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1.
Br J Clin Pharmacol ; 89(9): 2788-2797, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37161703

RESUMO

AIMS: To analyse the clinical characteristics and risk factors for tigecycline-induced pancreatitis (TIP) and evaluate the safety and efficiency of tigecycline use in non-TIP. METHODS: A retrospective case-control study was conducted on adult and juvenile patients administered tigecycline for >3 days. The adults were classified as TIP, non-TIP (pancreatitis with other causes) and non-pancreatitis. Univariate analyses were performed to compare TIP and non-pancreatitis, and multivariate analysis was used to identify risk factors for TIP. The clinical characteristics of TIP, and the safety and efficiency of tigecycline use in non-TIP were evaluated. RESULTS: A total of 3910 patients (3823 adults and 87 juveniles) were enrolled. The adult patients comprised 21 TIP, 82 non-TIP and 3720 non-pancreatitis. The TIP prevalence was 0.56% in adults and 1.15% in juveniles. The mean time from tigecycline use to symptom onset was 7.2 days, and all cases were mild pancreatitis. The mean time from tigecycline withdrawal to symptom relief was 3.6 days. The multivariate analysis identified comorbid renal insufficiency as an independent risk factor for TIP (odds ratio = 3.032). Among the 82 non-TIP patients, 81.7% had severe pancreatitis and 47.6% had necrotizing pancreatitis. The modified computed tomography severity score after tigecycline use was similar to that before tigecycline use, but the pancreatic enzymes and infection indices were significantly decreased. CONCLUSIONS: The prevalence of TIP was low. Comorbid renal insufficiency was as an independent risk factor for TIP. Tigecycline is safe and efficient for treatment of pancreatitis, especially necrotizing pancreatitis, with intra-abdominal infection.


Assuntos
Antibacterianos , Pancreatite Necrosante Aguda , Adulto , Humanos , Antibacterianos/efeitos adversos , Tigeciclina/efeitos adversos , Estudos Retrospectivos , Estudos de Casos e Controles , Centros de Atenção Terciária , Fatores de Risco , Pancreatite Necrosante Aguda/induzido quimicamente , Pancreatite Necrosante Aguda/tratamento farmacológico
2.
Exp Cell Res ; 406(2): 112727, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34370992

RESUMO

BACKGROUND: Epigenetic dysregulation participates in the initiation and progression of hepatocellular carcinoma (HCC). Bromodomain-containing protein 9 (BRD9) can identify acetylated lysine residues, contributing to several cancers. The function and molecular mechanism of BRD9 in HCC remain poorly understood. METHODS: BRD9 levels in tissues and cells of HCC and normal liver were evaluated using bioinformatic analysis, real-time PCR, and western blot. BRD9's association with clinical outcomes was investigated via survival analyses. Biological behaviors and pathways related to BRD9 were predicted using gene set enrichment analysis. BRD9's role in proliferation was verified via cell counting kit 8, colony formation, and 5-Ethynyl-2'-deoxyuridine assays. Its role in the cell cycle and apoptosis was assessed using flow cytometry. The role of BRD9 in vivo was investigated using xenograft tumor models. A rescue assay was performed to investigate the molecular mechanism of BRD9. RESULTS: BRD9 was markedly upregulated in HCC and higher BRD9 expression was associated with higher grade, advanced stage, greater tumor size, and poorer prognosis. BRD9 overexpression enhanced cell proliferation, cell cycle progress, but impeded cell apoptosis. BRD9 downregulation had the opposite effects. In vivo, BRD9 promoted xenograft tumor growth. Mechanistically, BRD9 activated Wnt/ß-catenin signaling, obstruction of which abrogated BRD9-mediated tumorigenesis. CONCLUSION: Increased BRD9 in HCC correlated with poor prognosis, which functioned via activating Wnt/ß-catenin signaling. Thus, BRD9 might be a promising biomarker and therapeutic target for patients with HCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , Fatores de Transcrição/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Ciclo Celular , Movimento Celular , Proliferação de Células , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Fatores de Transcrição/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem , beta Catenina/genética
3.
J Cell Physiol ; 235(6): 5084-5095, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31691973

