Search

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease and clinically manifests with cognitive decline and behavioral disabilities. Over the past years, mounting studies have demonstrated that the inflammatory response plays a key role in the onset and development of AD, and neuroinflammation has been proposed as the third major pathological driving factor of AD, ranking after the two well-known core pathologies, amyloid β (Aβ) deposits and neurofibrillary tangles (NFTs). Epigenetic mechanisms, referring to heritable changes in gene expression independent of DNA sequence alterations, are crucial regulators of neuroinflammation which have emerged as potential therapeutic targets for AD. Upon regulation of transcriptional repression or activation, epigenetic modification profiles are closely involved in inflammatory gene expression and signaling pathways of neuronal differentiation and cognitive function in central nervous system disorders. In this review, we summarize the current knowledge about epigenetic control mechanisms with a focus on DNA and histone modifications involved in the regulation of inflammatory genes and signaling pathways in AD, and the inhibitors under clinical assessment are also discussed. [ABSTRACT FROM AUTHOR]

This article considers the problem of adaptive prescribed performance tracking control via slow switching for a general class of uncertain switched nonlinear systems (SNSs) with unmodeled dynamics (UDs) and nonstrict-feedback structure. The UDs are not in their form of the input-to-state practical stability and their state information is unmeasurable. By reassigning the function variables, the coupling effects between UDs and the prescribed performance function are eliminated through the iterative process. In virtue of the neural networks (NNs) approximation capability, a novel adaptive backstepping procedure is proposed without adding extra first-order filters. By choosing an appropriate slow switching law, all the signals of the closed-loop system are bounded, and the system output tracks the reference signal with a prescribed performance level (PPL). [ABSTRACT FROM AUTHOR]

[Display omitted] • Inactivation of MAPK/mTOR pathway inhibited CCl 4 induced autophagy in liver. • Harmine suppressed inflammation induced by CCl 4 via TLR4/NF-κB pathway in mice. • Harmine relieved CCl 4 induced ALI by inhibiting autophagy and inflammation in mice. CCl 4 -induced acute liver injury (ALI) is characterized by heightened autophagy, inflammation, and oxidative damage. Accumulating evidence suggests that harmine exerts beneficial effects in countering CCl 4 -induced ALI by mitigating inflammation and oxidative stress. However, the impact of autophagy on CCl 4 -induced ALI and the protective role of harmine remain unclear. This study aimed to investigate the potential protective effects of harmine against CCl 4 -induced ALI in mice by suppressing autophagy and inflammation. Male Kunming mice were orally administered harmine or bifendate for seven days. Subsequently, one hour after the final administration, the model group and treatment groups were intraperitoneally injected with CCl 4 to induce ALI. The findings revealed that harmine significantly reduced the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, and ameliorated the liver histopathological changes induced by CCl 4. Furthermore, harmine diminished the levels of TNF-α and IL-6, restored the levels of glutathione (GSH) and superoxide dismutase (SOD), and suppressed the production of nitric oxide (NO) and malondialdehyde (MDA) in the liver. Mechanistically, harmine down-regulated LC3B II/I, p38 MAPK, TLR4, and NF-κB levels, while upregulating p62, Bcl-2, Beclin1, ULK1, and p-mTOR expression. In conclusion, harmine mitigated CCl 4 -induced ALI by inhibiting autophagy and inflammation through the p38 MAPK/mTOR autophagy pathway, the Bcl-2/Beclin1 pathway, and the TLR4/NF-κB pathway. [ABSTRACT FROM AUTHOR]

• Systemic administration of RSV dose-dependently inhibits CFA-induced TMJ inflammation. • RSV treatment recovers disturbed gut microbiota caused by intra-TMJ injection of CFA. • Gut microbiome perturbation is critical for development of TMJ inflammatory pain. Patients with temporomandibular disorders (TMDs) often experience persistent facial pain. However, the treatment of TMD pain is still inadequate. In recent years, the disturbance of gut microbiota has been shown to play an important role in the pathogenesis of different neurological diseases including chronic pain. In the present study, we investigated the involvement of gut microbiota in the development of temporomandibular joint (TMJ) inflammation. Intra-temporomandibular joint injection of complete Freund's adjuvant (CFA) was employed to induce TMJ inflammation. Resveratrol (RSV), a natural bioactive compound with anti-inflammatory property, was used to treat the CFA-induced TMJ inflammation. We observed that CFA injection not only induces persistent joint pain, but also causes the reduction of short-chain fatty acids (SCFAs, including acetic acid, propionic acid and butyric acid) in the gut as well as decreases relevant gut bacteria Bacteroidetes and Lachnospiraceae. Interestingly, systemic administration of RSV (i.p.) dose-dependently inhibits CFA-induced TMJ inflammation, reverses CFA-caused reduction of SCFAs and these gut bacteria. Moreover, CFA injection causes blood–brain barrier (BBB) leakage, activates microglia and enhances tumor necrosis factor alpha (TNFα) release in the spinal trigeminal nucleus caudalis (Sp5C). The RSV treatment restores the BBB integrity, inhibits microglial activation and decreases the release of TNFα in the Sp5C. Furthermore, fecal microbiota transplantation with feces from RSV-treated mice significantly diminishes the CFA-induced TMJ inflammation. Taken together, our results suggest that gut microbiome perturbation is critical for the development of TMJ inflammation and that recovering gut microbiome to normal levels could be a new therapeutic approach for treating such pain. [ABSTRACT FROM AUTHOR]

