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Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone modification, RNA modification, chromatin remodeling, and non-coding RNA regulation. These mechanisms and their associated enzymes convey genetic information independently of DNA base sequences, playing essential roles in organismal development and homeostasis. Conversely, disruptions in epigenetic landscapes critically influence the pathogenesis of various human diseases. This understanding has laid a robust theoretical groundwork for developing drugs that target epigenetics-modifying enzymes in pathological conditions. Over the past two decades, a growing array of small molecule drugs targeting epigenetic enzymes such as DNA methyltransferase, histone deacetylase, isocitrate dehydrogenase, and enhancer of zeste homolog 2, have been thoroughly investigated and implemented as therapeutic options, particularly in oncology. Additionally, numerous epigenetics-targeted drugs are undergoing clinical trials, offering promising prospects for clinical benefits. This review delineates the roles of epigenetics in physiological and pathological contexts and underscores pioneering studies on the discovery and clinical implementation of epigenetics-targeted drugs. These include inhibitors, agonists, degraders, and multitarget agents, aiming to identify practical challenges and promising avenues for future research. Ultimately, this review aims to deepen the understanding of epigenetics-oriented therapeutic strategies and their further application in clinical settings.

Beta-blockers are antihypertensive drugs and have shown potential in cancer prognosis. However, this benefit has not been well defined due to inconsistent results from the published studies. To investigate the association between administration of beta-blocker and cancer prognosis, we performed a meta-analysis. A literature search of PubMed, Embase, Cochrane Library, and Web of Science was conducted to identify all relevant studies published up to September 1, 2017. Thirty-six studies involving 319,006 patients were included. Hazard ratios were pooled using a random-effects model. Subgroup analyses were conducted by stratifying ethnicity, duration of drug use, cancer stage, sample size, beta-blocker type, chronological order of drug use, and different types of cancers. Overall, there was no evidence to suggest an association between beta-blocker use and overall survival (HR=0.94, 95% CI: 0.87-1.03), all-cause mortality (HR=0.99, 95% CI: 0.94-1.05), disease-free survival (HR=0.59, 95% CI: 0.30-1.17), progression-free survival (HR=0.90, 95% CI: 0.79-1.02), and recurrence-free survival (HR=0.99, 95% CI: 0.76-1.28), as well. In contrast, beta-blocker use was significantly associated with better cancer-specific survival (CSS) (HR=0.78, 95% CI: 0.65-0.95). Subgroup analysis generally supported main results. But there is still heterogeneity among cancer types that beta-blocker use is associated with improved survival among patients with ovarian cancer, pancreatic cancer, and melanoma. The present meta-analysis generally demonstrates no association between beta-blocker use and cancer prognosis except for CSS in all population groups examined. High-quality studies should be conducted to confirm this conclusion in future.

Background In this study, we aimed to identify novel biomarkers for polycystic ovary syndrome (PCOS) and analyze their potential roles in immune infiltration during PCOS pathogenesis. Methods Five datasets, namely GSE137684 , GSE80432 , GSE114419 , GSE138518 , and GSE155489 , were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were selected from the train datasets. The least absolute shrinkage and selection operator logistic regression model and support vector machine-recursive feature elimination algorithm were combined to screen potential biomarkers. The test datasets validated the expression levels of these biomarkers, and the area under the curve (AUC) was calculated to analyze their diagnostic value. Quantitative real-time PCR was conducted to verify biomarkers’ expression in clinical samples. CIBERSORT was used to assess differential immune infiltration, and the correlations of biomarkers with infiltrating immune cells were evaluated. Results Herein, 1265 DEGs were identified between PCOS and control groups. The gene sets related to immune response and adaptive immune response were differentially activated in PCOS. The two diagnostic biomarkers of PCOS identified by us were HD domain containing 3 (HDDC3) and syndecan 2 (SDC2; AUC, 0.918 and 0.816, respectively). The validation of hub biomarkers in clinical samples using RT-qPCR was consistent with bioinformatics results. Immune infiltration analysis indicated that decreased activated mast cells ( P  = 0.033) and increased eosinophils ( P  = 0.040) may be a part of the pathogenesis of PCOS. HDDC3 was positively correlated with T regulatory cells ( P  = 0.0064), activated mast cells ( P  = 0.014), and monocytes ( P  = 0.024) but negatively correlated with activated memory CD4 T cells ( P  = 0.016) in PCOS. In addition, SDC2 was positively correlated with activated mast cells ( P  = 0.0021), plasma cells ( P  = 0.0051), and M2 macrophages ( P  = 0.038) but negatively correlated with eosinophils ( P  = 0.01) and neutrophils ( P  = 0.031) in PCOS. Conclusion HDDC3 and SDC2 can serve as candidate biomarkers of PCOS and provide new insights into the molecular mechanisms of immune regulation in PCOS.

