RESUMEN
Dendritic cells (DCs) are crucial in initiating and shaping both innate and adaptive immune responses. Clinical studies and experimental models have highlighted their significant involvement in various autoimmune diseases, positioning them as promising therapeutic targets. Nicotinamide (NAM), a form of vitamin B3, with its anti-inflammatory properties, has been suggested, while the involvement of NAM in DCs regulation remains elusive. Here, through analyzing publicly available databases, we observe substantial alterations in NAM levels and NAM metabolic pathways during DCs activation. Furthermore, we discover that NAM, but not Nicotinamide Mononucleotide (NMN), significantly inhibits DCs over-activation in vitro and in vivo. The suppression of DCs hyperactivation effectively alleviates symptoms of psoriasis. Mechanistically, NAM impairs DCs activation through a Poly (ADP-ribose) polymerases (PARPs)-NF-κB dependent manner. Notably, phosphoribosyl transferase (NAMPT) and PARPs are significantly upregulated in lipopolysaccharide (LPS)-stimulated DCs and psoriasis patients; elevated NAMPT and PARPs expression in psoriasis patients correlates with higher psoriasis area and severity index (PASI) scores. In summary, our findings underscore the pivotal role of NAM in modulating DCs functions and autoimmune disorders. Targeting the NAMPT-PARP axis emerges as a promising therapeutic approach for DC-related diseases.
Asunto(s)
Enfermedades Autoinmunes , Células Dendríticas , Niacinamida , Nicotinamida Fosforribosiltransferasa , Poli(ADP-Ribosa) Polimerasas , Psoriasis , Transducción de Señal , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Células Dendríticas/inmunología , Niacinamida/farmacología , Humanos , Transducción de Señal/efectos de los fármacos , Animales , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Psoriasis/metabolismo , Enfermedades Autoinmunes/tratamiento farmacológico , Nicotinamida Fosforribosiltransferasa/metabolismo , Ratones , Poli(ADP-Ribosa) Polimerasas/metabolismo , FN-kappa B/metabolismo , Ratones Endogámicos C57BL , LipopolisacáridosRESUMEN
OBJECTIVES: Peptest is a new non-invasive reflux diagnostic test based on lateral flow technology that containing two highly specific human pepsin monoclonal antibodies for detecting pepsin, a biomarker for reflux disease. The primary aim of this multicenter clinical study was to validate the efficacy of Peptest in patients diagnosed with gastroesophageal reflux and healthy controls in China. METHODS: Patients with suspected gastroesophageal reflux underwent an endoscopy and were classified into non-erosive reflux disease and erosive esophagitis subgroups. A healthy control group was also recruited. All participants were given a reflux disease questionnaire-patients scoring greater than 12 and controls scoring zero. All participants provided a postprandial saliva sample and most patients gave an additional post-symptom sample for pepsin analysis. RESULTS: Altogether 1032 participants aged between 19 and 78 years were recruited. They consisted of 488 patients with non-erosive reflux disease, 221 with erosive esophagitis and 323 healthy controls. The number of postprandial and post-symptom samples analyzed totaled 1031 and 692, respectively. The results across all centers showed an overall pepsin-positive sensitivity of 85%, a specificity of 60%, a positive predictive value of 82%, a negative predictive value of 65% and a positive likelihood ratio of 2.12. CONCLUSION: The sensitivity of Peptest was high, but the specificity achieved in some centers was low, resulting overall in only a moderate specificity. Further diagnostic investigative studies are warranted.
Asunto(s)
Anticuerpos Monoclonales/análisis , Reflujo Gastroesofágico/diagnóstico , Pepsina A/inmunología , Adulto , Anciano , Anticuerpos Monoclonales/inmunología , Biomarcadores/análisis , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Saliva/química , Sensibilidad y Especificidad , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of Magnesium isoglycyrrhizinate in treatment of chronic liver diseases. METHODS: It is a randomized, double-blind, multi-doses, active drug controlled, multi-center study. 480 proper patients were randomly divided into group A (180 patients), group B (180 patients) or group C (120 patients). Patients in group A received magnesium isoglycyrrhizinate 100 mg once daily. Patients in group B received magnesium isoglycyrrhizinate 150 mg once daily. Patients in group C received compound glycyrrhizin 120 mg once daily. The treatment course was 4 weeks. Patients were followed up 2 weeks after the treatment. Patients visited once every 2 weeks. Clinical symptoms, ALT, AST were evaluated in all the patients before treatment, at week 2, at week 4 and at 2 weeks later after treatment. The other liver function test was done before treatment and at week 4. RESULTS: 412 patients completed the study according to the protocol,152 in group A, 160 in group B and 100 in group C. ALT and AST level were significantly decreased in all groups at week 2 and week 4 (P < 0.05). The degree of ALT decrease is greater in group B than in group C at week 2 (P < 0.01). The degree of ALT decrease was not significant different among three groups at week 4 (P > 0.05). The rates of ALT improvement at week 4 in group A, B, C were 92.59%, 91.76%, 88.29%, respectively (P > 0.05). The rates of symptoms improvement at week 4 in group A, B, C were 90.41%, 89.86%, 86.46% and 72.22%, 73.53%, 68.47%, respectively (P > 0.05). No relapse were found in all three groups after treatment. The rate of adverse event in three groups was similar (P > 0.05). CONCLUSION: Magnesium isoglycyrrhizinate is an effective and safe treatment for chronic liver diseases.
