This study aims to explore the causal association between the mediation of intestinal micrococci and the occurrence of breast cancer through CD45RA⁺ immune cells.

Mediating mendelian randomization (MR) analysis was used to establish the association between intestinal micrococci, CD45RA⁺ immune cells and breast cancer. The data of the gut microbiome were derived from the genome-wide association studies (GWAS) database, which included the metagenomic sequencing data of the gut microbiome of multiple populations. The breast cancer data originated from large-scale GWAS studies of the European female population. By filtering and selecting these data, we obtained the data associated with the occurrence of intestinal micrococci and breast cancer, and used MR analysis to remove weak instrumental variables. The role of CD45RA⁺ immune cells in the occurrence of breast cancer was explored by methods such as total effect analysis, reverse MR analysis, MR analysis of CD45RA⁺ immune cells in the Enterococcus family, MR analysis of CD45RA⁺ immune cells in breast cancer, mediating effect calculation, and sensitivity analysis.

The abundance of intestinal micrococci is positively correlated with the expression of CD45RA⁺ immune cells significantly (IVW OR = 1.385, 95% CI:1.017-1.684, P = 0.034). The expression of CD45RA⁺ immune cells was negatively correlated with the incidence of breast cancer (IVW OR = 0.769, 95% CI: 0.545-0.995, P = 0.017). The abundance of intestinal micrococci was significantly negatively correlated with the total effect on the incidence of breast cancer (IVW OR = 0.857, 95% CI: 0.745-0.955, P = 0.016) .

This study confirmed that the intestinal micrococcus family mediates the reduction of the risk of breast cancer incidence through CD45RA⁺ immune cells, providing a basis for the intervention strategy targeting the microbiota-immune axis.

To study the effect of circular enhancer of zeste homolog 2 (CircEZH2) on oxaliplatin (OXA) resistance in colon cancer cells by regulating the miR-340-5p/Pumilio RNA binding family member 1 (PUM1) axis.

Human colon cancer cell line HCT116 was cultured in vitro and its OXA resistant cell line HCT116/OXA was constructed using concentration gradient method. RT-qPCR and Western blot were applied to detect the expression of CircEZH2, miR-340-5p, and PUM1 in human colon cancer cell line HCT116 and its OXA resistant cell line HCT116/OXA. HCT116/OXA cells were cultured in vitro and randomly grouped into control group, OXA group, OXA+CircEZH2 negative control group, OXA+miR-340-5p negative control group, OXA+CircEZH2 knockdown group, and OXA+ CircEZH2 knockdown + miR-340- 5p inhibitor group. RT-qPCR and Western blot were applied to detect the expression of CircEZH2, miR- 340-5p, and PUM1 of cells in each group. CCK-8 assay and flow cytometry were applied to detect cell proliferation and apoptosis in each group. Western blot was applied to detect the expression of apoptotic proteins (Cleaved Caspase-3, Bax) and drug resistant proteins [breast cancer resistance protein (BCRP), P-glycoprotein (P-gp) ] in each group. HCT116/OXA cells were cultured in vitro and randomlydivided into control group, CircEZH2 knockdown group, negative control group, and CircEZH2 knockdown+miR-340-5p inhibitor group, CCK-8 assay was applied to detect the survival rate of cells in each group and calculating their drug resistance index. The double luciferase reporter gene experiment was applied to detect the targeted regulation of CircEZH2 on miR-340-5p and miR-340-5p on PUM1 in HCT116/OXA cells. One-way ANOVA was used for comparison between multiple groups, and SNK-q test was used for comparison between pairwise groups.

