Associations of Handgrip Strength Weakness and Asymmetry with Lower Cognitive Function: Results from the National Health and Nutrition Examination Survey (2011-2014).

Background: The joint associations of handgrip strength (HGS) weakness and asymmetry with cognitive decline remain understudied in older adults. Objective: To investigate the associations between HGS weakness, asymmetry, and lower cognitive function in a nationally representative sample of older Americans. Methods: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey 2011-2014. Weakness was defined as HGS <26 kg for men and <16 kg for women. Asymmetry was determined by calculating the ratio of dominant to non-dominant HGS. Participants with an HGS ratio <0.90 or >1.10 were classified as having any HGS asymmetry. Those with an HGS ratio >1.10 exhibited dominant HGS asymmetry, while those with an HGS ratio <0.90 displayed nondominant HGS asymmetry, respectively. Lower cognitive functioning was defined as global cognitive composite scores more than 1 standard deviation below the mean. Covariate-adjusted logistic regression models were used to analyze the associations between HGS asymmetry/weakness and lower cognitive functioning. Results: Compared to individuals with non-weak and symmetric HGS, those with any HGS asymmetry alone and weakness alone had 1.017 (95% confidence interval [CI]: 0.707-1.463) and 1.391 (95% CI: 0.542-3.571) greater odds for cognitive decline, while co-occurrence of both HGS asymmetry and weakness was associated with 3.724 (95% CI: 1.711-8.107) greater odds for lower cognitive function after controlling for confounders. Cnclusions: Individuals exhibiting both diminished and asymmetrical HGS demonstrated an elevated susceptibility to cognitive impairment, thereby implying that the inclusion of HGS asymmetry assessment in conjunction with weakness evaluation may enhance the accuracy of prognosticating cognitive decline.

Saikosaponin d (SSD) alleviates diabetic peripheral neuropathy by regulating the AQP1/RhoA/ROCK signaling in streptozotocin-induced diabetic rats.

AIMS: Diabetic peripheral neuropathy (DPN) is one of the most important complications of diabetes with a poor prognosis. Saikosaponin d (SSD) is a triterpenoid saponin isolated from Radix Bupleuri that has multiple pharmacological activities. However, whether SSD affects DPN is unclarified. METHODS: Sprague Dawley rats were treated with streptozotocin (STZ) and high-fat diet (HFD) to induce DPN, in the presence or absence of SSD, with or without transfection of lentivirus vectors carrying siRNA targeting aquaporin 1 (si-AQP1). The body weight, plasma glucose levels, mechanical and thermal hyperalgesia, and nerve conductive velocity (NCV) of rats were measured. Hematoxylin-Eosin staining was used for histopathological observation of sciatic nerves. RT-qPCR and western blotting were utilized for measuring expression levels of AQP1 and ras homolog family member A/Rho-associated protein kinase (RhoA/ROCK) signaling pathway-related markers in dorsal root ganglion (DRG) of rats. RESULTS: SSD increased the body weight, decreased plasma glucose levels, attenuated mechanical and thermal hyperalgesia, enhanced NCV and reduced proinflammatory cytokine levels in DPN rats. AQP1 displayed a high level in DPN rats and SSD treatment repressed the expression of AQP1. SSD enhanced the protective effect of AQP1 knockdown on the pathological changes of DPN. AQP1 depletion suppressed the activation of RhoA/ROCK signaling pathway in DPN rats. CONCLUSION: SSD alleviates STZ/HFD-induced DPN in rats by inhibiting the AQP1/RhoA/ROCK signaling pathway.

miR-369-5p Positively Modulates Plasticity-Related Proteins in Hippocampal Cultures and in a Mouse Model of Alzheimer's Disease.

MicroRNAs are reported to correlate with synaptic plasticity and exert functions in Alzheimer's disease (AD) pathogenesis. miR-369-5p is identified to be upregulated in AD mice. This study explores miR-369-5p roles in synaptic plasticity in hippocampal cells and in an AD mouse model. Wild-type C57BL/6J mice (6 months) were trained in a well-established object memory task. Two identical objects were presented to mice for 10 min. miR-369-5p expression in hippocampus, cortex, and striatum, and in hippocampal cells was measured by reverse transcription quantitative polymerase chain reaction. Then, 0.2 mM glycine and 100 nM amyloid-beta oligomers were used to treat primary hippocampal cells. The levels of plasticity-related proteins in hippocampal cells and hippocampus were evaluated by Western blotting. Object location memory (OLM) of 3xTg-AD mice was tested in an OLM protocol at 13 months of age. In this study, learning increased miR-369-5p level in the hippocampus. The increased levels of plasticity-related proteins induced by chemical long-term potentiation were inhibited by miR-369-5p inhibitors in hippocampal cultures. miR-369-5p upregulation rescued the Aßo-induced suppression in the levels of plasticity-related proteins in hippocampal cultures. miR-369-5p elevation increased GluA1 and GluA2 protein levels and rescued OLM impairment in an AD mouse model. In conclusion, miR-369-5p positively regulates the levels of plasticity-related proteins in hippocampal cultures and in an AD mice model.

