Is Matrix Metalloproteinase-9 Associated with Post-Stroke Cognitive Impairment or Dementia?

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is a significant protease required for synaptic plasticity, learning, and memory. Yet, the role of MMP-9 in the occurrence and development of cognitive decline after ischemic stroke is not fully understood. In this study, we used clinical data experiments to further investigate whether MMP-9 and genetic polymorphism are associated with post-stroke cognitive impairment or dementia (PSCID). MATERIALS AND METHODS: A total of 148 patients with PSCID confirmed by the Montreal Cognitive Assessment (MoCA) 3 months after onset (PSCID group) were included in the study. The MMP-9 rs3918242 polymorphisms were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism, and the serum level of MMP-9 was measured using enzyme-linked immunosorbent assay (ELISA). The same manipulations have been done on 169 ischemic stroke patients without cognitive impairment (NCI group) and 150 normal controls (NC group). RESULTS: The expression level of serum MMP-9 in the PSCID group and NCI group was higher compared to the NC group, and the levels in the PSCID group were higher than that in the NCI group (all p < 0.05). Diabetes mellitus, hyperhomocysteinemia, and increased serum MMP-9 levels were the main risk factors of cognitive impairment after ischemic stroke. The serum level of MMP-9 was negatively correlated with the MoCA score, including visual-spatial executive, naming, attention, language, and delayed recall. Genetic polymorphism showed that TC genotype with MMP-9 rs3918242 and CC genotype were associated with a significantly increased risk of PSCID; moreover, the TC genotype significantly increased the risk of cognitive impairment. In the TCCC genotype of MMP-9 rs3918242, diabetes mellitus and hyperhomocysteinemia were associated with the increased risk of PSCID; also, hyperhomocysteinemia could increase the risk of cognitive impairment. CONCLUSIONS: MMP-9 level and MMP-9 rs3918242 polymorphism have an important role in the occurrence and development of post-stroke cognitive impairment or dementia (PSCID).

Relationship between MMP-9 serum levels and tHcy levels and total imaging load and cognitive dysfunction.

OBJECTIVES: To investigate the correlation and predictive value of serum matrix metalloproteinase-9 (MMP-9) level with cognitive dysfunction and total imaging load in patients with cerebral small vessel disease (CSVD). METHODS: A total of 80 patients with CSVD who were admitted to the First Affiliated Hospital of Xinxiang Medical University between April 2019 and April 2020 were enrolled. All subjects underwent T1-weighted imaging (T1WI), T2WI, fluid-attenuated inversion recovery (FLAIR), diffusion weighted imaging (DWI), serum sample collection, and assessment of cognitive function at a specific time-point after admission. According to the results of the neuropsychological test, subjects were divided into cognitive dysfunction group (n=40) and normal cognitive function group (n=40). The total imaging load was estimated according to the neuroimaging findings. Serum MMP-9 level was measured by an enzyme-linked immunosorbent assay (ELISA) kit. Beside, serum MMP-9 level and total imaging load were compared between the two groups. RESULTS: Serum levels of MMP-9 and plasma total homocysteine (tHcy) were negatively correlated with cognitive function (P<0.05). Serum MMP-9 level was found as a significant factor for diagnosing cognitive impairment due to CSVD (area under the curve (AUC), 0.756; sensitivity and specificity were 97.5% and 75.0%, respectively). THcy level was also found as significant factor for diagnosing cognitive impairment due to CSVD (area under the curve (AUC), 0.727; sensitivity and specificity were 97.5% and 75.0%, respectively). CONCLUSION: Serum MMP-9 level and tHcy level were significantly correlated with cognitive function in patients with CSVD. Serum MMP-9 level has a specific correlation with the total imaging load in patients with CSVD. It plays an important role in diagnosing cognitive impairment in patients with CSVD.

Highly Conductive Ti3 C2 Tx MXene Hybrid Fibers for Flexible and Elastic Fiber-Shaped Supercapacitors.

