) analysis was performed to identified gene module associated with preeclampsia, hub genes were then identified using the logistic regression analysis. Finally, the immune cell infiltration level of genes was evaluated through the single sample gene set enrichment analysis (ssGSEA). Results A total of 681 DEGs (376 down-regulated and 305 up-regulated genes) were identified between normal and preeclampsia samples. Then, Dexamethasone, Prednisone, Rimexolone, Piretanide, Trazodone, Buflomedil, Scoulerin, Irinotecan, and Camptothecin drugs were screened based on these DEGs through the CMAP database. Two modules including yellow and brown modules were the most associated with disease through the WGCNA analysis. KEGG analysis revealed that the chemokine signaling pathway, Th1 and Th2 cell differentiation, B cell receptor signalling pathway and oxytocin signalling pathway were significantly enriched in these modules. Moreover, two key genes, PLEK and LEP were evaluated using the univariate and multivariate logistic regression analysis from the hub modules. These two genes were further validated in the external validation cohort GSE60438 and qRT-PCR experiment. Finally, we evaluated the relationship between immune cell and two genes. Conclusion In conclusion, the present study investigated key genes associated with PE pathogenesis that may contribute to identifying potential biomarkers, therapeutic agents and developing personalized treatment for PE.

Background: As an organelle essential for intracellular energy supply, mitochondria are involved in intracellular metabolism and inflammation, and cell death. The interaction of mitochondria with the NLRP3 inflammasome in the development of lung diseases has been extensively studied. However, the exact mechanism by which mitochondria mediate the activation of the NLRP3 inflammasome and trigger lung disease is still unclear. Methods: The literatures related to mitochondrial stress, NLRP3 inflammasome and lung diseases were searched in PubMed. Results: This review aims to provide new insights into the recently discovered mitochondrial regulation of the NLRP3 inflammasome in lung diseases. It also describes the crucial roles of mitochondrial autophagy, long noncoding RNA, micro RNA, altered mitochondrial membrane potential, cell membrane receptors, and ion channels in mitochondrial stress and regulation of the NLRP3 inflammasome, in addition to the reduction of mitochondrial stress by nuclear factor erythroid 2-related factor 2 (Nrf2). The effective components of potential drugs for the treatment of lung diseases under this mechanism are also summarized. Conclusion: This review provides a resource for the discovery of new therapeutic mechanisms and suggests ideas for the development of new therapeutic drugs, thus promoting the rapid treatment of lung diseases. [ABSTRACT FROM AUTHOR]

Background: Bone giant cell tumor (BGCT) is one of the world’s major disease types of locally aggressive bone tumors. In recent years, denosumab treatment has been introduced before curettage surgery. However, the current therapeutic was practical only sometimes, given the local recurrence effects after discontinuation of denosumab. Due to the complex nature of BGCT, this study aims to use bioinformatics to identify potential genes and drugs associated with BGCT.Methods: The genes that integrate BGCT and fracture healing were determined by text mining. The gene was obtained from the pubmed2ensembl website. We filtered out common genes for the function, and signal pathway enrichment analyses were implemented. The protein–protein interaction (PPI) networks and the hub genes were screened by MCODE built-in Cytoscape software. Lastly, the confirmed genes were queried in the Drug Gene Interaction Database to determine potential genes and drugs.Results: Our study finally identified 123 common specific genes in bone giant cell tumors and fracture healing text mining concepts. The GO enrichment analysis finally analyzed 115 characteristic genes in BP, CC, and MF. We selected 10 KEGG pathways and identified 68 characteristic genes. We performed protein–protein interaction analysis (PPI) on 68 selected genes and finally identified seven central genes. In this study, these seven genes were substituted into drug–gene interactions, and there were 15 antineoplastic drugs, 1 anti-involving drug, and 1 anti-influenza drug.Conclusion: The 7 genes (including ANGPT2, COL1A1, COL1A2, CTSK, FGFR1, NTRK2, and PDGFB) and 17 drugs, which have not been used in BGCT, but 6 of them approved by the FDA for other diseases, could be potential genes and drugs, respectively, to improve BGCT treatment. In addition, the correlation study and analysis of potential drugs through genes provide great opportunities to promote the repositioning of drugs and the study of pharmacology in the pharmaceutical industry.

Candida auris is a serious health concern of the current world that possesses a serious global health threat and is emerging at a high rate. Available antifungal drugs are failing to combat this pathogen as they are growing resistant to those drugs and some strains have already shown resistance to all three available antifungal drugs in the market. Hence, finding alternative therapies is essential for saving lives from this enemy. To make the development of new treatments easier, we conducted some in silico study of this pathogen to discover possible targets for drug design and also recommended some possible metabolites to test in vivo circumstances. The complete proteome of the representative strain was retrieved, and the duplicate, non-essential, human homologous, non-metabolic, and druggable proteins were then eliminated. As a result, out of a total of 5441 C. auris proteins, we were able to isolate three proteins (XP 028890156.1, XP 028891672.1, and XP 028891858.1) that are crucial for the pathogen's survival as well as host-non-homolog, metabolic, and unrelated proteins to the human microbiome. Their subcellular locations and interactions with a large number of proteins (10 proteins) further point to them being good candidates for therapeutic targets. Following in silico docking of 29 putative antifungals of plant origin against the three proteins we chose, Caledonixanthone E, Viniferin, Glaucine, and Jatrorrhizine were discovered to be the most effective means of inhibiting those proteins since they displayed higher binding affinities (ranging from −28.97 kcal/mol to −51.99 kcal/mol) than the control fluconazole (which ranged between −28.84 kcal/mol and −41.15 kcal/mol). According to the results of MD simulations and MM-PBSA calculations, Viniferin and Caledonixanthone E are the most effective ligands for the proteins XP 028890156.1, XP 028891672.1, and XP 028891858.1. Furthermore, they were predicted to be safe and also showed proper ADME properties.

