Potential Target Research Articles

Exploring the Potential Molecular Mechanism of the Shugan Jieyu Capsule in the Treatment of Depression through Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

Shugan Jieyu Capsule (SJC) is a pure Chinese medicine compound prepared with Hypericum perforatum and Acanthopanacis senticosi. SJC has been approved for the clinical treatment of depression, but the mechanism of action is still unclear. Network pharmacology, molecular docking, and molecular dynamics simulation (MDS) were applied in the present study to explore the potential mechanism of SJC in the treatment of depression. TCMSP, BATMAN-TCM, and HERB databases were used, and related literature was reviewed to screen the effective active ingredients of Hypericum perforatum and Acanthopanacis senticosi. TCMSP, BATMAN-TCM, HERB, and STITCH databases were used to predict the potential targets of effective active ingredients. GeneCards database, DisGeNET database, and GEO data set were used to obtain depression targets and clarify the intersection targets of SJC and depression. STRING database and Cytoscape software were used to build a protein-protein interaction (PPI) network of intersection targets and screen the core targets. The enrichment analysis on the intersection targets was conducted. Then the receiver operator characteristic (ROC) curve was constructed to verify the core targets. The pharmacokinetic characteristics of core active ingredients were predicted by SwissADME and pkCSM. Molecular docking was performed to verify the docking activity of the core active ingredients and core targets, and molecular dynamics simulations were performed to evaluate the accuracy of the docking complex. We obtained 15 active ingredients and 308 potential drug targets with quercetin, kaempferol, luteolin, and hyperforin as the core active ingredients. We obtained 3598 targets of depression and 193 intersection targets of SJC and depression. A total of 9 core targets (AKT1, TNF, IL6, IL1B, VEGFA, JUN, CASP3, MAPK3, PTGS2) were screened with Cytoscape 3.8.2 software. A total of 442 GO entries and 165 KEGG pathways (p <0.01) were obtained from the enrichment analysis of the intersection targets, mainly enriched in IL-17, TNF, and MAPK signaling pathways. The pharmacokinetic characteristics of the 4 core active ingredients indicated that they could play a role in SJC antidepressants with fewer side effects. Molecular docking showed that the 4 core active components could effectively bind to the 8 core targets (AKT1, TNF, IL6, IL1B, VEGFA, JUN, CASP3, MAPK3, PTGS2), which were related to depression by the ROC curve. MDS showed that the docking complex was stable. SJC may treat depression by using active ingredients such as quercetin, kaempferol, luteolin, and hyperforin to regulate targets such as PTGS2 and CASP3 and signaling pathways such as IL-17, TNF, and MAPK, and participate in immune inflammation, oxidative stress, apoptosis, neurogenesis, etc.

Prediction of molecular targets for antidepressant potential of hydroalcoholic extract of Tamarindus indica using network pharmacology approach and evaluating its efficacy in Chronic Unpredictable Mild Stress model in mice.

The prevalence of psychological disorders has surged since the 1990s, posing a significant global health burden with depressed individuals averaging six lost hours per week and contributing to over 20% of all missed workdays. Current antidepressants, while effective for some, have limited efficacy, dietary restrictions, and adverse effects, including liver damage and hypertension. Natural remedies offer promising therapeutic potential with minimal side effects. Tamarindus indica (TI) is a plant that grows in the shape of a tree. Network pharmacology of TI revealed the key targets MAPK, D1-6, 5HT, DAT, MAO, COMT, PKA, PKC, AKT, and VMAT, which are linked to prominent key pathways such as dopaminergic and serotonergic. The cell viability assays on SH-Sy5y cells indicated a favourable safety profile with an IC50 of 573.99µg/ml and further, the in vivo efficacy was observed through Chronic Unpredictable Mild Stress (CUMS) model in mice. The hydroalcoholic extract of TI demonstrated antidepressant effects, significantly reducing immobility time in the Tail Suspension Test (TST) and Forced Swim Test (FST). Additionally, locomotor activity, assessed via the Open Field Test (OFT), was significantly increased in the treatment group compared to CUMS mice. Biochemical analyses revealed elevated Brain Derived Neurotropic Factor (BDNF), decreased cortisol levels, and reduced catechol-O-methyltransferase (COMT) concentration in TI-treated (50mg/kg) groups. These findings underscore the potential of TI as a natural antidepressant, offering a promising avenue for further therapeutic development in depression management. The current study did not evaluate the level of neurotransmitters in the brain, which will be evaluated in future studies.

