The gut microbiota metabolite butyrate mitigates MPTP/MPP+ -induced Parkinson's disease by inhibiting the JAK2/STAT3 signaling pathway.

Butyrate (BU), a gut microbiota-derived metabolite, has been reported to play a neuroprotective role in Parkinson's disease (PD). However, the specific molecular mechanism of BU has not been fully interpreted. This work aimed to verify the protective effects of BU against MPTP/MPP+ -induced neurotoxicity and explore the mechanisms involved. The results showed that BU protected against MPTP-induced motor dysfunction and decreased tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels. Additionally, BU pretreatment improved PC12 cell viability and reduced MPP+ -induced PC12 cell apoptosis. BU treatment also attenuated MPP+ -stimulated oxidative stress and inflammatory response in PC12 cells. Furthermore, BU inhibited MPTP/MPP+ -induced hyperactivation of the JAK2/STAT3 signaling in mice and PC12 cells. Besides, a JAK2 agonist, Coumermycin A1 (C-A1), substantially reversed BU-mediated inhibition on JAK2/STAT3 phosphorylation in MPP+ -challenged PC12 cells and abated BU-induced repression on MPP+ -triggered apoptosis, oxidative stress, and inflammatory response in PC12 cells. To sum up, BU might exert neuroprotective effects against MPP+ /MPTP-induced neurotoxicity by inactivating the JAK2/STAT3 signaling.

Mechanisms of high ammonium loading promoted phosphorus release from shallow lake sediments: A five-year large-scale experiment.

The unprecedented global increase in the anthropogenic-derived nitrogen (N) input may have profound effects on phosphorus (P) dynamics and may potentially lead to enhanced eutrophication as demonstrated in short-term mesocosm experiments. However, the role of N-influenced P release is less well studied in large-scale ecosystems. To gain more insight into ecosystem effects, we conducted a five-year large-scale experiment in ten ponds (700-1000 m2 each) with two types of sediments and five targeted total N concentrations (TN) by adding NH4Cl fertilizer (0.5, 1, 5, 10, and 25 mg N L-1). The results showed that: (ⅰ) The sediment P release increased significantly when TN exceeded 10-25 mg N L-1. (ⅱ) The most pronounced sediment P release increase occurred in summer and from sediments rich in organic matter (OMSed). (ⅲ) TN, algal biomass, fish biomass, non-algal turbidity, sediment pH, and OMSed were the dominant factors explaining the sediment P release, as suggested by piecewise structural equation modeling. We propose several mechanisms that may have stimulated P release, i.e. high ammonium input causes a stoichiometric N:P imbalance and induce alkaline phosphatase production and dissolved P uptake by phytoplankton, leading to enhanced inorganic P diffusion gradient between sediment and water; higher pelagic fish production induced by the higher phytoplankton production may have led increased sediment P resuspension through disturbance; low oxygen level in the upper sediment caused by nitrification and organic decomposition of the settled phytoplankton and, finally, long-term N application-induced sediment acidification as a net effect of ammonium hydrolysis, nitrification, denitrification; The mechanisms revealed by this study shed new light on the complex processes underlying the N-stimulated sediment P release, with implications also for the strategies used for restoring eutrophicated lakes.

Arteriolosclerosis CSVD: a common cause of dementia and stroke and its association with cognitive function and total MRI burden.

Objective: Arteriolosclerosis cerebral small vessel disease (CSVD) is a common type of CSVD. This study aimed to explore the factors associated with cognitive function and total MRI burden related to the disease. Methods: The demographic characteristics, clinical manifestations, cognitive function score, Barthel Index (BI), blood test index, and follow-up results of arteriolosclerosis CSVD patients treated for the first time in our hospital from January 2014 to August 2022 were collected. White matter hyperintensity (WMH) Fazekas score, total MRI burden, and cerebral atrophy grade were evaluated according to brain MRI findings. Factors associated with CSVD cognitive function were analyzed by binary logistic regression. The correlative factors related to the total MRI burden of CSVD were analyzed by ordered multiple logistic regression. Results: A total of 146 patients were included in this study, of which 132 cases (90.4%) had hypertension. There were 108 patients (74.0%) with cognitive dysfunction, 97 patients (66.4%) with balance and gait disorders, and 83 patients (56.8%) with moderate-to-severe dependence in daily life (BI ≤ 60 points). Of 146 patients, 79 (54.1%) completed clinical and imaging follow-ups for a median of 3 years. The number of patients with cognitive impairment and BI ≤ 60 points after follow-up significantly increased compared with the first admission (P < 0.001). There were also significant differences in total MRI burden (P = 0.001), WMH Fazekas score, and cerebral atrophy grade (P < 0.001). Mean age (P = 0.012), median deep WMH Fazekas score (P = 0.028), and median deep (P < 0.001) and superficial (P =0.002) cerebral atrophy grade of patients with cognitive impairment at first admission were all higher than those with non-cognitive impairment. Multivariate analysis showed that deep cerebral atrophy was independently and significantly associated with cognitive impairment of CSVD (P = 0.024), and hypertension was significantly and independently associated with total MRI burden (P = 0.001). Conclusion: The disease course of arteriolosclerosis CSVD may be related to cognitive function and total MRI burden. Deep cerebral atrophy was an independent risk factor for cognitive dysfunction in arteriolosclerosis CSVD, and hypertension was an independent risk factor for total MRI burden.