Psoriasis is a chronic, prolonged, and recurrent inflammatory skin disease and the current therapeutics can only alleviate the symptoms rather than cure it completely. Therefore, we aimed to identify the molecular signatures and specific biomarkers of psoriasis to provide novel clues for psoriasis and targeted therapy. In the present study, the Gene Expression Omnibus (GEO) database was used to retrieve three microarray datasets (GSE166388, GSE50790 and GSE42632) and to explore the differentially expressed genes (DEGs) in psoriasis using the Affy package in R software. The gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment were utilized to determine the common DEGs and their capabilities. The STRING database was used to develop DEG-encoded proteins and a protein–protein interaction network (PPI) and the Cytohubba plugin to classify hub genes. Using the NetworkAnalyst platform, we detected transcription factors (TFs), microRNAs and drug candidates interacting with hub genes. In addition, the expression levels of hub genes in HaCaT cells were detected by western blot. We screened the up- and downregulated DEGs from the transcriptome microarrays of corresponding psoriasis patients. Functional enrichment of DEGs in psoriasis was mainly associated with positive regulation of leukocyte cell–cell adhesion and T cell activation, cytokine binding, cytokine activity and the Wnt signaling pathway. Through further data processing, we obtained 57 intersecting genes in the three datasets and probed them in STRING to determine the interaction of their expressed proteins and we obtained the critical 10 hub genes in the Cytohubba plugin, including TOP2A, CDKN3, MCM10, PBK, HMMR, CEP55, ASPM, KIAA0101, ESC02, and IL-1β. Using these hub genes as targets, we obtained 35 TFs and 213 miRNAs that may regulate these genes and 33 potential therapeutic agents for psoriasis. Furthermore, the expression levels of TOP2A, MCM10, PBK, ASPM, KIAA0101 and IL-1β were observably increased in HaCaT cells. In conclusion, we identified potential biomarkers, risk factors and drugs for psoriasis. [ABSTRACT FROM AUTHOR]

Six new chiral zinc(ii) complexes 1–6 based on ethylenediamine derivatives of terpenes were synthesized and characterized. The molecular structure of complex 2 was established by X-ray diffraction analysis. The modulating effect of complexes 1–6 on the functional state of mitochondria, which are organelles playing an utterly important role in maintaining the energy balance of cells, transfer of genetic material, and regulation of the processes of triggering the cell death by apoptosis, autophagy, and necrosis, was studied. It is shown that synthesized zinc complexes lead to depolarization of the mitochondrial membrane, an increase in the threshold of sensitivity of the organelles to calcium-induced opening of the mitochondrial permeability transition pores, and disruption of the operation of the respiratory chain complexes in these organelles. Such a dysfunctional state of mitochondria is one of the main causes of cell death through apoptosis due to the release of various proapoptotic factors into the intracellular space. In this regard, the newly synthesized zinc complexes 1–6 can be considered as destructive agents aimed at triggering cell death cascades by affecting mitochondrial functions. These properties are of paramount importance when searching for potential drugs with possible antitumor, antiprotozoal, or antifungal activity. [ABSTRACT FROM AUTHOR]

Topoisomerase inhibitors have been in use clinically for the treatment of several diseases for decades. Although those enzymes are significant molecular targets in antibacterial and anticancer chemotherapy very little is known about the possibilities to target fungal topoisomerase II (topo II). Raising concern for the fungal infections, lack of effective drugs and a phenomenon of multidrug resistance underlie a strong need to expand the range of therapeutic options. In this review paper, we discussed the usefulness of fungal topo II as a molecular target for new drug discovery. On the basis of previously published data, we described structural and biochemical differences between fungal and human enzymes as well as a molecular basis of differential sensitivity to known anticancer drugs targeting the latter. This review focuses especially on highlighting the differences that may underlie the selectivity of action of new inhibitors. Distinct sites within fungal topo II in comparison with human counterparts are observed and should be further studied to understand the significance of those sites and their possible usage in design of new drugs. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDs) are a diverse group of disorders characterized by the progressive degeneration and death of neurons, leading to a range of neurological symptoms. Despite the heterogeneity of these conditions, a common denominator is the implication of mitochondrial dysfunction in their pathogenesis. Mitochondria play a crucial role in creating biomolecules, providing energy through adenosine triphosphate (ATP) generated by oxidative phosphorylation (OXPHOS), and producing reactive oxygen species (ROS). When they’re not functioning correctly, becoming fragmented and losing their membrane potential, they contribute to these diseases. In this review, we explore how mitochondria fuse and undergo fission, especially in the context of NDs. We discuss the genetic and protein mutations linked to these diseases and how they impact mitochondrial dynamics. We also look at the key regulatory proteins in fusion (MFN1, MFN2, and OPA1) and fission (DRP1 and FIS1), including their post-translational modifications. Furthermore, we highlight potential drugs that can influence mitochondrial dynamics. By unpacking these complex processes, we aim to direct research towards treatments that can improve life quality for people with these challenging conditions.

Background: Preeclampsia is a pregnancy-related condition that causes high blood pressure and proteinuria after 20 weeks of pregnancy. It is linked to increased maternal mortality, organ malfunction, and foetal development limitation. In this view, there is a need critical to identify biomarkers for the early detection of preeclampsia. The objective of this study is to discover critical genes and explore medications for preeclampsia treatment that may influence these genes. Methods: Four datasets, including GSE10588, GSE25906, GSE48424 and GSE60438 were retrieved from the Gene Expression Omnibus database. The GSE10588, GSE25906, and GSE48424 datasets were then removed the batch effect using the "sva" R package and merged into a complete dataset. The differentially expressed genes (DEGs) were identified using the "limma" R package. The potential small-molecule agents for the treatment of PE was further screened using the Connective Map (CMAP) drug database based on the DEGs. Further, Weight gene Co-expression network (WGNCA) analysis was performed to identified gene module associated with preeclampsia, hub genes were then identified using the logistic regression analysis. Finally, the immune cell infiltration level of genes was evaluated through the single sample gene set enrichment analysis (ssGSEA). Results: A total of 681 DEGs (376 down-regulated and 305 up-regulated genes) were identified between normal and preeclampsia samples. Then, Dexamethasone, Prednisone, Rimexolone, Piretanide, Trazodone, Buflomedil, Scoulerin, Irinotecan, and Camptothecin drugs were screened based on these DEGs through the CMAP database. Two modules including yellow and brown modules were the most associated with disease through the WGCNA analysis. KEGG analysis revealed that the chemokine signaling pathway, Th1 and Th2 cell differentiation, B cell receptor signalling pathway and oxytocin signalling pathway were significantly enriched in these modules. Moreover, two key genes, PLEK and LEP were evaluated using the univariate and multivariate logistic regression analysis from the hub modules. These two genes were further validated in the external validation cohort GSE60438 and qRT-PCR experiment. Finally, we evaluated the relationship between immune cell and two genes. Conclusion: In conclusion, the present study investigated key genes associated with PE pathogenesis that may contribute to identifying potential biomarkers, therapeutic agents and developing personalized treatment for PE. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy (DCM) is a pathophysiological condition induced by diabetes mellitus that often causes heart failure (HF). However, their mechanistic relationships remain unclear. This study aimed to identify immune gene signatures and molecular mechanisms of DCM. Microarray data from the Gene Expression Omnibus (GEO) database from patients with DCM were subjected to weighted gene co-expression network analysis (WGCNA) identify co-expression modules. Core expression modules were intersected with the immune gene database. We analyzed and mapped protein-protein interaction (PPI) networks using the STRING database and MCODE and filtering out 17 hub genes using cytoHubba software. Finally, potential transcriptional regulatory factors and therapeutic drugs were identified and molecular docking between gene targets and small molecules was performed. We identified five potential immune biomarkers: proteosome subunit beta type-8 (PSMB8), nuclear factor kappa B1 (NFKB1), albumin (ALB), endothelin 1 (EDN1), and estrogen receptor 1 (ESR1). Their expression levels in animal models were consistent with the changes observed in the datasets. EDN1 showed significant differences in expression in both the dataset and the validation model by real-time quantitative PCR (qPCR) and Western blotting (WB). Subsequently, we confirmed that the potential transcription factors upstream of EDN1 were PRDM5 and KLF4, as its expression was positively correlated with the expression of the two transcription factors. To repurpose known therapeutic drugs, a connectivity map (CMap) database was retrieved, and nine candidate compounds were identified. Finally, molecular docking simulations of the proteins encoded by the five genes with small-molecule drugs were performed. Our data suggest that EDN1 may play a key role in the development of DCM and is a potential DCM biomarker. [ABSTRACT FROM AUTHOR]

