Prognostic value and immunological function of cuproptosis-related genes in lung adenocarcinoma.

Background: Lung cancer is one of the malignant tumors with the highest morbidity and fatality rates worldwide. The overall survival (OS) of lung adenocarcinoma (LUAD) is poor. Cuproptosis is a copper-triggered modality of mitochondrial cell death, however, its contribution to the emergence of lung cancer is unknown. The clinical implication and immunological function of cuproptosis-related genes (CRGs) in LUAD has yet to be established. Methods: TCGA, HPA, GEPIA, Kaplan-Meier, TIMER and CancerSEA database were used to explore the prognostic value and biological function of CRGs in LUAD. Results: CRGs are primarily involved in copper ion transport, the citrate cycle (TCA cycle) and central carbon metabolism in LUAD. The mRNA expression of COA6, UBE2D1, DLAT, SLC25A3, and DBH was significantly increased. The expression of COA6, DLAT, SLC25A3, DBH, and LOXL2 were all strongly associated with the clinicopathological stages in LUAD. Moreover, high expression of COA6, UBE2D1, DLAT, SLC25A3 and LOXL2 was related to poor OS. The expression of SLC25A3 and LOXL2 showed different association with immune cell infiltration. The single cell sequencing demonstrated that CRGs play important roles in the regulation of DNA damage response, inflammation and metastasis in LUAD. Conclusions: In summary, this study comprehensively uncovered that CRGs could be identified as potential prognostic and immunological biomarkers in LUAD. Our current research could provide a solid theoretical basis for LUAD survival research and clinical decision-making.

Astaxanthin exerts an adjunctive anti-cancer effect through the modulation of gut microbiota and mucosal immunity.

This study aimed to investigate the function of gut microbiota in astaxanthin's adjuvant anticancer effects. Our prior research demonstrated that astaxanthin enhanced the antitumor effects of sorafenib by enhancing the body's antitumor immune response; astaxanthin also regulated the intestinal flora composition of tumor-bearing mice. However, it is presently unknown whether this beneficial effect is dependent on the gut microbiota. We first used broad-spectrum antibiotics to eradicate gut microbiota of tumor-bearing mice, followed by the transplantation of fecal microbiota. The results of this study indicate that the beneficial effects of astaxanthin when combined with molecular targeting are dependent on the presence of intestinal microbiota. Astaxanthin facilitates the infiltration of CD8+ T lymphocytes into the tumor microenvironment and increases Granzyme B production by modulating the intestinal flora. Therefore, it strengthens the body's anti-tumor immune response and synergistically boosts the therapeutic efficacy of drugs. Astaxanthin stimulates the production of cuprocytes and mucus in the intestines by promoting the proliferation of Akkermansia. In addition, astaxanthin enhances the intestinal mucosal immunological function. Our research supports the unique ability of astaxanthin to sustain intestinal flora homeostasis and its function as a dietary immune booster for individuals with tumors.

Integrated investigation and experimental validation of PPARG as an oncogenic driver: implications for prognostic assessment and therapeutic targeting in hepatocellular carcinoma.

Peroxisome proliferator-activated receptor gamma (PPARG), a key transcription factor involved in lipid metabolism and glucose homeostasis, has been implicated in various types of cancer. However, its precise role in cancer remains unclear. In this study, we conducted a comprehensive pan-cancer analysis of PPARG expression using various types of cancer obtained from public databases. We observed significant heterogeneity in PPARG expression across different types of cancer. The association between PPARG expression and patient prognosis was investigated using Cox proportional hazards regression models and survival analysis. Clinical features and protein expression levels in the cohort showed that PPARG expression was strongly associated, suggesting its potential as a therapeutic target. We also evaluated the prognostic potential of PPARG by analyzing immune infiltration and genomic stability. We experimentally validated the potential of PPARG as a therapeutic target by analyzing drug sensitivity profiles, molecular docking simulations, and in vitro cell proliferation assays associated with PPARG expression. We identified common expression patterns of PPARG with other genes involved in key carcinogenic pathways. This provides deeper insights into the molecular mechanisms underlying its carcinogenic role. Additionally, functional enrichment analysis revealed significant enrichment of genes related to drug metabolism, cell proliferation, and immune response pathways associated with PPARG. Our findings highlight the importance of PPARG in the broader biology of cancer and suggest its potential as a diagnostic and therapeutic target for specific types of cancer. The results of our study provide strong support for the potential role of PPARG as a promising prognostic biomarker and immunotherapeutic target across various types of cancer.