RESUMO

Astrocyte elevated gene 1 (AEG-1) is overexpressed in hepatocellular carcinoma (HCC) and is strongly associated with tumor metastasis. Anoikis resistance and autophagy may play an important role in the survival of circulating tumor cells. However, the relationship among AEG-1, anoikis resistance, autophagy, and metastasis in HCC is still not clear. The results of this study indicate that AEG-1 expression is increased in HCC cell lines grown in suspension culture. AEG-1 could enhance anoikis resistance to promote the survival of detached HCC cells. Moreover, the anoikis resistance appears to be partly dependent on autophagy. Regulating AEG-1 expression changed the autophagy levels to modulate anoikis resistance, likely acting via the protein kinase RNA-like ER kinase (PERK)-eIF2α-ATF4-CHOP signaling axis. Finally, inhibiting autophagy by RNA interference prevented the AEG-1-promoted metastasis of HCC xenografts to the liver and lungs of nude mice. Taken together, AEG-1 is a key contributor to anoikis resistance and metastasis by inducing autophagy in vitro and in vivo, and it may be a potential target for therapeutic intervention in HCC.


Assuntos
Fator 4 Ativador da Transcrição/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas de Membrana/genética , Proteínas de Ligação a RNA/genética , eIF-2 Quinase/genética , Animais , Anoikis/genética , Autofagia/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Metástase Neoplásica , Transdução de Sinais/genética
4.
Int J Med Sci ; 17(9): 1224-1234, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547318

RESUMO

Background: Increasing evidence has implicated that lncRNAs (long non-coding RNAs) play significant roles in carcinogenesis and progression of HCC (hepatocellular carcinoma). LINC01503 is a new lncRNA related to several tumors. Nonetheless, its role in HCC still remains unclear. Methods: The expression levels of LINC01503 in HCC, normal liver tissues as well as HCC cell lines were evaluated by TCGA (The Cancer Genome Atlas) and real-time PCR assay, respectively. The relationship between LINC01503 levels and the prognosis of patients with HCC was evaluated using Kaplan-Meier survival analysis. Then the potential biological functions and pathways related to LINC01503 were investigated by GO (Gene Ontology) analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, and GSEA v4.0.1 software was employed. Furthermore, the influence of LINC01503 on the proliferation and apoptosis of HCC cells was confirmed using CCK8 assay, flow cytometry, and clone formation assay in cell experiments. Also the pro-tumor effect of LINC01503 was verified by mice xenograft experiment in vivo. In addition, the functional pathway of LINC01503 was proved by western blot and rescue experiments. Results: LINC01503 was highly expressed in HCC and positively correlated with large tumor size, high tumor grade, advanced tumor stage, and poor prognosis of HCC patients. Silencing LINC01503 with shRNA significantly restrained the proliferation of MHCC-97H HCC cells and strengthened the apoptosis, while up-regulation of LINC01503 in Huh7 HCC cells contributed to the contrary effects. Besides, LINC01503 promoted tumor growth of nude mice transplanted with liver cancer cells. Mechanistically, MAPK/ERK signaling pathway was activated by LINC01503, inhibition of which could alleviate the pro-tumor effect of LINC01503, consistent with the forecast of GSEA (Gene Set Enrichment Analysis). Conclusion: LINC01503 is highly expressed in HCC and promotes the progression of HCC via MAPK/ERK pathway, which maybe a new potential biomarker and therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , RNA Longo não Codificante/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose/genética , Apoptose/fisiologia , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Neoplasias Hepáticas/genética , Sistema de Sinalização das MAP Quinases/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
5.
J Gastroenterol Hepatol ; 34(3): 526-531, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30207000

RESUMO

BACKGROUND AND AIM: The treatment of patients with functional dyspepsia (FD) remains unsatisfactory. We assessed the efficacy of Zhizhu Kuanzhong (ZZKZ) capsule, a traditional Chinese medicine formula, in patients with postprandial distress syndrome (PDS) of FD. METHODS: The study was designed as a multicenter, randomized, double-blinded, controlled clinical trial. Three-hundred ninety-two patients with PDS defined by Rome III criteria from 16 centers in China were randomly assigned to receive either ZZKZ or placebo. The proportion of the responders at 4 weeks after randomization was considered primary endpoint. Secondary endpoint was the symptom score reduction of each dyspeptic symptom relative to the baseline at 4 weeks after randomization in all subjects. RESULTS: In terms of the primary endpoint, the proportion of the responders concerning the composite PDS symptom score was 38.8% and 54.7% in placebo group and ZZKZ group, respectively (P = 0.003), in per protocol analysis at 4 weeks after randomization. Concerning the individual evaluated upper gastrointestinal symptoms, only postprandial fullness and early satiety showed significant difference in symptom score reduction at 4 weeks after randomization between placebo and ZZKZ groups. CONCLUSIONS: Zhizhu Kuanzhong is superior to placebo in the treatment of PDS with FD. The exact mechanisms by which ZZKZ improves symptoms remain to be established (http://www.chictr.org.cn/ChinCTR-TRC-14004714).