Background: Behcet's disease (BD) is a chronic immune disease that involves multiple systems. As the pathogenesis of BD is not clear, and new treatments are needed, we used bioinformatics to identify potential drugs and validated them in mouse models. Methods: Behcet's disease-related target genes and proteins were screened in the PubMed and UVEOGENE databases. The biological functions and pathways of the target genes were analyzed in detail by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was constructed by the STRING database, and hub genes were identified by the Cytoscape plug-in CytoHubba. Gene-drug interactions were identified from the DGIdb database. Experimental autoimmune uveitis (EAU) mice were used as an animal model for drug validation. Results: A total of 249 target genes and proteins with significant differences in BD were screened, and the results of functional enrichment analysis suggested that these genes and proteins were more located on the cell membrane, involved in regulating the production of cytokines and affecting the activity of cytokines. They mainly regulated "Cytokine- Cytokine receptor interaction", "Inflammatory bowel disease (IBD)" and "IL-17 signaling Pathway". In addition, 10 hub genes were obtained through PPI network construction and CytoHubba analysis, among which the top 3 hub genes were closely related to BD. The DGIdb analysis enriched seven drugs acting together on the top 3 hub genes, four of which were confirmed for the treatment of BD or its complications. There is no evidence in the research to support the results in omeprazole, rabeprazole, and celastrol. However, animal experiments showed that rabeprazole and celastrol reduced anterior chamber inflammation and retinal inflammation in EAU mice. Conclusions: The functional analysis of genes and proteins related to BD, identification of hub genes, and validation of potential drugs provide new insights into the disease mechanism and potential for the treatment of BD. [ABSTRACT FROM AUTHOR]

BackgroundBehcet’s disease (BD) is a chronic immune disease that involves multiple systems. As the pathogenesis of BD is not clear, and new treatments are needed, we used bioinformatics to identify potential drugs and validated them in mouse models.MethodsBehcet’s disease-related target genes and proteins were screened in the PubMed and UVEOGENE databases. The biological functions and pathways of the target genes were analyzed in detail by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was constructed by the STRING database, and hub genes were identified by the Cytoscape plug-in CytoHubba. Gene-drug interactions were identified from the DGIdb database. Experimental autoimmune uveitis (EAU) mice were used as an animal model for drug validation.ResultsA total of 249 target genes and proteins with significant differences in BD were screened, and the results of functional enrichment analysis suggested that these genes and proteins were more located on the cell membrane, involved in regulating the production of cytokines and affecting the activity of cytokines. They mainly regulated “Cytokine- Cytokine receptor interaction”, “Inflammatory bowel disease (IBD)” and “IL-17 signaling Pathway”. In addition, 10 hub genes were obtained through PPI network construction and CytoHubba analysis, among which the top 3 hub genes were closely related to BD. The DGIdb analysis enriched seven drugs acting together on the top 3 hub genes, four of which were confirmed for the treatment of BD or its complications. There is no evidence in the research to support the results in omeprazole, rabeprazole, and celastrol. However, animal experiments showed that rabeprazole and celastrol reduced anterior chamber inflammation and retinal inflammation in EAU mice.ConclusionsThe functional analysis of genes and proteins related to BD, identification of hub genes, and validation of potential drugs provide new insights into the disease mechanism and potential for the treatment of BD.

The major characteristics of new bioactive microbial secondary metabolites are summarized in the review. A wide range of new molecular targets are implicated in discovery of new nonantibiotic compounds with some other pharmacological activities (noninfectious diseases). Microorganisms represent fascinating resources due to their production of novel products with broad spectra of bioactivities.

Psoriasis is a chronic, prolonged, and recurrent inflammatory skin disease and the current therapeutics can only alleviate the symptoms rather than cure it completely. Therefore, we aimed to identify the molecular signatures and specific biomarkers of psoriasis to provide novel clues for psoriasis and targeted therapy. In the present study, the Gene Expression Omnibus (GEO) database was used to retrieve three microarray datasets (GSE166388, GSE50790 and GSE42632) and to explore the differentially expressed genes (DEGs) in psoriasis using the Affy package in R software. The gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment were utilized to determine the common DEGs and their capabilities. The STRING database was used to develop DEG-encoded proteins and a protein–protein interaction network (PPI) and the Cytohubba plugin to classify hub genes. Using the NetworkAnalyst platform, we detected transcription factors (TFs), microRNAs and drug candidates interacting with hub genes. In addition, the expression levels of hub genes in HaCaT cells were detected by western blot. We screened the up- and downregulated DEGs from the transcriptome microarrays of corresponding psoriasis patients. Functional enrichment of DEGs in psoriasis was mainly associated with positive regulation of leukocyte cell–cell adhesion and T cell activation, cytokine binding, cytokine activity and the Wnt signaling pathway. Through further data processing, we obtained 57 intersecting genes in the three datasets and probed them in STRING to determine the interaction of their expressed proteins and we obtained the critical 10 hub genes in the Cytohubba plugin, including TOP2A, CDKN3, MCM10, PBK, HMMR, CEP55, ASPM, KIAA0101, ESC02, and IL-1β. Using these hub genes as targets, we obtained 35 TFs and 213 miRNAs that may regulate these genes and 33 potential therapeutic agents for psoriasis. Furthermore, the expression levels of TOP2A, MCM10, PBK, ASPM, KIAA0101 and IL-1β were observably increased in HaCaT cells. In conclusion, we identified potential biomarkers, risk factors and drugs for psoriasis.