Effect of postoperative sequential chemoradiotherapy and concurrent chemoradiotherapy in treating advanced endometrial cancer.

PURPOSE: To evaluate the efficacy and safety of the sequential chemoradiotherapy mode of chemotherapy-radiotherapy-consolidation chemotherapy and the concurrent chemoradiotherapy after operation for advanced (stage III-IV) endometrial cancer. METHODS: A total of 116 patients with stage III-IV endometrial cancer were divided into the Sequential group (n=58) and the Concurrent group (n=58) according to the different modes of postoperative adjunctive therapy. The levels of tumor markers in the serum and the occurrence of adverse reactions were compared between the two groups, and the survival and progression of the patients were followed up and recorded. Moreover, the factors influencing the tumor progression in patients were analyzed. RESULTS: The levels of serum carcino-embryonic antigen (CEA), cancer antigen (CA) 125, CA19-9 and adiponectin (APN) declined markedly after treatment with chemoradiotherapy in both groups compared with those before treatment (p<0.05). The median survival was 49.4±4.5 months and 47.9±4.0 months, and the median progression-free survival (PFS) was 47.1±4.6 months and 45.8±4.3 months, respectively, in the Sequential group and the Concurrent group. Besides, the 3-year overall survival (OS) rate in the Sequential group and the Concurrent group was 82.8% and 70.7%, respectively, and the 3-year PFS rate in the two groups was 79.3% and 58.6%, respectively. The 5-year OS rate was 60.3% and 48.3%, and the 5-year PFS rate was 51.7% and 32.8% in the two groups, respectively. Log-rank test indicated that the PFS in the Sequential group was evidently superior to that in the Concurrent group (p=0.017). The results of univariate and multivariate analyses manifested that surgical-pathological stage and postoperative Sequential chemoradiotherapy were independent risk factors for tumor progression in patients with advanced endometrial cancer. CONCLUSIONS: Compared with the concurrent chemoradiotherapy, the sequential chemoradiotherapy can prominently delay the progression of advanced endometrial cancer, induce no apparent adverse reactions and has good tolerance. Low surgical-pathological stage and postoperative sequential chemoradiotherapy are independent protective factors against tumor progression.

Synergy of Peptide-Nucleic Acid and Spherical Nucleic Acid Enabled Quantitative and Specific Detection of Tumor Exosomal MicroRNA.

Exosomal microRNAs are essential in intercellular communications and disease progression, yet it remains challenging to quantify the expression level due to their small size and low abundance in blood. Here, we report a "sandwich" electrochemical exosomal microRNA sensor (SEEmiR) to detect target microRNA with high sensitivity and specificity. In SEEmiR, neutrally charged peptide nucleic acid (PNA) enables kinetically favorable hybridization with the microRNA target relative to negatively charged DNA, particularly in a short sequence (10 nt). More importantly, this property allows PNA to cooperate with a spherical nucleic acid (SNA) nanoprobe that heavily loads with oligonucleotide-adsorbed electroactive tags to enhance detection sensitivity and specificity. Such a PNA-microRNA-SNA sandwich construct is able to minimize the background noise via PNA, thereby maximizing the SNA-mediated signal amplification in electrostatic adsorption-based SEEmiR. The synergy between PNA and SNA makes the SEEmiR sensor able to achieve a broad dynamic range (from 100 aM to 1 nM) with a detection limit down to 49 aM (2 orders of magnitude lower than that without SNA) and capable of distinguishing a single-base mismatch. This ultrasensitive sensor provides label-free and enzyme-independent microRNA detection in cell lysates, unpurified tumor exosomal lysates, cancer patients' blood, and accurately differentiates the patients with breast cancer from the healthy ones, suggesting its potential as a promising tool in cancer diagnostics.