Summary: This article presents a distributed adaptive integral‐type event‐triggered scheme (ETS) and an agent‐dependent switching strategy with dwell time to solve the cooperative output regulation problem for switched multiagent systems. First, by constructing an adaptive law to dynamically update the time‐varying coupling weights for all the communication links, a fully distributed ETS is designed, where only the local information of the topology is adopted. Based on the integral‐type triggering condition, the interevent interval is substantially enlarged and Zeno behavior is explicitly ruled out. Second, each agent permits all the subsystems to be unstabilizable. The switching signal for each agent is different, and any adjacent switches of each agent satisfy the preset dwell time. Under the designed switching strategy, the solvability of the regulation problem is guaranteed. Finally, the effectiveness of the designed ETS and switching strategy is substantiated by an example. [ABSTRACT FROM AUTHOR]

Abstract This paper studies the problem of the cooperative output regulation for a class of nonlinear multi-agent systems described by T-S fuzzy models subject to the jointly connected switching topology. The considered switching topology permits the topology to be disconnected at any time interval which is weaker than the connected topology assumption. By using the parallel distributed compensation, the fuzzy internal reference model for each agent is constructed to estimate the exogenous signal, based on which, the distributed dynamic fuzzy output feedback controller is designed. The constructed fuzzy internal reference model is a switched nonlinear system where each subsystem may be unstable. An efficient condition is presented to ensure the solvability of the cooperative output regulation. An example of coupled pendula illustrates the validity of the result. [ABSTRACT FROM AUTHOR]

In this study, a novel distributed event‐triggered scheme (ETS) using only triggered information is presented to solve the problem of the leader‐following consensus for a class of multi‐agent systems with general linear dynamics under fixed and switching topologies. First, the novel triggering conditions are proposed for fixed topology by virtue of discrete communications between neighbouring agents at the triggering times, which eliminates continuous inter‐agent communication and reduces the frequency of controller update simultaneously. Second, for switching topology including both graphs that have directed spanning tree and graphs that do not, the authors propose the topology‐dependent distributed ETS to guarantee consensus by an average dwell time approach. Noteworthily, Zeno behaviour of triggering time sequences is excluded under fixed and switching topologies. Examples validate the effectiveness and show the advantage of the proposed ETS by comparison. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to capture and explore family caregivers' lived experience of caring for hospitalised patients with cancer during the lockdown. Background: The unprecedented lockdown episodes due to COVID‐19 have brought significant changes in the hospital visiting policies and caregiving practices. As part of the precautionary measures for hospital visits, the bedside companion was restricted to one caregiver for patients with cancer in Shanghai hospitals. Design: This study adopted a descriptive phenomenological approach. Methods: Data were collected among 20 family caregivers recruited from the Oncology department of a tertiary hospital in Shanghai in May 2022, using purposive sampling method and followed by unstructured, open‐ended interviews. Colaizzi's seven‐step data analysis method was used to analyse the data to reveal the emergent themes and subthemes of the phenomenon. Results: Four themes were generated on family caregivers' lived experience of caring for hospitalised patients with cancer during the lockdown, including (1) Feeling scared for the patient; (2) Living a life feeling trapped under COVID‐19 surveillance; (3) Feeling neglected and unseen; (4) Growing resilience and appreciation. Conclusions: The lockdown exacerbated the burden of family caregivers when they cared for the hospitalised patients with cancer during the lockdown period. However, positive reframing of the lived experience facilitated their coping with the challenging situation. Relevance to Clinical Practice: Findings from this study highlighted the potential proactive roles the healthcare providers could play in improving family caregivers' health and supporting them during and beyond the COVID‐19 pandemic. Reporting Method: The study adhered to relevant EQUATOR guidelines; the study was reported according to the COREQ checklist. Patient or Public Contribution: Family caregivers of patients with cancer were involved in data collection and member‐checking of the transcripts and interpretations of their experiences. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionSystemic inflammatory response syndrome (SIRS) is an uncontrolled systemic inflammatory response. Proanthocyanidins (PC) is a general term of polyphenol compounds widely existed in blueberry fruits and can treat inflammation-related diseases. This study aimed to explore the regulatory effect of PC on lipopolysaccharide (LPS)-induced systemic inflammation and its potential mechanism, providing effective strategies for the further development of PC.Here, RAW264.7 macrophages were stimulated with LPS to establish an inflammation model in vitro, while endotoxin shock mouse models were constructed by LPS in vivo. The function of PC was investigated by MTT, ELISA kits, H&E staining, immunohistochemistry, and Western blot analysis.Functionally, PC could demonstrate the potential to mitigate mortality in mice with endotoxin shock, as well as attenuated the levels of inflammatory cytokines (IL-6, TNF-α) and biochemical indicators (AST, ALT, CRE and BUN). Moreover, it had a significant protective effect on lung and kidney tissues damage. Mechanistically, PC exerted anti-inflammatory effects by inhibiting the activation of the NF-κB/NLRP3 signaling pathway.PC might have the potential ability of anti-inflammatory effects via modulation of the NF-κB/NLRP3 signaling pathway. [ABSTRACT FROM AUTHOR]