Topoisomerase inhibitors have been in use clinically for the treatment of several diseases for decades. Although those enzymes are significant molecular targets in antibacterial and anticancer chemotherapy very little is known about the possibilities to target fungal topoisomerase II (topo II). Raising concern for the fungal infections, lack of effective drugs and a phenomenon of multidrug resistance underlie a strong need to expand the range of therapeutic options. In this review paper, we discussed the usefulness of fungal topo II as a molecular target for new drug discovery. On the basis of previously published data, we described structural and biochemical differences between fungal and human enzymes as well as a molecular basis of differential sensitivity to known anticancer drugs targeting the latter. This review focuses especially on highlighting the differences that may underlie the selectivity of action of new inhibitors. Distinct sites within fungal topo II in comparison with human counterparts are observed and should be further studied to understand the significance of those sites and their possible usage in design of new drugs.

The oxazole and pyrimidine rings are widely displayed in natural products and synthetic molecules. They are known as the prime skeletons for drug discovery. On the account of structural and chemical diversity, oxazole and pyrimidine‐based molecules, as central scaffolds, not only provide different types of interactions with various receptors and enzymes, showing broad biological activities, but also occupy a core position in medicinal chemistry, showing their importance for development and discovery of newer potential therapeutic agents (Curr Top Med Chem, 16, 2016, 3133; Int J Pharm Pharm Sci, 8, 2016, 8; BMC Chem, 13, 2019, 44). For a long time, relatively little attention has been paid to their fused rings that are oxazolopyrimidines, whose chemical structure is similar to that of natural purines because probably none of these compounds were found in natural products or their biological activities turned out to be unexpressed (Bull Chem Soc Jpn, 43, 1970, 187). Recently, however, a significant number of studies have been published on the biological properties of oxazolo[5,4‐d]pyrimidines, showing their significant activity as agonists and antagonists of signaling pathways involved in the regulation of the cell life cycle, whereas oxazolo[4,5‐d]pyrimidines, on the contrary, represent a poorly studied class of compounds. Limited access to this scaffold has resulted in a corresponding lack of biological research (Eur J Organ Chem, 18, 2018, 2148). Actually, oxazolo[5,4‐d]pyrimidine is a versatile scaffold used for the design of bioactive ligands against enzymes and receptors. This review focuses on biological targets and associated pathogenetic mechanisms, as well as pathological disorders that can be modified by well‐known oxazolopyrimidines that have been proven to date. Many molecular details of these processes are omitted here, which the interested reader will find in the cited literature. This work also does not cover the methods for the synthesis of the oxazolopyrimidines, which are exhaustively described by De Coen et al. (Eur J Organ Chem, 18, 2018, 2148). The review as well does not discuss the structure–activity relationship, which is described in detail in the original works and deliberately, whenever possible, cites not primary sources, but mostly relevant review articles, so that the reader who wants to delve into a particular problem will immediately receive more complete information. It is expected that the information presented in this review will help readers better understand the purpose of the development of oxazolopyrimidines and the possibility of their development as drugs for the treatment of a wide range of diseases. [ABSTRACT FROM AUTHOR]

Endometriosis, a common disease that presents as polymorphism, invasiveness, and extensiveness, with clinical manifestations including dysmenorrhea, infertility, and menstrual abnormalities, seriously affects quality of life in women. To date, its underlying etiological mechanism of action and the associated regulatory genes remain unclear. This study aimed to identify molecular markers and elucidate mechanisms underlying the development and progression of endometriosis. Specifically, we downloaded five microarray expression datasets, namely, GSE11691, GSE23339, GSE25628, GSE7305, and GSE105764, from the Gene Expression Omnibus (GEO) database. These datasets, obtained from endometriosis tissues, alongside normal controls, were subjected to in-depth bioinformatics analysis for identification of differentially expressed genes (DEGs), followed by analysis of their function and pathways via gene ontology (GO) and KEGG pathway enrichment analyses. Moreover, we constructed a protein–protein interaction (PPI) network to explore the hub genes and modules, and then applied machine learning algorithms support vector machine-recursive feature elimination and least absolute shrinkage and selection operator (LASSO) analysis to identify key genes. Furthermore, we adopted the CIBERSORTx algorithm to estimate levels of immune cell infiltration while the connective map (CMAP) database was used to identify potential therapeutic drugs in endometriosis. As a result, a total of 423 DEGs, namely, 233 and 190 upregulated and downregulated, were identified. On the other hand, a total of 1,733 PPIs were obtained from the PPI network. The DEGs were mainly enriched in immune-related mechanisms. Furthermore, machine learning and LASSO algorithms identified three key genes, namely, apelin receptor (APLNR), C–C motif chemokine ligand 21 (CCL21), and Fc fragment of IgG receptor IIa (FCGR2A). Furthermore, 16 small molecular compounds associated with endometriosis treatment were identified, and their mechanism of action was also revealed. Taken together, the findings of this study provide new insights into the molecular factors regulating occurrence and progression of endometriosis and its underlying mechanism of action. The identified therapeutic drugs and molecular markers may have clinical significance in early diagnosis of endometriosis. [ABSTRACT FROM AUTHOR]

The present study describes different chemical reactivity predictions of 6-O-hexanoylation of octyl β-D-glucopyranosides prepared from octyl β-D-glucopyranoside (OBG). Also, molecular docking of the OBGs was conducted against SARS-CoV-2 main protease (6LU7), urate oxidase (Aspergillus flavus; 1R51) and glucoamylase (Aspergillus niger; 1KUL). DFT optimization indicated that glucoside 1 and its ester derivatives 2-7 exist in 4C1 conformation with C1 symmetry. Interestingly, the addition of ester group(s) decreased the HOMO-LUMO gap (Δԑ) of glucosides indicating their good chemical reactivities, whereas the other chemical reactivity descriptors indicated their moderate reactive nature. This fact of moderate reactivity was confirmed by their molecular docking with 6LU7, 1R51 and 1KUL. All the esters showed a moderate binding affinity with these three proteins. More importantly, incorporation of the ester group(s) increased binding affinity with 6LU7 and 1R51, whereas decreased with 1KUL as compared to non-ester OBG 1.

