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1.
Antiviral Res ; 226: 105889, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38631661

RESUMEN

Hepatitis B virus (HBV) infections pose a major threat to human health. HBV can upregulate the expression of the transcription factor Yin Yang 1 (YY1) in in vitro cytological experiments, suggesting an association between YY1 and HBV infection. However, data on YY1 expression in chronic hepatitis B (CHB) patients are lacking. In this study, we aimed to assess the correlation between YY1 expression and HBV infection. We detected serum YY1 levels in 420 patients with chronic HBV infection, 30 patients with chronic hepatitis C virus infection, and 32 healthy controls using an enzyme-linked immunosorbent assay. The correlation between YY1 levels and clinical parameters was analyzed. Meanwhile, the changes of YY1 before and after interferon or entecavir treatment were analyzed. YY1 levels in the liver tissues were detected using immunofluorescence staining. The expression of YY1 in HBV-expressing cells was detected through western blotting. Meanwhile, we explored the effects of YY1 on HBV replication and gene expression. We found that YY1 was highly expressed in the serum and liver tissues of CHB patients. Serum YY1 levels positively correlated with HBV DNA and hepatitis B surface antigen (HBsAg). Additionally, HBV DNA levels increased but HBsAg levels decreased after HBV-expressing cells overexpress YY1. In conclusion, our study demonstrates that YY1 plays an important role in HBV replication and gene expression, providing a potential target for the treatment of CHB.


Asunto(s)
ADN Viral , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B Crónica , Hígado , Replicación Viral , Factor de Transcripción YY1 , Humanos , Factor de Transcripción YY1/metabolismo , Factor de Transcripción YY1/genética , Hepatitis B Crónica/virología , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/metabolismo , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/fisiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , ADN Viral/genética , ADN Viral/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/metabolismo , Hígado/virología , Hígado/metabolismo , Guanina/análogos & derivados , Antivirales/uso terapéutico , Antivirales/farmacología , Interferones/metabolismo , Células Hep G2
2.
World J Gastroenterol ; 30(13): 1911-1925, 2024 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-38659485

RESUMEN

BACKGROUND: Liuweiwuling Tablet (LWWL) is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus (HBV) infection. Previous studies have indicated an anti-HBV effect of LWWL, specifically in terms of antigen inhibition, but the underlying mechanism remains unclear. AIM: To investigate the potential mechanism of action of LWWL against HBV. METHODS: In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell lines. The in vivo experiment involved a hydrodynamic injection-mediated mouse model with HBV replication. Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL. RESULTS: In HepG2.1403F cells, LWWL (0.8 mg/mL) exhibited inhibitory effects on HBV DNA, hepatitis B surface antigen and pregenomic RNA (pgRNA) at rates of 51.36%, 24.74% and 50.74%, respectively. The inhibition rates of LWWL (0.8 mg/mL) on pgRNA/covalently closed circular DNA in HepG2.1403F, HepG2.2.15 and HepG2.A64 cells were 47.78%, 39.51% and 46.74%, respectively. Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis (PI3K-AKT, CASP8-CASP3 and P53 pathways). Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group (CG) among HBV-replicating cell lines, including HepG2.2.15 (2.92% ± 1.01% vs 6.68% ± 2.04%, P < 0.05), HepG2.A64 (4.89% ± 1.28% vs 8.52% ± 0.50%, P < 0.05) and HepG2.1403F (3.76% ± 1.40% vs 7.57% ± 1.35%, P < 0.05) (CG vs LWWL-treated group). However, there were no significant differences in apoptosis rates between the non-HBV-replicating HepG2 cells (5.04% ± 0.74% vs 5.51% ± 1.57%, P > 0.05), L02 cells (5.49% ± 0.80% vs 5.48% ± 1.01%, P > 0.05) and LX2 cells (6.29% ± 1.54% vs 6.29% ± 0.88%, P > 0.05). TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBV-replicating mouse model, while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replicating mouse model. CONCLUSION: Preliminary results suggest that LWWL exerts a potent inhibitory effect on wild-type and drug-resistant HBV, potentially involving selective regulation of apoptosis. These findings offer novel insights into the anti-HBV activities of LWWL and present a novel mechanism for the development of anti-HBV medications.


Asunto(s)
Antivirales , Apoptosis , ADN Viral , Medicamentos Herbarios Chinos , Virus de la Hepatitis B , Comprimidos , Replicación Viral , Apoptosis/efectos de los fármacos , Animales , Humanos , Virus de la Hepatitis B/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Ratones , Células Hep G2 , Antivirales/farmacología , Replicación Viral/efectos de los fármacos , Modelos Animales de Enfermedad , Antígenos de Superficie de la Hepatitis B/metabolismo , Masculino , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología , ARN Viral/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Hígado/virología
3.
Front Cell Infect Microbiol ; 14: 1356003, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38487354

