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1.
Fish Shellfish Immunol ; 119: 563-574, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34687884

RESUMO

CC motif chemokine ligand 25 (CCL25) is a key chemokine that attracts various types of leukocytes, such as activated peritoneal macrophages. However, information on CCL25 in fish is limited. Here, a CCL25 gene (LjCCL25) was identified from Japanese sea bass (Lateolabrax japonicus), showing upregulation in multiple tissues against Vibrio harveyi infection. The recombinant LjCCL25 (rLjCCL25) only significantly induced the migration of monocytes/macrophages (MO/MΦ) both in vitro and in vivo, but didn't induce that of neutrophils or lymphocytes. Additionally, rLjCCL25 only induced migration of the lipopolysaccharide-stimulated MO/MΦ (M1 type). Knockdown of Japanese sea bass CC chemokine receptor 9 (LjCCR9) expression in MO/MФ by RNA interference inhibited the LjCCL25-induced chemotaxis of resting and M1 type MO/MФ. Moreover, administration of 300 ng/g rLjCCL25 effectively increased the survival of V. harveyi-infected fish and decreased bacterial load. Our study demonstrates that LjCCL25 functions as an MO/MФ chemoattractant via LjCCR9 in Japanese sea bass against V. harveyi.

2.
Int Immunopharmacol ; 101(Pt A): 108169, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34607227

RESUMO

OBJECTIVE: This study was aimed to investigate the effect of monomer derivative of paeoniflorin (MDP) on macrophage pyroptosis mediated by TLR4/NLRP3/GSDMD signaling pathway in adjuvant arthritis (AA) rats. METHOD: Wistar rats were divided into normal group, AA model group, MDP (50 mg/kg) group and MTX (0.5 mg/kg) group. The expression of TLR4, NLRP3 and GSDMD in macrophage were detected by immunofluorescence assay. The expression of TLR4 and the ratio of macrophage pyroptosis were analyzed by flow cytometry. Cell morphology was observed by scanning electron microscopy. The cytokine levels of IL-18 and IL-1ß were detected by ELISA. The expressions of proteins related to macrophage pyroptosis were detected by western blot. RESULTS: MDP has a therapeutic effect on rats AA by reducing the secondary inflammation and improving pathological changes. The results of X-ray imaging and ultrasound images showed that MDP could inhibit bone erosion, soft tissue swelling, and joint space narrowing. Macrophage pyroptosis was found in secondary inflammation of AA rats. The expressions of TLR4, MyD88, NLRP3, Caspase-1, ASC, and GSDMD-N in macrophage were increased, the levels of IL-18 and IL-1ß were enhanced, and the morphology of pyroptosis could be observed. MDP could inhibit macrophage polarization and macrophage pyroptosis, and down-regulated the cytokine levels of IL-18 and IL-1ß in AA rats. MDP could regulate the M1/M2 ratio, decreased the ratio of macrophage pyroptosis and down-regulated the expressions of TLR4, MyD88, NLRP3, Caspase-1, ASC, and GSDMD-N in vivo and in vitro. CONCLUSION: Abnormal activation of TLR4/NLRP3/GSDMD signaling pathway may be involved in macrophage pyroptosis in AA rats. The therapeutic effect of MDP on AA rats is related to the inhibition of macrophage pyroptosis by regulating the TLR4/NLRP3/GSDMD signaling pathway.

3.
IUBMB Life ; 73(12): 1406-1422, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34590407

RESUMO

Deficiency of G protein-coupled receptor kinase 2 (GRK2) was found to protect mice from dextran sulfate sodium (DSS)-induced colitis. Paeoniflorin-6'-O-benzene sulfonate (CP-25) has been shown to exert anti-inflammatory immune regulatory effects in animal models of inflammatory autoimmune disease. This study aimed to investigate the of GRK2 in the pathogenesis of ulcerative colitis (UC) and its effects on macrophage polarization, macrophage subtype regulation of intestinal barrier function, and therapeutic effects of CP-25 in mice with DSS-induced colitis. We found imbalanced macrophage polarization, intestinal barrier dysfunction, and abnormal activation of GRK2 and TLR4-NF-κB-NLRP3 inflammasome signaling pathway in the colonic mucosa of patients with UC. CP-25, restored the damaged intestinal barrier function by inhibiting the transmembrane region of GRK2 in macrophages stimulated by lipopolysaccharides. CP-25 exerted therapeutic effects by ameliorating clinical manifestation, regulating macrophage polarization, and restoring abnormally activated TLR4-NF-κB-NLRP3 inflammasome signaling pathway by inhibiting GRK2. These data suggest the pathogenesis of UC may be related to the imbalance of macrophage polarization, which leads to abnormal activation of TLR4-NF-κB-NLRP3 inflammasome signaling pathway mediated by GRK2 and destruction of the intestinal mucosal barrier. CP-25 confers therapeutic effects on colitis by inhibiting GRK2 translocation to induce the downregulation of TLR4-NF-κB-NLRP3 inflammasome signaling in macrophages.

