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1.
Journal of Clinical Hepatology ; (12): 880-883, 2024.
Article in Chinese | WPRIM | ID: wpr-1030779

ABSTRACT

Highly effective oral antiviral therapy with low drug resistance can strongly inhibit HBV replication; however, some patients may still have low-level viremia (LLV) after receiving entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide, or tenofovir amibufenamide for 48 weeks or more. Multiple studies in China and globally show that LLV after antiviral therapy is closely associated with the progression of chronic hepatitis B liver fibrosis, the risk of decompensated liver cirrhosis and hepatocellular carcinoma, and the reduction in long-term survival rate. Therefore, this article reviews the development, risk factors, and clinical harm of LLV after first-line treatment with nucleos(t)ide analogues, as well as different treatment regimens, in order to provide a reference for the treatment of LLV in chronic hepatitis B patients in the future.

2.
Article in Chinese | WPRIM | ID: wpr-1006427

ABSTRACT

‍ ObjectiveTo investigate the serum level of HBV RNA in untreated or treatment-experienced patients with chronic hepatitis B (CHB) and the correlation between serum HBV RNA level and the duration of antiviral therapy with nucleos(t)ide analogues (NAs). MethodsA total of 300 patients with CHB who attended Department of Infectious Diseases in The First Affiliated Hospital of Shihezi University School of Medicine from February to July, 2022, were enrolled as subjects. Related clinical data were collected, and according to the duration of antiviral therapy, they were divided into untreated group with 73 patients, treatment duration ≤1 year group with 91 patients, and treatment duration >1 year group with 136 patients. Serum HBV RNA load, HBV DNA load, and HBsAg concentration were measured for all patients. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups, further pairwise comparison using Bonferroni method; the chi-square test was used for comparison of categorical data; a Spearman correlation analysis was used to investigate the degree of correlation between various indicators. ResultsThe positive rate of HBeAg was 18.3%, and among the patients with negative HBV DNA, the patients with positive HBV RNA accounted for 44.1% (86/195). There was a significant difference in the distribution of the serum levels of HBV RNA, HBV DNA, and HBsAg between the positive HBeAg group and the negative HBeAg group (Z=10.740, 6.300, and 7.280, all P<0.05). There was a significant difference in the distribution of DNA level between the untreated group and the treatment duration ≤1 year group (P<0.05); there was a significant difference in the distribution of HBV RNA and HBV DNA levels between the untreated group and the treatment duration >1 year group (P<0.05); there was a significant difference in the distribution of HBV RNA, HBV DNA, and HBsAg levels between the treatment duration ≤1 year group and the treatment duration >1 year group (P<0.05). The correlation analysis between the duration of antiviral therapy and the levels of HBV RNA, HBV DNA, and HBsAg showed that the duration of antiviral therapy had an extremely weak negative correlation with the levels of HBV RNA and HBsAg (r=-0.247 and -0.138, both P<0.05) and a strong negative correlation with the level of HBV DNA (r=-0.771, P<0.001). There was a low degree of correlation between the serum level of HBV RNA and the serum levels of HBV DNA and HBsAg (r=0.360 and 0.442, both P<0.001). Further stratified analysis showed that in the untreated group, there was a strong positive correlation between HBV RNA and HBV DNA (r=0.752, P<0.001) and a moderate positive correlation between HBV RNA and HBsAg (r=0.559, P<0.001); in the treatment duration ≤1 year group, there was a low degree of positive correlation between HBV RNA and HBV DNA/HBsAg (r=0.396 and r=0.388, both P<0.001); in the treatment duration >1 year group, there was a low degree of positive correlation between HBV RNA and HBsAg (r=0.352, P<0.001). ConclusionSerum HBV RNA is negatively correlated with the duration of treatment with NAs, and the correlation of HBV RNA with HBV DNA and HBsAg gradually decreases with the increase in the duration of treatment. Therefore, it can be used as a supplementary indicator for monitoring the level of virologic response in CHB patients to a certain extent, with a relatively high accuracy in reflecting the level of viral replication in untreated patients.

