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Tumor-associated macrophages (TAMs) are the most abundant inflammatory infiltrates in the tumor microenvironment and contribute to lymph node (LN) metastasis. However, the precise mechanisms of TAMs-induced LN metastasis remain largely unknown. Herein, we identify a long noncoding RNA, termed Lymph Node Metastasis Associated Transcript 1 ( LNMAT1 ), which is upregulated in LN-positive bladder cancer and associated with LN metastasis and prognosis. Through gain and loss of function approaches, we find that LNMAT1 promotes bladder cancer-associated lymphangiogenesis and lymphatic metastasis. Mechanistically, LNMAT1 epigenetically activates CCL2 expression by recruiting hnRNPL to CCL2 promoter, which leads to increased H3K4 tri-methylation that ensures hnRNPL binding and enhances transcription. Furthermore, LNMAT1 -induced upregulation of CCL2 recruits macrophages into the tumor, which promotes lymphatic metastasis via VEGF-C excretion. These findings provide a plausible mechanism for LNMAT1 -modulated tumor microenvironment in lymphatic metastasis and suggest that LNMAT1 may represent a potential therapeutic target for clinical intervention in LN-metastatic bladder cancer. Mechanism of lymph node (LN) metastasis induced by tumor associated macrophages (TAMs) remains unclear. Here they demonstrate that a long noncoding RNA LNMAT1 promotes LN metastasis of bladder cancer via recruitment of TAMs through epigenetic regulation of CCL2 expression.

Immune checkpoint inhibitors (ICIs) for cancer therapy may induce immune-related adverse events including myocarditis, which occurs infrequently but carries a high mortality rate. Crocins are the active constituents derived from Crocus sativus L. (saffron), and have demonstrated various bioactivities including anti-tumor, anti-inflammation, antioxidation, anti-ischemia, anti-aging, and neuroprotective effects. This study established a subcutaneous xenotransplanted tumor model of human liver cancer in nude mice to better mimic ICI-related myocarditis. Animal experimental results revealed that crocins improved cardiac function, relieved myocardial damage and autoimmune response, and suppressed oxidative stress and inflammatory reaction. Quantitative proteomics and Western blotting verification confirmed that crocins ameliorated experimental ICI-related myocarditis by targeting the Hpx/Nrf2/HO-1 pathway. Molecular docking revealed that the best docking activities were demonstrated by crocin I–HO-1, crocin II–Hpx, and crocin III–Nrf2. These findings shed new light on the development of therapeutic strategies for treating ICI-related myocarditis and provided the fundamental basis for expanding the clinical application of crocins.

Advanced natural killer/T cell lymphoma (NKTL) has demonstrated poor prognosis with currently available therapies. Here, we report the efficacy of anti-programmed death 1 (PD-1) antibody with the P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) regimen in advanced NKTL. Nine patients underwent six 21-day cycles of anti-PD-1 antibody (day 1), pegaspargase 2000 U/m2 (day 1), gemcitabine 1 g/m2 (days 1 and 8) and oxaliplatin 130 mg/m2 (day 1), followed by anti-PD-1 antibody maintenance every 3 weeks. Programmed death-ligand 1 (PD-L1) expression and genetic alterations were determined in paraffin-embedded pretreatment tissue samples using immunohistochemistry and next-generation sequencing (NGS) analysis. Responses were assessed using 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) and computed tomography or magnetic resonance imaging. Eight patients exhibited significant responses, comprising of seven complete remissions and one partial remission (overall response rate: 88.9%). After a median follow-up of 10.6 months, 6/9 patients (66.7%) remained in complete remission. The most common grade 3/4 adverse events were anemia (33.3%), neutropenia (33.3%), and thrombocytopenia (33.3%); all of which were manageable and resolved. Immunochemotherapy produced a high response rate in patients with positive PD-L1 expression (5/6, 83.3%). NGS analysis suggested that STAT3/JAK3/PD-L1 alterations and ARID1A mutation were associated with immunochemotherapy efficacy. Mutation in DDX3X and alteration in epigenetic modifiers of KMT2D, TET2, and BCORL1 might indicate a poor response to immunochemotherapy. In conclusion, the anti-PD-1 antibody plus P-GEMOX regimen demonstrated promising efficacy in advanced NKTL. PD-L1 expression combined with specific genetic alterations could be used as potential biomarkers to predict therapeutic responses to immunochemotherapy.

