Tianjin haihe hospital

To investigate the role of CD44 in papillary thyroid carcinoma (PTC) lymph node metastasis and its connotation with Treg-mediated immunosuppression through TGF-β and IL-10 signaling. Eighty-two benign thyroid nodule patients were compared with 122 PTC patients. Differentially expressed proteins (DEPs) were identified in both tissue and serum. CD44 expression was validated by ELISA, IHC and flow cytometry. The proportion of Treg and cytokines were analyzed in parallel. The tumor microenvironment architecture was examined using 3D tissue clearing and whole-mount imaging. The functional role of CD44 was further explored using TPC-1 human PTC cell line through gain-of-function and loss-of-function assays in vitro. Proteomic analysis identified 34 tissue and 17 serum DEPs involved in metastasis. CD44 levels in serum were significantly higher in PTC patients than in controls (345.45 ± 44.88 pg/mL vs. 73.33 ± 25.64 pg/mL, P < 0.001). Furthermore, CD44 expression in the serum of CLNM patients was further elevated (782.01 ± 168.38 pg/mL vs. 248.77 ± 55.33 pg/mL, P < 0.001). Multivariate analysis identified CD44 as an independent risk factor for PTC (OR = 5.271, 95% CI: 1.741 ~ 15.959) and CLNM (OR = 3.995, 95% CI: 1.298 ~ 12.298). CD44 levels showed positive correlations with increased TGF-β, IL-10 levels, and Treg frequency. CD44 levels were connected with amplified TGF-β, IL-10, and Treg frequency. IHC and 3D imaging also demonstrated colocalization of CD44⁺ tumor cells and Tregs in H&E sections and whole-mount. Importantly, CD44 knockdown suppressed, while CD44 overexpression enhanced, TPC-1 cell proliferation in vitro, suggesting a direct role of CD44 in promoting tumor cell growth. Our data suggest that CD44 may contribute to PTC metastasis by modulating the immunosuppressive microenvironment through TGF-β/IL-10 mediated Treg accumulation and by directly driving tumor cell proliferation. These findings highlight a potential pathogenic role of CD44 in PTC progression.

Radiation enteritis is a common complication in patients undergoing abdominal radiotherapy. Current management strategies face significant limitations: clinical agents like amifostine are hindered by systemic side effects and demanding administration; direct supplementation with radioprotective metabolites such as propionate suffers from low bioavailability and transient action; and conventional probiotics lack targeted therapeutic output. To address these challenges, we engineered Escherichia coli Nissle 1917 to function as a living therapeutic that continuously produces and delivers propionate directly in the gut. This propionate-engineered probiotic achieved a production yield of 181.33 ± 4.27mg/L in vitro. In a mouse model of abdominal irradiation, this engineered bacterium alleviated radiation-induced intestinal damage by continuously releasing propionate and enhancing intestinal epithelial barrier function. Multi-omics analysis revealed that the engineered bacterium could restore intestinal microbiota homeostasis, enhancing the abundance of advantageous bacteria with radioprotective properties (e.g., Dubosiella, Akkermansia). Moreover, it modulated intestinal microbiota metabolism, influencing the metabolism of ascorbic acid, aldoses, and other metabolites. Additionally, it protected the intestinal mucosal barrier from radiation-induced damage, which was associated with the modulation of the SOCS1/JAK2/STAT3 signaling pathway. This study introduces a novel biological therapy to mitigate the side effects of radiotherapy and could open new avenues for preventing and treating radiation-induced intestinal injury.

Immune-mediated bone marrow failure (AA) is characterized by T cell-mediated destruction of hematopoietic stem and progenitor cells (HSPCs). The JAK-STAT signaling pathway plays a crucial role in regulating immune responses, and JAK inhibitors have shown potential in treating immune-mediated disorders. This study investigates the effects of MMB, a JAK inhibitor, in a mouse model of immune-mediated bone marrow failure to evaluate its impact on hematopoiesis and immune cell function. In this study, immune-mediated AA was induced in B6D2F1 female mice through irradiation and lymphocyte infusion. The mice were treated with MMB monotherapy at doses of 6.25 and 12.5 mg/kg for 14 days. Peripheral blood cell counts, bone marrow cell counts, plasma cytokine levels, T lymphocyte subsets, Fas/FasL expression, and hematopoietic stem and progenitor cell (HSPC) levels were analyzed to assess the effects of MMB treatment on immune function and hematopoiesis. MMB treatment exacerbated the reduction in peripheral blood cell counts in marrow failure mice and decreased bone marrow hematopoietic cell numbers. Concurrently, MMB also reduced cytokine levels. The treatment also led to a significant reduction in CD4+ T cells and Tregs in both the spleen and bone marrow, while the low-dose MMB group exhibited a decrease in CD8+ T cell count. Additionally, MMB did not significantly improve HSPC levels, and a decrease in the more primitive LSK and LT-HSC populations was observed. However, later-stage stem and progenitor cells, such as ST-HSCs, MPPs, and CMPs, showed an increase in numbers. The treatment also resulted in downregulation of Fas expression on non-T cells, while FasL expression on lymphocytes increased. MMB treatment exacerbated peripheral blood cell reduction and impaired bone marrow hematopoiesis in the immune-mediated AA mouse model. Although MMB modulated T lymphocyte subsets, it did not significantly improve hematopoietic stem and progenitor cell function. These findings highlight the need for further research to explore the potential and limitations of JAK inhibitors like MMB in the treatment of immune-mediated bone marrow failure.