Background Excessive fructose intake can impact pregnancy health. Additionally, Polycystic ovary syndrome (PCOS) is associated with both elevated fructose levels and adverse pregnancy outcomes. Therefore, it is significant to investigate whether serum fructose levels influence pregnancy outcomes in patients with or without PCOS. Methods This case-control study included 270 participants (PCOS, n  = 135; non-PCOS, n  = 135). The serum fructose levels of consecutively treated women undergoing in vitro fertilization - embryo transfer treatment at the Center of reproductive medicine in Shengjing hospital of China Medical University, from June 2020 to June 2021, were measured. Pregnancies were monitored until the ultimate outcome was determined. The antenatal, delivery, and neonatal outcomes were extracted from hospital records. Results In patients with PCOS, those who experienced miscarriage had significantly higher serum fructose levels ( P  = 0.011). The incidence of miscarriage increased as the serum fructose quartiles increased in patients with PCOS ( P  = 0.010). There was a significant correlation between serum fructose levels and miscarriage ( r  = 0.258, P  = 0.002). The results of multivariate logistic regression analysis remain consistent (odd ratio [OR] = 10.138, P  = 0.005). Conversely, in women without PCOS, those who prematurely delivered had significantly higher serum fructose levels ( P  = 0.001). The incidence of preterm delivery increased as the serum fructose quartiles increased in patients without PCOS ( P  < 0.001). There was a significant correlation between serum fructose levels and preterm delivery ( r  = 0.311, P  < 0.001) in non-PCOS group. The multivariate logistic regression analysis indicated the identical results (OR = 18.359, P  = 0.008). The area under the curve for fructose-mediated prediction of miscarriage in PCOS was 0.686, while for prediction of preterm birth in non-PCOS individuals, the area under the curve was 0.731. Conclusions Serum fructose levels are positively associated with miscarriage risk in patients with PCOS. Within the non-PCOS cohort, fructose levels are linked to preterm birth. Further investigation is warranted to comprehensively elucidate the underlying mechanisms, thus enhancing our profound understanding.

People living with human immunodeficiency virus (PLWH) has been reported to have a high prevalence of depressive symptoms. Low-income populations account for a large proportion of PLWH, hence indicating a high level of depressive symptoms in low-income PLWH. Telephone-based therapy has been shown to be effective for treating PLWH’s depressive symptoms, but its effects among low-income PLWH remain unclear. The purpose of this meta-analysis was to evaluate the effects of telephone-based therapy targeting depressive symptoms among low-income PLWH. Six databases (PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, VIP Database and Wanfang Data) were searched until May 2020 using search terms related to telephone-based therapy, depressive symptoms, and PLWH. Eight studies were included in the meta-analysis. Both postintervention effects (primary outcome) and long-term effects (secondary outcome) were evaluated using a random effects model. The meta-analysis revealed a small to moderate effect size (ĝ = − 0.29, 95% CI − 0.51, − 0.06) on reducing depressive symptom scores (Z = 2.51, p = 0.01) in telephone-based intervention group compared with the control group at postintervention. However, there was no statistically significant long-term effects (Z = 0.77, p = 0.44) at follow-up. For postintervention effects, calculation of the I2 index indicated moderate heterogeneity (I2 = 50%); sensitivity analysis and subgroup analysis were performed to explore the source of heterogeneity. Ethnic group was classified into minority and majority which refers to most of the population were ethnic minority and majority respectively. Between-group differences were found across ethnic groups. The results suggested that there was a slightly stronger effect of telephone-based therapy in low-income PLWH than among PLWH in general, but its long-term effect requires future investigation. The effects of the intervention were better among the ethnic majority subgroups of low-income PLWH. Treatment format and intervention duration might also influence the intervention effects. However, the overall quality of evidence was low and directly impacted on the interpretation of our results, suggesting that more high-quality random controlled trial (RCT)/longitudinal studies with less selection and detection bias, less inconsistency and less indirectness are needed when applying telephone-based therapy to low-income PLWH with depressive symptoms in further studies.