3.
Article | IMSEAR | ID: sea-230987

ABSTRACT

Aims: Renal Failure and Chronic Kidney Disease (CKD) represent major health problems that affect more than 10% of the general population worldwide amounting to more than 800 million individuals. CKD is a congruence of many diseases like Diabetes, Hypertension, hypercholesterolemia, and different cardiovascular diseases as well as epigenetic factors contributing to the development of this Disease. We undertook this work as a pilot study to establish a database of genetic variants for novel or existing genes involved in the development and progress of CKD in the Saudi population. Methods: Patients' blood samples of 12 donors suffering from CKD were used to perform the Whole Exome Sequencing (WES) on genomic DNA on the Illumina Platform. Bioinformatics algorithms were used to perform different callset to explore different mechanisms such as nucleic acids interconversion, INDELS search as well as Transition/Transversion (Ts/Tv) ratio determination. Results: Patterns of Transition and Transversion Ratio (Ts &Tv) in the Patient samples demonstrated the dominance of transition substitutions over transversion. Our data revealed the mean ratio metrics of (Ts/Tv) is roughly 2.75 which is consistent with former literature findings. Indels with less than 3 bp have a total count of more than 1e+05 whereas those with larger gap are present at the level of trace. Since there is an intrinsic relation between nucleotides interconversions and the transition and transversion mechanisms, and based on the higher rate of transition over transversion mechanisms, our study supports this assertion at the levels of the nucleotides, with the state nucleotides conversion being as (67% A?G, 64% G?A, 67% T?C, and 67% C?T) which mirrors the dominance of transition effects and lower representation of transversion effects as exemplified by lower state of interconversion of : (13% T?A), (12% A?T), (19% C?G), (17% C?G), (17% G?T) and (20% T?G). Conclusion: CKD is a widespread disease that overlaps the spectrum of many diseases’ spectrum in terms of gene variant expressions. The transition and Transversion ratio profile is around 2.75. Nucleotides interconversions rim with the concept of transition and transversion and INDELS counts and distribution favor the shorter length as compared with larger INDELS.

4.
Journal of Clinical Hepatology ; (12): 1070-1075, 2023.
Article in Chinese | WPRIM | ID: wpr-973194

ABSTRACT

Objective To investigate the ability of combined baseline serum markers, i.e., HBV DNA, HBV RNA, HBsAg, and HBcrAg, to predict HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) treated by nucleos(t)ide analogues. Methods A retrospective analysis was performed for 83 HBeAg-positive patients selected as subjects from the prospective CHB follow-up cohort established by Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, from June 2007 to July 2008, and the baseline serum levels of HBV DNA, HBV RNA, HBsAg, and HBcrAg were analyzed. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman method was used for correlation analysis. A Cox regression model was established to calculate HBeAg seroconversion prediction score, and the time-dependent receiver operating characteristic curve was used to evaluate the ability of combined markers in predicting HBeAg seroconversion. The Kaplan-Meier method was used to calculate cumulative seroconversion rate in each group, and the Log-rank test was used for comparison between groups. Results For the 83 HBeAg-positive patients, the median follow-up time was 108 months, and 44.58%(37/83) of these patients achieved HBeAg seroconversion. Compared with the non-seroconversion group, the HBeAg seroconversion group had significantly lower baseline serum levels of HBV DNA [6.23(1.99-9.28) log 10 IU/mL vs 7.69(2.05-8.96) log 10 IU/mL, Z =-2.345, P =0.019] and HBV RNA [4.81(1.40-7.53) log 10 copies/mL vs 6.22(2.00-8.49) log 10 copies/mL, Z =-1.702, P =0.010], and there were no significant differences in the levels of HBsAg and HBcrAg between the two groups ( P > 0.05). The Cox regression equation constructed based on the above serum markers showed a median score of 0.95(range 0.37-3.45) for predicting HBeAg seroconversion. In the total population, the combined score was negatively correlated with HBsAg, HBV DNA, HBV RNA, and HBcrAg ( r =-0.697, -0.787, -0.990, and -0.819, all P < 0.001). Based on the median prediction score, the patients were divided into high HBeAg seroconversion group and low HBeAg seroconversion group; as for the prediction of HBeAg seroconversion rate at 36, 60, and 84 months, the high HBeAg seroconversion group had a seroconversion rate of 43.90%, 51.20%, and 63.10%, respectively, while the low HBeAg seroconversion group had a seroconversion rate of 9.60%, 17.00%, and 19.8%, respectively, and there was a significant difference between the two groups ( χ 2 =11.6, P < 0.001). Conclusion The combined prediction score based on baseline serum HBV markers can predict HBeAg seroconversion in CHB patients treated by nucleos(t)ide analogues.