Classification and function of γδT cells and its research progress in anti-glioblastoma.

Human peripheral blood T lymphocytes are classified into alpha-beta T (αßΤ) cells and gamma-delta T (γδΤ) cells based on the difference in T cell receptors (TCRs). αßT cells are crucial for the acquired immune response, while Î³Î´Τ cells, though only a small subset, can recognize antigenic substances. These antigens do not need to be processed and presented and are not restricted by MHC. This distinguishes Î³Î´Τ cells from αßT cells and highlights their distinct role in innate immunity. Despite their small number, Î³Î´Τ cells hold significant significance in anti-tumor, anti-infection and immune regulation. Glioblastoma (GBM) represents one of the most prevalent malignant tumors within the central nervous system (CNS). Surgical resection alone proves to be an ineffective method for curing this type of cancer. Even with the combination of surgical resection, radiotherapy, and chemotherapy, the prognosis of some individuals with glioblastoma is still poor, and the recurrence rate is high. In this research, the classification, biological, and immunological functions of γδT cells and their research progress in anti-glioblastoma were reviewed.

Immunity and reproduction protective effects of Chitosan Oligosaccharides in Cyclophosphamide/Busulfan-induced premature ovarian failure model mice.

Introduction: Premature ovarian failure (POF) is a major cause of infertility among women of reproductive age. Unfortunately, there is no effective treatment available currently. Researchers have shown that immune disorders play a significant role in the development of POF. Moreover, growing evidence suggest that Chitosan Oligosaccharides (COS), which act as critical immunomodulators, may have a key role in preventing and treating a range of immune related reproductive diseases. Methods: KM mice (6-8 weeks) received a single intraperitoneal injection of cyclophosphamide (CY, 120mg/kg) and busulfan (BUS, 30mg/kg) to establish POF model. After completing the COS pre-treatment or post-treatment procedures, peritoneal resident macrophages (PRMs) were collected for neutral erythrophagocytosis assay to detect phagocytic activity. The thymus, spleen and ovary tissues were collected and weighed to calculate the organ indexes. Hematoxylin-eosin (HE) staining was performed to observe the histopathologic structure of those organs. The serum levels of estrogen (E2) and progesterone (P) were measured via the enzyme-linked immunosorbent assay (ELISA). The expression levels of immune factors including interleukin 2 (IL-2), interleukin 4 (IL-4), and tumor necrosis factor α (TNF-α), as well as germ cell markers Mouse Vasa Homologue (MVH) and Fragilis in ovarian tissue, were analyzed by Western blotting and qRT-PCR. In addition, ovarian cell senescence via p53/p21/p16 signaling was also detected. Results: The phagocytic function of PRMs and the structural integrity of thymus and spleen were preserved by COS treatment. The levels of certain immune factors in the ovaries of CY/BUS- induced POF mice were found to be altered, manifested as IL-2 and TNF-α experiencing a significant decline, and IL-4 presenting a notable increase. Both pre-treatment and post-treatment with COS were shown to be protective effects against the damage to ovarian structure caused by CY/BUS. Senescence-associated ß-galactosidase (SA-ß-Gal) staining results showed that COS prevents CY/BUS-induced ovarian cell senescence. Additionally, COS regulated estrogen and progesterone levels, enhanced follicular development, and blocked ovarian cellular p53/p21/p16 signaling which participating in cell senescence. Conclusion: COS is a potent preventative and therapeutic medicine for premature ovarian failure by enhancing both the ovarian local and systemic immune response as well as inhibiting germ cell senescence.

Correlation between TCM syndrome and clinical indicators and disease activity in Sjogren's syndrome / 国际中医中药杂志