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Dispepsia/tratamento farmacológico , Fitoterapia , Período Pós-Prandial , Adulto , Cápsulas , Método Duplo-Cego , Dispepsia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome , Resultado do Tratamento
6.
Pflugers Arch ; 468(8): 1419-32, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27228994

RESUMO

The electrogenic Na(+)HCO3 (-) cotransporter NBCe1 (Slc4a4) is strongly expressed in the basolateral enterocyte membrane in a villous/surface predominant fashion. In order to better understand its physiological function in the intestine, isolated mucosae in miniaturized Ussing chambers and microdissected intestinal villi or crypts loaded with the fluorescent pH-indicator BCECF were studied from the duodenum, jejunum, and colon of 14- to 17-days-old slc4a4-deficient (KO) and WT mice. NBCe1 was active in the basal state in all intestinal segments under study, most likely to compensate for acid loads imposed upon the enterocytes. Upregulation of other basolateral base uptake mechanism occurs, but in a segment-specific fashion. Loss of NBCe1 resulted in severely impaired Cl(-) and fluid secretory response, but not HCO3 (-) secretory response to agonist stimulation. In addition, NBCe1 was found to be active during transport processes that load the surface enterocytes with acid, such as Slc26a3 (DRA)-mediated luminal Cl(-)/HCO3 (-) exchange or PEPT1-mediated H(+)/dipeptide uptake. Possibly because of the high energy demand for hyperventilation in conjunction with the fluid secretory and nutrient absorptive defects and the relative scarcity of compensatory mechanisms, NBCe1-deficient mice developed progressive jejunal failure, worsening of metabolic acidosis, and death in the third week of life. Our data suggest that the electrogenic influx of base via NBCe1 maintains enterocyte anion homeostasis and pHi control. Its loss impairs small intestinal Cl(-) and fluid secretion as well as the neutralization of acid loads imposed on the enterocytes during nutrient and electrolyte absorption.


Assuntos
Ânions/metabolismo , Dipeptídeos/metabolismo , Absorção Intestinal/fisiologia , Intestino Delgado/metabolismo , Simportadores de Sódio-Bicarbonato/deficiência , Simportadores de Sódio-Bicarbonato/metabolismo , Acidose/metabolismo , Animais , Bicarbonatos/metabolismo , Transporte Biológico/fisiologia , Cloretos/metabolismo , Eletrólitos/metabolismo , Enterócitos/metabolismo , Concentração de Íons de Hidrogênio , Mucosa Intestinal/metabolismo , Camundongos
7.
Cancer Sci ; 106(5): 559-66, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25683165

RESUMO

Sirtuin 6 (SIRT6) can function as a tumor suppressor by suppressing aerobic glycolysis and apoptosis resistance. However, the negative effect of SIRT6 on cellular senescence implies that it may also have the potential to promote tumor development. Here we report that the upregulation of SIRT6 expression was required for transforming growth factor (TGF)-ß1 and H2O2/HOCl reactive oxygen species (ROS) to promote the tumorigenicity of hepatocellular carcinoma (HCC) cells. Transforming growth factor-ß1/H2O2/HOCl could upregulate SIRT6 expression in HCC cells by inducing the sustained activation of ERK and Smad pathways. Sirtuin 6 in turn abrogated the inducing effect of TGF-ß1/H2O2/HOCl on cellular senescence of HCC cells, and was required for the ERK pathway to efficiently suppress the expression of p16 and p21. Sirtuin 6 altered the effect of Smad and p38 MAPK pathways on cellular senescence, and contributed to the inhibitory effect of the ERK pathway on cellular senescence. However, SIRT6 was inefficient in antagonizing the promoting effect of TGF-ß1/H2O2 HOCl on aerobic glycolysis and anoikis resistance. Intriguingly, if SIRT6 expression was inhibited, the promoting effect of TGF-ß1/H2O2/HOCl on aerobic glycolysis and anoikis resistance was not sufficient to enhance the tumorigenicity of HCC cells. Suppressing the upregulation of SIRT6 enabled TGF-ß1/H2O2/HOCl to induce cellular senescence, thereby abrogating the enhancement of HCC cell tumorigenicity by TGF-ß1/H2O2/HOCl. These results suggest that SIRT6 is required for TGF-ß1/H2O2/HOCl to enhance the tumorigenicity of HCC cells, and that targeting the ERK pathway to suppress the upregulation of SIRT6 might be a potential approach in comprehensive strategies for the therapy of HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Senescência Celular/efeitos dos fármacos , Neoplasias Hepáticas/patologia , Sirtuínas/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Anoikis , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Glicólise , Humanos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Ácido Hipocloroso/metabolismo , Ácido Hipocloroso/farmacologia , Neoplasias Hepáticas/metabolismo , Sistema de Sinalização das MAP Quinases , Camundongos Nus , Sirtuínas/genética , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Endoscopy ; 47(5): 415-20, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25590178