RESUMEN

Flavonoids, a diverse group of polyphenolic compounds found in various plant-based foods, have garnered attention for their potential in combating Hepatitis B Virus (HBV) infection. Flavonoids have demonstrated promising anti-HBV activities by interfering with multiple stages of the HBV life cycle, making them promising candidates for novel antiviral agents. Certain plant families, such as Theaceae, Asteraceae, Lamiaceae, and Gentianaceae, are of particular interest for their flavonoid-rich members with anti-HBV activities. Evidences, both in vitro and in vivo, supports the anti-HBV potential of flavonoids. These subsets of compound exert their anti-HBV effects through various mechanisms, including inhibiting viral entry, disrupting viral replication, modulating transcription factors, enhancing the immune response, and inducing autophagy. The antioxidant properties of flavonoids play a crucial role in modulating oxidative stress associated with HBV infection. Several flavonoids like epigallocatechin gallate (EGCG), proanthocyanidin (PAC), hexamethoxyflavone, wogonin, and baicalin have shown significant anti-HBV potential, holding promise as therapeutic agents. Synergistic effects between flavonoids and existing antiviral therapies offer a promising approach to enhance antiviral efficacy and reduce drug resistance. Challenges, including limited bioavailability, translation from preclinical studies to clinical practice, and understanding precise targets, need to be addressed. Future research should focus on clinical trials, combination therapies, and the development of flavonoid derivatives with improved bioavailability, and optimizing their effectiveness in managing chronic HBV infections.


Asunto(s)
Hepatitis B Crónica , Hepatitis B , Humanos , Virus de la Hepatitis B/fisiología , Antivirales/farmacología , Antivirales/uso terapéutico , Hepatitis B/tratamiento farmacológico , Hepatitis B Crónica/tratamiento farmacológico , Flavonoides/farmacología , Replicación Viral
4.
J Ethnopharmacol ; 328: 118072, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38508431

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Formula (BSF) is the effective traditional Chinese medicine (TCM) for chronic hepatitis B (CHB) according to our previous researches. However, the special effectiveness of BSF treating CHB patients in different stages and the immunoregulatory mechanisms remain to be explored. AIM OF THE STUDY: To compare the therapeutic effects of BSF in both treatment-naive patients and Peg-IFN-α-treated patients, and explore the potential mechanism of immunomodulation. MATERIALS AND METHODS: Ultra-high performance liquid chromatography-quadrupole electrostatic field-orbital trap high resolution mass spectrometry and the TCMSP database were used to determine the main components of BSF. Two hundred and sixty-six patients were enrolled in the retrospective study, and they were divided into the treatment group (T-Group, BSF plus Peg-IFN-α) and the control group (C-Group, Peg-IFN-α monotherapy). Within each group, patients were further grouped into subgroups, namely T1/C1 groups (treatment-naive patients, T1 = 34, C1 = 94) and T2/C2 groups (Peg-IFN-α-treated patients, T2 = 56, C2 = 82). Serum HBV markers, serum HBV DNA levels, serum ALT/AST and TCM symptoms were obtained from the record. Bioinformatics analysis was employed to obtain the potential immunoregulatory mechanisms of BSF treating CHB patients. Among patients in T2 and C2 group, peripheral mononuclear cells from 36 patients were used to analyze the characteristics of peripheral follicular helper T (Tfh) cells and B-cell subtypes by flow cytometry. Preparation of BSF-containing serum in rats. In vitro, the co-culture system of CXCR5+ cells and HepG2.2.15 cells was built to investigate the immunoregulatory effects of BSF. RESULTS: A total of 14 main active compounds were detected in BSF, which were deemed critical for the treatment of CHB. Our findings indicated that the T2-Group exhibited the higher percentage of HBsAg decline ≥ 1-log10 IU/ml and rate of HBeAg seroclearance compared to the C2-Group (35.7% vs. 15.9%, P = 0.033; 33.9% vs. 11.0%, P = 0.002). Additionally, the T2-Group demonstrated the higher percentage of HBsAg decline ≥ 1-log10 IU/ml and rate of HBeAg seroclearance compared to the T1-Group (35.7% vs. 14.7%, P = 0.031; 33.9% vs. 2.9%, P = 0.000). The total effective rate based on TCM clinical syndrome in T1-Group and T2-Group were significantly greater than those in C1-Group and C2-Group (85.3% vs. 61.7%, P = 0.012; 89.1% vs. 63.4%, P = 0.000). Bioinformatics analysis indicated that the immunoregulatory mechanisms of BSF treating CHB patients were mainly linked to the growth and stimulation of B-cell, T-cell differentiation, and the signaling pathway of the B-cell receptor. Furthermore, the frequencies of Tfh cells and its IL-21 level, and the IL-21R expressed by B-cell were all increased after BSF treatment. Additionally, in the co-culture system of CXCR5+ cells and HepG2.2.15 cells, HBsAg and HBeAg levels were decreased after BSF-containing serum treatment,as well as the up-regulating of Tfh cell frequencies and down-regulating of B-cell frequencies. CONCLUSIONS: BSF have the higher percentage of HBsAg decline and HBeAg seroclearance in Peg-IFN-α-treated patients compared with treatment-naive patients. The potential immunoregulatory mechanism may correlate with promoting the interaction between Tfh cells and B-cell through IL-21/IL-21R signaling pathway.


