Development of interleukin-27 recombinant Lactococcus lactis and its efficacy in treating psoriasis and colitis in mice.

Psoriasis and inflammatory bowel disease (IBD) are chronic immune-mediated diseases that adversely affect patients' quality of life. Interleukin (IL)-27 plays an important role in a variety of infectious diseases, autoimmune disorders, and cancers. However, its therapeutic effects in psoriasis and colitis remain underexplored. In this study, we evaluated the therapeutic potential of recombinant Lactococcus lactis (L. lactis) expressing IL-27 (pIL-27) in imiquimod-induced psoriasis and dextran sodium sulfate-induced colitis mouse models. In the psoriasis mouse model, oral administration of pIL-27 significantly reduced skin scaling, mitigated weight loss, lowered psoriasis area and severity index scores, diminished epidermal hyperplasia and inflammatory cell infiltration, and decreased inflammatory cytokine levels. In the colitis mouse model, oral administration of pIL-27 alleviated weight loss, improved disease activity index scores, prevented colon shortening, ameliorated histopathological changes, and decreased inflammatory cytokine levels. Furthermore, recombinant L. lactis expressing IL-27 could modulate the gut microbiota, increasing the amount of beneficial bacteria and reducing harmful bacteria in the intestine, thereby alleviating the progression of psoriasis and colitis. These results suggest the potential of IL-27 as a therapeutic option for treating psoriasis and IBD.

Immunogenicity and protective efficacy of a recombinant lactococcus lactis vaccine against HSV-1 infection.

BACKGROUND: Herpes simplex virus type 1 (HSV-1) is a major cause of viral encephalitis, genital mucosal infections, and neonatal infections. Lactococcus lactis (L. lactis) has been proven to be an effective vehicle for delivering protein antigens and stimulating both mucosal and systemic immune responses. In this study, we constructed a recombinant L. lactis system expressing the protective antigen glycoprotein D (gD) of HSV-1. RESULTS: To improve the stability and persistence of antigen stimulation of the local mucosa, we inserted the immunologic adjuvant interleukin (IL)-2 and the Fc fragment of IgG into the expression system, and a recombinant L. lactis named NZ3900-gD-IL-2-Fc was constructed. By utilizing this recombinant L. lactis strain to elicit an immune response and evaluate the protective effect in mice, the recombinant L. lactis vaccine induced a significant increase in specific neutralizing antibodies, IgG, IgA, interferon-γ, and IL-4 levels in the serum of mice. Furthermore, in comparison to the mice in the control group, the vaccine also enhanced the proliferation levels of lymphocytes in response to gD. Moreover, recombinant L. lactis expressing gD significantly boosted nonspecific immune reactions in mice through the activation of immune-related genes. Furthermore, following the HSV-1 challenge of the murine lung mucosa, mice inoculated with the experimental vaccine exhibited less lung damage than control mice. CONCLUSION: Our study presents a novel method for constructing a recombinant vaccine using the food-grade, non-pathogenic, and non-commercial bacterium L. lactis. The findings indicate that this recombinant vaccine shows promise in preventing HSV-1 infection in mice.

Novel therapeutic approach for psoriasis: Upregulating FcRn to inhibit ferroptosis and alleviate lesional skin.

Psoriasis, a chronic inflammatory skin disease, is characterized by complex immune dysregulation and oxidative stress responses. The neonatal Fc receptor (FcRn) plays a crucial role in the development of autoimmune diseases. Analysis of clinical psoriasis samples demonstrated a negative correlation between FcRn expression in skin lesions and disease severity. However, the role of FcRn in this process remains unclear. This study aimed to investigate the involvement of FcRn in the pathogenesis and progression of psoriasis. In an imiquimod (IMQ)-induced psoriasis-like mouse model, FcRn expression was significantly decreased in the lesional skin, and transcriptome sequencing of the skin revealed activation of the ferroptosis pathway in psoriasis. This led to the hypothesis that FcRn could potentially regulate ferroptosis via the signal transducer and activating transcription factor 3 (STAT3)/solute carrier family 7 member 11 (SLC7A11) axis. Further experiments showed exacerbated psoriasis-like lesional skin and ferroptosis in FcRn-knockout mice, whereas intervention with the ferroptosis inhibitor Fer-1 or STAT3 inhibitor Stattic alleviated these symptoms. Critical binding sites for the transcription factor STAT3 were identified in the SLC7A11 promoter region at positions -1185 and -564 using the luciferase reporter assays and chromatin immunoprecipitation. The administration of 1,4-naphthoquinone (NQ), an FcRn agonist, effectively alleviated psoriasis-like skin lesions by inhibiting ferroptosis. This study highlights the molecular mechanisms of action of FcRn in psoriasis and provides an experimental basis for the development of novel therapeutic strategies targeting FcRn.

