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This letter to the editor relates to the study entitled "Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B: A real-world study", which was recently published by Peng et al. Hepatitis B virus infection represents a significant health burden worldwide and can lead to cirrhosis and even liver cancer. The antiviral drugs currently used to treat patients with chronic hepatitis B infection still have many side effects, so it is crucial to identify safe and effective drugs to inhibit viral replication.
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Antivirales , Virus de la Hepatitis B , Hepatitis B Crónica , Tenofovir , Humanos , Antivirales/uso terapéutico , Antivirales/efectos adversos , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Tenofovir/uso terapéutico , Tenofovir/análogos & derivados , Tenofovir/efectos adversos , Virus de la Hepatitis B/efectos de los fármacos , Resultado del Tratamiento , Replicación Viral/efectos de los fármacos , Adenina/análogos & derivados , Adenina/uso terapéutico , Adenina/efectos adversos , Alanina/análogos & derivados , Alanina/uso terapéutico , Alanina/efectos adversosRESUMEN
Post-discharge re-positivity of Omicron SARS-CoV-2 is challenging for the sufficient control of this pandemic. However, there are few studies about the risk of re-positivity. We aimed to explore the association of neutralizing antibodies (nAbs, AU/mL) with the incidence of re-positivity among patients recovered from COVID-19. A retrospective cohort study selected 318 Omicron-infected patients was conducted in China between December 2021 and April 2022. The peak value of nAb levels (nAb-peak) within 14 days of disease onset was defined as the baseline and was mainly used for the subsequent analyses. In the unadjusted, minimally adjusted, fully adjusted, and additionally adjusted for IgG models, a per-standard deviation (SD) increase in the nAb-peak values was significantly associated with a 59 %, 59 %, 50 %, and 75 % decreased risk of Omicron SARS-CoV-2 re-positivity during post-discharge surveillance, respectively. Stratified analyses showed no significant changes in the relationship between nAbs and re-positivity. Our study suggested that the increase in baseline nAb levels independently associated with a low risk of re-positivity in patients recovered from COVID-19.
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COVID-19 , Humanos , SARS-CoV-2 , ARN Viral , Cuidados Posteriores , Estudios Retrospectivos , Alta del Paciente , Anticuerpos Neutralizantes , Anticuerpos AntiviralesRESUMEN
Globally, liver cancer ranks among the most lethal cancers, with chemotherapy being one of its primary treatments. However, poor selectivity, systemic toxicity, a narrow treatment window, low response rate and multidrug resistance limit its clinical application. Liver-targeted nanoparticles (NPs) exhibit excellent targeted delivery ability and promising effectivity in treating liver cancer. The present study aimed to investigate the liver-targeting and anti-liver cancer effect of artesunate (ART)-loaded and glycyrrhetinic acid (GA)-decorated polyethylene glycol (PEG)-poly (lactic-co-glycolic acid) (PLGA) (ART/GA-PEG-PLGA) NPs. GA-coated NPs significantly increased hepatoma-targeted cellular uptake, with micropinocytosis and caveolae-mediated endocytosis as its chief internalization pathways. Moreover, ART/GA-PEG-PLGA NPs exhibited pro-apoptotic effects on HepG2 cells, mainly via the induction of a high level of reactive oxygen species, decline in mitochondrial membrane potential and induction of cell cycle arrest. Additionally, ART/GA-PEG-PLGA NPs induced internal apoptosis pathways by upregulating the activity of cleaved caspase-3/7 and expression of cleaved poly (ADP-Ribose)-polymerase and Phos-p38 mitogen-activated protein kinase in HepG2 cells. Furthermore, ART/GA-PEG-PLGA NPs exhibited higher liver accumulation and longer mean retention time, resulting in increased bioavailability. Finally, ART/GA-PEG-PLGA NPs promoted the liver-targeting distribution of ART, increased the retention time and promoted its antitumour effects in vivo. Therefore, ART/GA-PEG-PLGA NPs afforded excellent hepatoma-targeted delivery and anti-liver cancer efficacy, and thus, they may be a promising strategy for treating liver cancer.
