[Effect of Sishen Pills and its split prescriptions on Tfr/Tfh9/Tfh17 cells in colitis mice].

This study aims to investigate the regulatory effect of Sishen Pills(SSP) and its split prescriptions Ershen Pills(EP) and Wuweizi Powder(WP) on T follicular helper(Tfh) cell subset in the dextran sodium sulfate(DSS)-induced colitis mice and the mechanism. A total of 60 male SPF BALB/c mice were used, 10 of which were randomly selected as the normal group. The rest 50 were induced with 3% DSS solution for colitis modeling. After modeling, they were randomized into 5 groups: model group, SSP group, EP group, WP group, and mesalazine group. Body mass, colon mass, colon mass index, colon length, and unit colon mass index in each group were observed. After hematoxylin-eosin(HE) staining, the pathological injury of colon tissue was scored. The expression levels of molecules related to the STAT/SOCS signaling pathway in colon tissues were analyzed by Western blot. Differentiation levels of Tfh cells such as CD4~+CXCR5~+IL-9~+(Tfh9), CD4~+CXCR5~+IL-17~+(Tfh17), and CD4~+CXCR5~+Foxp3~+(Tfr) in peripheral blood of mice were detected by flow cytometry. The results showed each treatment group demonstrated significant increase in body mass and colon length, decrease in colon mass, colon mass index, unit colon mass index, and histopathological score(P<0.05, P<0.01), reduction of the expression of p-STAT3, STAT3, p-STAT6, and STAT6(P<0.05, P<0.01), rise of the expression of SOCS1 and SOCS3(P<0.05, P<0.01), decrease of Tfh9 and Tfh17 cells, and increase of Tfr cells(P<0.05, P<0.01) compared with the model group. These results indicated that SSP and the split EP and WP may alleviate ulcerative colitis by inhibiting the activation of STAT/SOCS signaling pathway and regulating the balance of Tfr/Tfh9/Tfh17 cells.

Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high-risk Chinese individuals.

Identification of deleterious variants in hereditary breast and ovarian cancer (HBOC) susceptibility genes allows for increased clinical surveillance and early detection, and could predict the response to poly (ADP-ribose) polymerase (PARP) inhibitor in patients with advanced ovarian carcinomas. To determine the prevalence and clinical prediction factors for HBOC syndrome, 882 selected individuals underwent multigene panel testing for HBOC risk assessment during the period from January 2015 to March 2018. Overall, 176 deleterious mutations were observed in 19.50% (n = 172) of individuals. Twenty-six of 176 mutations could not be retrieved in related public databases and were considered to be novel. Among patients with ovarian cancer, 115 deleterious mutations were identified in 429 patients (48.6%) with significant enrichment for a family history of breast or ovarian cancer syndrome (P < .05). In the breast cancer subgroup, 31 deleterious mutations were identified in 261 patients. Besides BRCA1 (8; 25.8%) and BRCA2 (11; 35.5%), the most frequently occurring genes, an additional 12 deleterious mutations (38.7%) were found in seven other susceptibility genes. Higher mutation incidence (57.9%) was observed in subjects with histories of breast and ovarian cancer. Our results highlighted the genetic heterogeneity of HBOC and the efficiency of a multigene panel in carrying out risk assessment.

Changes of B cell subsets in central pathological process of autoimmune encephalomyelitis in mice.

