Rubusoside mitigates neuroinflammation and cellular apoptosis in Parkinson's disease, and alters gut microbiota and metabolite composition.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative condition characterized by the progressive loss of dopaminergic neurons within the substantia nigra. Neuroinflammation plays a pivotal role in the pathogenesis of PD, involving the activation of microglia cells, heightened production of proinflammatory cytokines, and perturbations in the composition of the gut microbiota. Rubusoside (Ru), the principal steviol bisglucoside present in Rubus chingii var. suavissimus (S.K.Lee) L.T.Lu (Rosaceae), has been documented for its anti-inflammatory properties in diverse disease models. Nonetheless, there is an imperative need to comprehensively assess and elucidate the protective and anti-inflammatory attributes of Ru concerning PD, as well as to uncover the underlying mechanism involved. OBJECTIVE: The aim of this study is to evaluate the neuroprotective and anti-inflammatory effects of Ru on PD and investigate its potential mechanisms associated with microbes. RESEARCH DESIGN AND METHODS: We pre-treated mice and cell lines with Ru in order to simulate the progression of PD and the neuroinflammatory state. The mouse model was induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), SN4741 cells were induced by 1-methyl-4-phenylpyridine (mpp+), and BV-2 cells were induced by lipopolysaccharide (LPS). We assessed the impact of Ru on motor function, neuroinflammation, neuron apoptosis, the composition of gut microbes, and their metabolites. RESULTS: Ru treatment reduces the release of pro-inflammatory mediators by inhibiting microglia activation. It also prevents neuronal apoptosis, thereby safeguarding dopaminergic neurons and ameliorating motor dysfunction. Furthermore, it induces alterations in the fecal microbiota composition and metabolites profile in PD mice. In vitro experiments have demonstrated that Ru inhibits neuronal apoptosis in SN4741 cells induced by mpp+, suppresses the production of pro-inflammatory mediators, and activates the c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase (p38 MAPK), and nuclear factor kappa-B (NF-κB) signaling pathways. CONCLUSION: Ru exhibits inhibitory effects on the MPTP-induced PD model by mitigating neuroinflammation and neuronal apoptosis while also inducing changes in the gut microbiota and metabolite composition.

The impact of platelet indices on ischemic stroke: a Mendelian randomization study and mediation analysis.

Introduction: Platelet indices (PIs) are hematological parameters that indicate the number, morphology, and activation of platelets. Although some clinical trials suggest an association between PIs and the risk of stroke, the lack of robust evidence is attributed to confounding effects and reverse causation. Objective: This study aimed to evaluate the association between PIs and stroke risk through Mendelian randomization (MR) while exploring the mediating effect of blood pressure in this association. Methods: We identified genetic variants associated with PIs, including platelet count (PLT), platelet distribution width (PDW), mean platelet volume (MPV), and platelet crit (PCT), in the UK Biobank (n = 350,474). Relevant genome-wide association studies were utilized to gather summary statistics pertaining to the traits of interest. We primarily used the inverse-variance weighted analysis to obtain estimates for individual causal power. Result: We observed a positive correlation between genetically predicted increases in PCT levels with the stroke onset [PCT: OR (95%CI) = 1.113(1.047, 1.183), p < 0.001]. However, no significant causal relationship was found between PLT, PDW, and MPV and the risk of stroke [PLT: OR (95%CI) = 1.037(0.979, 1.098), p = 0.221; PDW: OR (95%CI) = 0.973(0.923, 1.024), p = 0.294; MPV: OR (95%CI) = 0.990(0.945, 1.038), p = 0.675]. Multivariable MR analyses and mediation analysis found that the proportion mediated by systolic blood pressure (SBP) is 23.71% [95%CI (10.85-33.31%)] and the proportion mediated by diastolic blood pressure (DBP) is 28.09% [95%CI (12.92-39.63%)]. Conclusion: This large MR study presents evidence for the potential causal relationship between the PCT level and the risk of ischemic stroke, which might be mediated by blood pressure.