Asunto(s)
Subgrupos de Linfocitos B , Medicamentos Herbarios Chinos , Hepatitis B Crónica , Humanos , Ratas , Animales , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Células T Auxiliares Foliculares , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/diagnóstico , Antivirales/farmacología , Antivirales/uso terapéutico , Antígenos e de la Hepatitis B , Estudios Retrospectivos , Biomarcadores , ADN Viral , Resultado del Tratamiento , Polietilenglicoles/uso terapéutico
5.
J Ethnopharmacol ; 325: 117893, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38336184

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Erzhu Jiedu Recipe (EZJDR) is a formula of traditional Chinese medicine (TCM) for treating hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). However, its effective components and the mechanism of action remain unclear. AIM OF THE STUDY: To explain how the active compounds of EZJDR suppress the growth of hepatoma cells. METHODS: UHPLC-Q-Exactive Orbitrap HRMS was used to identify the chemical constituents of EZJDR and their distribution in the serum and liver of mice. Together with experimental investigations, network pharmacology unraveled the molecular mechanism of components of EZJDR underlying the inhibited Hep3B cells. RESULTS: A total of 138 compounds which can be divided into 18 kinds of components (such as sesquiterpenoids, diterpenoids, anthraquinones, flavonoids and so on) were found in the aqueous extract of EZJDR. Of these components, the tricyclic-diterpenoids exhibited a highest exposure in the serum (74.5%) and liver (94.7%) of mice. The network pharmacology revealed that multiple components of EZJDR interacted with key node genes involved in apoptosis, proliferation, migration and metabolism through various signaling pathways, including ligand binding and protein phosphorylation. In vitro experiments demonstrated that 6 tricyclic-diterpenoids, 2 anthraquinones and 1 flavonoid inhibited the viability of Hep3B cells, with IC50 values ranging from 3.81 µM to 37.72 µM. Dihydrotanshinone I had the most potent bioactivity, arresting the S phase of cell cycle and inducing apoptosis. This compound changed the expression of proteins, including Bad, Bax, Bcl-2, Bal-x, caspase3 and catalase, which were associated with mitochondria-mediated apoptotic pathways. Moreover, dihydrotanshinone I increased the levels of p21 proteins, but decreased the phosphorylated p53, suggesting accumulation of p53 protein prevented cell cycle progression of Hep3B cells with damaged DNA. CONCLUSIONS: These results suggested that multiple components of EZJDR-diterpenoid, anthraquinone and flavonoid-could be the effective material for the treatment of HBV-HCC. This research provided valuable insights into the molecular mechanism of action underlying the therapeutic effects of EZJDR.


Asunto(s)
Carcinoma Hepatocelular , Diterpenos , Medicamentos Herbarios Chinos , Furanos , Neoplasias Hepáticas , Fenantrenos , Quinonas , Humanos , Ratones , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Proteína p53 Supresora de Tumor , Cromatografía Líquida de Alta Presión , Farmacología en Red , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Flavonoides/farmacología , Flavonoides/uso terapéutico , Antraquinonas/uso terapéutico , Diterpenos/uso terapéutico
6.
BMC Public Health ; 24(1): 266, 2024 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-38262984

RESUMEN

BACKGROUND: Heavy metal pollution has emerged as a significant concern for human health, prompting increased awareness of its potential adverse effects. While previous research has established a connection between heavy metals and liver function biomarkers, the specific relationship between heavy metals and HBV infection remains unexplored. This cross-sectional study aims to investigate the potential correlations between five blood heavy metals - lead, cadmium, mercury, manganese, and selenium - and the presence of HBsAg, HBsAb, and HBcAb in adults. METHODS: The study utilized data from NHANES 2007-2018. Participants were classified into four groups based on their infectious status, and the association between heavy metals and HBV infection was analyzed using multiple logistic regression and stratification analysis. RESULTS: A total of 8431 participants were included, with 5 436 classified as Susceptible, 1 765 as Vaccinated, 865 as Natural Infection, and 103 as Acute/Chronic HBV Infection. The Vaccinated group exhibited a lower mean age (34.52 ± 14.16 years) compared to the other groups. Statistically significant differences in heavy metal concentrations (except selenium) were observed among the groups (P < 0.001). After adjusting for covariates, lead was significantly associated with HBV infection (Q2: OR 2.37, 95%CI 1.04-5.39; Q3: OR 2.34, 95%CI 1.01-5.40), and positive trends were observed for high blood concentrations of mercury (Q4: OR 3.03, 95%CI 1.31-7.04) and manganese (Q4: OR 2.52, 95%CI 1.20-5.28). Furtherly, the presence of lead reduced the protection of HBsAb (Q2: OR 0.84, 95%CI 0.73-0.97; Q3: OR 0.77, 95%CI 0.66-0.90; Q4: OR 0.83, 95%CI 0.70-0.98). Subgroup analysis indicated that cadmium was associated with an increased risk of HBV infection in Asians (OR 1.36, 95%CI 1.03-1.78) and individuals with a BMI range of 25 to 30 (OR 1.60, 95%CI 1.17-2.18). CONCLUSIONS: The study's findings suggest a correlation between elevated blood Pb concentrations and reduced immunization rates against hepatitis B. Individuals with a positive HBsAg exhibit lower blood Se concentrations and higher blood Hg and Mn concentrations.