RESUMO

BACKGROUND AND STUDY AIM: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains the most common complication of ERCP. Somatostatin may inhibit pancreatic secretion and has been tested for PEP prophylaxis. However, the results of previous studies are inconsistent. The aim of the current study was to investigate whether somatostatin can reduce the incidence of PEP. PATIENTS AND METHODS: The study was a multicenter, open-label, randomized controlled trial. A total of 908 patients with normal amylase levels who were undergoing ERCP were randomized to receive somatostatin 250 µg bolus injection before ERCP and 250 µg/hour intravenous infusion for 11 hours after ERCP (somatostatin group) or no somatostatin treatments (control group). The incidences of PEP and hyperamylasemia were compared in the two groups. RESULTS: The full analysis set included 900 patients (445 in the somatostatin group, 455 in the control group). PEP developed in 34 patients (7.5 %) in the control group (95 % confidence interval [CI] 5.4 % - 10.3 %) and in 18 patients (4.0 %) in the somatostatin group (95 %CI 2.6 % - 6.3 %; P = 0.03). Hyperamylasemia occurred in 46 patients (10.1 %) in the control group (95 %CI 7.7 % - 13.2 %) and in 27 patients (6.1 %) in the somatostatin group (95 %CI 4.2 % - 8.7 %; P = 0.03). No perforation or death occurred during the study. CONCLUSIONS: This study showed that somatostatin was effective and safe for the prevention of PEP and hyperamylasemia in ERCP patients.(ClinicalTrials.gov number, NCT01431781).


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Hormônios/uso terapêutico , Pancreatite/prevenção & controle , Somatostatina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Amilases/sangue , Feminino , Humanos , Hiperamilassemia/etiologia , Hiperamilassemia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Pancreatite/etiologia , Adulto Jovem
9.
Pflugers Arch ; 466(8): 1541-56, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24233434

RESUMO

The mixing of gastric and pancreatic juice subjects the jejunum to unique ionic conditions with high luminal CO2 tension and HCO3 − concentration. We investigated the role of the small intestinal apical anion exchangers PAT-1 (Slc26a6) and DRA (Slc26a3) in basal and CO2/HCO3 −-stimulated jejunal fluid absorption. Single pass perfusion of jejunal segments was performed in anaesthetised wild type (WT) as well as in mice deficient in DRA, PAT-1, Na+/H+ exchanger 3 (NHE3) or NHE2, and in carbonic anhydrase II (CAII). Unbuffered saline (pH 7.4) perfusion of WT jejunum resulted in fluid absorption and acidification of the effluent. DRA-deficient jejunum absorbed less fluid than WT, and acidified the effluent more strongly, consistent with its action as a Cl−/HCO3 − exchanger. PAT-1-deficient jejunum also absorbed less fluid but resulted in less effluent acidification. Switching the luminal solution to a 5 % CO2/HCO3 − buffered solution (pH 7.4), resulted in a decrease in jejunal enterocyte pHi in all genotypes, an increase in luminal surface pH and a strong increase in fluid absorption in a PAT-1- and NHE3- but not DRA-, CAII, or NHE2-dependent fashion. Even in the absence of luminal Cl−, luminal CO2/HCO3 − augmented fluid absorption in WT, CAII, NHE2- or DRA-deficient, but not in PAT-1- or NHE3-deficient mice, indicating the likelihood that PAT-1 serves to import HCO3 − and NHE3 serves to import Na+ under these circumstances. The results suggest that PAT-1 plays an important role in jejunal Na+HCO3 ­ reabsorption, while DRA absorbs Cl− and exports HCO3 − in a partly CAII-dependent fashion. Both PAT-1 and DRA significantly contribute to intestinal fluid absorption and enterocyte acid/base balance but are activated by different ion gradients.


