Monkeypox is a serious public health issue in tropical and subtropical areas. Antivirals that target monkeypox proteins might lead to more effective and efficient therapy. The F13 protein is essential for the growth and maturation of the monkeypox virus. F13 inhibition might be a viable therapeutic target for monkeypox. The in silico fragment-based drug discovery method for developing antivirals may provide novel therapeutic options. In this study, we generated 800 compounds based on tecovirimat, an FDA-approved drug that is efficacious at nanomolar quantities against monkeypox. These compounds were evaluated to identify the most promising fragments based on binding affinity and pharmacological characteristics. The top hits from the chemical screening were docked into the active site of the F13 protein. Molecular dynamics simulations were performed on the top two probable new candidates from molecular docking. The ligand–enzyme interaction analysis revealed that the C2 ligand had lower binding free energy than the standard ligand tecovirimat. Water bridges, among other interactions, were shown to stabilize the C2 molecule. Conformational transitions and secondary structure changes in F13 protein upon C2 binding show more native three-dimensional folding of the protein. Prediction of pharmacological properties revealed that compound C2 may be promising as a drug candidate for monkeypox fever. However, additional in vitro and in vivo testing is required for validation.

Malignant pleural mesothelioma (MPM) is a fatal disease of respiratory system. Despite the availability of invasive biomarkers with promising results, there are still significant diagnostic and therapeutic challenges in the treatment of MPM. One of three main mesothelioma cell types, epithelioid mesothelioma makes up approximately 70% of all mesothelioma cases. Different observational findings are under process, but the molecular heterogeneity and pathogenesis of epithelioid malignant pleural mesothelioma (eMPM) are still not well understood. Through molecular analysis, expression profiling data were used to determine the possibility and optimal number of eMPM molecular subtypes. Next, clinicopathological characteristics and different molecular pathways of each subtype were analyzed to prospect the clinical applications and advanced mechanisms of eMPM. In this study, we identified two distinct epithelioid malignant pleural mesothelioma subtypes with distinct gene expression patterns. Subtype I eMPMs were involved in steroid hormone biosynthesis, porphyrin and chlorophyll metabolism, and drug metabolism, while subtype II eMPMs were involved in rational metabolism, tyrosine metabolism, and chemical carcinogenesis pathways. Additionally, we identified potential subtype-specific therapeutic targets, including CCNE1, EPHA3, RNF43, ROS1, and RSPO2 for subtype I and CDKN2A and RET for subtype II. Considering the need for potent diagnostic and therapeutic biomarkers for eMPM, we are anticipating that our findings will help both in exploring underlying mechanisms in the development of eMPM and in designing targeted therapy for eMPM.

Long noncoding RNAs (lncRNAs) are pivotal regulators in the pathophysiology of diabetes mellitus and its complications, including diabetic retinopathy, nephropathy, and cardiomyopathy. They influence essential cellular processes such as angiogenesis, vascular smooth muscle cell behavior, inflammation, extracellular matrix remodeling, and apoptosis. In cardiomyopathy, lncRNA H19 promotes cardiomyocyte survival by regulating autophagy, highlighting its role in cardiovascular outcomes. In addition, lncRNAs hold promise as noninvasive biomarkers, detectable in extracellular fluids such as serum and urine, providing novel diagnostic tools. For example, elevated levels of HOX transcript antisense RNA and promoter of CDKN1A antisense DNA damage-activated RNA correlate with hyperglycemia and its complications, whereas maternally expressed gene 3 and metastasis-associated lung adenocarcinoma transcript 1 are linked to insulin resistance. However, the full scope of lncRNA mechanisms and therapeutic potential remains unclear. Recent research emphasizes the importance of studying the molecular pathways influenced by lncRNAs, such as the Janus kinase/signal transducer and activator of transcription and p38 mitogen-activated protein kinase pathways, which regulate inflammation and insulin signaling. Preclinical studies show promising outcomes for lncRNA-targeted therapies; however, challenges remain in precise detection and delivery. Addressing these gaps through advanced RNA sequencing and targeted therapies is crucial for developing lncRNA-based diagnostics and treatments for diabetes complications. This review explores lncRNAs as biomarkers and therapeutic targets, focusing on their regulatory mechanisms in diabetic complications such as retinopathy, nephropathy, and cardiomyopathy.

