Endometrial cancer (EC) is a prevalent gynecological malignancy with a complex molecular landscape, contributing to significant global morbidity and mortality. Dysregulated signaling pathways such as PI3K/AKT/mTOR and RAS/RAF/MEK drive EC progression by promoting uncontrolled cell proliferation, survival, angiogenesis, and metastasis. Mutations in genes like PTEN and PIK3CA further underpin tumor aggressiveness. Molecular alterations in these pathways not only serve as biomarkers for prognosis but also guide the formulation of targeted therapies, such as mTOR inhibitors and anti-angiogenic agents. While such therapies show promise, optimizing their efficacy and minimizing adverse effects requires further research. A comprehensive approach integrating early detection (e.g., addressing postmenopausal bleeding), preventive strategies (e.g., managing obesity), increasing diagnostic sensitivity (e.g., transvaginal ultrasound) and advanced molecularly tailored treatments (e.g., AI & ML) is critical to reducing the burden of this disease. By targeting key signaling pathways, leveraging AI-driven methodologies, and addressing treatment resistance, we can enhance patient outcomes, also mitigate the rising global impact of EC.

Acute liver injury is caused by various reasons and results in abnormal liver function, serving as the basis for various liver diseases. However, there has not been much progress in research on the prevention and treatment of acute liver injury, and drugs directly or specifically used for acute liver injury are still lacking. Recent studies have shown that several types of cell death are closely associated with the onset, progression, and prognosis of liver injury. In this study, we identified a small molecule compound, GNF-5837, which attenuates the severity of acute liver injury by inhibiting apoptosis, pyroptosis, and ferroptosis. Mechanically, we found that GNF-5837 reduces the generation of reactive oxygen species (ROS) and alleviates oxidative stress by capturing excessive oxidative free radicals generated during cell death, which effectively inhibits apoptosis, pyroptosis, and ferroptosis. The results of animal experiments showed that GNF-5837 can effectively alleviate Con A-induced acute liver injury in vivo by blocking multiple modes of cell death. Therefore, our research indicates that the small molecule compound GNF-5837 is an oxygen radical scavenger with significant peroxide removal effects, which offer a potential therapeutic approach for cell death caused by imbalances in intracellular oxidative stress levels and provides new insights into the study of acute liver injury.

Garden pea (Pisum sativum L.), is a temperate crop belonging to the Leguminosae family. Early maturing pea varieties complete their growth cycle in ∼80-90 days and fits very well within the crop rotation of rice, wheat, and maize, thereby providing an extra source of income to the farmers. Identification of genes associated with the earliness is very important for developing early maturing pea varieties. In the present study we investigated the genetics of earliness and identified the putative genomic regions associated with the earliness in F2 population derived from a cross between early-maturing (Matar Ageta-10) and late-maturing (Punjab-89) pea varieties using BSA-Seq approach. Genetic analysis revealed that earliness follows a monogenic recessive inheritance pattern. Two extreme phenotypic pools were constructed by identifying ten extreme early and ten extreme late plants from the F2 population, and QTL-seq analysis was performed to obtain major genomic region of 6.5Mb located at 418.46Mb to 424.97Mb on chromosome 7 and has been designated as PsE7. Further, a total of 907 SNPs were identified within this 6.5Mb genomic region of which seven SNPs were validated through KASP markers. Among these, one marker namely PS423028253 showed association with the earliness trait at distance of 1.7cM. This novel genomic region along with KASP marker (PS423028253) identified in this study could be used for marker-assisted selection in pea breeding programs and will aid in the identification of the candidate genes in future studies.

Artificial insulin-producing cells (IPCs) used to treat diabetes mellitus type 1 (DMT1) are naturally hampered by their carcinogenicity. This in vitro study aimed to examine the carcinogenic potential of IPCs produced by the differentiation of human adipose tissue-derived mesenchymal stem cells (hADSCs). hADSCs were transformed into IPCs by administering insulin-transferrin, selenium (ITS), and nicotinamide in a 14-day differentiation protocol. The cells were transfected with 20 μg of pure Pdx1-pIRES recombinant vector on the tenth day of differentiation. The successful transfection was confirmed by Pdx1 overexpression and GFP fluorescence activity. The differentiated cells' capacity to release insulin and glucose-dependent C-peptide was used to evaluate their functionality. Gene expression was assessed using real-time PCR. Meanwhile, protein expression was investigated using western blotting. The transfected cells exhibited fluorescence activity and Pdx1 overexpression. The differentiated IPCs were able to secrete C-peptide and insulin. The artificial IPCs showed significantly reduced Oct4 and Nanog expression. However, the differentiation process induced a noticeable elevation in tPA expression. The artificial IPCs expressed much lower c-MYC expression compared to undifferentiated hADSCs. The differentiated cells exhibited a significant elevation inGlut2, MMP-2, CD24, P16, and P21 expression. The differentiation technique used in this work produced functional beta-like cells devoid of typical markers of stem cells. The synthetic IPCs displayed characteristics of newly generated β-like cells. The artificial IPCs showed no signs of expressing tumor-associated markers. The findings imply that the artificial IPC cells lack tumor characteristics in vitro.