Assuntos
Antiporters/metabolismo , Absorção Intestinal/fisiologia , Equilíbrio Hidroeletrolítico/fisiologia , Animais , Concentração de Íons de Hidrogênio , Imuno-Histoquímica , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Confocal , Reação em Cadeia da Polimerase , Transportadores de Sulfato
10.
J Huazhong Univ Sci Technolog Med Sci ; 34(3): 343-347, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24939296

RESUMO

This study was aimed to screen human papillomavirus (HPV) types associated with esophageal squamous cell carcinoma of Kazakh in Xinjiang using the gene chip technique and study the clinical significance of this application. The DNAs were collected from esophageal squamous cell carcinoma tissues and healthy esophageal mucosa of Kazakh adults in Xinjiang, and amplified firstly using HPV MY09/11 and then using HPV G5+/6+ to screen positive HPV specimens. These positive specimens were further detected by the gene chip technique to screen highly pathogenic HPV types. After determination with nested PCR amplification with HPV MY09/11 and G5+/6+, the infection rate of HPV was 66.67% in the esophageal squamous cell carcinoma group and 12.12% in the healthy control group. By testing the positive HPV specimens from the esophageal squamous cell carcinoma group, the infection rate of HPV16 was 97.72% and the co-infection rate of HPV16 and HPV18 was 2.27%. HPV16 infection may be involved in the development of esophageal squamous cell carcinoma in Xinjiang Hazakh adults.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Papillomaviridae/genética , Infecções por Papillomavirus/genética , Idoso , Povo Asiático , Carcinoma de Células Escamosas/etnologia , Carcinoma de Células Escamosas/virologia , Estudos de Casos e Controles , China , DNA de Neoplasias/análise , DNA de Neoplasias/genética , DNA Viral/análise , DNA Viral/genética , Neoplasias Esofágicas/etnologia , Neoplasias Esofágicas/virologia , Feminino , Interações Hospedeiro-Patógeno/genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Masculino , Pessoa de Meia-Idade , Tipagem Molecular/métodos , Tipagem Molecular/estatística & dados numéricos , Papillomaviridae/classificação , Papillomaviridae/fisiologia , Infecções por Papillomavirus/etnologia , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase
11.
Precis Clin Med ; 7(2): pbae013, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38946731

RESUMO

Background: Myeloid differentiation factor 88 (MyD88) is the core adaptor for Toll-like receptors defending against microbial invasion and initiating a downstream immune response during microbiota-host interaction. However, the role of MyD88 in the pathogenesis of inflammatory bowel disease is controversial. This study aims to investigate the impact of MyD88 on intestinal inflammation and the underlying mechanism. Methods: MyD88 knockout (MyD88-/-) mice and the MyD88 inhibitor (TJ-M2010-5) were used to investigate the impact of MyD88 on acute dextran sodium sulfate (DSS)-induced colitis. Disease activity index, colon length, histological score, and inflammatory cytokines were examined to evaluate the severity of colitis. RNA transcriptome analysis and 16S rDNA sequencing were used to detect the potential mechanism. Results: In an acute DSS-colitis model, the severity of colitis was not alleviated in MyD88-/- mice and TJ-M2010-5-treated mice, despite significantly lower levels of NF-κB activation being exhibited compared to control mice. Meanwhile, 16S rDNA sequencing and RNA transcriptome analysis revealed a higher abundance of intestinal Proteobacteria and an up-regulation of the nucleotide oligomerization domain-like receptors (NLRs) signaling pathway in colitis mice following MyD88 suppression. Further blockade of the NLRs signaling pathway or elimination of gut microbiota with broad-spectrum antibiotics in DSS-induced colitis mice treated with TJ-M2010-5 ameliorated the disease severity, which was not improved solely by MyD88 inhibition. After treatment with broad-spectrum antibiotics, downregulation of the NLR signaling pathway was observed. Conclusion: Our study suggests that the suppression of MyD88 might be associated with unfavorable changes in the composition of gut microbiota, leading to NLR-mediated immune activation and intestinal inflammation.

12.
J Dig Dis ; 25(1): 27-35, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38342693

RESUMO

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.