Clustered regularly interspaced short palindromic repeats (CRISPR) technology, a transformative tool for genetic modifications, gene therapy, and treating various genetic diseases, has recently garnered significant attention for its applications in reproductive biology. In this realm, researchers are focusing on addressing gynecological disorders, refining assisted reproductive methods, and conducting precise germ cell editing. The potential impact of CRISPR in these areas is monumental; however, several research gaps persist, demanding further investigation into the long-term effects, safety implications, and unintended consequences of its applications in reproductive biology. Refining the precision and specificity of CRISPR technology is a critical aspect that necessitates addressing challenges such as off-target effects and cytotoxicity. These considerations underscore the urgency for ongoing research efforts to ensure the efficacy and safety of CRISPR applications. In addition, the establishment of robust regulatory frameworks and oversight mechanisms specific to CRISPR in reproductive contexts is imperative to guarantee the responsible and ethical use of this powerful technology. This comprehensive review delves into the advantages of CRISPR over traditional gene editing methods, providing insights into its applications in embryos, pluripotent stem cells, and germline cells. It further explores the risks and limitations associated with CRISPR, including ethical concerns related to designer babies and eugenics. The article sheds light on the regulatory landscape governing new CRISPR applications in reproductive biology, emphasizing the continuous improvements in the efficiency and specificity of CRISPR technology. In contributing to the ongoing discourse, this review aims to inform and guide the responsible and effective application of CRISPR in the dynamic field of reproductive biology.

Sirtuin 1 (SIRT1) plays a complex role in cancer, significantly influencing cancer prognosis. However, its true impact remains unclear, necessitating a comprehensive and unified analysis. This study investigates the prognostic value of SIRT1 expression across different cancers worldwide. Relevant studies were retrieved from Google Scholar, PubMed, and Web of Science. Only human studies exploring the prognostic role of SIRT1 in various cancers were included in the study. Data on patient demographics, SIRT1 expression levels, and overall survival (OS) rates were extracted, followed by subsequent analyses, including meta-regression for heterogeneity and Egger’s regression for publication bias. A total of 15 studies (pooled hazard ratio = 1.483 ± 0.2974 [95% CI: 0.900 – 2.065]), predominantly from Asia (n = 10), were selected for the meta-analysis. The analysis demonstrated a robust and consistent association between elevated SIRT1 expression and poorer OS across diverse variables (P < 0.001), with minimal heterogeneity (I2 = 0.0001). Subgroup analyses confirmed significant effects of SIRT1 on OS rates based on regions (Asia: P < 0.001; non-Asia: P < 0.001), study size (small: P = 0.001, medium: P = 0.002, and large cohorts: P = 0.021), and specific cancer types (ovarian: P = 0.041, lung: P = 0.025, and gastric cancer: P = 0.025). However, no significant impact was observed in breast (P = 0.136) and colorectal cancers (P = 0.221). Overall, SIRT1 demonstrates consistent prognostic significance across various cancers and populations. However, the assessment of its long-term prognostic effects remains elusive, highlighting the need for further mechanistic research to guide targeted interventions and precision medicine in cancer therapy.

Combination therapy has emerged as a promising strategy due to its synergistic therapeutic pathways that enhance anticancer efficacy and limits the emergence of drug resistance. In this work, MIL-88B type multivariate (MTV-1) nanocarriers based on mixed linker (1, 4-benzenedicarboxylic acid and biphenyl-4,4'-dicarboxylic acid ) and metals (iron and cobalt) were synthesized. Presence of the distinct linkers modified the pore makeup of MTV-1 and facilitated the co-encapsulation of two anticancer drugs of varying molecular sizes; 5-Fluorouracil (5-FU) and Curcumin (CUR). The drug loading measurements on MTV-1@5-FU+CUR represented a loading capacity of 15.9wt% for 5-FU and 9.3wt% for CUR, respectively. They further exhibited a pH-responsive drug release pattern with higher concentrations of 5-FU and CUR released at pH 5.5 (simulating cancer microenvironment) compared to pH 7.4 (physiological environment). Moreover, we also demonstrated that MTV-1 MOFs, due to the presence of mixed valence metal ions, could perform peroxidase-like activity and catalyzes H2O2 decomposition to produce •OH radicals for chemodynamic therapy. Cell cytotoxicity assays exhibited significant inhibitory effects of MTV-1@5-Fu+CUR against HepG2 cells with an IC50 of 78.7 g/mL. Together with dual-drug loading, pH-responsive release, and chemodynamic therapy, MTV-1 show excellent potential for multifunctional anticancer treatment.