Differential miRNA Profiling Reveals miR-4433a-5p as a Key Regulator of Chronic Obstructive Pulmonary Disease Progression via PIK3R2- mediated Phenotypic Modulation.

In this study, a high-throughput sequencing technology was used to screen the differentially expressed miRNA in the patients with "fast" and "slow" progression of chronic obstructive pulmonary disease (COPD). Moreover, the possible mechanism affecting the progression of COPD was preliminarily analyzed based on the target genes of candidate miRNAs. The "fast" progressive COPD group included 6 cases, "slow" and Normal progressive COPD groups included 5 cases each, and COPD group included 3 cases. The peripheral blood samples were taken from the participants, followed by total RNA extraction and high throughput miRNA sequencing. The differentially expressed miRNAs among the progressive COPD groups were identified using bioinformatics analysis. Then, the candidate miRNAs were externally verified. In addition, the target gene of this miRNA was identified, and its effects on cell activity, cell cycle, apoptosis, and other biological phenotypes of COPD were analyzed. Compared to the Normal group, a total of 35, 16, and 7 differentially expressed miRNAs were identified in the "fast" progressive COPD, "slow" progressive COPD group, and COPD group, respectively. The results were further confirmed using dual-luciferase reporter assay and transfection tests with phosphoinositide- 3-kinase, regulatory subunit 2 (PIK3R2) as a target gene of miR-4433a-5p; the result showed a negative regulatory correlation between the miRNA and its target gene. The phenotype detection showed that the activation of the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway might participate in the progression of COPD by promoting the proliferation of inflammatory A549 cells and inhibiting cellular apoptosis. MiR-4433a-5p can be used as a marker and potential therapeutic target for the progression of COPD. As a target gene of miR-4433a-5p, PIK3R2 can affect the progression of COPD by regulating phenotypes, such as cellular proliferation and apoptosis.

Effect of HPV Oncoprotein on Carbohydrate and Lipid Metabolism in Tumor Cells.

High-risk HPV infection accounts for 99.7% of cervical cancer, over 90% of anal cancer, 50% of head and neck cancers, 40% of vulvar cancer, and some cases of vaginal and penile cancer, contributing to approximately 5% of cancers worldwide. The development of cancer is a complex, multi-step process characterized by dysregulation of signaling pathways and alterations in metabolic pathways. Extensive research has demonstrated that metabolic reprogramming plays a key role in the progression of various cancers, such as cervical, head and neck, bladder, and prostate cancers, providing the material and energy foundation for rapid proliferation and migration of cancer cells. Metabolic reprogramming of tumor cells allows for the rapid generation of ATP, aiding in meeting the high energy demands of HPV-related cancer cell proliferation. The interaction between Human Papillomavirus (HPV) and its associated cancers has become a recent focus of investigation. The impact of HPV on cellular metabolism has emerged as an emerging research topic. A significant body of research has shown that HPV influences relevant metabolic signaling pathways, leading to cellular metabolic alterations. Exploring the underlying mechanisms may facilitate the discovery of biomarkers for diagnosis and treatment of HPV-associated diseases. In this review, we introduced the molecular structure of HPV and its replication process, discussed the diseases associated with HPV infection, described the energy metabolism of normal cells, highlighted the metabolic features of tumor cells, and provided an overview of recent advances in potential therapeutic targets that act on cellular metabolism. We discussed the potential mechanisms underlying these changes. This article aims to elucidate the role of Human Papillomavirus (HPV) in reshaping cellular metabolism and the application of metabolic changes in the research of related diseases. Targeting cancer metabolism may serve as an effective strategy to support traditional cancer treatments, as metabolic reprogramming is crucial for malignant transformation in cancer.