4.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(3): 341-346, 2021 Jun 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34041885

RESUMO

OBJECTIVES: To analyze the chromatic properties and translucency of porcelain veneers made from different ceramic materials against the background of tetracycline-stained teeth. METHODS: Porcelain specimens (A1, A3, B2, B4) measuring 0.50 mm in thickness were prepared by heat-press casting and layering. The L*, a*, and b* values of the specimens against simulated tetracycline tooth and black-and-white backgrounds were measured by a spectrophotometer, and color differences ΔE001 between specimens on simulated tetracycline backgrounds and the backgrounds themselves and ΔE002 between specimens on simulated tetracycline backgrounds and the white background were calculated. The translucent parameter (TP) was also evaluated. RESULTS: The ΔE001 of feldspathic specimens (IPS d.SIGN) with the opaque layer was significantly greater than that of glass ceramic specimens (IPS e.max Press LT), and the ΔE001 of group B4 was consistently greater than those of the other color groups (P<0.05). The ΔE002 values of all feldspathic specimens with the opaque layer were less than 1.25, and the ΔE002 values of the glass ceramic specimens were greater than 2.23. However, no significant difference was observed among the different color groups (P>0.05). The TP values of feldspathic specimens with the opaque layer were significantly lower than those of glass ceramic specimens(P<0.05), but no significant difference was observed among different color groups (P>0.05). CONCLUSIONS: When changing the color of tetracycline-stained teeth, 0.50 mm-thick IPS d.SIGN feldspathic veneers with an opaque layer provide better chromatic properties than IPS e.max Press LT glass ceramic veneers. However, the translucency of feldspathic veneers is generally poorer than that of glass ceramic veneers.


Assuntos
Porcelana Dentária , Facetas Dentárias , Cerâmica , Cor , Teste de Materiais , Tetraciclinas
5.
Acta Pharmacol Sin ; 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859345

RESUMO

Our previous study showed that chronic treatment with tumor necrosis factor-α (TNF-α) decreased cAMP concentration in fibroblast-like synoviocytes (FLSs) of collagen-induced arthritis (CIA) rats. In this study we investigated how TNF-α impairs cAMP homeostasis, particularly clarifying the potential downstream molecules of TNF-α and prostaglandin receptor 4 (EP4) signaling that would interact with each other. Using a cAMP FRET biosensor PM-ICUE3, we demonstrated that TNF-α (20 ng/mL) blocked ONO-4819-triggered EP4 signaling, but not Butaprost-triggered EP2 signaling in normal rat FLSs. We showed that TNF-α (0.02-20 ng/mL) dose-dependently reduced EP4 membrane distribution in normal rat FLS. TNF-α significantly increased TNF receptor 2 (TNFR2) expression and stimulated proliferation in human FLS (hFLS) via ecruiting TNF receptor-associated factor 2 (TRAF2) to cell membrane. More interestingly, we revealed that TRAF2 interacted with G protein-coupled receptor kinase (GRK2) in the cytoplasm of primary hFLS and helped to bring GRK2 to cell membrane in response of TNF-α stimulation, the complex of TRAF2 and GRK2 then separated on the membrane, and translocated GRK2 induced the desensitization and internalization of EP4, leading to reduced production of intracellular cAMP. Silencing of TRAF2 by siRNA substantially diminished TRAF2-GRK2 interaction, blocked the translocation of GRK2, and resulted in upregulated expression of membrane EP4 and intracellular cAMP. In CIA rats, administration of paroxetine to inhibit GRK2 effectively improved the symptoms and clinic parameters with significantly reduced joint synovium inflammation and bone destruction. These results elucidate a novel form of cross-talk between TNFR (a cytokine receptor) and EP4 (a typical G protein-coupled receptor) signaling pathways. The interaction between TRAF2 and GRK2 may become a potential new drug target for the treatment of inflammatory diseases.

