Vitamin D supplementation may be beneficial in improving the prognosis of patients with chronic obstructive pulmonary disease in the intensive care unit: a retrospective study.

Background: Vitamin D is a crucial fat-soluble vitamin that has garnered significant attention due to its potential impact on respiratory health. It is noteworthy that many patients with chronic obstructive pulmonary disease (COPD) often experience deficiencies or insufficiencies of vitamin D. To address this issue, our retrospective study aimed to explore the potential association between serum 25-hydroxyvitamin D concentration and the prognoses of COPD patients in the Intensive Care Unit (ICU). Methods: This study utilised data from the Medical Information Marketplace in Intensive Care IV (MIMIC-IV), a database of patients admitted to the Intensive Care Unit at Beth Israel Deaconess Medical Center (BIDMC) in the United States of America, with a focus on patients with a diagnosis of COPD. These patients were categorized into two groups: those who received vitamin D supplementation during their ICU stay and those who did not. We assessed in-hospital mortality and ICU mortality outcomes. Our analysis involved various analytical tools, including Kaplan-Meier survival curves, Cox proportional risk regression models, and subgroup analyses, to investigate the relationship between vitamin D supplementation and these outcomes. Additionally, we employed propensity-score matching (PSM) to enhance the reliability of our findings. Results: The study included a total of 3,203 COPD patients, with 587 in the vitamin D group and 2,616 in the no-vitamin D group. The Kaplan-Meier survival curve demonstrated a significant difference in survival probability between the two groups. After adjusting for potential confounders using Cox regression models, the vitamin D group exhibited a substantially lower risk of in-hospital and ICU mortalities compared to the no-vitamin D group. The hazard ratios for in-hospital and ICU mortalities in the vitamin D group were 1.7 (95% CI: 1.3, 2.3) and 1.8 (95% CI: 1.2, 2.6), respectively. Propensity-score matching (PSM) estimation yielded consistent results. Furthermore, in the subgroup analysis, female patients who received vitamin D supplementation showed a reduced risk of in-hospital mortality. Conclusion: The study suggests that vitamin D supplementation may be linked to a reduction in in-hospital and ICU mortalities among COPD patients in the ICU. Of particular note is the potential benefit observed in terms of in-hospital mortality, especially for female patients.

Blocking of oestrogen signals improves anti-tumour effect regardless of oestrogen receptor alpha expression in cancer cells.

BACKGROUND: Anti-oestrogenic therapy has been used for breast cancer patients with oestrogen susceptibility cancer cells. However, little has been known about its potential role for immune cell biology within TME, particularly in cancer patients without oestrogen sensitivity of tumour cells. Therefore, we aimed to study the effect of oestrogen on immunity within TME. METHODS: Using a clinical dataset, immune cells of humans and mice, female mice with and without ovaries, and several murine ERα-negative cancer cell lines, we evaluated the effect of oestrogen on immunity in TME. RESULTS: Clinical data analysis suggested oestrogen's suppressive efficacy against CTLs. Additionally, in vitro and in vivo experiments revealed intra-tumoural CTLs' direct repressive action by oestrogen in both mice and humans; blockade of oestrogen signals cancelled its immunosuppression resulting in tumour growth reduction in vivo. Most notably, immunotherapy (immune checkpoint inhibitor; ICI) combined with anti-oestrogenic therapy exhibited a dramatic anti-tumour effect. CONCLUSIONS: This study provides novel insights into how oestrogen contributes to tumour progression and a therapeutic rationale for blocking oestrogen signalling to boost the anti-tumour effect of ICI, regardless of tumour cells' ERα expression.

Cigarette smoke promotes chronic obstructive pulmonary disease (COPD) through the miR-130a/Wnt1 axis.

Cigarette smoke (CS) is a crucial factor in chronic obstructive pulmonary disease (COPD). Wnt/ß-catenin signaling deregulation may further contribute to COPD progression. The deregulation and dysfunction of miRNAs in COPD have been reported. Investigating the deregulated miRNAs and their potential role in COPD progression may provide novel strategies for COPD treatment. In the present study, we analyzed significantly differentially-expressed miRNAs in COPD according to GSE44531 and miR-130a was selected. We revealed the upregulation of miR-130a in COPD, both in cigarette smoke extract (CSE)-treated BEAS-2B cells and CS-exposed mice. MiR-130a negatively regulated three critical factors in Wnt/ß-catenin signaling, Wnt1, ß-Catenin, and LEF1. MiR-130a inhibition rescued CSE-blocked activation of Wnt/ß-catenin signaling in vitro. MiR-130a targets WNT1 3'UTR to inhibit its expression. Moreover, in CSE-stimulated BEAS-2B cells, miR-130a overexpression aggravated, while miR-130a inhibition partially attenuated CSE-caused suppression on cell migration and proliferation. MiR-130a aggravates CSE-induced cellular injury in BEAS-2B cells by targeting Wnt signaling. In summary, miR-130a has a pathogenetic role in CS-induced COPD and regulates Wnt/ß-catenin signaling via targeting Wnt1. Our findings indicate that miR-130a is a potential therapeutic target for the treatment of CS-induced COPD.