Targeting the Main Sources of Reactive Oxygen Species Production: Possible Therapeutic Implications in Chronic Pain.

Humans have long been combating chronic pain. In clinical practice, opioids are firstchoice analgesics, but long-term use of these drugs can lead to serious adverse reactions. Finding new, safe and effective pain relievers that are useful treatments for chronic pain is an urgent medical need. Based on accumulating evidence from numerous studies, excess reactive oxygen species (ROS) contribute to the development and maintenance of chronic pain. Some antioxidants are potentially beneficial analgesics in the clinic, but ROS-dependent pathways are completely inhibited only by scavenging ROS directly targeting cellular or subcellular sites. Unfortunately, current antioxidant treatments do not achieve this effect. Furthermore, some antioxidants interfere with physiological redox signaling pathways and fail to reverse oxidative damage. Therefore, the key upstream processes and mechanisms of ROS production that lead to chronic pain in vivo must be identified to discover potential therapeutic targets related to the pathways that control ROS production in vivo. In this review, we summarize the sites and pathways involved in analgesia based on the three main mechanisms by which ROS are generated in vivo, discuss the preclinical evidence for the therapeutic potential of targeting these pathways in chronic pain, note the shortcomings of current research and highlight possible future research directions to provide new targets and evidence for the development of clinical analgesics.

Non-oxidative modified low-density lipoproteins: The underappreciated risk factors for atherosclerosis.

Atherosclerosis, the pathological basis of most cardiovascular diseases, is a main risk factor causing about 20 million deaths each year worldwide. Oxidized low-density lipoprotein is recognized as the most important and independent risk factor in initiating and promoting atherosclerosis. Numerous antioxidants are extensively used in clinical practice, but they have no significant effect on reducing the morbidity and mortality of cardiovascular diseases. This finding suggests that researchers should pay more attention to the important role of non-oxidative modified low-density lipoprotein in atherosclerosis with a focus on oxidized low-density lipoprotein. This review briefly summarizes several important non-oxidative modified low-density lipoproteins associated with atherosclerosis, introduces the pathways through which these non-oxidative modified low-density lipoproteins induce the development of atherosclerosis in vivo, and discusses the mechanism of atherogenesis induced by these non-oxidative modified low-density lipoproteins. New therapeutic strategies and potential drug targets are provided for the prevention and treatment of atherosclerotic cardiovascular diseases.

Tectorigenin Inhibits Glycolysis-induced Cell Growth and Proliferation by Modulating LncRNA CCAT2/miR-145 Pathway in Colorectal Cancer.

Colorectal cancer (CRC) places a heavy burden on global health. Tectorigenin (Tec) is a type of flavonoid-based compound obtained from the Chinese medical herb Leopard Lily Rhizome. It was found to exhibit remarkable anti-tumor properties in previous studies. However, the effect and molecular mechanisms of Tec in colorectal cancer have not been reported. The objective of this study was to explore the action of Tec in proliferation and glycolysis in CRC and the potential mechanism with regard to the long non-coding RNA (lncRNA) CCAT2/micro RNA-145(miR-145) pathway in vitro and in vivo . The anti-tumor effect of Tec in CRC was examined in cell and animal studies, applying Cell Counting Kit-8 (CCK-8) assay as well as xenograft model experiments. Assay kits were utilized to detect glucose consumption and lactate production in the supernatant of cells and animal serum. The expression of the glycolysis-related proteins was assessed by Western Blotting, and levels of lncRNA CCAT2 and miR-145 in CRC tissue specimens and cells were assessed by realtime quantitative PCR (RT-qPCR). Tec significantly suppressed cell glycolysis and proliferative rate in CRC cells. It could decrease lncRNA CCAT2 in CRC cells but increase the expression of miR-145. LncRNA CCAT2 overexpression or inhibition of miR-145 could abolish the inhibitive effects of Tec on the proliferation and glycolysis of CRC cells. The miR-145 mimic rescued the increased cell viability and glycolysis levels caused by lncRNA CCAT2 overexpression. Tec significantly inhibited the growth and glycolysis of CRC xenograft tumor. The expression of lncRNA CCAT2 decreased while the expression of miR-145 increased after Tec treatment in vivo. Tec can inhibit the proliferation and glycolysis of CRC cells through the lncRNA CCAT2/miR-145 axis. Altogether, the potential targets discovered in this research are of great significance for CRC treatment and new drug development.