BACKGROUND: Multiple sclerosis is a demyelinating and autoimmune disease and its immune response is not fully elucidated. This study was conducted to examine the pathological changes and B cell subsets in experimental autoimmune encephalomyelitis (EAE) mice, and analyze the expression of triosephosphate isomerase (TPI) and GADPH to define the role of B cell subsets in the disease. RESULTS: Female C57BL/6 mice were randomly divided into EAE group (n = 18) and control (n = 18). During the experiments, the weight and nerve function scores were determined. The proportions of B cell subsets in the peripheral blood were measured by flow cytometry. Seven, 18 and 30 days after immunization, the brain and spinal cord tissues were examined for the infiltration of inflammatory cells using hematoxylin-eosin (HE) HE staining and the demyelination using Luxol fast blue staining. The expression of B cell-related proteins was detected immunohistochemistrially and the expression of antigenic TPI and GADPH was analyzed using enzyme-linked immunosorbent assay (ELISA). HE staining showed that mice had more severe EAE 18 d than 7 d after modelling, while the symptoms were significantly relieved at 30 d. The results were consistent with the weight measurements and neural function scores. Immunohistochemistry studies showed that B cells aggregated in the spinal cord, but not much in the brain. Flow cytometry studies showed that there were more B cells in control than in EAE models from day 7 and the difference was narrowed at day 30. The level of plasma cells increased continuously, reached the top at day 21 and obviously declined at day 30. On other hand, the numbers of memory B cells increased gradually over the experimental period. The numbers of plasma and memory B cells were similar between the control and EAE mice. ELISA data revealed that the brain contents of TPI and GAPDH were higher in EAE mice than in control at day 7, while at day 18, the levels were reversed. CONCLUSIONS: In the central pathological process of EAE mice, B cells exert role through the mechanism other than producing antibodies and the levels of brain TPI and GADPH are related to the severity of autoimmune induced-damage.

Rapid diagnosis of Propionibacterium acnes infection in patient with hyperpyrexia after hematopoietic stem cell transplantation by next-generation sequencing: a case report.

BACKGROUND: The rapid determination of pathogenic agent is very important to clinician for guiding their clinical medication. However, current diagnostic methods are of limitation in many aspects, such as detecting range, time-consuming, specificity and sensitivity. In this report, we apply our new-developing pathogen detection method to clarify that Propionibacterium acnes is the causative agent of a two-year-old boy with juvenile myelomonocytic leukemia presenting clinical symptoms including serious rash and hyperpyrexia while traditional clinical methods of diagnosis fail to detect the pathogenic agent and multiple antimicrobial drugs are almost ineffective Propionibacterium acnes is confirmed to be the infectious agent by quantitative real-time polymerase chain reaction. CASE PRESENTATION: After haploidentical hematopoietic stem cell transplantation, a two-year-old boy with juvenile myelomonocytic leukemia presented to a pediatrist in a medical facility with hyperpyrexia and red skin rash which later changed to black skin rash all over his body. Traditional diagnostic assays were unrevealing, and several routine antimicrobial treatments were ineffective, including the vancomycin, meropenem, tobramycin, cefepime and rifampin. In this case, pediatrist resorted to the next-generation sequencing technology for uncovering potential pathogens so as to direct their use of specific drugs against pathogenic bacteria. Therefore, based on the BGISEQ100 (Ion Proton System) which performed sequencing-by-synthesis, with electrochemical detection of synthesis, and each such reaction coupled to its own sensor, which are in turn organized into a massively parallel sensor array on a complementary metal-oxidesemiconductor chip, we detect and identify the potential pathogens. As a result, we detected a significantly higher abundance of skin bacteria Propionibacterium acnes in patient's blood than controls. It had been reported that patients infected by Propionibacterium acnes almost always had history of immunodeficiency, trauma or surgery. Considering this possible cause, antimicrobial treatment was adjusted to target this rare opportunistic pathogen. Fever and black skin rashes were rapidly reduced after administrating specific drugs against Propionibacterium acnes. CONCLUSION: This case showed our new-developing pathogen detection method was a powerful tool in assisting clinical diagnosis and treatment. And it should be paid more attention to Propionibacterium acnes infection in clinical cases.