Epsilon toxin, which is synthesized by Clostridium perfringens, is a type of pore-forming protein that is associated with the development of enterotoxemia in ruminants. As toxins are agents of bioterrorism, exposure to toxin aerosols causes endothelial cell damage and cytotoxicity in human lung cells. However, little information is available regarding the cytotoxicity and mechanisms associated with lung cancer cell lines. The aim of the present study was to explore the cytotoxic effects of epsilon toxin on the human lung cell line A549 and its involvement in the PI3K/AKT/mTOR signaling pathway to clarify the underlying molecular mechanism involved. A549 cells were treated with epsilon toxin, and cytotoxicity was assessed via MTT and LDH assays. Flow cytometry evaluated ROS levels, cell cycle arrest, and apoptosis, while Hoechst 33,258 staining confirmed apoptotic morphology. qRT‒PCR and Western blotting measured apoptosis-, autophagy-, and PI3K/AKT/mTOR-related markers. Epsilon toxin reduced cell viability and increased membrane leakage in a concentration-dependent manner, accompanied by ROS overproduction. It upregulated autophagy markers (beclin-1, LC3 II/I, p62) and suppressed PI3K/AKT/mTOR signaling. Cell cycle arrest at the sub-G1 phase and apoptosis were induced via p53 activation, Bax/Bcl-2 imbalance, and caspase-3 cleavage, as confirmed by annexin V/PI and Hoechst 33,258 staining. Epsilon toxin triggers cytotoxicity in A549 cells by activating apoptosis and autophagy through PI3K/AKT/mTOR pathway inhibition. These findings elucidate molecular mechanisms underlying epsilon toxin's action in lung cancer cells, highlighting its dual role in programmed cell death and potential therapeutic relevance.

NF2-related schwannomatosis (NF2) is a rare genetic disease that significantly impacts patients' quality of life due to the occurrence of multiple tumors within the nervous system. The high clinical heterogeneity in tumor number, location, and size makes predicting each patient's clinical outcome impossible. Genetic investigation can be crucial in diagnosis, prognosis, and management. This study aims to explore the genetic basis of eight Iranian patients with NF2. To investigate potential genetic causes, we conducted comprehensive medical evaluations, whole-exome sequencing (WES), and multiplex ligation-dependent probe amplification (MLPA) on the probands of each family. The identified variants in the family members were confirmed using Sanger sequencing and MLPA. The variants were classified according to the American College of Medical Genetics and Genomics guidelines. Seven distinct variants linked to the NF2 gene were identified as causes of NF2-related schwannomatosis in these patients, among which the c.862_863del frameshift was a novel variant not previously reported. Seventy-five percent of these mutations were de novo. The mean diagnostic age was lower among patients with truncating mutations compared to other patients. This study identified a novel mutation in the NF2 gene and showed a high rate of de novo mutations in Iranian NF2 patients. Moreover, patients with truncating mutations experienced earlier symptoms than others. Comparing the manifestations of each patient with similar mutations to previous reports expands our understanding of the phenotype of NF2. These results can provide more comprehensive insights into prognosis and early interventions.

Lon peptidase 1 (LONP1), a member of the AAA + family, is essential for maintaining mitochondrial function. Recent studies have revealed that LONP1 serves as a multifunctional enzyme, acting not only as a protease but also as a molecular chaperone, interacting with mitochondrial DNA (mtDNA), and playing roles in mitochondrial dynamics, oxidative stress, cellular respiration, and energy metabolism. LONP1 is evolutionarily highly conserved, and mutations or dysfunctions in LONP1 can lead to diseases. There is growing evidence linking LONP1 to various human diseases, such as tumors, neurodegenerative diseases, and heart diseases. This review discusses the discovery, molecular structure, subcellular localization, tissue distribution, and mitochondrial function of LONP1. Furthermore, it summarizes the associations between LONP1 and tumors, neurodegenerative diseases, and heart diseases, exploring its role in different diseases and potential molecular mechanisms. It also analyzes the regulatory effects of related inhibitors and agonists on LONP1. Considering the pleiotropic effects of LONP1, the study of LONP1 is crucial to understanding the relevant pathophysiological processes and developing strategies to modulate and control these related diseases.

Patients diagnosed with type 2 diabetes have an increased risk of developing cardiovascular complications. The researchers are currently working on understanding how to prevent these progressions from occurring. Since 2006, dipeptidyl-peptidase-4 inhibitors have been made available to patients as a relatively new treatment for diabetes. These substances inhibit the enzyme known as dipeptidyl peptidase-4 (DPP-4), which in turn increases the levels of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). This results in an increase in the effectiveness of insulin release after meals, which in turn has a positive impact on glycemic control. Regarding the safety of this category of medication in the treatment of cardiovascular disorders, there have been a great deal of debates. Emerging research suggests that DPP-4 inhibitors could be useful in the treatment of a variety of cardiovascular conditions, including coronary atherosclerosis, heart failure, and hypertension, among others. In order to investigate the possibility of using dipeptidyl-peptidase-4 inhibitors as a treatment option for cardiovascular disease, the molecular pathways that are thought to be responsible for their cardioprotective effect will be clarifies throughout the course of this review.