Insights into the Roles of Natural Killer Cells in Osteoarthritis.

Osteoarthritis (OA) is now widely acknowledged as a low-grade inflammatory condition, in which the intrinsic immune system plays a significant role in its pathogenesis. While the involvement of macrophages and T cells in the development of OA has been extensively reviewed, recent research has provided mounting evidence supporting the crucial contribution of NK cells in both the initiation and advancement of OA. Accumulated evidence has emerged in recent years indicating that NK cells play a critical role in OA development and progression. This review will outline the ongoing understanding of the utility of NK cells in the etiology of OA, focusing on how NK cells interact with chondrocytes, synoviocytes, osteoclasts, and other immune cells to influence the course of OA disease.

Cathepsin G promotes arteriovenous fistula maturation by positively regulating the MMP2/MMP9 pathway.

BACKGROUND: Arteriovenous fistula (AVF) is currently the preferred vascular access for hemodialysis patients. However, the low maturation rate of AVF severely affects its use in patients. A more comprehensive understanding and study of the mechanisms of AVF maturation is urgently needed. METHODS AND RESULTS: In this study, we downloaded the publicly available datasets (GSE119296 and GSE220796) from the Gene Expression Omnibus (GEO) and merged them for subsequent analysis. We screened 84 differentially expressed genes (DEGs) and performed the functional enrichment analysis. Next, we integrated the results obtained from the degree algorithm provided by the Cytohubba plug-in, Molecular complex detection (MCODE) plug-in, weighted gene correlation network analysis (WGCNA), and Least absolute shrinkage and selection operator (LASSO) logistic regression. This integration allowed us to identify CTSG as a hub gene associated with AVF maturation. Through the literature search and Pearson's correlation analysis, the genes matrix metalloproteinase 2 (MMP2) and MMP9 were identified as potential downstream effectors of CTSG. We then collected three immature clinical AVF vein samples and three mature samples and validated the expression of CTSG using immunohistochemistry (IHC) and double-immunofluorescence staining. The IHC results demonstrated a significant decrease in CTSG expression levels in the immature AVF vein samples compared to the mature samples. The results of double-immunofluorescence staining revealed that CTSG was expressed in both the intima and media of AVF veins. Moreover, the expression of CTSG in vascular smooth muscle cells (VSMCs) was significantly higher in the mature samples compared to the immature samples. The results of Masson's trichrome and collagen I IHC staining demonstrated a higher extent of collagen deposition in the media of immature AVF veins compared to the mature. By constructing an in vitro CTSG overexpression model in VSMCs, we found that CTSG upregulated the expression of MMP2 and MMP9 while downregulating the expression of collagen I and collagen III. Furthermore, CTSG was found to inhibit VSMC migration. CONCLUSIONS: CTSG may promote AVF maturation by stimulating the secretion of MMP2 and MMP9 from VSMCs and reducing the extent of medial fibrosis in AVF veins by inhibiting the secretion of collagen I and collagen III.

The efficacy and safety of fexuprazan in treating erosive esophagitis: a phase III, randomized, double-blind, multicenter study.

BACKGROUND AND AIM: Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE). METHODS: This was a phase III, randomized, double-blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4-8 weeks. The healing rates of EE, symptom response, GERD-health-related quality life (GERD-HRQL), and treatment-emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group. RESULTS: A total of 332 subjects were included in full analysis set (FAS) and 311 in per-protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD-HRQL. The incidence of drug-related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm. CONCLUSION: This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561.

Drug Self-Delivery Nanocubes Enhance O2 -Economized Photodynamic-Immunotherapy of Triple-Negative Breast Cancer by Downregulating Wnt/ß-catenin Signaling.

Although the combination of chemotherapy and immune checkpoint inhibitors (ICIs) can treat triple-negative breast cancer (TNBC), the severe effects of chemotherapy on immune cells significantly reduce the efficacy of the ICIs. Photodynamic therapy (PDT) with high selectivity is an alternative to chemotherapy that can also effectively treat hypoxic TNBC. However, high levels of immunosuppressive cells, and low infiltration of cytotoxic T lymphocytes (CTLs) limit the efficacy of PDT combined with ICIs. This study aims to evaluate the role of drug self-delivery nanocubes (ATO/PpIX-SMN) combined with anti-PD-L1 in TNBC treatment. Anti-malarial atovaquone (ATO) enhances protoporphyrin IX (PpIX)-mediated PDT-induced immunogenic cell death and downregulates tumor Wnt/ß-catenin signaling. Furthermore, the nanocubes combined with anti-PD-L1, which synergistically induce maturation of dendritic cells, promote infiltration of CTLs, reduce regulatory T cells, and significantly activate the host immune system, thus treating primary and distal tumors. This work demonstrates that ATO/PpIX-SMN can enhance the response rate of anti-PD-L1 in TNBC treatment via O2 -economized photodynamic-downregulating Wnt/ß-catenin signaling.