Objective:To explore the correlation between Traditional Chinese Medicine (TCM) syndrome types of Sj?gren syndrome (SS) and blood test parameters, immunological function and disease activity.Methods:A retrospective cross-sectional study was conducted. The clinical data of 242 SS inpatients in the Rheumatology and Immunology Department of Jiangsu Province Hospital of TCM from February 2021 to June 2022 were analyzed retrospectively. We compared the general data (gender, age, course of disease, BMI), blood parameters [WBC, hemoglobin (Hb), PLT, neutrophil count (NEUT), lymphocyte count(LYMPH), neutrophil/lymphocyte ratio (NLR)], immunological indicators (globulin, IgG, IgA, IgM, rheumatoid factor (RF), anti-SSA antibody, anti-SSB antibody, anti-Ro-52 antibody) .The distribution difference of disease activity [Disease Activity Index of Sjogren's syndrome (ESSDAI) and Patient Report Index of Sjogren's syndrome (ESSPRI)], the correlation between each syndrome type and blood routine parameters, immunological indicators and inflammatory indicators was analyzed by binary logistic regression.Results:They were divided into 82 cases of qi yin deficiency syndrome, 61 cases of yin deficiency and fluid deficiency syndrome, 59 cases of yin deficiency and blood stasis syndrome, 32 cases of yin deficiency and heat toxin syndrome, and 8 cases of other syndrome types. Because the number of other syndrome types was small, they were not included in this study. Logistic regression analysis showed that the positive rate of anti SSA antibody was negatively correlated with IgM [ OR (95% CI)=0.570 (0.407, 0.798)] ( P<0.01). The positive rates of anti SSB antibody and anti Ro-52 antibody were negatively correlated with LYMPH [ OR (95% CI)=0.445 (0.223, 0.886), 0.457 (0.224, 0.932), respectively] ( P<0.05). The positive rates of anti SSB antibody and anti Ro-52 antibody were positively correlated with IgG [ OR (95% CI)=1.171 (1.034, 1.325), 1.159 (1.014, 1.325), respectively] ( P<0.05). Qi Yin deficiency syndrome was positively correlated with WBC [ OR (95% CI)=2.590 (1.120, 5.987)] ( P<0.05), and negatively correlated with LYMPH [ OR (95% CI)=0.090 (0.017, 0.470)] and IgA [ OR (95% CI)=0.728 (0.553, 0.959)] ( P<0.05). Yin deficiency and fluid deficiency syndrome were negatively correlated with PLT [ OR (95% CI)=0.991 (0.984, 0.998)], ESSPRI [ OR (95% CI)=0.705 (0.506, 0.983)], ESSDAI [ OR (95% CI)=0.716 (0.534, 0.960)] ( P<0.05). Yin deficiency and blood stasis syndrome was positively correlated with IgA [ OR (95% CI)=1.184 (1.028, 1.363)] ( P<0.05), and negatively correlated with anti SSB antibody positive rate [ OR (95% CI)=0.247 (0.093, 0.659)] ( P<0.05). Yin deficiency heat toxin syndrome was positively correlated with IgA [ OR (95% CI)=1.368 (1.037, 1.803)] ( P<0.05), and negatively correlated with anti SSB antibody positive rate [ OR (95% CI)=0.278 (0.085, 0.909)] ( P<0.05). Conclusion:The level of immunoglobulin, inflammatory index and disease activity of yin deficiency and blood stasis syndrome and yin deficiency and heat toxin syndrome are high, and blood system damage and exocrine gland disease are easy to occur, which can provide clinical basis for the combination of disease and syndrome differentiation and treatment of SS.

High miRNA-378 expression has high diagnostic values for pulmonary tuberculosis and predicts adverse outcomes.

BACKGROUND: Pulmonary tuberculosis (TB) is a chronic infectious disease. microRNA (miR)-378 is involved in TB diagnosis. This study explored the effects of miR-378 on TB patients. METHODS: A total of 126 TB patients were selected, including 63 active TB and 63 latent TB, with 62 healthy subjects as controls. Serum miR-378 expression was detected. The diagnostic value of miR-378 in TB was analyzed using the ROC curve. Immune inflammatory factor levels were detected and their correlations with miR-378 expression were analyzed. The drug resistance of active TB patients was recorded after standard treatment. miR-378 expression in drug-resistant TB patients was detected. The effects of miR-378 on adverse outcome incidence were analyzed. RESULTS: miR-378 expression was highly expressed in TB and the expression was higher in the active group than the latent group. Serum miR-378 expression > 1.490 had high sensitivity and specificity in TB diagnosis. miR-378 expression was correlated with TB clinical indexes. IL-4, IL-6, and IL-1ß levels were highly expressed, while IFN-γ, TNF-α, and IL-12 levels were lowly expressed in TB patients. Serum miR-378 level in the active group was positively correlated with serum IL-4, IL-6, and IL-1ß, and negatively correlated with serum IFN-γ, TNF-α, and IL-12 concentrations. miR-378 expression was downregulated in the TB treated, single (SDR TB) and multi-drug resistance (MDR TB) groups, the miR-378 expression in SDR TB and MDR TB groups was higher than the TB treated group and lower in the SDR TB group than the MDR TB group. High miR-378 expression predicted higher adverse outcome incidence. CONCLUSIONS: High miR-378 expression assisted TB diagnosis and predicted adverse outcomes.