Ten‐eleven translocation (TET) family proteins are Fe(II)‐ and α‐ketoglutarate‐dependent dioxygenases, comprising three family members: TET1, TET2, and TET3. These enzymes drive DNA demethylation by sequentially oxidizing 5‐methylcytosine to 5‐hydroxymethylcytosine, 5‐formylcytosine, and 5‐carboxylcytosine. Through these reactions, TET proteins remodel the epigenetic landscape and interact with transcription factors and RNA polymerase II to regulate gene expression, cell lineage specification, and embryonic development. Mutations and dysregulation of TETs have been associated with the pathogenesis of various diseases, including the nervous system, immune system, and metabolic diseases, as well as cancers. Therapeutic modulation of TETs may be an effective strategy for the treatment of these diseases. Here, we provide a comprehensive overview of the mechanisms by which TET proteins mediate DNA demethylation and detail their biological functions. Additionally, we highlight recent advances in understanding the molecular mechanisms linking TET dysregulation to disease pathogenesis and explore their potential as therapeutic targets. This review supplements the current understanding of the critical role of epigenetic regulation in disease pathogenesis and further facilitates the rational design of targeted therapeutic agents for diseases associated with mutations and dysregulation of TETs. TET family proteins play a critical role in DNA demethylation, and their mutations and dysregulation contribute to the onset of multiple diseases. With a deeper understanding of the molecular mechanisms of TET involvement in disease, drug therapy targeting TET proteins shows great potential, which provides insights into new therapeutic strategies.

Coronavirus disease 2019 (COVID‐19) has experienced a global pandemic, and currently, the emergence of its variants has posed challenges in terms of prevention and treatment. Nonetheless, the effect of COVID‐19 infection on female reproductive function is unclear. This study aimed to systematically evaluate for the first time the causal effect of COVID‐19 on female reproductive function. Genetic correlations were assessed using linkage disequilibrium score regression. Mendelian randomization (MR) analysis was performed using summary statistics of two variables, including COVID‐19 severity and eight female reproductive traits. The three degrees of severity had genetically significant associations with sex hormone‐binding globulin (SHBG) concentrations ( r g  = –0.153, p  = 0.004; r g  = –0.187, p  < 0.001; r g  = –0.180, p  = 0.003). Additionally, MR showed that SHBG ( β  = –0.020, p  = 0.040) and total testosterone levels ( β  = –0.061, p  = 0.009) followed a decreasing trend, as the COVID‐19 infection higher. No significant genetic association was found between COVID‐19 infection and total estradiol concentrations, menstruation, and female infertility. Simultaneously, MR found no causal relationships between COVID‐19 infection and total estradiol concentrations, menstruation, and female infertility (all p  > 0.05). In conclusion, COVID‐19 was causally associated with lower SHBG and total testosterone concentrations, offering invaluable insights that will help guide clinical decision‐making.

