PIWI-interacting RNAs (piRNAs), PIWI proteins, and piRNA biogenesis-associated proteins form a conserved RNA network that protects germline genome integrity and is increasingly linked to cancer biology. Most cancer reviews have emphasized altered piRNA abundance or PIWI expression, whereas the upstream machinery that generates, loads, trims, and stabilizes piRNAs has received less critical attention. For the RNA Networks and Biology section, this Review re-evaluates piRNA biogenesis proteins as RNA-network regulators rather than as isolated tumor biomarkers. We summarize the biochemical logic of precursor selection, mitochondrial processing, PIWI loading, 3-end maturation, and effector complex assembly, focusing on PIWIL1-4, PLD6/MitoPLD, MOV10L1, DDX4/VASA, GASZ, TDRKH, PNLDC1, HENMT1, Tudor-domain proteins, HSP90, and MAEL. We then assess cancer evidence by distinguishing direct perturbation studies from expression associations, animal-germline mechanisms, and computational inference. Current evidence supports tumor-context-specific roles for PIWIL1, PIWIL2, DDX4, TDRD1, MAEL, and emerging PLD6 biology in selected tumors, whereas several canonical maturation or scaffold proteins remain underexplored in human cancer. We propose that dysregulated piRNA biogenesis proteins may influence cancer through piRNA-dependent small-RNA imbalance and piRNA-independent reactivation of germline RNA-processing, epigenetic, metabolic, and immune programs. Finally, we discuss biomarker and therapeutic opportunities while emphasizing unresolved controversies, technical limitations in piRNA detection, reproductive toxicity, and the need for causal validation in human tumor models.

The therapeutic potential of stem cell therapy critically depends on precise epigenetic regulation mediated by PIWI/piRNA complexes. This review synthesizes current literature to analyze the structure, interaction mechanisms, and epigenetic functions of PIWI proteins and their associated piRNAs (24-32 nt non-coding RNAs), with emphasis on stem cell therapy and disease modeling applications. PIWI/piRNA complexes critically regulate transcriptional control, chromatin remodeling, and stem cell plasticity. These complexes maintain stemness while promoting differentiation, serving as key biomarkers and therapeutic targets in cancers and skeletal disorders. However, translational challenges regarding specificity, delivery stability, and safety profiles persist. Advancing PIWI/piRNA-based therapeutics requires innovative technologies and expanded clinical validation to develop safe, targeted stem cell treatments for diverse pathologies.

Prostate cancer is the second most common malignancy among men in the world, posing a serious threat to men's health and lives. RB1 is the first human tumor suppressor gene to be described, and it is closely associated with the development, progression, and suppression of a variety of tumors. It was found that the loss of RB1 is an early event in prostate cancer development and is closely related to prostate cancer development, progression and treatment resistance. This paper reviews the current status of research on the relationship between RB1 and prostate cancer from three aspects: RB1 and prostate cell lineage plasticity; biological behavior; and therapeutic resistance. Providing a novel perspective for developing new therapeutic strategies for RB1-loss prostate cancer.

The treatment of prostate cancer (PCa) has made great progress in recent years, but treatment resistance always develops and can even lead to fatal disease. Exploring the mechanism of drug resistance is of great significance for improving treatment outcomes and developing biomarkers with predictive value. It is increasingly recognized that mechanism of drug resistance in advanced PCa is related to lineage plasticity and tissue differentiation. Specifically, one of the mechanisms by which castration-resistant prostate cancer (CRPC) cells acquire drug resistance and transform into neuroendocrine prostate cancer (NEPC) cells is lineage plasticity. NEPC is a subtype of PCa that is highly aggressive and lethal, with a median survival of only 7 months. With the development of high-throughput RNA sequencing technology, more and more non-coding RNAs have been identified, which play important roles in different diseases through different mechanisms. Several ncRNAs have shown great potential in PCa lineage plasticity and as biomarkers. In the review, the role of ncRNA in PCa lineage plasticity and its use as biomarkers were reviewed.