TIPE2 protein restrains invariant NKT activation and protects against immune-mediated hepatitis in mice.

BACKGROUND AND AIMS: Concanavalin A (ConA) administration induces a rapid and severe liver injury in mice, and invariant natural killer T (iNKT) cells are recognized to be the key effector cells in this process. However, the underlying regulatory mechanisms are not well defined. APPROACH AND RESULTS: We found that iNKT cells constitutively expressed TIPE2 (Tumor necrosis factor-α-induced protein 8-like 2, or TNFAIPL2). Genetic TIPE2 ablation strongly sensitized mice to ConA-induced hepatitis, accompanied with hyperactivation of iNKT cells. Moreover, Tipe2-/- mice were also more susceptible to α-galactosylceramide (αGalCer)-induced liver injury, with elevated serum ALT level and enhanced proinflammatory cytokine production. CD1d signaling blockade or iNKT cell elimination through antibodies reduced the effect of TIPE2 deficiency on liver injury. Mechanistic studies revealed that TIPE2 in iNKT cells functioned as a negative regulator, limiting iNKT cell activity and cytokine production through PIP3- AKT/mTOR pathway. TIPE2-mediated protection from liver injury was further validated by the administration of adeno-associated viruses expressing TIPE2, which effectively ameliorated ConA-induced hepatic injury. However, TIPE2 was dispensable in two other liver injury models, including D-GalN/LPS and APAP-induced hepatitis. CONCLUSION: Our findings reveal a new role of TIPE2 in the attenuation of iNKT cell-mediated hepatic injury. We propose that TIPE2 serves as an important regulator of immune homeostasis in the liver, and might be exploited for the therapeutic treatment of autoimmune liver diseases.

Staphylococcus warneri strain XSB102 exacerbates psoriasis and promotes keratinocyte proliferation in imiquimod-induced psoriasis-like dermatitis mice.

Psoriasis is one of the common chronic inflammatory skin diseases worldwide. The skin microbiota plays a role in psoriasis through regulating skin homeostasis. However, the studies on the interactions between symbiotic microbial strains and psoriasis are limited. In this study, Staphylococcus strain XSB102 was isolated from the skin of human, which was identified as Staphylococcus warneri using VITEK2 Compact. To reveal the roles of Staphylococcus warneri on psoriasis, XSB102 were applied on the back of imiquimod-induced psoriasis-like dermatitis mice. The results indicated that it exacerbated the psoriasis and significantly increased the thickening of the epidermis. Furthermore, in vitro experiments confirmed that inactivated strain XSB102 could promote the proliferation of human epidermal keratinocytes (HaCaT) cell. However, real-time quantitative PCR and immunofluorescence results suggested that the expression of inflammatory factors such as IL-17a, IL-6, and so on were not significantly increased, while extracellular matrix related factors such as Col6a3 and TGIF2 were significantly increased after XSB102 administration. This study indicates that Staphylococcus warneri XSB102 can exacerbate psoriasis and promote keratinocyte proliferation independently of inflammatory factors, which paves the way for further exploration of the relationship between skin microbiota and psoriasis.

Anti-interleukin 33 treatment alleviates psoriatic dermatitis in mice induced imiquimod.