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Objective: Silibinin, a natural product extracted from the seeds of the Silybum marianum, is versatile with various pharmacological effects. However, its clinical application was strongly hampered by its low bioavailability and poor water solubility. Herein, a series of glycosylated silibinin derivatives were identified as novel anti-tumor agents. Materials and Methods: The cell viability was evaluated by CCK8 assay. Furthermore, cell apoptosis and cell cycle progression were tested by flow cytometry. In addition, the pharmacokinetic assessment of compound 15 and silibinin through intravenous administration (i.v., 2 mg/kg) to ICR mice were performed. Results: The synthesized compounds showed better water solubilities than silibinin. Among them, compound 15 exhibited inhibitory activity against DU145 cells with IC50 value of 1.37 ± 0.140 µM. Moreover, it arrested cell cycle at G2/M phase and induced apoptosis in DU145 cells. Additionally, compound 15 also displayed longer half-life (T1/2 = 128.3 min) in liver microsomes than that of silibinin (T1/2 = 82.5 min) and appropriate pharmacokinetic parameters in mice. Conclusion: Overall, glycosylation of silibinin would be a valid strategy for the development of silibinin derivatives as anti-tumor agents.
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Antineoplásicos , Silimarina , Ratones , Animales , Silibina/farmacología , Silimarina/farmacología , Glicosilación , Ratones Endogámicos ICR , Antineoplásicos/farmacología , Apoptosis , Agua , Línea Celular TumoralRESUMEN
BACKGROUND: Long noncoding RNAs (lncRNAs) are closely associated with the initiation, progression, metastasis, and recurrence of hepatocellular carcinoma (HCC). They could therefore serve as markers for the early diagnosis and for the prognosis of HCC patients. METHODS: This was an observational prospective cohort study. A total of 101 participants were included, comprising patients with HCC (n = 61), liver cirrhosis (LC) (n = 20), or healthy controls (HC) (n = 20). The baseline characteristics of participants in each group were compared. Serum levels of the lncRNAs HOTAIR, BRM and ICR were determined in each group by reverse transcription and quantitative real-time polymerase chain reaction (qRT-PCR). Correlations between the serum levels of the three lncRNAs and multiple clinical parameters were analysed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic potential for HCC of each lncRNA individually, or in combination with AFP. Multivariate Cox regression analysis was used to evaluate the accuracy of these lncRNAs for predicting the outcome and survival of HCC patients. RESULTS: The serum levels of HOTAIR, BRM and ICR were significantly higher in HCC patients compared to LC patients and healthy subjects. The HOTAIR level was positively correlated to tumour-node metastasis (TNM), Barcelona Clinic Liver Cancer (BCLC) stage, extrahepatic metastasis, vascular invasion, portal vein tumour thrombus (PVTT), and tumour size. The BRM level was positively associated with TNM stage, BCLC stage, vascular invasion, PVTT, and tumour size, while the ICR level was positively correlated with PVTT. A combination of the three lncRNAs and AFP showed the highest diagnostic accuracy for HCC, with an AUC of 0.998, sensitivity of 98.4%, and specificity of 100.0%. This combination showed a better diagnostic accuracy than the individual lncRNAs or AFP alone. Serum levels of the HOTAIR and ICR lncRNAs decreased significantly following surgery. CONCLUSIONS: Serum levels of the HOTAIR, BRM and ICR lncRNAs are potential prognostic markers for HCC. Upregulation of HOTAIR, BRM and ICR may facilitate early diagnosis and indicate poor prognosis for HCC. These lncRNAs could potentially serve as therapeutic targets for HCC. Combination of the three lncRNAs with AFP may increase the diagnostic accuracy for HCC. Further studies in larger cohorts of patients are needed to validate these findings.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , ARN Largo no Codificante/genética , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Estudios Prospectivos , Curva ROC , alfa-Fetoproteínas/genéticaRESUMEN