Primer sequences for the knockdown of PSCA and ITGA4 genes and the control

PSCA expression had no effect on the adhesion of PCa cells to extracellular matrix proteins-fibronectin, laminin and vitronectin.

PSCA had no effect on the expression levels of integrin αv (ITGAV), integrin β1 (ITGB1) and integrin β3 (ITGB3) in PCa cells. A. Western blot analyses. B. qRT-PCR analyses.

The effects of blocking antibodies to integrins on PCa cell adherence and migration. A. Adhesion assays showed that the GFP-labeled cancer cells (Green) adhesion to BMECs could be significantly blocked by the antibodies to ITGA4, but not to integrins alpha v, β1, and β3. B. The TEM assay showed the similar results with A. Error bars represent the mean {plus minus} S.D. of three independent experiments. *P < 0.05, **P < 0.01 and ***P < 0.001.

Table S1: Univariate and multivariate cox regression analyses for overall survival and progression-free survival in non-metastasis ccRCC patients

N6-methyladenosine (m6A), as a reversible chemical modification of RNA, is a new type of posttranscriptional gene regulation, which plays an important role in cell differentiation and tumorigenesis, and is also a research hotspot in epigenetic transcriptomics in recent years. The purpose of this study was to discuss the action mechanism of m6A demethylase ALKBH5 in the occurrence of prostate cancer (PCa). We found that ALKBH5 was lowly expressed in PCa, and the decreased expression of ALKBH5 was responsible for the poor prognosis of prostate carcinomas. Moreover, ALKBH5 downregulated the expression of Krüppel-like factor 4 (KLF4) by reducing its mRNA stability, which reduced the transcriptional activity of KLF4 on the downstream target telomerase reverse transcriptase (TERT) and decreased TERT expression and telomerase activity, eventually inhibiting PCa cell growth. The findings of this study reveal the action mechanism of ALKBH5 in PCa from the perspective of epitranscriptomics, which would provide new ideas for the prevention of PCa.

Primer sets used in the study, related to the PCR and qRT-PCR

PIWI proteins have a strong correlation with PIWI-interacting RNAs (piRNAs), which are significant in development and reproduction of organisms. Recently, emerging evidences have indicated that apart from the reproductive function, PIWI/piRNAs with abnormal expression, also involve greatly in varieties of human cancers. Moreover, human PIWI proteins are usually expressed only in germ cells and hardly in somatic cells, so the abnormal expression of PIWI proteins in different types of cancer offer a promising opportunity for precision medicine. In this review, we discussed current researches about the biogenesis of piRNA, its epigenetic regulatory mechanisms in human cancers, such as N6-methyladenosine (m6A) methylation, histone modifications, DNA methylation and RNA interference, providing novel insights into the markers for clinical diagnosis, treatment and prognosis in human cancers.

Inflammation, the main factor in the progression of osteoarthritis (OA), impairs the chondrogenesis of bone mesenchymal stem cells (BMSCs), which is an appealing process to target to regenerate impaired articular cartilage. This article aimed to investigate whether SP600125, a competitive ATP-specific inhibitor of the JNK pathway, could promote the chondrogenesis of BMSCs by enhancing their anti-inflammatory capacity. Chondrogenic differentiation was assessed by Alcian blue staining, immunofluorescence staining, and Western blot. The inflammation level was associated with the expression of matrix metalloproteinases (Mmp), evaluated by Western blot. Intra-articular injection of BMSCs pretreated with or without SP600125 was carried out on C57BL/6 mice after inducing OA by surgical destabilization of the medial meniscus. Safranin O-fast green (SO) and hematoxylin-eosin staining were employed to evaluate the cartilage destruction and immunohistochemical analysis was adopted to detect the expression of Col2 and Mmp-13 proteins in the mouse knee joint. We showed that SP600125 could inhibit inflammation induced by tumor necrosis factor-alpha (TNF-alpha) and promote the chondrogenesis of BMSCs. In the presence of TNF-alpha, the expression of aggrecan (Agc) and collagen type II alpha 1 (Col2) was significantly decreased compared with that in the control group and increased with the addition of SP600125. Moreover, the expression of Mmp-1, Mmp-3, and Mmp-13 was increased in BMSCs treated only with TNF-alpha and downregulated in SP600125-treated BMSCs. In vivo study showed that SP600125 could enhance protective effects of BMSCs on OA mice. Our results indicated that SP600125 rescued the chondrogenesis of BMSCs by inhibiting inflammation induced by TNF-alpha, which provides a theoretical basis for solving the problem of cartilage repair under inflammatory conditions.

