Association of Combined Healthy Lifestyle Factors With Incident Dementia in Participants With and Without Multimorbidity: A Large Population-Based Prospective Cohort Study.

BACKGROUND: The effect of a healthy lifestyle on dementia associated with multimorbidity is not well understood. Our objective is to examine whether the adoption of a healthy lifestyle could potentially reduce the elevated risk of dementia in individuals with and without multimorbidity. METHODS: We utilized data from the UK Biobank cohort. A comprehensive healthy lifestyle score, ranging from 0 to 6, was generated. Cox proportional hazards models were used to examine the associations between multimorbidity, the healthy lifestyle score, and the incidence risk of dementia. RESULTS: Over a median follow-up period of 12.5 years, 5 852 all-cause dementia were recorded. Multimorbidity including cardiovascular, metabolic, neuropsychiatric, and inflammation-related diseases was associated with a higher risk of subsequent dementia. Each additional chronic disease was associated with a hazard ratio (HR) of 1.38 (95% CI: 1.33, 1.44). Compared to individuals without multimorbidity and a healthy lifestyle score of 5-6, patients with multimorbidity and a lifestyle score of 0-1 had a significantly higher risk of dementia (HR: 3.13; 95% CI: 2.64, 3.72), but the risk was markedly attenuated among those with multimorbidity and a lifestyle score of 5-6. Among patients with 3 or more diseases, the HR for dementia was 0.53 (95%CI: 0.42, 0.68) when comparing a lifestyle score of 5-6 to 0-1. And we observed more pronounced association between them among people younger than 60 years old. CONCLUSIONS: Adherence to a combination of healthy lifestyle factors, especially at a young age, was associated with a significantly lower risk of dementia among participants with multimorbidity.

Exosomal miR-1910-3p promotes proliferation, metastasis, and autophagy of breast cancer cells by targeting MTMR3 and activating the NF-κB signaling pathway.

Exosomes are key mediators of intercellular communication and play a role in the pathogenesis and progression of cancer. Exosomes in circulating body fluids serve as molecular markers for cancer diagnosis. This study aimed to investigate the role of exosomal microRNA (miR)-1910-3p in breast cancer and determine its clinical diagnostic value. MiR-1910-3p promoted proliferation and migration of breast cancer cells in vitro and in vivo. In vitro, exosomes enriched in miR-1910-3p transferred miR-1910-3p to mammary epithelial cells and breast cancer cells, promoting proliferation and migration, inhibiting apoptosis, and inducing autophagy. In vivo, exosomes enriched in miR-1910-3p promoted the proliferation and migration of breast cancer cells. MiR-1910-3p downregulated myotubularin-related protein 3, activated the NF-κB and wnt/ß-catenin signaling pathway, and promoted breast cancer progression. Serum miR-1910-3p in exosomes was an effective diagnostic marker that improved the sensitivity of breast cancer diagnosis when used in combination with the traditional tumor marker CA153. In conclusion, breast cancer cell-derived exosomes promoted the growth, metastasis, and autophagy of breast cancer cells by transferring miR-1910-3p. MiR-1910-3p in serum exosomes may serve as a novel molecular marker for breast cancer diagnosis.

Toll-like receptor 2 promotes invasion by SGC-7901 human gastric carcinoma cells and is associated with gastric carcinoma metastasis.

Toll-like receptors (TLRs) play a key role in cancer metastasis. The biological role of TLR2 in invasion and metastasis in gastric carcinoma cells and gastric carcinoma is not clear; therefore, we aimed to investigate the biological role of TLR2 in invasion by SGC-7901 human gastric carcinoma cells and to determine whether TLR2 is associated with gastric carcinoma metastasis. RT-PCR, real-time PCR, flow cytometry, and western blotting showed that TLR2 activation significantly increased TLR2 expression at the mRNA and protein levels and notably promoted the transcription of genes related to angiogenesis and invasion, such as VEGF-C and MMP-9. The invasive capacity of SGC-7901 cells was strikingly advanced by TLR2 stimulation on Transwell invasion assay. IL-6 in the supernatants of cultured SGC-7901 cells was increased under the condition of TLR2 stimulation and reduced after TLR2 blockade by ELISA. Combined with clinicopathological parameters, the expression of TLR2 protein examined by immunohistochemical analysis was higher in gastric carcinoma tissues than in adjacent non-cancerous tissues (p<0.001). There was a significant relationship between TLR2 expression and lymph node metastasis (p<0.01), distant metastasis (p<0.01). There was no significant correlation between gastric carcinoma and age (p>0.05), sex (p>0.05), or degree of differentiation (p>0.05). These findings indicate that TLR2 may participate in the progression and metastasis of human gastric carcinoma and provide a new therapeutic target against metastasis of gastric carcinoma.