Mechanism of Tianma-Gouteng granules lowering blood pressure based on the bile acid-regulated Farnesoid X Receptor-Fibroblast Growth Factor 15- Cholesterol 7α-hydroxylase pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Tianma-Gouteng granules (TGG) is a traditional Chinese medicine (TCM) compound that was first recorded by modern medical practitioner Hu Guangci in "New Meaning of the Treatment of Miscellaneous Diseases in Traditional Chinese Medicine". It is widely used to treat hypertensive vertigo, headache and insomnia. AIM OF STUDY: To investigate the antihypertensive effect of TGG and explore its mechanism. MATERIALS AND METHODS: Spontaneously hypertensive rats (SHR) were prepared a model of the ascendant hyperactivity of liver yang syndrome (AHLYS), blood pressure and general state of rats were recorded. A series of experiments were performed by enzyme-linked immunosorbent assay (ELISA), ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS), 16S rRNA sequencing, real-time fluorescence quantitative PCR (RT-qPCR), and enzymatic colorimetry. RESULTS: TGG can effectively lower blood pressure and improve related symptoms. TGG significantly reduced the levels of IL-1ß, IL-6, TNF-α, Renin and AngII. A total of 17 differential metabolites were found in plasma, with the two most potent metabolic pathways being glycerophospholipid metabolism and primary bile acid biosynthesis. After TGG intervention, 7 metabolite levels decreased and 10 metabolite levels increased. TGG significantly increased the relative abundance of Desulfovibio, Lachnoclostridium, Turicibacter, and decreased the relative abundance of Alluobaculum and Monoglobu. TGG also downregulated Farnesoid X Receptor (FXR) and Fibroblast Growth Factor 15 (FGF15) levels in the liver and ileum, upregulated Cholesterol 7α-hydroxylase (CYP7A1) levels, and regulated total bile acid (TBA) levels. CONCLUSION: TGG can regulate bile acid metabolism through liver-gut axis, interfere with related intestinal flora and plasma metabolites, decrease blood pressure, and positively influence the pathologic process of SHR with AHLYS. When translating animal microbiota findings to humans, validation studies are essential to confirm reliability and applicability, particularly through empirical human research.

Bibliometric study and review of Klotho research: global characteristics and trends from 2000 to 2023.

BACKGROUND: Although Klotho-related research has seen a significant upsurge, the field lacks comprehensive analytical representation and in-depth exploration of pertinent areas such as prevailing research trends and key focus areas. METHOD: This review presents a bibliometric analysis of literature data gathered from the Web of Science Core Collection databases from January 1, 2000, to April 30, 2023. Parameters such as co-authorship, co-citation, co-occurrence, and the emergence of publications, countries, categories, references, and keywords were scrutinized predominantly using Citespace software. RESULTS: Our investigation amassed a total of 3548 papers, with the United States leading in the quantity of publications (1175, accounting for 33.12%), followed by China (867, representing 24.44%), and Japan (439, accounting for 12.37%). While the United States is preeminent in the overall volume of publications, Scotland holds prominence in terms of centrality. Out of a total of 96 subject categories, urology and nephrology (573), and endocrinology and metabolism (542) were the two leading domains of Klotho-related publications. The 2011 paper titled "FGF23 induces left ventricular hypertrophy" by Faul C et al. holds the distinction of being the most frequently cited. The keywords "fibroblast growth factor 23," "phosphate homeostasis," and "functional variants" demonstrated the highest intensity, underscoring the potential of these research areas. CONCLUSION: As the volume of literature grows, the role of Klotho in disease management and its applicability as a marker in disease progression warrant vigilant tracking and study.

[Effects of scorpion and centipede on IL-2, IL-4, and IL-10 in the small intestinal mucosa and joint injury of rats with collagen induced arthritis].

OBJECTIVE: To observe the effects of scorpion and centipede on interleukin (IL)-2, IL-4, IL-10 in the small intestinal mucosa and joint injury of rats with collagen induced arthritis (CIA). METHODS: Sixty Wistar rats were randomly divided into 6 groups: the normal control group, the model group, the low dose scorpion and centipede group, the middle dose scorpion and centipede group, the high dose scorpion and centipede group, and the type II collagen treatment group. The joints' volume was measured 40 days after type II collagen (CII) induced rheumatoid arthritis model was established. The joint injury was observed by naked eyes. The expression levels of IL-2, IL-4, and IL-10 in the small intestine tissue homogenate were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: The joint injury score and volume of two hind limbs were obviously higher in the model group than in the normal control group since the 23rd day (P < 0.01). Rats were accompanied with red, swollen, and deformed foot toes and ankle joints. Walking was even affected. Meanwhile, the joint injury score and volume of two hind limbs were obviously lowered by medicated with 0.4, 0.2, 0.1 g/kg scorpion and centipede, as well as CII on the 32nd day after medication (P <0.05, P < 0.01). The expression levels of IL-2, IL-4, and IL-10 in the small intestine tissue homogenate were obviously lower in the model group than in the normal control group (P < 0.05, P < 0.01). Compared with the model group, only the expression levels of IL-2 and IL-4 in the small intestine tissue homogenate of the high dose scorpion and centipede group and the type II collagen treatment group significantly increased. The expression level of IL-10 significantly increased in the high and middle dose scorpion and centipede groups, as well as the type II collagen treatment group, showing statistical difference (P < 0.05, P < 0.01). CONCLUSIONS: Scorpion and centipede could effectively release the joint injury of rats with CIA. Its mechanism might be correlated with increased expression levels of IL-2, IL-4, and IL-10 in the small intestine mucosa.

