Exploring the relationship between gut microbiota and breast cancer risk in European and East Asian populations using Mendelian randomization.

BACKGROUND: Several studies have explored the potential link between gut microbiota and breast cancer; nevertheless, the causal relationship between gut microbiota and breast cancer remains unclear. METHODS: We utilized summary statistics from genome-wide association studies (GWAS) of the gut microbiome from the MiBioGen project with summary data from GWAS on breast cancer from the FinnGen consortium and the IEU database, with the IEU data sourced from the Biobank Japan. Preliminary statistical analyses were conducted using inverse variance weighting (IVW), supplemented by various sensitivity analysis methods, including MR-Egger regression, weighted median, weighted mode, simple median, and simple mode, to ensure the robustness of our findings. Heterogeneity and pleiotropy were assessed to avoid misleading conclusions caused by unconsidered confounders or non-specific effects of genetic variants, ensuring that the results reflect a genuine causal relationship. RESULTS: In European populations, four types of gut microbiota were associated with breast cancer. The genus Erysipelatoclostridium was positively associated with the risk of breast cancer, with an odds ratio (OR) of 1.21 (95% confidence interval [CI] 1.083-1.358), false discovery rate (FDR) = 0.0039. The class Coriobacteriia, order Coriobacteriales, and family Coriobacteriaceae, which belong to the same phylogenetic system, showed a consistent inversely association with breast cancer risk, with an OR of 0.757 (95% CI 0.616-0.930), FDR = 0.0281. In East Asian populations, three types of gut microbiota were related to breast cancer. The Eubacterium ruminantium group was positively associated with breast cancer risk, with an OR of 1.259 (95% CI 1.056-1.499), FDR = 0.0497. The families Porphyromonadaceae and Ruminococcaceae were inversely associated with breast cancer risk, with ORs of 0.304 (95% CI 0.155-0.596), FDR = 0.0005, and 0.674 (95% CI 0.508-0.895), FDR = 0.03173, respectively. However, these two taxa had limited instrumental variables, restricting the statistical power and potentially affecting the interpretation of the results. CONCLUSION: This MR analysis demonstrated a probable causal link between specific gut microbiota and breast cancer. This study, through Mendelian randomization analysis comparing European and East Asian populations, reveals that gut microbiota may influence breast cancer risk differently across populations, providing potential directions for developing targeted prevention and treatment methods.

Recent progress in mesenchymal stem cell-based therapy for acute lung injury.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening diseases in critically ill patients. Although pathophysiology of ALI/ARDS has been investigated in many studies, effective therapeutic strategies are still limited. Mesenchymal stem cell (MSC)-based therapy is emerging as a promising therapeutic intervention for patients with ALI. During the last two decades, researchers have focused on the efficacy and mechanism of MSC application in ALI animal models. MSC derived from variant resources exhibited therapeutic effects in preclinical studies of ALI with different mechanisms. Based on this, clinical studies on MSC treatment in ALI/ARDS has been tried recently, especially in COVID-19 caused lung injury. Emerging clinical trials of MSCs in treating COVID-19-related conditions have been registered in past two years. The advantages and potential of MSCs in the defense against COVID-19-related ALI or ARDS have been confirmed. This review provides a brief overview of recent research progress in MSC-based therapies in preclinical study and clinical trials in ALI treatment, as well as the underlying mechanisms.

Vitamin D and Lung Cancer; Association, Prevention, and Treatment.

Lung cancer is one of the common types of malignant disorders and the most prevalent cause of cancer-related mortality in the world. Although a wide range of approaches has been examined, strategies in prevention and treatment of lung cancer are still inadequate. Studies show that Vitamin D (VitD) is involved in various biological pathways and has been associated with the etiopathogenesis of several diseases, like cancers. In Vitro and In Vivo experiments have disclosed that VitD plays immunomodulatory and anti-tumor functions. Several lines of evidence have indicated that VitD is involved in the inflammatory settings of the lung. Epidemiological studies have reported that sufficient levels of VitD might be critical in the prevention of lung cancer. Polymorphisms in the genes encoding the different molecules involved in the signaling of VitD might affect the lung cancer risk as well as the quality and quantity of responses to different treatments. In this review article, we intended to clarify the implications of VitD in the normal biology and physiology of the lung and discuss diverse line of evidence about the possible role of VitD in the prevention or treatment of lung cancer.

miR-135a inhibits the proliferation of HBV-infected hepatocellular carcinoma cells by targeting HOXA10.

Background: The incidence of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) is extremely high. MicroRNAs (miRNAs) are a type of endogenous non-coding small RNA with novel molecular therapeutic mechanisms that plays an important role in the occurrence and development of cancers. This study aimed to explore the regulation mechanism of miR-135a and HOXA10 in the proliferation, invasion, and apoptosis of HCC cells. Methods: Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was used to detect the expression level of miR-135a. Overexpression of miR-135a was used to measure the roles of miR-135a in the proliferation, invasion, and apoptosis of HCC cells. A dual luciferase experiment was performed to assess the relationship between HOXA10 and miR-135a. Western blot was applied to observe the protein levels of p-p38, p-ERK, and p-JNK. Results: The expression levels of miR-135a were significantly decreased in HCC tissues and cells. Overexpression of miR-135a inhibited the proliferation and invasion but promoted the apoptosis of HCC cells. Importantly, our results confirmed that HOXA10 was a direct target of miR-135a. Under HBV infection, silencing of HOXA10 significantly blocked the proliferation and invasion and promoted the apoptosis of HCC cells. In addition, miR-135a/HOXA10 regulated the expressions of p-p38, p-ERK, and p-JNK through the miR-135a/HOXA10 axis, thereby inhibiting the activation of the MAPK pathway. Conclusions: HBV promoted the proliferation and invasion, and inhibited the apoptosis of HCC cells by regulating the miR-135a/HOXA10 pathway. These findings provide a theoretical basis for improving the treatment of HBV-infected HCC patients.

