Genetic predisposition to white blood cells in relation to the risk of frailty.

BACKGROUND: Observational studies have suggested an association between white blood cells (WBCs) and frailty, but considering the susceptibility to reverse causality and confounding, the causal direction and magnitude of this association remain ambiguous. Our aim was to investigate the causal effect of WBCs on frailty by means of a Mendelian randomization (MR) analysis. METHODS: Based on the genome-wide association study (GWAS) summary statistics data provided by the European Bioinformatics Institute (EBI), we carried out a two-sample MR study. We applied the genetically predicted independent WBCs from GWAS as a measure of exposure data. The Rockwood Frailty Index (FI) was used as outcome measure, which was derived from a meta-analysis from GWAS in UK Biobank European ancestry participants and Swedish TwinGene participants. Our study applied inverse variance weighted (IVW), weighted median, Mendelian randomization-Egger (MR-Egger) and outlier test (MR-PRESSO) methods to explore relationships between various WBCs and frailty. RESULTS: In our study, a possible causal relationship between eosinophil levels and frailty was demonstrated by two-sample MR analysis. Eosinophils were associated with FI (beta:0.0609; 95% CI 0.0382, 0.0836; P = 1.38E-07). Our results suggest that as the level of eosinophils increases, so does the risk of frailty. No meaningful causal relationship between neutrophils, lymphocytes, monocytes or basophils and FI was found in the MR results (P > 0.05). CONCLUSIONS: According to this MR study, higher eosinophil counts are related to an increased risk of frailty. To validate these findings and investigate the mechanisms underlying these connections, future studies are warranted.

Gastrodia elata and parishin ameliorate aging induced 'leaky gut' in mice: Correlation with gut microbiota.

BACKGROUND: The aging-induced decrease in intestinal barrier function contributes to many age-related diseases. Studies on preventive measures for "leaky gut" may help improve the quality of life of geriatric patients. The potent anti-aging effect of Gastrodia elata and parishin, which is one of its active ingredients, has been reported previously. However, their effects on the gut remain elusive, and the effect of parishin on mammals has not been studied. METHODS: We used quantitative RT-PCR, western blotting, immunohistochemical analysis, and 16S rRNA sequencing to investigate the effect of G. elata and parishin on the intestinal barrier function of D-Gal-induced aging mice. RESULTS: G. elata and parishin prevented the decrease in tight junction protein (TJP) expression and morphological changes, modulated the composition of fecal microbiota to a healthier state, and reversed the translocation of microbial toxins and systemic inflammation. The correlation analyses showed that TJP expression and systemic inflammation were significantly positively or negatively correlated with the composition of fecal microbiota after G. elata and parishin administration. Additionally, TJP expression was also correlated with systemic inflammation. Moreover, G. elata and parishin administration reversed the decreased or increased expression of aging-related biomarkers, such as FOXO3a, SIRT1, CASPASE3 and P21, in the gut. CONCLUSIONS: These results suggested that G. elata and parishin could prevent gut aging and ameliorate the "leaky gut" of aged mice and that the underlying mechanism is related to the mutual correlations among barrier function, fecal microbiota composition, and inflammation.

Anti-N-methyl-D-aspartate receptor encephalitis with occult ovarian teratoma: a case report.

A 31-year-old female was admitted with headache, memory disturbance, abnormal behavior, incontinence, confusion, complex partial seizures, decreased oxygen saturation and increased temperature. Anti-NMDAR antibodies were positive in serum and cerebrospinal fluid. Subsequently, a regimen of immunotherapy that included intravenous immunoglobulins, methylprednisolone, plasma exchange and their combinations were used. But the treatment was ineffective. Though both transvaginal ultrasonography and abdominal CT scan contrast revealed left ovarian cyst, the patient had left oophorectomy. And during surgery we found a small cyst mass contained fat-like liquid with air in her left ovarian. Pathological examination demonstrated mature cystic teratoma accompanied with brain tissue. She has made gradual and steady improvement after surgery, but not fully recovery. By combining this case with previous studies of others, we further discuss the clinical characteristics, treatment and prognosis of the disease.

Nerve growth factor rescues diabetic mice heart after ischemia/reperfusion injury via up-regulation of the TRPV1 receptor.

AIMS: Nerve growth factor (NGF), a member of the neurotrophin family, plays an essential role in diabetic neuropathy and ischemic heart disease. In the present study, we explored the potential role of NGF and the involvement of TRPV1 receptor in isolated diabetic mouse hearts following ischemia/reperfusion (I/R) injury. METHODS: Adenovirus-mediated NGF gene delivery was performed on diabetic and sham hearts 8weeks after streptozotocin treatment. The sciatic nerve conduction velocity was recorded using a biological signal acquisition system. Forty-eight hours after heart surgery, mice were subjected to I/R injury using a Langendorff system. Several cardiac parameters and the expression of associated molecules were analyzed during the experiment. RESULTS: The sciatic nerve conduction velocity was reduced in diabetic mice compared with that in control mice. Decreased expression of NGF, TRPV1, and the downstream neurotransmitters CGRP and SP was observed in the diabetic hearts. Adenovirus-mediated NGF overexpression reversed the reduction in TRPV1 and downstream neuropeptides, resulting in improved cardiac recovery post-I/R injury in diabetic hearts. The protective effect of NGF was abolished by CGRP8-37 (a selective CGRP antagonist), while it was preserved by low-dose capsaicin. CONCLUSIONS: The NGF-induced up-regulation of TRPV1 via the increased synthesis and release of endogenous CGRP leads to improved cardiac performance in I/R-injured diabetic heart.