Recombinant bivalent subunit vaccine combining truncated VP4 from P[7] and P[23] induces protective immunity against prevalent porcine rotaviruses.

Porcine rotaviruses (PoRVs) cause severe economic losses in the swine industry. P[7] and P[23] are the predominant genotypes circulating on farms, but no vaccine is yet available. Here, we developed a bivalent subunit PoRV vaccine using truncated versions (VP4*) of the VP4 proteins from P[7] and P[23]. The vaccination of mice with the bivalent subunit vaccine elicited more robust neutralizing antibodies (NAbs) and cellular immune responses than its components, even at high doses. The bivalent subunit vaccine and inactivated bivalent vaccine prepared from strains PoRVs G9P[7] and G9P[23] were used to examine their protective efficacy in sows and suckling piglets after passive immunization. The immunized sows showed significantly elevated NAbs in the serum and colostrum, and the suckling piglets acquired high levels of sIgA antibodies from the colostrum. Challenging subunit-vaccinated or inactivated-vaccinated piglets with homologous virulent strains did not induce diarrhea, except in one or two piglets, which had mild diarrhea. Immunization with the bivalent subunit vaccine and inactivated vaccine also alleviated the microscopic lesions in the intestinal tissues caused by the challenge with the corresponding homologous virulent strain. However, all the piglets in the challenged group displayed mild to watery diarrhea and high levels of viral shedding, whereas the feces and intestines of the piglets in the bivalent subunit vaccine and inactivated vaccine groups had lower viral loads. In summary, our data show for the first time that a bivalent subunit vaccine combining VP4*P[7] and VP4*P[23] effectively protects piglets against the diarrhea caused by homologous virulent strains.IMPORTANCEPoRVs are the main causes of diarrhea in piglets worldwide. The multisegmented genome of PoRVs allows the reassortment of VP4 and VP7 genes from different RV species and strains. The P[7] and P[23] are the predominant genotypes circulating in pig farms, but no vaccine is available at present in China. Subunit vaccines, as nonreplicating vaccines, are an option to cope with variable genotypes. Here, we have developed a bivalent subunit candidate vaccine based on a truncated VP4 protein, which induced robust humoral and cellular immune responses and protected piglets against challenge with homologous PoRV. It also appears to be safe. These data show that the truncated VP4-protein-based subunit vaccine is a promising candidate for the prevention of PoRV diarrhea.

Isolation and characterization of a G9P[23] porcine rotavirus strain AHFY2022 in China.

Rotavirus group A (RVA) is a main pathogen causing diarrheal diseases in humans and animals. Various genotypes are prevalent in the Chinese pig herd. The genetic diversity of RVA lead to distinctly characteristics. In the present study, a porcine RVA strain, named AHFY2022, was successfully isolated from the small intestine tissue of piglets with severe diarrhea. The AHFY2022 strain was identified by cytopathic effects (CPE) observation, indirect immunofluorescence assay (IFA), electron microscopy (EM), high-throughput sequencing, and pathogenesis to piglets. The genomic investigation using NGS data revealed that AHFY2022 exhibited the genotypes G9-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1, using the online platform the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) (https://www.bv-brc.org/). Moreover, experimental inoculation in 5-day-old and 27-day-old piglets demonstrated that AHFY2022 caused severe diarrhea, fecal shedding, small intestinal villi damage, and colonization in all challenged piglets. Taken together, our results detailed the virological features of the porcine rotavirus G9P[23] from China, including the whole-genome sequences, genotypes, growth kinetics in MA104 cells and the pathogenicity in suckling piglets.

Structural and functional properties of whey protein isolate-inulin conjugates prepared with ultrasound or wet heating method.

BACKGROUND: Whey protein isolate (WPI) generally represents poor functional properties such as thermal stability, emulsifying activity and antioxidant activity near its isoelectric point or high temperatures, which limit its application in the food industry. The preparation of WPI-polysaccharide covalent conjugates based on Maillard reaction is a promising method to improve the physical and chemical stability and functional properties of WPI. In this research, WPI-inulin conjugates were prepared through wet heating method and ultrasound method and their structural and functional properties were examined. RESULTS: In conjugates, the free amino acid content was reduced, the high molecular bands were emerged at sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), new C-N bonds were formed in Fourier-transform infrared (FTIR) spectroscopy, and fluorescence intensity was reduced compared with WPI. Furthermore, the result of circular dichroism (CD) spectroscopy also showed that the secondary structure of conjugates was changed. Conjugates with ultrasound treatment had better structural properties compared with those prepared by wet heating treatment. The functional properties such as thermal stability, emulsifying activity index (EAI), emulsion stability (ES) and antioxidant activity of conjugates with wet heating treatment were significantly improved compared with WPI. The EAI and ES of conjugates with ultrasound treatment were the highest, but the thermal stability and antioxidant activity were only close to that of the conjugates with wet heating treatment for 2 h. CONCLUSION: This study revealed that WPI-inulin conjugates prepared with ultrasound or wet heating method not only changed the structural characteristics of WPI but also could promote its functional properties including thermal stability, EAI, ES and antioxidant activity. © 2024 Society of Chemical Industry.

