CircRNA Regulation of T Cells in Cancer: Unraveling Potential Targets.

T lymphocytes play a critical role in antitumor immunity, but their exhaustion poses a significant challenge for immune evasion by malignant cells. Circular RNAs (circRNAs), characterized by their covalently closed looped structure, have emerged as pivotal regulators within the neoplastic landscape. Recent studies have highlighted their multifaceted roles in cellular processes, including gene expression modulation and protein function regulation, which are often disrupted in cancer. In this review, we systematically explore the intricate interplay between circRNAs and T cell modulation within the tumor microenvironment. By dissecting the regulatory mechanisms through which circRNAs impact T cell exhaustion, we aim to uncover pathways crucial for immune evasion and T cell dysfunction. These insights can inform innovative immunotherapeutic strategies targeting circRNA-mediated molecular pathways. Additionally, we discuss the translational potential of circRNAs as biomarkers for therapeutic response prediction and as intervention targets. Our comprehensive analysis aims to enhance the understanding of immune evasion dynamics in the tumor microenvironment by facilitating the development of precision immunotherapy.

LncRNAs in Kawasaki disease and Henoch-Schönlein purpura: mechanisms and clinical applications.

Kawasaki disease (KD) and Henoch-Schönlein purpura (HSP) are the two most predominant types of childhood vasculitis. In childhood vasculitis, factors such as lack of sensitive diagnostic indicators and adverse effects of drug therapy may cause multiorgan system involvement and complications and even death. Many studies suggest that long noncoding RNAs (lncRNAs) are involved in the mechanism of vasculitis development in children and can be used to diagnose or predict prognosis by lncRNAs. In existing drug therapies, lncRNAs are also involved in drug-mediated treatment mechanisms and are expected to improve drug toxicity. The aim of this review is to summarize the link between lncRNAs and the pathogenesis of KD and HSP. In addition, we review the potential applications of lncRNAs in multiple dimensions, such as diagnosis, treatment, and prognosis prediction. This review highlights that targeting lncRNAs may be a novel therapeutic strategy to improve and treat KD and HSP.

Dietary regulation of intestinal stem cells in health and disease.

Diet is a critical regulator for physiological metabolism and tissue homeostasis, with a close relation to health and disease. As an important organ for digestion and absorption, the intestine comes into direct contact with many dietary components. The rapid renewal of its mucosal epithelium depends on the continuous proliferation and differentiation of intestinal stem cells (ISCs). The function and metabolism of ISCs can be controlled by a variety of dietary patterns including calorie restriction, fasting, high-fat, ketogenic, and high-sugar diets, as well as different nutrients including vitamins, amino acids, dietary fibre, and probiotics. Therefore, dietary interventions targeting ISCs may make it possible to prevent and treat intestinal disorders such as colon cancer, inflammatory bowel disease, and radiation enteritis. This review summarised recent research on the role and mechanism of diet in regulating ISCs, and discussed the potential of dietary modulation for intestinal diseases.

Autoimmune CD8+ T cells in type 1 diabetes: from single-cell RNA sequencing to T-cell receptor redirection.

Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by pancreatic ß cell destruction and mediated primarily by autoreactive CD8+ T cells. It has been shown that only a small number of stem cell-like ß cell-specific CD8+ T cells are needed to convert normal mice into T1D mice; thus, it is likely that T1D can be cured or significantly improved by modulating or altering self-reactive CD8+ T cells. However, stem cell-type, effector and exhausted CD8+ T cells play intricate and important roles in T1D. The highly diverse T-cell receptors (TCRs) also make precise and stable targeted therapy more difficult. Therefore, this review will investigate the mechanisms of autoimmune CD8+ T cells and TCRs in T1D, as well as the related single-cell RNA sequencing (ScRNA-Seq), CRISPR/Cas9, chimeric antigen receptor T-cell (CAR-T) and T-cell receptor-gene engineered T cells (TCR-T), for a detailed and clear overview. This review highlights that targeting CD8+ T cells and their TCRs may be a potential strategy for predicting or treating T1D.

The role and mechanism of RNA-binding proteins in bone metabolism and osteoporosis.

