ObjectiveNeuroinflammation plays a crucial role in both the onset and progression of ischemic stroke, exerting a significant impact on the recovery of the central nervous system. Excessive neuroinflammation can lead to secondary neuronal damage, further exacerbating brain injury and impairing functional recovery. As a result, effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients. Among various approaches, targeting immune regulation to control inflammation has gained increasing attention. This study aims to investigate the role of in vitro induced regulatory T cells (Treg cells) in suppressing neuroinflammation after ischemic stroke, as well as their potential therapeutic effects. By exploring the mechanisms through which Tregs exert their immunomodulatory functions, this research is expected to provide new insights into stroke treatment strategies. MethodsNaive CD4⁺ T cells were isolated from mouse spleens using a negative selection method to ensure high purity, and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines. The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated. In the middle cerebral artery occlusion (MCAO) model, after Treg cells transplantation, their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined. To further investigate the role of Treg cells in stroke recovery, the changes in cytokine expression and their effects on immune cell interactions was analyzed. Additionally, infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells. By integrating multiple indicators, the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed. ResultsTreg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cytokines in vitro and in vivo, effectively balancing the immune response and suppressing excessive inflammation. Additionally, Treg cells inhibited the activation and activity of inflammatory cells, thereby reducing neuroinflammation. In the MCAO mouse model, Treg cells were observed to accumulate in the infarcted brain region, where they significantly reduced the infarct size, demonstrating their neuroprotective effects. Furthermore, Treg cell therapy notably improved behavioral scores, suggesting its role in promoting functional recovery, and increased the survival rate of ischemic stroke mice, highlighting its potential as a promising therapeutic strategy for stroke treatment. ConclusionIn vitro induced Treg cells can effectively suppress neuroinflammation caused by ischemic stroke, demonstrating promising clinical application potential. By regulating the balance between pro-inflammatory and anti-inflammatory cytokines, Treg cells can inhibit immune responses in the nervous system, thereby reducing neuronal damage. Additionally, they can modulate the immune microenvironment, suppress the activation of inflammatory cells, and promote tissue repair. The therapeutic effects of Treg cells also include enhancing post-stroke recovery, improving behavioral outcomes, and increasing the survival rate of ischemic stroke mice. With their ability to suppress neuroinflammation, Treg cell therapy provides a novel and effective strategy for the treatment of ischemic stroke, offering broad application prospects in clinical immunotherapy and regenerative medicine.

ObjectiveTo explore the effect of timosaponin BⅡ （TBⅡ） combined with icariin （ICA） on osteoclast （OC）-osteoblast （OB） coupling and decipher the mechanism from the cellular level. MethodsThe cell counting kit-8 （CCK-8） was used to assess the effects of different concentrations of TBⅡ and different concentrations of TBⅡ+ICA on the growth of RAW264.7 cells. Soluble receptor activator of nuclear factor-κB ligand （sRANKL） was used to induce the differentiation of RAW264.7 pre-osteoclasts into osteoclasts. The cells were allocated into sRANKL， TBⅡ （1， 5， 10 μmol·L^-1）， and TBⅡ+ICA groups. Tartrate-resistant acid phosphatase staining was performed to assess the effects of TBⅡ and TBⅡ+ICA on osteoclast differentiation. Real-time quantitative polymerase chain reaction （Real-time PCR） was conducted to examine the effects of TBⅡ+ICA on the expression of key genes involved in osteoclast differentiation and osteoclast-derived coupling factors. The osteogenic differentiation conditioned medium mixed with osteoclast supernatant was used to induce osteogenic differentiation of MC3T3-E1 cells. Alkaline phosphatase staining and alizarin red S staining were employed to determine the effect of TBⅡ+ICA on osteogenic differentiation. Real-time PCR was employed to evaluate the effects of conditioned medium on key genes involved in osteogenic differentiation. ResultsTBⅡ at 1， 5， 10 μmol·L^-1 had no significant effect on the cell survival rate. Compared with the sRANKL group， TBⅡ inhibited osteoclast differentiation in a dose-dependent manner and achieved the best effect at 10 μmol·L^-1 （P<0.01）. Compared with the sRANKL group， different concentrations of TBⅡ down-regulated the mRNA levels of osteoclast differentiation-related genes c-Fos， RANK， and RANKL （P<0.05）. None of 10 μmol·L^-1 TBⅡ， 10 μmol·L^-1 TBⅡ+10^-4 μmol·L^-1 ICA， or 10 μmol·L^-1 TBⅡ+10^-3 μmol·L^-1 ICA affected the viability of RAW264.7 cells. TBⅡ and/or ICA inhibited osteoclast differentiation （P<0.01）， and TBⅡ + ICA had the best effect （P<0.01）. Compared with the sRANKL group， TBⅡ and/or ICA down-regulated the mRNA levels of c-Fos， RANK， and RANKL （P<0.05）. The single application of TBⅡ and ICA had no significant effect on the mRNA levels of Wnt10b， Cthrc1， and C3a， while TBⅡ+ICA exerted up-regulating effects （P<0.05）. Compared with those in the blank group， the bone differentiation and mineralization abilities of the normal osteogenic induction group and each osteogenic induction + osteoclast supernatant group were improved （P<0.01）. Compared with the blank group， the normal osteogenic induction group and the osteogenic induction + osteoclast supernatant group showed up-regulated mRNA levels of Runx2 and OCN （P<0.01）. ConclusionTBⅡ+ICA can inhibit osteoclast differentiation， maintain the normal osteoclast-osteoblast coupling， and promote osteogenic differentiation.