Endometriosis, a common disease that presents as polymorphism, invasiveness, and extensiveness, with clinical manifestations including dysmenorrhea, infertility, and menstrual abnormalities, seriously affects quality of life in women. To date, its underlying etiological mechanism of action and the associated regulatory genes remain unclear. This study aimed to identify molecular markers and elucidate mechanisms underlying the development and progression of endometriosis. Specifically, we downloaded five microarray expression datasets, namely, GSE11691, GSE23339, GSE25628, GSE7305, and GSE105764, from the Gene Expression Omnibus (GEO) database. These datasets, obtained from endometriosis tissues, alongside normal controls, were subjected to in-depth bioinformatics analysis for identification of differentially expressed genes (DEGs), followed by analysis of their function and pathways via gene ontology (GO) and KEGG pathway enrichment analyses. Moreover, we constructed a protein–protein interaction (PPI) network to explore the hub genes and modules, and then applied machine learning algorithms support vector machine-recursive feature elimination and least absolute shrinkage and selection operator (LASSO) analysis to identify key genes. Furthermore, we adopted the CIBERSORTx algorithm to estimate levels of immune cell infiltration while the connective map (CMAP) database was used to identify potential therapeutic drugs in endometriosis. As a result, a total of 423 DEGs, namely, 233 and 190 upregulated and downregulated, were identified. On the other hand, a total of 1,733 PPIs were obtained from the PPI network. The DEGs were mainly enriched in immune-related mechanisms. Furthermore, machine learning and LASSO algorithms identified three key genes, namely, apelin receptor (APLNR), C–C motif chemokine ligand 21 (CCL21), and Fc fragment of IgG receptor IIa (FCGR2A). Furthermore, 16 small molecular compounds associated with endometriosis treatment were identified, and their mechanism of action was also revealed. Taken together, the findings of this study provide new insights into the molecular factors regulating occurrence and progression of endometriosis and its underlying mechanism of action. The identified therapeutic drugs and molecular markers may have clinical significance in early diagnosis of endometriosis.

Background: Pancreatic cancer (PC) is a highly fatal and aggressive disease with its incidence and mortality quite discouraging. An effective prediction model is urgently needed for the accurate assessment of patients' prognosis to assist clinical decision-making. Methods: Gene expression data and clinicopathological data of the samples were acquired from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases. Differential expressed genes (DEGs) analysis, univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression analysis, random forest screening and multivariate Cox regression analysis were applied to construct the risk signature. The effectiveness and independence of the model were validated by time-dependent receiver operating characteristic (ROC) curve, Kaplan–Meier (KM) survival analysis and survival point graph in training set, test set, TCGA entire set and GSE57495 set. The validity of the core gene was verified by immunohistochemistry and our own independent cohort. Meanwhile, functional enrichment analysis of DEGs between the high and low risk groups revealed the potential biological pathways. Finally, CMap database and drug sensitivity assay were utilized to identify potential small molecular drugs as the risk model-related treatments for PC patients. Results: Four histone modification-related genes were identified to establish the risk signature, including CBX8, CENPT, DPY30 and PADI1. The predictive performance of risk signature was validated in training set, test set, TCGA entire set and GSE57495 set, with the areas under ROC curve (AUCs) for 3-year survival were 0.773, 0.729, 0.775 and 0.770 respectively. Furthermore, KM survival analysis, univariate and multivariate Cox regression analysis proved it as an independent prognostic factor. Mechanically, functional enrichment analysis showed that the poor prognosis of high-risk population was related to the metabolic disorders caused by inadequate insulin secretion, which was fueled by neuroendocrine aberration. Lastly, a cluster of small molecule drugs were identified with significant potentiality in treating PC patients. Conclusions: Based on a histone modification-related gene signature, our model can serve as a reliable prognosis assessment tool and help to optimize the treatment for PC patients. Meanwhile, a cluster of small molecule drugs were also identified with significant potentiality in treating PC patients. [ABSTRACT FROM AUTHOR]

Background: Dysfunction in myocardial energy metabolism plays a vital role in the pathological process of Dilated Cardiomyopathy (DCM). However, the precise mechanisms remain unclear. This study aims to investigate the key molecular mechanisms of energy metabolism and potential therapeutic agents in the progression of dilated cardiomyopathy with heart failure. Methods: Gene expression profiles and clinical data for patients with dilated cardiomyopathy complicated by heart failure, as well as healthy controls, were sourced from the Gene Expression Omnibus (GEO) database. Gene sets associated with energy metabolism were downloaded from the Molecular Signatures Database (MSigDB) for subsequent analysis. Weighted Gene Co-expression Network Analysis (WGCNA) and differential expression analysis were employed to identify key modules and genes related to heart failure. Potential biological mechanisms were investigated through Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and the construction of a competing endogenous RNA (ceRNA) network. Molecular docking simulations were then conducted to explore the binding affinity and conformation of potential therapeutic drugs with hub genes. Results: Analysis of the left ventricular tissue expression profiles revealed that, compared to healthy controls, patients with dilated cardiomyopathy exhibited 234 differentially expressed genes and 2 genes related to myocardial energy metabolism. Additionally, Benzoylaconine may serve as a potential therapeutic agent for the treatment of dilated cardiomyopathy. Conclusion: The study findings highlight the crucial role of myocardial energy metabolism in the progression of Dilated Cardiomyopathy. Notably, Benzoylaconine emerges as a potential candidate for treating Dilated Cardiomyopathy, potentially exerting its therapeutic effects by targeted modulation of myocardial energy metabolism through NRK and NT5., 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 © 2024 Wang, Cai, Yu, Li, Zhu, Liu and Wang.)

BackgroundThe coronavirus disease 2019 (COVID-19) has become a worldwide public health crisis. At present, there are no effective antiviral drugs to treat COVID-19. Although some vaccines have been developed, late-stage clinical trials that allow licensure by regulatory agencies are still needed. Previous reports have indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV are highly homologous and both use angiotensin-converting enzyme 2 (ACE2) as the receptor to enter cells, and SARS-CoV infection reduces the ACE2 expression in the lung. Therefore, the analysis of genes co-expressed with ACE2 in the lung may uncover the underlying mechanism of COVID-19. Finally, we used the Connectivity map (Cmap) database to search for candidate drugs using transcriptome profiles of patients with COVID-19.MethodBased on the differentially expressed genes (DEGs), indicated by the expression of RNAs isolated from bronchoalveolar lavage fluid (BALF) cells of patients with COVID-19, we performed functional enrichment analysis and hub gene cluster analysis. Furthermore, we identified genes co-expressed with ACE2 in healthy lung samples and analyzed the significant genes. Additionally, to identify several candidate drugs for the treatment of COVID-19, we queried Cmap using DEGs and genes co-expressed with ACE2.Results and ConclusionThe up-regulated genes in the BALF cells of patients with COVID-19 are related to viral mRNA translation. The down-regulated genes are related to immune response functions. Genes positively correlated with ACE2 are related to immune defense and those negatively correlated are enriched in synaptic transmission functions. The results reflected prosperous viral proliferation and immune dysfunction in patients. Furthermore, ACE2 may not only mediate viral entrance, but also play an important role in immune defense. By using Cmap with transcriptome profiles of patients with COVID-19, we identified candidate drugs for the treatment of COVID-19, such as amantadine and acyclovir.