Interleukin-33（IL-33), is constitutively expressed in the epithelial cells of the skin. It has been reported that IL-33 contributed to the severity of the disease in psoriasis-like mouse models. In the current study, we evaluated the effect of anti-IL-33 antibody (Ab) in imiquimod-induced psoriatic dermatitis in mice. Our observations showed that anti-IL-33 Ab ameliorated the erythema, scaling, epidermal thickness and spleen index. Additionally, we found anti-IL-33 Ab significantly decreased the expression of psoriasis-related cytokines. Moreover, anti-IL-33 Ab significantly reduced Ki-67 positive cells, CD3+CD4+T cells, and CD3+CD8+T cells in the skin lesions. Furthermore, anti-IL-33 Ab treatment down-regulated the expression of phosphorylation of STAT3 and IL-33 in model mouse. These results indicated that the anti-IL-33 Ab alleviated the seriousness of skin lesions, inhibited the activation of the STAT3, lymphocyte infiltration and the secretion of pro-inflammatory cytokines in imiquimod-induced psoriatic dermatitis in mice, suggesting IL-33 may be a therapeutic target for the treatment of psoriasis.

A Half-Sandwich Ruthenium(II) (N

Efficacy of clinical chemotherapeutic agents depends not only on direct cytostatic and cytotoxic effects but also involves in eliciting (re)activation of tumour immune effects. One way to provoke long-lasting antitumour immunity is coined as immunogenic cell death (ICD), exploiting the host immune system against tumour cells as a "second hit". Although metal-based antitumour complexes hold promise as potential chemotherapeutic agents, ruthenium (Ru)-based ICD inducers remain sparse. Herein, we report a half-sandwich complex Ru(II) bearing aryl-bis(imino) acenaphthene chelating ligand with ICD inducing properties for melanoma in vitro and in vivo. Complex Ru(II) displays strong anti-proliferative potency and potential cell migration inhibition against melanoma cell lines. Importantly, complex Ru(II) drives the multiple biochemical hallmarks of ICD in melanoma cells, i. e., the elevated expression of calreticulin (CRT), high mobility group box 1 (HMGB1), Hsp70 and secretion of ATP, followed by the decreased expression of phosphorylation of Stat3. In vivo the inhibition of tumour growth in prophylactic tumour vaccination model further confirms that mice with complex Ru(II)-treated dying cells lead to activate adaptive immune responses and anti-tumour immunity by the activation of ICD in melanoma cells. Mechanisms of action studies show that complex Ru(II)-induced ICD could be associated with mitochondrial damage, ER stress and impairment of metabolic status in melanoma cells. We believe that the half-sandwich complex Ru(II) as an ICD inducer in this work will help to design new half-sandwich Ru-based organometallic complexes with immunomodulatory response in melanoma treatments.

Haze Exposure Changes the Skin Fungal Community and Promotes the Growth of Talaromyces Strains.

Haze pollution has been a public health issue. The skin microbiota, as a component of the first line of defense, is disturbed by environmental pollutants, which may have an impact on human health. A total of 74 skin samples from healthy students were collected during haze and nonhaze days in spring and winter. Significant differences of skin fungal community composition between haze and nonhaze days were observed in female and male samples in spring and male samples in winter based on unweighted UniFrac distance analysis. Phylogenetic diversity whole-tree indices and observed features were significantly increased during haze days in male samples in winter compared to nonhaze days, but no significant difference was observed in other groups. Dothideomycetes, Capnodiales, Mycosphaerellaceae, etc. were significantly enriched during nonhaze days, whereas Trichocomaceae, Talaromyces, and Pezizaceae were significantly enriched during haze days. Thus, five Talaromyces strains were isolated, and an in vitro culture experiment revealed that the growth of representative Talaromyces strains was increased at high concentrations of particulate matter, confirming the sequencing results. Furthermore, during haze days, the fungal community assembly was better fitted to a niche-based assembly model than during nonhaze days. Talaromyces enriched during haze days deviated from the neutral assembly process. Our findings provided a comprehensive characterization of the skin fungal community during haze and nonhaze days and elucidated novel insights into how haze exposure influences the skin fungal community. IMPORTANCE Skin fungi play an important role in human health. Particulate matter (PM), the main haze pollutant, has been a public environmental threat. However, few studies have assessed the effects of air pollutants on skin fungi. Here, haze exposure influenced the diversity and composition of the skin fungal community. In an in vitro experiment, a high concentration of PM promoted the growth of Talaromyces strains. The fungal community assembly is better fitted to a niche-based assembly model during haze days. We anticipate that this study may provide new insights on the role of haze exposure disturbing the skin fungal community. It lays the groundwork for further clarifying the association between the changes of the skin fungal community and adverse health outcomes. Our study is the first to report the changes in the skin fungal community during haze and nonhaze days, which expands the understanding of the relationship between haze and skin fungi.

