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1.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(7): 606-612, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31537245

RESUMO

Objective To investigate the effect of fibroblast growth factor 21 (FGF21) on the lipid accumulation and inflammation induced by palmitate treatment in L02 hepatocytes and the underlying mechanism. Methods L02 cells were infected with lentivirus expressing SIRT1 shRNA to knockdown SIRT1 expression. Wild-type and SIRT1-knockdown L02 cells were treated with 250 mol/L palmitate for 5 days, and then administrated with 1 g/ml FGF21 for 72 hours. Triglycerides in the cells were detected with the infinity triglycerides reagent. Malondialdehyde (MDA) in the cells was assessed by MDA detection assay. Tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) levels in supernatant were measured by ELISA. Reactive oxygen species (ROS) levels were tested by the specific Amplex red ROS detection assay kit from Thermo Fisher Company. The gene expression of SIRT1, peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α), superoxide dismutase 2 (SOD2) and catalase (CAT) were measured by real-time quantitative PCR. The protein levels of SIRT1, PGC1α, SOD2 and CAT were detected by Western blot analysis. Mitochondrial membrane potentials were detected by the JC-1staining kit. Mitochondrial oxygen consumption rate (OCR) was detected with the Seahorse XF Mito stress test kit. Results Palmitate increased the triglycerides level, induced the oxidative stress in both the cells and the mitochondria, decreased the gene expression and protein levels of SIRT1, PGC1α, SOD2 and CAT, increased the levels of TNF-α and IL-6, decreased the mitochondrial membrane potential, and impaired the mitochondrial function. FGF21 treatment could attenuate all of these effects caused by palmitate, while SIRT1 knockdown blocked most of the FGF21 effects on the L02 hepatocytes. Conclusion FGF21 activates SIRT1 pathway and inhibites the lipid accumulation, improves the mitochondrial function, and decreases the oxidative stress as well as inflammation in palmitate-treated L02 cells.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Hepatócitos/metabolismo , Inflamação/metabolismo , Sirtuína 1/metabolismo , Catalase/metabolismo , Linhagem Celular , Hepatócitos/efeitos dos fármacos , Humanos , Interleucina-6/metabolismo , Estresse Oxidativo , Palmitatos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Superóxido Dismutase-1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
2.
Biol Res ; 52(1): 49, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492195

RESUMO

BACKGROUND: Psoriasis is a common and intractable skin disease affecting the physical and mental health of patients. The accumulation of ROS is involved in the pathogenesis of psoriasis and antioxidants are believed to be therapeutic. This study aimed to investigate the therapeutic efficacy of astilbin on ROS accumulation in psoriasis. RESULTS: The study showed that 50 µg/ml astilbin could inhibit the growth and reduce the accumulation of ROS in HaCaT cells stimulated by IL-17 and TNF-α. Astilbin could elevate the Nrf2 accumulation in the nuclei, eventually leading to the transcriptional activation of various antioxidant proteins and reducing the expression of VEGF. CONCLUSIONS: Our results collectively suggest that astilbin could induce Nrf2 nucleus translocation, which is contribute to reduce the ROS accumulation and VEGF expression, and inhibit the proliferation of HaCaT cells.


Assuntos
Flavonóis/administração & dosagem , Queratinócitos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Psoríase/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Interleucina-17/metabolismo , Queratinócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/metabolismo , Psoríase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
3.
Braz J Med Biol Res ; 52(9): e8525, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31411316

RESUMO

Many compounds of ginsenosides show anti-inflammatory properties. However, their anti-inflammatory effects in intervertebral chondrocytes in the presence of inflammatory factors have never been shown. Increased levels of pro-inflammatory cytokines are generally associated with the degradation and death of chondrocytes; therefore, finding an effective and nontoxic substance that attenuates the inflammation is worthwhile. In this study, chondrocytes were isolated from the nucleus pulposus tissues, and the cells were treated with ginsenoside compounds and IL-1ß, alone and in combination. Cell viability and death rate were assessed by CCK-8 and flow cytometry methods, respectively. PCR, western blot, and immunoprecipitation assays were performed to determine the mRNA and protein expression, and the interactions between proteins, respectively. Monomeric component of ginsenoside Rd had no toxicity at the tested range of concentrations. Furthermore, Rd suppressed the inflammatory response of chondrocytes to interleukin (IL)-1ß by suppressing the increase in IL-1ß, tumor necrosis factor (TNF)-α, IL-6, COX-2, and inducible nitric oxide synthase (iNOS) expression, and retarding IL-1ß-induced degradation of chondrocytes by improving cell proliferation characteristics and expression of aggrecan and COL2A1. These protective effects of Rd were associated with ubiquitination of IL-1 receptor accessory protein (IL1RAP), blocking the stimulation of IL-1ß to NF-κB. Bioinformatics analysis showed that NEDD4, CBL, CBLB, CBLC, and ITCH most likely target IL1RAP. Rd increased intracellular ITCH level and the amount of ITCH attaching to IL1RAP. Thus, IL1RAP ubiquitination promoted by Rd is likely to occur by up-regulation of ITCH. In summary, Rd inhibited IL-1ß-induced inflammation and degradation of intervertebral disc chondrocytes by increasing IL1RAP ubiquitination.