ortho-C(sp3)-H arylation of aromatic aldehydes using 2-amino-N-methyl-acetamide as a L,L-type transient directing group.

Pd-catalyzed ortho-C(sp3)-H arylation of aromatic aldehydes using 2-amino-N-methyl-acetamide as a simple, efficient and commercially available L,L-type transient directing group (TDG) is reported. The reaction exhibited excellent substrate compatibility and generated the desired products in moderate-to-high yields up to 78%. Further acid-catalyzed cyclization and dehydrative aromatization were also tested, and furnished some polycyclic aromatic hydrocarbons with excellent yields up to 96%. The X-ray crystal structure of a 2-methylbenzaldehyde ortho-C(sp3)-H palladation intermediate was obtained. Then, a plausible reaction mechanism involving the formation of a [5,6]-fused palladacycle was proposed. This approach offers valuable insights for exploiting novel L,L-type TDGs.

Organic photoredox catalyzed C(sp3)-H functionalization of saturated aza-heterocycles via a cross-dehydrogenative coupling reaction.

Herein we present a novel protocol to access α-functionalized saturated aza-heterocycles, and a variety of nucleophilic groups, such as indole, naphthol, phenol, pyrrole, furyl, nitromethyl, and cyano, could be easily installed into saturated aza-heterocycles. Furthermore, a range of biologically valuable 3,3'-diindolylmethane derivatives could also be readily accessed under mild photocatalytic conditions.

Effects of group mindfulness-based cognitive therapy and group cognitive behavioural therapy on symptomatic generalized anxiety disorder: a randomized controlled noninferiority trial.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) is a promising alternative treatment for generalized anxiety disorder (GAD). The objective of this study was to examine whether the efficacy of group MBCT adapted for treating GAD (MBCT-A) was noninferior to group cognitive behavioural therapy (CBT) designed to treat GAD (CBT-A), which was considered one of first-line treatments for GAD patients. We also explored the efficacy of MBCT-A in symptomatic GAD patients compared with CBT-A for a variety of outcomes of anxiety symptoms, as well as depressive symptoms, overall illness severity, quality of life and mindfulness. METHODS: This was a randomized, controlled, noninferiority trial with two arms involving symptomatic GAD patients. Adult patients with GAD (n = 138) were randomized to MBCT-A or CBT-A in addition to treatment as usual (TAU). The primary outcome was the anxiety response rate assessed at 8 weeks after treatment as measured using the Hamilton Anxiety Scale (HAMA). Secondary outcomes included anxiety remission rates, scores on the HAMA, the state-trait anxiety inventory (STAI), the Hamilton Depression Scale (HAMD), the Severity Subscale of the Clinical Global Impression Scale (CGI-S), and the 12-item Short-Form Health Survey (SF-12), as well as mindfulness, which was measured by the Five Facet Mindfulness Questionnaire (FFMQ). Assessments were performed at baseline, 8 weeks after treatment, and 3 months after treatment. Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed for primary analyses. The χ2 test and separate two-way mixed ANOVAs were used for the secondary analyses. RESULTS: ITT and PP analyses showed noninferiority of MBCT-A compared with CBT-A for response rate [ITT rate difference = 7.25% (95% CI: -8.16, 22.65); PP rate difference = 5.85% (95% CI: - 7.83, 19.53)]. The anxiety remission rate, overall illness severity and mindfulness were significantly different between the two groups at 8 weeks. There were no significant differences between the two groups at the 3-month follow-up. No severe adverse events were identified. CONCLUSIONS: Our data indicate that MBCT-A was noninferior to CBT-A in reducing anxiety symptoms in GAD patients. Both interventions appeared to be effective for long-term benefits. TRIAL REGISTRATION: Registered at chictr.org.cn (registration number: ChiCTR1800019150 , registration date: 27/10/2018).