Asunto(s)
Hepatitis B , Mercurio , Metales Pesados , Selenio , Adulto , Humanos , Adulto Joven , Persona de Mediana Edad , Virus de la Hepatitis B , Estudios Transversales , Cadmio , Manganeso , Antígenos de Superficie de la Hepatitis B , Encuestas Nutricionales , Anticuerpos contra la Hepatitis B
7.
EClinicalMedicine ; 68: 102419, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38292041

RESUMEN

Background: With increasingly prevalent coexistence of chronic hepatitis B (CHB) and hepatic steatosis (HS), simple, non-invasive diagnostic methods to accurately assess the severity of hepatic inflammation are needed. We aimed to build a machine learning (ML) based model to detect hepatic inflammation in patients with CHB and concurrent HS. Methods: We conducted a multicenter, retrospective cohort study in China. Treatment-naive CHB patients with biopsy-proven HS between April 2004 and September 2022 were included. The optimal features for model development were selected by SHapley Additive explanations, and an ML algorithm with the best accuracy to diagnose moderate to severe hepatic inflammation (Scheuer's system ≥ G3) was determined and assessed by decision curve analysis (DCA) and calibration curve. This study is registered with ClinicalTrials.gov (NCT05766449). Findings: From a pool of 1,787 treatment-naive patients with CHB and HS across eleven hospitals, 689 patients from nine of these hospitals were chosen for the development of the diagnostic model. The remaining two hospitals contributed to two independent external validation cohorts, comprising 509 patients in validation cohort 1 and 589 in validation cohort 2. Eleven features regarding inflammation, hepatic and metabolic functions were identified. The gradient boosting classifier (GBC) model showed the best performance in predicting moderate to severe hepatic inflammation, with an area under the receiver operating characteristic curve (AUROC) of 0.86 (95% CI 0.83-0.88) in the training cohort, and 0.89 (95% CI 0.86-0.92), 0.76 (95% CI 0.73-0.80) in the first and second external validation cohorts, respectively. A publicly accessible web tool was generated for the model. Interpretation: Using simple parameters, the GBC model predicted hepatic inflammation in CHB patients with concurrent HS. It holds promise for guiding clinical management and improving patient outcomes. Funding: This research was supported by the National Natural Science Foundation of China (No. 82170609, 81970545), Natural Science Foundation of Shandong Province (Major Project) (No. ZR2020KH006), Natural Science Foundation of Jiangsu Province (No.BK20231118), Tianjin Key Medical Discipline (Specialty), Construction Project, TJYXZDXK-059B, Tianjin Health Science and Technology Project key discipline special, TJWJ2022XK034, and Research project of Chinese traditional medicine and Chinese traditional medicine combined with Western medicine of Tianjin municipal health and Family Planning Commission (2021022).

8.
Am J Med ; 137(3): 258-265.e3, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38000687

RESUMEN

BACKGROUND: Hepatitis B virus (HBV) and latent tuberculosis infection are associated with a significant global burden, but both are underdiagnosed and undertreated. We described the screening patterns and risk factors for co-infection with latent tuberculosis and HBV within a large healthcare system. METHODS: Using data from Kaiser Permanente Southern California during 2008-2019, we described HBV infections, defined as a positive HBV surface antigen, e-antigen, or DNA test, and latent tuberculosis, defined as a positive Mantoux tuberculin skin test or interferon-gamma release assay test. We estimated adjusted odds ratios (aOR) for co-infection among screened adults with either infection. RESULTS: Among 1997 HBV patients screened for latent tuberculosis, 23.1% were co-infected, and among 35,820 patients with latent tuberculosis screened for HBV, 1.3% were co-infected. Among HBV patients, co-infection risk was highest among Asians compared with White race/ethnicity (29.4% vs 5.7%, aOR 4.78; 95% confidence interval [CI], 2.75-8.31), and persons born in a high-incidence country compared with low-incidence countries (31.0% vs 6.6%; aOR 4.19; 95% CI, 2.61-6.73). For patients with latent tuberculosis, risk of co-infection was higher among Asian (aOR 9.99; 95% CI, 5.79-17.20), or Black race/ethnicity (aOR 3.33; 95% CI, 1.78-6.23) compared with White race/ethnicity. Persons born in high-incidence countries had elevated risk of co-infection compared with persons born in low-incidence countries (aOR 2.23; 95% CI, 1.42-3.50). However, Asians or persons born in high-incidence countries were screened at similar rates to other ethnicities or persons born in low-incidence countries. CONCLUSIONS: Latent tuberculosis risk is elevated among HBV patients, and vice versa. Risk of co-infection was highest among persons born in high-incidence countries and Asians. These findings support recent guidelines to increase HBV and tuberculosis screening, particularly among persons with either infection.


Asunto(s)
Coinfección , Prestación Integrada de Atención de Salud , Hepatitis B , Tuberculosis Latente , Adulto , Humanos , Virus de la Hepatitis B , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Coinfección/epidemiología , Factores de Riesgo , Hepatitis B/complicaciones , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , California/epidemiología , Prevalencia
9.
Artículo en Chino | WPRIM | ID: wpr-1005265