Asunto(s)
Alanina Transaminasa/sangre , Antiinflamatorios/uso terapéutico , Ácido Glicirrínico/uso terapéutico , Hepatopatías/tratamiento farmacológico , Saponinas/uso terapéutico , Triterpenos/uso terapéutico , Antiinflamatorios/efectos adversos , Antiinflamatorios/farmacología , Aspartato Aminotransferasas/sangre , Enfermedad Crónica , Método Doble Ciego , Hígado Graso/sangre , Hígado Graso/tratamiento farmacológico , Femenino , Ácido Glicirrínico/efectos adversos , Ácido Glicirrínico/farmacología , Humanos , Inyecciones Intravenosas , Hígado/efectos de los fármacos , Hígado/patología , Hepatopatías/sangre , Hepatopatías Alcohólicas/sangre , Hepatopatías Alcohólicas/tratamiento farmacológico , Masculino , Saponinas/efectos adversos , Saponinas/farmacología , Triterpenos/efectos adversos , Triterpenos/farmacologíaRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of Capsule metadoxine in the treatment of alcoholic liver disease. METHODS: A randomized double blind multicenter placebo-controlled clinical study was performed to evaluate the therapeutic effectiveness and safety of capsule metadoxine. Patients in metadoxine group received capsule metadoxine 500mg tid po. Patients in placebo group received placebo 2 pillows tid po. The treatment duration was 6 weeks. Patients were followed up 2 weeks after the treatment. Patients were visited once every 3 weeks during the treatment period. Clinical symptoms and liver function were evaluated in all the patients before treatment, at week 3, week 6 and 2 weeks after therapy. CT scan was done in some patients before treatment and at the end point of therapy. RESULTS: 254 patients were recruited in the study, 126 in metadoxine group and 128 in placebo group. Median ALT, AST, GGT level in metadoxine group were decreased from 80.0 U/L, 59.2 U/L, 123.0 U/L (before treatment) to 41.1 U/L, 36.0 U/L, 57.0 U/L (after 6 weeks therapy). The improvement in liver function was more significant in metadoxine group than in placebo group (P less than 0.05). For the patients who stopped drinking during the study, the total effective rate of improvement in liver function was 82.8% in metadoxine group, much higher than that in placebo group (55.7% , P=0.0000). For the patients who did not stop drinking during the study, the total effective rate of improvement in liver function was 65.4% in metadoxine group, which is not significantly higher than that in placebo group (44.8%, P=0.1767). The CT value ratio of liver to spleen was significantly improved in metadoxine group (P=0.0023), and there was no significant difference between the two groups (P=0.6293). The rate of adverse was 1.6% in both of groups. CONCLUSION: Capsule metadoxine is an effective and safe treatment for alcoholic liver disease.