Effects of levodopa on gut bacterial antibiotic resistance in Parkinson's disease rat.

The second most prevalent neurodegenerative ailment, Parkinson's disease (PD), is characterized by both motor and non-motor symptoms. Levodopa is the backbone of treatment for PD at the moment. However, levodopa-induced side effects, such as dyskinesia, are commonly seen in PD patients. Recently, several antibiotics were found to present neuroprotective properties against neurodegenerative and neuro-inflammatory processes, which might be developed to effective therapies against PD. In this study, we aimed to identify if levodopa treatment could influence the gut bacterial antibiotic resistance in PD rat. Fecal samples were collected from healthy rats and 6-OHDA induced PD rats treated with different doses of levodopa, metagenomic sequencing data showed that levodopa resulted in gut bacteria composition change, the biomarkers of gut bacteria analyzed by LEfSe changed as well. More interestingly, compared with levodopa (5 mg/kg)-treated or no levodopa-treated PD rats, levodopa (10 mg/kg) caused a significant decrease in the abundance of tetW and vanTG genes in intestinal bacteria, which were related to tetracycline and vancomycin resistance, while the abundance of AAC6-lb-Suzhou gene increased apparently, which was related to aminoglycosides resistance, even though the total quantity of Antibiotic Resistance Gene (ARG) and Antibiotic Resistance Ontology (ARO) among all groups did not significantly differ. Consequently, our results imply that the combination of levodopa and antibiotics, such as tetracycline and vancomycin, in the treatment of PD may decrease the amount of corresponding antibiotic resistance genes in gut bacteria, which would give a theoretical basis for treating PD with levodopa combined with tetracycline and vancomycin in the future.

Remote Loading of Hydrophilic Drug into Cubosomes by Transmembrane pH-Gradient and Characterization of Drug-Loaded Cubosomes Prepared by Different Method.

The encapsulation efficiency (EE) of hydrophobic drug into cubosomes was high by conventional methods, while poor for the hydrophilic drug. In this study, a remote loading method based on transmembrane pH-gradient was applied to prepare hydrophilic drug loaded cubosomes. Several hydrophilic drugs were selected and studied. Results showed just part of the investigated drugs were successfully loaded into cubosomes by the remote loading method, whereas all the drugs failed to be encapsulated by the high-pressure homogenization method. The EE based on remote loading method was affected by the solubility, LogP, number of rings, and polarizability of the drug independent of the number of hydrogen acceptor and hydrogen donor. And the drugs that had high EE by remote loading method were BCS class 1 or 2. In addition, the EE base on remote loading method was significantly affected by the external water pH of cubosomes and drug concentration. The size of drug-loaded cubosomes by remote loading method mainly depended on the pre-formed blank cubosomes, which was bigger than that by high-pressure homogenization method. The preparation method affected the liquid crystalline structure of acidic drug loaded cubosomes, while showed no obvious effect on that of basic drug loaded cubosomes. The release of drug was susceptible to the pH of release medium independent of the preparation method. The drug-loaded cubosomes prepared by different method all showed favorable stability during storage. The remote loading method was a promising approach for the efficient encapsulation of hydrophilic drug into cubosomes. This study laid a foundation for the application of remote loading method on the preparation of hydrophilic drug loaded cubosomes.

Methotrexate showed efficacy both in Crohn's disease and ulcerative colitis, predictors of surgery were identified in patients initially treated with methotrexate monotherapy.