Cytokine Profiles and the Relationship of Disease Severity in Patients with Psoriasis.

Background: Psoriasis is a chronic skin disease characterized by hyperproliferation of keratinocytes and increased inflammation. Previous studies have detected the levels of cytokines in the serum of patients with psoriasis, yet few multi-cytokine combination studies have been reported. Objective: The aim of the study was to compare the levels of cytokines in the serum between patients with psoriasis and healthy controls, elucidate which factors influence the psoriasis progression. Methods: A total of 39 psoriasis patients and 30 healthy volunteers were enrolled. The venous blood was collected and the levels of 13 inflammatory cytokines were measured by human inflammation panel 1 kit. The severity of the disease was determined according to the psoriasis area and severity index (PASI) score. Results: Compared with healthy controls, the levels of nine cytokines (IFN-γ, TNF-α, IL-1ß, IL-6, IL-10, IL-12P40, IL-18, IL-17A and IL-23) were significantly increased, while the level of MCP-1 decreased in psoriatic patients. In addition, except for MCP-1, IL-10 and IL-12P40, these cytokine levels were positively correlated with the PASI score. Furthermore, there were higher serum lever of IFN-γ, TNF-α, IL-1ß, IL-6, IL-17A, IL-18 and IL-23 in active psoriasis than healthy controls and retrograde psoriasis. Conclusions: Increased serum levels of IFN-γ, TNF-α, IL-1ß, IL-6, IL-17A, IL-18 and IL-23 in psoriatic patients were associated with PASI and the stage of disease, which suggested that these cytokines play an important role in the pathogenesis of psoriasis. The detection of these cytokines can better observe the disease activity of psoriasis and optimize the treatment strategy.

Eucommia ulmoides bark extract reduces blood pressure and inflammation by regulating the gut microbiota and enriching the Parabacteroides strain in high-salt diet and N(omega)-nitro-L-arginine methyl ester induced mice.

Hypertension is a major threat to human health. Eucommia ulmoides Oliv. (EU) is a small tree and EU extract is widely used to improve hypertension in East Asia. However, its major constituents have poor absorption and stay in the gut for a long time. The role of the gut microbiota in the anti-hypertensive effects of EU is unclear. Here, we examined the anti-hypertensive effects of EU in high-salt diet and N(omega)-nitro-L-arginine methyl ester (L-NAME) induced mice. After receiving EU for 6 weeks, the blood pressure was significantly reduced and the kidney injury was improved. Additionally, EU restored the levels of inflammatory cytokines, such as serum interleukin (IL)-6 and IL-17A, and renal IL-17A. The diversity and composition of the gut microbiota were influenced by administration of EU; 40 significantly upregulated and 107 significantly downregulated amplicon sequence variants (ASVs) were identified after administration of EU. ASV403 (Parabacteroides) was selected as a potential anti-hypertensive ASV. Its closest strain XGB65 was isolated. Furthermore, animal studies confirmed that Parabacteroides strain XGB65 exerted anti-hypertensive effects, possibly by reducing levels of inflammatory cytokines, such as renal IL-17A. Our study is the first to report that EU reduces blood pressure by regulating the gut microbiota, and it enriches the Parabacteroides strain, which exerts anti-hypertensive effects. These findings provide directions for developing novel anti-hypertensive treatments by combining probiotics and prebiotics.

TNFAIP8 protein functions as a tumor suppressor in inflammation-associated colorectal tumorigenesis.