Mycotoxins binder supplementation alleviates aflatoxin B1 toxic effects on the immune response and intestinal barrier function in broilers.

This experiment was conducted to evaluate whether a commercial mycotoxins-binder, XL, could effectively attenuate the negative effects of Aflatoxin B1 (AFB1) on growth performance, immunological function, and intestinal health in birds. Two hundred forty 1-day-old Arbor Acres broiler chickens were randomly divided into 4 treatments using a 2 × 2 factorial randomized design with 2 levels of dietary mycotoxins binder (0 or 2g /kg) and 2 AFB1 supplemented levels (0 or 200 µg/kg) from 0 to 42 d. Results showed that AFB1 exposure impaired growth performance by decreasing BWG in 1-21 d and 1-42 d, decreasing FI in 1-21 d, increasing FCR in 1-21 d and 1-42 d (P < 0.05). Broilers fed AFB1- contaminated diet impaired the immune function, as evident by decreasing IgA contents, Newcastle disease antibody titers in serum, and sIgA contents of jejunal mucosa at 21 d (P < 0.05). On the other hand, AFB1 challenge significantly increased the gene expression of proinflammatory factors in spleen at 21 d and liver at 42 d, and significantly decreased claudin-1 expression at 42 d and occludin expression at 21 d, and increased claudin-2 at 21 d in jejunum of broiler chickens (P < 0.05) compared to the basal diet group. Dietary XL supplementation significantly decreased the gene expression of IL-6 in spleen at 21 d and IL-1ß in liver at 42 d, cytochrome P450 3A4 (CYP3A4) expression in liver at 21 d of broilers (P < 0.05) compared with the nonsupplemented birds, regardless of AFB1 challenged or not. Inclusion of 2 g/kg XL increased serum ALB at 42 d, IgM and IgA at 42 d, Newcastle disease antibody titer level at 35 d (P < 0.05). Dietary XL addition enhanced intestinal barrier function by increasing the expression of claudin-1 at 21 d and Occludin at 42 d (P < 0.05) in jejunum. Conclusively, 2 g/kg mycotoxins-binder can relieve the toxic effect of AFB1 on broilers.

Roles of matrix metalloproteinases in development, immunology, and ovulation in fruit Fly (Drosophila).

Matrix metalloproteinase (MMP), a protease enzyme, participates in proteolytic cleavage of extracellular matrix proteins from Drosophila and mammals. But, recent studies have revealed other physiologically important roles of MMP in Drosophila. MMP contributes to cardioblast movement and distribution of collagen proteins during cardiogenesis in developing Drosophila. Tissue remodeling, especially tracheal development is also maintained by MMP. MMP regulates certain immunological functions in Drosophila such as wound repairing, plasmatocyte assemblage at the injured site of the basement membrane and glial response to axon degeneration in Drosophila nervous system. But, the contribution of MMP to tumor formation and metastasis in Drosophila has made it an interesting topic among researchers. Ovulation and egg laying are also found to be affected positively by MMP in Drosophila.

Traditional Chinese medicine improves myasthenia gravis by regulating the symbiotic homeostasis of the intestinal microbiota and host.

Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies that is dependent on T-cell immunity and complement participation and mainly involves neuromuscular junctions. In this study, 30 patients with myasthenia gravis were selected and divided into pretreatment (Case group) and posttreatment (Treatment group) and 30 healthy volunteers (CON group) were included. Among them, the treatment group was treated with Modified Buzhong Yiqi Decoction (MBZYQD), and the levels of antibodies such as AChR, Musk and Titin in blood and intestinal microbiota were compared before treatment (Case group), after treatment (Treatment group) and in healthy volunteers (CON group). The results showed that after treatment with MBZYQD, the antibody levels of AChR, MuSK, and Titin and the inflammatory factor level of IL-6, IL-1ß, and IL-22 in MG patients decreased significantly and nearly returned to a healthy level. In addition, after treatment with MBZYQD, the diversity, structure and function of intestinal microorganisms in MG patients also recovered to a healthy level. At the phylum level, the relative abundance of Proteobacteria in the Case group increased significantly, accompanied by a significant decrease in the relative abundance of Bacteroides compared with that in the CON group, the relative abundance of Proteobacteria and Bacteroides in the Treatment group was similar to that in the CON group. At the genus level, the relative abundance of Shigella in the Case group was significantly increased, accompanied by a significant decrease in the relative abundance of Prevotella, and the relative abundance of Shigella and Prevotella in Treatment group was similar to that in the CON group. Moreover, the fluorobenzoate degradation pathway (KO00364) was significantly increased in the Case group, while this pathway was significantly decreased in the Treatment group. In conclusion, MBZYQD can improve the immune function of the host by regulating the diversity, structure and function of the intestinal microbiota to treat myasthenia gravis.