BACKGROUND: The data of the impact of tenofovir (TDF) on kidney damage in Chinese HIV-1 infected patients are limited. OBJECTIVE: The study aims to evaluate the incidence and risk factors of stage 3 chronic kidney disease (CKD) and rapid kidney function decline (RKFD) among Chinese HIV-1 infected patients starting with a TDF-based regimen. METHODS: We enrolled 797 TDF-initiated HIV-1-infected patients in a Chinese cohort. Kidney dysfunctions were defined as stage 3 CKD (eGFR < 60 mL/min/1.73 m2 during follow-up) and RKFD (eGFR decline > 10 mL/min/1.73 m2/year). A linear mixed-effects model was used to quantify the average eGFR change per 48 weeks. A generalized estimating equation regression analysis was conducted to determine the risk factors associated with renal dysfunction. The method of multiple imputations was used to reduce the bias caused by missing data. RESULTS: In this retrospective study, 14 (2%) patients experienced stage 3 CKD, and 272 (34%) individuals experienced RKFD during a median of 26 (IQR, 4-78; maximum 325) weeks follow-up period. The mean loss in eGFR per 48 weeks increased consistently over time, from -2.59 mL/min/1.73 m2 before 48 weeks to -17.61 mL/min/1.73 m2 after 288 weeks. For every 10 mL/min/1.73 m2 increase of eGFR, the risk of RKFD increased by 29% (95%CI: 18%, 40%). Each 10 years older and every 10 mL/min/1.73 m2 higher in baseline eGFR, the risk of stage 3 CKD increased to 1.56 (95% CI: 1.00, 2.43) and decreased by 65% (95% CI: 48%, 76%), respectively. Anemia and higher viral load were significantly associated with RKFD. The results were robust across a range of multiple imputation analyses. CONCLUSION: TDF-associated CKD is rare in HIV-1 infected Chinese adults. Longer TDF-exposed patients are more likely to have renal dysfunction, especially those with older age, anemia, lower baseline eGFR, and higher viral load.
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Insuficiencia Renal Crónica , Adulto , Fármacos Anti-VIH/efectos adversos , Estudios de Cohortes , Tasa de Filtración Glomerular , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Incidencia , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Estudios Retrospectivos , Tenofovir/efectos adversosRESUMEN
BACKGROUND: Camrelizumab (SHR-1210), an immune checkpoint inhibitor, is clinically used as a therapeutic option for various types of tumors. However, reports of adverse reactions associated with camrelizumab are gradually increasing. Anaphylactic shock due to camrelizumab has not been reported previously, until now. We report here, for the first time, a case of anaphylactic shock associated with camrelizumab in a patient with esophageal squamous cell carcinoma. CASE SUMMARY: An 84-year-old male esophageal cancer patient received radiotherapy and chemotherapy 11 years ago. He was diagnosed with advanced esophageal squamous cell carcinoma with liver metastasis (TxN1M1) and received the first immunotherapy (camrelizumab 200 mg/each time, once every 3 wk) dose in December 2020, with no adverse reactions. Three weeks later, a generalized rash was noted on the chest and upper limbs; palpitations and breathing difficulties with a sense of dying occurred 10 min after the patient had been administered with the second camrelizumab therapy. Electrocardiograph monitoring revealed a 70 beats/min pulse rate, 69/24 mmHg (1 mmHg = 0.133 kPa) blood pressure, 28 breaths/min respiratory rate, and 86% pulse oximetry in room air. The patient was diagnosed with anaphylactic shock and was managed with intravenous fluid, adrenaline, dexamethasone sodium phosphate, calcium glucosate, and noradrenaline. Approximately 2 h after treatment, the patient's anaphylactic shock symptoms had been completely relieved. CONCLUSION: Due to the widespread use of camrelizumab, attention should be paid to anti-programmed cell death 1 antibody therapy-associated hypersensitivity or anaphylactic shock.