深度融合信息技术,推动医学教育改革的进一步发展已被医学教育者所广泛接受和认可,文中就多种现代信息技术在医学生临床技能教学中的应用进行了初步的探讨,并对现代信息技术深度融合背景下的医学生临床技能培养模式及发展前景做了展望.

Osteoarthritis (OA), characterized by the degeneration and destruction of articular cartilage, is one of the most significant public health issues around the world. In the course of OA, inflammatory response is an important factor leading to cartilage destruction and exacerbation of symptoms. The low immunogenicity, multi-directional differentiation and high portability properties make bone marrow mesenchymal stem cells (BMSCs) ideal seed cells for OA. Here, we review recent literature relating to the application of BMSCs for OA cell therapy and consider the following aspects: migration and homing of BMSCs, immunomodulatory and anti-inflammatory effects of BMSCs, anti-fibrotic effects of BMSCs, the application of biological scaffolds in cartilage regeneration by BMSCs and chondrogenic differentiation of BMSCs. Injecting BMSCs into joints with an inflammatory environment may increase the risk of osteoproliferation and ectopic calcification in patients. Further evidence and studies are needed to ensure the improvement and maintenance of the intra-articular environment for cartilage repair and regeneration.

Bone metastasis is the major cause of morbidity and mortality in patients with prostate cancer (PCa). However, the underlying mechanism of bone-specific metastasis remain vague. Recently, with the deep research of N6-methyladenine (m6A) mRNA methylation, many studies directly focus on the role of m6A modification in human diseases, especially in cancers. Here we found that methyltransferase-like 3 (METTL3) expression is higher in PCa than in normal prostate tissues, especially in PCa with bone metastasis. High METTL3 expression was positively correlated with advanced progression and a poor prognosis of PCa. Functional assays demonstrated that METTL3 regulates the expression of Integrin β1 (ITGB1) through m6A-HuR-dependent mechanism, which affects the binding of ITGB1 to Collagen I and tumor cell motility, so as to promote the bone metastasis of PCa. The findings of this study reveal a novel mechanism of PCa osteotropism and suggest METTL3 as a therapeutic target for PCa bone metastasis.

Abstract Distant metastasis, predominantly to bone, is the leading cause of morbidity and mortality in prostate cancer. However, the mechanisms underlying prostate cancer metastases remain unknown. Prostate cancer cells exhibited discrete adhesion to bone marrow endothelial cells (BMEC), resulting in osteotropic metastasis. Prior data showed an increased metastatic propensity of prostate stem cell antigen (PSCA)–positive prostate cancer cells. The current study sought to characterize the roles of PSCA in the adhesion of prostate cancer cells to BMECs. Cell adhesion was assessed using the adhesion assay and transendothelial migration. The expression and regulation of integrins were evaluated by qRT-PCR, Western blot, promoter-luciferase activity, and chromatin immunoprecipitation (ChIP). Functionally, the potential interacting partners of PSCA in prostate cancer cells were identified by coimmunoprecipitation and mass spectrometry (MS) analysis. The association of PSCA expression with bone metastasis was further analyzed in an in vivo model and prostate cancer patients. We found that overexpression of PSCA enhanced the adhesion capability of prostate cancer cells to BMECs through upregulating integrin-α4 expression, concurrent with transcriptionally activated NF-κB. Growth factor progranulin (PGRN) was identified as a potential interacting partner of PSCA in prostate cancer cells. Functional studies showed that downregulation of PGRN and PSCA with siRNAs in prostate cancer cells significantly suppressed the integrin-α4 expression and the adhesion to BMECs in vitro, respectively, which were restorable by exogenous PGRN. Importantly, PSCA depletion significantly reduced tumors' presence in the bone of a mouse model. Furthermore, PSCA expression is elevated in prostate cancer tissue, and significantly associated with increased Gleason score, advanced stage, bone metastasis, and poor prognosis in prostate cancer patients. We conclude that PSCA/PGRN promoted the adhesion of prostate cancer cells to BMECs through NF-κB/integrin-α4 pathways, to facilitate metastases. Implications: The findings presented here suggest PSCA/PGRN as a potential therapeutic target for prostate cancer metastases, especially for bone metastasis.

