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Visit-to-visit variability of glycated hemoglobin (HbA1c) is a marker of long-term glycemic fluctuation, which has been related to increased risk of macrovascular complications in patients with type 2 diabetes mellitus (T2DM). The association between HbA1c variability and retinopathy in patients with T2DM, however, has been inconsistent in previous studies. In order to fully evaluate the above association, we conducted a meta-analysis. Observational studies related to the aim of the meta-analysis were identified by search of PubMed, Web of Science, and Embase databases. Studies with HbA1c variability evaluated as the standard deviation (SD) and/or the coefficients of variation (CV) of HbA1c were included. The results were analyzed using a random-effects model that incorporated potential heterogeneity between studies. Twelve observational studies involving 44 662 T2DM patients contributed to the meta-analysis. Overall, 5150 (11.5%) patients developed retinopathy. Pooled results showed that compared to patients with lower HbA1c variability, T2DM patients with higher HbA1c-SD (relative risk [RR]: 1.48, 95% confidence interval [CI]: 1.24 to 1.78, p<0.001, I2=34%) and higher HbA1c-CV (RR: 1.29, 95% CI: 1.05 to 1.59, p=0.02, I2=0%) were both associated with higher risk of DR. For studies with HbA1c-SD, the association was not significantly affected by study characteristics such as country, study design, mean age, disease duration, adjustment of mean HbA1c, or quality scores (p for subgroup difference all>0.05). In conclusion, higher HbA1c variability may be associated with an increased risk of retinopathy in patients with T2DM. [ABSTRACT FROM AUTHOR]

Syringaresinol-di-O-β-D-glucoside (SOG) is a phenolic compound extracted from Polygonatum sibiricum. The present study aimed to investigate the antidiabetic effect of SOG on streptozocin (STZ)-induced diabetic mice and determine the potential underlying mechanisms. In the present study, fasting blood glucose and organ indexes of mice were analyzed. Body weight, water intake and food intake were also recorded. Furthermore, serum fasting insulin, pancreatic insulin and pancreatic interleukin-6 levels of mice were determined using ELISA kits to investigate the effect of SOG on the levels of insulin. Levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C) and free fatty acid (FFA) in the serum of mice, and levels of TC, TG and total protein in the kidney, were also determined to investigate the effects of SOG on lipid and protein metabolism in mice. Furthermore, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) levels, as well as total antioxidant capacity (T-AOC), in the kidneys of mice were determined to investigate the effect of SOG on oxidative stress. Western blotting was also performed to determine the expression of proteins associated with oxidative stress. The results demonstrated that SOG (25, 50 and 75 mg/kg) induced a significant antidiabetic effect in mice. Treatment with SOG promoted insulin secretion and decreased TC, TG, LDL-C, VLDL-C, FFA, MDA, SOD, CAT, AST, ALT and ALP levels in the kidneys of mice, as well as kidney TC and TG levels, but increased the levels of kidney total protein and the T-AOC in kidneys. Furthermore, SOG treatment could significantly downregulate the expressions of nitrotyrosine and transforming growth factor-β1 in diabetic mice. Therefore, the present study indicated that SOG may exert an antidiabetic effect on STZ-induced diabetic mice and that the mechanism of SOG may be associated with its antioxidative activity. [ABSTRACT FROM AUTHOR]

Aim: We investigated the mechanism, whereby tumor necrosis factor‐like ligand 1A (TL1A) mediates the A1 differentiation of astrocytes in postoperative cognitive dysfunction (POCD). Methods: The cognitive and behavioral abilities of mice were assessed by Morris water maze and open field tests, while the levels of key A1 and A2 astrocyte factors were detected by RT‐qPCR. Immunohistochemical (IHC) staining was used to examine the expression of GFAP, western blot was used to assay the levels of related proteins, and enzyme‐linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory cytokines. Results: The results showed that TL1A could promote the progression of cognitive dysfunction in mice. Astrocytes differentiated into A1 phenotype, while unobvious changes were noted in astrocyte A2 biomarkers. Knockout of NLRP3 or intervention with NLRP3 inhibitor could inhibit the effect of TL1A, improving the cognitive dysfunction and suppressing the A1 differentiation. Conclusion: Our results demonstrate that TL1A plays an important role in POCD in mice, which promotes the A1 differentiation of astrocytes through NLRP3, thereby exacerbating the progression of cognitive dysfunction. [ABSTRACT FROM AUTHOR]