The protective effect of Qingfei Huatan decoction on pulmonary function and its influence on the immunological function in children with severe pneumonia.

OBJECTIVE: This research explores and analyzes the protective effect of the mixed Chinese herbs Qingfei Huatan decoction on the pulmonary and immunological functions in children with severe pneumonia. METHODS: 120 children with severe pneumonia hospitalized from May 2018 to May 2020 were enrolled in the study and randomly placed into an observation group or a control group (n=60 in each group). The control group was administered conventional treatment, and the observation group was administered the mixed Chinese herbs Qingfei Huatan decoction in addition to the treatment administered to the control group. The therapeutic efficacy, the changes in pulmonary function, the serum inflammatory levels, and the peripheral blood T lymphocyte subsets were compared between the two groups. RESULTS: The total effective treatment rate in the observation group was critically superior to the total effective treatment rate in the control group (P<0.05). The FVC, FEV1, and FEV1/FVC levels in the two groups after the treatment were remarkably higher than they were before the treatment (P<0.05), and the observation group had superior post-treatment pulmonary function than the control group (P<0.05). The TNF-α, IL-6, and CRP levels in the two groups in after the treatment were lower than they were before the treatment (P<0.05), and the observation group had lower post-treatment inflammatory cytokine levels than the control group (P<0.05). The two groups' CD4+ and CD4+/CD8+ levels increased substantially after the treatment compared to before the treatment (P<0.05), and the posttreatment levels in the observation group were notably higher than they were in the control group (P<0.05). CONCLUSION: The mixed Chinese herbs Qingfei Huatan decoction and the routine treatment combination has a good clinical effectiveness in children with severe pneumonia. It can effectively promote the pulmonary function of children. Its effect may be correlated with the suppression of inflammation in the body and the improvement of the immunological function in children.

[Effect of moxibustion combined with Guifu Yuhe decoction on the conversion score of idiopathic constitution, serum total lgE and blood EOS in the patients with allergic acne].

OBJECTIVE: To observe the therapeutic effect of moxibustion combined with Guifu Yuhe decoction on allergic acne and the influence on immunologic function in the patients. METHODS: A total of 60 patients with allergic acne were rando-mized into an observation group (30 cases) and a control group (30 cases).Thirty healthy employees were in the healthy group. In the control group, Guifu Yuhe decoction was prescribed for oral administration, while in the observation group, on the base of the treatment as the control group, moxibustion was exerted at Dazhui (GV14) and Shenque (GV8). The treatment duration was 8 weeks. Before and after treatment, serum IgE, blood EOS, CD4+T cell, CD8+ T cell and CD4+T/CD8+T, as well as the conversion score of idiopathic constitution and the symptom score were compared in the patients of two groups. The clinical therapeutic effect was observed in the two groups. RESULTS: Before treatment, compared with the healthy group, IgE and EOS, CD4+T cell and CD8+T cell all increased (P<0.05), and CD4+T/CD8+T decreased in the two groups (P<0.05). After treatment, IgE, EOS and CD4+T cell and CD8+T cell decreased (P<0.05), and CD4+T/CD8+T increased (P<0.05) in the intra-group comparison in the patients. The changes of IgE, EOS, CD4+T cell and CD8+T cell in the observation group were more larger than those in the control group (P<0.05). After treatment, the conversion score of body constitution and symptom score all decreased in either group (P<0.05) and the scores in the observation group were lower than those of the control group (P< 0.05). The total effective rate of the observation group (29/30, 96.7%) was higher than that of the control group (22/30, 73.3%, P<0.05). CONCLUSION: Moxibustion combined with Guifu Yuhe decoction can significantly improve immune function and body constitution of the patients with allergic acne, which may be related to rectifying idiopathic constitution, improving in lymphocyte subsets dysfunction and inhibiting allergic reaction.

