Protective effects of pulsed electromagnetic field therapy attenuates autophagy and apoptosis in osteoporotic osteoarthritis model rats by activating PPARγ.

Osteoporotic osteoarthritis (OPOA) is a specific phenotype of OA with high incidence and severe cartilage damage. This study aimed to explore the protective efficacy of PEMF on the progression of OPOA and observed the effects of PEMF on PPARγ, autophagy- and apoptosis-related proteins in OPOA rats. Rats were randomly divided into three groups: control group, OPOA group, and PEMF group (n = 6). One week after surgery, the rats in PEMF group were subjected to PEMF (3.82 mT, 8 Hz, 40 min/day and 5 day/week) for 12 weeks. Results showed that PEMF retarded cartilage degeneration and bone loss, as evidenced by pathological staining image, decreased MMP-13 expression and increased bone mineral density. PEMF inhibited the serum levels of inflammatory cytokines, and the expressions of caspase-3 and caspase-8, while upregulated the expression of PPARγ. Moreover, PEMF significantly improved the autophagy disorders, represented by decrease expressions of Beclin-1, P62, and LC3B. The research demonstrates that PEMF can effectively prevent cartilage and subchondral bone destruction in OPOA rats. The potential mechanism may be related to upregulation of PPARγ, inhibition of chondrocyte apoptosis and inflammation, and improvement of autophagy disorder. PEMF therapy thus shows promising application prospects in the treatment of postmenopausal OA.

Osteoporotic osteoarthritis (OPOA) is a very common combination disease, that characterized by chronic pain, swollen joints and susceptibility to fractures. It is particularly common in postmenopausal women. At present, drug therapy is the main treatment method, but the adverse reactions are serious and can not stop the progression of the disease. PEMF is a safe physical therapy that has been shown to increase bone density, reduce pain, and improve joints mobility. In this study, we aimed to explore the protective effect and potential mechanism of PEMF on OPOA. We found that PEMF significantly inhibited the inflammatory response, ameliorated the damaged cartilage and subchondral bone in OPOA rats, that maybe related to the regulation of chondrocyte autophagy and apoptosis. This study provided a new vision for PEMF' treatment on OPOA and has positive significance for the clinical promotion of PEMF.

Research progress in rapid eye movement sleep behavior disorder. / å¿«é€Ÿçœ¼åŠ¨ç¡çœ è¡Œä¸ºéšœç¢çš„ç ”ç©¶è¿›å±•.

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by abnormal dream acting behavior such as vocalization and twitching related to dream content during REM sleep. The diagnosis requires polysomnography demonstrating a loss of normal skeletal muscle atonia during REM sleep. Both idiopathic RBD and secondary RBD are highly related to synucleinopathy including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Almost all idiopathic RBD patients will develop synucleinopathy after a few years. Therefore, RBD may be an early marker in the progression of synucleinopathy.

The predictive role of the platelet-to-lymphocyte ratio for the risk of non-alcoholic fatty liver disease and cirrhosis: a nationwide cross-sectional study.

Background: The associations between platelet-to-lymphocyte ratio (PLR) and non-alcoholic fatty liver disease (NAFLD) and cirrhosis are unclear, and there are still no effective means for diagnosing or monitoring disease progression. Methods: Data from the National Health and Nutrition Examination Surveys were collected for analysis. Logistic regression and restricted cubic splines were used to evaluate the associations between PLR and NAFLD and cirrhosis in different populations. The Area Under Curve Receiver Operating Characteristic (AUCROC) was used to distinguish the models. Threshold analysis was performed by constructing a two-piecewise linear regression. Correlation analysis was performed separately on either side of the inflection point. Results: A total of 5724 adults were included. Logistic regression analysis revealed that the PLR was associated with NAFLD and cirrhosis (AUCROC of NAFLD: 0.803; AUCROC of cirrhosis: 0.851). The AUCROC of the PLR for predicting NAFLD incidence was 0.762 in the diabetic population and 0.804 in the nondiabetic population. High PLR predicted cirrhosis in the diabetic population, with an AUCROC of 0.824, whereas a high PLR was not associated with cirrhosis in the nondiabetic population. The restricted cubic spline revealed a negative linear correlation between the PLR and NAFLD incidence. The inflection point of the PLR for NAFLD was 180.74. A PLR ≤180.74 was statistically significant (odds ratio=0.997, 95% confidence interval=0.995-0.999). In the NAFLD population, the PLR was negatively correlated with cirrhosis at a PLR ≤130.5 (odds ratio=0.987, 95% confidence interval=0.977-0.996) and positively correlated with cirrhosis at a PLR > 130.5 (odds ratio=1.006, 95% confidence interval=1.001-1.012). Conclusions: The PLR and NAFLD were negatively correlated in the U.S. population. The PLR had a U-shaped relationship with cirrhosis in the NAFLD population. The PLR has potential value in monitoring NAFLD patient progression to cirrhosis.