[Regulation effect of scorpio and scolopendra on CD4 + CD25 + FoxP3 + Treg cell in peripheral blood from rats with collagen-induced arthritis (CIA)].

OBJECTIVE: To study the regulation effect of Scorpio and Scolopendra on CD4 + CD25 + FoxP3 + Treg Cell in peripheral blood from rats with collagen-induced arthritis. METHODS: Sixty female Wistar rats were randomly divided into 6 groups, normal control group, model control group, low-dose, middle-dose and high-dose Scorpio and Scolopendra group,and the type II collagen group. Rats' arthritis was induced by collagen. The number of CD4 + CD25 + FoxP3 + Treg cell in peripheral blood was tested by flow cytometry, and the level of IL-2 in serum was detected by enzyme linked immunosorbent assay. RESULTS: Compared with the model groups,the levels of CD4 + CD25 + Treg cell and CD4 + CD25 + FoxP3 + Treg cell were increased obviously in the high and low dose of Scorpio and Scolopendra groups (P < 0.05 or P < 0.01), while the level of IL-2 in serum was decreased remarkably in the middle and low dose of Scorpio and Scolopendra groups (P < 0.05 or P < 0.01). CONCLUSION: It is realized that Scorpio and Scolopendra effectively treat RA by regulating the level of CD4 + CD25 + FoxP3 + Treg cell to restore immunological tolerance.

[Effect of oral scorpio and scolopendra powder on T-cell subsets in peripheral blood and intestine from rats with collagen induced arthritis].

OBJECTIVE: To observe effect of oral scorpio and scolopendra powder on T-cell subsets in peripheral blood and intestine from rats with collagen induced arthritis (CIA). METHOD: 60 rats were randomly divided into 6 groups: normal control group, model control group, low-dose scorpio and scolopendra group, middle-dose scorpio and scolopendra group, high-dose scorpio and scolopendra group, and type II collagen group. Rat's rheumatoid arthritis was induced by collagen II (C II). Level of T-cell subsets from peripheral blood and intestine was measured by flow cytometry. RESULT: CD4+ T cellular level was obviously increased (P < 0.05 or P < 0.01) or kept increased tendency in peripheral blood and intestine from the model group compared with that of the normal group, while the ratio of CD4+/CD8+ in intestine was obviously descent but the contrary in peripheral blood (P < 0.05 or P < 0.01). CD4+, CD8+ T cellular level in intestine were obviously descent and the ratio of CD4+ /CD8+ increased in all treated groups when compared with in the model group (P < 0.05 or P < 0.01). However, CD4+ T cellular level and the ratio of CD4+/CD8+ in peripheral blood were remarkablely decreased. CONCLUSION: The mechanism that scorpio and scolopendra could treat rat's rheumatoid arthritis may be regulating balance of T-lymphocyte subsets in peripheral blood and intestine.

[Regulation of sishen wan on Bax/Bcl-2 mRNA, Fas/FasL in colonic tissue from rats with colitis].