A retrospective study of individualized endovascular treatment for symptomatic intracranial atherosclerotic stenosis in patients with ischemic stroke/transient ischemic attack.

Background: Endovascular treatment (EVT) is one of the effective treatment procedure for the symptomatic intracranial atherosclerotic stenosis (sICAS). Aim and methods: We evaluated the efficacy and safety of individualized endovascular treatment for sICAS patients. Clinical and imaging follow-ups were carried out to collect the data of 29 sICAS patients after 6 months of individualized endovascular treatment. Different treatment strategies are selected based on arterial access and lesion morphology of patients. If standard surgical path, narrow artery straight, stenosis length ≤10 mm, then the appropriate specifications of balloon-mounted stent (BMS) treatment. the surgical path is tortuous, the narrow artery is curved, the angle is apparent, the diameter of the near and far ends is significantly different, or the length of the stenosis is >10 mm, self-expanding stent (SES) with appropriate specifications is selected for treatment. If the narrowed artery is hyper flexed and the surgeon deems stenting inappropriate, balloon dilation angioplasty (BDA) treatment is chosen. Results and conclusion: 31 lesions of 29 sICAS patients received endovascular treatment. The median age was 61 years (IQR 54-69 years). The median preoperative stenosis was 90% (IQR 80-95%), and the mean stenosis length was (8.10 ± 3.27) mm. The most commonly used surgical procedure was Balloon-Mounted Stent (BMS) in 19 cases (65.52%), Self-expanding Stent (SES) in seven cases (24.14%), Balloon Dilation Angioplasty (BDA) in three cases (10.34%). (11.86 + 1.46 mm) was greater than that in the BMS group (6.14 + 1.59 mm) (P < 0.001). The median stenosis was 90% (IQR 80-92.5%) in the BMS group, lower than 99% (IQR 95-100%) in the SES group (P < 0.001). The median post-operative residual stenosis was 20% (IQR 15-25%), significantly improved compared with preoperative (P < 0.001). The success rate of the surgical technique was 93.10% (27/29). One patient (3.45%) had IS recurrence within 48 h after surgery, and the restenosis rate within 6 months after surgery was 6.90% (2/29). No patient died or had recurrent IS. Our data demonstrated that individualized endovascular treatment method could be potentially significant and safe for sICAS patients. This study will provide an important reference for the endovascular treatment of sICAD.

Secretory expression of a novel human spermatozoa antigen in E. coli and its application to a protein chip.

OBJECTIVE: To produce a recombinant spermatozoa antigen peptide using the E. coli: PhoA system on a protein chip for screening anti-sperm antibodies (ASA). RESULTS: The purity of the recombinant spermatozoa antigen exceeded 95% after two-step purification, as assessed using SDS-PAGE and HPLC. The diagnostic performance of a protein chip coated with the recombinant antigen peptide was evaluated by examining ASA in 51 infertile patients in comparison with a commercial ELISA kit. The area under the receiver operating characteristic curve (AUC) was 0.944, which indicated that the protein chip coated with recombinant spermatozoa antigen peptide was consistent with ELISA for ASA detection. CONCLUSION: A recombinant spermatozoa antigen was expressed in the E. coli PhoA secretory expression system and its potential application for clinical ASA detection was validated.

Neuroprotective effects of bisperoxovanadium on cerebral ischemia by inflammation inhibition.

PTEN is a dual specificity phosphatase and is implicated in inflammation and apoptosis of cerebral ischemia and reperfusion (I/R) injury. Bisperoxovanadium (Bpv), a specific inhibitor of PTEN's phosphatase activity, has demonstrated powerful neuroprotective properties. We investigated the neuroprotective roles of Bpv in the rat model of middle cerebral artery occlusion (MCAO) cerebral I/R injury, and explored the modulation of inflammatory mediators and PI3K/Akt/GSK-3ß pathways by Bpv. Our results showed that treatment with Bpv (0.2 mg/kg/day) significantly decreased neurological deficit scores at 7 days after MCAO and infarct volume at 4 days after MCAO. The IL-10 concentration was increased and TNF-α concentration was decreased in the ischemic boundary zone of the cerebral cortex at 4 days after MCAO by Bpv. Furthermore, Bpv (0.2 mg/kg/day) treatment significantly reduced PTEN mRNA and protein levels and increased PI3K, Akt and p-GSK-3ß proteins expression in the ischemic boundary zone of the cerebral cortex at 4 days after MCAO. In conclusions, Bpv treatment demonstrates neuroprotective effects on cerebral ischemia and reperfusion injury of ischemic stroke rats and is associated with its modulation of inflammatory mediator production and up-regulation of PTEN downstream proteins PI3K, Akt and p-GSK-3ß.