PPT1 Promotes Growth and Inhibits Ferroptosis of Oral Squamous Cell Carcinoma Cells.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers with poor prognosis in the head and neck. Elucidating molecular mechanisms underlying OSCC occurrence and development is important for the therapy. Dysregulated palmitoylation-related enzymes have been reported in several cancers but OSCC. To explore the role of palmitoyl-protein thioesterase 1 (PPT1) in OSCC. Differentially expressed genes (DEGs) and related protein-protein interaction networks between normal oral epithelial and OSCC tissues were screened and constructed via different online databases. Tumor samples from 70 OSCC patients were evaluated for the relationship between PPT1 expression level and patients'clinic characteristics. The role of PPT1 in OSCC proliferation and metastasis was studied by functional experiments including MTT, colony formation, EdU incorporation and transwell assays. Lentivirus-based constructs were used to manipulate gene expression. FerroOrange probe and malondialdehyde assay were used to determine ferroptosis. Growth of OSCC cells in vivo was investigated by a xenograft mouse model. A total of 555 DEGs were obtained, and topological analysis revealed that PPT1 and GPX4 might play critical roles in OSCC. Increased PPT1 expression was found to be correlated with poor prognosis of OSCC patients. PPT1 effectively promoted the proliferation, migration and invasion while inhibited the ferroptosis of OSCC cells. PPT1 affected the expression of glutathione peroxidase 4 (GPX4). PPT1 promoted growth and inhibited ferroptosis of OSCC cells. PPT1 might be a potential target for OSCC therapy.

SPHK1 promotes bladder cancer metastasis via PD-L2/c-Src/FAK signaling cascade

SPHK1 (sphingosine kinase type 1) is characterized as a rate-limiting enzyme in sphingolipid metabolism to phosphorylate sphingosine into sphingosine-1-phosphate (S1P) that can bind to S1P receptors (S1PRs) to initiate several signal transductions leading to cell proliferation and survival of normal cell. Many studies have indicated that SPHK1 is involved in several types of cancer development, however, a little is known in bladder cancer. The TCGA database analysis was utilized for analyzing the clinical relevance of SPHK1 in bladder cancer. Through CRISPR/Cas9 knockout (KO) and constitutive activation (CA) strategies on SPHK1 in the bladder cancer cells, we demonstrated the potential downstream target could be programmed cell death 1 ligand 2 (PD-L2). On the other hand, we demonstrated that FDA-approved SPHK1 inhibitor Gilenya® (FTY720) can successfully suppress bladder cancer metastasis by in vitro and in vivo approaches. This finding indicated that SPHK1 as a potent therapeutic target for metastatic bladder cancer by dissecting the mechanism of action, SPHK1/S1P-elicited Akt/β-catenin activation promoted the induction of PD-L2 that is a downstream effector in facilitating bladder cancer invasion and migration. Notably, PD-L2 interacted with c-Src that further activates FAK. Here, we unveil the clinical relevance of SPHK1 in bladder cancer progression and the driver role in bladder cancer metastasis. Moreover, we demonstrated the inhibitory effect of FDA-approved SPHK1 inhibitor FTY720 on bladder cancer metastasis from both in vitro and in vivo models.