Compared with control group, cell viability[ (45.84 ± 7.63) % vs (100.00 ± 0.00) %] and the expression of P-gp protein (0.31 ± 0.05 vs 0.92 ± 0.20) in the OXA+CircEZH2 knockdown group were decreased, while the apoptosis rate [ (57.92 ± 9.84) % vs (1.60 ± 0.53) %] was increased (all P < 0.05). Compared with the OXA group, cell viability [ (45.84 ± 7.63) % vs (93.46 ± 16.75) %] and the expression of P-gp protein (0.31 ± 0.05 vs 0.78 ± 0.18) in the OXA+CircEZH2 knockdown group were decreased, while the apoptosis rate [ (57.92 ± 9.84) % vs (2.74 ± 0.81) %] was increased (all P < 0.05). Compared with the OXA+CircEZH2 knockdown group, cell viability [ (85.79 ± 18.93 ) % vs (45.84 ± 7.63) %] and the expression of P-gp protein (0.73 ± 0.11 vs 0.31 ± 0.05) in the the OXA+CircEZH2 knockdown+miR-340-5p inhibitor group were increased, while the apoptosis rate [ (3.93 ± 1.22) % vs (57.92 ± 9.84) %] was decreaseds (all P < 0.05). Compared with the control group, the drug resistance index (1.08 ± 0.15 vs 3.19 ± 0.30) of the CircEZH2 knockdown group was decreased significantly (P < 0.05). Compared with the CircEZH2 knockdown group, the drug resistance index (3.06 ± 0.19 vs 1.08 ± 0.15) of the CircEZH2 knockdown+miR-340-5p inhibitor group was increased signiticantly (P < 0.05). CircEZH2 was able to target and down-regulation the expression of miR-340-5p in HCT116/OXA cells, and miR-340- 5p could target and down-regulation the expression of PUM1.

Knocking down CircEZH2 can down-regulate PUM1 expression by up-regulating miR-340-5p, reducing OXA resistance in colon cancer cells, enhancing the killing power of OXA on colon cancer cells, and inducing apoptosis of HCT116/OXA cells under OXA treatment.

This study aims to investigate the expression of stress-induced phosphoprotein 1 (STIP1) in breast cancer tissues and its relationship with immune cell infiltration.

The GEPIA2 and Ualcan databases were used to analyze the expression difference of STIP1 in different types of breast cancer. Kaplan-Meier Plotter was used to analyze the relationship between the expression of STIP1 and the survival of breast cancer patients with different subtypes. TIMER database was used to analyze the correlation between STIP1 and immune cell infiltration in different types of breast cancer. The String database was used to analyze the STIP1 related interaction proteins. The difference expression of STIP1 between breast cancer and adjacent normal tissue is compared by Wilcoxon test. The difference of other indexes between two groups were compared by Mann-Whitney U test. The difference among groups were compared by Kruskal-Wallis H test, and pairwise comparisons between groups were conducted using the Dunn test. Kaplan-Meier curve was used to analyze the relapse-free survival (RFS) of STIP1 expression differences in different types of breast cancer, and Spearman correlation coefficient was used to evaluate the correlation between the proportion of immune cell infiltration and the expression level of STIP1.

Compared with normal tissues, STIP1 expression is upregulated in different types of breast cancer. High expression of STIP1 is associated with reduced RFS in breast cancer patients, especially in Luminal A breast cancer. STIP1 is positively correlated with the infiltration levels of various immune cells such as CD8⁺ T cells, CD4⁺ T cells, and neutrophils. STIP1 interacts with multiple proteins such as PTGES3, ASHA1, and PRNP, which are mainly involved in biological processes such as protein folding, protein stability, heat stress response, cell cycle, and apoptosis regulation.

The upregulation of STIP1 in breast cancer is associated with poor prognosis for patients, especially in Luminal A subtype breast cancer. STIP1 may play a significant role in the immune microenvironment of breast cancer, influencing tumor development and prognosis by modulating the functional status of immune cells.