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Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Glioblastoma/diagnóstico por imagen , Glioblastoma/cirugía , Humanos , Ventrículos Laterales/diagnóstico por imagen , Ventrículos Laterales/cirugía , Imagen por Resonancia MagnéticaRESUMEN
Data on the impact of lymphocytes and neutrophils on the incidence of liver dysfunction in COVID-19 patients are limited. This study aimed to investigate the lateral and longitudinal associations of lymphocyte ratio (LR) and neutrophil ratio (NR) on liver dysfunction in COVID-19 patients. We tested 1,409 blood samples from 245 COVID-19 patients in China between January 2020 and June 2021. The lateral U-shaped relationships, determined by smooth curve fitting and the piecewise-linear mixed-effect model, were observed between LR, NR, and AST and the incidence of AST-linked liver dysfunction, with the threshold cutoffs of 26.1 and 62.0, respectively. Over the 1,409 tests, the LR ≤ 26.1 and NR ≥ 62.0 related to the occurrence of mild liver dysfunction (HR: 1.36; 95% CI: 1.01, 1.82), moderate liver dysfunction (HR: 1.37; 95% CI: 1.01, 1.85), and severe liver dysfunction (HR: 1.72; 95% CI: 1.02, 2.90). For the patients with preexisting AST ≥ 35 U/L, the baseline LR ≤ 26.1 and NR ≥ 62.0 (b.LLCHN) groups had a fully adjusted 8.85-, 7.88-, and 5.97-fold increased risk of mild and moderate liver dysfunction after being hospitalized of 3, 6, and 9 days compared to the baseline LR > 26.1 and NR < 62.0 (b.normal) groups. Severe liver dysfunction only presents significant differences after being adjusted for age, sex, and BMI. Consistently, Kaplan-Meier analyses showed that b.LLCHN reflects a better predictive value for different subsequent magnitude liver dysfunctions after admission of 3 and 6 days. To improve liver function in patients with preexisting AST ≥35 U/L, future management strategies should pay more attention to baseline LR ≤ 26.1 and NR ≥ 62.0 patients.
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COVID-19/fisiopatología , Hígado/fisiopatología , Linfocitos/patología , Neutrófilos/patología , Adulto , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , COVID-19/sangre , China/epidemiología , Femenino , Humanos , Recuento de Leucocitos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , SARS-CoV-2RESUMEN
To compare clinical and imaging features between patients with an initial negative reverse-transcription-polymerase chain-reaction (RT-PCR) test and patients with an initial positive RT-PCR test. CT follow-up analysis in the negative RT-PCR group is also described.Thirty-three patients with SARS-CoV-2 infection confirmed by RT-PCR, with 216 lesions upon CT, were included. Demographic information and chest CT imaging features were collected.The average age in the whole study group was 46.9â±â11.1 years, with 18 males and 15 females. Patients in the positive RT-PCR test group were more likely to have a fever than patients in the negative RT-PCR test group (85.7% vs 50%, Pâ<â.05). Lesions in the positive group were more likely to be located in the peripheral area than lesions in the negative group (83.6% vs 68.2%, Pâ<â.05). Regarding the appearance of 216 lesions, ground-glass opacities (GGOs) with consolidation (43.2%) was the most common appearance in the negative group, followed by pure GGOs (31.8%), while in the positive group, pure GGOs (32%) and GGOs with interlobular septal thickening (32.8%) were both most frequent, and the difference between them was evident (Pâ<â.05). For the follow-up analysis, the largest short-axis of a lesion was smaller upon follow-up (median size 13.6âmm vs 14âmm), albeit by a smaller margin. Pure GGOs decreased in frequency, from 31.3% to 21.3%, while consolidation increased in frequency, from 7.5% to 12.5%.The manifestations of COVID-19 in patients with a first negative RT-PCR test and patients with a positive first RT-PCR test are different to some extent. The consolidation component may increase after follow-up.