Sleep deprivation (SD) has emerged as a significant modifiable risk factor for Alzheimer’s disease (AD), with mounting evidence demonstrating its multifaceted role in accelerating AD pathogenesis through diverse molecular, cellular, and systemic mechanisms. SD is refined within the broader spectrum of sleep-wake and circadian disruption, emphasizing that both acute total sleep loss and chronic sleep restriction destabilize the homeostatic and circadian processes governing glymphatic clearance of neurotoxic proteins. During normal sleep, concentrations of interstitial Aβ and tau fall as cerebrospinal fluid oscillations flush extracellular waste; SD abolishes this rhythm, causing overnight rises in soluble Aβ and tau species in rodent hippocampus and human CSF. Orexinergic neurons sustain arousal, and become hyperactive under SD, further delaying sleep onset and amplifying Aβ production. At the molecular level, SD disrupts Aβ homeostasis through multiple converging pathways, including enhanced production via beta-site APP cleaving enzyme 1 (BACE1) upregulation, coupled with impaired clearance mechanisms involving the glymphatic system dysfunction and reduced Aβ-degrading enzymes (neprilysin and insulin-degrading enzyme). Cellular and histological analyses revealed that these proteinopathies are significantly exacerbated by SD-induced neuroinflammatory cascades characterized by microglial overactivation, astrocyte reactivity, and sustained elevation of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) through NF‑κB signaling and NLRP3 inflammasome activation, creating a self-perpetuating cycle of neurotoxicity. The synaptic and neuronal consequences of chronic SD are particularly profound and potentially irreversible, featuring reduced expression of critical synaptic markers (PSD95, synaptophysin), impaired long-term potentiation (LTP), dendritic spine loss, and diminished neurotrophic support, especially brain-derived neurotrophic factor (BDNF) depletion, which collectively contribute to progressive cognitive decline and memory deficits. Mechanistic investigations identify three core pathways through which SD exerts its neurodegenerative effects: circadian rhythm disruption via BMAL1 suppression, orexin system hyperactivity leading to sustained wakefulness and metabolic stress, and oxidative stress accumulation through mitochondrial dysfunction and reactive oxygen species overproduction. The review critically evaluates promising therapeutic interventions including pharmacological approaches (melatonin, dual orexin receptor antagonists), metabolic strategies (ketogenic diets, and Mediterranean diets rich in omega-3 fatty acids), lifestyle modifications (targeted exercise regimens, cognitive behavioral therapy for insomnia), and emerging technologies (non-invasive photobiomodulation, transcranial magnetic stimulation). Current research limitations include insufficient understanding of dose-response relationships between SD duration/intensity and AD pathology progression, lack of long-term longitudinal clinical data in genetically vulnerable populations (particularly APOE ε4 carriers and those with familial AD mutations), the absence of standardized SD protocols across experimental models that accurately mimic human chronic sleep restriction patterns, and limited investigation of sex differences in SD-induced AD risk. The accumulated evidence underscores the importance of addressing sleep disturbances as part of multimodal AD prevention strategies and highlights the urgent need for clinical trials evaluating sleep-focused interventions in at-risk populations. The review proposes future directions focused on translating mechanistic insights into precision medicine approaches, emphasizing the need for biomarkers to identify SD-vulnerable individuals, chronotherapeutic strategies aligned with circadian biology, and multi-omics integration across sleep, proteostasis and immune profiles may delineate precision-medicine strategies for at-risk populations. By systematically examining these critical connections, this analysis positions sleep quality optimization as a viable strategy for AD prevention and early intervention while providing a comprehensive roadmap for future mechanistic and interventional research in this rapidly evolving field.