6.
Acta Pharmacol Sin ; 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33864023

RESUMO

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovitis and the destruction of small joints. Emerging evidence shows that immunoglobulin D (IgD) stimulation induces T-cell activation, which may contribute to diseases pathogenesis in RA. In this study, we investigated the downstream signaling pathways by which IgD activated T cells as well as the possible role of IgD in the T-B interaction. Peripheral blood mononuclear cells were isolated from peripheral blood of healthy controls and RA patients. We demonstrated that IgD activated T cells through IgD receptor (IgDR)-lymphocyte-specific protein tyrosine kinase (Lck)-zeta-associated protein 70 (ZAP70)/phosphatidylinositol 3-kinase (PI3K)/nuclear factor kappa-B (NF-κB) signaling pathways; IgD-induced CD4+ T cells promoted the proliferation of CD19+ B cells in RA patients. A novel fusion protein IgD-Fc-Ig (composed of human IgD-Fc domain and IgG1 Fc domain, which specifically blocked the IgD-IgDR binding) inhibited the coexpression of IgDR and phosphorylated Lck (p-Lck) and the expression levels of p-Lck, p-ZAP70, p-PI3K on CD4+ T cells, and decreased NF-κB nuclear translocation in Jurkat cells. Meanwhile, IgD-Fc-Ig downregulated the expression levels of CD40L on CD4+ T cells as well as CD40, CD86 on CD19+ B cells in RA patients and healthy controls. It also decreased the expression levels of CD40L on CD4+ T cells and CD40 on CD19+ B cells from spleens of collagen-induced arthritis (CIA) mice and reduced IL-17A level in mouse serum. Moreover, administration of IgD-Fc-Ig (1.625-13 mg/kg, iv, twice a week for 4 weeks) in CIA mice dose-dependently decreased the protein expression levels of CD40, CD40L, and IgD in spleens. IgD-Fc-Ig restrains T-cell activation through inhibiting IgD-IgDR-Lck-ZAP70-PI3K-NF-κB signaling, thus inhibiting B-cell activation. Our data provide experimental evidences for application of IgD-Fc-Ig as a highly selective T cell-targeting treatment for RA.

7.
Acta Pharmacol Sin ; 42(10): 1665-1675, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33483588

RESUMO

B cell activating factor of TNF family (BAFF) is a member of TNF ligand superfamily and plays a key role in B cell homeostasis, proliferation, maturation, and survival. In this study, we detected BAFF level, the expressions of BAFF receptors and important molecules in NF-κB pathway in rheumatoid arthritis (RA) patients and analyzed the correlation between BAFF level and clinical variables, laboratory parameters or X-ray scores in order to elucidate the roles of BAFF in RA. A total of 50 RA patients and 50 healthy controls (HCs) were enrolled. We showed that the serum BAFF level in RA patients was significantly higher than that of HCs, and the percentages of B cell subsets (CD19+ B cells, CD19+CD27+ B cells, CD19+CD20+CD27+ B cells, and CD19+CD20-CD27+ B cells) in the serum of RA patients were significantly increased compared with those of HCs. The percentages of CD19+BAFFR+ B cells, CD19+ BCMA+ B cells, and CD19+ TACI+ B cells in RA patients were significantly increased compared with those in HCs. The expression of important molecules in the NF-κB pathway (MKK3, MKK6, p-P38, p-P65, TRAF2, and p52) was significantly higher in RA patients than in HCs, but p100 level in RA patients was lower than that in HCs. The serum BAFF level was positively correlated with C-reactive protein, rheumatoid factor, disease activity score (in 28 joints), swollen joint counts, tender joint counts, and X-ray scores. When normal B cells were treated with BAFF in vitro, the percentages of the B cell subset and the expression of BAFF receptors were significantly upregulated. BAFF also promoted the expression of MKK3, MKK6, p-P38, p-P65, TRAF2, and p52. In conclusion, this study demonstrates that BAFF level is correlated with the disease activity and bone destruction of RA. BAFF is involved in the differentiation, proliferation, and activation of B cells in RA through NF-κB signaling pathway, suggesting that BAFF might be an ideal therapeutic target for RA.