The up-regulation of SYNCRIP promotes the proliferation and tumorigenesis via DNMT3A/p16 in colorectal cancer

Heterogeneous nuclear ribonucleoproteins (hnRNPs), a group of proteins that control gene expression, have been implicated in many post-transcriptional processes. SYNCRIP (also known as hnRNP Q), a subtype of hnRNPs, has been reported to be involved in mRNA splicing and translation. In addition, the deregulation of SYNCRIP was found in colorectal cancer (CRC). However, the role of SYNCRIP in regulating CRC growth remains largely unknown. Here, we found that SYNCRIP was highly expressed in colorectal cancer by analyzing TCGA and GEPIA database. Furthermore, we confirmed the expression of SYNCRIP expression in CRC tumor and CRC cell lines. Functionally, SYNCRIP depletion using shRNA in CRC cell lines (SW480 and HCT 116) resulted in increased caspase3/7 activity and decreased cell proliferation, as well as migration. Meanwhile, overexpression of SYNCRIP showed opposite results. Mechanistically, SYNCRIP regulated the expression of DNA methyltransferases (DNMT) 3A, but not DNMT1 or DNMT3B, which affected the expression of tumor suppressor, p16. More importantly, our in vivo experiments showed that SYNCRIP depletion significantly inhibited colorectal tumor growth. Taken all together, our results suggest SYNCRIP as a potent therapeutic target in colorectal cancer.

Protective role of TRPM7 knockdown in ulcerative colitis via blocking NLRP3 inflammasome-mediated pyroptosis

Transient receptor potential melastatin 7 (TRPM7) has been emerged as a potent drug target for immunomodulation with ion conductance and kinase activities. The research is projected to characterize the influences of TRPM7 on the course of ulcerative colitis (UC) and dissect the latent response mechanisms. The in vivo murine model and in vitro cell model of UC were both stimulated by DSS. RT-qPCR and western blotting tested the abundance of TRPM7. Colonic damage was estimated by Hematoxylin-eosin staining, calculation of colon length, measurement of DAI and MPO assay kit. CCK-8 method and TUNEL staining severally ascertained cell activity and apoptosis. ELISA method assayed the inflammatory levels and relevant assay kits determined oxidative stress levels. FITC-dextran flux, immunohistochemistry, TEER as well as western blotting evaluated intestinal barrier function. Immunofluorescence staining and western blotting appraised NLR family pyrin domain containing 3 (NLRP3)-dependent pyroptosis. Depleted TRPM7 retarded inflammation, oxidative damage as well as intestinal barrier damage both in vitro and in vivo. TRPM7 reduction repressed the pyroptosis mediated by NLRP3 inflammasome. NLRP3 agonist nigericin partly abolished the protection elicited by TRPM7 silencing against inflammation, oxidative damage as well as intestinal barrier damage in vitro. Collectively, TRPM7 deletion might possess the therapeutic potential in UC, the working mechanism of which might involve the inactivation of NLRP3-dependent pyroptosis.

PFKFB3 deprivation attenuates the cisplatin resistance via blocking its autophagic elimination in colorectal cancer cells.