Fiber-shaped supercapacitors (FSCs) are promising energy storage solutions for powering miniaturized or wearable electronics. However, the scalable fabrication of fiber electrodes with high electrical conductivity and excellent energy storage performance for use in FSCs remains a challenge. Here, an easily scalable one-step wet-spinning approach is reported to fabricate highly conductive fibers using hybrid formulations of Ti3 C2 Tx MXene nanosheets and poly(3,4-ethylenedioxythiophene):polystyrene sulfonate. This approach produces fibers with a record conductivity of ≈1489 S cm-1 , which is about five times higher than other reported Ti3 C2 Tx MXene-based fibers (up to ≈290 S cm-1 ). The hybrid fiber at ≈70 wt% MXene shows a high volumetric capacitance (≈614.5 F cm-3 at 5 mV s-1 ) and an excellent rate performance (≈375.2 F cm-3 at 1000 mV s-1 ). When assembled into a free-standing FSC, the energy and power densities of the device reach ≈7.13 Wh cm-3 and ≈8249 mW cm-3 , respectively. The excellent strength and flexibility of the hybrid fibers allow them to be wrapped on a silicone elastomer fiber to achieve an elastic FSC with 96% capacitance retention when cyclically stretched to 100% strain. This work demonstrates the potential of MXene-based fiber electrodes and their scalable production for fiber-based energy storage applications.

Elastic Fiber Supercapacitors for Wearable Energy Storage.

The development of wearable devices such as smart watches, intelligent garments, and wearable health-monitoring devices calls for suitable energy storage devices which have matching mechanical properties and can provide sufficient power for a reasonable duration. Stretchable fiber-based supercapacitors are emerging as a promising candidates for this purpose because they are lightweight, flexible, have high energy and power density, and the potential for easy integration into traditional textile processes. An important characteristic that is oftentimes ignored is stretchability-fiber supercapacitors should be able to accommodate large elongation during use, endure a range of bending motions, and then revert to its original form without compromising electrical and electrochemical performance. This article summarizes the current research progress on stretchable fiber-based supercapacitors and discusses the existing challenges on material preparation and fiber-based device fabrication. This article aims to help researchers in the field to better understand the challenges related to material design and fabrication approaches of fiber-based supercapacitors, and to provide insights and guidelines toward their wearability.

IL-33 Aggravates DSS-Induced Acute Colitis in Mouse Colon Lamina Propria by Enhancing Th2 Cell Responses.

Interleukin- (IL-) 33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated diseases. IL-33 was expressed in high level on epithelial cells of intestinal tract. It suggested that IL-33 plays a potential role in inflammatory bowel diseases (IBD). We investigated the role of interleukin- (IL-) 33 in dextran sulphate sodium- (DSS-) induced acute colitis in mice using recombinant mouse IL-33 protein (rIL-33). We found that DSS-induced acute colitis was aggravated by rIL-33 treatment. rIL-33-treated DSS mice showed markedly reduced levels of interferon- (IFN-)γ and IL-17A in their colon lamina propria lymphocytes (LPL), but the levels of Th2 cytokines, such as IL-5 and IL-13, in these cells were significantly increased, compared to DSS mice treated with PBS. Our results suggested that IL-33 stimulated CD4(+)T cells and caused the cell to adopt a Th2-type response but at the same time suppressed Th17 and Th1 cell responses. Therefore, IL-33 may be involved in pathogenesis of DSS-induced acute colitis by promoting Th2 cell response in intestinal mucosa of mice. Modulation of IL-33/ST2 signaling by monoclonal antibody (mAb) could be a novel biological therapy in DSS-induced acute colitis.

Analysis of 1782 Pediatric Hoarseness Cases: A Clinical Retrospect Study.