The mechanism of greenhouse tomato growth and yield under the integrated water and fertilizer of moistube irrigation (MI) is not clear. Thus, to fill the research gap, a completely randomized trial design was used to study the effects of different irrigation amounts (I; to realize different I, the tube working pressure was 1 (I1), 2 (I2), 3 (I3) m) and fertilizer amounts (F, N-P-K: 20%-20%-20%; the F at a single time was 100 (F1), 200 (F2) and 300 (F3) kg/ha) on growth and yield of tomato. The results showed that with an increase in I, the photosynthetic rate (Pn) of leaves and total dry matter mass (TDM) first increased and then decreased, while the nutrition and the flavor indexes of fruit decreased. With an increase in F, the Pn of leaves, the TDM of tomato and the fruit quality increased at first and then decreased. The effects of I on the yield of tomato was higher than that of F. With an increase in I, the partial fertilizer productivity (PFP) increased at first and then decreased, and the water use efficiency (WUE) decreased by 13.96%. With an increase in F, the WUE increased at first and then decreased, and the PFP decreased by 148.97%. The conclusion based on a spatial analysis was consistent with the comprehensive evaluation of yield and water use efficiency, which showed that I2F2 was the best.

Wound healing of the oral and maxillofacial area affects the quality of life and mental health of the patient; therefore, effective therapies are required to promote wound healing. However, traditional treatment methods have limited efficacy. Exosomes secreted by stem cells used for oral and maxillofacial wound healing have shown outstanding results. Stem cell-derived exosomes possess the regenerative and repair ability of stem cells. Moreover, they are nontumorigenic and have good biosafety. However, the application of natural stem cell exosomes is limited owing to their low yield, impurity, lack of targeting, and low drug delivery rate. Many modification methods have been developed to engineered stem cell exosomes with beneficial properties, such as modifying parent cells and directly processing stem cell exosomes. These methods include coincubation, genetic engineering, electroporation, ultrasound, and artificial synthesis of engineered stem cell exosomes. These engineered stem cell exosomes can cargo nucleic acids, proteins, and small molecules. This gives them anti-inflammatory and cell proliferation regulatory abilities and enables the targeted promotion of efficient soft tissue repair after trauma. Engineered stem cell exosomes can decrease inflammation, promote fibroblast proliferation, and angiogenesis, and decrease scar formation to promote oral and maxillofacial wound healing, including diabetic and burn wounds. Thus, engineered stem cell exosomes are an effective treatment that has the potential for oral and maxillofacial wound healing.

China has the highest global disease burden for both lung cancer and tuberculosis (TB). Mobile low-dose computed tomography (LDCT) screening offers dual detection of early-stage lung malignancies and active TB radiographic manifestations. However, evidence regarding community-based post-screening compliance remains inadequate. This study aimed to evaluate hospital follow-up adherence and its associated factors among individuals who screened positive for lung cancer or TB in a community-based, non-risk-based LDCT screening program. A prospective cohort study was conducted in Dongfang, Hainan Province, from June to September 2024. Permanent residents aged ≥40 years were enrolled in a community-based, non-risk-stratified mobile LDCT screening program. At the time of screening, participants completed a structured questionnaire to capture demographic characteristics, risk factors, and health status. Screening images were interpreted according to established guidelines; individuals with findings indicative of Lung-RADS category 4 (4 A, 4B, 4X) or suspected active pulmonary TB were considered screen-positive. The primary outcome, adherence to hospital-based diagnostic follow-up within six months, was objectively assessed by linking screening records to the provincial medical insurance claims database. Multivariable logistic regression was used to identify factors associated with adherence, stratified by screening finding. Among 22,933 participants (14,134 female and 8799 men), 547 (2.4%) had LDCT findings classified as Lung-RADS 4 and 653 (2.9%) displayed radiological features compatible with TB. Diagnostic follow-up within six months was completed by 303/547 lung-cancer suspects (55.4%) and 336/653 pulmonary TB suspects (51.5%). Among adherent individuals, 98 lung cancers (32.3%) and 95 active pulmonary TB cases (28.3%) were confirmed. In the lung-cancer cohort, respiratory symptoms increased the likelihood of follow-up (adjusted odds ratio [aOR] 2.47, 95% CI 1.13-5.41), whereas retired status decreased it (aOR 0.52, 0.32-0.85). In the pulmonary TB cohort, female sex was positively associated with adherence (aOR 1.39, 1.02-1.90), while formal employment was negatively associated (aOR 0.53, 0.31 - 0.90). This study highlights the need for targeted interventions to optimize diagnostic follow-up and maximize the clinical and public health impact of integrated lung cancer-TB screening programs.