Teleost CD4+ helper T cells: Molecular characteristics and functions and comparison with mammalian counterparts.

CD4+ helper T cells play key and diverse roles in inducing adaptive immune responses in vertebrates. The CD4 molecule, which is found on the surfaces of CD4+ helper T cells, can be used to distinguish subsets of helper T cells. Teleosts are the oldest living species with bona-fide CD4 coreceptors. Although some components of immune systems of teleosts and mammals appear to be similar, many physiological differences are represented between them. Previous studies have shown that two CD4 paralogs are present in teleosts, whereas only one is present in mammals. Therefore, in this review, the CD4 molecular structure, expression profiles, subpopulations, and biological functions of teleost CD4+ helper T cells were summarized and compared with those of their mammalian counterparts to understand the differences in CD4 molecules between teleosts and mammals. This review provides suggestions for further studies on the CD4 molecular function and regulatory mechanism of CD4+ helper T cells in teleost fish and will help establish therapeutic strategies to control fish diseases in the future.

3'UTR enhances hCD47 cell surface expression, self-signal function, and reduces ER stress in porcine fibroblasts.

INTRODUCTION: Macrophages contribute to xenograft rejection by direct cytotoxicity and by amplifying T cell-mediated immune responses. It has been shown that transgenic expression of hCD47 protects porcine cells from human macrophages by restoring the CD47-SIRPα self-recognition signal. It has also been reported that the long 3' untranslated region (3'UTR) of the hCD47 gene, which is missing from constructs previously used to make hCD47 transgenic pigs, is critical for efficient cell surface expression in human cells. The aim of this study was to investigate the impact of a modified form of the 3'UTR on the expression, localization, and function of hCD47 in transfected porcine cells. METHODS: hCD47 constructs with and without the modified 3'UTR were knocked into the GGTA1 locus in porcine fetal fibroblasts using CRISPR. Flow cytometry of the transfected cells was used to analyze hCD47 localization. Endoplasmic reticulum (ER), mitochondrial, and oxidative stress were examined by gene expression analysis and confocal microscopy. Phagocytosis of transfected cells by human macrophages was measured by flow cytometry, and stimulation of human/non-human (NHP) primate lymphocytes by the cells was examined using a PBMCs proliferation assay. RESULTS: Cells transfected with the construct lacking the 3'UTR (hCD47(3'UTR-)) exhibited predominantly intracellular expression of hCD47, and showed evidence of ER stress, dysregulated mitochondrial biogenesis, oxidative stress, and autophagy. Inclusion of the 3'UTR (hCD47(3'UTR+)) decreased intracellular expression of hCD47 by 36% and increased cell surface expression by 53%. This was associated with a significant reduction in cellular stress markers and a higher level of protection from phagocytosis by human macrophages. Furthermore, hCD47(3'UTR+) porcine cells stimulated significantly less proliferation of human/NHP T cells than hCD47(3'UTR-) cells. CONCLUSION: Our results suggest the potential benefits of using hCD47 constructs containing the 3'UTR to generate genetically engineered hCD47-expressing donor pigs.

The therapeutic effect of Gansu tablet combined with entecavir on severe hepatitis B patients and its influence on their immune function / 公共卫生与预防医学

Objective To explore the therapeutic effect of Gansu tablets combined with entecavir on patients with severe hepatitis B and the effect on patients’ immune function. Methods A total of 108 cases of severe hepatitis B patients who were treated in our hospital from January 2018 to January 2019 were randomly divided into two groups: entecavir group and combination treatment group, 54 cases each. Entecavir group was treated with entecavir, and combination treatment group was treated with Gansu tablets and entecavir. The levels of AST, GGT, alt, FIB, APTT, Pt, GSH Px, LPO and MDA in serum were measured by enzyme-linked immunosorbent assay. T-lymphocyte subsets were measured by cell analyzer. The therapeutic effect and adverse reactions were compared between the two groups. Results The levels of AST, GGT and ALT in the combined treatment group were significantly lower than those in the entecavir group (P 0.05). Conclusion The use of Gansu tablets combined with entecavir in the treatment of severe hepatitis B patients was able to improve liver function, improve coagulation function, reduce oxidative stress injury, and improve the immune function of patients, demonstrating a potential clinical application value.