OBJECTIVE: To evaluate therapeutic effect of Sishen Wan on experimental colitis, and explore its mechanism by expression of Bax/Bcl-2 mRNA, Fas/FasL in colonic tissue. METHOD: Experimental colitis was induced by rectal administration of trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol. The model animals were divided into four groups: the induced colitis but untreated group, the induced colitis groups treated with the high, middle, low dose of Sishen Wan, and the induced colitis group treated with salicylazosulfapyridine (SASP). After 10 day administration, the body weight, colonic wet weight, colonic weight index, colonic damage score and pathological change were evaluated, and the level of Fas and FasL by flow cytometry, Bax mRNA and Bcl-2 mRNA by reverse transcription polymerase chain reaction (RT-PCT). RESULT: Compared with the model group, the colonic wet weight and colonic weight index were remarkably decreased in the middle dose of Sishen Wan group (P < 0.05). The colonic injury scores were significantly reduced after rats were treated with the three doses of Sishen Wan (P < 0.05). Representative restored features were observed including fewer inflammatory cellular infiltration and follicular hyperplasia, superficial and little ulcer with fibroplasia in colonic mucosa from the treated groups. The expression of Fas in the colonic mucosa was obviously down-regulated (P < 0.05) and the ratio of Bcl-2 mRNA/Bax mRNA was significantly up-regulated (P < 0.05) in the groups treated with the three doses of Sishen Wan. CONCLUSION: Sishen Wan might postpone colonic epithelium apoptosis or improve inflammatory cell apoptosis by regulating the expression of Fas/ FasL and Bax/Bcl-2 mRNA in colonic tissue, which is possible potential path to effectively treat experimental colitis by enema.

Butylphthalide Combined With Conventional Treatment Attenuates MMP-9 Levels and Increases VEGF Levels in Patients With Stroke: A Prospective Cohort Study.

Background and Purpose: Butylphtalide increases the vascular endothelial growth factor (VEGF) and decreases matrix metalloproteinase (MMP)-9 in animal models of stroke and might be of use in the management of stroke. To explore whether butylphthalide combined with conventional treatment can change the levels of MMP-9 and VEGF and the National Institutes of Health Stroke Scale (NIHSS) scores of patients with stroke. Methods: This was a prospective cohort study involving inpatients admitted to the Jiangxi Provincial People's Hospital (January-June 2019) due to acute cerebral infarction. The patients received conventional treatments with or without butylphthalide. The changes in the NIHSS scores were compared between groups. Plasma MMP-9 and VEGF were measured by enzyme-linked immunosorbent assay. Results: A total of 24 patients were included in the conventional treatment group and 46 in the butylphthalide group. The butylphthalide group showed lower MMP-9 (130 ± 59 vs. 188 ± 65, p = 0.001) and higher VEGF (441 ± 121 vs. 378 ± 70, p = 0.034) levels on day 6 compared with the conventional treatment group. The changes in MMP-9 and VEGF were significant, starting on day 3 in the butylphthalide group but on day 6 in the conventional treatment group. There were no differences between the two groups in the NIHSS scores at admission and at discharge (p > 0.05). The overall response rate was higher in the butylphthalide group compared with the conventional treatment group (63.0 vs. 37.5%, p = 0.042). Conclusion: Butylphthalide combined with conventional treatment can decrease MMP-9 levels and increase VEGF levels. The patients showed the reduced NIHSS scores, possibly suggesting some improvement in prognosis after stroke. Still, the conclusions need to be confirmed in a larger sample and in different etiological subtypes of stroke.

Combination of Chronic Alcohol Consumption and High-Salt Intake Elicits Gut Microbial Alterations and Liver Steatosis in Mice.

Alcohol is a globally well-established cause of fatty liver disease (FLD). Increased salt consumption is associated with an increased prevalence of adipocyte hypertrophy and liver injury. In this study, high dietary salt potentiated chronic alcohol-induced hepatic damage. We explored the physiological mechanism of alcoholic FLD in the gastrointestinal tract. Male C57BL/6J mice (8-week-old) were fed a high-salt diet (HSD; 4% NaCl) with or without chronic ethanol (CE) for 1 month. The fecal microbiota, serum biochemical indices, intestinal permeability, level of liver damage, and liver mitochondria were evaluated. The HSD, CE, and their combination (HSDE) significantly changed the gut microbiota's structure, and the HSDE mice contained more probiotic species (e.g., Bifidobacterium and Lactobacillus). The serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels were increased, and the lipid was accumulated in the liver tissues in the CE, HSD, and HSDE groups, which indicated liver damage, especially in the HSDE group. The increased intestinal permeability and mitochondrial dysfunction in the liver cells caused greater injury in the HSDE group than in the other groups. Thus, consuming HSD with alcohol contributes to FLD development and progression.