Osteoporosis is a prevalent chronic metabolic bone disease that poses a significant risk of fractures or mortality in elderly individuals. Its pathophysiological basis is often attributed to postmenopausal estrogen deficiency and natural aging, making the progression of primary osteoporosis among elderly people, especially older women, seemingly inevitable. The treatment and prevention of osteoporosis progression have been extensively discussed. Recently, as researchers delve deeper into the molecular biological mechanisms of bone remodeling, they have come to realize the crucial role of posttranscriptional gene control in bone metabolism homeostasis. RNA-binding proteins, as essential actors in posttranscriptional activities, may exert influence on osteoporosis progression by regulating the RNA life cycle. This review compiles recent findings on the involvement of RNA-binding proteins in abnormal bone metabolism in osteoporosis and describes the impact of some key RNA-binding proteins on bone metabolism regulation. Additionally, we explore the potential and rationale for modulating RNA-binding proteins as a means of treating osteoporosis, with an overview of drugs that target these proteins.

LncRNA-mediated cartilage homeostasis in osteoarthritis: a narrative review.

Osteoarthritis (OA) is a degenerative disease of cartilage that affects the quality of life and has increased in morbidity and mortality in recent years. Cartilage homeostasis and dysregulation are thought to be important mechanisms involved in the development of OA. Many studies suggest that lncRNAs are involved in cartilage homeostasis in OA and that lncRNAs can be used to diagnose or treat OA. Among the existing therapeutic regimens, lncRNAs are involved in drug-and nondrug-mediated therapeutic mechanisms and are expected to improve the mechanism of adverse effects or drug resistance. Moreover, targeted lncRNA therapy may also prevent or treat OA. The purpose of this review is to summarize the links between lncRNAs and cartilage homeostasis in OA. In addition, we review the potential applications of lncRNAs at multiple levels of adjuvant and targeted therapies. This review highlights that targeting lncRNAs may be a novel therapeutic strategy for improving and modulating cartilage homeostasis in OA patients.

Dysregulation of ferroptosis-related genes in granulosa cells associates with impaired oocyte quality in polycystic ovary syndrome.

Background: Poor oocyte quality remains one of the major challenges for polycystic ovary syndrome (PCOS) patients during in vitro fertilization (IVF) treatment. Granulosa cells (GCs) in PCOS display altered functions and could cause an unfavorable microenvironment for oocyte growth and maturation. Ferroptosis is a new form of programmed cell death, but its role in PCOS has been largely unclarified. Methods: Ferroptosis-related differentially expressed genes (DEGs) of GCs in women with PCOS were identified by bioinformatic analyses of GSE155489 and GSE168404 datasets. Functional enrichment analyses were conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Core ferroptosis-related genes were further screened by random forest, and evaluated for diagnostic value by receiver operating characteristic curve analyses. Gene expression was validated by real-time quantitative polymerase chain reaction of collected GC samples, and analyzed for association with oocyte quality. In addition, gene regulatory network was constructed based on predicted RNA interactions and transcription factors, while potential therapeutic compounds were screened through molecular docking with crystallographic protein structures. Results: A total of 14 ferroptosis-related DEGs were identified. These DEGs were mainly enriched in reactive oxygen species metabolic process, mitochondrial outer membrane, antioxidant activity as well as ferroptosis and adipocytokine signaling pathways. Eight core ferroptosis-related genes (ATF3, BNIP3, DDIT4, LPIN1, NOS2, NQO1, SLC2A1 and SLC2A6) were further selected in random forest model, which showed high diagnostic performance for PCOS. Seven of them were validated in GC samples, and five were found to be significantly and positively correlated with one or more oocyte quality parameters in PCOS patients, including oocyte retrieval rate, mature oocyte rate, normal fertilization rate, and good-quality embryo rate. Gene regulatory network revealed JUN and HMGA1 as two important transcription factors, while dicoumarol and flavin adenine dinucleotide were predicted as small molecules with therapeutic potential. Conclusions: This is the first comprehensive report to study the differential expression of ferroptosis-related genes in GCs of PCOS and their clinical relevance with oocyte quality. Our findings could provide novel insights on the potential role of GC ferroptosis in PCOS pathogenesis, diagnosis, and targeted treatment.