• Neocryptotanshinone can repair brain injury after ischemia. • Neocryptotanshinone can inhibit M1 polarization of microglia and inhibit neuroya. • Neocryptotanshinone can promote the opening of collateral circulation and promote angiogenesis. This study explored the protective function and mechanism of neocryptotanshinone (NEO) on cerebral ischemia. Lipopolysaccharide/γ-interferon(LPS/IFN-γ)was employed to mimic the polarization of mouse microglial cells BV2. After NEO treatment, the M1 polarization level of BV2 cells was identified using flow cytometry (FCM), fluorescent cell staining and enzyme linked immunosorbent assay(ELISA). Moreover, the mouse endothelial cells bEnd.3 were applied to be the study objects, which were intervened with NEO under the hypoxic condition. Thereafter, based on in-vitro tubule formation assay and fluorescence staining, the in-vitro tubule formation ability of bEnd.3 cells was detected. By adopting middle cerebral artery occlusion(MCAO) method, we constructed the mouse model of cerebral ischemia. After NEO intervention, the pathological changes of brain tissues were identified, while CD34 expression was measured by immunohistochemical (IHC) staining, nerve injury was detected by Nissl staining, and the changes in neurological behaviors of mice were also detected. Our results showed that NEO suppressed M1 polarization of BV2 cells, which exerted its effect through suppressing NF-κB and STAT3 signals, thereby decreasing the levels of iNOS, CD11b and inflammatory factors. NEO stimulated tubule formation in bEnd.3 cells based on the hypoxic situation, which exerted its effect through activating the Vascular endothelial growth factor-Vascular Endothelial Growth Factor Receptor 2-Notch homolog 1(VFGF-VEGFR2-Notch1) signal. Furthermore, NEO suppressed cerebral ischemia in mice and lowered the ischemic penumbra. NEO also improved the neurological behaviors of mice, increased the CD34 levels and decreased the expression of inflammatory factors. NEO has well protective effect against cerebral ischemia, and its mechanisms are related to suppressing M1 polarization of microglial cells and promoting cerebral angiogenesis, which are the mechanisms of NEO in treating ischemic encephalopathy. [ABSTRACT FROM AUTHOR]

Purpose: The dysfunction of trophoblast during inflammation plays an important role in PE. Formyl peptide receptor 2 (FPR2) plays crucial roles in the development of inflammation-associated disease. This present study aimed to explore the effect of FPR2 on a trophoblast cellular model of preeclampsia. Methods: The expression of FPR2 in placenta was detected by immunohistochemical staining and western blotting. Transfection of siRNA was used to knockdown FPR2 in HTR-8/SVneo cells. Inflammatory cytokines were detected by ELISA. CCK8, Transwell, wound healing, FACS and tube formation assays were performed to observe the abilities of cell proliferation, migration, invasion, apoptosis and angiogenesis. Western blotting was implemented to clarify that NF-κB signaling pathway was downstream of FPR2. Results: The expression levels of FPR2 were higher in placental tissues of patients with PE. Knockdown of FPR2 expression by siFPR2 or inhibition of its activity by WRW4 decreased the release of proinflammatory cytokines in HTR8/SVneo cells treated with LPS. Knockdown of FPR2 expression or inhibition of its activity further reversed the LPS-induced attenuation of the proliferation, migration, invasion and angiogenesis and increase in apoptosis in HTR8/SVneo cells. Moreover, the NF-κB signaling pathway was activated in both placental tissues of patients with PE and LPS-treated HTR8/SVneo cells. However, the activation was attenuated when FPR2 was knocked down or inhibited. Conclusion: Suppression of FPR2 expression alleviated the effects of inflammation induced by LPS on trophoblasts via the NF-κB signaling pathway, which provided a novel and potential strategy for the treatment of PE. [ABSTRACT FROM AUTHOR]