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3) is highly expressed in several cancers and plays important roles during the whole pathological process of cancer. It is also involved in chemoresistance, while the intrinsic mechanism needs to be further revealed. The different responses to cisplatin (DDP) between wild type (WT) and DDP-resistant (DDR) colorectal cancer (CRC) cells were analyzed by several assays. Coumarin conjugated DDP (CP-DDP) was utilized to trace the distribution of DDP. Pharmacological and genetic methods were used to deprive autophagy and PFKFB3, and the effects were investigated. The mouse xenograft model was performed to confirm the effect of the PFKFB3 inhibitor on reversing DDP resistance. DDR cells showed a lower capacity for apoptosis upon DDP treatment, but exhibited higher levels of autophagy and PFKFB3. CP-DDP partly co-localized with LC3, and its content lessened faster in DDR cells. Deprivation of both autophagy and PFKFB3 attenuated CP-DDP elimination, and reversed the DDP resistance. Moreover, PFKFB3 inhibition reduced DDP-induced autophagy. PFKFB3 inhibitor in combination with DDP led to a remarkable reduction in tumor growth in vivo. Inhibition of PFKFB3 reduced the autophagy induced by DDP, and therefore extended the retention time of CP-DDP. Meanwhile, PFKFB3 deprivation reversed the DDP resistance and made it a potent therapeutic target for CRC.

Effect and Mechanisms of Huangqi-Shanzhuyu in the Treatment of Diabetic Nephropathy based on Network Pharmacology and In Vitro Experiments.

Huangqi-Shanzhuyu (HS), a classic combination of Chinese herbal formulae, has been widely used for the treatment of diabetic nephropathy (DN). However, its pharmacological mechanism of action is still unclear. The active ingredients of HS and their potential targets were identified through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the DN-related targets were determined from GeneCards, Online Mendelian Inheritance in Man (OMIM), PharmGkb, and Therapeutic Target Database (TTD). The Cytoscape software was used to construct a herb-disease-target network and screen core genes. STRING was employed to generate a protein-protein interaction (PPI) network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the mechanism of action of HS in DN. Animal experiments and molecular docking were used to verify the potential mechanism. In total, 40 active ingredients and 180 effective targets of HS in DN were identified and 1115 DN-related targets were retrieved. From the PPI network, VEGFA, AKT1, IL6, IL1B, TP53, MMP9, PTGS2, CASP3, EGF and EGFR were identified as core genes. The anti-DN mechanism mainly involved multiple signaling pathways such as AGEs-RAGE. Animal experiments and molecular docking analysis confirmed that HS downregulated the expression of IL-1 and IL-6 via kaempferol-mediated inhibition of JNK1 phosphorylation. HS exhibits a therapeutic effect in DN through its multiple ingredients that act on several targets and multiple signaling pathways, including AGEs-RAGE.

A Review on Synthetic Thiazole Derivatives as an Antimalarial Agent.

Thiazole is a widely studied core structure in heterocyclic chemistry and has proven to be a valuable scaffold in medicinal chemistry. The presence of thiazole in both naturally occurring and synthetic pharmacologically active compounds demonstrates the adaptability of these derivatives. The current study attempted to review and compile the contributions of numerous researchers over the last 20 years to the medicinal importance of these scaffolds, with a primary focus on antimalarial activity. The review is based on an extensive search of PubMed, Google Scholar, Elsevier, and other renowned journal sites for a thorough literature survey involving various research and review articles. A comprehensive review of the antimalarial activity of the thiazole scaffold revealed potential therapeutic targets in Plasmodium species. Furthermore, the correlation of structure-activity-relationship (SAR) studies from various articles suggests that the thiazole ring has therapeutic potential. This article intends to point researchers in the right direction for developing potential thiazole-based compounds as antimalarial agents in the future.

Role of Cav2.3 (R-type) Calcium Channel in Pain and Analgesia: A Scoping Review.