This study aimed to explore influencing factors for respite services among family caregivers in disabled elderly individuals, and develop a nomogram model to rank these factors. 356 family caregivers of disabled elderly individuals were collected and divided into a training set (n=249) and a validation set (n=107) in a 7:3 ratio. Univariate and multivariate logistic regression analyses were performed to identify risk factors, and a nomogram model was constructed in the training set. The predictive performance was evaluated using receiver operating characteristic (ROC) curves and calibration curves. Decision curve analysis (DCA) was used to assess the clinical utility. In the training set, 131 (52.61%) family caregivers showed a demand for respite services, while 56 (52.34%) patients showed a demand for respite services in the validation set. Multivariate logistic regression revealed that caregiver age, household income, caregiving duration, caregiving frequency, self-care ability, and community support were independent influencing factors for respite services (all P <0.05). The nomogram model demonstrated good calibration and predictive performance in both training and validation sets, with C-index values of 0.883 and 0.823, respectively. The areas under ROC curve (AUC) were 0.859 (95%CI：0.805-0.912) and 0.894 (95%CI：0.820-0.969), with sensitivity and specificity values of 0.943, 0.783 and 0.907, 0.871, respectively. This study identified key influencing factors for respite services in family caregivers of disabled elderly individuals. The predictive model exhibited strong predictive performance and clinical applicability, aiding relevant authorities in accurately identifying caregivers in need.

Background Metastatic prostate cancer is a leading cause of cancer-related death in men. Cancer stem cells (CSCs) are involved in tumor progression and metastasis, including in prostate cancer. There is an obvious and urgent need for effective cancer stem cells specific therapies in metastatic prostate cancer. MicroRNAs (miRNAs) are an important class of pervasive genes that are involved in a variety of biological functions, especially in cancer. The goal of this study was to identify miRNAs involved in prostate cancer metastasis and cancer stem cells. Methods A microarray and qRT-PCR were performed to investigate the miRNA expression profiles in PC-3 sphere cells and adherent cells. A transwell assay was used to evaluate the migration of PC-3 sphere cells and adherent cells. MiR-143 was silenced with antisense oligonucleotides in PC-3, PC-3-M and LNCaP cells. The role of miR-143 in prostate cancer metastasis was measured by wound-healing and transwell assays in vitro and bioluminescence imaging in vivo. Bioinformatics and luciferase report assays were used to identify the target of miR-143. Results The expression of miR-143 and the migration capability were reduced in PC-3 sphere cells and progressively increased during sphere re-adherent culture. Moreover, the down-regulation of miR-143 suppressed prostate cancer cells migration and invasion in vitro and systemically inhibited metastasis in vivo. Fibronectin type III domain containing 3B (FNDC3B), which regulates cell motility, was identified as a target of miR-143. The inhibition of miR-143 increased the expression of FNDC3B protein but not FNDC3B mRNA in vitro and vivo. Conclusions These data demonstrate for the first time that miR-143 was up-regulated during the differentiation of prostate cancer stem cells and promoted prostate cancer metastasis by repressing FNDC3B expression. This sheds a new insight into the post-transcriptional regulation of cancer stem cells differentiation by miRNAs, a potential approach for the treatment of prostate cancer.

Although human papillomavirus (HPV) infection is a major cause leading to the development of cervical intraepithelial neoplasia (CIN), the relationship between genital microbiome and HPV persistence/clearance is not well established. Loop electrosurgical excision procedure (LEEP) is one of standard treatments of CIN 2/3 globally, yet little is known about how the LEEP influence genital microbiota. We conducted a prospective study of 26 patients with CIN2/3 who underwent analysis of cervical microbiome before and after 3 months of LEEP treatment. Cervical swabs were collected, and microbiomes were analyzed by 16S ribosomal RNA gene sequencing. A decrease of cervical microbial diversity was observed after 3 months of LEEP treatment. Notably, a significant shift from community type of a Prevotella -containing and lack of a consistent dominant species to lactobacillus iners dominated microbiome correlated with LEEP. Particularly, Leptotrichia and clostridium were further decreased after LEEP treatment ( P  = 0.049 and P  = 0.002, respectively). Our results suggest that the cervical microbiome is altered after LEEP treatment in patients with CIN2/3. Further studies with larger sample sizes are needed to validate these findings.

Background Treatment options beyond the first-line setting for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) are limited. The role of the multitarget tyrosine kinase inhibitor anlotinib in RM-NPC is unclear. Methods In this prospective, single-arm, phase 2 trial, patients with histologically confirmed RM-NPC and failure of at least two lines of prior systemic treatments were eligible. Anlotinib was given at 12 mg once daily on days 1–14 every 3 weeks until disease progression or intolerable toxicities. The primary end point was disease control rate, defined as the percentage of patients achieving complete response, partial response, or stable disease by RECIST criteria. Results From April 2019 to March 2021, 39 patients were enrolled and received a median of 4 cycles (range, 0.5–20) of anlotinib treatment. Partial response and stable disease were observed in 8 and 20 patients, respectively. The disease control rate was 71.8%, and objective response rate was 20.5%. With a median follow-up of 17.2 months, the median progression-free survival was 5.7 months. The 12-month overall survival was 58.3%, and the median overall survival was not reached. The most frequent grade 3/4 treatment-related adverse events were hand-foot syndrome (23.7%), oral mucositis (21.0%), hypertension (7.9%), and triglyceride elevation (7.9%). Hemorrhage, all grade 1 or 2, occurred in 34.2% of the patients. Conclusions Anlotinib monotherapy exhibited promising anti-tumor activities and disease control for heavily pretreated RM-NPC patients with a tolerable toxicity profile. Trial registration ClinicalTrials.gov: NCT03906058.