Phytoplasmic SAP11 effectors alter host plant architecture and flowering time. However, the exact mechanisms have yet to be elucidated. Two SAP11‐like effectors, SJP1 and SJP2, from ‘Candidatus Phytoplasma ziziphi’ induce shoot branching proliferation. Here, the transcription factor ZjTCP7 was identified as a central target of these two effectors to regulate floral transition and shoot branching. Ectopic expression of ZjTCP7 resulted in enhanced bolting and earlier flowering than did the control. Interaction and expression assays demonstrated that ZjTCP7 interacted with the ZjFT‐ZjFD module, thereby enhancing the ability of these genes to directly bind to the ZjAP1 promoter. The effectors SJP1 and SJP2 unravelled the florigen activation complex by specifically destabilising ZjTCP7 and ZjFD to delay floral initiation. Moreover, the shoot branching of the ZjTCP7‐SRDX transgenic Arabidopsis lines were comparable to those of the SJP1/2 lines, suggesting the involvement of ZjTCP7 in the regulation of shoot branching. ZjTCP7 interacted with the branching repressor ZjBRC1 to enhance suppression of the auxin efflux carrier ZjPIN3 expression. ZjTCP7 also directly bound to and upregulated the auxin biosynthesis gene ZjYUCCA2, thereby promoting auxin accumulation. Our findings confirm that ZjTCP7 serves as a bifunctional regulator destabilised by the effectors SJP1 and SJP2 to modulate plant development. [ABSTRACT FROM AUTHOR]

Aim: We investigated the effects and target of gastrodin (GAS) for treating depression through network pharmacology combined with experimentation. Methods: The therapeutic target and signal of GAS for depression were analyzed by network pharmacology. Depression in mice was mimicked with a chronic unpredictable mouse stress (CUMS) model. Through open field, elevated plus maze, forced swimming, and tail suspension tests, the effects of GAS on the CUMS mice behaviors were examined, and the levels of neurotransmitters were detected. The histopathological changes were assayed by H&E and IHC staining, and the protein expressions were detected by Western blotting. Small molecule‐protein docking and molecular dynamics experiments were conducted to simulate the binding mode between GAS and Caspase‐3. Results: Network pharmacological analysis revealed that Caspase‐3 was the action target of GAS. GAS could improve depression‐like behaviors in CUMS mice, elevate their neurotransmitter levels, ameliorate their nerve cell injury, and inhibit their Caspase‐3 expression. After knocking out Caspase‐3, the effects of GAS were inhibited. Molecular dynamics simulation and small molecule‐protein docking found that GAS bound to Caspase‐3 at SER25, inhibiting the maturation and activation of Caspase‐3. Conclusion: We find that GAS can act as a Caspase‐3 inhibitor, which improves depression‐like behaviors and nerve cell injury in CUMS mice by inhibiting Caspase‐3‐mediated apoptosis. [ABSTRACT FROM AUTHOR]