8.
Nanotheranostics ; 5(1): 73-89, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391976

RESUMO

Microfluidic chip is not a chip in the traditional sense. It is technologies that control fluids at the micro level. As a burgeoning biochip, microfluidic chips integrate multiple disciplines, including physiology, pathology, cell biology, biophysics, engineering mechanics, mechanical design, materials science, and so on. The application of microfluidic chip has shown tremendous promise in the field of cancer therapy in the past three decades. Various types of cell and tissue cultures, including 2D cell culture, 3D cell culture and tissue organoid culture could be performed on microfluidic chips. Patient-derived cancer cells and tissues can be cultured on microfluidic chips in a visible, controllable, and high-throughput manner, which greatly advances the process of personalized medicine. Moreover, the functionality of microfluidic chip is greatly expanding due to the customizable nature. In this review, we introduce its application in developing cancer preclinical models, detecting cancer biomarkers, screening anti-cancer drugs, exploring tumor heterogeneity and producing nano-drugs. We highlight the functions and recent development of microfluidic chip to provide references for advancing cancer diagnosis and treatment.


Assuntos
Técnicas Analíticas Microfluídicas/instrumentação , Neoplasias/diagnóstico , Antineoplásicos/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico
9.
Phytother Res ; 35(2): 1033-1047, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33006176

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects not only joints but also multiple organ systems including cardiovascular system. Endothelial dysfunction plays an important role in cardiovascular diseases (CVD). In RA, endothelial dysfunction exists at both the macrovascular and the microvascular levels, which is a precursor to vasculitis. This study aimed to investigate the pathogenesis of vasculitis and the therapeutic effect of CP-25 on vasculitis in high-fat diet (HFD) collagen-induced arthritis (CIA) rats. Experimental groups were divided into normal group, HFD group, CIA group, HFD CIA group, CP-25 group and MTX group. In vitro, IL-17A was used to stimulate human umbilical vein endothelial cells (HUVECs), and then CP-25 was used to intervene. Results showed that CP-25 reduced global scoring (GS), arthritis index (AI), and swollen joint count (SJC) scores, improved histopathological score, reduced T cells percentage, and decreased IL-17A and ICAM-1 levels. Besides, CP-25 reduced the expression of p-STAT3 to normal levels in vascular of HFD CIA rats. In vitro, IL-17A promoted the expression of p-JAK1, p-JAK2, p-JAK3, pSTAT3, and ICAM-1, and CP-25 inhibited the expression of p-JAK1, p-JAK2, p-JAK3, p-STAT3, and ICAM-1. In conclusion, CP-25 might inhibit endothelial cell activation through inhibiting IL-17A/JAK/STAT3 signaling pathway, which improves vasculitis in HFD CIA rats.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Dieta Hiperlipídica/métodos , Células Endoteliais/metabolismo , Glucosídeos/uso terapêutico , Interleucina-17/metabolismo , Monoterpenos/uso terapêutico , Vasculite/tratamento farmacológico , Animais , Modelos Animais de Doenças , Glucosídeos/farmacologia , Humanos , Masculino , Monoterpenos/farmacologia , Ratos , Transdução de Sinais
10.
Acta Pharmacol Sin ; 42(5): 755-766, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32855529

RESUMO

ß-arrestin2 (ß-arr2) is, a key protein that mediates desensitization and internalization of G protein-coupled receptors and participates in inflammatory and immune responses. Deficiency of ß-arr2 has been found to exacerbate collagen antibody-induced arthritis (CAIA) through unclear mechanisms. In this study we tried to elucidate the molecular mechanisms underlying ß-arr2 depletion-induced exacerbation of CAIA. CAIA was induced in ß-arr2-/- and wild-type (WT) mice by injection of collagen antibodies and LPS. The mice were sacrificed on d 13 after the injection, spleen, thymus and left ankle joints were collected for analysis. Arthritis index (AI) was evaluated every day or every 2 days. We showed that ß-arr2-/- mice with CAIA had a further increase in the percentage of plasma cells in spleen as compared with WT mice with CAIA, which was in accordance with elevated serum IgG1 and IgG2A expression and aggravating clinical performances, pathologic changes in joints and spleen, joint effusion, and joint blood flow. Both LPS stimulation of isolated B lymphocytes in vitro and TNP-LPS challenge in vivo led to significantly higher plasma cell formation and antibodies production in ß-arr2-/- mice as compared with WT mice. LPS treatment induced membrane distribution of toll-like receptor 4 (TLR4) on B lymphocytes, accordingly promoted the nuclear translocation of NF-κB and the transcription of Blimp1. Immunofluorescence analysis confirmed that more TLR4 colocalized with ß-arr2 in B lymphocytes in response to LPS stimulation. Depletion of ß-arr2 restrained TLR4 on B lymphocyte membrane after LPS treatment and further enhanced downstream NF-κB signaling leading to additional increment in plasma cell formation. In summary, ß-arr2 depletion exacerbates CAIA and further increases plasma cell differentiation and antibody production through inhibiting TLR4 endocytosis and aggravating NF-κB signaling.


