Frailty and depressive disorders exhibit a high prevalence and comorbidity rate in the elderly population.Their coexistence significantly reduces patients'quality of life,increases the risk of disability and mortality,and substantially exacerbates the socioeconomic burden.Emerging evidence indicates a significant bidirectional causal relationship between frailty and depressive disorders.The underlying comorbid mechanisms may be related to elevated levels of pro-inflammatory cytokines such as C-reactive protein,neutrophils,and white blood cells.Grey matter volume reduces in specific brain regions including the bilateral thalamus and right precentral gyrus.And abnormal hormone secretion,such as cortisol,resulting from the overactivation of the hypothalamic-pituitary-adrenal axis.Exercise interventions demonstrate positive effects in preventing and managing both frailty and depressive disorders,indicating broad application prospects.However,the underlying mechanisms require further validation.In summary,the comorbidity of frailty and depressive disorders in the elderly requires greater attention.Current evidence supports exercise intervention as an effective therapeutic strategy for improving health outcomes in this population.

Frailty and depressive disorders exhibit a high prevalence and comorbidity rate in the elderly population.Their coexistence significantly reduces patients'quality of life,increases the risk of disability and mortality,and substantially exacerbates the socioeconomic burden.Emerging evidence indicates a significant bidirectional causal relationship between frailty and depressive disorders.The underlying comorbid mechanisms may be related to elevated levels of pro-inflammatory cytokines such as C-reactive protein,neutrophils,and white blood cells.Grey matter volume reduces in specific brain regions including the bilateral thalamus and right precentral gyrus.And abnormal hormone secretion,such as cortisol,resulting from the overactivation of the hypothalamic-pituitary-adrenal axis.Exercise interventions demonstrate positive effects in preventing and managing both frailty and depressive disorders,indicating broad application prospects.However,the underlying mechanisms require further validation.In summary,the comorbidity of frailty and depressive disorders in the elderly requires greater attention.Current evidence supports exercise intervention as an effective therapeutic strategy for improving health outcomes in this population.

We prepared a polymorphic form of valnemulin hydrogen tartrate (Form I) to overcome the instability and irritating odor of valnemulin hydrochloride that affect its use in the production and application of veterinary drugs. The physicochemical properties of Form I were characterized by scanning electron microscopy, X-ray powder diffraction, infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. The results showed the crystal structure and thermal properties of Form I were very different from those of a commercially available form of valnemulin hydrogen tartrate (Form II). Form I and Form II were more stable than valnemulin hydrochloride after storage under irradiation and high humidity conditions, respectively. The solubility of Form I was 2.6 times that of Form II, and Form I was selected for use in pharmaceutical kinetics experiments in vivo. Compared to valnemulin hydrochloride, after oral administration at a dose of 10 mg/kg in pigs, Form I had similar pharmaceutical kinetic behavior but a slightly higher area under the concentration–time curve from time zero to the last measurable concentration. Consequently, Form I should be suitable for the development of simple formulations and be effective in the clinical application of veterinary drugs.
Administration, Oral ; Calorimetry, Differential Scanning ; Humidity ; Hydrogen ; Kinetics ; Microscopy, Electron, Scanning ; Odors ; Pharmacokinetics ; Powder Diffraction ; Solubility ; Spectrum Analysis ; Swine ; Veterinary Drugs

Objective: To investigate the effect of high expression of TET1 catalytic domain (TET1-CD) gene on the proliferation and migration of breast cancer MDA-MB-231 cells and its underlying mechanism. Methods: MDA-MB-231 cell line with high TET1-CD expression was established by lentiviral transfection. Real-time quantitative PCR was used to detect the mRNA expression of TET1-CD. Transwell assay and cell scratch assay were used to detect cell migration ability, MTT assay and colony formation assay were used to detect cell proliferation capacity. And WB was adopted to detect the expressions of EMT-related proteins (E-cadherin, Vimentin, MMP2) and Wnt, Hedgehog pathway-related proteins in MDA-MB-231 cells. Results: The MDA-MB-231 cell line with high TET1-CD expression was successfully constructed (all P<0.01). TET1-CD over-expression significantly inhibited the proliferation and migration of breast cancer MDA-MB-231 cells (P<0.01); in addition, TET1-CD over-expression increased the expression of E-cadherin, but down-regulated the expressions of Vimentin, MMP2, β-catenin, Gli1, C-myc and CyclinD1 (all P<0.05). Conclusion: TET1-CD may inhibit the proliferation and migration of breast cancer MDA-MB-231 cells by inhibiting the EMT through Wnt and HH signaling pathway.