Ongoing search for treatment to ease COVID-19 pandemic concentrate on development of a vaccine or medication to prevent and treat this disease. One of the possibilities is developing new antiviral drugs that are aiming at both a virus replication or the host factor(s) that are critical to virus’s replication. Serine proteases, which activate the viral spike glycoproteins and facilitate virus-cell membrane fusions for host cell entry, its replication and spread, are proposed as the potential targets for antiviral drug design. Existing literature is already providing evidence that transmembrane protease serine 2 (TMPRSS2) is one of the promising targets. When inhibited it can slow or stop replication of viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One of the convincing evidences of the critical role of TMPRSS2 in the coronavirus’s replication was provided by animal study. The replication of influenza viruses was inhibited in TMPRSS2(-/-) knockout mice in comparison to wild type (WT) mice, which developed high mortality rate. Existing inhibitors of TMPRSS2 can be divided into two groups. The first include drugs already approved by FDA or other organizations for treatment of different diseases. That include: Camostat (from Japan, produced by Ono Pharmaceutical), aprotinin (Trasylol, produced by Nordic Group Pharmaceuticals) and rimantadine (Flumadine, produced by Forest Pharmaceuticals, Inc.). Existing in vitro, in vivo and some limited human studies show that this type of drugs limit reproduction of coronaviruses and/or prevented the development of viral pneumonia. One study indicated that combined treatment by aprotinin and rimantadine prevented the development of fatal hemorrhagic viral pneumonia, and protected about 75% animals, when the separate administration of aprotinin or rimantadine induced less protection. The second group includes potential drugs not approved for the human use yet. That include plasminogen activator inhibitor type 1 (PAI-1) and recently developed small molecular inhibitors. PAI-1 is a serine protease inhibitor that regulates physiological breakdown of blood clots by inhibiting of tissue (tPA) and urokinase (uPA) plasminogen activators. But PAI-1 is also an effective inhibitor of various membrane-anchored serine proteases including TMPRSS2. It was reported that PAI-1 inhibited trypsin- and TMPRSS2-mediated cleavage of hemagglutinin and suppressed influenza virus in animals. PAI-1 is human in origin and engineered forms with extended half-life were developed and could be an attractive addition to the existing TMPRSS2 inhibitors. And finally, derivatives of sulfonylated 3-amindinophenylalanylamide were found to inhibit TMPRSS2 with a high affinity and efficiently block the influenza virus propagation in human cells. This paper is intended to provide review on possible or hypothetical beneficial effects of (TMPRSS2) inhibitors as one of options to fight infection with Covid-19.

Background: The coronavirus disease 2019 (COVID-19) has become a worldwide public health crisis. At present, there are no effective antiviral drugs to treat COVID-19. Although some vaccines have been developed, late-stage clinical trials that allow licensure by regulatory agencies are still needed. Previous reports have indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV are highly homologous and both use angiotensin-converting enzyme 2 (ACE2) as the receptor to enter cells, and SARS-CoV infection reduces the ACE2 expression in the lung. Therefore, the analysis of genes co-expressed with ACE2 in the lung may uncover the underlying mechanism of COVID-19. Finally, we used the Connectivity map (Cmap) database to search for candidate drugs using transcriptome profiles of patients with COVID-19. Method: Based on the differentially expressed genes (DEGs), indicated by the expression of RNAs isolated from bronchoalveolar lavage fluid (BALF) cells of patients with COVID-19, we performed functional enrichment analysis and hub gene cluster analysis. Furthermore, we identified genes co-expressed with ACE2 in healthy lung samples and analyzed the significant genes. Additionally, to identify several candidate drugs for the treatment of COVID-19, we queried Cmap using DEGs and genes co-expressed with ACE2. Results and Conclusion: The up-regulated genes in the BALF cells of patients with COVID-19 are related to viral mRNA translation. The down-regulated genes are related to immune response functions. Genes positively correlated with ACE2 are related to immune defense and those negatively correlated are enriched in synaptic transmission functions. The results reflected prosperous viral proliferation and immune dysfunction in patients. Furthermore, ACE2 may not only mediate viral entrance, but also play an important role in immune defense. By using Cmap with transcriptome profiles of patients with COVID-19, we identified candidate drugs for the treatment of COVID-19, such as amantadine and acyclovir. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a common hematological malignancy. Although recent clinical applications of immunomodulatory drugs, proteasome inhibitors and CD38-targeting antibodies have significantly improved the outcome of MM patient with increased survival, the incidence of drug resistance and severe treatment-related complications is gradually on the rise. This review article summarizes the characteristics and clinical investigations of several MM drugs in clinical trials, including their structures, mechanisms of action, structure-activity relationships, and clinical study progress. Furthermore, the application potentials of the drugs that have not yet entered clinical trials are also reviewed. The review also outlines the future directions of MM drug development. [Display omitted] • Drug resistance and severe treatment-related complications increase in Multiple Myeloma. • Drug's structure, mechanism, structure-activity relationship and clinical study were summarized. • Novel drugs have not yet entered clinical trials provide insights for the future MM treatment. [ABSTRACT FROM AUTHOR]

Background Masticatory Myofascial Pain Dysfunction Syndrome (MMPDS) is a musculoligamentous disorder that shares similarities with temporomandibular joint pain and odontogenic pain. It manifests as dull or aching pain in masticatory muscles, influenced by jaw movement. Computer-aided drug design (CADD) encompasses various theoretical and computational approaches used in modern drug discovery. Molecular docking is a prominent method in CADD that facilitates the understanding of drug-bimolecular interactions for rational drug design, mechanistic studies & the formation of stable complexes with increased specificity and potential efficacy. The docking technique provides valuable insights into binding energy, free energy, and complex stability predictions. Aim The aim of this study was to use the docking technique for myosin inhibitors. Materials and methods Four inhibitors of myosin were chosen from the literature. These compound structures were retrieved from the Zinc15 database. Myosin protein was chosen as the target and was optimized using the RCSB Protein Data Bank. After pharmacophore modeling, 20 novel compounds were found and the SwissDock was used to dock them with the target protein. We compared the binding energies of the newly discovered compounds to those of the previously published molecules with the target. Results The results indicated that among the 20 molecules ZINC035924607 and ZINC5110352 exhibited the highest binding energy and displayed superior properties compared to the other molecules. Conclusion The study concluded that ZINC035924607 and ZINC5110352 exhibited greater binding affinity than the reported inhibitors of myosin. Therefore, these two molecules can be used as a potential and promising lead for the treatment of MMPDS and could be employed in targeted drug therapy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Suresh et al.)