Assuntos
Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Plasmócitos/metabolismo , beta-Arrestina 2/deficiência , Animais , Anticorpos Monoclonais/imunologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/patologia , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/patologia , Peso Corporal/fisiologia , Diferenciação Celular/fisiologia , Colágeno Tipo II/imunologia , Imunidade Humoral/fisiologia , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Ativação Linfocitária/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Transdução de Sinais/fisiologia , Receptor 4 Toll-Like/metabolismo
11.
Medicine (Baltimore) ; 99(51): e23661, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371102

RESUMO

ABSTRACT: This analysis of clinical data from systemic lupus erythematosus (SLE) patients with chylothorax and/or chylous ascites was conducted to guide further clinical work.From June 2008 to June 2019, 15 SLE patients (14 females and 1 male) with chylothorax and/or chylous ascites were hospitalized at the Beijing Shijitan Hospital. Sixty SLE patients without chylothorax and chylous ascites were randomly selected as controls. Patients', clinical data was investigated.The mean age of onset of chylothorax and/or chylous ascites in patients with SLE was 35.7 ±â€Š3.7 years (range, 15-69 years). The mean disease duration of chylothorax and/or chylous ascites in patients with SLE was 13.7 ±â€Š3.4 months (range, 1-48 months). Patients with chylothorax and/or chylous ascites were always diagnosed at later stages of SLE compared with the controls. Among cases, glomerulonephritis and hematologic system involvement were the most common complications. Anti-Sjogren's syndrome antigen A antibody was positive in 7 cases (46.7%). Among cases, direct lymphangiography was performed in 13 patients, indicating thoracic duct outlet obstruction or a poor backflow at the terminal of the thoracic duct. Subsequently, 13 patients were treated with corticosteroids, combined with immunosuppressants in 11 patients and thoracic duct surgery in 6 patients. Eleven patients were followed up for 0.5 to 7.0 years. One patient died of infection. Eight patients (53.3%) achieved remission.Chylothorax and/or chylous ascites are rare complications of SLE. An early diagnosis and timely initiation of glucocorticoids, immunosuppressants, and surgery are critical to relieve symptoms and to improve prognosis.


Assuntos
Quilotórax/etiologia , Ascite Quilosa/etiologia , Lúpus Eritematoso Sistêmico/complicações , Adolescente , Adulto , Idoso , Criança , China/epidemiologia , Quilotórax/epidemiologia , Quilotórax/terapia , Ascite Quilosa/epidemiologia , Ascite Quilosa/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
12.
Front Pharmacol ; 11: 579068, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33041823

RESUMO

Integrins are the adhesion molecules and receptors of extracellular matrix (ECM). They mediate the interactions between cells-cells and cells-ECM. The crosstalk between cancer cells and their microenvironment triggers a variety of critical signaling cues and promotes the malignant phenotype of cancer. As a type of transmembrane protein, integrin-mediated cell adhesion is essential in regulating various biological functions of cancer cells. Recent evidence has shown that integrins present on tumor cells or tumor-associated stromal cells are involved in ECM remodeling, and as mechanotransducers sensing changes in the biophysical properties of the ECM, which contribute to cancer metastasis, stemness and drug resistance. In this review, we outline the mechanism of integrin-mediated effects on biological changes of cancers and highlight the current status of clinical treatments by targeting integrins.

13.
Medicine (Baltimore) ; 99(35): e21930, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871933

RESUMO

BACKGROUND: This study will systematically assess the efficacy and safety of Bacillus Calmette-Guerin (BCG) for patients with bladder cancer (BC). METHODS: Literature searches will be performed in multiple electronic databases from inception to present: MEDLINE, EMBASE, CINAHL, Science Direct, Cochrane Library, Web of Science, and China National Knowledge Infrastructure. We will also examine grey literature through identifying conference proceedings, thesis, dissertations, and website of clinical trials registry. Two investigators will independently scan all citation titles, abstracts, and full-text studies. The study quality will be assessed by Cochrane Risk of Bias Tool. If possible, we will perform meta-analysis. Additional analyses will be carried out to test the potential sources of heterogeneity among included trials. RESULTS: The present study will summarize high quality trials on investigating the efficacy and safety of BCG for patients with BC. CONCLUSION: The results of this study will supply helpful evidence to determine whether BCG is effective or not for BC. STUDY REGISTRATION NUMBER: INPLASY202070042.


