Prediabetes and the incidence of Parkinson’s disease: A meta-analysis

Diabetes has been associated with an elevated risk of Parkinson’s disease (PD), yet the relationship between prediabetes (PreD) and the incidence of PD in the adult population remains unclear. Therefore, a systematic review and meta-analysis was conducted to evaluate if PreD is also associated with a higher risk of PD. We conducted comprehensive searches of the PubMed, Embase, and Web of Science databases to identify relevant observational studies with longitudinal follow-up. The random-effects model was employed to synthesize the data, mitigating the potential impact of study heterogeneity on the outcomes. Our analysis incorporated seven datasets from five cohort studies, encompassing 18,170,592 adult participants without a PD diagnosis at baseline. Among them, 2,432,148 (13.3%) had PreD. During the follow-up, a total of 46,682 patients were diagnosed with PD. The pooled results indicated that PreD was associated with an increased incidence of PD (risk ratio [RR] 1.09, 95% confidence interval [CI] 1.02 - 1.16; P = 0.02; I2 = 52%), after adjusting for potential confounding factors such as age, sex, body mass index (BMI), and smoking. Subsequent pilot subgroup analyses suggested that the association between PreD and PD might not be significantly influenced by the country of the study, its design, age or sex of the participants, definition of PreD, or the quality scores of the study (P for subgroup difference all > 0.05). In conclusion, adult population with PreD may have a mildly increased risk of developing PD compared to those with normoglycemia

Non-neuronal cholinergic activity is potentiated in myasthenia gravis

Background: Non-neuronal acetylcholine (ACh) restricts autoimmune responses and attenuates inflammation by cholinergic anti-inflammation pathway. To date, the implication of ACh in myasthenia gravis (MG) remained unexplored. This study aimed to investigate the possible relationship between ACh levels, anti-muscle-specific tyrosine kinase (MuSK) antibody titers, main clinical features and outcomes of MG patients. Methods: We successfully measured ACh levels in human peripheral blood mononuclear cells (PBMCs) from 125 MG patients and 50 matched healthy controls by using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We assessed the quantitative MG (QMG) scores for each patient and titered anti-MuSK antibody. Results: We found that PBMC-derived ACh level was significantly higher in MG patients, especially in patients of class III, IV-V, compared with that in controls (0.142 ± 0.108 vs. 0.075 ± 0.014 ng/million cells, p = 0.0003) according to the Myasthenia Gravis Foundation of America clinical classification. Importantly, we also found that ACh levels were positively correlated with QMG scores (r = 0.83, p \u3c 0.0001) and anti-MuSK Ab levels (r = 0.85, p \u3c 0.0001). Conclusions: Our demonstration of elevated ACh levels in PBMCs of MG patients foreshadows potential new avenues for MG research and treatment

Evaluation of Metformin on Cognitive Improvement in Patients With Non-dementia Vascular Cognitive Impairment and Abnormal Glucose Metabolism

Objective: Recent studies have suggested that metformin can penetrate the blood–brain barrier, protecting neurons via anti-inflammatory action and improvement of brain energy metabolism. In this study, we aim to investigate the effect of metformin on cognitive function in patients with abnormal glucose metabolism and non-dementia vascular cognitive impairment (NDVCI).Methods: One hundred patients with NDVCI and abnormal glucose metabolism were randomly allocated into two groups: metformin and donepezil (n = 50) or acarbose and donepezil (n = 50). The neuropsychological status, glucose metabolism, and common carotid arteries intima–media thickness (CCA-IMT) before and after a year of treatment, were measured and compared between the groups.Results: Ninety four patients completed all the assessment and follow-up. After a year of treatment, there was a decrease in Alzheimer’s disease Assessment Scale-Cognitive Subscale scores and the duration of the Trail Making Test in the metformin-donepezil group. Furthermore, these patients showed a significant increase in World Health Organization–University of California–Los Angeles Auditory Verbal Learning Test scores after treatment (all P < 0.05). However, there was no obvious improvement in cognitive function in the acarbose-donepezil group. We also observed a significant decrease in the level of fasting insulin and insulin resistance (IR) index in the metformin-donepezil group, with a lower CCA-IMT value than that in the acarbose-donepezil group after a year of treatment (P < 0.05).Conclusion: We conclude that metformin can improve cognitive function in patients with NDVCI and abnormal glucose metabolism, especially in terms of performance function. Improved cognitive function may be related to improvement of IR and the attenuated progression of IMT.Trial Registration:ChiCTR-IPR-17011855

Enzymatic hydrogelation of self-assembling peptide I4K2 and its antibacterial and drug sustained-release activities

Hydrogels provide great potential for biomedical applications. For clinical use, hydrogels could be used as scaffold materials for cell culture, regenerative medicine and drugs release with bactericidal properties. The amphiphilic peptide I4K2 is designed to inhibit bacterial growth through membrane permeation mechanisms. I4K2 is found to be able to self-assemble into nanofibers and form hydrogels in the presence of an enzyme (plasma amine oxidase, PAO). HPLC and MALDI-TOF-MS data show that PAO promoted the oxidation of the 3-amine of the lysine side chain. The cross-linking of I4K2 molecules catalyzed by PAO leads to a decrease in the amount of the positive charge of the system, which enhances the interaction between the self-assembled nanofibers and contributes to the formation of hydrogels. This self-supported hydrogel showed antibacterial activity against both G(+) and G(-) bacteria and has low cytotoxicity, which enable it be consequently used as an antimicrobial agent or biological engineering scaffold material. The hydrogel also possesses good drug sustained-release activities. These advantages result in the great potential of this enzymatic I4K2 hydrogel for biomedical applications