Successful Intravenous Thrombolysis in Ischemic Stroke Caused by Tuberculous Meningitis: A Case Report.

Tuberculous meningitis (TBM) has a variety of clinical manifestations and complications, and ischemic stroke is a common complication of TBM. However, there is no established prevention or treatment for stroke associated with TBM, and the safety and efficiency of thrombolysis in acute stroke caused by TBM remain unknown. Herein, we present a case of successful intravenous thrombolysis in ischemic stroke caused by TBM. A 50-year-old male patient with cerebral infarction had substantially improved neurological function after intravenous thrombolysis, and he was subsequently found to have TBM. Our findings suggest that intravenous thrombolysis might be an effective acute treatment method for infectious stroke.

Preliminary Findings on Proline-Rich Protein 14 as a Diagnostic Biomarker for Parkinson's Disease.

The nuclear envelope component proline-rich protein 14 (PRR14) is involved in the nuclear morphological alteration and activation of the mTOR (mammalian target of rapamycin) signaling pathway, and has been repeatedly shown to be upregulated in patients with Parkinson's disease (PD). The aim of this study was to explore whether PRR14 can be used as a potential biomarker for the diagnosis of PD. We compared PRR14 expression in PD patients and normal controls in gene expression omnibus (GEO) data. Quantitative enzyme-linked immunosorbent assay (ELISA) was used to detect PRR14 expression in PD patients and age- and sex-matched controls. The relationship between serum PRR14 and clinical phenotype was evaluated using correlation analysis and logistic regression. The expression of PRR14 in whole blood, substantia nigra, and medial substantia nigra was significantly higher in PD patients than in the healthy control group. Compared to plasma, serum was more suitable for the detection of PRR14. Furthermore, serum PRR14 level in PD patients was significantly higher than that in age- and sex-matched controls. The area under the curve for serum PRR14 level in the ability to identify PD versus age- and sex-matched controls was 0.786. In addition, serum PRR14 level was found to correlate with constipation in PD patients. Our findings demonstrate for the first time that serum PRR14 is a potential biomarker for PD.

MicroRNA-409-3p Targeting at ATXN3 Reduces the Apoptosis of Dopamine Neurons Based on the Profile of miRNAs in the Cerebrospinal Fluid of Early Parkinson's Disease.

Precise recognition of early Parkinson's disease (PD) has always been a challenging task requiring more feasible biomarkers to be integrated to improve diagnostic accuracy. MicroRNAs (miRNAs) of cerebrospinal fluid (CSF) are believed to be potential and promising candidate biomarkers for PD. However, the role of altered miRNAs of CSF play in PD is unclear. Here, we recruited patients with early stages of PD and controls to analyze the expression of miRNA in CSF by the Next Generation Sequencing (NGS). Furthermore, we tested the levels of these miRNA in SH-SY5Y cells treated with MPP+ using real-time quantitative PCR. We found 21 miRNAs were upregulated in CSF of early PD patients and miR-409-3p, one of the identified 21 miRNAs, was further confirmed in SH-SY5Y cells treated with MPP+. Also, more cells survived in the overexpression of the miR-409-3p group when SH-SY5Y cells and mice were treated with MPP+ and MPTP, respectively. Mechanistically, we demonstrated the binding of miR-409-3p and 3'UTR of ATXN3 through a dual luciferase reporter gene assay. Moreover, miR-409-3p mimic reduced the aggregation of polyglutamine-expanded mutant of ATXN3 and apoptosis. Our results provide experimental evidence for miR-409-3p in CSF as a diagnostic marker of PD.