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder characterized by systemic inflammation, endothelial dysfunction, and placental insufficiency. While inadequate trophoblast invasion and impaired spiral artery remodeling have long been recognized as central to its pathogenesis, emerging evidence underscores the critical roles of dysregulated iron metabolism and its crosstalk with immune responses, particularly macrophage-mediated inflammation, in driving PE development. This review systematically explores the dynamic changes in iron metabolism during pregnancy, including increased maternal iron demand, placental iron transport mechanisms, and the molecular regulation of placental iron homeostasis. We further explore the contribution of ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, to trophoblast dysfunction and pregnancy-related diseases, including PE. Macrophages, pivotal immune regulators at the maternal–fetal interface, exhibit distinct polarization states that shape tissue remodeling and immune tolerance. We outline their origin, distribution, and polarization in pregnancy, and emphasize their aberrant phenotype and function in PE. The bidirectional crosstalk between iron and macrophages is also dissected: iron shapes macrophage polarization and function, while macrophages reciprocally modulate iron homeostasis. Notably, excessive reactive oxygen species (ROS) and pro-inflammatory cytokines secreted by M1-polarized macrophages may exacerbate trophoblast ferroptosis, amplifying placental injury. Within the context of PE, we delineate how iron overload and macrophage dysfunction synergize to potentiate placental inflammation and oxidative stress. Key iron-responsive immune pathways, such as the HO-1/hepcidin axis and IL-6/TNF-α signaling, are discussed in relation to disease severity. Finally, we highlight promising therapeutic strategies targeting the iron–immune axis, encompassing three key modalities—iron chelation therapy, precision immunomodulation, and metabolic reprogramming interventions—which may offer novel avenues for PE prevention and treatment.

The association between vitamin intake and gastric cancer (GC) has been widely debated due to the relatively weak evidence. In this study, a meta-analysis of prospective and well designed observational studies were performed to explore this association. MEDLINE, Cochrane Library, and Sciencedirect were searched for studies of vitamin consumption and gastric cancer. This produced 47 relevant studies covering 1,221,392 human subjects. Random effects models were used to estimate summary relative risk (RR). Dose-response, subgroup, sensitivity, meta-regression, and publication bias analyses were conducted. The RR of gastric cancer in the group with the highest vitamin intake was compared to that of the lowest intake group. Total vitamin intake was 0.78 (95% CI, 0.71-0.83). In 9 studies that individuals were given doses at least 4 times above the tolerable upper intake (UL) vitamins, the RR was 1.20 (95% CI, 0.99-1.44). However, in 17 studies that individuals received doses below the UL, the RR was 0.76 (95% CI, 0.68-0.86). Dose-response analysis was conducted on different increments in different types of vitamins (vitamin A: 1.5 mg/day, vitamin C: 100 mg/day, vitamin E: 10 mg/day) intake with a significant reduction in the risk of gastric cancer, respectively, 29% in vitamin A, 26% in vitamin C, and 24% in vitamin E. This meta-analysis clearly demonstrated that low doses of vitamins can significantly reduce the risk of GC, especially vitamin A, vitamin C, vitamin E.

Regulating the catalytic activity of nanozymes is significant for their applications in various fields. Here, we demonstrate a new strategy to achieve reversible regulation of the nanozyme's activity for sensing purpose. This strategy involves the use of zero-dimensional MoS2 quantum dots (MQDs) as the building blocks of nanozymes which display very weak peroxidase (POD)-like activity. Interestingly, such POD-like activity of the MQDs largely enhances in the presence of Fe3+ while diminishes with the addition of captopril thereafter. Further investigations identify the mechanism of Fe3+-mediated aggregation-induced enhancement of the POD-like activity and the inhibitory effect of captopril on the enhancement, which is highly dependent on their concentrations. Based on this finding, a colorimetric method for the detection of captopril is developed. This sensing approach exhibits the merits of simplicity, rapidness, reliability, and low cost, which has been successfully applied in quality control of captopril in pharmaceutical products. Moreover, the present sensing platform allows smartphone read-out, which has promising applications in point-of-care testing devices for clinical diagnosis and drug analysis. [Display omitted] •A new post-synthesis strategy is developed to achieve reversible regulation of nanozyme's activity.•Fe3+-mediated aggregation can enhance the peroxidase-like activity of MoS2 quantum dots more than 10 times.•Quality control of captopril in pharmaceutical products is realized by manipulating nanozyme's catalytical activity.•This sensing approach allows smartphone read-out, which has promising applications in point-of-care testing.