HBV Promotes the Proliferation of Liver Cancer Cells through the hsa_circ_0000847/miR-135a Pathway.

Hepatocellular carcinoma (HCC) is currently one of the most common tumors, with a high morbidity and mortality rate. HCC induced by persistent hepatitis B virus (HBV) infection is the most common liver cancer subtype at present, and HBV-related HCC is highly malignant and its development mechanism still needs to be explored in depth. This study aimed to explore the molecular mechanism of hsa_circ_0000847 targeting miR-135a-5p (miR-135a) to regulate the proliferation, invasion, and apoptosis of liver cancer cells. The study found that the expression level of hsa_circ_0000847 in liver cancer tissues and cells was significantly increased, while the expression level of miR-135a was significantly decreased. Hsa_circ_0000847 promoted the proliferation of liver cancer cells and elevated the expression of the proliferation-related protein. In addition, hsa_circ_0000847 could promote the invasion of HBV-infected liver cancer cells and inhibit the cell apoptosis of liver cancer cells. At the same time, it significantly promoted the expression of antiapoptotic proteins and inhibited the expression of proapoptotic protein. Interestingly, the dual luciferase experiment proved that hsa_circ_0000847 directly targeted miR-135a. On the other hand, the combined effect of hsa_circ_0000847 and miR-135a further illustrated the effect of hsa_circ_0000847 on the proliferation, invasion, and apoptosis of liver cancer cells. In addition, further experiments have also found that HBV could promote the expression of p-p38, p-ERK, and p-JNK through the hsa_circ_0000847/miR-135a axis, thereby further activating the MAPK pathway. In short, HBV promotes the proliferation and invasion of liver cancer cells and inhibits apoptosis by regulating the hsa_circ_0000847/miR-135a pathway, which provided a theoretical basis for effective treatment of HBV-infected liver cancers.

Risk factors and prediction of postoperative hypoparathyroidism among patients with papillary thyroid carcinoma.

BACKGROUND: We aimed to study the incidence rate of hypoparathyroidism, its risk factors, and identify its predictive factors among patients with papillary thyroid carcinoma (PTC) who had undergone total or near-total thyroidectomy and central neck dissection (CND). METHODS: Ninety-three PTC patients who had undergone total or near-total thyroidectomy and CND were analyzed for hypoparathyroidism. The association between clinicopathological factors and hypoparathyroidism was tested by χ2 test and multivariate logistic regression. The ROC curve and a 2×2 contingency table were used to evaluate the performance of postoperative parathyroid hormone (PTH) and serum calcium concentration in prediction of hypothyroidism. RESULTS: Hypothyroidism was observed in 46 patients (49.5%), among whom 2 had permanent hypothyroidism. Univariate analysis showed that tumor size (P=0.034), extraglandular invasion (P=0.028), bilateral tumors (P=0.045), and bilateral CND (P=0.028) were significant risk factors of hypothyroidism. Multivariate analysis showed that extraglandular invasion (P=0.003) and bilateral CND (P=0.044) were independent risk factors. The patients with hypothyroidism had an average PTH level of 8.51 ng/L on the first day after surgery, and those without, 21.39 ng/L (P<0.001). When the PTH level on the first day after surgery was used to predict postoperative hypothyroidism, the ROC curve analysis showed that the area under curve (AUC) was 0.875. CONCLUSIONS: Hypothyroidism is a common complication of total or near-total thyroidectomy and CND, for which extraglandular invasion and bilateral CND are independently significant risk factors and the level of PTH is a reliable and early predictor.

The role of CXCL12 in tumor microenvironment.

The chemokine ligand C-X-C motif chemokine ligand 12 (CXCL12) is a kind of small molecules of cytokines that widely expressed in diversified tissues. Recent evidence suggests that CXCL12 plays an important role in the communication of tumor cells with their surrounding microenvironment. The interaction of CXCL12 and its receptors subsequently excite the downstream signaling pathways to affect tumor angiogenesis, tumor cell proliferation and chemoresistance, and thus represents a potential target for cancer therapy. Outpouring molecules targeting CXCL12/CXCR4 axis in tumor microenvironment combined with traditional chemotherapy have drawn more and more attentions, which will be a promising method in anti-cancer therapies. Our review focuses on these roles of CXCL12 and summarizes strategies for treating cancer by disrupting this interaction with special emphasis on the CXCR4/CXCL12 axis.

CXCR4-mediated signaling regulates autophagy and influences acute myeloid leukemia cell survival and drug resistance.

CXCR4 surface expression is considered an independent prognostic factor for disease relapse and survival in acute myeloid leukemia (AML) patients. Herein, we investigated targetable autophagy-related mechanisms of CXCR4 for AML therapy. Our experiments show that activation of CXCR4 signaling in AML cells increases autophagic activity and decreases cytarabine-induced apoptosis. Accordingly, combined use of autophagy inhibitors significantly increased the sensitivity of AML cells to cytarabine in vitro and in vivo. Moreover, expression of autophagy-related protein SIRT1 was correlated with SDF-1α-CXCR4 signaling, which interacts with autophagy proteins, such as ATG5 and LC3. Furthermore, in primary human AML samples, high CXCR4 expression was associated with elevated expression levels of SIRT1 and other autophagy-related proteins. Collectively, our data suggest new roles of SDF-1α-CXCR4 signaling on autophagy induction in AML cells, which further promoted their survival under stress. Targeting the SDF-1α-CXCR4-autophagy signaling may contribute to an enhanced efficacy of active treatments.