• Salvianolic acid C improves cerebral ischemia reperfusion injury through suppressing microglial cell M1 polarization. • Salvianolic acid C improves cerebral ischemia reperfusion injury through promoting cerebral angiogenesis. • Salvianolic acid C inhibits microglia polarization through glucose metabolism signals. This study aimed to investigate the mechanism of salvianolic acid C (SAC), the active ingredient in Salvia miltiorrhiza , in improving cerebral ischemia injury. The mouse microglial cells BV2 and mouse endothelial cells bEnd.3 were used as the objects of study. LPS/IFN-γ was applied to simulate the BV2 polarization, and bEnd.3 cells were treated under hypoxic condition. The BV2 cell polarization level was measured through flow cytometry (FCM), the TLR4 and MyD88 expression levels were detected by fluorescence staining, whereas the expression of inflammatory factors TNF-α, IL-6 and IL-1β was analyzed through ELISA. Tubule formation assay was also conducted to observe the tubule formation ability of bEnd.3 cells in vitro, and the level of VEGFR2 was detected by fluorescence staining. Cells were treated with the PKM2 inhibitor IN3, aiming to observe the influence of SAC on glycolysis of BV2 cells. In addition, the mouse model of cerebral ischemia was constructed through the middle cerebral artery occlusion (MCAO) method, and the pathological changes in brain tissues were detected after SAC intervention. Meanwhile, the levels of IBA-1, CD31 and ZO-1 were determined through histochemical staining. Nissl staining to detect nerve cell damage. In BV2 cell experiment, SAC suppressed the M1 polarization of BV2 cells, reduced the inflammatory factor levels, and inhibited the activation of TLR4 signal through suppressing glycolysis. When PKM2 was suppressed, the effects of SAC were antagonized. In the bEnd.3 model, SAC promoted tubule formation in bEnd.3 cells under hypoxic condition, and increased the expression of VEGFR2 and Notch1. In the mouse model, SAC improved the neurological function in MCAO mice, and inhibited the activation of microglial cells and the expression of inflammatory factors. At the same time, SAC up-regulated the expression of ZO-1 and CD31, and maintained the blood-brain barrier (BBB) function. As a major component of Salvia miltiorrhiza , SAC can suppress microglial cell polarization and promote tubule formation in endothelial cells to exert the neurological repair function in cerebral ischemia. SAC is a multi-functional neuroprotective small molecule. [ABSTRACT FROM AUTHOR]

This paper takes the 2014 pilot project of accelerated depreciation of fixed assets as a quasi-natural experiment, and builds a Propensity Score Matching–Difference in Differences (PSM-DID) model based on the data of Chinese listed companies from 2000 to 2019 to test the impact of tax preference on enterprise investment efficiency and its mechanism. The results show that the policy inhibits supported enterprises investment efficiency significantly. Heterogeneity analysis shows that the policy causes greater investment efficiency losses for small and medium-sized enterprises, non-state-owned enterprises and asset-heavy enterprises. The mechanism test found the reason why the policy eased financing constraints but inhibited investment efficiency in short-term. After a variety of robustness tests, the above basic conclusions are still valid. Although the accelerated depreciation policy of fixed assets is conducive to expanding the scale of investment, the incentive effect on investment efficiency is not obvious, and even shows a restraining effect. Given the existence of heterogeneity, the design of the policy should not only distinguish industries, but also pay attention to the differences between different enterprises in the same industry. Strengthening research and development (R&D) innovation and improving the matching mechanism between human capital and fixed investment will help give full play to the incentive effect of this policy. The research in this paper helps to deepen the understanding of the microeconomic effects of tax policy and identify the internal mechanism, which not only enriches the relevant literature, but also provides a reference for the government to better use tax policy to promote the high-quality development of enterprises. [ABSTRACT FROM AUTHOR]

Background: Long noncoding RNAs (lncRNAs) OGFRP1 is up-regulated in endometrial cancer and cervical carcinoma, and OGFRP1 suppression inhibits the malignant behavior of cancer cells. Here, we evaluated the expression pattern, biological function and potential mechanism of OGFRP1 in non-small cell lung cancer (NSCLC). Methods: The expression of target genes in 25 pairs of clinically collected NSCLC and normal lung tissue samples was detected by qRT-PCR or western blot. We screened the siRNA (siOGFRP1) to down-regulate the expression of OGFRP1 in A549 and H1299 cells. The biological function of A549 and H1299 cells were examined by CCK8, wound healing and transwell assays. The molecular mechanism of OGFRP1 was further explored. Results: The expression of OGFRP1 in NSCLC tissues were higher than that in normal lung tissue. siOGFRP1 inhibited the proliferation, migration and invasion of A549 and H1299 cells. In addition, the expression of EMT-related and apoptosis-related proteins was changed by siOGFRP1 transfection. OGFRP1 can directly interact with miR-4640-5p, and siOGFRP1 increased the level of miR-4640-5p. Moreover, miR-4640-5p could directly bind to the 3' UTR region of eIF5A mRNA. eIF5A was highly expressed in NSCLC tissues, and predicted a poor prognosis. In addition, the expression of miR-4640-5p and eIF5A in NSCLC tissues were negatively correlated, while the expression of OGFRP1 and eIF5A were positively correlated. Knockdown of OGFRP1 inhibited the expression of eIF5A, while transfection of miR-4640-5p inhibitor up-regulated the expression of eIF5A. Conclusions: Taken together, we demonstrated that down-regulation of OGFRP1 inhibited the progression of NSCLC through miR-4640-5p/eIF5A axis. [ABSTRACT FROM AUTHOR]