Assuntos
Condrócitos/efeitos dos fármacos , Ginsenosídeos/farmacologia , Proteína Acessória do Receptor de Interleucina-1/metabolismo , Interleucina-1beta/efeitos dos fármacos , Degeneração do Disco Intervertebral/metabolismo , Adulto , Idoso , Agrecanas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/citologia , Condrócitos/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Feminino , Ginsenosídeos/metabolismo , Humanos , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Dor Lombar/metabolismo , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase/metabolismo , Núcleo Pulposo/citologia , Núcleo Pulposo/efeitos dos fármacos , Núcleo Pulposo/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ubiquitinação
4.
Acta Cir Bras ; 34(6): e201900604, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31432995

RESUMO

PURPOSE: In view of the principal role of Toll-like receptor 4 (TLR4) in mediating sterile inflammatory response contributing to osteoarthritis (OA) pathogenesis, we used lipopolysaccharide (LPS), a known TLR4 activator, to clarify whether modulation of TLR4 contributed to the protective actions of intra-articular administration of curcumin in a classical rat OA model surgically induced by anterior cruciate ligament transection (ACLT). METHODS: The rats underwent ACLT and received 50µl of curcumin at the concentration of 1 mg mL-1 and 10 µg LPS by intra-articular injection once a week for 8 weeks. Morphological changes of the cartilage and synovial tissues were observed. Apoptotic chondrocytes were detected using TUNEL assay. The concentrations of IL-1ß and TNF-ɑ in synovial fluid were determined using ELISA kits. The mRNA and protein expression levels of TLR4 and NF-κB p65 were detected by real-time PCR and Western blotting, respectively. RESULTS: Intra-articular administration of curcumin significantly improved articular cartilage injury, suppressed synovial inflammation and down-regulated the overexpression of TLR4 and its downstream NF-κB caused by LPS-induced TLR4 activation in rat osteoarthritic knees. CONCLUSION: The data suggested that the inhibition of TLR4 signal might be an important mechanism underlying a protective effect of local curcumin administration on OA.


Assuntos
Ligamento Cruzado Anterior/cirurgia , Curcumina/farmacologia , Osteoartrite/prevenção & controle , Receptor 4 Toll-Like/metabolismo , Animais , Ligamento Cruzado Anterior/patologia , Western Blotting , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Injeções Intra-Articulares , Interleucina-1beta/metabolismo , Lipopolissacarídeos , Masculino , NF-kappa B/metabolismo , Osteoartrite/induzido quimicamente , Osteoartrite/metabolismo , Reação em Cadeia da Polimerase , Ratos , Receptor 4 Toll-Like/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
5.
Acta Cir Bras ; 34(6): e201900609, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31433000

RESUMO

PURPOSE: The research is intended for clarification of the efficacy as well as the underlying mechanism of GSK-3ß inhibitors on the advancement of acute lung injuries in acute necrotizing pancreatitis (ANP) in rats. METHODS: Seventy-two rats were randomly divided into 6 groups: (1)ANP-vehicle; (2)ANP-TDZD-8;(3)ANP-SB216763;(4)Sham-vehicle;(5)Sham-TDZD-8;(6)Sham-SB216763; Blood biochemical test, histopathological examination and immunohistochemical analysis of rats pancreas and lung tissues were performed. The protein expression of GSK-3ß, phospho-GSK-3ß (Ser9), iNOS, ICAM-1, TNF-α, and IL-10 were detected in lung tissues by Western-blot. RESULTS: The outcomes revealed that the intervention of GSK-3ß inhibitors alleviated the pathological damage of pancreas and lung (P<0.01), reduced serum amylase, lipase, hydrothorax and lung Wet-to-Dry Ratio, attenuated serum concentrations of IL-1ß and IL-6 (P<0.01), inhibited the activation of NF-κB, and abated expression of iNOS, ICAM-1 and TNF-α protein, but up-regulated IL-10 expression in lung of ANP rats (P<0.01). The inflammatory response and various indicators in ANP-TDZD-8 groups were lower than those in ANP-SB216763 groups. CONCLUSIONS: Inhibition of GSK-3ß weakens acute lung injury related to ANP via the inhibitory function of NF-κB signaling pathway. Different kinds of GSK-3ß inhibitors have different effects to ANP acute lung injury.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Pancreatite Necrosante Aguda/complicações , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Modelos Animais de Doenças , Imuno-Histoquímica , Interleucina-1beta/metabolismo , Masculino , NF-kappa B/metabolismo , Pancreatite Necrosante Aguda/patologia , Fosforilação , Ratos , Ratos Wistar , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
6.
Zhonghua Fu Chan Ke Za Zhi ; 54(7): 464-469, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31365959