The changes of local field potentials (LFP, mainly gamma rhythm and theta rhythm) in the brain are closely related to learning and memory formation. Reduced gamma rhythm (20–50 Hz) and theta rhythm (4–10 Hz) has been observed in the progression of Alzheimer's disease (AD), but it is not clear whether it is related to cognition in AD. Here, we investigated behaviorally driven gamma rhythm and theta rhythm in APP/PS1 mice, and optogenetically stimulated GABAergic neurons in the brain to better understand the relationship between the changes of LFP, cognition, and cellular pathologies. Optogenetically driving GABAergic neurons rescued memory formation in a water maze task and normalized theta and gamma rhythm in the EEG. Furthermore, the optogenetic stimulation alleviated neuroinflammation and levels of amyloid-β (Aβ)1–42 fragments, and induced autophagy. GABA blockers also reversed the normalization of theta and gamma rhythms in the brain by optogenetic stimulation. The results demonstrate that stimulation of GABAergic interneurons not only rescues LFP rhythms and memory formation, but furthermore activates autophagy and reduces neuroinflammation, which have beneficial additional effects such as clearing amyloid. This is a proof of concept for a novel therapeutic approach to AD treatment. • Activating GABAergic interneurons in the hippocampus has therapeutic effects. • The memory impairment in these mice is reversed. • EEG Theta and Gamma is normalized. • And β-amyloid levels are reduced via autophagy. [ABSTRACT FROM AUTHOR]

Objective: This study aims to explore the role of connexin 43 (Cx43) in the autophagy of RAW264.7 cell induced by oxidized low-density lipoprotein (ox-LDL). Methods. The ox-LDL (100 μg/mL. 24 h) was used to establish the model of autophagy and foam cell formation. RAW264.7 mouse mononuclear macrophage lines were randomly divided into control group. ox-LDL group. ox-LDL+Gap26 group and ox-LDL+Gap19 group. The mRNA levels of Cx43. autophagy protein Beclin-1 and LC3B were detected by qRT-PCR. The protein levels of Cx43. Beclin-1 and LC3B were detected by Western blot. The expression and localization of Cx43. Beclin-1 and LC3B were detected by cellular immunofluorescence. Results.The results of oil red O staining showed that red lipid droplets appeared in the cell plasma of the ox-LDL group and cells were foamy 24 h after ox-LDL intervention in RAW264.7 cells. By Western blot. qRT-PCR and immunofluorescence 24 h after ox-LDL intervention in RAW264.7 cells. the expression level of Cx43 in the cells of the ox-LDL group was increased. the expression levels of Beclin-1. LC3B mRNA and protein were decreased in the cells of the ox-LDL group compared with the control group. the expression levels of Beclin-1 and LC3B were decreased in the ox-LDL+Gap26 group compared with the ox-LDL group. and the expression levels of autophagy-related proteins in the ox LDL+Gap19 group were increased compared with the ox-LDL group. Conclusion.Cx43 blocking can significantly promote RAW264.7 autophagy induced by ox-LDL. [ABSTRACT FROM AUTHOR]