Analysis of the serological characteristics and transfusion strategy of the autoantibody with specificity

Objective: To explore the detection methods and transfusion strategies of autoantibodies with specificity against Rh blood group system to provide timely and effective transfusion treatment for those patients. Methods: A case of a patient with autoantibodies with anti-Ce specificity was studied through serological tests, including ABO and Rh blood group identification, Coombs tests, antibody identification test and acid elution test. PCR-SSP was carried out to identify the Rh phenotype. The cross-matching test should avoid the specificity of anti-Ce autoantibody. The hemoglobin was measured pre- and post- the transfusion. Results: The results of the serological tests showed the blood group of the patient was AB type, RhD positive, and Rh blood group was CcEe before transfusion Direct antiglobulin test (DAT), and indirect antiglobulin test (IAT) were positive. According to the identification of antibodies, there were autoantibodies with anti-Ce specificity in the patient’s serum. The Rh antigen phenotyping was C+, c+, E+, e+ through the gene analysis. The results of the cross-matching were negative and the blood group of the red blood cell were AB, ccDEE. The hemoglobin of the patient increased from 48 g/L to 60 g/L and 58 g/L to 88 g/L rapidly after transfusion. Conclusions: In rare cases, autoantibodies can also show the characteristics of the complete antibodies rather than the pattern which could be agglutination with all the red blood cells for antibodies identification but there were strength differences. During blood transfusion treatment for those patients, we should try to avoid the specificity of autoantibodies, and carry out cross matching test before transfusion. After the titter of the autoantibodies decreased or disappeared, homotypic red blood cells for transfusion could be carried out

Radiosensitization by Inhibiting Survivin in Human Hepatoma HepG2 Cells to High-LET Radiation

In this study, whether survivin plays a direct role in mediating high-LET radiation resistance in human hepatoma cells was investigated. Small interfering RNA (siRNA) targeting survivin mRNA was designed and transfected into human hepatoma HepG2 cells. Real-time PCR and western blotting analyses revealed that survivin expression in HepG2 cells decreased at both transcriptional and post-transcriptional levels after treatment with survivin-specific siRNA. Caspase-3 activity was determined with a microplate reader assay as well. Following exposure to high-LET carbon ions, a reduced clonogenic survival effect, increased apoptotic rates and caspase-3 activity were observed in the cells treated with the siRNA com- pared to those untreated with the siRNA. The cells with transfection of the survivin-specific siRNA also increased the level of G2/M arrest. These results suggest that survivin definitely plays a role in mediating the resistance of HepG2 cells to high-LET radiation and depressing survivin expression might be useful to improve the therapeutic efficacy of heavy ions for radioresistant solid tumors

Radiosensitization by Inhibiting Survivin in Human Hepatoma HepG2 Cells to High-LET Radiation

In this study, whether survivin plays a direct role in mediating high-LET radiation resistance in human hepatoma cells was investigated. Small interfering RNA (siRNA) targeting survivin mRNA was designed and transfected into human hepatoma HepG2 cells. Real-time PCR and western blotting analyses revealed that survivin expression in HepG2 cells decreased at both transcriptional and post-transcriptional levels after treatment with survivin-specific siRNA. Caspase-3 activity was determined with a microplate reader assay as well. Following exposure to high-LET carbon ions, a reduced clonogenic survival effect, increased apoptotic rates and caspase-3 activity were observed in the cells treated with the siRNA compared to those untreated with the siRNA. The cells with transfection of the survivin-specific siRNA also increased the level of G(2)/M arrest. These results suggest that survivin definitely plays a role in mediating the resistance of HepG2 cells to high-LET radiation and depressing survivin expression might be useful to improve the therapeutic efficacy of heavy ions for radioresistant solid tumors

Vinpocetine Inhibits NF-κB-Dependent Inflammation in Acute Ischemic Stroke Patients

Immunity and inflammation play critical roles in the pathogenesis of acute ischemic stroke. Therefore, immune intervention, as a new therapeutic strategy, is worthy of exploration. Here, we tested the inflammation modulator, vinpocetine, for its effect on the outcomes of stroke. For this multi-center study, we recruited 60 patients with anterior cerebral circulation occlusion and onset of stroke that had exceeded 4.5 h but lasted less than 48 h. These patients, after random division into two groups, received either standard management alone (controls) or standard management plus vinpocetine (30 mg per day intravenously for 14 consecutive days, Gedeon Richter Plc., Hungary). Vinpocetine treatment did not change the lymphocyte count; however, nuclear factor kappa-light-chain-enhancer of activated B cell activation was inhibited as seen not only by the increased transcription of IκBα mRNA but also by the impeded phosphorylation and degradation of IκBα and subsequent induction of pro-inflammatory mediators. These effects led to significantly reduced secondary lesion enlargement and an attenuated inflammation reaction. Compared to controls, patients treated with vinpocetine had a better recovery of neurological function and improved clinical outcomes during the acute phase and at 3-month follow-up. These findings identify vinpocetine as an inflammation modulator that could improve clinical outcomes after acute ischemic stroke. This study also indicated the important role of immunity and inflammation in the pathogenesis of acute ischemic stroke and the significance of immunomodulatory treatment. CLINICAL TRIAL REGISTRATION INFORMATION: www.clinicaltrials.gov . Identifier: NCT02878772