Aim To investigate the therapeutic effect of the MW-9 on ulcerative colitis(UC)and reveal the underlying mechanism, so as to provide a scientific guidance for the MW-9 treatment of UC. Methods The model of lipopolysaccharide(LPS)-stimulated RAW264.7 macrophage cells was established. The effect of MW-9 on RAW264.7 cells viability was detected by MTT assay. The levels of nitric oxide(NO)in RAW264.7 macrophages were measured by Griess assay. Cell supernatants and serum levels of inflammatory cytokines containing IL-6, TNF-α and IL-1β were determined by ELISA kits. Dextran sulfate sodium(DSS)-induced UC model in mice was established and body weight of mice in each group was measured. The histopathological damage degree of colonic tissue was assessed by HE staining. The protein expression of p-p38, p-ERK1/2 and p-JNK was detected by Western blot. Results MW-9 intervention significantly inhibited NO release in RAW264.7 macrophages with IC50 of 20.47 mg·L-1 and decreased the overproduction of inflammatory factors IL-6, IL-1β and TNF-α(P<0.05). MW-9 had no cytotoxicity at the concentrations below 6 mg·L-1. After MW-9 treatment, mouse body weight was gradually reduced, and the serum IL-6, IL-1β and TNF-α levels were significantly down-regulated. Compared with the model group, MW-9 significantly decreased the expression of p-p38 and p-ERK1/2 protein. Conclusions MW-9 has significant anti-inflammatory activities both in vitro and in vivo, and its underlying mechanism for the treatment of UC may be associated with the inhibition of MAPK signaling pathway.

ObjectiveThis study aims to explore the potential mechanism of Danggui Niantongtang in treating knee osteoarthritis （KOA） by regulating the intestinal flora through 16S rDNA analysis. MethodThirty-six C57BL/6J mice were subjected to anterior cruciate ligament transection （ACLT） to establish a KOA model and were randomly divided into the sham surgery group， model group， low-dose Danggui Niantongtang group （0.819 g·kg^-1）， medium-dose Danggui Niantongtang group （1.638 g·kg^-1）， high-dose Danggui Niantongtang group （3.276 g·kg^-1）， and Meloxicam group （0.975 mg·kg^-1）， with 6 mice in each group. Except for the treatment groups， the sham surgery group and model group were given normal saline by gavage. After 4 weeks of continuous intervention， feces and intact knee joints of the mice were collected. Hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining were performed to observe the pathological changes in knee joint tissue morphology. The 16S rDNA sequencing was used to analyze changes in the abundance and diversity of intestinal microorganisms before and after treatment， along with corresponding functional predictions. ResultHigh-dose Danggui Niantongtang and Meloxicam significantly relieved pain symptoms in KOA mice， improved the disorder of joint structure， maintained the integrity of knee articular cartilage， increased the expression of type Ⅱ collagen alpha 1 （Col2a1） in articular cartilage， and decreased the expression of matrix metalloproteinase-13 （MMP-13）. The results of 16S rDNA sequencing showed that high-dose Danggui Niantongtang could adjust the abundance and structure of intestinal microbial species. Compared with the sham surgery group， the abundance of Proteobacteria， Actinobacteria， Ruminococcus， and Bacteroides was significantly increased in the model group （P<0.05）， while in the Danggui Niantongtang group， the abundance of these four flora was significantly reduced compared with the model group. Compared with the sham surgery group， the abundance of Verrucomicrobia， Oscillospira， and Akkermansia was significantly decreased in the model group （P<0.05）， while in the Danggui Niantongtang groups， the abundance of these three flora was significantly increased compared with the model group （P<0.05）. Functional pathway prediction of differential genera revealed that species differences among groups mainly involved metabolic pathways with high abundance associated with biosynthesis and precursors， as well as energy production， including amino acid biosynthesis， nucleotide and nucleoside biosynthesis， cofactors， prosthetic groups， electron carriers， and vitamin biosynthesis. ConclusionDanggui Niantongtang can effectively protect articular cartilage and delay the progression of KOA， possibly by regulating the structure of the intestinal flora， promoting probiotics， and inhibiting the growth of harmful pathogenic bacteria.

Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.

Objective To observe the clinical efficacy of acupuncture combined with rehabilitation training in treating qi deficiency and blood stasis type of hypertensive cerebral hemorrhage in the recovery stage.Methods A total of 132 patients with qi deficiency and blood stasis type of hypertensive cerebral hemorrhage in the recovery period were randomly divided into observation group and control group,with 66 cases in each group,the control group was given western medicine conventional treatment combined with rehabilitation training,and the observation group was treated with acupuncture on the basis of the control group.Both groups of patients were treated for 12 consecutive weeks.After 12 weeks of treatment,the clinical efficacy of the two groups was evaluated.The changes of simplified Fugl-Meyer Assessment(FMA),National Institutes of Health Neurological Impairment Scale(NIHSS),and traditional Chinese medicine(TCM)syndrome scores,as well as the changes of serum interleukin 6(IL-6),homocysteine(Hcy),and endothelin 1(ET-1),serum matrix metalloproteinase 9(MMP-9),and brain-derived neurotrophic factor(BDNF)levels were observed before and after the treatment of the patients in the two groups.The changes of serum serine-threonine protein kinase(AKT),phosphatidylinositol-3 kinase(PI3K),and Bcl-2-related X protein(bax)levels were compared between the two groups before and after treatment.Results(1)After treatment,the serum IL-6,Hcy,ET-1 levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the serum IL-6,Hcy,ET-1 levels,and the difference was statistically significant(P＜0.05).(2)After treatment,the serum MMP-9 and BDNF levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving serum MMP-9 and BDNF levels,with statistically significant differences(P＜0.05).(3)After treatment,the serum AKT,PI3K,bax levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving serum AKT,PI3K,bax levels,and the difference was statistically significant(P＜0.05).(4)After treatment,the FMA score,TCM syndrome scores,and NIHSS score of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the FMA score,TCM syndrome scores,and NIHSS score,and the differences were statistically significant(P＜0.05).(5)The total effective rate was 93.34%(62/66)in the observation group and 81.82%(54/66)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion Acupuncture combined with rehabilitation training for the treatment of patients recovering from hypertensive cerebral hemorrhage of qi deficiency and blood stasis type can significantly reduce the patient's inflammatory response,regulate the level of neurofactors,inhibit neuronal apoptosis,and promote the recovery of neurological function,and the clinical efficacy is remarkable.

Corona virus disease 2019(COVID-19)epidemic has been effectively controlled,but its related complications still cannot be ignored,especially the cardiovascular circulatory system is the active site of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Angiotensin-converting enzyme 2(ACE2)is a type Ⅰ transmembrane glycoprotein that is highly expressed in heart,kidney and testis.Spike protein of SARS-CoV-2 invades host cells by binding to the cell surface receptor ACE2.However,there are still many deficiencies in the clinical application of vaccines and drugs developed based on this target.As a molecular chaperone,cyclophilin A(CypA)promotes protein folding and T cell activation.CD147 is one of the most widely studied CypA receptors,and the interaction of CypA/CD147 plays an important role in the entry of SARS-CoV-2 into host cells.However,there are few reports on the invasion of SARS-CoV-2 into the cardiovascular system through the CypA/CD147 signaling pathway.Based on this,this article summarizes the previous research evidence and the research basis of the research group,and reviews the structure and function of CypA/CD147,the role of CypA/CD147 in cardiovascular disease,and the cardiovascular disease caused by SARS-CoV-2 targeting CypA/CD147 signal pathway,in order to provide reference for the diagnosis and treatment of the COVID-19 complicated with cardiovascular system diseases.

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.

ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.