Association of grip strength and comorbidities with all-cause mortality in the older hypertensive adults.

Background: With growing concerns about global population aging, comorbidity, and disability have emerged as key variables that influence the health of the older adults in terms of disease and function. This study sought to examine the impact of comorbidity and impairment using disease and functional status indicators of all-cause mortality in the older adults. Hypertension, which was chosen as the indicator chosen for disease, has the greatest prevalence in the older population. A total of 15 self-reported chronic conditions were added as indicators of comorbidity, and grip strength was chosen as a measure of functional status. The study also evaluated the association between grip strength and comorbidity, as well as its consequences on all-cause death and survival in a hypertensive senior population. Methods: We chose a total of 2,990 hypertensive participants aged ≥60 years whose data for grip strength were collected in the National Health and Nutrition Examination Survey conducted between 2011 and 2014. The association of all-cause death with grip strength and comorbidity was examined using a Cox proportional hazard regression model. The interaction between comorbidity and all-cause mortality, as well as its association with grip strength, was also examined. Results: The hazard ratio [95% confidence intervals (CIs)] for all-cause mortality in the highest grip strength tertile was 0.266 (0.168-0.419), compared to the lowest grip strength tertile. The all-cause mortality decreased with an increase in the number of co-morbidities [2.677 (1.557-4.603) in the group with ≥3 chronic diseases]. The weighted generalized model revealed a negative correlation between grip strength and comorbidities in more than three groups after accounting for all possible variables (ß = -2.219, -3.178 ~ -1.260, p < 0.001). The risk of mortality reduced with increasing grip strength in patients with ≥3 comorbidities (p-value for trend <0.05), but no meaningful difference was found in the interaction between comorbidities and grip strength (p-value for interaction >0.05). Conclusion: In older hypertension patients, grip strength and comorbidities were correlated with all-cause death, and there was a negative correlation between grip strength and comorbidities. Higher grip strength was associated with fewer fatalities in patients with ≥3 comorbidities, suggesting that functional exercise can improve the prognosis of comorbidities.

CNS Organoid Surpasses Cell-Laden Microgel Assembly to Promote Spinal Cord Injury Repair.

The choice of therapeutic agents remains an unsolved issue in the repair of spinal cord injury. In this work, various agents and configurations were investigated and compared for their performance in promoting nerve regeneration, including bead assembly and bulk gel of collagen and Matrigel, under acellular and cell-laden conditions, and cerebral organoid (CO) as the in vitro preorganized agent. First, in Matrigel-based agents and the CO transplantations, the recipient animal gained more axon regeneration and the higher Basso, Beattie, and Bresnahan (BBB) scoring than the grafted collagen gels. Second, new nerves more uniformly infiltrated into the transplants in bead form assembly than the molded chunks. Third, the materials loaded the neural progenitor cells (NPCs) or the CO implantation groups received more regenerated nerve fibers than their acellular counterparts, suggesting the necessity to transplant exogenous cells for large trauma (e.g., a 5 mm long spinal cord transect). In addition, the activated microglial cells might benefit from neural regeneration after receiving CO transplantation in the recipient animals. The organoid augmentation may suggest that in vitro maturation of a microtissue complex is necessary before transplantation and proposes organoids as the premium therapeutic agents for nerve regeneration.

Role of 18FDG PET/CT metabolic parameters in predicting hematological toxicity during chemoradiotherapy for locally advanced cervical cancer.