Bletilla striata , a traditional medicinal plant, has been utilized as a folk medicine for many years because of its superior biological activity in China. However, Bletilla striata polysaccharide (BSP) has received less attention, and its specific mechanism for ameliorating pulmonary fibrosis is completely unclear. In this study, we aim to assess BSP on the treatment of PF and explore potential mechanisms. BSP was successfully extracted and purified from Bletilla striata. The mechanisms were assessed in bleomycin-induced pulmonary fibrosis model and lung fibroblasts activated by transforming growth factor-β1 (TGF-β1). Histological analysis, immunofluorescence, Western blot and flow cytometry were used to explore the alterations after BSP intervention. The results in vivo showed an anti-PF effect of BSP treatment, which reduced pathogenic damages. Furthermore, TGF-β1-induced abnormal migration and upregulated expression of collagen I (COL1A1), vimentin and α-smooth muscle actin (α-SMA) were suppressed by BSP in L929 cells. Moreover, the abnormal proliferation was retarded by inhibiting the cell cycle of G1 to S phase. Immunofluorescence assay showed that BSP activated autophagy and played an antifibrotic role by inhibiting the expression of p62 and phospho-mammalian target of rapamycin (p-mTOR). Last but not least, the suppression of TGF-β1/Smad signaling pathway was critical for BSP to perform therapeutic effects in vitro and in vivo. The possible mechanisms were involved in improving ECM deposition, regulating cell migration and proliferation, and promoting cellular autophagy. Briefly, all of the above revealed that BSP might be a novel therapy for treating pulmonary fibrosis. [Display omitted] • BSP treatment reduced pulmonary fibrosis in BLM-induced mice. • BSP inhibited proliferation and migration in TGF-β1-induced L929. • BSP activated autophagy in TGF-β1-induced L929. • BSP attenuated pulmonary fibrosis via the TGF-β1/Smad signaling pathway. • The present study demonstrated a new application of BSP in anti-pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Severe acute pancreatitis (SAP) is an inflammatory disease of the pancreas with a high mortality rate. Macrophages play a crucial role in the pathogenesis of pancreatitis. Tectoridin (Tec) is a highly active isoflavone with anti-inflammatory pharmacological activity. However, the role of Tec in the SAP process is not known. The purpose of this study was to investigate the therapeutic effect and potential mechanism of Tec on SAP. To establish SAP mice by intraperitoneal injection of caerulein and Lipopolysaccharide (LPS), the role of Tec in the course of SAP was investigated based on histopathology, biochemical indicators of amylase and lipase and inflammatory factors. The relationship between Tec and macrophage polarization was verified by immunofluorescence, real-time quantitative PCR and Western blot analysis. We then further predicted the possible targets and signal pathways of action of Tec by network pharmacology and molecular docking, and validated them by in vivo and in vitro. In this study, we demonstrated that Tec significantly reduced pancreatic injury in SAP mice, and decreased serum levels of amylase and lipase. The immunofluorescence and Western blot analysis showed that Tec promoted macrophage M2 polarization. Network pharmacology and molecular docking predicted that Tec may target ERK2 for the treatment of SAP, and in vivo and in vitro experiments proved that Tec inhibited the ERK MAPK signal pathway. In summary, Tec can target ERK2, promote macrophage M2 polarization and attenuate pancreatic injury, Tec may be a potential drug for the treatment of SAP. [Display omitted] • Tectoridin ameliorated pancreatic injury and inflammation in SAP mice. • Tectoridin regulated macrophage polarization and promoted M2 macrophage polarization. • Tectoridin targeted ERK2 to inhibit ERK MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Endophytic diazotrophic Serratia sp. Wed4 with high nitrogenase activity (1260.9 ± 8.3 nmol C 2 H 4 mL−1h−1) was isolated from G lycine max Linn growing in PAH contaminated soil for improving PAH removal and crop growth. Strain Wed4 biodegraded 37.0% of pyrene within 14 d via phthalate pathway in vitro and could biodegraded other PAHs with 2–5 rings effectively. Its capabilities on promoting crop growth included indole acetic acid (IAA) production (30.8 ± 3.3 μg mL−1), iron carrier production (A/Ar = 0.841 ± 0.002), inorganic phosphate dissolution (D/d = 1.184 ± 0.032) and organic phosphate dissolution (D/d = 1.154 ± 0.025). Strain Wed4 successfully colonized in barley tissues (>104 CFU g−1 FW), significantly promoted barley growth and nitrogen nutrition, reduced pyrene residues especially in shoots. Under sufficient nitrogen condition, strain Wed4 significantly promoted the dry weight of barley by 18.9%–33.9%, and decreased the pyrene residues by 46.4% in shoots and by 32.1% in roots. Meanwhile, under the deficient nitrogen condition, strain Wed4 significantly promoted the dry weight of barley by 40.1%–63.3% and decreased the pyrene residues by 39.0% in shoots and by 28.0% in roots. The pyrene contents were significantly negatively correlated with the total nitrogen contents in barley tissues, suggesting that nitrogen fixation of strain Wed4 also stimulated the pyrene removal. Based on its performance, Serratia sp. Wed4 provided a great potential to increasing crop yield and reducing PAH pollution in nitrogen deficient soils. [Display omitted] • Serratia sp. Wed4 simultaneously removed PAHs and enhanced nitrogen fixation. • Serratia sp. Wed4 successfully survived and multiplied in barley. • Pyrene accumulation in barley was significantly decreased after Wed4 inoculated. • Nitrogen fixation would improve the biodegradation of PAHs by Wed4. [ABSTRACT FROM AUTHOR]