Objective: This study was mainly conducted to explore the expression changes of GSDMD and conventional markers (including T‐Tau, Tau181p, and Aβ1–42) in the cerebrospinal fluid among patients with Alzheimer's disease (AD) and vascular dementia (VD), followed by determination of role of GSDMD in diagnosing and identifying AD and VD. Methods: In this study, 60 patients with VD, 60 patients with AD, and 50 healthy controls were enrolled. Lumbar puncture was performed to collect cerebrospinal fluid samples. Patients with VD and patients with AD were evaluated using the Mini‐Mental State Examination (MMSE) scale, Montreal Cognitive Assessment (MoCA) scale, Clinical Dementia Rating (CDR) scale, Activity of Daily Living (ADL) scale, and Neuropsychiatric Inventory (NPI) questionnaire, aiming to determine the behavioral ability of patients. ELISA kit was purchased to determine the levels of GSDMD, T‐Tau, Tau181p, and Aβ1–42 in cerebrospinal fluid, and the expression of inflammatory factors, IL‐1β and IL‐6, was also detected. Results: (1) The levels of GSDMD, T‐Tau, and Tau181p in the cerebrospinal fluid were higher in patients with AD than those of patients with VD and healthy controls, while the levels of Aβ1‐42 in the cerebrospinal fluid were lower in patients with AD than that in healthy controls and patients with VD. (2) GSDMD had good diagnostic accuracy in AD. Additionally, GSDMD, T‐Tau, Tau181p, and Aβ1‐42 had good discrimination accuracy in distinguishing AD and VD. (3) The expression levels of inflammatory factors (IL‐1β and IL‐6) in cerebrospinal fluid were higher in patients with AD than those of healthy controls and patients with VD, which were positively correlated with GSDMD expression. Conclusion: The expression of GSDMD was increased in patients with AD, which could be used as a biomarker for AD diagnosis and identification from VD. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's disease (PD) is a common degenerative disease of the central nervous system (CNS). The main pathological change is the apoptosis of dopaminergic neurons in the substantia nigra pars compacta (SNPc), thereby leading to dopamine reduction in nigral striatum. 6‐Hydroxydopamine (6‐OHDA), a neurotoxic substance, mediates apoptosis of dopaminergic neurons and causes Parkinson‐like symptoms in mice. Methods: Our team previously found that Antrodia camphorata polysaccharide (ACP) exerted a good behavioral improvement effect on the PD mouse model established by 6‐OHDA; however, the mechanism remains unknown. Therefore, in this study, we focused on ROS‐NLRP3 signal to investigate the mechanism of 6‐OHDA‐induced apoptosis of dopaminergic neurons MES23.5 and the protective effects of ACP on dopaminergic neurons. Result: 6‐OHDA could further activate the expression of inflammasome NLRP3 by inducing ROS, thereby resulting in apoptosis of MES23.5 cells. ACP could inhibit the expression of ROS‐NLRP3 induced by 6‐OHDA, exerting a protective role in MES23.5 cells. Animal experiments also confirmed that ACP intervention could reduce the activation level of ROS‐NLRP3 in the substantia nigra–striatum and improve the exercise capacity of PD mice. Conclusion: Our study validated that 6‐OHDA could induce apoptosis of dopaminergic neurons via ROS‐NLRP3 activation. ACP could inhibit this signal and protect dopaminergic neurons, which might be promising in research of PD therapeutics. [ABSTRACT FROM AUTHOR]