RESUMO

Objective: To evaluate the effects of parthenolide on estradiol-synthesizing enzyme, steroidogenic acute regulatory protein (StAR), and ER isoforms,VEGF in human endometriotic stromal cells. Methods: Primary endometriotic stromal cells were treated with different concentrations (1, 5, 10 and 20 µmol/L) of parthenolide. The mRNA of StAR, ER isoforms (ERα and ERß), PR, vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), tumour necrosis factor-α (TNFα), tumour necrosis factor receptor (TNFR) 1, TNFR2 were measured by real-time PCR. The levels of estradiol and progesterone in the cell supernatant were measured by ELISA. Results: Different concentrations of parthenolide could up-regulate the mRNA of StAR in primary endometriotic stromal cells (F=5.722, P<0.05); the mRNA of StAR in the group of 20 µmol/L was significantly higher than that of the control group [2.6±0.3 versus 1.0, P<0.01]. Different concentrations of parthenolide could down-regulate the mRNA of ERα (F=6.921, P<0.01); the mRNA of ERα in the group of 20 µmol/L and 10 µmol/L were significantly lower than those of the control group [0.2±0.3 versus 0.3±0.3 versus 1.0, all P<0.05]. Different concentrations of parthenolide could down-regulate the ratios of ERα/ERß mRNA levels (F=4.209, P<0.05). Different concentrations of parthenolide could up-regulate the mRNA of VEGF and TNFR1 (F=10.964, P<0.01; F=7.286, P<0.01). There were no statiscal significances with different concentrations of parthenolide on the mRNA of ERß, PR, IL-6, TNFα and TNFR2, and the levels of estradiol and progesterone in the cell supernatant (all P>0.05). Conclusions: Parthenolide may regulate the expression of estradiol-synthesizing enzyme, ER isoforms and angiogenesis in endometriotic stromal cells. Parthenolide may promote the development of endometriosis.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Endometriose , Endométrio/efeitos dos fármacos , Sesquiterpenos/farmacologia , Células Estromais/metabolismo , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Endometriose/induzido quimicamente , Endometriose/genética , Endométrio/metabolismo , Endométrio/patologia , Estradiol , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Isoformas de Proteínas , Células Estromais/efeitos dos fármacos , Células Estromais/patologia , Fator de Necrose Tumoral alfa/metabolismo
7.
Chem Biol Interact ; 311: 108790, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31400342

RESUMO

Preclinical assays play a key role in research in research on the neurobiology of pain and the development of novel analgesics. Drugs available for the treatment of inflammatory pain are not fully effective and show adverse effects. Thus, we investigated the antinociceptive, anti-inflammatory and anti-hyperalgesic effects of bis(3-amino-2-pyridine) diselenide (BAPD), a new analgesic drug prototype. BAPD effects were investigated using nociception models induced by chemical (glutamate), immunologic (Freund's Complete Adjuvant - CFA) and thermal stimuli in Swiss mice. Mice were orally (p.o.) treated with BAPD (0.1-50 mg/kg) 30 min prior to the glutamate and hot-plate tests and a time-course (0.5 up to 8 h) of the antinociceptive effect of BAPD (50 mg/kg, p. o.) was evaluated in a CFA model. In the CFA model, BAPD effects on cyclooxygenase-2 (COX-2), tumor necrosis factor (TNFα) and interferon-γ (INF-γ) expression, myeloperoxidase (MPO) activity, oxidative (2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels) and histological parameters were evaluated. The safety of the compound (50 and 300 mg/kg, p. o.) was verified for 72 h. BAPD reduced the licking time induced by glutamate and caused an increase in latency response to thermal stimulus. Naloxone reversed the antinociceptive effect of BAPD. Paw edema formation induced by glutamate or CFA injection was reduced by BAPD. Mechanical hyperalgesia induced by CFA was attenuated by BAPD. BAPD did not protect against the increase in MPO activity and decrease of the 2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels induced by CFA. BAPD protected against histological alterations and reduction on the levels of gene expression COX-2 and INF-γ in the paw of mice exposed to CFA. BAPD was safe at the doses and time evaluated. BAPD exerts acute antinociceptive, anti-inflammatory and anti-hyperalgesic actions, suggesting that it may represent an alternative in the future development of new therapeutic strategies.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/metabolismo , Interferon gama/metabolismo , Nociceptividade/efeitos dos fármacos , Receptores Opioides/metabolismo , Analgésicos/química , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Ciclo-Oxigenase 2/genética , Edema/tratamento farmacológico , Edema/patologia , Comportamento Exploratório/efeitos dos fármacos , Pé/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Interferon gama/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Dor/tratamento farmacológico , Dor/patologia , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores Opioides/genética , Testes de Toxicidade Aguda , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
8.
Sheng Li Xue Bao ; 71(4): 575-580, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31440754