Targeting the gut microbiota and its metabolites for type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia and insulin resistance. The incidence of T2DM is increasing globally, and a growing body of evidence suggests that gut microbiota dysbiosis may contribute to the development of this disease. Gut microbiota-derived metabolites, including bile acids, lipopolysaccharide, trimethylamine-N-oxide, tryptophan and indole derivatives, and short-chain fatty acids, have been shown to be involved in the pathogenesis of T2DM, playing a key role in the host-microbe crosstalk. This review aims to summarize the molecular links between gut microbiota-derived metabolites and the pathogenesis of T2DM. Additionally, we review the potential therapy and treatments for T2DM using probiotics, prebiotics, fecal microbiota transplantation and other methods to modulate gut microbiota and its metabolites. Clinical trials investigating the role of gut microbiota and its metabolites have been critically discussed. This review highlights that targeting the gut microbiota and its metabolites could be a potential therapeutic strategy for the prevention and treatment of T2DM.

Research progress on the premature ovarian failure caused by cisplatin therapy.

Cisplatin is a common anticancer drug able to kill tumor cells, but it causes adverse reactions in the kidney, digestive tract, and other systems. The antitumor effects of cisplatin are mainly due to its ability to bind to the DNA in tumor cells to prevent replication, thereby reducing RNA and protein syntheses, leading to cell damage and death. Cisplatin has a wide range of applications; it can be used to treat cervical, thyroid, ovarian, and other cancers. Cisplatin has a beneficial therapeutic effect, but its therapeutic selectivity is poor. In addition to eliminating diseased target cells, cisplatin can damage normal cells; in women of reproductive age being treated for cancer, cisplatin can lead to ovarian function impairment, premature ovarian failure (POF), and/or infertility. Therefore, reducing the adverse effects of cisplatin on ovarian function is an important topic in clinical research. In this paper, we explore the research progress on the POF caused by cisplatin treatment.

The perspectives of NETosis on the progression of obesity and obesity-related diseases: mechanisms and applications.

Obesity is a disease commonly associated with urbanization and can also be characterized as a systemic, chronic metabolic condition resulting from an imbalance between energy intake and expenditure. The World Health Organization (WHO) has identified obesity as the most serious chronic disease that is increasingly prevalent in the world population. If left untreated, it can lead to dangerous health issues such as hypertension, hyperglycemia, hyperlipidemia, hyperuricemia, nonalcoholic steatohepatitis, atherosclerosis, and vulnerability to cardiovascular and cerebrovascular events. The specific mechanisms by which obesity affects the development of these diseases can be refined to the effect on immune cells. Existing studies have shown that the development of obesity and its associated diseases is closely related to the balance or lack thereof in the number and function of various immune cells, of which neutrophils are the most abundant immune cells in humans, infiltrating and accumulating in the adipose tissues of obese individuals, whereas NETosis, as a newly discovered type of neutrophil-related cell death, its role in the development of obesity and related diseases is increasingly emphasized. The article reviews the significant role that NETosis plays in the development of obesity and related diseases, such as diabetes and its complications. It discusses the epidemiology and negative impacts of obesity, explains the mechanisms of NETosis, and examines its potential as a targeted drug to treat obesity and associated ailments.

Landscapes and mechanisms of CD8+ T cell exhaustion in gastrointestinal cancer.

CD8+ T cells, a cytotoxic T lymphocyte, are a key component of the tumor immune system, but they enter a hyporeactive T cell state in long-term chronic inflammation, and how to rescue this depleted state is a key direction of research. Current studies on CD8+ T cell exhaustion have found that the mechanisms responsible for their heterogeneity and differential kinetics may be closely related to transcription factors and epigenetic regulation, which may serve as biomarkers and potential immunotherapeutic targets to guide treatment. Although the importance of T cell exhaustion in tumor immunotherapy cannot be overstated, studies have pointed out that gastric cancer tissues have a better anti-tumor T cell composition compared to other cancer tissues, which may indicate that gastrointestinal cancers have more promising prospects for the development of precision-targeted immunotherapy. Therefore, the present study will focus on the mechanisms involved in the development of CD8+ T cell exhaustion, and then review the landscapes and mechanisms of T cell exhaustion in gastrointestinal cancer as well as clinical applications, which will provide a clear vision for the development of future immunotherapies.