• Sal B treatment has neuroprotective and antiepileptic effects against a PTZ-induced seizure rat model. • The effects of Sal B may be attributed to inhibition of neuronal apoptosis. • Our findings provide a novel intervention strategy for human epilepsy. Neuronal apoptosis is a regulated intrinsic cell mechanism and common pathological phenomenon after seizures, which involves the protein kinase B/cAMP response element binding protein / brain derived neurotrophic factor (AKT/CREB/ BDNF) signaling pathway. In this study, we aimed to identify the effects of salvianolic acid B (Sal B), a major water-soluble component of the Chinese herb, Danshen, on rats in which seizures had been induced by pentylenetetrazole (PTZ) and the underlying molecular mechanisms mediating these effects. For this, 60 adult male Sprague-Dawley rats were divided into a control group, a 'PTZ' group and a 'PTZ + Sal B' group. The animals in the control group received an intraperitoneal (i.p.) injection of saline on alternate days for a total of 15 injections and saline orally once a day for 29 days. The animals in the 'PTZ' group received PTZ (40 mg/kg, i.p.) on alternate days for a total of 15 injections and saline orally once a day for 29 days. Similarly, the animals in the 'PTZ + Sal B' group received PTZ (40 mg/kg, i.p.) on alternate days and Sal B (20 mg/kg) orally once a day for 29 days. Neural density was then evaluated using immunofluorescence (IF) staining of microtubule-associated protein 2 (MAP2). Neuronal apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. In addition, the expression of several proteins related to AKT/CREB/BDNF signaling was measured using Western blotting. The results indicated that more severe seizures, decreased neural density, decreased expression of Bcl-2, increased expression of Bax and cleaved caspase-3, and inactivation of AKT/CREB/BDNF signaling occurred in the 'PTZ' group in comparison with the control group. However, those changes were suppressed by Sal B. Thus, these data suggest that Sal B has anticonvulsant and anti-apoptotic effects in a PTZ-induced seizure model through activation of the AKT/CREB/BDNF signaling pathways. [ABSTRACT FROM AUTHOR]

• Antcin K has a therapeutic effect on depression in mice and can improve the behavior of depression. • Antcin K mainly improves neuroinflammation, thereby improving the behavior of depression. • NLRP3 is the target of Antcin K, and A regulates depression-related neuroinflammation by inhibiting NLRP3. We aimed to explored the role of Antcin K in resisting depression and its targets. LPS/IFN-γwas used to induce the activation of microglial BV2 cells. Following Antcin K pretreatment, the proportion of M1 cells was determined using flow cytometry (FCM), the expression of cytokines was measured through ELISA, and that of CDb and NLRP3 was analyzed by cell fluorescence staining. The protein levels were detected by Western-blot assay. After NLRP3 was knocked down in BV2 cells (BV2- nlrp3-/-), the M1 polarization level was detected with Antcin K treatment. The targeted binding relation of Antcin K with NLRP3 was confirmed through small molecule-protein docking and co-immunoprecipitation assay. The chronic unpredictable stress model (CUMS) was constructed to mimic the depression mice. After the administration of Antcin K, the neurological behavior of CUMS mice were detected by open-field test (OFT), elevated plus maze, forced swimming test (FST), and tail suspension test (TST). In addition, the expression of CD11b and IBA-1 was detected through histochemical staining, and the tissue pathological changes were detected by H&E staining. Antcin K suppressed the M1 polarization of BV2 cells and reduced the expression of inflammatory factors. Meanwhile, NLRP3 exhibited targeted binding relation with Antcin K, and Antcin K lost its effect after NLRP3 knockdown. In the CUMS mouse model, Antcin K improved the depression status and neurological behaviors in mice, and decreased central neuroinflammation and microglial cell polarization. Antcin K targets NLRP3 to suppress microglial cell polarization, alleviate central inflammation in mice and improve their neurological behaviors. [ABSTRACT FROM AUTHOR]