Assuntos
Medicamentos de Ervas Chinesas , Gastrite Atrófica , Infecções por Helicobacter , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Gastrite Atrófica/tratamento farmacológico , Gastrite Atrófica/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/patologia , Metaplasia , Ácido Fólico/uso terapêutico , Mucosa Gástrica/patologia
13.
Zhonghua Gan Zang Bing Za Zhi ; 21(2): 121-4, 2013 Feb.
Artigo em Zh | MEDLINE | ID: mdl-23663884

RESUMO

OBJECTIVE: To determine the expression of nerve growth factor (NGF) in hepatic tissues and serum of patients with primary liver cancer (PLC), and to investigate the relationship of serum NGF levels with clinicopathological features of PLC. METHODS: Hepatocellular carcinoma (HCC) samples and patient-matched tumor-adjacent liver samples were collected from 26 PLC patients to assess the mRNA and protein expressions of NGF by reverse transcription-PCR, western blotting (b-actin normalized), and immunohistochemistry. In addition, serum samples were collected from 40 PLC patients, 40 liver cirrhosis patients, 40 chronic hepatitis patients (including hepatitis B or C virus infections), and 30 healthy (normal) controls. The serum levels of NGF were measured by enzyme-linked immunosorbent assay. Intergroup differences were assessed by the t-test, and correlation with sex, age, presence of cirrhosis, tumor size, and TNM classification were assessed by the Kruskal-Wallis H test followed the Mann-Whitney U test. RESULTS: HCC tissues showed higher mRNA and protein expressions of NGF than the corresponding tumor-adjacent non-HCC tissues. Hepatic NGF expression was mainly localized to the tumor cell cytoplasm. Serum NGF expression was significantly higher in PLC patients (33.86+/-16.11 pg/ml) and cirrhosis patients (20.57+/-9.73 pg/ml) than in normal controls (11.13+/-6.12 pg/ml) and chronic hepatitis patients (13.20+/-6.23 pg/ml) (P less than 0.01). Furthermore, when the PLC patients were stratified according to tumor size and TNM stage, the serum NGF level was found to be significantly higher in patients with tumors more than 5 cm (vs. less than 5 cm; U=83.000, P=0.002) or of TNM stage III/IV (vs. stage I/II; U=103.500, P=0.009). CONCLUSION: Elevated expression of NGF in liver cancer tissues and serum of PLC patients is related with tumor size and TNM staging. These findings suggest that NGF may play a role in HCC tumorigenesis and/or that serum NGF may represent a prognostic marker of PLC.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fator de Crescimento Neural/metabolismo , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Neural/sangue , Prognóstico , Adulto Jovem
14.
ACS Nano ; 17(4): 3873-3888, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36791326

RESUMO

Accurate diagnosis and timely therapeutic intervention of inflammatory bowel disease (IBD) is essential in preventing the progression of the disease, although it still represents an insurmountable challenge. Here we report the design of bacterial-flagella-inspired polydiiododiacetylene (PIDA) nanofibers and its performance in targeted computed tomography (CT) imaging and on-demand therapeutic intervention of IBD. With a morphology mimicking bacterial flagella, PIDA nanofibers attach on the mucus layer of the gastrointestinal (GI) tract after oral administration, evenly distributing on the GI surface to portray the GI lining under CT scan within 2 h. PIDA can retain for a longer time in the damaged mucosa at the inflamed lesions than in normal GI tissues to enable the targeted CT visualization of IBD. PIDA also scavenges reactive oxygen species and ameliorates gut dysbiosis attributed to its iodine-substituted polydiacetylene structure, so that the enriched PIDA nanofibers at the targeted IBD lesions can alleviate the inflammation while maintaining the gut microbiota homeostasis, thus promoting the rebalance of GI microenvironment and the mucosal healing.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Nanofibras , Humanos , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inflamação , Tomografia Computadorizada por Raios X
15.
Curr Med Sci ; 43(2): 268-273, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36864248