Asunto(s)
Disuasivos de Alcohol/uso terapéutico , Hepatopatías Alcohólicas/tratamiento farmacológico , Piridoxina/uso terapéutico , Ácido Pirrolidona Carboxílico/uso terapéutico , Administración Oral , Adulto , Anciano , Alanina Transaminasa/sangre , Disuasivos de Alcohol/administración & dosificación , Análisis de Varianza , Aspartato Aminotransferasas/sangre , Cápsulas , Método Doble Ciego , Combinación de Medicamentos , Hígado Graso Alcohólico/sangre , Hígado Graso Alcohólico/tratamiento farmacológico , Hígado Graso Alcohólico/patología , Femenino , Estudios de Seguimiento , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Hepatopatías Alcohólicas/sangre , Hepatopatías Alcohólicas/patología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Piridoxina/administración & dosificación , Ácido Pirrolidona Carboxílico/administración & dosificación , Resultado del Tratamiento , Ultrasonografía , Adulto Joven , gamma-Glutamiltransferasa/sangreRESUMEN
OBJECTIVE: It is important to use noninvasive methods to differentiate liver fibrosis and liver cirrhosis. A prospective study was conducted to evaluate the validity of ultrasonography (US) in evaluating the severity of liver fibrosis in patients with chronic viral hepatitis in reference to the pathologic diagnosis of their liver biopsy specimens. METHODS: The liver fibrosis status of 324 chronic viral hepatitis patients was evaluated by both needle biopsy and US. Histologically their liver fibrosis was graded as S0-S4, and the inflammatory reaction in the liver was graded as G1-G4. The US examination included qualitative description of the liver surface and liver parenchyma, and the quantitative parameters were vascular diameters, blood flow volume and spleen size. RESULTS: US qualitative description of the liver surface and liver parenchyma was correlated to the severity of fibrosis and the degree of the inflammation seen in the liver biopsies. An analysis of US quantitative parameters showed that a cut-off value of 12.1 cm for the length of spleen had a sensitivity of 60.0%, and specificity of 75.3% in detecting early liver fibrosis. For other quantitative parameters, the cut-off values were 8mm for the diameter of the splenic vein, 30.5 cm/sec for maximal blood flow velocity in the portal vein and 12 mm in diameter of the main portal vein. The diagnostic sensitivities for these parameters were 60.0%, 78.6% and 76.7%; the diagnostic specificities were 78.1%, 66.9% and 44.6% respectively. CONCLUSION: Early cirrhosis can be detected by US, and the sonographic results were well paralleled with their pathologic diagnoses made by liver biopsies. Individual US parameter has limited sensitivity and specificity in diagnosing early cirrhosis. In clinical practice a combination of 2-3 parameters could be used to detect or exclude severe liver fibrosis.
Asunto(s)
Hepatitis B Crónica/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Adulto , Femenino , Hepatitis B Crónica/diagnóstico por imagen , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico por imagen , Humanos , Cirrosis Hepática/virología , Masculino , Estudios Prospectivos , UltrasonografíaRESUMEN
OBJECTIVES: To observe the role of PPARgamma during the activation process of hepatic stellate cells (HSC). METHODS: By morphology and RT-PCR, we study the changes of expression of PPARgamma in culture-activated HSC or in vivo activated HSC induced by dimethylnitrosamine (DMN). RESULTS: In vitro, the expression level of PPARgamma in freshly isolated HSC (0.72+/-0.01) significantly reduced to 0.48+/-0.03 on the third day of culture (t = 19.8372, P<0.01), and reduced 70% on the seventh culture-day and could not be detected after the second passage. In vivo, HSC freshly isolated from normal control rats expressed PPARgamma (0.76+/-0.01). During the development of rat liver fibrosis induced by DMN, the expression level significantly reduced to 0.46+/-0.02 after the third injection of DMN (t = 29.5318, P<0.01), and reduced 66% on the end of first week and could not be detected on the end of second and third week. CONCLUSION: The expression of PPARgamma might play an important role on the maintenance of resting-form of HSC, and the reduction of expression of PPARgamma might be an early event during the activation process of HSC.
Asunto(s)
Cirrosis Hepática/etiología , Hígado/citología , Receptores Citoplasmáticos y Nucleares/fisiología , Factores de Transcripción/fisiología , Animales , Cirrosis Hepática/patología , Masculino , ARN Mensajero/análisis , Ratas , Ratas WistarRESUMEN
AIM: To study the inhibitory effect of oxymatrine on serum hepatitis B virus (HBV) DNA in HBV transgenic mice. METHODS: HBV transgenic mice model was established by microinjection, and identified by HBV DNA integration and replication. Transgenic mice with replicating HBV were divided into 3 groups, and injected with normal saline (group A, n=9), 50 mg/kg (group B, n=8) and 100 mg/kg (group C, n=9) oxymatrine intraperitoneally once a day for 30 d, respectively. Quantitation of serum HBV DNA in HBV transgenic mice was performed by competitive polymerase chain reaction (PCR) in combination with DNA hybridization quantitative detection technique before and after treatment. RESULTS: Compared with pre-treatment, the serum HBV DNA in group A (F=1.04, P=0.9612) and group B (F=1.13, P=0.8739) had no changes after treatment. However, in group C serum HBV DNA was significantly decreased (F=13.97, P=0.0012). The serum HBV DNA after treatment was lower in group C than in groups B and A (F=8.65, P=0.0068; F=12.35, P=0.0018; respectively). The serum HBV DNA after treatment was lower in group B than in group A, but there was no statistical significance (F=1.43, P=0.652). CONCLUSION: Oxymatrine has inhibitory effects on serum HBV DNA in HBV transgenic mice.