RESUMO

The aim of the present study was to investigate the effect of salidroside (Sal) on inflammatory activation induced by lipopolysaccharide (LPS) in the co-culture of rat alveolar macrophages (AM) NR 8383 and type II alveolar epithelial cells (AEC II) RLE-6TN. CCK-8 colorimetric method was used to detect cell proliferation percentage. The enzyme-linked immunosorbent assay (ELISA) was used to determine the content of tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein-2 (MIP-2) and interleukin-10 (IL-10) in the supernatant. Western blot was used to examine the expression levels of phosphorylated AKT (p-AKT) and total AKT protein. The results showed that pretreatment of RLE-6TN cells or co-culture of RLE-6TN and NR 8383 cells with 32 and 128 µg/mL Sal for 1 h, followed by continuous culture for 24 h, significantly increased the cell proliferation (P < 0.05). Compared with control group, 32 and 128 µg/mL Sal pretreatment significantly increased the ratio of p-AKT/AKT in RLE-6TN cells (P < 0.05). Pretreatment of 32 µg/mL Sal not only inhibited the secretion of TNF-α and MIP-2 by NR 8383 cells induced by LPS (P < 0.05), but also enhanced the inhibitory effect of RLE-6TN and NR 8383 cells co-culture on the secretion of TNF-α and MIP-2 by NR 8383 cells induced by LPS (P < 0.05). In addition, 32 µg/mL Sal pretreatment promoted LPS-induced IL-10 secretion by NR 8383 cells (P < 0.05), and enhanced the promoting effect of co-culture of RLE-6TN and NR 8383 cells on the IL-10 secretion by LPS-induced NR 8383 cells (P < 0.05). In conclusion, Sal may directly inhibit LPS-induced inflammatory activation of AM (NR 8383), promote the proliferation of AEC II (RLE-6TN) through PI3K/AKT signaling pathway, and enhance the regulatory effect of AEC II on LPS-induced inflammatory activation of AM.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Glucosídeos/farmacologia , Macrófagos Alveolares/efeitos dos fármacos , Fenóis/farmacologia , Transdução de Sinais , Células Epiteliais Alveolares/metabolismo , Animais , Linhagem Celular , Quimiocina CXCL2/metabolismo , Técnicas de Cocultura , Interleucina-10/metabolismo , Lipopolissacarídeos , Macrófagos Alveolares/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Fator de Necrose Tumoral alfa/metabolismo
9.
Exp Parasitol ; 205: 107736, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31442455

RESUMO

Goats are frequently described as an intermediate host for the protozoan Neospora caninum, manifesting the disease mainly by recurrent abortions with placentitis and encephalitis in fetuses. Several reports of natural and experimental infections in cattle and mice show differences in the immune response, and the outcome of the infection can be variable depending on the species affected and by the behavior of the infective strain. This study describes for the first time two Neospora caninum strains isolated from naturally infected goats from the state of Minas Gerais, Brazil. One placenta and one brain from different goats were processed for a first bioassay in gerbils (Meriones unguiculatus). Subsequently, a second bioassay was performed by inoculating the processed brain samples from gerbils into Interferon gamma (IFN-γ) knockout mice (KO mice). Tachyzoites collected from the peritoneal fluid of the KO mice were inoculated into VERO cell monolayers, where they presented a very slow growth rate. The tachyzoites were also inoculated into BALB/c mice with a dose of 106 tachyzoites per animal. After a 5-week follow up, the animals infected with both of the strains developed a strong polarized Th1 response with increased serum and spleen gene expression levels of pro-inflammatory cytokines (mainly IFN-γ and TNF-α) in the first week. Tissue lesions were mild in the animals infected with both strains. Despite the strong immune response preventing an infection in the visceral organs, the parasite was able to reach the brain, causing progressive brain lesions from the second to fifth week post infection. The NC-goat1-infected mice presented with severe meningoencephalitis, but the NC-goat2-infected animals had considerable histological brain lesions only at week 5. Immunohistochemical analysis of the mouse brains revealed a different pattern of inflammatory cells compared to the naturally infected goats. A severe inflammatory infiltrate of CD3+ T lymphocytes was found in the NC-goat1-infected mice. A more discrete infiltrate of CD3+ T cells was found in the NC-goat2-infected animals. Additionally, IBA1 IHC revealed an intense microglial reaction and monocyte perivascular cuffs in the NC-goat1-infected animals and lower microglia/monocyte infiltrates in the NC-goat2-infected mice. This work contributes knowledge on the pathogenicity of new Neospora caninum strains in mice, comparable with other well-established mouse models of the disease, and demonstrates the importance of studying goats as an intermediate host of this parasite.


Assuntos
Coccidiose/veterinária , Doenças das Cabras/parasitologia , Neospora/patogenicidade , Animais , Bioensaio/veterinária , Encéfalo/parasitologia , Encéfalo/patologia , Cercopithecus aethiops , Coccidiose/parasitologia , Coccidiose/patologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Gerbillinae , Doenças das Cabras/patologia , Cabras , Imuno-Histoquímica/veterinária , Interferon gama/genética , Interferon gama/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neospora/isolamento & purificação , Pâncreas/patologia , Placenta/patologia , Gravidez , Baço/metabolismo , Baço/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Células Vero
10.
Ecotoxicol Environ Saf ; 182: 109398, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31276887

RESUMO

Cadmium(Cd) is a serious environmental and occupational contaminant that represents a serious health hazard to humans and other animals. Reproductive health problems have been reported in men exposed to Cd. Testicular damage is one of the deleterious effects due to Cd exposure. Cd-induced testicular toxicity is mediated through oxidative stress, inflammation, testosterone inhibition and apoptosis. Thus, the present study was performed to assess the possible protective role of infliximab (IFX), anti-TNFα agent, against Cd-induced testicular damage and spermiotoxicity in rats. The rats were randomly allotted into six experimental groups: control, Cd sulphate treated, Cd sulphate treated with infliximab (5 mg/kg), Cd sulphate with infliximab (7 mg/kg), infliximab alone (5 mg/kg), and infliximab alone (7 mg/kg). The control group received saline. To induce testicular damage, Cd sulphate (1.5 mg/100 gm body weight/day) was dissolved in normal saline and orally administrated for 3 consecutive weeks. The rats in infliximab-treated groups were given a weekly dose of 5 mg/kg/week or 7 mg/kg/week of infliximab intraperitoneally. In the current study Cd exposure reduced sperm count, markers of testicular function, sperm motility as well as gene expression of testicular 3ß-HSD and 17ß-HSD and serum testosterone level. Additionally, it increased testicular oxidative stress, inflammatory and apoptotic markers. The histopathologic studies supported the biochemical findings. Treatment with infliximab significantly attenuated Cd-induced injury verified by the restoration of testicular architecture, enhancement of steroidogenesis, preservation of spermatogenesis, modulation of the inflammatory reaction along with suppression of oxidative stress and apoptosis. It was concluded that infliximab, through its antioxidant, anti-inflammatory and anti-apoptotic effects, represents a potential therapeutic option to protect the testicular tissue from the detrimental effects of Cd.