Purpose: The aim of this study is to evaluate the value of 18FDG PET/CT metabolic parameters in predicting hematological toxicity (HT) during chemoradiotherapy (CRT) for locally advanced cervical cancer (LACC). Methods and materials: Forty-one patients with LACC undergoing concurrent CRT were retrospectively analyzed. The correlations among age, body mass index, FIGO stage, differentiation, maximum diameter of primary lesion, parametrial invasion, lymph node metastasis, pelvic active bone marrow volume (BMACT), BMACT volume percentage (BMACT%), maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and HT were analyzed using hypothesis testing and logistic regression. A p-value< 0.05 was considered significant unless otherwise specified. Results: Among the 41 patients, 19 had grade 3-4 HT and 22 had grade 0-2 HT. Only SUVmax (Z = -1.961, p = 0.050) and BMACT% (χ2 = 7.769, p = 0.020) showed statistically significant difference in univariate analysis. In logistic regression, grade 3-4 HT was not associated with SUVmax. The probability of HT occurrence in<30% BMACT% was 0.071 times less than in 30%-40% BMACT% (p = 0.010, OR = 0.071, 95% CI = 0.010-0.532), and the probability of HT occurrence in >40% BMACT% was 0.148 times less than in 30%-40% BMACT% (p = 0.037, OR = 0.148, 95% CI = 0.025-0.892). Conclusion: Baseline 18FDG PET/CT BMACT% could help predict the severity of HT during CRT for LACC.

Differences of Sleep Disorders Between Vestibular Migraine and Benign Paroxysmal Positional Vertigo.

Introduction: Sleep disorders can affect the overall health and quality of life of patients. This study was conducted to compare the differences of sleep disorders in vestibular migraine (VM) patients and benign paroxysmal positional vertigo (BPPV) patients. Methods: VM patients, BPPV patients, and healthy controls (HCs) were recruited. Pittsburgh sleep quality index and polysomnography monitoring were used as subjective and objective, respectively, evaluation methods to evaluate the sleep quality of participants in the latest month. Results: Fifty-seven BPPV patients, 48 VM patients, and 42 HCs were included in this study. There were 79.16% VM patients, 54.39% BPPV patients, and 14.28% HCs with sleep disorders. The difference in the incidence rate of sleep disorders was significant between VM patients and BPPV patients (p = 0.008) and significantly higher in both the VM group (p < 0.00001) and BPPV group (p = 0.00004) than in the HC groups (14.28%). Compared with BPPV patients, the VM patients had the significantly lower sleep efficiency (p < 0.001) and N3 (p < 0.001) and the significantly higher time of wake-up after sleep onset (p < 0.001), N1 (p < 0.001), and N2 (p < 0.001). Meanwhile, the VM patients had significantly higher incidence rates of severe obstructive sleep apnea hypoventilation syndrome (p = 0.001) and periodic leg movement in sleep (p = 0.016). Conclusion: The incidence rate of sleep disorders was significantly higher in both VM and BPPV patients than in the HC groups. To improve the curative effects, clinicians should pay more attention to the comorbidity of sleep disorders in treating VM and BPPV.

Diabetes Mellitus Promotes Atrial Structural Remodeling and PARP-1/Ikkα/NF-κB Pathway Activation in Mice.

BACKGROUND: Diabetes mellitus (DM) has been demonstrated to be linked to atrial fibrillation (AF). However, the underlying mechanisms of the DM-associated increase in AF susceptibility and the potential effects of DM on atrial remodeling remain unclear. METHODS AND RESULTS: Twenty-five C57BL/6 mice were randomly assigned to the normal/control group (Con, n=10) and model group (n=15). Mice in the model group were administered a high-fat diet combined with multiple injections of low-dose streptozocin (STZ) (35 mg/kg). Eleven mice were ultimately included in DM group. Left atrial tissue structural and inflammatory alterations were assessed. In our study, the atrial weights of DM mice were markedly heavier than those of mice in the Con group. DM mice exhibited significantly increased fasting plasma glucose, fasting insulin, and dyslipidaemia. Furthermore, H&E and Masson's staining revealed broadened interstitial spaces, myocyte disarray and atrial fibrosis in DM mice. The expression levels of the atrial inflammation-associated factor nuclear factor κB (NF-κB) and its pathway were significantly altered in the atria of DM mice. CONCLUSION: DM could induce atrial structural remodeling and inflammation in mice.