RESUMO

OBJECTIVE: Gastric precancerous conditions such as atrophic gastritis (AG) and intestinal metaplasia (IM) are considered independent risk factors for gastric cancer (GC). The suitable endoscopic monitoring interval is unclear when we attempt to prevent GC development. This study investigated the appropriate monitoring interval for AG/IM patients. METHODS: Totally, 957 AG/IM patients who satisfied the criteria for evaluation between 2010 and 2020 were included in the study. Univariate and multivariate analyses were used to determine the risk factors for progression to high-grade intraepithelial neoplasia (HGIN)/GC in AG/IM patients, and to determine an appropriate endoscopic monitoring scheme. RESULTS: During follow-up, 28 AG/IM patients developed gastric neoplasia lesions including gastric low-grade intraepithelial neoplasia (LGIN) (0.7%), HGIN (0.9%), and GC (1.3%). Multivariate analysis identified H. pylori infection (P=0.022) and extensive AG/IM lesions (P=0.002) as risk factors for HGIN/GC progression (P=0.025). CONCLUSION: In our study, HGIN/GC was present in 2.2% of AG/IM patients. In AG/IM patients with extensive lesions, a 1-2-year surveillance interval is recommended for early detection of HIGN/GC in AG/IM patients with extensive lesions.


Assuntos
Gastrite Atrófica , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/epidemiologia , Gastrite Atrófica/etiologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/complicações , Lesões Pré-Cancerosas/epidemiologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Fatores de Risco , Endoscopia/efeitos adversos
16.
J Dig Dis ; 24(11): 603-610, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37902019

RESUMO

OBJECTIVE: This pilot study aimed to evaluate the efficacy and safety of domperidone for the treatment of Chinese patients with functional dyspepsia (FD) who were diagnosed according to the Rome IV criteria and to identify the FD subtypes that potentially responded better to domperidone. METHODS: This multicenter prospective study was conducted in China from August 2018 to July 2020, consisting of a 1-week screening phase and a 2-week double-blind treatment phase. Participants were randomized to receive domperidone 10 mg or matching placebo tablets thrice daily for 14 days. The primary end-point was the overall treatment effect (OTE) response rate after 2-week therapy. RESULTS: Altogether 160 patients were included, with 80 patients in each group. The OTE response rate after 2-week therapy was significantly higher for domperidone compared with placebo (60.7% vs 46.0%; relative risk [RR] 1.318, 95% confidence interval [CI] 0.972-1.787). Moreover, the OTE response rate after 2-week domperidone or placebo treatment was 60.3% versus 54.9% for postprandial distress syndrome (PDS) (RR 1.098, 95% CI 0.750-1.607) and 60.6% versus 35.2% for overlapping PDS-epigastric pain syndrome (EPS) (RR 1.722, 95% CI 0.995-2.980). Adverse events were reported by seven patients in the domperidone group and 12 patients in the placebo group. None of the adverse events in the domperidone group were serious. CONCLUSION: Domperidone showed a positive pattern regarding OTE response rates after 2-week therapy compared to placebo in patients with FD, as well as in subtypes of PDS and overlapping PDS-EPS. No new safety issue was observed.


Assuntos
Dispepsia , Adulto , Humanos , Dispepsia/tratamento farmacológico , Domperidona/efeitos adversos , Projetos Piloto , Estudos Prospectivos , Método Duplo-Cego , Resultado do Tratamento
18.
Hepatogastroenterology ; 59(116): 1245-50, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22580676

RESUMO

BACKGROUND/AIMS: The aim of this study was to investigate the effect of HBV-induced Mig and role of autophagy in the process. METHODOLOGY: Adxsi-1.3 x HBV plasmid was constructed and identified. The three cell lines (L02, HepG2, SMMC-7721) were infected with adenovirus-HBV. HBsAg and HBeAg were assessed by electrochemiluminescence immunoassay. HBV DNA, HBx, Beclin 1 and Mig expression were detected by quantitative real-Time PCR, western blotting and ELISA. The level of autophagy was evaluated by transmission electron microscope. RESULTS: Human fetal liver cells and hepatocellular carcinoma cells were successfully transfected with overlength HBV genome using an adenovirus vector (Ad-HBV). Ad-HBV induced Mig production and cell autophagy through up-regulation of Beclin 1 expression. We further demonstrated that the increased autophagy extent was in association with HBV-induced Mig expression. CONCLUSIONS: Autophagy may be a crucial intracellular mechanism of Mig induction in response to HBV infection. The results provide new insights into the pathogenesis of HBV.