Objective: This study aimed to evaluate methotrexate efficacy in patients with Crohn's disease (CD) and ulcerative colitis (UC), and identify predictors of surgery for patients who were initially treated with methotrexate monotherapy. Design: We performed a retrospective analysis of 34,860 patients with inflammatory bowel disease (IBD) in the IBD Bioresource (United Kingdom) prior to 9 November 2021. Logistic regression was used to identify factors associated with methotrexate efficacy. The data were randomly stratified into training and testing sets (7:3). Nomograms were developed based on Cox regression analysis outcomes. The predictive accuracy and discriminative ability were determined using the concordance index (C-index) and calibration curves. Results: Overall, 1,042 patients (CD: 791, UC: 251) were included. Independent factors associated with effective methotrexate monotherapy were younger age at diagnosis, latest therapy period, exclusive upper gastrointestinal tract disease (for CD), and longer duration between diagnosis and methotrexate initiation (for UC). For CD, predictors in the nomogram were gender, treatment era, tolerance, lesion site, perianal involvement, disease behaviour, and biologics requirements (C-index: 0.711 and 0.732 for training and validation cohorts, respectively). For UC, the factors were age at diagnosis and sex (C-index: 0.784 and 0.690 for training and validation cohorts, respectively). Calibration curves demonstrated good agreement between predictions and actual observations.

Vedolizumab in the treatment of immune checkpoint inhibitor-induced colitis: Two case reports.

BACKGROUND: Immune check-point inhibitors-induced colitis (ICPIs-induced colitis) is one of the immune-related side effects. Steroids and Infliximab are commonly used to treat it. The patients of our report were treated by Vedolizumab. CASE SUMMARY: The two patients went to the doctor with bloody stools and were treated by Sintilimab and Camrelizumab, respectively, for their malignant tumors. They were diagnosed as ICPIs-induced colitis based on endoscopic and histologic examination. The original immunotherapy was ceased while the anti-inflammatory therapy was introduced. The patients' colitis symptoms disappeared after the treatment and no recurrence was found during the follow-up period. The unique feature about the case reports is that Vedolizumab combined with short-term corticosteroids had achieved good therapeutic effects. CONCLUSION: For the symptoms of bloody diarrhea after the ICPIs treatment of cancer, the possibility of ICPIs-induced colitis should be considered. Vedolizumab combined with short-term corticosteroids may be appropriate for the treatment.

Therapeutic drug monitoring in inflammatory bowel disease treatments.

Recently, biological drugs have played a leading role in the treatment of inflammatory bowel disease, and therapeutic drug monitoring (TDM) may be useful in maximizing their effectiveness. TDM involves the measurement of serum drug and anti-drug antibodies concentrations as the basis for dosage adjustments or drug conversions to achieve a higher response rate. We believe that concentration thresholds should be individualized based on patients' disease severity, extent and phenotype, and therapeutic purposes should also be considered, with higher cut-offs mainly needed for endoscopic and fistula healing than for symptomatic remission. Proactive and reactive TDM can help optimize treatment, especially in patients receiving anti-tumour necrosis factor, and guide dose adjustment or drug conversion with lower cost. TDM is a promising approach to achieve precision medicine and targeted medicine in the future.

Drug self-delivery nanorods enhance photodynamic therapy of triple-negative breast cancer by inhibiting oxidative phosphorylation.

Photodynamic therapy (PDT) shows very high potential for the clinical treatment of triple-negative breast cancer. However, the efficacy of PDT is significantly weakened by tumor hypoxia, the relatively high intracellular glutathione levels and the active proliferation of cancer cells. To address these issues, we developed a novel drug self-delivery nanorod (defined as AINRs) through the hydrophobic interaction among the mitochondrial complex III inhibitor (atovaquone, ATO), the photosensitizer (indocyanine green, ICG) and the dispersion stabilizer (distearoyl phosphoethanolamine-polyethylene glycol 2000, DSPE-PEG 2000). The AINRs showed a rod-like morphology with a mean diameter of 120.6 ± 5.4 nm, a zeta potential of -26.35 ± 1.63 mV and a significantly high drug loading rate of 93.48%. The results of in vitro cell experiments involving triple-negative breast cancer cell lines (4T1 cells and MDA-MB-231 cells) indicated that the AINRs could effectively block the oxidative phosphorylation of cancer cells through the inhibition of mitochondrial complex III, which results in the reduction of endogenous oxygen consumption and the decrease of the intracellular ATP level. The reduction of ATP content further inhibited the glutathione synthesis and arrested the cell cycle at the S-phase, which results in enhanced in vitro PDT efficacy of ICG. The results of in vivo antitumor activity in 4T1-bearing mice showed that the tumor growth inhibition rate of the AINRs with near-infrared laser irradiation (NIR) was greater than 90%, whereas the tumor growth inhibition rates of the AINRs without NIR, ICG with NIR and doxorubicin (3 mg/kg) were only 31.68%, 61.15% and 24.59%, respectively. In addition, the results of safety studies, including body weights, biochemical indicators and H&E staining images of the main organs demonstrated the security of the AINRs. In summary, this study showed that the oxidative phosphorylation inhibition of triple-negative breast cancer was a safe and effective method to enhance its PDT efficacy.