Evodiamine Inhibits Lipopolysaccharide (LPS)-Induced Inflammation in BV-2 Cells via Regulating AKT/Nrf2-HO-1/NF-κB Signaling Axis.

Neuroinflammation is caused by excessive activation of microglia and plays an essential role in neurodegenerative diseases. After activation, microglia produce several kinds of inflammatory mediators, trigger an excessive inflammatory response, and ultimately destroy the surrounding neurons. Therefore, agents that inhibit neuroinflammation may be potential drug candidates for neurodegenerative diseases. Evodiamine (EV) has anti-inflammatory functions in peripheral tissues. However, whether EV exerts the same function in neuroinflammation is not known. In the present study, the aim was to explore whether EV attenuates microglial overactivation and therefore suppresses the development of neuroinflammation in lipopolysaccharide (LPS)-stimulated BV-2 cells. It was found that EV effectively inhibited expression of proinflammatory mediators (cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)) via AKT/Nrf2/HO-1 activation and suppressed NF-κB p65 phosphorylation. In addition, EV could suppress LPS-induced inflammatory response and loss of dopaminergic neuron in mouse mesencephalic neuron--glia cells. Hence, these findings demonstrate that EV suppresses neuroinflammation caused by overactivated microglia via regulating the AKT/Nrf2/HO-1/NF-κB signaling axis.

Beta-naphthoflavone inhibits LPS-induced inflammation in BV-2 cells via AKT/Nrf-2/HO-1-NF-κB signaling axis.

Numerous studies have shown that over-activation of microglia could cause neuroinflammation and release pro-inflammatory mediators, which could result in neurodegenerative diseases, like Parkinson's disease, Alzheimer's disease etc. Beta-naphthoflavone (BNF) has anti-oxidant and anti-inflammatory effects in borderline tissues, but BNF has not been reported the effect associated with neuroinflammation. Therefore, the purpose of this experiment is to inquiry the impact and mechanism of BNF on neuroinflammation. The results indicated that BNF significantly inhibited the production of pro-inflammatory mediators (inducible nitric-oxide synthase (iNOS), Cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) andinterleukin-6 (IL-6)) in LPS-exposed BV-2 cells. Analysis of western blot results found that BNF accelerated the activation of AKT/Nrf-2/HO-1 signaling pathway and suppressed NF-κB pathway activation. Further study showed that BNF inhibited activation of NF-κB pathway via promoting HO-1, and SnPP IX (a HO-1 inhibitor) could inhibit anti-inflammatory function of BNF. We also found that BNF reduced the apoptosis rate of Human neuroblastoma cells (SHSY5Y) and mouse hippocampal neuron cell line (HT22) by inhibiting release of inflammatory mediators in LPS-exposed BV2 cells. In a word, our results suggested that BNF could inhibit inflammatory response via AKT/Nrf-2/HO-1-NF-κB signaling axis in BV-2 cells and exerts neuroprotective impact via inhibiting the activation of BV2 cells.

Analysis of factors affecting the prognosis of patients with cervical intraepithelial neoplasia 2.