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Betacoronavirus/aislamiento & purificación , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico por imagen , Neumonía Viral/diagnóstico por imagen , Radiografía Torácica/estadística & datos numéricos , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto , COVID-19 , Prueba de COVID-19 , Vacunas contra la COVID-19 , Infecciones por Coronavirus/diagnóstico , Reacciones Falso Negativas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/diagnóstico , Estudios Retrospectivos , SARS-CoV-2RESUMEN
The testosterone levels decreased by T-2 toxin in mouse Leydig cells were reported previously. It is not known, however, whether l-arginine improves the situation and what's the mechanism. Leydig cells were isolated and cultured with control, 10â¯nM T-2 toxin, 0.25, 0.5 or 1.0â¯mM l-arginine, and 10â¯nM T-2 toxin supplemented with 0.25, 0.5 or 1.0â¯mM l-arginine for 24â¯h. Cells and supernatants were collected to detect the mRNA expression and activities of P450scc (cholesterol side-chain cleavage enzyme), 3ß-HSD-1 (3ß-hydroxysteroid dehydrogenase/isomerase-1) and StAR (steroidogenic acute regulatory protein). Results revealed that l-arginine increased the testosterone levels declined by T-2 toxin and up-regulated the activities and mRNA expression of P450scc, 3ß-HSD-1 and StAR down-regulated by T-2 toxin in Leydig cells. Therefore, we concluded that l-arginine ameliorated the testosterone levels decreased by T-2 Toxin via regulating the mRNA expression and activities of P450scc, 3ß-HSD-1 and StAR in mouse Leydig cells.
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Arginina/farmacología , Células Intersticiales del Testículo/metabolismo , Sustancias Protectoras/farmacología , Toxina T-2/toxicidad , Testosterona/biosíntesis , Animales , Células Cultivadas , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/metabolismo , Masculino , Ratones , ARN Mensajero/metabolismoRESUMEN
To explore the protective mechanism of l-arginine against T-2 toxin-induced oxidative damage in mouse Leydig cells, Leydig cells were isolated and cultured with control, T-2 toxin (10 nM), l-arginine (0.25, 0.5, and 1.0 mM), and T-2 toxin (10 nM T-2 toxin) with l-arginine (0.25, 0.5, or 1.0 mM) for 24 hours. Cells and supernatants were harvested to examine cell viability, activities, and messenger RNA (mRNA) expression of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT), malondialdehyde (MDA) content, and DNA damage. Results showed that T-2 toxin significantly reduced cell viability, improved MDA content and DNA damage, and decreased activities and mRNA expression of GSH-Px, SOD, and CAT. However, l-arginine reduced T-2 toxin-induced oxidative damage and tended to maintain normal levels. Furthermore, l-arginine upregulated mRNA expressions of GSH-Px, SOD, and CAT. Collectively, l-arginine, due to its antioxidative ability, could ameliorate T-2 toxin-induced cytotoxicities in mouse Leydig cells by regulating oxidative stress.
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Arginina/farmacología , Células Intersticiales del Testículo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Toxina T-2/toxicidad , Animales , Catalasa/genética , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Daño del ADN , Glutatión Peroxidasa/genética , Células Intersticiales del Testículo/enzimología , Células Intersticiales del Testículo/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , ARN Mensajero/genética , Superóxido Dismutasa/genéticaRESUMEN
We report that ultra-small, monodisperse, water-dispersible magnetite (Fe(3)O(4)) nanoparticles can be synthesized by a facile one-pot approach using trisodium citrate as crystal grain growth inhibitor and stabilizer in polyol solution. The resultant Fe(3)O(4) nanoparticles exhibit an excellent long-term colloidal stability in various buffer solutions without any modification. They are also superparamagnetic at room temperature and their magnetic property relies heavily on their size. Due to the low magnetization and good water-dispersibility, the 1.9 nm-sized Fe(3)O(4) nanoparticles reveal a low r(2)/r(1) ratio of 2.03 (r(1) = 1.415 mM(-1) s(-1), r(2) = 2.87 mM(-1) s(-1)), demonstrating that they can be efficient T(1) contrast agents. On the other hand, because of the excellent magnetic responsivity, the 13.8 nm-sized Fe(3)O(4) nanoparticles can be readily modified with nitrilotriacetic acid and used to separate the protein simply with the assistance of a magnet. In addition, these Fe(3)O(4) nanoparticles may be useful in other fields, such as hyperthermia treatment of cancer and targeted drug delivery based on their size-dependent magnetic property and excellent stability.