Assessing the Effects of Vitamin D on Neural Network Function in Patients With Parkinson's Disease by Measuring the Fraction Amplitude of Low-Frequency Fluctuation.

Background: Recently, many studies have shown that low vitamin D (VD) levels may be related to an increased risk of Parkinson's disease (PD), but the underlying mechanisms remain unclear. Objective: To explore the relationship between PD and VD levels, as well as to analyze the effects of VD on spontaneous brain activity and explore the possible mechanism of its involvement in PD risk. Methods: In a cross-sectional study, we quantified the difference in VD levels between 330 PD patients and 209 healthy controls (HC) to explore the correlation between VD and PD risk. We also acquired resting-state Functional Magnetic Resonance Imaging (rs-fMRI) data from 46 PD patients and 21 HC. The PD patients were divided into three groups according to 25(OH)D levels: PD patients with VD deficiency (PD + VDD), PD patients with VD insufficiency (PD + VDI), and PD patients with normal VD (PD + NVD). The effect of VD status on spontaneous neuronal activity in the whole brain was analyzed by measuring the fraction amplitude of low-frequency fluctuation (fALFF). Results: Compared with HC, the PD patients had lower serum 25(OH)D levels (23.60 ± 7.27 vs. 25.60 ± 5.78, P < 0.001). The 25(OH)D level may have a potential dose-dependent effect on the risk of PD (P trend = 0.007). A high risk of PD was associated with VD deficiency [25(OH)D < 20 ng/mL, OR = 2.319], and the lowest quartile of 25(OH)D concentration was associated with a high risk of PD (OR = 1.941). In the rs-fMRI study, PD + VDD patients had wider brain regions with altered fALFF than other PD groups when compared with the corresponding HC groups. Both PD + VDD and PD + VDI showed higher fALFF in the cuneus, left precuneus, calcarine cortex and right lingual, as well as lower fALFF in the left middle temporal gyrus. PD + VDD patients also showed higher fALFF in the left superior, middle and inferior frontal gyri, as well as the left precentral gyrus than HC. Among PD patients, there was only a statistically significant difference in fALFF between the PD + VDD and PD + NVD groups. Compared with the PD + NVD group, PD + VDD patients exhibited higher fALFF in the left precentral and left postcentral gyrus, as well as the left inferior parietal lobule. Conclusion: These results demonstrate that PD patients had lower serum VD levels than HC, and VD may have a potential dose-dependent effect on PD risk. Lower serum VD levels can affect the spontaneous neuronal activity of default-mode network (DMN) and visual pathway neurons in PD patients, providing a possible mechanism for its effect on PD risk.

The relationships of vitamin D, vitamin D receptor gene polymorphisms, and vitamin D supplementation with Parkinson's disease.

In recent years, many studies have investigated the correlations between Parkinson's disease (PD) and vitamin D status, but the conclusion remains elusive. The present review focuses on the associations between PD and serum vitamin D levels by reviewing studies on the associations of PD with serum vitamin D levels and vitamin D receptor (VDR) gene polymorphisms from PubMed, Web of Science, Cochrane Library, and Embase databases. We found that PD patients have lower vitamin D levels than healthy controls and that the vitamin D concentrations are negatively correlated with PD risk and severity. Furthermore, higher vitamin D concentrations are linked to better cognitive function and mood in PD patients. Findings on the relationship between VDR gene polymorphisms and the risk of PD are inconsistent, but the FokI (C/T) polymorphism is significantly linked with PD. The occurrence of FokI (C/T) gene polymorphism may influence the risk, severity, and cognitive ability of PD patients, while also possibly influencing the effect of Vitamin D3 supplementation in PD patients. In view of the neuroprotective effects of vitamin D and the close association between vitamin D and dopaminergic neurotransmission, interventional prospective studies on vitamin D supplementation in PD patients should be conducted in the future.