According to the 2014 World Health Organization Classification of Tumors of Female Reproductive Organs, patients with cervical intraepithelial neoplasia 2 (CIN2) have an equivocal diagnosis, but p16 is considered as the reference index for CIN2. Positive p16 expression in CIN2 is associated with high-grade squamous intraepithelial lesions (HSIL), whereas p16 negative lesions are low-grade squamous intraepithelial lesions. The purpose of the present study was to examine the clinical value of p16 and human papillomavirus (HPV) E6/E7 mRNA in the prognostication of patients with CIN2. From January 2013 to January 2016, 108 patients were diagnosed with CIN2 by biopsy and followed up at 6-month intervals at Peking University People's Hospital (Beijing, China). The expression of HPV E6/E7 mRNA was detected by in situ hybridization, while the expression of p16 and Ki-67 proteins was detected by immunohistochemistry. Of the 108 CIN2 cases, 20 progressed to HSIL/CIN3, 36 cases demonstrated persistence with CIN2 after the follow-up and 52 cases achieved regression (≤CIN1). Of the p16-positive 82 cases, 20 cases were detected to have progressed, whereas in the p16-negative group, no progression was observed. There were statistically significant differences among the p16-positive and negative groups (P<0.05). In the HPV E6/E7 mRNA-positive 69 cases, 18 cases were detected to have progressed, whereas in the HPV E6/E7 mRNA-negative 39 cases, progression was detected in only 2 cases. There were statistically significant differences among the HPV E6/E7 mRNA-positive and negative groups (P<0.05). The area under the receiver operating characteristics curve was plotted; the area under the curve for HPV E6/E7 mRNA was 0.745, that for p16 was 0.546 and that for Ki-67 was 0.501. The detection of HPV E6/E7 mRNA may provide important predictive information for the prognosis of CIN2, however p16 and Ki-67 proteins may provide little value.

miR-129-5p attenuates hypoxia-induced apoptosis in rat H9c2 cardiomyocytes by activating autophagy.

BACKGROUND: Autophagy is closely associated with apoptosis in H9c2 cardiomyocytes as a result of hypoxia. The present study aimed to determine whether microRNAs (miRs) mediated apoptosis and autophagy in hypoxia-stimulated H9c2 cardiomyocytes. METHODS: miR microarrays and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays were used to detect differentially expressed miRs in H9c2 cardiomyocytes following hypoxia stimulation. Annexin V-fluorescein isothiocyanate double staining was performed to evaluate hypoxia-induced cell apoptosis, and the protein expression levels of autophagy-associated genes were detected using western blotting. RESULTS: miR microarrays and qRT-PCR assays showed that the expression of miR-129-5p is significantly decreased in hypoxia-exposed H9c2 cardiomyocytes. Under hypoxic stimulation, miR-129-5p mimics alleviated hypoxia-induced cell apoptosis and also restored autophagy in H9c2 cardiomyocytes. However, transfection with miR-129-5p inhibitors accelerated hypoxia-induced cell apoptosis and autophagy deficiency in H9c2 cardiomyocytes. Furthermore, overexpression of miR-129-5p enhanced cell viability and reduced the release of lactate dehydrogenase in hypoxia-stimulated H9c2 cardiomyocytes. CONCLUSIONS: These findings highlight the protective effect of miR-129-5p against hypoxia-induced apoptosis in H9c2 cardiomyocytes through the activation of autophagy.

α-Cyperone Attenuates H2O2-Induced Oxidative Stress and Apoptosis in SH-SY5Y Cells via Activation of Nrf2.

α-Cyperone, extracted from Cyperus rotundus, has been reported to inhibit microglia-mediated neuroinflammation. Oxidative stress and apoptosis play crucial roles in the course of Parkinson's disease (PD). PD is a common neurodegenerative disease characterized by selective death of dopaminergic neurons. This study was designed to investigate the neuroprotective effects of α-cyperone against hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in dopaminergic neuronal SH-SY5Y cells. Neurotoxicity was assessed by MTT assay and the measurement of lactic dehydrogenase (LDH) release. The level of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescin diacetate (DCFH-DA) staining. The apoptosis of SH-SY5Y cells was evaluated by annexin-V-FITC staining. The translocation of NF-E2-related factor 2 (Nrf2) was determined by western blot and immunofluorescence staining. Western blot analysis was conducted to determine the expression level of cleaved-caspase-3, the pro-apoptotic factor Bax, and the anti-apoptotic factor, Bcl-2. The results showed that α-cyperone substantially decreased H2O2-induced death, release of LDH, and the production of ROS in SH-SY5Y cells. In addition, we found that α-cyperone attenuated H2O2-induced cellular apoptosis. Moreover, α-cyperone remarkably reduced the expression of cleaved-caspase-3 and Bax, and upregulated Bcl-2. Furthermore, α-cyperone enhanced the nuclear translocation of Nrf2. Pretreatment with brusatol (BT, an Nrf2 inhibitor) attenuated α-cyperone-mediated suppression of ROS, cleaved-caspase-3, and Bax, as well as α-cyperone-induced Bcl-2 upregulation in H2O2-treated SH-SY5Y cells. α-cyperone neuroprotection required Nrf2 activation. In conclusion, α-cyperone attenuated H2O2-induced oxidative stress and apoptosis in SH-SY5Y cells via the activation of Nrf2, suggesting the potential of this compound in the prevention and treatment of PD.