Tumor necrosis factor-α-induced protein 8 (TNFAIP8 or TIPE) is a member of the TNFAIP8 family. While TIPE was broadly considered to be pro-cancerous, its precise roles in carcinogenesis especially those of the intestinal tract are not clear. Here, we show that genetic deletion of TIPE in mice exacerbated chemical-induced colitis and colitis-associated colon cancer. Loss of TIPE exacerbated inflammatory responses and inflammation-associated dysbiosis, leading to the activation of NF-κB and STAT3, and it also accelerated dysplasia, DNA damage and proliferation of intestinal epithelial cells. We further show that colon microbiota were essential for increased tumor growth and progression in Tipe-/- mice. The tumor suppressive function of TIPE originated primarily from the non-hematopoietic compartment. Importantly, TIPE was downregulated in human colorectal cancers, and patients with low levels of Tipe mRNA were associated with reduced survival. These results indicate that TIPE serves as an important modulator of colitis and colitis-associated colon cancer.

Tumor Necrosis Factor-α-Induced Protein 8-Like 2 Fosters Tumor-Associated Microbiota to Promote the Development of Colorectal Cancer.

Although increasing evidence links the gut microbiota with the development of colorectal cancer, the molecular mechanisms for microbiota regulation of tumorigenesis are not fully understood. Here, we found that a member of the TNFα-induced protein 8 (TNFAIP8) family called TIPE2 (TNFAIP8-like 2) was significantly upregulated in murine intestinal tumors and in human colorectal cancer, and colorectal cancer with high expression of Tipe2 mRNA associated with reduced survival time of patients. Consistent with these findings, TIPE2 deficiency significantly inhibited the development of colorectal cancer in mice treated with azoxymethane/dextran sodium sulfate and in Apcmin/+ mice. TIPE2 deficiency attenuated the severity of colitis by successfully resolving and restricting colonic inflammation and protected colonic myeloid cells from death during colitis. Transplantation of TIPE2-deficient bone marrow into wild-type mice successfully dampened the latter's tumorigenic phenotype, indicating a hematopoietic-specific role for TIPE2. Mechanistically, restricting the expansion of Enterobacteriaceae/Escherichia coli (E. coli) decreased intestinal inflammation and reduced the incidence of colonic tumors. Collectively, these data suggest that hematopoietic TIPE2 regulates intestinal antitumor immunity by regulation of gut microbiota. TIPE2 may represent a new therapeutic target for treating colorectal cancer.

Clinical significance of high mobility group box 1/toll-like receptor 4 in obese diabetic patients.

High mobility group box 1 (HMGB1) is an alarmin that may link to obesity and type 2 diabetes mellitus (T2DM). The present study analyzed the correlation between HMGB1/ Toll-like receptor 4 (TLR4) and certain biochemical parameters in obese (OB) diabetic patients. 40 normal glucose tolerant subjects (NGT) and 40 patients with newly diagnosed T2DM were enrolled. All patients were further divided into non-obese NGT (NGT-NOB), obese NGT (NGT-OB), non-obese T2DM (T2DM-NOB) and obese T2DM (T2DM-OB) groups according to body mass index (BMI).The levels of HMGB1 in serum were quantified using ELISA, whereas the mRNA expression levels of TLR4 in peripheral blood mononuclear cells were assessed using reverse transcription-quantitative PCR. The results suggested that the levels of HMGB1 and TLR4 were higher in NGT-OB and T2DM-NOB groups compared with those in NGT-NOB group. Similarly, the levels of these two markers were higher in T2DM-OB group compared with those in NGT-OB group. Correlation analysis indicated that the levels of HMGB1 and TLR4 were positively correlated with triglyceride (TG), fasting plasma glucose (FPG) levels and BMI, whereas a negative correlation between HMGB1 and high density lipoprotein (HDL) was noted. Linear regression analysis suggested that HMGB1 was associated with FPG and TG levels, whereas TLR4 was strongly associated with TG levels and BMI. The results demonstrated that the expression levels of HMGB1 and TLR4 in patients with T2DM or obesity were increased, which were associated with glycolipid metabolism disorders. Therefore, the HMGB1/TLR4 may serve a role in inflammatory process associated with obesity and T2DM.