OBJECTIVE: This study aims to clarify the clinical characteristics of pediatric voice disorders. METHODS: The clinical data of 1782 pediatric patients presenting with voice disorders were retrospectively analyzed. These cases were categorized into four age-based cohorts: 0-3, 4-7, 8-11, and 12-15years. Variables such as gender disparities, laryngoscopic manifestation, disease types, and acoustic parameters were thoroughly examined. RESULTS: A total of 1782 children with acoustic hoarseness were included in this study, comprising 1325 males and 457 females. When the sex ratio among the children in each group was compared, males were found to outnumber females. A notable male predominance was observed across all age groups. Laryngoscopic results revealed that the most prevalent condition was vocal cord nodules (1363 cases, 76.48%), followed by vocal cord polyps (271 cases, 15.20%). Other diseases included laryngeal papillomas, vocal fold movement impairment, vocal cord cysts, functional dysphonia, leukoplakia of the vocal cords, and benign laryngeal tumors such as laryngeal amyloidosis and subglottic granular cell tumors. Among these, adenoid hypertrophy was presented in 382 children (21.44%). Additionally, the Reflux Finding Score (RFS) was conducted, and 799 cases (44.83%) were found to have a score above 7. The distribution of various diseases across different age groups indicated that children with vocal cord nodules (637 cases, 46.74%), vocal cord polyps (109 cases, 40.22%), and laryngeal papillomas (35, 36.84%) were predominantly found in the 4-7 years age group. Pediatric acute laryngitis (three cases, 75%) and vocal fold movement impairment (eight cases, 36.36%) were more common in the 0-3 years age group. Functional dysphonia (four cases, 66.67%) and vocal cord leukoplakia (four cases, 80%) were mainly observed in the 12-15 years age group, while vocal cord cysts were predominantly seen in the 8-11 years age group (four cases, 57.14%). A comparative analysis of acoustic parameters among 153 children showed statistically significant differences in jitter, fundamental frequency (F0), voice handicap index (VHI), reflux symptom index (RSI), and RFS across different pathologies. CONCLUSION: This study highlighted that vocal cord nodules, vocal cord polyps, and laryngeal papillomas were the primary causes of pediatric hoarseness, although the possibility of tumors and rare diseases cannot be disregarded. There was a noticeable gender bias towards males, and functional dysphonia was significantly more prevalent in older children.

Serum exosomal miR-146a-3p associates with disease severity and efficacy of sublingual immunotherapy in allergic rhinitis.

BACKGROUND: Sublingual immunotherapy (SLIT) is an effective treatment for allergic rhinitis (AR), but its efficacy is variable among individuals. This study aimed to characterize serum exosome-derived microRNAs (miRNAs) and evaluate their abilities in predicting the efficacy of SLIT in AR. METHODS: RNA sequencing was performed to explore differentially expressed exosomal miRNAs in serum exosomes between AR patients and healthy controls (HCs). Sequencing analysis results were verified in an independent cohort, and the correlations between the levels of exosome-derived miRNAs and disease severity were evaluated. The most promising miRNAs were further tested in two AR cohorts treated with SLIT to assess their abilities in predicting short and long-term efficacy, respectively. RESULTS: The exosome-derived miRNAs profiling in the AR group was significantly different from the HC group, and differentially expressed genes were enriched and clustered in pathways such as PI3K-Akt and ErbB signalling pathways. The top three most significant miRNAs were verified by reverse transcription-polymerase chain reaction (qRT-PCR), and results showed that miR-146a-3p levels were significantly elevated in the AR group and correlated with the total and specific gE levels, the visual analogue scale of the total nasal symptom score (all p < 0.05). Further data in the first validation cohort suggested that miR-146a-3p levels were significantly downregulated in the effective group, and logistic regression showed that miR-146a-3p levels were associated with the short-term efficacy of SLIT(p < 0.05). The receiver operating characteristic (ROC) curve showed that miR-146a-3p could early predict SLIT efficacy (AUC = 0.669, p = 0.047). In the second validation cohort, miR-146a-3p levels were also decreased in the effective group and the ROC curve further confirmed its reliable accuracy in predicting the long-term efficacy of SLIT in AR patients (AUC = 0.749, p < 0.001). CONCLUSION: Serum exosome-derived miRNAs may be involved in the development of AR and associated with its disease severity. Serum exosome-derived miR-146a-3p seems to be a novel biomarker for predicting the short and long-term efficacies of SLIT in AR patients.