Assuntos
Antioxidantes/metabolismo , Cádmio/toxicidade , Infliximab/farmacologia , Testículo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Inflamação , Masculino , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Motilidade Espermática/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testosterona/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
11.
Ecotoxicol Environ Saf ; 182: 109420, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31299472

RESUMO

Mancozeb (MZ), chlorothalonil (CT), and thiophanate methyl (TM) are pesticides commonly used in agriculture due to their efficacy, low acute toxicity to mammals, and short environmental persistence. Although the toxic effects of these pesticides have been previously reported, studies regarding their influence on the immune system are limited. As such, this study focused on the immunomodulatory effect of MZ, CT, and TM pesticides on macrophage cells. RAW 264.7 cells were exposed to a range of concentrations (0.1-100 µg/mL) of these pesticides. CT exposure promoted an increase in reactive oxygen species (ROS) and nitric oxide (NO) levels. The MTT and ds-DNA assay results demonstrated that MZ, CT, and TM exposure induced macrophage proliferation. Moreover, MZ, CT, and TM promoted cell cycle arrest at S phase, strongly suggesting macrophage proliferation. The levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, and IFN-γ) and caspases (caspase 1, 3, and 8) in macrophages exposed to MZ, CT, and TM pesticides increased, whereas the anti-inflammatory cytokine levels decreased. These results suggest that MZ, CT, and TM exert an immunomodulatory effect on the immune system, inducing macrophage activation and enhancing the inflammatory response.


Assuntos
Praguicidas/toxicidade , Animais , Citocinas/metabolismo , Imunomodulação , Interleucina-1beta/metabolismo , Macrófagos/efeitos dos fármacos , Maneb/toxicidade , Óxido Nítrico/metabolismo , Nitrilos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Tiofanato/toxicidade , Testes de Toxicidade , Fator de Necrose Tumoral alfa/metabolismo , Zineb/toxicidade
12.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(6): 680-683, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31315722

RESUMO

OBJECTIVE: To explore the correlation between major inflammatory factors and septic shock in intensive care unit (ICU) patients, and to provide a basis for the diagnosis and treatment of septic shock. METHODS: The patients admitted to ICU of the Third People's Hospital of Datong from March 2017 to August 2018 were selected as the research objects. According to the diagnostic criteria of septic shock, the patients were divided into septic shock group and non-septic group. The basic information and inflammatory factors levels of the two groups, including age, gender, body mass index (BMI), course of disease, acute physiology and chronic health evaluation II (APACHE II), infection site and pathogenic; and C-reactive protein (CRP), procalcitonin (PCT), neutrophil lymphocyte ratio (NLR), N-terminal pro-B-type natriuretic peptide (NT-proBNP), tumor necrosis factor-α (TNF-α), γ-interferon (IFN-γ), interleukins (IL-1ß, IL-2, IL-6, IL-8) at 8 hours after diagnosis, were compared. Logistic regression was used to analyze the influencing factors of septic shock in ICU patients. RESULTS: A total of 154 ICU patients were selected, of whom 74 had septic shock. The APACHE II score of septic shock group was significantly higher than that of non-sepsis group (23.42±3.64 vs. 15.67±2.26, P < 0.05). There was no significant difference in other baseline data between the two groups. The levels of CRP, NT-proBNP, TNF-α, IFN-γ, PCT, IL-6, IL-8 in the septic shock group were significantly higher than those in the non-septic group [CRP (mg/L): 164.3±22.6 vs. 52.3±16.2, NT-proBNP (ng/L): 426.3±288.9 vs. 167.3±80.6, TNF-α (ng/L): 193.4±39.3 vs. 88.1±20.3, IFN-γ (ng/L): 133.3±52.0 vs. 97.0±56.1, PCT (ng/L): 27.6±10.2 vs. 7.3±4.1, IL-6 (ng/L): 83.0±17.6 vs. 20.9±6.4, IL-8 (ng/L): 445.8±34.0 vs. 84.0±25.7, all P < 0.05]. It was shown by Logistic regression analysis that CRP, NT-proBNP, TNF-α, PCT, IL-6 were independent risk factors for septic shock [CRP: odds ratio (OR) = 1.662, 95% confidence interval (95%CI) = 1.132-2.567; NT-proBNP: OR = 14.688, 95%CI = 3.580-20.238; TNF-α: OR = 1.093, 95%CI = 1.043-1.343; PCT: OR = 6.378, 95%CI = 4.556-12.243; IL-6: OR = 9.641, 95%CI = 2.242-13.786; all P < 0.05]. CONCLUSIONS: The levels of inflammatory factors CRP, NT-proBNP, TNF-α, PCT and IL-6 were significantly increased, which were important factors for early diagnosis of septic shock.