Assuntos
Adenoviridae/genética , Autofagia/fisiologia , Quimiocina CXCL9/biossíntese , Vírus da Hepatite B/patogenicidade , Proteínas Reguladoras de Apoptose/biossíntese , Proteína Beclina-1 , Células Cultivadas , Classe III de Fosfatidilinositol 3-Quinases/fisiologia , DNA Viral/análise , Vetores Genéticos , Células Hep G2 , Antígenos de Superfície da Hepatite B/análise , Antígenos E da Hepatite B/análise , Humanos , Proteínas de Membrana/biossíntese , Transativadores/análise , Transfecção , Proteínas Virais Reguladoras e Acessórias
19.
J Huazhong Univ Sci Technolog Med Sci ; 32(3): 353-357, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22684557

RESUMO

Metastasis contributes to the poor prognosis of hepatocellular carcinoma (HCC). However, the mechanism through which a primary HCC cell develops into a metastatic phenotype is not well understood. The purpose of this study was to examine the correlation between metadherin (MTDH)/astrocyte elevated gene-1 (AEG-1) expression in HCC cell lines of different metastatic potentials and such metastatic phenotypes as orientation chemotaxis and adhesion. MTDH/AEG-1 expression was detected by RT-PCR and western blotting in HCC cell lines (HepG2, Huh7, Sk-HEP-1, MHCC-97H). Distribution of MTDH/AEG-1 was observed by immunofluorescence staining and confocal laser scanning microscopy. The abilities of orientation chemotaxis and adhesion and the index of interaction between HCC cell lines and microvascular endothelial cell lines (MVECs, including HUVECs and HPMECs) were measured by chemotaxis assay and adhesion assay, respectively. The results showed that MTDH/AEG-1 protein expression was significantly higher in high metastatic potential cancer cell lines (Sk-HEP-1, MHCC-97H) than in low metastatic potential cell lines (HepG2, Huh7) (P<0.05). The MTDH/AEG-1 protein was localized in the perinuclear region of HCC cells. Furthermore, the abilities of orientation chemotaxis and adhesion of HCC cells to HPMECs were increased as compared with those of HCC cells to HUVECs (P<0.05). The abilities of orientation chemotaxis and adhesion were much stronger in Sk-HEP-1 and MHCC-97H cells with MTDH/AEG-1 highly expressed than in HepG2 and Huh7 cells with MTDH/AEG-1 lowly expressed (P<0.05). These results suggested that the expression of MTDH/AEG-1 gene in HCC cell lines of different metastatic potentials was closely positively related to the abilities of orientation chemotaxis and adhesion of HCC cells. It was deduced that MTDH/AEG-1 might play a pivotal role in the lung-specific metastasis of HCC, which may be mediated through orientation chemotaxis and adhesion abilities of HCC cells. MTDH/AEG-1 may serve as a potential therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular/fisiopatologia , Carcinoma Hepatocelular/secundário , Moléculas de Adesão Celular/metabolismo , Adesão Celular , Polaridade Celular , Quimiotaxia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Células Hep G2 , Humanos , Proteínas de Membrana , Proteínas de Ligação a RNA
20.
World J Clin Cases ; 10(5): 1702-1708, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35211612

RESUMO

BACKGROUND: Infectious abscesses in the abdominal wall can be secondary to retained foreign bodies (e.g., stones, use of artificial mesh, use of silk yarn in surgical suture), inflammatory diseases (e.g., acute appendicitis), and perforated malignancies of the digestive tract (particularly the colon). Aseptic abscesses (AAs) are relatively rare. To the best of our knowledge, this is the first report of an AA in the abdominal wall accompanied by monoclonal gammopathy of undetermined significance (MGUS) at 5 years after laparoscopic proctectomy. CASE SUMMARY: A 72-year-old female patient presented with an enlarged painless mass in the lower abdomen for 1 year. She had a history of obesity, diabetes, and MGUS. Her surgical history was laparoscopic resection for rectal cancer 6 years prior, followed by chemotherapy. She was afebrile. Abdominal examination revealed a smooth abdomen with a clinically palpable solid mass under a laparotomy scar in the left lower quadrant. No obvious tenderness or skin redness was spotted. Laboratory data were not remarkable. Computed tomography scan revealed a low-density mass of 4.8 cm in diameter in the lower abdominal wall, which showed high uptake on positron emission tomography. The preoperative diagnosis was an abscess or tumor, and surgical resection was recommended. The mass was confirmed to be an AA by microbiological and pathological examinations. The patient recovered well after surgery. There was no evidence of recurrence 2 years later. CONCLUSION: It is important to consider underlying conditions (diabetes, chemotherapy, MGUS) which may contribute to AA formation in the surgical wound.

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