Mechanisms and therapeutic strategies of immune checkpoint molecules and regulators in type 1 diabetes.

Background: Considered a significant risk to health and survival, type 1 diabetes (T1D) is a heterogeneous autoimmune disease characterized by hyperglycemia caused by an absolute deficiency of insulin, which is mainly due to the immune-mediated destruction of pancreatic beta cells. Scope of review: In recent years, the role of immune checkpoints in the treatment of cancer has been increasingly recognized, but unfortunately, little attention has been paid to the significant role they play both in the development of secondary diabetes with immune checkpoint inhibitors and the treatment of T1D, such as cytotoxic T-lymphocyte antigen 4(CTLA-4), programmed cell death protein-1(PD-1), lymphocyte activation gene-3(LAG-3), programmed death ligand-1(PD-L1), and T-cell immunoglobulin mucin protein-3(TIM-3). Here, this review summarizes recent research on the role and mechanisms of diverse immune checkpoint molecules in mediating the development of T1D and their potential and theoretical basis for the prevention and treatment of diabetes. Major conclusions: Immune checkpoint inhibitors related diabetes, similar to T1D, are severe endocrine toxicity induced with immune checkpoint inhibitors. Interestingly, numerous treatment measures show excellent efficacy for T1D via regulating diverse immune checkpoint molecules, including co-inhibitory and co-stimulatory molecules. Thus, targeting immune checkpoint molecules may exhibit potential for T1D treatment and improve clinical outcomes.

[Expression of Bax and Caspase-3 and apoptosis in human lumbar intervertebral disc degeneration].

OBJECTIVE: To detect the cell density, apoptotic incidence and the expressions of Bax and Caspase-3 in human lumbar intervertebral discs, so as to further understand the mechanism of human lumbar intervertebral disc degeneration and provide a new idea for biologic treatment of it in future. METHODS: From May to December in 2006, 30 human lumbar intervertebral discs in experimental group (L2 to S1) were surgically collected from 27 patients undergoing posterior lumbar intervertebral discoidectomy and fusion. All the cases were affirmed by MRI and they never experienced discography, collagenolysis of nucleus pulposus and percutaneous laser disc decompression. The control group consisted of 20 human lumbar intervertebral discs (L2 to S1) harvested from 5 young men without spine-related condition immediately after their accidental death. Apoptotic disc cells were detected by TUNEL and histomorphology, and immunohistochemical staining with SP method was performed to examine the expressions of Bax and Caspase-3 in all specimens. RESULTS: HE staining disclosed that the average cell density in control group (17.16 +/- 1.22)/HP was higher than that in experimental group (12.41 +/- 0.95)/HP (P < 0.01). However, TUNEL staining observed that the average TUNEL positive incidence in control group (6.97% +/- 0.92%) was lower than that in experimental group (12.59% +/- 0.95%), (P < 0.01). Immunohistochemical staining with SP method showed that the Bax and Caspase-3 positive incidence of nucleus pulposus in control group (11.02% +/- 1.18%, 9.01% +/- 1.00%) were lower than those in experimental group (19.29% +/- 1.18%, 15.07% +/- 0.97%), (P < 0.01). The results of the average gray scale value of nucleus pulposus in control group were 187.33 +/- 7.88 and 185.68 +/- 3.26, respectively, with 124.98 +/- 6.69 and 160.13 +/- 4.37 in experimental group. There was significant difference between the two groups (P < 0.01). When the total 50 specimens in the two groups were analyzed, TUNEL positive incidence showed significant inverse correlations with their respectively corresponding cell densities (r = - 0.88, r = - 0.93, P < 0.01). The Bax and Caspase-3 positive incidence of nucleus pulposus showed significant positive correlation with the TUNEL positive incidence of nucleus pulposus (r = 0.83, r = 0.91, P < 0.01). CONCLUSION: The decrease of cell density is involved in the development of human lumbar intervertebral disc degeneration. Bax and Caspase-3 might play a role in disc cell apoptosis in nucleus pulposus of human lumbar intervertebral disc.