Semiquantitative microscopic pore characterizations of the metamorphic rock reservoir in the central paleo-uplift belt, Songliao Basin.

Currently, metamorphic rock is a common target for natural gas exploration, and reservoirs are the key factors restricting natural gas exploration and development in metamorphic rocks. The deep metamorphic rock gas reservoir in the central paleo-uplift of the northern Songliao Basin has good exploration and development potential. In this study, we use a combination of qualitative descriptions and quantitative analysis to comprehensively analyze the pore characteristics of the reservoir and explore the factors controlling the pore characteristics of the metamorphic rock reservoir in the central paleo-uplift belt of the Songliao Basin. The metamorphic rock reservoir in the central paleo-uplift belt contains three types of lithologies: chlorite schist, mica schist and mylonite, each with different protoliths and metamorphic histories. The results of high-pressure mercury intrusion and nitrogen adsorption indicate that the pore size distributions of the schist and mylonite differ. Compared with the mylonite, the schist has larger reservoir space, more heterogeneity, smaller pore size, larger specific surface area and larger adsorbed gas storage capacity. This paper also studies the formation process of the reservoir and divides it into four stages. Finally, this article discusses in detail the factors controlling the microscopic pore characteristics of metamorphic rock reservoirs in the central paleo-uplift belt; the metamorphic rock protolith is the most important controlling factor.

Potential neuroprotection by Dendrobium nobile Lindl alkaloid in Alzheimer's disease models.

At present, treatments for Alzheimer's disease can temporarily relieve symptoms but cannot prevent the decline of cognitive ability and other neurodegenerative changes. Dendrobium nobile Lindl alkaloid is the main active component of Dendrobium nobile Lindl. Dendrobium nobile Lindl alkaloid has been shown to resist aging, prolong life span, and exhibit immunomodulatory effects in animals. This review summarizes the mechanisms behind the neuroprotective effects reported in Alzheimer's disease animal models. The neuroprotective effects of Dendrobium nobile Lindl alkaloid have not been studied in patients. The mechanisms by which Dendrobium nobile Lindl alkaloid has been reported to improve cognitive dysfunction in Alzheimer's disease animal models may be associated with extracellular amyloid plaque production, regulation of tau protein hyperphosphorylation, inhibition of neuroinflammation and neuronal apoptosis, activation of autophagy, and enhanced synaptic connections.

Factors influencing quality of transnational education: Evidence from a Sino-UK MA program.

With the internationalization of higher education, transnational education (TNE) has gradually become one of the main means to mobility of education resources in many countries. There have been many studies on service quality research, but not many of these studies attempt to directly explore the in-depth factors contributing to service quality. This study investigated the factors impacting the quality of TNE based on the interpretation of students' experiences on a Sino-UK MA program. Semi-structured interviews with seven participants revealed that high-quality educational resources and professional and sympathetic lecturers are the two major factors impacting the service quality. The results suggested that educational resources that meet the local social needs are considered desirable service offerings. Lecturers are key factors guaranteeing the service delivery. This study sheds light on service quality components of TNE that have not been given much attention in the literature of previous research, as well as informs host and export institutions on TNE programming.

Resveratrol Alleviates Levodopa-Induced Dyskinesia in Rats.

Dyskinesia is a serious complication of Parkinson's disease during levodopa (L-DOPA) treatment. The pathophysiology of L-DOPA-induced dyskinesia (LID) is complex and not fully illuminated. At present, treatment of dyskinesia is quite limited. Recent studies demonstrated neuroinflammation plays an important role in development of LID. Thus, inhibition of neuroinflammation might open a new avenue for LID treatment. Resveratrol (RES) is the most well-known polyphenolic stilbenoid and verified to possess a large variety of biological activities. DA neurotoxicity was assessed via behavior test and DA neuronal quantification. The movement disorders of dyskinesia were detected by the abnormal involuntary movements scores analysis. Effects of RES on glial cells-elicited neuroinflammation were also explored. Data showed that RES attenuated dyskinesia induced by L-DOPA without affecting L-DOPA's anti-parkinsonian effects. Furthermore, RES generated neuroprotection against long term treatment of L-DOPA-induced DA neuronal damage. Meanwhile, RES reduced protein expression of dyskinesia molecular markers, ΔFOS B and ERK, in the striatum. Also, there was a strong negative correlation between DA system damage and ΔFOS B level in the striatum. In addition, RES inhibited microglia and astroglia activation in substantia nigra and subsequent inflammatory responses in the striatum during L-DOPA treatment. RES alleviates dyskinesia induced by L-DOPA and these beneficial effects are closely associated with protection against DA neuronal damage and inhibition of glial cells-mediated neuroinflammatory reactions.