Assuntos
Choque Séptico/diagnóstico , Choque Séptico/metabolismo , APACHE , Proteína C-Reativa/metabolismo , Feminino , Humanos , Unidades de Terapia Intensiva , Interleucina-6/metabolismo , Masculino , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Pró-Calcitonina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
13.
Chem Biol Interact ; 311: 108762, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31348917

RESUMO

Neurotoxicity caused by particulate matter (PM) has been highlighted as being a potential risk factor for neurodegenerative diseases. However, the effects of brain inflammation in response to traffic-related PM remain unclear. The objective of this study was to investigate the effects of traffic-related PM on microglial responses. We determined the cytotoxicity, oxidative stress, lipid peroxidation, inflammation, activation, autophagy, and apoptosis due to exposure to carbon black (CB) and diesel exhaust particles (DEPs) in Bv2 microglial cells. Additionally, cells were pretreated with corticosteroid to determine alterations in microglial activation and inflammation. For in vivo confirmation, Sprague Dawley (SD) rats were whole-body exposed to traffic-related PM1 (PM with an aerodynamic diameter of <1 µm) for 3 and 6 months. We observed that a decrease in cell viability and increases in dichlorodihydrofluorescein (DCFH), lactate dehydrogenase (LDH), and thiobarbituric acid-reactive substances (TBARSs) occurred due to CB and DEP. Production of interleukin (IL)-6 and soluble tumor necrosis factor (TNF)-α was significantly stimulated by CB and DEP, whereas production of cellular TNF-α was significantly stimulated by CB. Iba1 and prostaglandin E2 (PGE2) significantly increased due to CB and DEP. Consistently, we observed significant increases in Iba1 in the hippocampus of rats after 3 and 6 months of exposure to traffic-related PM1. We found that the light chain 3II (LC3II)/LC3I ratio and caspase-3 activity increased due to CB and DEP exposure. Subsequently, LDH, TBARS, LC3II/I, and caspase-3 activities did not clearly respond to corticosteroid pretreatment followed by DEP exposure in BV2 cells. Results of the present study suggested that traffic-related PM induced cytotoxicity, lipid peroxidation, microglial activation, and inflammation as well as autophagy and caspase-3 regulation in microglia. We demonstrated that microglial activation and inflammation may play important roles in the response of the brain to traffic-related PM.


Assuntos
Inflamação/etiologia , Microglia/efeitos dos fármacos , Material Particulado/toxicidade , Animais , Autofagia/efeitos dos fármacos , Encéfalo/patologia , Proteínas de Ligação ao Cálcio/análise , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dinoprostona/análise , Interleucina-6/metabolismo , L-Lactato Desidrogenase/metabolismo , Masculino , Proteínas dos Microfilamentos/análise , Microglia/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos , Emissões de Veículos/toxicidade
14.
J Biol Regul Homeost Agents ; 33(4): 1063-1072, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31353880

RESUMO

Acute lung injury (ALI) is a disease with high incidence and no effective therapeutic treatments. miR- 145-5p has been reported to be aberrantly expressed in lung injury tissues, suggesting a potential role in the progression and development of ALI. To validate this hypothesis and explore the underlying mechanism, a mouse model of ALI was established using lipopolysaccharide (LPS). Hematoxylin and eosin (Hand E) staining verified the successful establishment of mouse model with ALI. Levels of interleukin (IL)-1ß, IL- 6, tumor necrosis factor α (TNF-α) and myeloperoxidase (MPO) were detected by both enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. Mouse type II alveolar epithelial cells (AT II) were isolated and treated with LPS. miR-145-5p was significantly down-regulated both in mice with acute lung injury and LPS-induced AT II cells. Dual luciferase assays confirmed miR-145-5p could target and regulate Toll Like Receptor 4 (TLR4). Further analysis showed that miR-145-5p overexpression decreased the expression levels of IL-1ß, IL-6 and TNF-α in LPS-induced AT II cells. miR-145-5p overexpression also blocked the LPS-induced activation of nuclear factor kappa B (NF-κB) pathway and reactive oxygen species (ROS) accumulation in AT II cells. Finally, in ALI mouse model, miR-145-5p overexpression alleviated lung tissue injury, decreased the expression levels of IL-1ß, IL-6 and TNF-α and reduced MPO activity. In conclusion, miR-145-5p participated in the progression and development of ALI by decreasing the production of pro-inflammatory cytokines, inhibiting NF-κB pathway and suppressing ROS accumulation, shedding light on miR-145-5p as a potential therapeutic target for the treatment of ALI.