Therapeutic effect of curcumin on experimental colitis mediated by inhibiting CD8+CD11c+ cells.

AIM: To verify whether curcumin (Cur) can treat inflammatory bowel disease by regulating CD8+CD11c+ cells. METHODS: We evaluated the suppressive effect of Cur on CD8+CD11c+ cells in spleen and Peyer's patches (PPs) in colitis induced by trinitrobenzene sulfonic acid. Mice with colitis were treated by 200 mg/kg Cur for 7 d. On day 8, the therapeutic effect of Cur was evaluated by visual assessment and histological examination, while co-stimulatory molecules of CD8+CD11c+ cells in the spleen and PPs were measured by flow cytometry. The levels of interleukin (IL)-10, interferon (IFN)-γ and transforming growth factor (TGF)-ß1 in spleen and colonic mucosa were determined by ELISA. RESULTS: The disease activity index, colon weight, weight index of colon and histological score of experimental colitis were obviously decreased after Cur treatment, while the body weight and colon length recovered. After treatment with Cur, CD8+CD11c+ cells were decreased in the spleen and PPs, and the expression of major histocompatibility complex II, CD205, CD40, CD40L and intercellular adhesion molecule-1 was inhibited. IL-10, IFN-γ and TGF-ß1 levels were increased compared with those in mice with untreated colitis. CONCLUSION: Cur can effectively treat experimental colitis, which is realized by inhibiting CD8+CD11c+ cells.

Curcumin improves regulatory T cells in gut-associated lymphoid tissue of colitis mice.

AIM: To explore the probable pathway by which curcumin (Cur) regulates the function of Treg cells by observing the expression of costimulatory molecules of dendritic cells (DCs). METHODS: Experimental colitis was induced by administering 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)/ethanol solution. Forty male C57BL/6 mice were randomly divided into four groups: normal, TNBS + Cur, TNBS + mesalazine (Mes) and TNBS groups. The mice in the TNBS + Cur and TNBS +Mes groups were treated with Cur and Mes, respectively, while those in the TNBS group were treated with physiological saline for 7 d. After treatment, the curative effect of Cur was evaluated by colonic weight, colonic length, weight index of the colon, and histological observation and score. The levels of CD4(+)CD25+Foxp3(+) T cells (Treg cells) and costimulatory molecules of DCs were measured by flow cytometry. Also, related cytokines were analyzed by enzyme-linked immunosorbent assay. RESULTS: Cur alleviated inflammatory injury of the colonic mucosa, decreased colonic weigh and histological score, and restored colonic length. The number of Treg cells was increased, while the secretion of TNF-α, IL-2, IL-6, IL-12 p40, IL-17 and IL-21 and the expression of costimulatory molecules (CD205, CD54 [ICAM-1], TLR4, CD252[OX40 L], CD256 [RANK] and CD254 [RANK L]) of DCs were notably inhibited in colitis mice treated with Cur. CONCLUSION: Cur potentially modulates activation of DCs to enhance the suppressive functions of Treg cells and promote the recovery of damaged colonic mucosa in inflammatory bowel disease.

Curcumin Suppressed Activation of Dendritic Cells via JAK/STAT/SOCS Signal in Mice with Experimental Colitis.

Dendritic cells (DCs) play a pivotal role as initiators in the pathogenesis of inflammatory bowel disease and are regulated by the JAK/STAT/SOCS signaling pathway. As a potent anti-inflammatory compound, curcumin represents a viable treatment alternative or adjunctive therapy in the management of chronic inflammatory bowel disease (IBD). The mechanism of curcumin treated IBD on DCs is not completely understood. In the present study, we explored the mechanism of curcumin treated experimental colitis by observing activation of DCs via JAK/STAT/SOCS signaling pathway in colitis mice. Experimental colitis was induced by 2, 4, 6-trinitrobenzene sulfonic acid. After 7 days treatment with curcumin, its therapeutic effect was verified by decreased colonic weight, histological scores, and remitting pathological injury. Meanwhile, the levels of major histocompatibility complex class II and DC costimulatory molecules (CD83, CD28, B7-DC, CD40, CD40 L, and TLR2) were inhibited and followed the up-regulated levels of IL-4, IL-10, and IFN-γ, and down-regulated GM-CSF, IL-12p70, IL-15, IL-23, and TGF-ß1. A key finding was that the phosphorylation of the three members (JAK2, STAT3, and STAT6) of the JAK/STAT/SOCS signaling pathway was inhibited, and the three downstream proteins (SOCS1, SOCS3, and PIAS3) from this pathway were highly expressed. In conclusion, curcumin suppressed the activation of DCs by modulating the JAK/STAT/SOCS signaling pathway to restore immunologic balance to effectively treat experimental colitis.