Assuntos
Vacina BCG/efeitos adversos , Vacina BCG/uso terapêutico , Revisões Sistemáticas como Assunto , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Pancreas ; 49(7): 967-974, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32658083

RESUMO

OBJECTIVE: The study concerns identifying risk factors and developing nomogram for pancreatic pseudocyst (PPC) in idiopathic chronic pancreatitis (ICP) to facilitate early diagnosis. METHODS: From January 2000 to December 2013, ICP patients admitted to our center were enrolled. Cumulative incidence of PPC was determined by Kaplan-Meier method. Patients were randomized into training group and validation group in a 2:1 ratio. Risk factors of PPC were determined through Cox proportional hazards regression model based on training cohort. The nomogram was constructed according to risk factors. RESULTS: Totally, 1633 ICP patients were included with a median follow-up duration of 9.8 years. Pancreatic pseudocyst was observed in 14.7% (240/1633) of patients after ICP onset. The cumulative incidences of PPC were 8.2%, 10.4%, and 12.9% at 3, 5, and 10 years after ICP onset, respectively. Male sex, smoking history, history of severe acute pancreatitis, and chronic pain at/before diagnosis of ICP and complex pathologic changes in main pancreatic duct were recognized as risk factors of PPC development. The nomogram constructed with these risk factors achieved good concordance indexes. CONCLUSIONS: Risk for PPC could be estimated through the nomogram. High-risk patients were suggested to be followed up closely to help early diagnosis of PPC.


Assuntos
Nomogramas , Pseudocisto Pancreático/diagnóstico , Pancreatite Crônica/diagnóstico , Medição de Risco/estatística & dados numéricos , Adulto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pseudocisto Pancreático/etiologia , Pancreatite Crônica/complicações , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Medição de Risco/métodos , Fatores de Risco
15.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(1): 27-32, 2020 Jan 28.
Artigo em Chinês | MEDLINE | ID: mdl-32476370

RESUMO

OBJECTIVE: To study whether the two methods of energy calculation affects the value of relative energy contribution in men's T54 wheelchair racing events. METHODS: Ten men's T54 wheelchair racers (age (22.9±5.2) yrs、sitting height (90.9±3.2) cm、body mass (59.3±8.3) kg) participate in 1 incremental test and 4 time trials (400 m、800 m、1 500 m、5 000 m). A portable gas analyzer, polar heart rate belt and a blood lactate analyzer were used to measure VO2 at every breath, HR and blood lactate changes. The energetic contribution was measured with phosphocreatine-lactate-oxygen(PCr-La-O2) and maximal accumulated oxygen deficit(MAOD) methods. RESULTS: The anaerobic and total energy portions from MAOD were lower than those from PCr-La-O2 ( especially in 400 m: WTOT (50.8 ±12.7) KJ vs (65.2±13.5) KJ、WANA (31.0±9.0) KJ vs (45.4±11.4) KJ, P<0.05), resulting in WAER% calculated by MAOD was generally higher than PCr-La-O2 method (especially in 400 m : WAER% 39.0% ±1.2% vs 30.4%±8.4 %,P<0.05). CONCLUSION: The study proves that the two-calculation method causes WAER% difference. MAOD method does lead to an overestimate of WAER%. Recommend to use the same calculation method for diagnosis and monitoring in the longitudinal study of long-term scientific research (such as the 4-year Olympic Games),to avoiding the difference in results caused by different calculation methods, which will further influence the development of coaches' training plans and training implementation effect.


Assuntos
Metabolismo Energético , Consumo de Oxigênio , Esportes para Pessoas com Deficiência , Cadeiras de Rodas , Teste de Esforço , Humanos , Ácido Láctico , Masculino
16.
Front Pharmacol ; 11: 676, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32477138