• Ori suppressed ROS production and regulated the M1 polarization of KCs, thus protecting the liver in NAFLD. • Regulating the M2 polarization of KCs can inhibit NAFLD inflammation and promote liver recovery. • ROS is an important signal that regulates the M2 polarization of KCs cells. Oridonin (Ori) is a kind of diterpenoid small molecule, but its role in nonalcoholic fatty liver disease (NAFLD) has not been reported yet. This study aimed to explore the pharmacological function of Ori in liver protection through the reactive oxygen species (ROS)-mediated polarization of Kupffer cells (KCs). In the present work, KCs were adopted for study in vitro. To be specific, LPS and IFN-γ were utilized to induce M1 polarization, then the influence of Ori intervention on the expression of inflammatory factors IL-1β, IL-6 and TNF-α was detected by enzyme-linked immunosorbent assay (ELISA), that of CD86 and P 65 was measured through fluorescence staining, that of p- P 65 and p-P50 was detected by Western blotting (WB) assay, and ROS expression was measured by using the DCFH-DA probe. The C57BL/6J mice were fed with the high fat diet (HFD) to construct the NAFLD model, and intervened with Ori. The blood glucose (BG), body weight (BW), food intake and water intake of mice were monitored; meanwhile, glucose and insulin tolerance tests were conducted. The liver tissues of mice were subjected to H&E staining and oil red O staining. Moreover, the serum ALT, AST and TG levels in mice were monitored, the CD86 and CD206 levels were measured through histochemical staining, the expression of inflammatory factors was detected by ELISA, and the p- P 65 and p-P50 protein levels were detected by WB assay. Ori suppressed the M1 polarization of KCs, reduced the levels of inflammatory factors, and decreased the expression of ROS, p- P 65 and p-P50. In animal experiments, Ori improved lipid deposition and liver injury in the liver tissues of NAFLD mice, increased the proportion of M2 cells (up-regulated CD206 expression), reduced that of M1 cells (down-regulated CD86 expression), and decreased the serum ALT, AST and TG levels. This study discovered that Ori suppressed ROS production and regulated the M1 polarization of KCs, thus protecting the liver in NAFLD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a central degenerative disease characterized by cognitive impairment. Polymerization of β-amyloid has been reported to cause the entanglement of nerve cells, leading to the progressive loss of nerve cells. Accumulative studies have confirmed the important roles of neuroinflammation in the development of AD. In this study, the gut microbiota from AD patients were transplanted into APP/PS1 double transgenic mice. As a result, the expression of NLRP3 was increased in the intestinal tract of mice, and the expression levels of inflammatory factors in peripheral blood were also increased. Consistently, the cognitive impairment was more severe in mice receiving gut microbiota from AD patients than those did not, with activation of microglia in the central hippocampus of mice, and increased expression of neuroinflammatory factors. In APP/PS1 mice transplanted with gut microbiota from AD patients, transplantation of healthy human gut microbiota or oral administration of minocycline was further used to improve the composition of gut microbiota. Consequently, the intestinal expression of NLRP3 was down-regulated, the cognitive ability of mice was improved, the activation of microglia in central hippocampus was suppressed and the expression of neuroinflammatory factors was also down-regulated. After transplantation of gut microbiota from AD patients in C57BL/6 mice, the intestinal expression of NLRP3 was up-regulated. Although the cognitive ability of mice was not significantly changed, the microglia in the hippocampus of mice were still activated and the expression of inflammatory factors was up-regulated. In this study, we found that gut microbiota in AD patients could induce the activation of NLRP3 inflammasome in the intestinal tract of mice, subsequently causing the release of inflammatory factors. The absorption and circulation of inflammatory factors through the intestinal tract could further aggravate the inflammation in the nervous tissues and the activation of microglia. Therefore, improving the composition of gut microbiota in AD patients can further attenuate neuroinflammation, which is considered as a novel idea for AD treatment. • GM in AD patients can promote intestinal inflammatory response by activating intestinal NLRP3 inflammasome. • After reaching the brain tissue through circulation, inflammatory factors can promote microglia activation and inflammatory response in hippocampus, further aggravating the pathological progression of AD, leading to declined cognitive and behavioral abilities. • Improving intestinal bacteria can inhibit the central inflammation caused by NLRP3. [ABSTRACT FROM AUTHOR]