Asunto(s)
Alcaloides/farmacología , Antivirales/farmacología , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Animales , ADN Viral/sangre , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/crecimiento & desarrollo , Hepatitis B Crónica/virología , Ratones , Ratones Endogámicos ICR , Ratones Transgénicos , Quinolizinas , Integración Viral/efectos de los fármacos , Replicación Viral/efectos de los fármacosRESUMEN
AIM: To explore the relationship between clinical findings of patients with chronic liver diseases and the pathologic grading and staging of liver tissues. METHODS: The inflammatory activity and fibrosis of consecutive liver biopsies from 200 patients were determined according to the diagnosis criteria of chronic hepatitis in China established in 1995. A comparative analysis was carried out for 200 patients with chronic liver diseases by comparing their clinical manifestations, serum biochemical markers with the grading and staging of liver tissues. RESULTS: It was revealed that age, index of clinical symptoms and physical signs were obviously relevant to the pathologic grading and staging of liver tissues (P<0.05). Blood platelet, red blood cells, aspartate aminotransferase (AST), N-terminal procollagen III (PIII NP) were apparently correlated with the degree of inflammation. PGA (prothrombin time, GGT, apoprotein A1) index, PGAA (PGA+delta2-macroglobulin) index, albumin and albumin/globulin were relevant to both inflammation and fibrosis. Hyaluronic acid (HA) was an accurate variable for the severity of hepatic inflammation and fibrosis. The combination of serum markers for fibrosis could increase the diagnostic accuracy. It was notable that viral replication markers were not relevant to the degree of inflammation and fibrosis. CONCLUSION: There is a good correlation between clinical findings and the pathologic grading and staging of liver tissues, which may give aid to the noninvasive diagnosis of liver fibrosis.
Asunto(s)
Hepatopatías/patología , Hepatopatías/fisiopatología , Hígado/patología , Enfermedad Crónica , Pruebas Diagnósticas de Rutina , Humanos , Inflamación , Cirrosis Hepática/patología , Hepatopatías/clasificación , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
AIM: To explore the grade and stage of pathology and the relationship between grading and staging of hepatic fibrosis and noninvasive diagnostic parameters. METHODS: Inflammatory activity and fibrosis of consecutive liver biopsies from 200 patients with chronic liver disease were determined according to the Diagnostic Criteria of Chronic Hepatitis in China, 1995. A comparative analysis was made in these patients comparing serum markers, Doppler ultrasonography, CT and/or MR imaging with the findings of liver biopsy. RESULTS: With increase of inflammatory activity, the degree of fibrosis also rose. There was a close correlation between liver fibrosis and inflammatory activity. AST, GGT, albumin, albumin/globulin, ALP, AFP, hyaluronic acid, N-terminal procollagen III(P III NP), collagen type IV(Col IV), tissue inhibitors of metalloproteinases-1 (TIMP-1), alpha-2-macroglobulin, natural killer cells(NK), some parameters of Doppler ultrasonography, CT and/or MR imaging were all related to the degree of inflammatory activity. GGT, albumin, albumin/globulin, ALP, AFP, hyaluronic acid, Col IV, TIMP-1, alpha-2- macroglobulin, transforming growth factor-beta 1 (TGFbeta1), NK, some parameters of Doppler ultrasonography, CT and/or MR imaging were all related to the staging of fibrosis. By regression analysis, the parameters used in combination to differentiate the presence or absence of fibrosis were age, GGT, the parameter of blood flow of portal vein per minute, the maximum oblique diameter of right liver by B ultrasound, the wavy hepatic surface contour by CT and/or MR. The sensitivity, specificity and accuracy of the above parameters were 80.36%, 86.67%, and 81.10%, respectively. CONCLUSION: There is close correlation between liver fibrosis and inflammatory activity. The grading and staging of liver fibrosis are related to serum markers, Doppler ultrasonography, CT and/or MR imaging. The combination of the above mentioned noninvasive parameters are quite sensitive and specific in the diagnosis of hepatic fibrosis.