Serum Expression of IL-33 and ST2 in Patients with Psoriasis Vulgaris.

BACKGROUND: Psoriasis vulgaris (PsV) is an immune-mediated skin disease of unknown mechanism. Interleukin 33 (IL-33) is a member of IL-1 cytokine family and suppression of tumorigenicity 2 (ST2) is the specific ligand of IL-33. It has been found that IL-33 and ST2 are increased in psoriatic lesions, but the expression levels in serum and their relationship to clinical features are still unclear. The aim of this study is to assess IL-33, ST2, IL-17 and IL-5 serum levels as well as serum concentration of blood glucose and blood lipids in PsV patients and their relationship with clinical characteristics. METHODS: Sixty-eight PsV samples and 60 healthy individuals were recruited. Serum levels of IL-33, ST2, IL-17 and IL-5 were measured by enzyme-linked immunosorbent assay and blood glucose and blood lipid were assayed by automatic biochemical analyzer. RESULTS: Serum levels of IL-33, ST2, IL-17 and IL-5 were increased significantly in PsV patients compared with controls (P<0.01). Cytokines were overexpressed in PsV patients during active stages compared with controls (P<0.05). Expression levels of IL-33, ST2 and IL-17 confirmed a significance in different severity groups of PsV patients (P<0.05). Serum concentration of triglyceride (TG) was also increased compared with controls (P=0.024). IL-33 levels were positively correlated with total cholesterol (TC) levels (r=0.319, P=0.008). CONCLUSION: IL-33/ST2 could generally reflect the activity and disease severity in PsV patients, which indicates that the IL-33/ST2 signaling pathway plays an important role in the pathogenesis of PsV.

Effects of IL-33 on 3T3-L1 cells and obese mice models induced by a high-fat diet.

Obesity is a syndrome that attributes to many factors such as genetics, diet, lifestyle and environment, which includes an imbalance of immune regulation. IL-33, as a new member of the IL-1 family, is classically associated with type 2 immune responses. Here, IL-33 was investigated for its ability to optimize lipid aggregation and ameliorate the inflammatory response in obesity. In vitro experimental results showed that, compared with the induction group, the treatment with 30 ng/mL IL-33 displayed a reduction in the number of lipid droplets. The expression levels of AceCS1 and PPARγ also decreased in the 30 ng/mL IL-33 group compared to the induction group. For confirmation in vivo, three groups of C57BL/6 mice were treated for 14 weeks: mice in control were fed with a normal diet; mice in the HFD and IL-33 groups were fed with a high-fat diet (HFD) and with sterile PBS or recombinant IL-33, respectively. Liver, muscle, spleen and four types of adipose tissue, as well as serum, were collected for further testing. Our data demonstrated that after 4-week treatment with recombinant IL-33, metabolic parameters in mice were improved significantly (visceral fat weight, glucose and insulin tolerance, liver steatosis, expression of lipid synthesis index and inflammatory response). Moreover, IL-33 treatment regulated the original distribution of IL-33 among different tissues. Hence, IL-33 modulated lipid metabolism and inflammatory response in obesity, which would be a novel therapeutic target for obesity and related metabolic diseases.

Geographic distribution of the cagA, vacA, iceA, oipA and dupA genes of Helicobacter pylori strains isolated in China.