New insights into pathogenesis of l-DOPA-induced dyskinesia.

Parkinson's disease (PD) is a progressive and self-propelling neurodegenerative disorder, which is characterized by motor symptoms, such as rigidity, tremor, slowness of movement and problems with gait. These symptoms become worse over time. To date, Dopamine (DA) replacement therapy with 3, 4-dihydroxy-l-phenylalanine (L-DOPA) is still the most effective pharmacotherapy for motor symptoms of PD. Unfortunately, motor fluctuations consisting of wearing-off effect actions and dyskinesia tend to occur in a few years of starting l-DOPA. Currently, l-DOPA-induced dyskinesia (LID) is troublesome and the pathogenesis of LID requires further investigation. Importantly, a new intervention for LID is imminent. Thus, this review mainly summarized the clinical features, risk factors and pathogenesis of LID to provide updatefor the development of therapeutic targets and new approaches for the treatment of LID.

Mucosal lesions of the upper gastrointestinal tract in patients with ulcerative colitis: A review.

Ulcerative colitis (UC) is a chronic, nonspecific, relapsing inflammatory bowel disease. The colorectum is considered the chief target organ of UC, whereas upper gastrointestinal (UGI) tract manifestations are infrequent. Recently, emerging evidence has suggested that UC presents complications in esophageal, stomachic, and duodenal mucosal injuries. However, UC-related UGI tract manifestations are varied and frequently silenced or concealed. Moreover, the endoscopic and microscopic characteristics of UGI tract complicated with UC are nonspecific. Therefore, UGI involvement may be ignored by many clinicians. In addition, no standard criteria have been established for patients with UC who should undergo fibrogastroduodenoscopy. Furthermore, specific treatment recommendations may be needed for patients with UC-associated UGI lesions. Herein, we review the esophageal, gastric, and duodenal mucosal lesions of the UC-associated UGI tract, as well as the potential pathogenesis and therapy.

Fenretinide regulates macrophage polarization to protect against experimental colitis induced by dextran sulfate sodium.

Fenretinide (4-HPR), a synthetic retinoid, has attracted attention for its anti-inflammation activity. However, few studies have evaluated the effects of 4-HPR on ulcerative colitis (UC). The present study was performed to investigate the therapeutic effects of 4-HPR on UC, and to explore the mechanisms mainly focused on macrophage polarization involved in this progress. Intraperitoneally administered 4-HPR particularly at dose of 100 mg/kg obviously alleviated UC symptoms and restrained the mRNA expression of colonic IL-1ß, IL-6, and TNF-α in dextran sulfate sodium (DSS)-induced mice. Further analysis showed that 4-HPR decreased the mRNA expression of M1 macrophage markers IL-12 and iNOS, while increased M2 macrophage markers Ym1, Arg1 and MRC1 in colonic tissue of mice received DSS. Consistently, an in vitro study revealed that 4-HPR decreased inflammatory response and M1 polarization, while enhanced M2 polarization in LPS-induced RAW264.7 cells. Interestingly, 4-HPR remarkably activated PPAR-γ which was an important regulator of macrophage polarization both in colonic tissue of UC mice and in LPS-induced RAW264.7 cells. Furthermore, these effects of 4-HPR in vivo and in vitro including anti-inflammation and modulation of macrophage polarization were partially abolished by treatment with PPAR-γ antagonist GW9662, indicating that 4-HPR activated PPAR-γ to exert its activities. Taken together, this study demonstrated that 4-HPR might be a potent anti-UC agent that works by regulating macrophage polarization via PPARγ.

Physiological Concentration of H2O2 Supports Dopamine Neuronal Survival via Activation of Nrf2 Signaling in Glial Cells.