Background: The abundance of circulating monocytes is closely associated with the development of atherosclerosis in humans., Objective: This study aimed to further research into diagnostic biomarkers and targeted treatment of carotid atherosclerosis (CAS)., Methods: We performed transcriptomics analysis through weighted gene co-expression network analysis (WGCNA) of monocytes from patients in public databases with and without CAS. Differentially expressed genes (DEGs) were screened by R package limma. Diagnostic molecules were derived by the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) algorithms. NetworkAnalyst, miRWalk, and Star- Base databases assisted in the construction of diagnostic molecule regulatory networks. The Drug- Bank database predicted drugs targeting the diagnostic molecules. RT-PCR tested expression profiles., Results: From 14,369 hub genes and 61 DEGs, six differentially expressed monocyte-related hub genes were significantly associated with immune cells, immune responses, monocytes, and lipid metabolism. LASSO and SVM-RFE yielded five genes for CAS prediction. RT-PCR of these genes showed HMGB1 was upregulated, and CCL3, CCL3L1, CCL4, and DUSP1 were downregulated in CAS versus controls. Then, we constructed and visualized the regulatory networks of 9 transcription factors (TFs), which significantly related to 5 diagnostic molecules. About 11 miRNAs, 19 lncRNAs, and 39 edges centered on four diagnostic molecules (CCL3, CCL4, DUSP1, and HMGB1) were constructed and displayed. Eleven potential drugs were identified, including ibrutinib, CTI-01, roflumilast etc. Conclusion: A set of five biomarkers were identified for the diagnosis of CAS and for the study of potential therapeutic targets., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Many evidences have confirmed that chromatin regulator factors (CRs) are involved in the progression of cancer, but its potential mechanism of affecting hepatitis B related hepatocellular carcinoma still needs to be studied. Our study detected the CRs that affect hepatitis B related hepatocellular carcinoma (HBV-HCC) through machine learning analysis, conducted the analysis of immune cells, constructed the relevant risk model and immune function infiltration, and predicted the potential therapeutic drugs. We found that these CRs were significantly related to the immune cells of Macrophages, B cells, CD8 + T cells, etc., and PBK, AURKA, TOP2A and AURKB were the potential risk CRs of HBV-HCC. The expression levels of these four CRs increased in HepG2.2.15 cells and the liver of HBV-HCC patients, consistent with the predicted risk model. Subsequently, ten potential drugs closely related to the risk CRs were finally obtained, experimental research on resveratrol has shown that it can inhibit the proliferation of HepG2.2.15 cells and potentially inhibit the occurrence and development of HBV-HCC. Our study provides novel insights into the function of CRs in HBV-HCC and certain ideas for more accurate targeted therapy.Communicated by Ramaswamy H. Sarma.

Arctium lappa L. is a common specie of Asteraceae. Its main active ingredient, Arctigenin (AG), in mature seeds exerts pharmacological effects on the Central Nervous System (CNS). To review studies on the specific effects of the AG mechanism on various CNS diseases and elucidate signal transduction mechanisms and their pharmacological actions. This investigation reviewed the essential role of AG in treating neurological disorders. Basic information on Arctium lappa L. was retrieved from the Pharmacopoeia of the People's Republic of China. The related articles from 1981 to 2022 on the network database (including CNKI, PubMed, and Wan Fang and so on) were reviewed using AG and CNS diseases-related terms such as Arctigenin and Epilepsy. It was confirmed that AG has a therapeutic effect on Alzheimer's disease, Glioma, infectious CNS diseases (such as Toxoplasma and Japanese Encephalitis Virus), Parkinson's disease, Epilepsy, etc. In these diseases, related experiments such as a Western blot analysis revealed that AG could alter the content of some key factors (such as the reduction of Aβ in Alzheimer's disease). However, in-vivo AG's metabolic process and possible metabolites are still undetermined. Based on this review, the existing pharmacological research has indeed made objective progress to elucidate how AG prevents and treats CNS diseases, especially senile degenerative disease such as Alzheimer's diseases. It was revealed that AG could be used as a potential nervous system drug as it has a wide range of effects in theory with markedly high application value, especially in the elder group. However, the existing studies are limited to in-vitro experiments; therefore, little is known about how AG metabolizes and functions in-vivo , limiting its clinical application and requiring further research. [Display omitted] • Arctigenin interferes in the proceedings of AD by reducing the synthesis of Aβ protein. • Arctigenin alleviates Multiple sclerosis by promoting AMPK /PPARγ pathway. • Metabolic process needs to be explored before Arctigenin was used as a potential drug. • Provides clinical references for some diseases and issues that need to be addressed. [ABSTRACT FROM AUTHOR]

The curiosity and attention that researchers have devoted to alkaloids are due to their bioactivities, structural diversity, and intriguing chemistry. Marine-derived macrocyclic alkaloids (MDMAs) are considered to be a potential source of drugs. Trabectedin, a tetrahydroisoquinoline derivative, has been approved for the treatment of metastatic soft tissue sarcoma and ovarian cancers. MDMAs displayed potent activities that enabled them to be used as anticancer, anti-invasion, antimalarial, antiplasmodial, and antimicrobial. This review presents the reported chemical structures, biological activities, and structure–activity relationships of macrocyclic alkaloids from marine organisms that have been published since their discovery until May 2020. This includes 204 compounds that are categorized under eight subclasses: pyrroles, quinolines, bis-quinolizidines, bis-1-oxaquinolizidines, 3-alkylpiperidines, manzamines, 3-alkyl pyridinium salts, and motuporamines.

Tumor microenvironment (TME) is closely correlated to the occurrence and progression of breast cancer, however its potentiality in assisting diagnosis and therapeutic decision remains unclear. Therefore, the major aim of this study is to explore the prognostic value of TME related gene in breast cancer. Expression matrices and clinical data of breast cancer obtained from public databases were divided into TME relevant clusters according to immune characterization. A 12-gene molecular classifier was generated through the utilization of differentially expressed genes identified between distinct Tumor Microenvironment (TME) clusters, coupled with correlative regression analysis. The performance of this TME-driven prognostic signature (TPS) were examined across both the training and validation cohorts. Furthermore, our study revealed that breast cancer cases classified as high-risk based on the TPS exhibited the phenotype with elevated immune cell infiltration, higher tumor mutational burden, and a notably worse overall prognostic outcome. To conclude, the novel TME-based TPS was able to serve as a superior prognosis indicator for breast cancer, alone or jointly with other clinical factors. Also, breast cancer patients belong to different risk subgroups of TPS were found potentially suitable for distinguished therapeutic agents, which might improve personalized treatment for breast cancer in the future., 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., (© 2023 The Authors. Published by Elsevier Ltd.)