Voltage-gated calcium channels (VGCCs) play an important role in pain development and maintenance. As Cav2.2 and Cav3.2 channels have been identified as potential drug targets for analgesics, the participation of Cav2.3 (that gives rise to R-type calcium currents) in pain and analgesia remains incompletely understood. Identify the participation of Cav2.3 in pain and analgesia. To map research in this area as well as to identify any existing gaps in knowledge on the potential role of Cav2.3 in pain signalling, we conducted this scoping review. We searched PubMed and SCOPUS databases, and 40 articles were included in this study. Besides, we organized the studies into 5 types of categories within the broader context of the role of Cav2.3 in pain and analgesia. Some studies revealed the expression of Cav2.3 in pain pathways, especially in nociceptive neurons at the sensory ganglia. Other studies demonstrated that Cav2.3-mediated currents could be inhibited by analgesic/antinociceptive drugs either indirectly or directly. Some articles indicated that Cav2.3 modulates nociceptive transmission, especially at the pre-synaptic level at spinal sites. There are studies using different rodent pain models and approaches to reduce Cav2.3 activity or expression and mostly demonstrated a pro-nociceptive role of Cav2.3, despite some contradictory findings and deficiencies in the description of study design quality. There are three studies that reported the association of single-nucleotide polymorphisms in the Cav2.3 gene (CACNA1E) with postoperative pain and opioid consumption as well as with the prevalence of migraine in patients. Cav2.3 is a target for some analgesic drugs and has a pro-nociceptive role in pain.

Gene expression analysis of microRNA-1285 in the South Indian oral squamous cell carcinoma population.

Oral squamous cell carcinoma (OSCC) is the most common oral malignant tumor, which has poor prognosis. The traditional investigative modality is invasive biopsy which is the gold standard for diagnosis. In recent years, alternative methods like non-invasive biomarkers have been studied for their potential role in early diagnosis and prognosis. Among them, microRNAs (miRNAs or miRs) are short non-coding RNAs that regulate gene expression in various diseases, including OSCC. Several miRNAs are being researched as non-invasive biomarkers as well as novel therapeutic targets in the treatment of OSCC. MiR expression can be upregulated or downregulated in OSCC. Among the reported miRNAs, miR-1285 is an important miRNA found to be involved in OSCC. The aim of the current study was to quantify the levels of miR-1285 in OSCC samples and to validate their potential role as biomarkers for OSCC detection. Sixteen samples of cancer tissue and normal tissue were evaluated from a total of 25 patients, in the study, conducted in the Department of Oral and Maxillofacial Surgery. The tissues were processed for H&E staining and gene expression analysis of miR-1285. The samples were collected after proper informed consent from the patients. Total RNA isolated was reverse transcribed into cDNA which was used in the gene expression analysis using qRT-PCR. The histopathological examination confirmed the OSCC cases and the gene expression analysis revealed that miR-1285 was significantly downregulated in OSCC tissues. Since miR-1285 showed significant difference between the OSCC and normal tissues it could be postulated as a potential biomarker and therapeutic target for OSCC. Further in-vitro and in-vivo studies could validate their functional role in OSCC.

In silico Identification of MHC Displayed Tumor Associated Peptides in Ovarian Cancer for Multi-Epitope Vaccine Construct.

Recognizing the potential of the immune system, immunotherapies have brought about a revolution in the treatment of cancer. Low tumour mutational burden and strong immunosuppression in the peritoneal tumor microenvironment (TME) lead to poor outcomes of immune checkpoint inhibition (ICI) and CART cell therapy in ovarian cancer. Alternative immunotherapeutic strategies are of utmost importance to achieve sound clinical success. The development of peptide vaccines based on tumor-associated antigens (TAAs) for ovarian cancer cells can be a potential target to provoke an anti-tumor immune response and subsequent clearance of tumour cells. The purpose of this in silico study was to find potential epitopes for a multi-epitope vaccine construct using the immunopeptidomics landscape of ovarian carcinoma. The four TAAs (MUC16, IDO1, FOLR1, and DDX5) were selected for potential epitopes prediction. The epitopes for B-cells, helper T-lymphocytes (HTL), and Cytotoxic Tlymphocytes (CTL) were predicted on the basis of antigenic, allergenic, and toxic properties. These epitopes were combined with suitable linkers and an adjuvant to form a multi-epitope construct. Four HTLs, 13 CTLs, and 6 potential B-cell epitopes were selected from the predicted epitope. The designed multi-epitope construct was potentially immunogenic, non-toxic, and non-allergenic. Physicochemical properties and higher-order structural analyses of the final construct revealed a potential vaccine candidate. The designed vaccine construct has the potential to trigger both humoral and cellular immune responses and may be employed as a therapeutic immunization candidate for ovarian malignancies. However, further in vitro and animal experimentation is required to establish the efficacy of the vaccine candidate.