Molecular and Functional Diversity of Crustin-Like Genes in the Shrimp Litopenaeus vannamei.

Crustins are crustacean cationic cysteine-rich antimicrobial peptides that contain one or two whey acidic protein (WAP) domain(s) at the carboxyl terminus and mainly show antimicrobial and/or proteinase inhibitory activities. Here, we performed genome and transcriptome screening and identified 34 full-length crustin-like encoding genes in Litopenaeus vannamei. Multiple sequence analysis of the deduced mature peptides revealed that these putative crustins included 10 type Ia, two type Ib, one type Ic, 11 type IIa, three type IIb, four type III, one type IV, one type VI, and one type VII. These putative crustins were clustered into different groups. Phylogenetic analysis, considering their domain composition, showed that different types of crustin-like genes in crustaceans might be originated from the WAP core region, along with sequence insertion, duplication, deletion, and amino acid substitution. Tissue distribution analysis suggested that most crustin-like genes were mainly detected in immune-related tissues while several crustin-like genes exhibited tissue-specific expression patterns. Quantitative PCR analysis on 15 selected crustin-like genes showed that most of them were apparently upregulated after Vibrio parahaemolyticus or white spot syndrome virus (WSSV) infection. One type Ib crustin-like gene, mainly expressed in the ovary, showed the highest expression levels before the gastrula stage and was hardly detected after the limb bud stage, suggesting that it was a maternal immune effector. Collectively, the present data revealed the molecular and functional diversity of crustins and their potential evolutionary routes in crustaceans.

[Study on immunological functions of heat shock protein 40 kDa of Schistosoma japonicum].

OBJECTIVE: To investigate the immunological functions of heat shock protein 40 kDa of Schistosoma japonicum (SjHSP40). METHODS: The homology of the SjHSP40 protein sequence was analyzed and the B and T cell epitopes of SjHSP40 were predicted using bioinformatics tools. The full-length SjHSP40 gene was amplified using a PCR assay, and cloned into the prokaryotic expression vector pGEX-6P-1, which was transformed into Escherichia coli BL-21. The protein expression was induced with isopropyl ß-D-thiogalactoside (IPDG), and then, the recombinant protein was purified with glutathione-sepharose 4B resin to yield the fusion protein GST-SjHSP40, which was checked with SDS-PAGE and Western blotting. Following immunization with GST-SjHSP40, the serum levels of anti-SjHSP40 IgG antibody and IgG1 and IgG2a subtypes were detected in BALB/c mice using ELISA. In addition, the effect of SjHSP40 on CD4+ T-cell subset differentiation was examined using flow cytometry. RESULTS: SjHSP40 contained 7 potential B cell epitopes and multiple T cell epitopes (CTL epitopes and Th epitopes). The prokaryotic expression plasmid pGEX-6p-1-SjSHP40 was successfully constructed, and the fusion protein GST-SjHSP40 was obtained following IPDG induction and protein purification. Significantly higher serum levels of anti-SjHSP40 IgG, IgG1 and IgG2a antibodies were detected in mice immunized with GST-SjHSP40 than in other groups; however, SjHSP40 showed no remarkable effects on CD4+ T-cell subset differentiation. CONCLUSIONS: SjHSP40 may induce specific humoral immune responses in mice; however, it does not affect the balance of Th immune responses. It is suggested that SjHSP40 may be a potential vaccine candidate.

The Potential Role of Complement System in the Progression of Ovarian Clear Cell Carcinoma Inferred from the Gene Ontology-Based Immunofunctionome Analysis.

Ovarian clear cell carcinoma (OCCC) is the second most common epithelial ovarian carcinoma (EOC). It is refractory to chemotherapy with a worse prognosis after the preliminary optimal debulking operation, such that the treatment of OCCC remains a challenge. OCCC is believed to evolve from endometriosis, a chronic immune/inflammation-related disease, so that immunotherapy may be a potential alternative treatment. Here, gene set-based analysis was used to investigate the immunofunctionomes of OCCC in early and advanced stages. Quantified biological functions defined by 5917 Gene Ontology (GO) terms downloaded from the Gene Expression Omnibus (GEO) database were used. DNA microarray gene expression profiles were used to convert 85 OCCCs and 136 normal controls into to the functionome. Relevant offspring were as extracted and the immunofunctionomes were rebuilt at different stages by machine learning. Several dysregulated pathogenic functions were found to coexist in the immunopathogenesis of early and advanced OCCC, wherein the complement-activation-alternative-pathway may be the headmost dysfunctional immunological pathway in duality for carcinogenesis at all OCCC stages. Several immunological genes involved in the complement system had dual influences on patients' survival, and immunohistochemistrical analysis implied the higher expression of C3a receptor (C3aR) and C5a receptor (C5aR) levels in OCCC than in controls.