A novel nephrometry scoring system for predicting peri-operative outcomes of retroperitoneal laparoscopic partial nephrectomy.

BACKGROUND: Although the impact of tumor complexity on peri-operative outcomes has been well established using several nephrometry scoring systems, the impact of adherent perirenal fat remains poorly defined. This study aimed to develop a novel nephrometry scoring system for predicting the peri-operative outcomes of laparoscopic partial nephrectomy (LPN) by integrating and optimizing the RENAL score (RNS) and Mayo adhesive probability (MAP) score. METHODS: We retrospectively evaluated 159 patients treated with retroperitoneal LPN. The patients' demographic parameters, RNSs, and MAP scores were evaluated as potential predictors of perioperative outcomes, including operation time, estimated blood loss (EBL), and margin, ischemia, and complication (MIC) achievement rate. The independent predictors were used to develop a novel nephrometry scoring system. The predictive value and inter-observer agreement for the novel nephrometry scoring system were evaluated. RESULTS: Tumor radius (R score), nearness to the renal sinus or collecting system (N score), and posterior perinephric fat thickness were independent predictors of peri-operative outcomes and were used to develop the RNP score. The univariate analysis revealed that the RNP score was significantly associated with operation time, EBL, and MIC achievement rate (P < 0.050). The RNP score was an independent predictor of operation time (P < 0.001), EBL (P = 0.018), and MIC achievement rate (P = 0.023) in the multivariate analysis. The RNP score was not inferior to RNS in the area under the curve for predicting peri-operative outcomes and performed better in inter-observer agreement (76.7% vs. 57.8%) and kappa value (0.804 vs. 0.726). CONCLUSION: The RNP score, combining the advantages of the RNS and MAP score, demonstrated a good predictive value for the peri-operative outcomes of retroperitoneal LPN and better inter-observer agreement.

Farrerol protects dopaminergic neurons in a rat model of lipopolysaccharide-induced Parkinson's disease by suppressing the activation of the AKT and NF-κB signaling pathways.

Neuroinflammation, characterized by the activation of microglia, is one of the major pathologic processes of Parkinson's disease (PD). Overactivated microglia can release many pro-inflammatory cytokines, which cause an excessive inflammatory response and eventually damage dopaminergic neurons. Therefore, the inhibition of neuroinflammation that results from the overactivation of microglia may be an method for the treatment of PD. Farrerol is a 2,3-dihydro-flavonoid obtained from Rhododendron, and it possesses various biological functions, including anti-inflammatory, antibacterial and antioxidant activities. However, the effect of farrerol on neuroinflammation has not been investigated. The present study uncovered a neuroprotective role for farrerol. In vitro, farrerol markedly decreased the production of inflammatory mediators, including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), cyclooxygenase 2 (COX-2) and induced nitric oxide synthase (iNOS), induced by lipopolysaccharide (LPS) in BV-2 cells. This anti-inflammatory effect was regulated via inhibiting NF-κB p65 and AKT phosphorylation. Furthermore, we found that farrerol alleviated microglial activation and dopaminergic neuronal death in rats with LPS-induced PD. Pretreatment with farrerol markedly improved motor deficits in rats with LPS-induced PD. Taken together, our results indicate that the neuroprotective effect of the farrerol, which prevents microglial overactivation in rats with LPS-induced PD, may provide a potential therapy for patients suffering from PD.