SKP2 Contributes to AKT Activation by Ubiquitination Degradation of PHLPP1, Impedes Autophagy, and Facilitates the Survival of Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid carcinoma. Despite a good prognosis, approximately a quarter of PTC patients are likely to relapse. Previous reports suggest an association between S-phase kinase-associated protein 2 (SKP2) and the prognosis of thyroid cancer. SKP1 is related to apoptosis of PTC cells; however, its role in PTC remains largely elusive. This study aimed to understand the expression and molecular mechanism of SKP2 in PTC. SKP2 expression was upregulated in PTC tissues and closely associated with clinical diagnosis. In vitro and in vivo knockdown of SKP2 expression in PTC cells suppressed cell growth and proliferation and induced apoptosis. SKP2 depletion promoted cell autophagy under glucose deprivation. SKP2 interacted with PH domain leucine-rich repeat protein phosphatase-1 (PHLPP1), triggering its degradation by ubiquitination. Furthermore, SKP2 activates the AKT-related pathways via PHLPP1, which leads to the cytoplasmic translocation of SKP2, indicating a reciprocal regulation between SKP2 and AKT. In conclusion, the upregulation of SKP2 leads to PTC proliferation and survival, and the regulatory network among SKP2, PHLPP1, and AKT provides novel insight into the molecular basis of SKP2 in tumor progression.

The effect of VAV3 polymorphisms on thyroid cancer.

BACKGROUND: The incidence of thyroid cancer is rising rapidly in China, but there are few studies on the risk factors of thyroid cancer in the Chinese Han population. METHODS: We performed this case-control study of 510 patients and 509 controls to for determine the linkage of VAV3 variants (rs17019602, rs7521681, rs4915076, and rs1777451) with thyroid cancer susceptibility by computing the odds ratio (OR) and 95% confidence intervals (CI). Multi-factor dimension reduction (MDR) analysis was conducted to assess interaction of VAV3 genetic variants. RESULTS: We found that rs7521681 was remarkably related to a higher risk of thyroid cancer (OR = 1.74, p = 0.012), whereas rs4915076 (OR = 0.66, p = 0.001) significantly decreased thyroid cancer susceptibility. Stratified analyses showed that rs4915076 had a protective role in thyroid cancer in both ages >45 years (OR = 0.70, p = 0.017) and age ≤45 years (OR = 0.63, p = 0.007). Rs17019602 could increase the susceptibility of thyroid cancer in men (OR = 4.76, p = 0.049). Rs7521681 was related to an increased risk of thyroid cancer in women (OR = 1.97, p = 0.012). Rs4915076 could protect individuals from thyroid cancer both in men (OR = 0.60, p = 0.031) and women (OR = 0.68, p = 0.010). Moreover, rs4915076 was the best single-locus model to predict thyroid cancer. Interestingly, the interaction model of rs17019602, rs7521681, rs4915076, rs1777451, and age was a candidate gene-environment model. CONCLUSION: Our results indicated VAV3 variants were associated with thyroid cancer, which provides a new sight into etiology of thyroid cancer.

Review of aromatherapy essential oils and their mechanism of action against migraines.

ETHNOPHARMACOLOGICAL RELEVANCE: Migraines have become a major threat to human health, as they significantly affect human health and quality of life due to a high prevalence rate, attack rate and pain intensity. Aromatherapy, with its comfortable and pleasant natural characteristics and rapid and efficient characteristics, is widely favored by patients in the folk. Chinese folk also have the application history and related records of aromatic plants in the treatment of migraine. AIM OF THE STUDY: This study was conducted to review the pathogenesis of migraine, the application of plant essential oils in the treatment of migraine, and further explore the material basis and mechanism of action of plant essential oils against migraine. MATERIALS AND METHODS: Search the electronic literature of essential oils with anti-migraine effect in Google Scholar, PubMed and China National Knowledge Infrastructure, and further search the research situation of the monomer components of essential oils in migraine, inflammation, pain and other aspects. RESULTS: studies show that there are 10 types of plant essential oils that could relieve migraine symptoms, and that 16 monomers may play a role in migraine treatment by effectively inhibiting neurogenic inflammation, hyperalgesia and balancing vasorelaxation. CONCLUSION: Aromatic plant essential oils can relieve migraine effectively, these findings can be used as an important part of the development of anti-migraine drugs.

Oridonin Induces Apoptosis of Laryngeal Carcinoma via Endoplasmic Reticulum Stress.