RESUMEN

ObjectiveTo investigate the preventive and therapeutic effects of Tiaogan Huaxian pills combined with entecavir on hepatic fibrosis in chronic hepatitis B with liver Qi stagnation, spleen deficiency, and blood stasis syndrome and its effect on diffusion-weighted imaging (DWI). MethodClinical data of 117 patients with liver disease who visited the Department of Hepatology at the First Affiliated Hospital of Guangxi University of Chinese Medicine from January 2021 to April 2022 were retrospectively analyzed. According to different treatment plans, they were divided into a control group (59 cases) and a treatment group (58 cases). Both groups of patients received entecavir-based etiology treatment, and the treatment group added Tiaogan Huaxian pills on the basis of basic treatment. Both groups were treated for 24 weeks. Before and after treatment, the two groups were compared in terms of alanine aminotransferase (ALT), advanced surgical technologies (AST), total bilirubin (TBil), hepatitis B virus (HBV)-DNA conversion rate, liver stiffness measurement (LSM), four items of liver fibrosis (hyaluronidase, type Ⅲ pro-collagen, type Ⅳ collagen, and laminin), the fibrosis index based on four factors (FIB-4), the aspartate aminotransferase to platelet ratio index (APRI), the apparent diffusion coefficient (ADC) value in magnetic resonance imaging (MRI), and traditional Chinese medicine symptom scores, so as to analyze the efficacy of the two groups. ResultBefore treatment, there was no significant difference in ALT, AST, TBil, LSM, four items of liver fibrosis, FIB-4, APRI, HBV-DNA conversion rate, ADC value, and traditional Chinese medicine symptom scores between the two groups. After treatment, both groups of patients showed significant reductions in ALT, AST, TBil, LSM, hyaluronidase, type Ⅲ pro-collagen, type Ⅳ collagen, laminin, FIB-4, and APRI (P<0.05) and a significant increase in ADC value (P<0.05) and HBV-DNA conversion rate (P<0.01). The traditional Chinese medicine symptom score of the treatment group decreased significantly (P<0.05). Compared with the control group after treatment, the effective rate of clinical traditional Chinese medicine in the treatment group was 91.38% (53/58), which was significantly higher than that of the control group (54.23%, 32/59) (Z=-4.325, P<0.01). In the treatment group, ALT, AST, TBil, LSM, hyaluronidase, type Ⅲ pro-collagen, type Ⅳ collagen, laminin, FIB-4, APRI, and traditional Chinese medicine symptom scores all decreased significantly (P<0.05), and the increase in ADC values was more significant (P<0.05), while the difference in HBV-DNA conversion rate was not statistically significant. There were no serious adverse reactions or events in either group. ConclusionTiaogan Huaxian pills combined with entecavir have significant clinical efficacy in the treatment of hepatic fibrosis in chronic hepatitis B, which can reduce liver inflammation activity, delay hepatic fibrosis progression, and reduce traditional Chinese medicine symptom scores. It is worthy of clinical promotion and application.

10.
Phytochemistry ; 217: 113912, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37918620

RESUMEN

Artemisia argyi Levl. Et Vant, commonly known as "Chinese Mugwort," has been utilized in traditional Chinese medicine and cuisine for centuries. Aged Chinese Mugwort has been uncovered to possess superior quality and safety, and its ethyl acetate extract has been found to exhibit anti-hepatitis B virus (HBV) activity. In this study, twenty-five sesquiterpenoids were isolated and characterized from three-year-aged A. argyi. Among them, 14 previously undescribed sesquiterpenoids (1-14), featuring double bond oxidation or ring opening. It is hypothesized that during the aging process, sesquiterpenes undergo oxidative transformation of their double bonds to form alcohols due to external factors and inherent properties. The anti-HBV activity and cytotoxicity of all compounds were assessed in vitro using HepG 2.2.15 cells, and their structure-activity relationships were analyzed through three-dimensional quantitative structure-activity relationship (3D-QASR) techniques. The α-methylene-γ-lactone sesquiterpenoid derivatives were discovered to have potent inhibitory activity against HBV. This research may broaden the potential applications of Chinese Mugwort and offer further guidance for its development and utilization as functional food or traditional Chinese medicine.


Asunto(s)
Artemisia , Sesquiterpenos , Virus de la Hepatitis B , Relación Estructura-Actividad Cuantitativa , Artemisia/química , Medicina Tradicional China , Sesquiterpenos/farmacología
11.
World J Clin Cases ; 11(32): 7785-7794, 2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-38073682

RESUMEN

BACKGROUND: Osteomalacia (OM) is frequently confused with various musculoskeletal or other rheumatic diseases, especially in patients with adult-onset widespread musculoskeletal pain because of its low prevalence and non-specific manifestations. AIM: To facilitate the early diagnosis and etiology-specific treatment of adult-onset hypophosphatemic OM. METHODS: A retrospective review of medical records was performed to screen adult patients who visited a physiatry locomotive medicine clinic (spine and musculoskeletal pain clinic) primarily presenting with widespread musculoskeletal pain at a single tertiary hospital between January 2011 and December 2019. We enrolled patients with hypophosphatemia, high serum bone-specific alkaline phosphatase levels, and at least one imaging finding suggestive of OM. RESULTS: Eight patients with adult-onset hypophosphatemic OM were included. The back was the most common site of pain. Proximal dominant symmetric muscle weakness was observed in more than half of the patients. Bone scintigraphy was the most useful imaging modality for diagnosing OM because radiotracer uptake in OM showed characteristic patterns. Six patients were diagnosed with adefovir (ADV)-induced Fanconi syndrome, and the other two patients were diagnosed with tumor-induced OM and light-chain nephropathy, respectively. After phosphorus and vitamin D supplementation and treatment for the underlying etiologies, improvements in pain, muscle strength, and gait were observed in all patients. CONCLUSION: Mechanical pain characteristics, hypophosphatemia, and distinctive bone scintigraphy patterns are the initial diagnostic indicators of adult-onset hypophosphatemic OM. ADV-induced Fanconi syndrome is the most common etiology of hypophosphatemic OM in hepatitis B virus-endemic countries.