Assuntos
Lesão Pulmonar Aguda/terapia , MicroRNAs/genética , Animais , Células Cultivadas , Células Epiteliais/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos , Camundongos , NF-kappa B/metabolismo , Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
15.
J Agric Food Chem ; 67(28): 7869-7879, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31287296

RESUMO

Carnitine, a dietary quaternary amine mainly from red meat, is metabolized to trimethylamine (TMA) by gut microbiota and subsequently oxidized to trimethylamine-N-oxide (TMAO) by host hepatic enzymes, flavin monooxygenases (FMOs). The objective of this study aims to investigate the effects of flavonoids from oolong tea and citrus peels on reducing TMAO formation and protecting vascular inflammation in carnitine-feeding mice. The results showed that mice treated with 1.3% carnitine in drinking water significantly (p < 0.05) increased the plasma levels of TMAO compared to control group, whereas the plasma TMAO was remarkedly reduced by flavonoids used. Meanwhile, these dietary phenolic compounds significantly (p < 0.05) decreased hepatic FMO3 mRNA levels compared to carnitine only group. Additionally, oolong tea extract decreased mRNA levels of vascular inflammatory markers such as tissue necrosis factor-alpha (TNF-α), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Polymethoxyflavones significantly lowered the expression of VCAM-1 and showed a decreasing trend in TNF-α and E-selectin mRNA expression compared to the carnitine group. Genus-level analysis of the gut microbiota in the cecum showed that these dietary phenolic compounds induced an increase in the relative abundances of Bacteroides. Oolong tea extract-treated group up-regulated Lactobacillus genus, compared to the carnitine only group. Administration of polymethoxyflavones increased Akkermansia in mice.


Assuntos
Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Camellia sinensis/química , Carnitina/metabolismo , Citrus/química , Flavonas/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Aterosclerose/genética , Aterosclerose/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Biotransformação/efeitos dos fármacos , Feminino , Flavonas/análise , Microbioma Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Humanos , Metilaminas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/análise , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo
16.
Chem Pharm Bull (Tokyo) ; 67(7): 640-647, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257319

RESUMO

Neuroinflammation manifested by over-activation of microglial cells plays an essential role in neurodegenerative diseases. Short-term activation of microglia can be beneficial, but chronically activated microglia can aggravate neuronal dysfunction possibly by secreting potentially cytotoxic substances such as tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO), which can result in dysfunction and death of neurons. Therefore inhibiting over-activation of microglia and the production of cytotoxic intermediates may become an effective therapeutic approach for neuroinflammation. In this paper, we review our continuous research on natural inhibitors of over-activated microglia from traditional herbals, including flavonoids, lignans, sesquiterpene coumarins, and stilbenes.


Assuntos
Produtos Biológicos/química , Microglia/metabolismo , Animais , Produtos Biológicos/farmacologia , Cumarínicos/química , Cumarínicos/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Lignanas/química , Lignanas/farmacologia , Microglia/citologia , Microglia/efeitos dos fármacos , Óxido Nítrico/biossíntese , Estilbenos/química , Estilbenos/farmacologia , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/metabolismo
17.
Gene ; 712: 143959, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31278964

RESUMO

Blockade of Hedgehog signaling can prevent osteoarthritis (OA) syndromes. However, the amelioration of related inflammation condition is limited. The purpose of this study was to observe the effect of combined use of Hedgehog signaling inhibitor GANT-61 and common clinical anti-inflammatory drug indomethacin on cartilage injury and inflammation in experimental OA mice. We found that GANT-61 and indomethacin synergistically attenuate cartilage damage and serum levels of inflammatory cytokines TNF-α, IL-2 and IL-6 in OA mice. Moreover, in vitro treatment of GANT-61 and indomethacin synergistically reduced the mRNA expression of TNF-α, IL-2 and IL-6 in lipopolysaccharide (LPS)-stimulated C28/I2 chondrocytes. Mechasnistic studies showed that GANT-61 and indomethacin synergistically attenuate the expressions of cell pyroptosis-related genes caspase-1, IL-1ß and IL-18 at mRNA and protein level. To conclude, our study showed that GANT-61 and indomethacin had a synergistically ameliorating effect on osteoarthritis by mediating chondrocytes pyroptosis.


Assuntos
Cartilagem/efeitos dos fármacos , Condrócitos/citologia , Proteínas Hedgehog/antagonistas & inibidores , Indometacina/farmacologia , Osteoartrite/tratamento farmacológico , Piridinas/administração & dosagem , Pirimidinas/administração & dosagem , Animais , Anti-Inflamatórios/farmacologia , Cartilagem/patologia , Caspase 1/metabolismo , Linhagem Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Interleucina-2/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Piroptose , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
18.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2317-2323, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359658

RESUMO

This paper was mainly to discuss the potential role and mechanism of Lianhua Qingwen Capsules(LHQW) in inhibiting pathological inflammation in the model of acute lung injury caused by bacterial infection. For in vitro study, the mRNA expression of MCP-1 in RAW264.7 cells and THP-1 cells, the content of MCP-1 in cell supernatant, as well as the effect of LHQW on chemotaxis of macrophages were detected. For in vivo study, mice were randomly divided into 7 groups, including normal group, model group(LPS 5 mg·kg~(-1)), LHQW 300, 600 and 1 200 mg·kg~(-1)(low, middle and high dose) groups, dexamethasone 5 mg·kg~(-1) group and penicillin-streptomycin group. Then, the anal temperature was detected two hours later. Dry weight and wet weight of lung tissues in mice were determined; TNF-α and MCP-1 levels in alveolar lavage fluid and MCP-1 in serum were detected. In addition, the infiltration of alveolar macrophages was also observed and the infiltration count of alveolar macrophages was measured by CCK-8 method. HE staining was also used to observe the inflammatory infiltration of lung tissues in mice. Both of the in vitro and in vivo data consistently have confirmed that: by down-regulating the expression of MCP-1, LHWQ could efficiently decrease the chemotaxis of monocytes toward the pulmonary infection foci, thus blocking the disease development in ALI animal model.