Polydatin Prevents Lipopolysaccharide (LPS)-Induced Parkinson's Disease via Regulation of the AKT/GSK3ß-Nrf2/NF-κB Signaling Axis.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by selective loss of dopaminergic neurons in the substantia nigra (SN). Neuroinflammation induced by over-activation of microglia leads to the death of dopaminergic neurons in the pathogenesis of PD. Therefore, downregulation of microglial activation may aid in the treatment of PD. Polydatin (PLD) has been reported to pass through the blood-brain barrier and protect against motor degeneration in the SN. However, the molecular mechanisms underlying the effects of PLD in the treatment of PD remain unclear. The present study aimed to determine whether PLD protects against dopaminergic neurodegeneration by inhibiting the activation of microglia in a rat model of lipopolysaccharide (LPS)-induced PD. Our findings indicated that PLD treatment protected dopaminergic neurons and ameliorated motor dysfunction by inhibiting microglial activation and the release of pro-inflammatory mediators. Furthermore, PLD treatment significantly increased levels of p-AKT, p-GSK-3ßSer9, and Nrf2, and suppressed the activation of NF-κB in the SN of rats with LPS-induced PD. To further explore the neuroprotective mechanism of PLD, we investigated the effect of PLD on activated microglial BV-2 cells. Our findings indicated that PLD inhibited the production of pro-inflammatory mediators and the activation of NF-κB pathways in LPS-induced BV-2 cells. Moreover, our results indicated that PLD enhanced levels of p-AKT, p-GSK-3ßSer9, and Nrf2 in BV-2 cells. After BV-2 cells were pretreated with MK2206 (an inhibitor of AKT), NP-12 (an inhibitor of GSK-3ß), or Brusatol (BT; an inhibitor of Nrf2), treatment with PLD suppressed the activation of NF-κB signaling pathways and the release of pro-inflammatory mediators in activated BV-2 cells via activation of the AKT/GSK3ß-Nrf2 signaling axis. Taken together, our results are the first to demonstrate that PLD prevents dopaminergic neurodegeneration due to microglial activation via regulation of the AKT/GSK3ß-Nrf2/NF-κB signaling axis.

Protective effect of diltiazem on myocardial ischemic rats induced by isoproterenol.

The aim of the present study was to analyze the effect of diltiazem on myocardial fibrosis and remodeling of connexin43 (Cx43) in myocardial ischemic rats and mechanisms underlying these processes. A total of 36 Sprague­Dawley rats were randomly allocated into three groups (control, isoproterenol and isoproterenol with diltiazem). The myocardial ischemic model was established by 5 mg/kg/day isoproterenol administration for 7 days, and the diltiazem group received 25 mg/kg/day diltiazem for 4 weeks. Following the treatment, paraffin sections were prepared to observe microstructural changes and to evaluate the concentration of Ca2+ in myocardium. The expression of transforming growth factors­ß1 (TGF­ß1), mothers against decapentaplegic homologues (Smad)2 and 7 and Cx43, were analyzed by reverse transcription-quantitative polymerase chain reaction and western blotting. The percentage Cx43 expression in intercalated disks was evaluated using immunohistochemistry. Fibrosis did not differ significantly between the control and the diltiazem­treated group. The concentration of Ca2+ increased in the myocardium of model rats. The expression of Smad7 and Cx43 was decreased in the rat model, while the expression of TGF­ß1 and Smad2 was increased. There was a significant decrease in the relative abundance of intercalated disk Cx43 in the model group. The results of the present study suggest that diltiazem may serve a protective role during remodeling of myocardial ischemia, especially in fibrosis and Cx43 remodeling.

Exposure to a chronic high-fat diet promotes atrial structure and gap junction remodeling in rats.

