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Microglia respond to stressors by secreting cytokines or growth factors, playing a crucial role in maintaining brain homeostasis. While the antidepressant-like effects of Polygonatum sibiricum polysaccharides (PSPs) have been observed in mice, their potential effectiveness involving microglial regulation remains unknown. This study investigates the antidepressant-like mechanism of PSP by regulating microglial phenotype and signaling pathways in the prefrontal cortex of chronic restraint stress (CRS)-induced mice. PSP was extracted, purified, characterized, and orally administered to CRS mice. High-performance gel permeation chromatography (HPGPC) revealed that PSP has a molecular weight of 5.6 kDa. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) showed that PSP exhibited a layered structure with densely packed, irregular surfaces. PSP treatment significantly increased sucrose preference (low: 71%, p < 0.01; medium: 69%, p < 0.05; high: 75%, p < 0.001 vs. CRS: 58%) and reduced immobility time (low: 74 s, p < 0.01; medium: 68 s, p < 0.01; high: 79 s, p < 0.05 vs. CRS: 129 s), indicating the alleviation of depressive-like behaviors. PSP inhibited microglial activation (PSP, 131/mm2 vs. CRS, 173/mm2, p = 0.057), reversing CRS-induced microglial hypertrophy and hyper-ramification. Furthermore, PSP inactivated microglial activation by inhibiting NLRP3/ASC/caspase-1/IL-1β signaling pathways, increasing BDNF synthesis and activating brain-derived neurotrophic factor (BDNF)-mediated neurogenesis (PSP, 80/per DG vs. CRS, 49/per DG, p < 0.01). In conclusion, PSP exerts antidepressant-like effects through the regulation of microglial activity and neuroinflammatory pathways, indicating it as a potential natural compound for depression treatment. [ABSTRACT FROM AUTHOR]

Background: The clinical implication of plasma ESR1 mutations in the estrogen receptor (ER)-positive metastatic breast cancer (MBC) patients who had progressed after prior aromatase inhibitor (AI)-based therapy remains controversial. We conducted the first meta-analysis to investigate the prognostic significance and predictive role of plasma ESR1 mutations in MBC patients with prior exposure to AI therapy. Materials and methods: We searched PubMed, Embase, and Cochrane Library databases for eligible studies. Meta-analysis was conducted to calculate combined hazard ratios (HRs) with 95% CIs for progression-free survival (PFS) and overall survival (OS). Subgroup and sensitivity analyses were also performed. Results: This study enrolled a total of 1,530 patients with ER-positive MBC cases from six articles, including 429 ESR1 mutation carriers (28.04%). Meta-analysis demonstrated that plasma ESR1 mutation carriers had significantly worse PFS (HR: 1.40, 95% CI: 1.17–1.66; P [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic, debilitating condition with limited therapeutic options. Dietary components like blueberries have emerged as potential modulators of inflammation and tissue repair in gastrointestinal diseases. This study investigated endoplasmic reticulum (ER) stress-mediated apoptosis mediated protective effects of blueberries in ameliorating dextran sulfate sodium (DSS)-induced IBD. Firstly, a total of 86 anthocyanin compounds were identified in blueberry extract by LC-MS spectroscopy, including 35 cyanidin, 9 delphinidin, 14 malvidin, 10 peonidin, and 9 petunidin. Then, the animal study showed that blueberry supplementation notably ameliorated DSS-induced IBD symptoms, as evidenced by improved histopathological scores and a reduced disease activity index (DAI) score. Additionally, blueberries attenuated ER stress by inhibiting the colonic PERK/eIF2α/ATF4/CHOP signaling pathway. Furthermore, blueberries inhibited the expression of the pro-apoptotic protein, caspase-3, and decreased colonic apoptosis, as evidenced by TUNEL assay results. However, it did not affect the expression of anti-apoptotic proteins, bcl-2 and bcl-xl. Finally, blueberries enhanced the intestinal barrier by upregulating ZO-1, claudin-1, occludin, and E-cadherin. In conclusion, blueberries demonstrate therapeutic potential against DSS-induced IBD-like symptoms in mice, possibly by regulating ER stress-mediated apoptosis pathways. These findings suggest that blueberries might be an effective dietary intervention for IBD management.