Study on immunological functions of heat shock protein 40 kDa of Schistosoma japonicum / 中国血吸虫病防治杂志

Objective To investigate the immunological functions of heat shock protein 40 kDa of Schistosoma japonicum (SjHSP40). Methods The homology of the SjHSP40 protein sequence was analyzed and the B and T cell epitopes of SjHSP40 were predicted using bioinformatics tools. The full-length SjHSP40 gene was amplified using a PCR assay, and cloned into the prokaryotic expression vector pGEX-6P-1, which was transformed into Escherichia coli BL-21. The protein expression was induced with isopropyl β-D-thiogalactoside (IPDG), and then, the recombinant protein was purified with glutathione-sepharose 4B resin to yield the fusion protein GST-SjHSP40, which was checked with SDS-PAGE and Western blotting. Following immunization with GST-SjHSP40, the serum levels of anti-SjHSP40 IgG antibody and IgG1 and IgG2a subtypes were detected in BALB/c mice using ELISA. In addition, the effect of SjHSP40 on CD4+ T-cell subset differentiation was examined using flow cytometry. Results SjHSP40 contained 7 potential B cell epitopes and multiple T cell epitopes (CTL epitopes and Th epitopes). The prokaryotic expression plasmid pGEX-6p-1-SjSHP40 was successfully constructed, and the fusion protein GST-SjHSP40 was obtained following IPDG induction and protein purification. Significantly higher serum levels of anti-SjHSP40 IgG, IgG1 and IgG2a antibodies were detected in mice immunized with GST-SjHSP40 than in other groups; however, SjHSP40 showed no remarkable effects on CD4+ T-cell subset differentiation. Conclusions SjHSP40 may induce specific humoral immune responses in mice; however, it does not affect the balance of Th immune responses. It is suggested that SjHSP40 may be a potential vaccine candidate.

Transcutaneous Electrical Acupoint Stimulation Improves Immunological Function During the Perioperative Period in Patients With Non-Small Cell Lung Cancer Undergoing Video-Assisted Thoracic Surgical Lobectomy.

The immunological function of patients with malignant tumors may be suppressed during the perioperative period. However, details on the effects of transcutaneous electrical acupoint stimulation (TEAS) on immunological function are relatively lacking. We designed this study to examine the effects of TEAS on the immunological function of patients with non-small cell lung cancer (NSCLC) during the perioperative period. Participants (n = 144) were enrolled and randomly assigned into group TEAS or group sham TEAS. TEAS on bilateral Feishu (BL13), Hegu (L14), and Zusanli (ST36) was performed continuously throughout the procedure. The primary outcome was the quantities of natural killer (NK) cells at 30 minutes before induction (T0), 5 minutes after intubation (T1), at the beginning of the operation (T2), at the beginning of the lobectomy (T3), at the beginning of the lymphadenectomy (T4), and immediately after extubation (T5). The secondary outcomes were the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) at T0 to T5, the mean arterial pressure (MAP) and heart rate (HR), the intraoperative consumption of propofol and remifentanil, the incidence of hypoxemia, postoperative nausea and vomiting (PONV), and the length of hospital stay. The quantities of NK cells were decreased in group sham TEAS after intubation compared to that in group TEAS, while the quantities of NK cells in group TEAS were similar at T0 to T5. Meanwhile, the quantities of NK cells in group sham TEAS at T1 ( P = .012), T2 ( P < .001), T3 ( P = .027), T4 ( P = .045), and T5 ( P = .021) were lower than those in group TEAS. In group TEAS, the serum levels of TNF-α were lower at T1 to T5, while the levels of IL-6 were lower at T2 to T5. Furthermore, the intraoperative MAP and HR were more stable, the total propofol and remifentanil consumptions were lower, and the length of hospital stay was shorter than those in group sham TEAS. The application of TEAS can effectively reverse the decrease in NK cells, decrease the serum levels of TNF-α and IL-6, maintain hemodynamic stability during the perioperative period, decrease the consumption of propofol and remifentanil, and shorten the length of the hospital stay.