A targeted next-generation sequencing method for identifying clinically relevant mutation profiles in lung adenocarcinoma.

Molecular profiling of lung cancer has become essential for prediction of an individual's response to targeted therapies. Next-generation sequencing (NGS) is a promising technique for routine diagnostics, but has not been sufficiently evaluated in terms of feasibility, reliability, cost and capacity with routine diagnostic formalin-fixed, paraffin-embedded (FFPE) materials. Here, we report the validation and application of a test based on Ion Proton technology for the rapid characterisation of single nucleotide variations (SNVs), short insertions and deletions (InDels), copy number variations (CNVs), and gene rearrangements in 145 genes with FFPE clinical specimens. The validation study, using 61 previously profiled clinical tumour samples, showed a concordance rate of 100% between results obtained by NGS and conventional test platforms. Analysis of tumour cell lines indicated reliable mutation detection in samples with 5% tumour content. Furthermore, application of the panel to 58 clinical cases, identified at least one actionable mutation in 43 cases, 1.4 times the number of actionable alterations detected by current diagnostic tests. We demonstrated that targeted NGS is a cost-effective and rapid platform to detect multiple mutations simultaneously in various genes with high reproducibility and sensitivity.

Poly[(µ5-3-carboxybenzene-1,2-dicarboxylato)lead(II)]: a helical lead(II) coordination polymer.

In the title polymer, [Pb(C9H4O6)]n, the asymmetric unit contains a monomer of a Pb(II) cation with a doubly deprotonated 3-carboxybenzene-1,2-dicarboxylate dianion (1,2,3-Hbtc(2-)). Each Pb(II) centre is seven-coordinated by seven O atoms of bridging carboxy/carboxylate groups from five 1,2,3-Hbtc(2-) ligands, forming a distorted pentagonal bipyramid. The Pb(II) cations are bridged by 1,2,3-Hbtc(2-) anions, yielding two-dimensional chiral layers. The layers are stacked above each other to generate a three-dimensional supramolecular architecture via a combination of C-H···O interactions. The thermogravimetric and optical properties are also reported.

Scorpio and Scolopendra attenuate inflammation and articular damage in rats with collagen-induced arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Scorpio and Scolopendra (SS) are two traditional Chinese medicines, which are generally used to treat rheumatoid arthritis (RA) in China. However, the mechanism is so far unclear. The purpose of this study was to explore the effects and mechanisms of SS in attenuating inflammation and joint injury in collagen-induced arthritis in rats. MATERIALS AND METHODS: RA was induced in Wistar rats by injection of collagen, meanwhile, the rats were administrated daily either SS (0.4 g/kg, 0.2 g/kg, and 0.1 g/kg) or vehicle (physiological saline) for 42 days. The therapeutic effect of SS on RA was evaluated by pathological methods. T lymphocyte subsets and anti-collagen type II (CII) antibody were tested in peripheral blood. Tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), interleukin-4 (IL-4) and interleukin-10 (IL-10) were assessed in tissue homogenate of fresh joints. RESULTS: The inflammation and articular damage in SS powder-treated rats were attenuated significantly. In addition, SS powder was revealed to modulate the equilibrium of T lymphocyte subsets, down-regulate TNF-α and IL-1ß, up-regulate IL-4 and IL-10, and significantly suppress the level of anti-CII antibody. CONCLUSIONS: Scorpio and Scolopendra, when used as a combination, reveal desirable effect for treatment of rheumatoid arthritis, and this beneficial effect may be accomplished through normalization of T lymphocyte subsets and the balance of Th1/Th2 cytokines.