PURPOSE: Oridonin, a bioactive diterpenoid derived from Rabdosia rubescens, has been widely reported to exhibit anticancer activity in multiple types of cancer. However, the molecular mechanism of oridonin in human laryngeal carcinoma has not been clearly elucidated. This study investigated the function of oridonin in laryngeal carcinoma to provide a research basis for laryngeal carcinoma therapy. METHODS: The proliferation of laryngeal carcinoma Hep-2 and TU212 cells treated with oridonin was determined by MTT assay. The apoptotic induction effect of oridonin on Hep-2 and TU212 cells was analyzed by flow cytometry, Western blot analysis and caspase3 activity assay. In addition, the caspase inhibitor, Z-VAD-fmk, was synergistically treated with oridonin to detect the function of caspase cascade in oridonin-mediated apoptosis. Then, the expressions of endoplasmic reticulum (ER) stress-related proteins (GRP78, phosphorylated-PERK, phosphorylated-eIF2α and CHOP) were measured in Hep-2 and TU212 cells by Western blotting. The cells were treated with 4-PBA (an ER stress inhibitor) or knockdown of CHOP to explore the role of ER stress in oridonin-mediated apoptosis in laryngeal carcinoma. Subsequently, a nude mouse xenograft model was constructed to confirm the function of oridonin in laryngeal carcinoma in vivo. RESULTS: Oridonin was found to significantly inhibit the proliferation of laryngeal carcinoma Hep-2 and TU212 cells in a concentration-dependent manner. Then, we confirmed that oridonin could induce apoptosis in human laryngeal carcinoma cells. The caspase inhibitor, Z-VAD-fmk, could partially reverse the pro-apoptotic effect of oridonin on human laryngeal carcinoma cells. Subsequently, Western blotting analysis demonstrated that endoplasmic reticulum (ER) stress-related proteins (GRP78, phosphorylated-PERK, phosphorylated-eIF2α and CHOP) were up-regulated in Hep-2 and TU212 cells exposed to oridonin. In addition, 4-PBA (an ER stress inhibitor) or knockdown of CHOP could antagonize oridonin-induced apoptosis. Oridonin significantly decreased the tumorigenicity of Hep-2 cells in a nude mouse xenograft model. CONCLUSION: Oridonin-induced apoptosis of human laryngeal carcinoma through the activation of ER stress.

Suppression of Th17 Cell Response in the Alleviation of Dextran Sulfate Sodium-Induced Colitis by Ganoderma lucidum Polysaccharides.

BACKGROUND: Ganoderma lucidum polysaccharides (GLP) has anti-inflammatory and immunomodulatory effects. Dysregulated immune responses are involved in the pathogenesis of dextran sulfate sodium (DSS)-induced colitis. The aim of this study was to assess the therapeutic potential of GLP to alleviate DSS-induced colitis. METHODS: The mice were administered with GLP by intragastric gavage daily for two weeks prior to the DSS treatment. Mice were orally administered with 2.5% DSS dissolved in drinking water with GLP or water treatment for 6 days. The mice were killed on day 7 after induction of colitis. Survival rates, body weight loss, colon lengths, histological changes, and disease activity index scores (DAI) were evaluated. RESULTS: GLP significantly improved survival rates, colon length shortening, body weight loss, histopathological score, and DAI scores in mice with DSS-induced colitis. GLP markedly suppressed the secretions of TNF-α, IL-1ß, IL-6, IL-17A, and IL-4 and significantly affected populations of Th17 cells, B cells, NK cells, and NKT cells in the lamina propria lymphocytes. CONCLUSIONS: GLP prevented inflammation, maintained intestinal homeostasis, and regulated the intestinal immunological barrier functions in mice with DSS-induced colitis.

Th1/Th2 Balance and Th17/Treg-Mediated Immunity in relation to Murine Resistance to Dextran Sulfate-Induced Colitis.