RESUMO

Objective: To explore the role of B cells in rheumatoid arthritis (RA) and the potential effects and mechanisms of etanercept on B cells. Methods: In RA patients, the levels of tumor necrosis factor-α (TNF-α) and B cell activating factor (BAFF) were detected by ELISA. The percentage of B cell subsets was measured by flow cytometry. Laboratory indicators (rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate) and clinical indicators (disease activity score in 28 joints, health assessment questionnaire score, swollen joint counts, tender joint counts) were measured. The correlation between B cell subsets and laboratory indicators or clinical indicators was analyzed. In mice, B cells proliferation was detected by CCK-8 kit. The expression of TNFRII and the percentage of B cell subsets in spleen were detected by flow cytometry. The expressions of TRAF2, p38, P-p38, p65, P-p65 in B cells were detected by WB. Results: The percentage of CD19-CD27+CD138+ plasma B cells was positively correlated with ESR or RF. Etanercept could decrease the percentage of CD19+ total B cells, CD19+CD27+ memory B cells and CD19-CD27+CD138+ plasma B cells, reduce the levels of TNF-α, BAFF, relieve clinical and laboratory indicators in RA patients. In addition, etanercept could inhibit the proliferation of B cells, bate the differentiation of transitional B cells to mature B cells, down-regulate the expression of TNFRII, TRAF2, P-p38, P-p65 in B cells. Conclusion: B cells act a key role in the pathogenesis of RA. Etanercept inhibits B cells differentiation by down-regulating TNFRII/TRAF2/NF-κB signaling pathway.

17.
Sci Rep ; 10(1): 10448, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32591619

RESUMO

Bimodal classification of idiopathic chronic pancreatitis (ICP) into early-onset (<35 years) and late-onset (>35 years) ICP was proposed in 1994 based on a study of 66 patients. However, bimodal distribution wasn't sufficiently demonstrated. Our objective was to examine the validity and relevance of the age-based bimodal classification of ICP. We analyzed the distribution of age at onset of ICP in our cohort of 1633 patients admitted to our center from January 2000 to December 2013. Classify ICP patients into early-onset ICP(a) and late-onset ICP(a) according to different cut-off values (cut-off value, a = 15, 25, 35, 45, 55, 65 years old) for age at onset. Compare clinical characteristics of early-onset ICP(a) and late-onset ICP(a). We found slightly right skewed distribution of age at onset for ICP in our cohort. There were differences between early-onset and late-onset ICP with respect to basic clinical characteristics and development of key clinical events regardless of the cut off age at onset i.e. 15, 25, 35, 45 or even higher. The validity of the bimodal classification of early-onset and late-onset ICP could not be established in our large patient cohort and therefore such a classification needs to be reconsidered.


Assuntos
Pancreatite Crônica/classificação , Adolescente , Adulto , Idade de Início , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite Crônica/patologia , Reprodutibilidade dos Testes , Adulto Jovem
18.
Front Pharmacol ; 11: 156, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32180721

RESUMO

Infantile cholestatic hepatopathy (ICH) is a clinical syndrome characterized by the accumulation of cytotoxic bile acids in infancy, leading to serious liver cirrhosis or liver failure. The aetiology of ICH is complicated and some of them is unknown. Regardless of the aetiology, the finial pathology of ICH is hepatocyte apoptosis caused by severe and persistent cholestasis. It is already known that activation of calcium-sensing receptor (CaSR) could lead to the apoptosis of cardiomyocytes. However, the mechanism by CaSR-mediated cholestasis-related hepatocyte apoptosis is not fully understood. Li-Dan-He-Ji (LDHJ), a Traditional Chinese Medicine prescription, was developed to treat ICH. Another aim of this study was to investigate the possible mechanisms of LDHJ in cholestasis-related hepatocyte apoptosis. Using the primary hepatocytes, we first investigated the molecular mechanism of CaSR-mediated hepatocyte apoptosis in cholestasis. Then we prepared LDHJ granules and used ultra-high-performance liquid chromatography to identify the predominant drugs; confirmed the stability of the main substances; and for cell experiments screened forsythoside-A, emodin and chlorogenic acid as the three active substances of LDHJ granules. In the young rats with ANIT-induced intrahepatic cholestasis and the primary hepatocytes with TCDC-induced cholestasis-related hepatocyte apoptosis, the levels of liver injury and cholestasis-related biomarkers, calcium-sensing receptor (CaSR), hepatocyte apoptosis, Bax/Bcl-2 ratio, Cytochrome-C, caspase-3, phosphorylated-c-Jun NH2-terminal kinase (p-JNK)/JNK, and p-P38/P38 were all increased, while the levels of p-extracellular signal-regulated kinase (p-ERK)/ERK were decreased. However, LDHJ granules and its three active substances effectively reversed these changes. Furthermore, the three active substances reduced the increases in the intracellular calcium concentration ([Ca2+]i) and ROS levels and attenuated the dissipation of the mitochondria membrane potential in the TCDC-induced primary hepatocytes. The opposite results were obtained from the TCDC-induced primary hepatocytes treated with an agonist of CaSR (GdCl3) plus forsythoside-A, emodin or chlorogenic acid. Based on the results from in vivo and in vitro studies, LDHJ functions as an antagonist of CaSR to regulate hepatocyte apoptosis in cholestasis through the mitochondrial pathway and mitogen-activated protein kinase pathway.