Adipose-derived mesenchymal stem cells (ADMSCs) and bone marrow-derived mesenchymal stem cells (BMSCs), as crucial sources of adult stem cells, exhibiting significant potential in the fields of immunomodulation and tissue repair. This article systematically reviews the regulatory mechanisms of ADMSCs and BMSCs on T cells (Th1/Th2/Th17/Treg), B cells, dendritic cells, macrophages, and natural killer (NK) cells, elucidating their shared and distinct characteristics in immunosuppressive pathways. Their spatiotemporal synergistic effects significantly enhance therapeutic efficacy, while heterologous cell combination therapy faces biosafety challenges. Furthermore, this study proposes a standardized quality control system and dynamic dosage regulation strategy, providing a theoretical foundation and translational pathway for optimizing stem cell therapy.

Regenerative medicine aims to repair damaged tissues or organs, which is commonly employed in treating various refractory diseases. Current multimodal regenerative approaches include transplantation of healthy organs, tissues, or cells, stimulation of the body to activate the self-repair response in damaged tissues, and combined application of cells with biodegradable scaffolds to achieve functional tissues. Mesenchymal stem cells (MSCs), presenting in nearly all tissues, exhibiting characteristics such as easy accessibility, self-renewal capacity, multidirectional differentiation potential, and significant regenerative medicine applications. This article summarizes the applications of MSCs in regenerative medicine—primarily encompassing bone, skin, kidney, liver, heart, ovary, cornea, tracheal, and neural tissue repair—and addressing potential risks and considerations associated with their use, providing references for fundamental and clinical application research.

Total pancreatectomy with islet autotransplantation (TPIAT) is the preferred treatment for debilitating chronic pancreatitis (CP) and recurrent acute pancreatitis (RAP) in adults and children who have failed pharmacological and endoscopic therapies. This approach has been practiced in Europe and the United States for nearly 50 years. In 2014, Professor Bellin initiated a large-scale multicenter prospective observational study (POST) on TPIAT to systematically investigate the key questions regarding the patient selection, risks of persistent pain and disability, diabetes risk, optimal timing for surgery, intervention strategies, and the economic viability of the procedure, publishing a series of research works. This review outlines the background of the POST and its published research findings, and also reviewed the results of other teams' research surrounding these directions, aiming to enhance healthcare professionals' understanding of TPIAT technology and its advancements, thereby provide reference for the development of clinical TPIAT work in China.

Premature ovarian failure (POF) is a common complication after hematopoietic stem cell transplantation in patients, which is mainly caused by ovarian toxicity induced by radiotherapy and chemotherapy, and involves complex mechanisms such as cells apoptosis, vascular injury, immune microenvironmental disturbances, oxidative stress and autophagy. POF has a profound impact on female patients' fertility and long-term quality of life, searching for effective ovarian repair methods is a critical issue that needs to be urgently addressed. Umbilical cord mesenchymal stem cells (UC-MSCs) have become a hotspot for POF treatment in recent years due to their low immunogenicity and other advantages. Preclinical studies have shown that UC-MSCs demonstrate potential for repairing ovarian function through various mechanisms such as differentiation and tissue repair, promoting angiogenesis and anti-fibrosis, immune regulation and anti-inflammation, and antioxidation and autophagy regulation. Different routes of injection (e.g. intravenous and local) have shown significant efficacy. Nevertheless, clinical studies are still in the preliminary stage, only small- scale trials and case reports have demonstrated the efficacy of UC-MSCs. Their long-term safety and standardised therapeutic regimens still require further research and validation.

Neural stem cells (NSCs) play a crucial role in the development, regeneration and repair of the nervous system. In recent years, with the in-depth research on the characteristics of NSCs, the immortalization technology of NSCs has gradually become a research hotspot in the field of neurobiology. This technique is not only able to overcome the problem of limited division capacity of NSCs in vitro culture, but also offers the possibility of their widespread use in basic research and clinical applications. However, there are still many challenges and problems in the mechanism, technical methods and clinical application of immortalized NSCs. This article summarizes the latest research progress of neural stem cell immortalization, and discusses its application potential in the field of neurodegenerative diseases and brain injury repair, hoping to provide a new perspective for the future research direction of stem cells and further promote the clinical application of immortalization technology of NSCs.