Efficacy and safety of preoperative versus postoperative NSAIDs on pain relief in patients undergoing hip arthroscopy surgery: A multicentre, randomized, controlled trial.

WHAT IS KNOWN AND OBJECTIVE: Postoperative pain relief is a critical issue for hip arthroscopy surgery (HAS). This study aimed to investigate the effect of preemptive non-steroidal anti-inflammatory drugs (NSAIDs) for postoperative analgesia in femoroacetabular impingement (FAI) patients receiving HAS. METHODS: This multicenter, randomized, controlled study enrolled 204 FAI patients receiving HAS, then assigned them to preoperative (PRE, N = 103) or postoperative (POS, N = 101) group as a 1:1 ratio; the PRE group administrated NSAIDs from 24 h pre-surgery to day 7 (D7) post-surgery, while the POS group administrated NSAIDs from 12 h post-surgery to D7 post-surgery. RESULTS AND DISCUSSION: Pain at rest was reduced at D1 (p = 0.016) and D2 (p = 0.023); pain at movement was decreased at D1 (p = 0.002), D2 (p = 0.020), and D3 (p = 0.030) in the PRE group compared with POS group, but not at other time points (all p > 0.05). Patient's satisfaction was increased at D1 (p = 0.013) and D3 (p = 0.029) in the PRE group compared to the POS group, but not at D7 (p = 0.145). Pethidine was less consumed at D3 (p = 0.038) and D7 (p = 0.017) in the PRE group in contrast with the POS group. Harris hip scores were similar at D7 (p = 0.124), month 1 (M1) (p = 0.273), and M3 (p = 0.360) between groups. Adverse events incidence was similar between groups (all p > 0.05). Besides, subgroup analysis discovered that pain was not influenced by the types of NSAID in both groups (all p > 0.05). WHAT IS NEW AND CONCLUSION: Starting NSAIDs before HAS provides better short-term pain relief and improves patient's satisfaction compared with its postoperative utilization, while does not induce additional adverse events in FAI patients.

Optical design of connecting electrodes for tandem organic light-emitting diodes.

Connecting electrodes play a crucial role to assist charge injection into the adjacent electroluminescent units in tandem organic light-emitting diodes (OLEDs). In this study, we demonstrate that Mg:Ag alloy is an effective connecting electrode for bottom- and top-emitting tandem OLEDs. Optical cavity design and simulation are also conducted to predict the luminance of tandem OLEDs. It is found that the theoretical luminance of tandem OLEDs is close to but not higher than twofold enhancement over the luminance of a single OLED optimized to the first resonance mode, which is theoretically higher than high-order resonance modes. It is also found that the optical properties of Mg:Ag connecting electrodes, while having relatively small influence on weak microcavity bottom-emitting tandem OLEDs, have large influence on strong microcavity top-emitting tandem OLEDs.

H3K4me3 Is a Potential Mediator for Antiproliferative Effects of Calcitriol (1α,25(OH)2D3) in Ovarian Cancer Biology.

Posttranslational histone modification plays an important role in tumorigenesis. Histone modification is a dynamic response of chromatin to various signals, such as the exposure to calcitriol (1α,25(OH)2D3). Recent studies suggested that histone modification levels could be used to predict patient outcomes in various cancers. Our study evaluated the expression level of histone 3 lysine 4 trimethylation (H3K4me3) in a cohort of 156 epithelial ovarian cancer (EOC) cases by immunohistochemical staining and analyzed its correlation to patient prognosis. The influence of 1α,25(OH)2D3 on the proliferation of ovarian cancer cells was measured by BrdU proliferation assay in vitro. We could show that higher levels of H3K4me3 were correlated with improved overall survival (median overall survival (OS) not reached vs. 37.0 months, p = 0.047) and identified H3K4me3 as a potential prognostic factor for the present cohort. Ovarian cancer cell 1α,25(OH)2D3 treatment induced H3K4me3 protein expression and exhibited antiproliferative effects. By this, the study suggests a possible impact of H3K4me3 expression on EOC progression as well as its relation to calcitriol (1α,25(OH)2D3) treatment. These results may serve as an explanation on how 1α,25(OH)2D3 mediates its known antiproliferative effects. In addition, they further underline the potential benefit of 1α,25(OH)2D3 supplementation in context of ovarian cancer care.

[Effects and pathophysiological significance of intestinal flora on the enteric neuro-endocrine-immune system].