19.
Acta Pharmacol Sin ; 41(6): 800-812, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31937932

RESUMO

IgD-Fc-Ig fusion protein, a new biological agent, is constructed by linking a segment of human IgD-Fc with a segment of human IgG1-Fc, which specifically blocks the IgD-IgDR pathway and selectively inhibits the abnormal proliferation, activation, and differentiation of T cells. In this study we investigated whether IgD-Fc-Ig exerted therapeutic effects in collagen-induced arthritis (CIA) rats. CIA rats were treated with IgD-Fc-Ig (1, 3, and 9 mg/kg) or injected with biological agents etanercept (3 mg/kg) once every 3 days for 40 days. In the PBMCs and spleen lymphocytes of CIA rats, both T and B cells exhibited abnormal proliferation; the percentages of CD3+ total T cells, CD3+CD4+ Th cells, CD3+CD4+CD25+-activated Th cells, Th1(CD4+IFN-γ+), and Th17(CD4+IL-17+) were significantly increased, whereas the Treg (CD4+CD25+Foxp3+) cell percentage was decreased. IgD-Fc-Ig administration dose-dependently decreased the indicators of arthritis; alleviated the histopathology of spleen and joint; reduced serum inflammatory cytokines levels; decreased the percentages of CD3+ total T cells, CD3+CD4+ Th cells, CD3+CD4+CD25+-activated Th cells, Th1 (CD4+IFN-γ+), and Th17(CD4+IL-17+); increased Treg (CD4+CD25+Foxp3+) cell percentage; and down-regulated the expression of key molecules in IgD-IgDR-Lck-NF-κB signaling (p-Lck, p-ZAP70, p-P38, p-NF-κB65). Treatment of normal T cells with IgD (9 µg/mL) in vitro promoted their proliferation. Co-treatment with IgD-Fc-Ig (0.1-10 µg/mL) dose-dependently decreased IgD-stimulated T cell subsets percentages and down-regulated the IgD-IgDR-Lck-NF-κB signaling. In summary, this study demonstrates that IgD-Fc-Ig alleviates CIA and regulates the functions of T cells through inhibiting IgD-IgDR-Lck-NF-κB signaling.


Assuntos
Artrite Experimental/imunologia , Imunoglobulina D/imunologia , Fragmentos Fc das Imunoglobulinas/imunologia , NF-kappa B/metabolismo , Receptores de IgG/imunologia , Transdução de Sinais , Linfócitos T/imunologia , Ácido Acético , Animais , Artrite Experimental/induzido quimicamente , Imunoglobulina D/química , Fragmentos Fc das Imunoglobulinas/química , Masculino , Ratos , Ratos Wistar , Receptores de IgG/metabolismo
20.
J Gastroenterol Hepatol ; 35(2): 343-352, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31318997

RESUMO

BACKGROUND AND AIM: Diabetes mellitus (DM) is a common complication of idiopathic chronic pancreatitis (ICP), which impairs the quality of life for patients. This study aimed to identify risk factors and develop nomogram for DM in ICP to help early diagnosis. METHODS: Idiopathic chronic pancreatitis patients admitted to our center from January 2000 to December 2013 were included. Cumulative rates of DM were calculated by Kaplan-Meier method. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on training cohort, risk factors for DM were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: Totally, 1633 patients with ICP were finally enrolled. The median follow-up duration was 9.8 years. DM was found in 26.3% (430/1633) of patients after the onset of CP. Adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct were identified risk factors for DM development. The nomogram achieved good concordance indexes in the training and validation cohorts, respectively, with well-fitted calibration curves. CONCLUSIONS: Risk factors were identified, and nomogram was developed to determine the risk of DM in ICP patients. Patients with one or more of the risk factors including adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct have higher incidence of DM.


Assuntos
Diabetes Mellitus/etiologia , Nomogramas , Pancreatite Crônica/complicações , Idade de Início , Ductos Biliares/patologia , Constrição Patológica , Humanos , Ductos Pancreáticos/patologia , Fatores de Risco , Esteatorreia
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