Obesity has been demonstrated to be linked to atrial fibrillation (AF) with atrial enlargement and tissue fibrosis. Long-term high calorie intake is the main reason for the prevalence of obesity. To investigate the possible causes of AF, such as chronic high-fat diet (HFD), and to identify the underlying mechanisms, the present study analyzed a variety of structural and gap junctional electrophysiological alterations in the atria of female rats fed an HFD. After consistent HFD feeding of female rats for 12 weeks, hematoxylin and eosin (H&E) and Masson's staining, RT-qPCR, western blotting, immunofluorescence and TUNEL staining were performed. In our study, approximately 3/5 of the HFD-fed rats (HFD-OB, n=13) displayed a significant increase in body weight, while the other 2/5 did not (HFD-NOB, n=8). In addition, the atrial weight of the HFD-OB and HFD-NOB rats was markedly heavier, as compared to the rats fed a normal diet (CT, n=20). According to the plasma lipid levels, both HFD-OB and HFD-NOB rats exhibited dyslipidemia. Furthermore, H&E staining revealed broadened interstitial space and myocyte disarray in atria of the HFD-fed rats (i.e., HFD-OB and HFD-NOB rats). Expression levels of atrial fibrosis relevant factors, transforming growth factor-ß1 and matrix metalloproteinase-2, were significantly upregulated in the HFD-fed rat atria. In addition, we found a gap junction remodeling with distinct alterations in expression and distribution of connexin 40 (Cx40) and Cx43 in the HFD-fed rat atria. Moreover, a modest increase in apoptotic cell death in both the HFD-OB and HFD-NOB rat atria was detected. Taken together, our findings demonstrated that the impact of chronic HFD on atria displayed in the diet-induced obese rats was observed in HFD-fed rats in the absence of obesity as well.

Ni0.85Se@MoSe2 Nanosheet Arrays as the Electrode for High-Performance Supercapacitors.

In this study, we report novel Ni0.85Se@MoSe2 nanosheet arrays prepared by a facile one-step hydrothermal method through nickel (Ni) foam as Ni precursor and the framework of MoSe2. Owing to the unique interconnection and hierarchical porous nanosheet array architecture, the Ni0.85Se@MoSe2 nanosheet arrays exhibit a high specific capacitance of 774 F g-1 at the current density of 1 A g-1, which is almost 2 times higher than that (401 F g-1) of the Ni0.85Se matrix and about 7 times greater than that (113 F g-1) of the MoSe2 nanoparticles. Moreover, we report an asymmetric supercapacitor (ASC), which is fabricated by using the Ni0.85Se@MoSe2 nanosheet arrays as the positive electrode and the graphene nanosheets (GNS) as the negative electrode, with aqueous KOH as the electrolyte. The Ni0.85Se@MoSe2//GNS ASC possesses an output voltage of 1.6 V, an energy density of 25.5 Wh kg-1 at a power density of 420 W kg-1, and a cycling stability of 88% capacitance retention after 5000 cycles. These results indicate that the Ni0.85Se@MoSe2 nanosheet arrays are a good electrode for supercapacitors.

Inverted organic photovoltaic cells.

The advance in lifestyle, modern industrialization and future technological revolution are always at high expense of energy consumption. Unfortunately, there exist serious issues such as limited storage, high cost and toxic contamination in conventional fossil fuel energy sources. Instead, solar energy represents a renewable, economic and green alternative in the future energy market. Among the photovoltaic technologies, organic photovoltaics (OPVs) demonstrate a cheap, flexible, clean and easy-processing way to convert solar energy into electricity. However, OPVs with a conventional device structure are still far away from industrialization mainly because of their short lifetime and the energy-intensive deposition of top metal electrode. To address the stability and cost issue simultaneously, an inverted device structure has been introduced into OPVs, bridging laboratory research with practical application. In this review, recent progress in device structures, working mechanisms, functions and advances of each component layer as well their correlations with the efficiency and stability of inverted OPVs are reviewed and illustrated.