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A superparamagnetic reduced graphene oxide-Fe(3)O(4) hybrid composite (rGO-Fe(3)O(4)) was prepared via a facile and straightforward method through the solvothermal reaction of iron (III) acetylacetonate (Fe(acac)(3)) and graphene oxide (GO) in ethylenediamine (EDA) and water. By this method, chemical reduction of GO as well as the formation of Fe(3)O(4) nanoparticles (NPs) can be achieved in one step. The Fe(3)O(4) NPs are firmly deposited on the surfaces of rGO, avoiding their reassembly to graphite. The rGO sheets prevent the agglomeration of Fe(3)O(4) NPs and enable a uniform dispersion of these metal oxide particles. The size distribution and coverage density of Fe(3)O(4) NPs deposited on rGO can be controlled by varying the initial mass ratio of GO and iron precursor, Fe(acac)(3). With an initial mass ratio of GO and Fe(acac)(3) of 5:5, the surfaces of rGO sheets are densely covered by spherical Fe(3)O(4) NPs with an average size of 19.9 nm. The magnetic-functionalized rGO hybrid exhibits a good magnetic property and the specific saturation magnetization (M(s)) is 13.2 emu g(-1). The adsorption test of methylene blue from aqueous solution demonstrates the potential application of this rGO-Fe(3)O(4) hybrid composite in removing organic dyes from polluted water.
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Cristalización/métodos , Compuestos Férricos/química , Grafito/química , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Calor , Sustancias Macromoleculares/química , Campos Magnéticos , Ensayo de Materiales , Conformación Molecular , Óxidos/química , Tamaño de la Partícula , Solventes/química , Propiedades de SuperficieRESUMEN
OBJECTIVE: To study the impact of IFN-gamma on liver fibrosis and its possible mechanism. Thirty healthy male SD rats were randomly divided into two groups: fibrosis model group, IFN-gamma treatment group. Experimental liver fibrosis was induced by subcutaneous injection of CCl4. After 12-week-treatment, serum hyalurnic acid and TGF-beta1 was examined, histopathological changes and degrees of fibrosis were observed by optical microscopy. Meanwhile, the expression of TGF-beta1, TbetaR- I and Smad2/3 proteins was detected by immunohistochemistry and quantified by using computerized image analysis. RESULTS: (1) Pathological observation of hepatic specimens: histological examination showed that there were significant difference between normal group and fibrosis model group by comparing with the degrees of inflammation and fibrosis (P < 0.05). And the difference between fibrosis model group and IFN-gamma treatment group was significant (P < 0.05). (2) Changes of the hepatic fibrosis index (serum HA and TGF-beta1): the levels of serum HA, TGF-beta1 in fibrosis model group were higher than IFN-gamma treatment groups (P < 0.05). (3) Changes of gene protein levels about TGF-beta1/Smad: the expressions of TGF-beta1, TbetaR- I and Smad2/3 in rat hepatic tissue were detected with immunohistochemistry techniques. The expressions of the three items in model group were higher than normal group (P < 0.01). The difference between model group and IFN-gamma treatment group was significant (P < 0.05); CONCLUSION: IFN-gamma treatment group had significant results on treating experimental hepatic fibrosis. By the way of inhibiting expressions of TGF-beta1, TbetaR- I, Smad2/3, IFN-gamma treatment group exerted its anti-fibrosis effect.