12.
Chin Med ; 18(1): 159, 2023 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-38042824

RESUMEN

Chronic hepatitis B (CHB) remains a major world's most serious public health issues. Despite the remarkable effect of nucleos(t)ide analogues (NAs) in inhibiting hepatitis B virus (HBV) deoxyribonucleic acid (DNA) as the first-line drug, there are several limitations still, such as poor antigen inhibition, drug resistance, low-level viremia, restricting patients' functional cure. Due to the constraints of NAs, traditional medicines, such as traditional Chinese medicine (TCM), have become more prevalently used and researched in the clinical treatment of CHB as complementary alternative therapies. As a consequence, the review focuses on the background based on HBV's life cycle as well as the NAs' limitations, progress based on direct and indirect pathway of targeting HBV of TCM, and challenges of TCM. We found TCMs play an increasingly important role in anti-HBV. In a direct antiviral way, they regulate HBV infection, replication, assembly, and other aspects of the HBV life cycle. As for indirect way, TCMs can exert anti-HBV effects through targeting the host, including immune regulation, apoptosis, autophagy, oxidative stress, etc. Especially, TCMs have the advantages of strong antigenic inhibition compared to NAs. Specifically, we can combine the benefits of TCMs in strong HBV antigen inhibition with the benefits of NAs in targeted antiviral effects, in order to find a suitable combination of "TCM + NAs" to contribute to Chinese knowledge of the realisation of the "global elimination of HBV by 2030" goal of the World Health Organization.

13.
J Virol ; 97(11): e0108723, 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-37929990

RESUMEN

IMPORTANCE: Hepatitis B virus (HBV) spliced variants are associated with viral persistence or pathogenicity. Hepatitis B doubly spliced protein (HBDSP), which has been previously reported as a pleiotropic transactivator protein, can potentially serve as an HBV virulence factor. However, the underlying mechanisms of HBDSP in HBV-associated liver diseases remain to be elucidated. In this study, we revealed that HBDSP promotes cellular apoptosis and induces wt-p53-dependent apoptotic signaling pathway in wt-p53 hepatocellular cells by transactivating p53 transcription, and increases the release of HBV progeny. Therefore, HBDSP may promote the HBV particles release through wt-p53-dependent hepatocellular apoptosis. Our findings suggest that blocking HBDSP-induced wt-p53-dependent apoptosis might have therapeutic values for chronic hepatitis B.


Asunto(s)
Apoptosis , Carcinoma Hepatocelular , Hepatitis B , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/virología , Factor de Transcripción GATA2/metabolismo , Hepatitis B/complicaciones , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/metabolismo , Neoplasias Hepáticas/virología , Proteína Proto-Oncogénica c-ets-1/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Factor de Transcripción YY1/metabolismo
14.
Indian J Community Med ; 48(5): 727-733, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37970165

RESUMEN

Backgrounds: The Universal Immunization Program of India is one of the most cost-effective interventions in public health. Missing or delaying vaccination may elicit an uncertain immune response in the body, making the population susceptible to vaccine-preventable diseases. The objectives of this study were to determine the coverage of newborn immunization for birth doses under the National Immunization Schedule and its epidemiological determinants in the rural areas of the Dehradun district, Uttarakhand. Materials and Methods: A community-based cross-sectional study was conducted for a period of one year with a sample size of 570. World Health Organization (WHO) 30 Cluster sampling technique was used with 19 children in each cluster. The data on determinants were collected using a semi-structured, pre-designed schedule through a house-to-house survey. Multivariate analysis was conducted to identify factors associated with immunization coverage, taking the significance level as P < 0.05. Results: The coverage of the Bacillus Calmette-Guérin vaccine, oral polio vaccine zero dose and hepatitis B birth dose were 100%, 91.9%, and 58.8%, respectively in the study area with an overall prevalence of incomplete coverage of newborn immunization as 42.5%. The most cited reason for children being unimmunized with birth doses was the unavailability of vaccines at the birthplace center (29.6%). Conclusions: The prevalence of incomplete coverage of newborn immunization was quite high, which was undermining the holistic approach of the National Immunization Program. Vaccine availability and accessibility at the birthplace with capacity building and training of the healthcare workers may be considered to ensure coverage of birth doses.