体格检查是临床基本技能的重要组成部分,是临床医师必须熟练掌握的基本功,而有效的体格检查考试方法,是教师教学水平和教学成果的试金石.因此,在本科教育中探索一种有效的体格检查考试方式能够使教师更好地掌握学生在学习中的薄弱环节,利于以后教学中的查漏补缺,进一步加强医学生临床基本技能的培养,提高教学质量.

Objective: To assess whether radiotherapy (RT) for prostate cancer (PCa) was a risk factor for secondary bladder cancer (BLCa) through a meta-analysis. Materials and methods: The MEDLINE, Embase, and the Cochrane Library were systematically searched for all studies investigating the risk of BLCa in patients with RT. The association between RT and risk of BLCa was summarized using hazard ratio with a 95% CI. The protocol for this meta-analysis is available from PROSPERO (CRD42018090075). Results: Overall, 619,479 participants (age: 57-79 years) were included from 15 studies, 206,852 of whom were patients who received RT. Synthesis of results indicated that RT was significantly associated with an increased risk of BLCa compared with the risk in those who received radical prostatectomy or non-RT (overall HR=1.6, 95% CI: 1.33-1.92, P<0.001). The results were consistent when restricted to a 5-year lag period (HR=1.84, 95% CI: 1.26-2.69, P=0.002) and multivariable adjustment (HR=1.96, 95% CI: 1.47-2.62, P<0.001), but not for 10-year lag period (HR=1.93, 95% CI: 0.9-4.16, P=0.093) and brachytherapy subgroup (HR=1.33, 95% CI: 0.87-2.05, P=0.188). The GRADE-profiler revealed that the rate of events of BLCa on average in the RT-patients and the non-RT control was 2,462/183,669 (1.3%) and 4,263/382,761(1.1%), respectively; the overall quality of the evidence was low. Conclusion: Patients who received RT for PCa was associated with higher risks of developing secondary BLCa compared to those unexposed to RT, but the absolute effect was low.

Objective. To evaluate the therapeutic effect of Shengjing capsules on nonobstructive azoospermia (NOA) in the rat model. Methods. Twenty-five male Sprague–Dawley rats were randomly divided into five groups as follows (n=5 per group): normal group, NOA group, and three Shengjing capsule treatment groups (low-dose, medium-dose, and high-dose groups, respectively). HE staining and semen smear were performed to assess sperm quality. The expression levels of PI3K/AKT and integrin α6/β1 were measured by qRT-PCR and western blot analyses. Results. In the NOA group, almost all of the seminiferous tubules were vacuolated with a thin layer of basal compartment containing some spermatogonial stem cells. The counts of sperms in the NOA group were strongly lower than those of the normal group (P=0.0001). The expression of PI3K/AKT and integrin α6/β1 was scarcely expressed in the NOA group. All indexes mentioned above were significantly different from those of the medium- and high-dose groups (P=0.001, all). The sperm count of rats treated with Shengjing capsules was significantly higher than that of the NOA group (P=0.0001). The rats of Shengjing capsule groups had more layers of spermatogonial stem cells and spermatocytes, and some had intracavitary sperms. Conclusions. Shengjing capsules may be a promising therapeutic medicine for NOA. The underlying mechanisms might involve activating SSCs by upregulating the integrin α6/β1 expression via the PI3K/AKT pathway.