Purpose: There is no research evidence demonstrate which is the better partner strategy, endocrine therapy or chemotherapy, to combine with anti-HER2 therapy as the first-line management of hormone receptor (HR)-positive (HR+) and HER2-positive (HER2+) metastatic breast cancer (MBC). We wished to ascertain if trastuzumab plus endocrine therapy is noninferior to trastuzumab plus chemotherapy., Patients and Methods: We conducted an open-label, noninferiority, phase III, randomized, controlled trial (NCT01950182) at nine hospitals in China. Participants, stratified by previous adjuvant endocrine therapy and disease status (recurrent disease vs. de novo metastasis), were assigned randomly (1:1) to receive trastuzumab plus endocrine therapy (per investigator's choice of oestrogen-receptor modulators or aromatase inhibitor, with/without concurrent ovarian suppression) or chemotherapy (per investigator's choice of taxanes, capecitabine, or vinorelbine). The primary endpoint was progression-free survival (PFS) with a noninferiority upper margin of 1.35 for the HR. The intention-to-treat population was used in primary and safety analyses., Results: A total of 392 patients were enrolled and assigned randomly to receive trastuzumab plus endocrine therapy (ET group, n = 196) or trastuzumab plus chemotherapy (CT group, n = 196). After a median follow-up of 30.2 months [interquartile range (IQR) 15.0-44.7], the median PFS was 19.2 months [95% confidence interval (CI), 16.7-21.7)] in the ET group and 14.8 months (12.8-16.8) in the CT group (hazard ratio, 0.88; 95% CI, 0.71-1.09; Pnoninferiority < 0.0001). A significantly higher prevalence of toxicity was observed in the CT group compared with the ET group., Conclusions: Trastuzumab plus endocrine therapy was noninferior to trastuzumab plus chemotherapy in patients with HR+HER2+ MBC., (©2021 The Authors; Published by the American Association for Cancer Research.)

Importance: Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and death are needed., Objective: To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer., Design, Setting, and Participants: Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy., Interventions: Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy., Main Outcomes and Measures: The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events., Results: Among 443 women who were randomized, 434 were included in the full analysis set (mean [SD] age, 46 [9.9] years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio [HR] for risk of recurrence or death, 0.64 [95% CI, 0.42-0.95]; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 [95% CI, 0.38-0.92]; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 [95% CI, 0.47-1.19]; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 [95% CI, 0.46-1.13]; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event., Conclusions and Relevance: Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival., Trial Registration: ClinicalTrials.gov Identifier: NCT01112826.

Background: Triple-negative breast cancer (TNBC) is associated with poor prognosis. There is an urgent need for elucidation of novel targets for TNBC therapy and to improve the prognosis of patients. The aim of this study was to evaluate the prognostic value of p62 expression in TNBC., Methods and Results: Expression of p62 in tissue microarray was evaluated by immunohistochemistry in 163 patients with TNBC. The prognostic value of p62 expression was assessed by a Cox regression model adjusted for clinical characteristics. Overexpression of p62 was observed in 51 (31.3%) of 163 TNBC, and significantly correlated with advanced stage and a higher proportion of positive lymph nodes and lymphovascular invasion. A significant correlation was found between p62 expression and disease-free survival and overall survival. Accordingly, the 10-year distant metastasis-free survival for p62-overexpression and p62-underexpression patients were 58.9% and 92.5%, respectively (P<0.0001). Multivariate analysis indicated that p62-negative was a significant independent prognostic factor of disease-free survival (P=0.017), but not for overall survival (P=0.845) in all patients., Conclusion: Our results suggest that overexpression of p62 in TNBC is associated with a higher risk of distant metastases. This finding could open new avenues for the development of novel therapy strategies for TNBC.

Purpose: The aim of the present study was to assess the association of psychological stress and social support with anxiety and depressive symptoms in Chinese newly diagnosed breast cancer patients., Methods: Four hundred and one patients with breast cancer were recruited. Their demographic characteristics, psychological stress and social support were determined with a structured questionnaire, and their anxiety and depressive symptoms were assessed with the Hospital Anxiety and Depression Scale., Results: Psychological stressors caused by breast cancer diagnosed originated from five major sources, as determined by factor analysis. These included "Worrying about health being harmed, " "Fear of decline of physical function, " "Fear of work being harmed, " "Worry about daily life and social relationship being restricted, " and "Fear of family being harmed. " Hierarchical linear regression analysis indicated that, after adjusting for gender, age, marital status, educational level, and duration of illness, solid social support can alleviate such symptoms., Conclusions: The results of this study suggest that there are strong associations between patients' needs and psychological distress with newly diagnosed breast cancer. Social support might affect these associations in Chinese women with breast cancer.