15.
Front Microbiol ; 14: 1218654, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37908540

RESUMEN

Viral hepatitis is a major public health concern globally. World health organization aims at eliminating viral hepatitis as a public health threat by 2030. Among the hepatitis causing viruses, hepatitis B and C are primarily transmitted via contaminated blood. Hepatitis A and E, which gets transmitted primarily via the feco-oral route, are the leading cause of acute viral hepatitis. Although vaccines are available against some of these viruses, new cases continue to be reported. There is an urgent need to devise a potent yet economical antiviral strategy against the hepatitis-causing viruses (denoted as hepatitis viruses) for achieving global elimination of viral hepatitis. Although zinc was known to mankind for a long time (since before Christ era), it was identified as an element in 1746 and its importance for human health was discovered in 1963 by the pioneering work of Dr. Ananda S. Prasad. A series of follow up studies involving zinc supplementation as a therapy demonstrated zinc as an essential element for humans, leading to establishment of a recommended dietary allowance (RDA) of 15 milligram zinc [United States RDA for zinc]. Being an essential component of many cellular enzymes and transcription factors, zinc is vital for growth and homeostasis of most living organisms, including human. Importantly, several studies indicate potent antiviral activity of zinc. Multiple studies have demonstrated antiviral activity of zinc against viruses that cause hepatitis. This article provides a comprehensive overview of the findings on antiviral activity of zinc against hepatitis viruses, discusses the mechanisms underlying the antiviral properties of zinc and summarizes the prospects of harnessing the therapeutic benefit of zinc supplementation therapy in reducing the disease burden due to viral hepatitis.

16.
Reumatol Clin (Engl Ed) ; 19(10): 533-548, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38008602

RESUMEN

OBJECTIVE: To present recommendations based on the available evidence and the consensus of experts, for risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis. METHODS: Clinical research questions relevant to the purpose of the document were identified. These questions were reformulated in PICO format (patient, intervention, comparison, outcome or outcome) by a panel of experts, selected based on their experience in the area. A systematic review of the evidence was carried out, grading according to the GRADE criteria (Grading of Recommendations Assessment, Development, and Evaluation). Specific recommendations were then formulated. RESULTS: 6 PICO questions were proposed by the panel of experts based on their clinical relevance and the existence of recent information regarding the risk of occurrence of serious infections, the risk of reactivation of the hepatitis B virus, the risk of reactivation of the virus varicella-zoster, the risk of appearance of skin (melanoma and non-melanoma) or haematological cancer, the risk of appearance of thromboembolic disease and the risk of progression of the human papilloma virus. A total of 28 recommendations were formulated, structured by question, based on the evidence found and the consensus of the experts. CONCLUSIONS: The SER recommendations on risk management of treatment with biologic therapies and JAK inhibitors in rheumatoid arthritis are presented.


Asunto(s)
Artritis Reumatoide , Inhibidores de las Cinasas Janus , Reumatología , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Terapia Biológica , Inhibidores de las Cinasas Janus/uso terapéutico , Gestión de Riesgos , Revisiones Sistemáticas como Asunto , Guías de Práctica Clínica como Asunto
17.
Chin J Nat Med ; 21(11): 803-811, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38035936

RESUMEN

Chronic hepatitis B (CHB) infections caused by the hepatitis B virus (HBV) continue to pose a significant global public health challenge. Currently, the approved treatments for CHB are limited to interferon and nucleos(t)ide analogs, both of which have their limitations, and achieving a complete cure remains an elusive goal. Therefore, the identification of new therapeutic targets and the development of novel antiviral strategies are of utmost importance. Natural products (NPs) constitute a class of substances known for their diverse chemical structures, wide-ranging biological activities, and low toxicity profiles. They have shown promise as potential candidates for combating various diseases, with a substantial number demonstrating anti-HBV properties. This comprehensive review focuses on the current applications of NPs in the fight against HBV and provides a summary of their antiviral mechanisms, considering their impact on the viral life cycle and host hepatocytes. By offering insights into the world of anti-HBV NPs, this review aims to furnish valuable information to support the future development of antiviral drugs.


Asunto(s)
Productos Biológicos , Hepatitis B Crónica , Humanos , Virus de la Hepatitis B , Hepatitis B Crónica/tratamiento farmacológico , Antivirales/farmacología , Antivirales/uso terapéutico , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Hepatocitos
18.
Front Cell Infect Microbiol ; 13: 1273031, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38029250

RESUMEN

Objective: Traditional Chinese medicine (TCM) has been used for the treatment of chronic liver diseases for a long time, with proven safety and efficacy in clinical settings. Previous studies suggest that the therapeutic mechanism of TCM for hepatitis B cirrhosis may involve the gut microbiota. Nevertheless, the causal relationship between the gut microbiota, which is closely linked to TCM, and cirrhosis remains unknown. This study aims to utilize two-sample Mendelian randomization (MR) to investigate the potential causal relationship between gut microbes and cirrhosis, as well as to elucidate the synergistic mechanisms between botanical drugs and microbiota in treating cirrhosis. Methods: Eight databases were systematically searched through May 2022 to identify clinical studies on TCM for hepatitis B cirrhosis. We analyzed the frequency, properties, flavors, and meridians of Chinese medicinals based on TCM theories and utilized the Apriori algorithm to identify the core botanical drugs for cirrhosis treatment. Cross-database comparison elucidated gut microbes sharing therapeutic targets with these core botanical drugs. MR analysis assessed consistency between gut microbiota causally implicated in cirrhosis and microbiota sharing therapeutic targets with key botanicals. Results: Our findings revealed differences between the Chinese medicinals used for compensated and decompensated cirrhosis, with distinct frequency, dosage, properties, flavors, and meridian based on TCM theory. Angelicae Sinensis Radix, Salviae Miltiorrhizae Radix Et Rhizoma, Poria, Paeoniae Radix Alba, Astragali Radix, Atrctylodis Macrocephalae Rhizoma were the main botanicals. Botanical drugs and gut microbiota target MAPK1, VEGFA, STAT3, AKT1, RELA, JUN, and ESR1 in the treatment of hepatitis B cirrhosis, and their combined use has shown promise for cirrhosis treatment. MR analysis demonstrated a positive correlation between increased ClostridialesvadinBB60 and Ruminococcustorques abundance and heightened cirrhosis risk. In contrast, Eubacteriumruminantium, Lachnospiraceae, Eubacteriumnodatum, RuminococcaceaeNK4A214, Veillonella, and RuminococcaceaeUCG002 associated with reduced cirrhosis risk. Notably, Lachnospiraceae shares key therapeutic targets with core botanicals, which can treat cirrhosis at a causal level. Conclusion: We identified 6 core botanical drugs for managing compensated and decompensated hepatitis B cirrhosis, despite slight prescription differences. The core botanical drugs affected cirrhosis through multiple targets and pathways. The shared biological effects between botanicals and protective gut microbiota offer a potential explanation for the therapeutic benefits of these key herbal components in treating cirrhosis. Elucidating these mechanisms provides crucial insights to inform new drug development and optimize clinical therapy for hepatitis B cirrhosis.