Flexibility predicts chronic anxiety and depression during the first year of the COVID-19 pandemic-A longitudinal investigation of mental health trajectories.

The COVID-19 pandemic is a significant stressor, potentially putting the well-being of the general population at risk. However, a significant proportion of the population exhibits resilience, raising questions regarding psychological constructs that could contribute to resilient coping. Studies indicate that flexibility, defined as the ability to adapt to changing contextual demands by employing various emotional, cognitive, and behavioral strategies, may significantly contribute to coping with long-term stressors such as COVID-19. Cognitive and coping flexibility domains and longitudinal trajectories of anxiety and depression were assessed at three-time points across 13 months in 571 Israelis. Analyses revealed four different trajectories for anxiety: resilient (66%), chronic (22%), emerging (7%), and improving (6%), and two trajectories for depression: resilient (87%) and chronic (13%). Individuals in the chronic trajectory group (for both anxiety and depression) exhibited lower cognitive flexibility and coping flexibility levels than individuals in the resilient trajectory group. Across time, anxiety and depression were linked to clinically significant posttraumatic stress disorder-like symptoms. Low cognitive and coping flexibility are linked to the probability of experiencing chronic mental health problems, making them a potential target for prevention and treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Research Progress on Anti-angiogenesis Drugs in Hepatocellular Carcinoma

Primary liver cancer is the sixth most prevalent cancer worldwide and ranked in third for cancer-related mortality rate. Hepatocellular carcinoma (HCC) accounts for about 90% of all primary liver cancers. High vascularization of HCC implies the significance of angiogenesis in the development and pathogenesis of HCC. Several angiogenic pathways have been identified as being dysregulated in HCC, highlighting potential therapeutic targets for the treatment of HCC. In 2007, sorafenib was approved as the standard first-line treatment for advanced HCC, catapulting the therapeutic approach of HCC into the avenue of targeted therapy. In recent years, the approval of several novel targeted drugs and the progress in combination of immunotherapy and targeted therapies provide more alternatives for the treatment of HCC. The progress of anti-angiogenesis therapies in HCC over the past few decades is reviewed and the future prospect of anti-angiogenesis therapy for HCC is also discussed.

Designing with building-integrated photovoltaics (BIPV): A pathway to decarbonize residential buildings

The ambitious targets set for greenhouse gas emissions and energy efficiency by 2050 demand a critical increase of building renovation rates. This challenge is shared by most Western nations, including Europe and Switzerland, where the current annual renovation rate stands at a mere 0.6 %. In this context, designing renovation strategies using building integrated photovoltaic (BIPV) components as a new building material is one of the most promising ways to achieve decarbonization of the building stock in an economical and environmentally efficient manner. To this end, building design teams are key, especially in promoting BIPV-based projects to their clients and taking this approach into account from the initial design phase where pivotal decisions with significant impact are made. This article illustrates the potential impact of specific choices in renovation processes on the overall building performance, considering a Life-Cycle Analysis/Cost (LCA/LCC) and multi-criteria analysis. It uses a 1970's residential building as case study, examining different refurbishment scenarios. Findings reveal that scenarios integrating BIPV can significantly enhance energy savings, achieving up to 122 % in energy efficiency gains, and can meet the 2050 targets for cumulative energy demand (CED) and global warming potential (GWP). Additionally, the most effective BIPV scenarios demonstrate economic viability with a payback period of 14–18 years and internal rates of return (IRR) between 5.3 % and 5.9 %. These results underscore the economic and environmental benefits of BIPV in building renovations and advocate for its broader adoption to achieve national and international climate goals.