BACKGROUND: There are geographic variations in the genotypes of Helicobacter pylori (H. pylori) cagA, vacA, iceA, oipA and dupA. The aim of the study was to investigate the distribution of these genotypes among H. pylori strains from five regions of China and their association with clinical outcomes. MATERIALS AND METHODS: Gastric biopsy specimens were obtained from 348 patients with different gastrointestinal diseases in the five regions of China. The regional distribution was 89 patients from Shandong, 91 from Guangxi, 57 from Hunan, 58 from Qinghai and 53 from Heilongjiang. The presence of cagA, vacA, iceA, oipA and dupA genotypes was determined by polymerase chain reaction (PCR) from H. pylori DNA. RESULTS: A total of 269 H. pylori isolates were obtained, of which 74 isolates were from Shandong, 78 from Guangxi, 46 from Hunan, 33 from Qinghai and 38 from Heilongjiang. The cagA-positive status was predominant in the five regions. The predominant vacA genotypes were s1c (73.4%), m2 (70.6%) and i1 (92.9%). In strains from Shandong, s1a and m1 were dominant. By contrast, s1c was dominant in Guangxi and i1 was dominant in Hunan and Heilongjiang. The prevalence of m2 subtype in Qinghai (78.8%) was significantly higher than that in other regions (P < 0.05). The predominant iceA genotype was iceA1 and the frequency of iceA1 was significantly more prevalent in Hunan than in other regions (P < 0.05). The oipA status "on" gene was more frequent in Shandong (91.9%) and Guangxi (91%) than in Heilongjiang (71.7%) (P < 0.05). Conversely, the dupA-positive status was less than half in Shandong (31.1%) and Guangxi (15.4%), whereas it was 73.9% in Hunan and 81.8% in Qinghai (P < 0.001). There were no significant associations between the cagA, vacA, iceA, oipA genotypes and clinical outcomes. The dupA-positive strains were more common in peptic ulcer disease (PUD) patients than in non-ulcer dyspepsia (NUD) patients in Shandong and Guangxi (P < 0.05), but the association was not observed in other geographic regions. CONCLUSIONS: There was significant geographic diversity of H. pylori genotypes in different regions of China and the presence of dupA gene can be considered as a marker for the development of gastroduodenal diseases. However, the cagA, iceA, vacA and oipA genes cannot be regarded for prediction of the clinical presentation of H. pylori infection in China.

Alterations of fatty acid composition and metabolism in APP/PS1 transgenic mice.

Accumulating evidence suggests that abnormal fatty acid composition is related to the development of Alzheimer's disease (AD). However, there is no consistency in the fatty acid profile and metabolism associated with AD pathogenesis. This study aims to define the characteristics of fatty acid composition and metabolism in AD. Using 6-month-old APP/PS1 transgenic mice with wild-type mice as a control, we examined the serum lipids, brain fatty acid composition, and the expression levels of various genes involved in liver fatty acid ß-oxidation. The results of our study demonstrate that APP/PS1 mice present decreased serum free fatty acids, altered brain fatty acid profiles, and minimal change in liver fatty acid ß-oxidation. Our results suggest that abnormal fatty acid compositions and contents may play potential roles in AD progression. This study provides further evidence for the metabolic basis of AD pathogenesis.

Preparation and application of a beta-d-glucan microsphere conjugated protein A/G.

Antibodies (Abs) have been widely used in both immunodiagnostics and immunotherapy for the treatment of various diseases and, in recent years, scientific research applications. With the increasing use of Abs, there has been an urgent demand for low-cost and highly efficient purification methods. In this study, we present a novel formulation based on a ß-d-glucan particle loaded protein A/G (GP-protein A/G conjugates) by the carbodiimide method for the purification of immunoglobulin (IgG) antibodies. The prepared GP-protein A/G conjugates exhibit high stability and isolation efficiency. The microspheres also constitute an essential specialty reagent useful for isolating IgG from mammalian species such as goat, mouse and rabbit. Recovery of IgG showed that up to a purity of 92% was reached in the elution step. In addition, they has been shown to be important tools for molecular purification methods such as immunoprecipitation and co-immunoprecipitation. Taken together, these results suggest that the GP-protein A/G system has the potential to be used as a platform for purification techniques.

Pattern Recognition Receptor-Mediated Chronic Inflammation in the Development and Progression of Obesity-Related Metabolic Diseases.

Obesity-induced chronic inflammation is known to promote the development of many metabolic diseases, especially insulin resistance, type 2 diabetes mellitus, nonalcoholic fatty liver disease, and atherosclerosis. Pattern recognition receptor-mediated inflammation is an important determinant for the initiation and progression of these metabolic diseases. Here, we review the major features of the current understanding with respect to obesity-related chronic inflammation in metabolic tissues, focus on Toll-like receptors and nucleotide-binding oligomerization domain-like receptors with an emphasis on how these receptors determine metabolic disease progression, and provide a summary on the development and progress of PRR antagonists for therapeutic intervention.