Interactions among the nervous, the endocrine and the immune systems enable the gut to respond to the dietary products, pathogens and microbiota, which maintains the homeostasis of the body. However, dysbiosis may induce or aggravate the gastrointestinal (GI) and extra-GI diseases through changing the activities of enteric nervous system (ENS), enteroendocrine cells and enteric immune cells. Here we review recent advances in the understandings on how intestinal flora may impact the enteric neuro-endocrine-immune system in the gut, thereby contributing to the regulation of pathophysiological processes.

How to balance the bioinformatics data: pseudo-negative sampling.

BACKGROUND: Imbalanced datasets are commonly encountered in bioinformatics classification problems, that is, the number of negative samples is much larger than that of positive samples. Particularly, the data imbalance phenomena will make us underestimate the performance of the minority class of positive samples. Therefore, how to balance the bioinformatic data becomes a very challenging and difficult problem. RESULTS: In this study, we propose a new data sampling approach, called pseudo-negative sampling, which can be effectively applied to handle the case that: negative samples greatly dominate positive samples. Specifically, we design a supervised learning method based on a max-relevance min-redundancy criterion beyond Pearson correlation coefficient (MMPCC), which is used to choose pseudo-negative samples from the negative samples and view them as positive samples. In addition, MMPCC uses an incremental searching technique to select optimal pseudo-negative samples to reduce the computation cost. Consequently, the discovered pseudo-negative samples have strong relevance to positive samples and less redundancy to negative ones. CONCLUSIONS: To validate the performance of our method, we conduct experiments base on four UCI datasets and three real bioinformatics datasets. According to the experimental results, we clearly observe the performance of MMPCC is better than other sampling methods in terms of Sensitivity, Specificity, Accuracy and the Mathew's Correlation Coefficient. This reveals that the pseudo-negative samples are particularly helpful to solve the imbalance dataset problem. Moreover, the gain of Sensitivity from the minority samples with pseudo-negative samples grows with the improvement of prediction accuracy on all dataset.

The efficacy of group cognitive-behavioural therapy plus duloxetine for generalised anxiety disorder versus duloxetine alone.

OBJECTIVE: To explore whether and how group cognitive-behavioural therapy (GCBT) plus medication differs from medication alone for the treatment of generalised anxiety disorder (GAD). METHODS: Hundred and seventy patients were randomly assigned to the GCBT plus duloxetine (n=89) or duloxetine group (n=81). The primary outcomes were Hamilton Anxiety Scale (HAMA) response and remission rates. The explorative secondary measures included score reductions from baseline in the HAMA total, psychic, and somatic anxiety subscales (HAMA-PA, HAMA-SA), the Hamilton Depression Scale, the Severity Subscale of Clinical Global Impression Scale, Global Assessment of Functioning, and the 12-item Short-Form Health Survey. Assessments were conducted at baseline, 4-week, 8-week, and 3-month follow-up. RESULTS: At 4 weeks, HAMA response (GCBT group 57.0% vs. control group 24.4%, p=0.000, Cohen's d=0.90) and remission rates (GCBT group 21.5% vs. control group 6.2%, p=0.004; d=0.51), and most secondary outcomes (all p<0.05, d=0.36-0.77) showed that the combined therapy was superior. At 8 weeks, all the primary and secondary significant differences found at 4 weeks were maintained with smaller effect sizes (p<0.05, d=0.32-0.48). At 3-month follow-up, the combined therapy was only significantly superior in the HAMA total (p<0.045, d=0.43) and HAMA-PA score reductions (p<0.001, d=0.77). Logistic regression showed superiority of the combined therapy for HAMA response rates [odds ratio (OR)=2.12, 95% confidence interval (CI) 1.02-4.42, p=0.04] and remission rates (OR=2.80, 95% CI 1.27-6.16, p=0.01). CONCLUSIONS: Compared with duloxetine alone, GCBT plus duloxetine showed significant treatment response for GAD over a shorter period of time, particularly for psychic anxiety symptoms, which may suggest that GCBT was effective in changing cognitive style.

Risk of inflammatory bowel disease in patients with rosacea: Results from a nationwide cohort study in Taiwan.