BACKGROUND: The role of the Th17/Treg balance in the development of experimental colitis remains poorly understood. METHODS: We exploited the differential response of BALB/c mice and C57BL/6 mice towards drinking water mediated by dextran sulfate sodium (DSS) challenge. RESULTS: DSS-resistant BALB/c mice were characterized by low levels of IFN-γ and TNF-α but high levels of IL-4, IL-6, IL-10, IL-17A, IL-17F, and colon lamina propria and mesenteric lymph node (MLN) CD4+CD25+FoxP3+ T cells when compared to C57BL/6 mice. Collectively, these data indicate the propensity of BALB/c mice towards a Th2/Th17/Treg-polarized immunity protecting these animals against DSS challenge, whereas Th1-polarization of C57BL/6 mice confers sensitivity to DSS-induced colitis. CONCLUSIONS: The intrinsic congenital capacity of mouse strains with respect to T cell proliferation determines sensitivity to experimental colitis.

Sodium selenite ameliorates dextran sulfate sodium-induced chronic colitis in mice by decreasing Th1, Th17, and γδT and increasing CD4(+)CD25(+) regulatory T-cell responses.

AIM: To assess the effect of sodium selenite on the severity of dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice. METHODS: Mice were randomly divided into four groups (n = 10/group): normal group, selenium (Se) group, chronic colitis group, and Se + chronic colitis group. The mice were sacrificed on day 26. Survival rates, clinical symptoms, colon length, and histological changes were determined. The percentages and absolute numbers of immune system cells in the lamina propria lymphocytes (LPL) of the colon, the expression of mRNA in colon tissue, and the concentrations of Th1, Th17, and Treg cytokines in LPL from the large intestine, were measured. RESULTS: Se significantly ameliorated the symptoms of colitis and histological injury (P < 0.05 each), increasing the proportions of neutrophils and CD4+ CD25+ T cells (P < 0.05 each) and decreasing the proportions of γδT cells, CD4+, CD4+CD44+, and CD4+ CD69+ T cells in LPL (P < 0.05 each). Moreover, Se reduced the expression of IL-6, IFN-γ, IL-17A, IL-21, T-bet, and RORγt (P < 0.05 each), but enhanced the expression of IL-10 and Foxp3 (P < 0.05 each). CONCLUSION: These results suggest that Se protects against DSS-induced chronic colitis perhaps by increasing the number of CD4(+)CD25(+) Tregs that suppress the secretion of proinflammatory cytokines and populations of Th1, Th17, and γδT cells.

Dextran sulfate sodium-induced acute experimental colitis in C57BL/6 mice is mitigated by selenium.

BACKGROUND: Sodium selenite has been shown to have a protective role in experimental colitis. Th1 and Th17 responses are involved in the pathogenesis of dextran sulfate sodium (DSS)-induced colitis and inflammatory bowel disease. This study investigated whether sodium selenite can suppress Th1/Th17-mediated experimental colitis. METHODS: Mice were administered sodium selenite (2µg/g body weight) by gavage daily for 30days. Beginning on day 21, mice were administered 2.5% oral DSS for 9days. The mice were sacrificed on day 31. Survival rates, clinical symptoms, colon lengths, and histological changes were determined. RESULTS: Pretreatment with sodium selenite (2µg/g body weight) improved survival rates, colon shortening, body weight loss, disease activity index, and histopathological score in mice with DSS-induced colitis. Pretreatment with sodium selenite restored interleukin-10 and Foxp3 excretion, as well as reducing the levels of interferon-γ and interleukin-17A. CONCLUSIONS: Pretreatment with sodium selenite showed therapeutic potential for preventing colitis in mice. This effect may be mediated by the immunomodulation of regulatory T cells, expressing anti-inflammatory genes that suppress Th1 and Th17 responses.

IL-33 alleviates DSS-induced chronic colitis in C57BL/6 mice colon lamina propria by suppressing Th17 cell response as well as Th1 cell response.