Asunto(s)
Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Hepatitis B , Humanos , Medicina Tradicional China , Análisis de la Aleatorización Mendeliana , Medicamentos Herbarios Chinos/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Minería de Datos , Hepatitis B/tratamiento farmacológico
19.
Int J Gen Med ; 16: 5183-5192, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38021059

RESUMEN

Introduction: Hepatitis B virus (HBV) infection is a global health problem. Anti-hepatitis B surface antigen (HBsAg) levels increase along with vitamin D levels in adults. However, few studies have examined this relationship in adolescents. Few studies have examined the relationship between vitamin D and HBsAg antibody levels, especially in Indonesia. Methods: This cross-sectional study examined vitamin D and anti-HBsAg levels before and after hepatitis B immunisation. All subjects blood was taken to check for vitamin D level. This study was part of the Safety and Preliminary of Immunogenicity Following Recombinant Hepatitis B (Bio Farma) Vaccine in Adults and Children Phase I trial. Results: This study found that 25-hydroxyvitamin D [25(OH)D] status was primarily deficient based on endocrine criteria. The children's hepatitis B antibody response was mostly <10 mIU/mL before and ≥10 mIU/mL after vaccination. There was a relationship between sex and 25(OH)D status, with median 25(OH)D levels higher in females (18.2 ng/mL) than in males (9.8 ng/mL). However, the relationship between vitamin 25(OH)D status and anti-HBsAg levels pre- and post-vaccination was not significant. Discussion: However, some research found that vitamin D supplementation after immunisation did not impact vaccine response, several studies have reported that vitamin D can decrease HBV replication through various mechanisms, including reducing viral transcription and interfering with viral protein synthesis. Conclusion: There was no relationship between 25(OH)D status and anti-HBsAg levels. Further research is needed to elucidate the underlying mechanisms and establish optimal treatment strategies.

20.
AIDS Rev ; 26(3): 127-135, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37879632

RESUMEN

Sexually transmitted infections (STIs) have become the second in the global rating of infectious diseases after respiratory infections. Globally, over 1 million, new STI is diagnosed every day. Although four conditions are the most representative and of obligatory declaration (gonorrhea, syphilis, chlamydia, and human immunodeficiency virus [HIV]), there are many other prevalent STI, including trichomona, herpes simplex, papillomavirus, and viral hepatitis. Herein, we perform a narrative and retrospective review, analyzing information from public databases from distinct Spanish government institutions. STI significantly declined in Spain during 2020 as a result of lockdown and social isolation measures dictated in response to the COVID-19 pandemic. After releasing restrictions, a major STI rebound occurred in 2021. Increases were 49% for gonorrhea, 45% for HIV, 39% for chlamydia, and 32% for syphilis. Based on nationwide statistics, we build a narrative review of the recent STI surge after COVID-19. In summary, we propose a holistic approach to confront the current re-emergence of STI. On one hand, new innovative medical advances must be implemented, including new rapid tests, novel vaccines, pre-exposure prophylaxis beyond HIV, and long-acting antivirals. On the other hand, information to citizens needs to be reformulated with interventions aimed to build a healthier society, alike it has been undertaken with tobacco, alcohol, diet, and lifestyle. STI determines important sexual, reproductive, and maternal-child health consequences. To promote human well-being or flourishing, the education of adolescents and young adults should be aligned with human ecology. Therefore, it is urgent to address new approaches in sexual health that represent a clear benefit for individual persons and society. In this way, favoring a cultural evolution aimed to delay the age of first sexual intercourse and the avoidance of multiple sex partners should be prioritized.


Asunto(s)
COVID-19 , Gonorrea , Infecciones por VIH , Enfermedades de Transmisión Sexual , Sífilis , Adolescente , Humanos , Masculino , Adulto Joven , Control de Enfermedades Transmisibles , COVID-19/epidemiología , Gonorrea/diagnóstico , Gonorrea/epidemiología , VIH , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Pandemias , Enfermedades de Transmisión Sexual/epidemiología , Sífilis/diagnóstico , Sífilis/epidemiología , Femenino
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