BACKGROUND: A link between rosacea and inflammatory bowel disease (IBD) has been proposed with unknown mechanisms. Epidemiologic evidence of this association needs to be examined. METHODS: In this nationwide cohort study, a total of 89,356 patients with rosacea and 178,712 matched patients without rosacea between 1997 and 2013 were identified in the Taiwanese National Health Insurance Research Database. Cumulative incidences of IBD were compared between these 2 cohorts. Frailty Cox proportional hazard model was used and subgroup analyses were conducted to examine the risk factors for IBD. RESULTS: The 15-year cumulative incidences of IBD were 0.036% (95% confidence interval [CI] 0.00%-1.57%) and 0.019% (95% CI 0.00%-0.83%) in rosacea and nonrosacea cohorts, respectively (P = .05). Rosacea (adjusted hazard ratio 1.94, 95% CI 1.04-3.63, P = .04) and male gender (adjusted hazard ratio 3.52, 95% CI 2.03-6.11, P < .01) were independently associated with IBD, after adjustment for major comorbidities. Multivariate subgroup analyses revealed consistent results. The incidence rates of IBD decreased with increasing antibiotic use in patients with rosacea, but without statistical significance. LIMITATION: Information related to lifestyle, diet, alcohol, and smoking was not included in the database. CONCLUSION: Patients with rosacea may have an increased risk of IBD.

Preparation and In Vitro Evaluation of a MRI Contrast Agent Based on Aptamer-Modified Gadolinium-Loaded Liposomes for Tumor Targeting.

The aim of this study was to prepare aptamer-modified liposomes loaded with gadolinium (Gd) to enhance the effective diagnosis for tumor by MRI. A modified GBI-10 (GBI-10m) was used to prepare targeted liposomes (GmLs). Liposomes with GBI-10 aptamer (GLs) and without aptamer (non-targeted liposomes (NLs)) were also prepared as controls. The particle size and zeta potential of GmLs, GLs, and NLs were all assayed. A clinical 3.0 T MR scanner was employed to assess the imaging efficiency and measure the longitudinal relaxivity (r 1) of the above liposomes. Confocal laser scanning microscopy and flow cytometry were used to analyze and compare the targeting effects of GmLs, GLs, and NLs to MDA-MB-435s cells at 37°C. The particle size of the prepared liposomes was scattered at 100-200 nm, and their values of r 1 were ∼4 mM-1 s-1. The images of confocal laser scanning microscopy showed that GmLs in the cytoplasm were significantly more than GLs and both GmLs and GLs were more than NLs. The fluorescence intensity of GmLs was increased by about two times than that of GLs and three times than that of NLs by flow cytometry. Therefore, the GmLs in this initial study were suggested to be a potential MRI contrast agent at 37°C for diagnosing tumors with the protein of tenascin-C over-expressed.

Identification and Characterization of a New 7-Aminocephalosporanic Acid Deacetylase from Thermophilic Bacterium Alicyclobacillus tengchongensis.

UNLABELLED: Deacetylation of 7-aminocephalosporanic acid (7-ACA) at position C-3 provides valuable starting material for producing semisynthetic ß-lactam antibiotics. However, few enzymes have been characterized in this process before now. Comparative analysis of the genome of the thermophilic bacterium Alicyclobacillus tengchongensis revealed a hypothetical protein (EstD1) with typical esterase features. The EstD1 protein was functionally cloned, expressed, and purified from Escherichia coli BL21(DE3). It indeed displayed esterase activity, with optimal activity at around 65°C and pH 8.5, with a preference for esters with short-chain acyl esters (C2 to C4). Sequence alignment revealed that EstD1 is an SGNH hydrolase with the putative catalytic triad Ser15, Asp191, and His194, which belongs to carbohydrate esterase family 12. EstD1 can hydrolyze acetate at the C-3 position of 7-aminocephalosporanic acid (7-ACA) to form deacetyl-7-ACA, which is an important starting material for producing semisynthetic ß-lactam antibiotics. EstD1 retained more than 50% of its initial activity when incubated at pH values ranging from 4 to 11 at 65°C for 1 h. To the best of our knowledge, this enzyme is a new SGNH hydrolase identified from thermophiles that is able to hydrolyze 7-ACA. IMPORTANCE: Deacetyl cephalosporins are highly valuable building blocks for the industrial production of various kinds of semisynthetic ß-lactam antibiotics. These compounds are derived mainly from 7-ACA, which is obtained by chemical or enzymatic processes from cephalosporin C. Enzymatic transformation of 7-ACA is the main method because of the adverse effects chemical deacylation brought to the environment. SGNH hydrolases are widely distributed in plants. However, the tools for identifying and characterizing SGNH hydrolases from bacteria, especially from thermophiles, are rather limited. Here, our work demonstrates that EstD1 belongs to the SGNH family and can hydrolyze acetate at the C-3 position of 7-ACA. Moreover, this study can enrich our understanding of the functions of these enzymes from this family.