Sulfur is an essential macronutrient in plants, involved in the synthesis of proteins, amino acids, cofactors, and secondary metabolites, as well as in stress responses. In plants, sulfate transporters (SULTRs) are membrane proteins that mediate the uptake, distribution, and remobilization of sulfate. This review examines the diversity of functions, physiological roles, and interactions of plant SULTRs. We also review the complex regulatory mechanisms that control SULTR gene expression and transporter activity, enabling plants to dynamically adapt to environmental fluctuations and changing nutrient requirements. Additionally, we review the role of SULTRs in mediating plant responses to abiotic and biotic stresses, including drought, salinity, heavy metal toxicity, and pathogen infections. Recent evidence highlights extensive crosstalk between SULTRs and other nutrient pathways, particularly nitrogen and phosphate, as well as their integration with phytohormone signaling networks. Advances in genomics, transcriptomics, and proteomics over the past decade have significantly enhanced our understanding of the complex interactions between SULTRs and other nutrient pathways, phytohormones, and signaling molecules. These findings highlight the pivotal role of SULTRs in maintaining sulfur homeostasis and enhancing nutrient use efficiency. By synthesizing recent discoveries, this review identifies SULTRs as promising molecular targets for crop improvement, stress resilience, and sustainable nutrient management, particularly under sulfur-deficient conditions.

Stage II-III colorectal cancer (CRC) represents the initial phase of tumor invasion and lymph node metastasis. Surgery is the preferred treatment option for patients at this stage, however, due to the complex progression mechanisms of the disease, incomplete tumor resection, postoperative cancer cell metastasis, and the development of drug resistance to chemotherapy often lead to poor prognosis. The present study aimed to investigate the status of poor postoperative prognosis in patients with stage II-III CRC following radical surgery, analyze the impact of preoperative albumin-hemoglobin (ALB-Hb) score and serum microRNA-497-5p (miR-497-5p) levels on adverse outcomes and develop a predictive model for poor prognosis. Baseline data of 154 patients with stage II-III CRC treated at Tianjin Haihe Hospital (Tianjin, China) or Guangzhou First People's Hospital (Guangzhou, China) between December 2021 and December 2024 were retrospectively selected. Patients were stratified into the poor and good prognosis groups based on clinical outcomes. Univariate analysis was performed on baseline characteristics and laboratory parameters. Variables demonstrating notable differences were subsequently evaluated for multicollinearity. Factors without collinearity were incorporated into a Cox proportional hazards regression model to identify determinants of postoperative prognosis in patients treated with radical resection. These predictors were then used to construct a prognostic nomogram, with model accuracy verified through calibration curves. Among the 154 patients with stage II-III CRC, 63 cases (40.91%) had poor prognosis and 91 cases (59.09%) had good prognosis. Univariate and collinearity analyses revealed marked differences in preoperative levels of miR-497-5p, Kallikrein-related peptidase 5 (KLK5), angiopoietin-2 (Ang-2) and ALB-Hb scores, with no collinearity observed (P<0.05; variation inflation factor ≤10; tolerance ≥0.1). Cox proportional hazards regression model demonstrated that all these indicators were independent factors influencing poor prognosis following radical surgery in patients with stage II-III CRC (all P<0.05). Based on these findings, a nomogram was constructed and calibration curves closely approximated the ideal curve. Preoperative ALB, Hb, miR-497-5p, KLK5, Ang-2 levels and ALB-Hb scores were notable prognostic factors for patients with stage II-III CRC following radical resection, demonstrating high predictive value for poor postoperative outcomes. The present study provided clinically relevant indicators to screen high-risk patients with potential poor prognosis following radical surgery for stages II-III CRC.