Interleukin (IL)-33, a member of the IL-1 cytokine family, is associated with autoimmune diseases including inflammatory bowel diseases (IBD). A few studies on animal models have shown that IL-33 can suppress Th1 cell response and improve Th2 cell response in mesenteric lymph nodes (MLN) and sera. However, there is little data published about the effect of IL-33 on Th17 cell in and Th1/Th2 cell in colon lamina propria. The aim of this study was to investigate the effect of IL-33 on Th17 cell in colon lamina propria of mice with dextran sulfate sodium (DSS) induced chronic colitis. We studied the influence of IL-33 on colonic tissue injury and clinical symptoms of colitis. The T cell subsets were measured by flow cytometry and the production of cytokines secreted by lamina propria lymphocytes (LPL) was measured by Enzyme-Linked Immunosorbent Assay (ELISA) and quantitative real-time PCR. We have found that rIL-33 treatment led to a significant alleviation of DSS induced chronic colitis as evidenced by 1) alleviation of weight loss, DAI, macroscopic changes and histological score; 2) down-regulating the rates and absolute cell numbers of Th17 and Th1 cell in LPL; 3) inducing secretion of lower levels of IFN-γ and IL-17A. It is therefore concluded that IL-33 may play a therapeutic role in DSS-induced chronic colitis in mice by suppressing Th17 response and switching Th1 to Th2 response.

CD226 as a genetic adjuvant to enhance immune efficacy induced by Ag85A DNA vaccination.

Antigen-85A (Ag85A) is one of the major proteins secreted by Mycobacterium tuberculosis. Many studies on animal models have shown that vaccination with the recombinant Ag85A-DNA or Ag85A protein induces powerful immune response. However, these vaccines cannot generate sufficient protective immunity in the systemic compartment. CD226, a member of the immunoglobulin superfamily, is expressed in the majority of NK cells, T cells, monocytes, and platelets, and can be served as a co-stimulator that contributes to multiple innate and adaptive responses. However, there has been no study where either CD226 protein or DNA has been used as an adjuvant for vaccine development. The aim of this study was to develop a novel Ag85A DNA vaccine with CD226 as the genetic adjuvant to increase the immune efficacy induced by Ag85A. Oral vaccination with pcDNA3.1-Ag85A-CD226 DNA induced potent immune responses in mice. CD226 was an effective genetic adjuvant that improved the immune efficacy induced by Ag85A and enhanced the activity of cytotoxic T lymphocytes (CTL) and NK cells in mice. Th1 dominant cytokines (i.e. IL-2, IFN-γ and TNF-α), cellular immunity (i.e. CD4(+)IFN-γ(+)T cells and CD8(+)IFN-γ(+)T cells in splenocytes) and MLNs were also significantly elevated by pcDNA3.1-Ag85A-CD226 DNA vaccination. Our results suggest that CD226 is an effective adjuvant to enhance the immune efficacy induced by Ag85A. Our findings provide a new strategy for the development of a DNA vaccine co-expressing Ag85A and CD226.

Enhanced therapeutic effects against murine colon carcinoma induced by a Colon 26/Ag85A-CD226 tumor cell vaccine.

Genetically modified tumor cells represent one of the most effective cancer vaccine strategies. In the present study, we describe our approach for inducing an immune response against a colon carcinoma in BALB/c mice, using a Colon 26 tumor cell line expressing Ag85A and CD226. We investigated whether CD226 plays a promotive role for Ag85A against Colon 26 colon carcinoma. The therapeutic efficacy was investigated. The cytotoxic T lymphocyte (CTL) and natural killer (NK) cell cytotoxicity were assessed. Dynamic changes in interferon (IFN)-γ levels in the spleen and the number of IFN-γ-producing CD4+ or CD8+ T cells in the spleen or mesenteric lymph nodes were detected by enzyme-linked immunoabsorbent assay or flow cytometry. Extended survival times, delayed appearances of tumors, and reduced tumor volumes were achieved by preventive vaccination with the Colon 26/Ag85A-CD226 tumor cell vaccine. NK cell or CTL cytotoxicity in the spleens of mice immunized with the Colon 26/Ag85A-CD226 tumor cell vaccine was significantly higher than that in the other treatment groups. The numbers of CD4+ IFN-γ+ and CD8+ IFN-γ+ T cells were both significantly increased in mice immunized with the Colon 26/Ag85A-CD226 tumor cell vaccine in both the spleen and mesenteric lymph nodes. Our results indicated that the tumor vaccine expressing Ag85A and CD226 induced more intensive antitumor immunity than tumor vaccine expressing Ag85A or CD226 only. Moreover, the results suggest that Ag85A and CD226 play a synergistic antitumor effect and CD226 could be used as a genetic adjuvant to enhance the effects of Ag85A vaccine against murine colon carcinoma.