Herein we report the synthesis of two new organic compounds, diisobutyl- and diisopentyl N,N′-methylene-(S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoate. A one-pot procedure was carried out by adding the reducing agent and carbonyl compound into the methanol solution of the parent compounds (iso-butyl and iso-pentyl esters of (S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoic acid) in appropriate stoichiometric ratios. The compounds were fully characterized by infrared, ESI-MS, 1D (1H, 13C) and 2D (COSY, HSQC, HMBC) NMR spectroscopy and elemental analysis. The spectral data confirm the presence of -CH2- group introduced between nitrogen atoms of the ethylenediamine moiety revealing neutral form of potential bidentate ligand. [Projekat Ministarstva nauke Republike Srbije, br. 172035. The authors also acknowledge the support of the FP7 RegPot project FCUB ERA GA No. 256716. The EC does not share responsibility for the content of the article]

As an essential nutrient, copper's redox properties are both beneficial and toxic to cells. Therefore, leveraging the characteristics of copper-dependent diseases or using copper toxicity to treat copper-sensitive diseases may offer new strategies for specific disease treatments. In particular, copper concentration is typically higher in cancer cells, making copper a critical limiting nutrient for cancer cell growth and proliferation. Hence, intervening in copper metabolism specific to cancer cells may become a potential tumor treatment strategy, directly impacting tumor growth and metastasis. In this review, we discuss the metabolism of copper in the body and summarize research progress on the role of copper in promoting tumor cell growth or inducing programmed cell death in tumor cells. Additionally, we elucidate the role of copper-related drugs in cancer treatment, intending to provide new perspectives for cancer treatment., 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 © 2023 Tang, Yan, Miao, Ha, Li, Yang and Mi.)

Background: Bone giant cell tumor (BGCT) is one of the world's major disease types of locally aggressive bone tumors. In recent years, denosumab treatment has been introduced before curettage surgery. However, the current therapeutic was practical only sometimes, given the local recurrence effects after discontinuation of denosumab. Due to the complex nature of BGCT, this study aims to use bioinformatics to identify potential genes and drugs associated with BGCT. Methods: The genes that integrate BGCT and fracture healing were determined by text mining. The gene was obtained from the pubmed2ensembl website. We filtered out common genes for the function, and signal pathway enrichment analyses were implemented. The protein-protein interaction (PPI) networks and the hub genes were screened by MCODE built-in Cytoscape software. Lastly, the confirmed genes were queried in the Drug Gene Interaction Database to determine potential genes and drugs. Results: Our study finally identified 123 common specific genes in bone giant cell tumors and fracture healing text mining concepts. The GO enrichment analysis finally analyzed 115 characteristic genes in BP, CC, and MF. We selected 10 KEGG pathways and identified 68 characteristic genes. We performed protein-protein interaction analysis (PPI) on 68 selected genes and finally identified seven central genes. In this study, these seven genes were substituted into drug-gene interactions, and there were 15 antineoplastic drugs, 1 anti-involving drug, and 1 anti-influenza drug. Conclusion: The 7 genes (including ANGPT2 , COL1A1 , COL1A2 , CTSK , FGFR1 , NTRK2 , and PDGFB ) and 17 drugs, which have not been used in BGCT, but 6 of them approved by the FDA for other diseases, could be potential genes and drugs, respectively, to improve BGCT treatment. In addition, the correlation study and analysis of potential drugs through genes provide great opportunities to promote the repositioning of drugs and the study of pharmacology in the pharmaceutical industry., 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 © 2023 Chen, Zhang, Hong, Xu, Sha and Ding.)

Candida auris is a serious health concern of the current world that possesses a serious global health threat and is emerging at a high rate. Available antifungal drugs are failing to combat this pathogen as they are growing resistant to those drugs and some strains have already shown resistance to all three available antifungal drugs in the market. Hence, finding alternative therapies is essential for saving lives from this enemy. To make the development of new treatments easier, we conducted some in silico study of this pathogen to discover possible targets for drug design and also recommended some possible metabolites to test in vivo circumstances. The complete proteome of the representative strain was retrieved, and the duplicate, non-essential, human homologous, non-metabolic, and druggable proteins were then eliminated. As a result, out of a total of 5441  C. auris proteins, we were able to isolate three proteins (XP 028890156.1, XP 028891672.1, and XP 028891858.1) that are crucial for the pathogen's survival as well as host-non-homolog, metabolic, and unrelated proteins to the human microbiome. Their subcellular locations and interactions with a large number of proteins (10 proteins) further point to them being good candidates for therapeutic targets. Following in silico docking of 29 putative antifungals of plant origin against the three proteins we chose, Caledonixanthone E, Viniferin, Glaucine, and Jatrorrhizine were discovered to be the most effective means of inhibiting those proteins since they displayed higher binding affinities (ranging from -28.97 kcal/mol to -51.99 kcal/mol) than the control fluconazole (which ranged between -28.84 kcal/mol and -41.15 kcal/mol). According to the results of MD simulations and MM-PBSA calculations, Viniferin and Caledonixanthone E are the most effective ligands for the proteins XP 028890156.1, XP 028891672.1, and XP 028891858.1. Furthermore, they were predicted to be safe and also showed proper ADME properties., 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., (© 2023 The Authors.)

The COVID-19 has led to a devastating global health crisis, which emphasizes the urgent need to deepen our understanding of the molecular mechanism and identifying potential antiviral drugs. Here, we comprehensively analyzed the transcriptomic and proteomic profiles of 178 COVID-19 patients, ranging from asymptomatic to critically ill. Our analyses found that the RNA binding proteins (RBPs) were likely to be perturbed in infection. Interactome analysis revealed that RBPs interact with virus proteins and the viral interacting RBPs were likely to locate in central regions of human protein-protein interaction network. Functional enrichment analysis revealed that the viral interacting RBPs were likely to be enriched in RNA transport, apoptosis and viral genome replication-related pathways. Based on network proximity analyses of 299 human complex-disease genes and COVID-19-related RBPs in the human interactome, we revealed the significant associations between complex diseases and COVID-19. Network analysis also implicated potential antiviral drugs for treatment of COVID-19. In summary, our integrative characterization of COVID-19 patients may thus help providing evidence regarding pathophysiology and potential therapeutic strategies for COVID-19., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Possible in vitro inhibition of aromatic amino acid decarboxylase (AAD, EC 4.1.1.28) by a group of phenylsulfonylbenzoic acid derivatives VÚFB 19363, 19369, 19370, 19371, and 19760 as new potential anti-inflammatory compounds was studied using the substrate L-tyrosine. Enzyme inhibition by 2.7x10–5 M concentration of compound VÚFB 19363 (Quinlukast) was 17 %, AAD inhibition at 3.75 x 10–5 M concentration of compounds VÚFB 19369, 19370, 19371, and 19760 ranged between 9–23 %. There were distinct differences between individual compounds. Evaluation of inhibition kinetics suggested full reversibility with VÚFB 19369 and the uncompetitive type of inhibition in the case of compound VÚFB 19363. Considering the anti-inflammatory activity of the compounds studied, the weak AAD inhibition found is rather favourable for their prospective pharmacological effect.