Cardiovascular comorbidities in patients with rosacea: A nationwide case-control study from Taiwan.

BACKGROUND: Rosacea is a chronic inflammatory skin disease. Inflammation plays a prominent role in atherosclerosis and its complications. OBJECTIVE: We sought to investigate the associations of rosacea with cardiovascular disease risk factors and cardiovascular diseases from a nationwide population-based database. METHODS: A total of 33,553 patients with rosacea and 67,106 age- and gender-matched control subjects were identified from the National Health Insurance Research Database in Taiwan from 1997 to 2010. Multivariate logistic regressions were performed to compare the odds of comorbidities between the 2 groups. RESULTS: Dyslipidemia (odds ratio 1.41; 95% confidence interval 1.36-1.46), coronary artery disease (odds ratio 1.35, 95% confidence interval 1.29-1.41), and hypertension (odds ratio 1.17, 95% confidence interval 1.12-1.21) were significantly associated with rosacea. Coronary artery disease remained independently associated with rosacea after adjustment for hypertension, diabetes mellitus, and dyslipidemia. Male patients with rosacea had higher risks for all comorbidities than female patients with rosacea. LIMITATIONS: The National Health Insurance Research Database does not contain information regarding rosacea subtypes or disease severity, or laboratory data. CONCLUSION: Patients with rosacea are more likely to have dyslipidemia and hypertension. They are also at increased risk of coronary artery disease after adjustment for cardiovascular disease risk factors.

Autoimmune disease comorbidities in patients with atopic dermatitis: a nationwide case-control study in Taiwan.

BACKGROUND AND OBJECTIVES: Atopic dermatitis (AD) is a chronic relapsing dermatitis of unknown etiology. It is thought that abnormal regulation of Th1 and Th2 is not only the major cause of AD, but also the vital pathogenesis of many autoimmune diseases. To date, no large-scale studies have been performed on the relationship between AD and autoimmune disease. By conducting a nationwide population-based study with case-controls in Taiwan, we sought to clarify the association of AD with other autoimmune diseases to obtain a better understanding of its pathogenesis. METHODS: Data were obtained from the National Health Insurance Research Database (NHIRD) of Taiwan from 1997 to 2010. In total, 41950 patients with AD and 167800 age- and gender-matched controls were enrolled. RESULTS: Patients with AD tended to have a high risk of associated lupus erythematosus (LE) (OR: 1.94, 95% CI: 1.48-2.54). The risk of LE was higher in female AD patients (OR: 2.05, 95% CI: 1.53-2.76) than in male AD patients (OR: 1.48, 95% CI: 0.76-2.85). Juvenile patients younger than 18 yrs with AD had higher risk of LE (OR: 3.02, 95% CI: 1.30-7.03) than adult patients with AD (OR: 1.68, 95% CI: 1.26-2.24). CONCLUSIONS: Our study confirmed the association between AD and LE. Early survey for LE in juvenile patients with AD is recommended.

Asiaticoside Attenuates Blood-Spinal Cord Barrier Disruption by Inhibiting Endoplasmic Reticulum Stress in Pericytes After Spinal Cord Injury.

The blood-spinal cord barrier (BSCB) plays a vital role in the recovery of spinal cord function after spinal cord injury (SCI). Pericytes, pluripotent members of the neurovascular unit (NVU), receive signals from neighboring cells and are critical for maintaining CNS function. Therapeutic targets for the BSCB include endothelial cells (ECs) and glial cells, but few drugs target pericytes. This study was designed to explore whether asiaticoside has a positively effect on pericytes and the integrity of the BSCB. In this study, we found that asiaticoside could inhibit the loss of junction proteins just 1 day after SCI in vivo, but our in vitro study showed no significant differences in the expression of endothelial junction proteins between the control and asiaticoside treatment groups. We also found that asiaticoside could inhibit endoplasmic reticulum (ER) stress and pericyte apoptosis, which might be associated with the inhibition of junction protein reduction in ECs. Thus, we investigated the interactions between pericytes and ECs. Our results showed that asiaticoside could decrease the release of matrix metalloproteinase (MMP)-9 in pericytes and therefore upregulate the expression of junction proteins in ECs. Furthermore, the protective effect of asiaticoside on pericytes is related to the inhibition of ER stress via the MAPK signaling pathway. Taken together, our results demonstrate that asiaticoside treatment inhibits BSCB disruption and enhances functional recovery after SCI.