Traditionally, hydrogen peroxide (H2O2) was formed from cellular oxidative metabolism and often viewed as toxic waste. In fact, H2O2 was a benefit messenger for neuron-glia signaling and synaptic transmission. Thus, H2O2 was a double-edged sword and neuroprotection vs. neurotoxicity produced by H2O2 was difficult to define. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been implicated as an intracellular regulator of neuronal growth. Inactivation of Nrf2 participated in the development of Parkinson's disease (PD). Thus, suitable activation of Nrf2 was essential for the prevention and treatment of PD. This study aimed to explore whether H2O2-conferred neuroprotective effects to support neuronal survival. H2O2 were added into primary neuron-glia, neuron-astroglia and neuron-microglia co-cultures in concentration- and time-dependent manners. H2O2 increased dopamine (DA) neuronal survival in concentration- and time-dependent manners. In addition, glial cells Nrf2 activation involved in H2O2-supported DA neuronal survival with the following phenomenons. First, H2O2 activated Nrf2 signaling pathway. Second, H2O2 generated beneficial neuroprotection in neuron-glia, neuron-astroglia and neuron-microglia co-cultures but not in neuron-enriched cultures. Third, silence of Nrf2 in glial cells abolished H2O2-conferred DA neuronal survival. This study demonstrated that physiological concentration of H2O2-supported DA neuronal survival via activation of Nrf2 signaling in glial cells. Our data permit to re-evaluate the role of H2O2 in the pathogenesis and therapeutic strategies for PD.

Ellagic acid protects dopamine neurons from rotenone-induced neurotoxicity via activation of Nrf2 signalling.

Parkinson's disease (PD) is the second most prevalent central nervous system (CNS) degenerative disease. Oxidative stress is one of key contributors to PD. Nuclear factor erythroid-2-related factor 2 (Nrf2) is considered to be a master regulator of many genes involved in anti-oxidant stress to attenuate cell death. Therefore, activation of Nrf2 signalling provides an effective avenue to treat PD. Ellagic acid (EA), a natural polyphenolic contained in fruits and nuts, possesses amounts of pharmacological activities, such as anti-oxidant stress and anti-inflammation. Recent studies have confirmed EA could be used as a neuroprotective agent in neurodegenerative diseases. Here, mice subcutaneous injection of rotenone (ROT)-induced DA neuronal damage was performed to investigate EA-mediated neuroprotection. In addition, adult Nrf2 knockout mice and different cell cultures including MN9D-enciched, MN9D-BV-2 and MN9D-C6 cell co-cultures were applied to explore the underlying mechanisms. Results demonstrated EA conferred neuroprotection against ROT-induced DA neurotoxicity. Activation of Nrf2 signalling was involved in EA-mediated DA neuroprotection, as evidenced by the following observations. First, EA activated Nrf2 signalling in ROT-induced DA neuronal damage. Second, EA generated neuroprotection with the presence of astroglia and silence of Nrf2 in astroglia abolished EA-mediated neuroprotection. Third, EA failed to produce DA neuroprotection in Nrf2 knockout mice. In conclusion, this study identified EA protected against DA neuronal loss via an Nrf2-dependent manner.

Correlation of Intestinal Mucosal Healing and Tight Junction Protein Expression in Ulcerative Colitis Patients.

BACKGROUND: The aim of this study was to investigate the relationship between intestinal mucosal healing and tight junction (TJ) protein expression in patients with ulcerative colitis (UC). MATERIALS AND METHODS: A total of 40 patients with UC were included as an experimental group and UC disease activity was evaluated using the Mayo clinic score (MCS) and 8 patients with normal distal colon served as the control group. The expression of TJ proteins including occludin, ZO-1 and claudin-2 were determined by immunohistochemistry and their correlation with clinical characteristics were also analyzed. RESULTS: Statistically significant differences regarding the MCS and Mayo endoscopic subscore (MES) were observed in both groups (P < 0.01). The Geboes index was significantly increased in patients with active UC compared to patients with quiescent UC and normal controls (P < 0.01). Patients with active and quiescent UC had upregulated expression of claudin-2 and reduced expression of occludin and ZO-1 compared to those of normal controls. The expression of ZO-1 was significantly higher in patients with quiescent UC with mucosa healing (P < 0.05) compared with those without mucosal healing. The expression of ZO-1 and occludin was negatively correlated with MCS, MES, Geboes, C-reaction protein and erythrocyte sedimentation rate. The expression of claudin-2 was positively correlated with MCS, MES, Geboes, C-reaction protein and erythrocyte sedimentation rate. CONCLUSIONS: These findings suggest that TJ proteins play a crucial role in mucosal healing, and may be a potential marker of response when evaluating therapeutic interventions.