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Interferón gamma/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/genética , Proteína Smad2/genética , Proteína smad3/genética , Factor de Crecimiento Transformador beta1/genética , Animales , Modelos Animales de Enfermedad , Humanos , Hígado/efectos de los fármacos , Hígado/metabolismo , Cirrosis Hepática/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
OBJECTIVE: To investigate the dynamic expression of TGF-beta1/Smad protein in rats with liver fibrosis induced by carbon tetrachloride (CCl4), to study mechanism of TGF-beta1/Smad signaling and the relationship between its transduction and liver fibrosis. METHODS: Fifty healthy male SD rats were randomly divided into two groups: normal control group and model group. Experimental liver fibrosis was induced by subcutaneous injection of CCl4. After six weeks and nine weeks, histopathological changes and degrees of fibrosis were observed by optical microscopy. Meanwhile, the expression of TGF-beta1, TP3R-I, Smad2/3 and Smad7 proteins was detected by immunohistochemistry. RESULTS: (1) Pathological observation of hepatic specimens: hepatic tissue of model group rat had inflammation and fibrosis in different degrees. By comparing with the degrees of inflammation and fibrosis model groups were more severe than normal control group (P < 0.05). (2) Changes of protein levels about TGF-beta1/Smad: the expressions of TGF-beta1, TbetaR-I, Smad2/3 and Smad7 in rat hepatic tissue were detected with immunohistochemistry techniques. The expressions of the four items in model group were higher than those of normal control group (P < 0.01). In fibrosis model group, there exist considerable positive correlations among expressions of TGF-beta1, TbetaR-I, Smad2/3, Smad7 and degrees of fibrosis in livers (P < 0.05 or 0.01). CONCLUSION: There is close relation between the level of TGF-beta1, TbetaR-I, Smad2/3, Smad7 and the different liver fibrosis grades due to CCl4. The up regulation of TGF-beta1, TbetaR- I, Smad2/3 and Smad7 in liver tissue is involved in the progression of hepatic fibrosis.
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Cirrosis Hepática/genética , Proteína Smad2/genética , Proteína smad3/genética , Proteína smad7/genética , Factor de Crecimiento Transformador beta1/genética , Regulación hacia Arriba , Animales , Tetracloruro de Carbono/efectos adversos , Modelos Animales de Enfermedad , Humanos , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/metabolismo , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Proteína smad7/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
OBJECTIVE: To detect the level of serum and liver tissue TGF-beta1 in patients with chronic hepatitis B, to study their relation to liver fibrosis and gain the evidence for diagnosis of liver fibrosis. METHODS: The liver fibrosis grades (S0-S4) of 131 cases with chronic HBV infection were diagnosed after liver biopsy. Serum TGF-beta1 was detected by enzyme-linked immunosorbent assay, and the semiquantitative analysis was applied after detecting the expression of TGF-beta1 in liver tissue with immunohistochemistry. Their relations to liver fibrosis were analyzed. RESULTS: Serum and tissue level of TGF-beta1 increased significantly with the development of fibrosis, and the same result was obtained between themselves (P < 0.01). There was very significant difference for serum level of TGF-beta1 among the groups with different fibrosis grades (P < 0.01). Serum levels of TGF-beta1 were decreased significantly comparing the Group S0 or S1 to S4 (P < 0.005). There were significant difference for serum level of TGF-beta1 among S0 and the others (P < 0.005). And there was significant difference between S1 and S3 (P < 0.005). The expression level of TGF-beta1 in liver tissue has no significant difference between group S3 and S4 (P > 0.05). However, the differences were significantly among the other comparisons (P < 0.01). CONCLUSION: There is close relation between the level of TGF-beta1 and the different liver fibrosis grades due to chronic hepatitis B. The serum level of TGF-beta1 is a potential noninvasive maker for diagnosis of liver fibrosis.