Assuntos
Lesão Pulmonar Aguda/microbiologia , Infecções Bacterianas/tratamento farmacológico , Quimiotaxia , Medicamentos de Ervas Chinesas/farmacologia , Macrófagos/efeitos dos fármacos , Animais , Líquido da Lavagem Broncoalveolar , Cápsulas , Quimiocina CCL2/metabolismo , Humanos , Lipopolissacarídeos , Pulmão , Camundongos , Células RAW 264.7 , Distribuição Aleatória , Células THP-1 , Fator de Necrose Tumoral alfa/metabolismo
19.
Zhongguo Zhong Yao Za Zhi ; 44(12): 2566-2571, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359725

RESUMO

This study was to investigate the mechanism of safflower yellow injection for regulating inflammatory response against myocardial ischemia-reperfusion injury( MIRI) in rats. Male Wistar rats were randomly divided into sham operation group,model group,Hebeishuang group,safflower yellow injection high,medium and low dose groups. MIRI model was established by ligating left anterior descending coronary artery. Myocardial histopathological changes were observed by HE staining; myocardial infarct size was detected by TTC staining; content and changes of tumor necrosis factor-α( TNF-α) and interleukin-6( IL-6),serum creatine kinase( CK),aspartate aminotransferase( AST),and lactate dehydrogenase( LDH) were detected by biochemical method or enzyme-linked immunosorbent assay( ELISA). Western blot assay was used to detect the protein expression of Toll-like receptor 4( TLR4) and nuclear factor-κB( NF-κB p65) in myocardial tissues. The results showed that as compared with the sham operation group,the myocardial arrangement of the model group was disordered,with severe edemain the interstitial,significantly increased area of myocardial infarction,increased activities of AST,CK and LDH in serum,and significantly increased contents of TNF-α and IL-6; the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were also increased. As compared with the model group,the myocardial tissues were arranged neatlyin the Hebeishuang group and safflower yellow injection high,medium and low dose groups; the edema was significantly reduced; the myocardial infarct size was significantly reduced; the serum AST,CK,LDH activity and TNF-α,IL-6 levels were significantly decreased,and the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were decreased. As compared with the Hebeishuang group,the myocardial infarct size was larger in the safflower yellow injection high,medium and low dose groups; the activities of AST,CK and LDH in serum and the contents of TNF-α and IL-6 in serum were higher,but there was no statistically significant difference in the expression levels of TLR4 and NF-κB( p65) protein in tissues. It is suggested that safflower yellow injection has a significant anti-MIRI effect,and its mechanism may be related to the regulation of TLR-NF-κB pathway to inhibit inflammatory response.


Assuntos
Anti-Inflamatórios/farmacologia , Chalcona/análogos & derivados , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Receptor 4 Toll-Like/metabolismo , Fator de Transcrição RelA/metabolismo , Animais , Aspartato Aminotransferases/sangue , Chalcona/farmacologia , Creatina Quinase/sangue , Interleucina-6/metabolismo , L-Lactato Desidrogenase/sangue , Masculino , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
20.
Acta Gastroenterol Belg ; 82(2): 285-290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31314190

RESUMO

BACKGROUND AND AIM: Intestinal barrier dysfunction has been implicated in the development of infectious complications of acute pancreatitis. Nucleotide-Binding Oligomerization DomainContaining Protein 2 (NOD2) plays an important role in the proper functioning of intestinal defense mechanisms. Here, we investigated the frequency of NOD2 variants in patients with mild and severe acute pancreatitis. MATERIALS AND METHODS: Groups 1, 2 and 3 comprised healthy participants and patients with mild and severe pancreatitis, respectively. Four NOD2 variants and serum interleukin-6 (IL-6), Tumor Necrosis Factor-a (TNF-a) and lipopolysaccharide-binding protein (LBP) levels were analyzed. RESULTS: Three patients (3/32, 9.4%) in the severe pancreatitis group were positive for the p.R702W variant. This variant was negative in other groups. One, three and three patients in the healthy (1/27, 3.7%), mild (3/36, 8.3%) and severe pancreatitis (3/32, 9.4%) groups tested positive for the 1007fs variant, respectively. No significant differences in the frequencies of NOD2 variants were evident among the groups. Serum IL-6, TNF-a and LBP levels were markedly higher in the severe pancreatitis than the healthy and mild pancreatitis groups (all p<0.001). We observed no significant correlation between cytokine levels and NOD2 variants. CONCLUSION: Our results support an association between the presence of the p.R702W variant and severe pancreatitis.


Assuntos
Proteínas de Transporte/sangue , Interleucina-6/sangue , Glicoproteínas de Membrana/sangue , Proteína Adaptadora de Sinalização NOD2/metabolismo , Pancreatite/sangue , Fator de Necrose Tumoral alfa/sangue , Doença Aguda , Proteínas da Fase Aguda/metabolismo , Proteínas de Transporte/metabolismo , Estudos de Casos e Controles , Voluntários Saudáveis , Humanos , Interleucina-6/metabolismo , Intestinos , Glicoproteínas de Membrana/metabolismo , Nucleotídeos , Pancreatite/diagnóstico , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/metabolismo
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