5.
International Journal of Surgery ; (12): 223-229,F3, 2023.
Article in Chinese | WPRIM | ID: wpr-989437

ABSTRACT

Objective:To evaluate the effects of pegylated interferon (Peg-IFN) alfa-2b combined with nucleotide analogues (NAs) on the recurrence of hepatitis B-related liver cancer after resection, and to explore the changes of HBsAg and HBV DNA in patients with chronic hepatitis B liver cancer during postoperative treatment.Methods:The prospective study was conducted. Clinical data of 43 patients with hepatitis B-related liver cancer who underwent radical resection treated in 900th Hospital of People′s Liberation Army were prospectively analyzed from January 2020 to December 2021. Among 43 patients, there were 39 males and 4 females, the age was 30-76 years. According to different treatment methods they were divided into two groups, the patients treated by Peg-IFN alfa-2b combined with NAs were devided into the IFN group( n=10), and those treated by NAs alone into the NAs group( n=33). Two-pair semi-quantitative were collected every 3 months after operation. The recurrence-free survival rate, recurrence time after 2 years in the two groups, the clearance rate and the negative rate of HBsAg and HBV DNA in the two groups. Peg-IFN alfa-2b was evaluated in improving the prognosis of hepatitis B-related liver cancer. The measurement data of normal distribution were expressed by mean±standard deviation ( ± s), and t-test was used for comparison between the two groups. Chi-square test was used for comparison between the two groups of count data. Repeated analysis of measurement variance was used for analysis HBsAg and HBV DNA changes of the interferon group overall survival time and recurrence-free surrival time of patients was estimated using Kaplan-Meier method and the difference between groups was assessed using Log-rank test. Results:HBsAg and HBV DNA: The HBsAg clearance rate at 24 weeks and that at 48 weeks in the IFN group were 24.6% and 59.0% respectively. The HBsAg negative rate at 48 weeks was 16.7%. The HBV DNA clearance rate at 24 weeks and that at 48 weeks were 33.9% and 53.8% respectively. The HBV DNA negative rate was 0 at 48 weeks. The levels of HBsAg and HBV DNA in the IFN group decreased gradually with time. There were statistically differences between the levels of HBsAg and HBV DNA at 0 weeks, 24 weeks and 48 weeks( P<0.05). The 2-year overall survival rates of IFN group and NAs group were 100% and 90.9% respectively. The 2-year recurrence-free survival rates were 90.0% and 63.6% respectively. There were no significant statistical differences in the overall survival rate and recurrence-free survival rate between the groups ( P>0.05). The postoperative recurrence time of the IFN group and the NAs group were (15.00±7.07) months and (5.78±3.39) months respectively. The difference between the two groups was statistically significant ( t=3.160, P<0.01). Conclusion:Long-term antiviral therapy of Peg-IFN alfa-2b combined with NAs can prolong the recurrence time of liver cancer, reduce the levels of HBsAg and HBV DNA in serum, and potentially improve the survival rate of the patients compared with therapy of NAs alone.

6.
Article in Chinese | WPRIM | ID: wpr-990329

ABSTRACT

Sufficient and organized sleep is a key factor during the developmental process of infancy while disrupted sleep schedule and diseases might lead to sleeping disorders in infants. Breastfeeding is considered to be the most beneficial way to meet the nutritional needs of infants for optimal growth and development. The α-lactalbumin-tryptophan-melatonin axis, nucleotides, and other factors are breast milk components that may affect infant sleep. Meanwhile, diet, feeding schedule, tobacco smoking, alcohol intake, and caffeine consumption will affect the circadian rhythms which might lead to the fluctuations of sleep-influencing factors in breast milk. This study reviews literature of previous studies on this topic to summarize information that can be considered for both breastfeeding practice and future basic research on the establishment of organized sleep patterns in infants.

7.
Article in Chinese | WPRIM | ID: wpr-913156

ABSTRACT

Objective To investigate the difference in the prognosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) caused by hepatitis recurrence after withdrawal of nucleos(t)ide analogues (NUC) and possible causes in HBeAg-positive versus HBeAg-negative chronic hepatitis B (CHB) patients. Methods A total of 108 CHB patients with HBV-ACLF caused by withdrawal of NUC who were admitted to The First Affiliated Hospital of Nanchang University from January 2017 to December 2018 were enrolled, and according to HBeAg status, these patients were divided into HBeAg-positive group with 57 patients and HBeAg-negative group with 51 patients. The two groups were compared in terms of sex, age, clinical manifestation, signs, levels of total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, prothrombin time, activated partial thromboplastin time, prothrombin time/international normalized ratio, and HBV DNA quantification on admission, complications (including hepatic encephalopathy, hepatorenal syndrome, and spontaneous bacterial peritonitis), and prognosis of HBV-ACLF. In addition, 48 CHB patients with continuous NUC antiviral therapy for > 2 years and HBV DNA < 20 IU/mL were enrolled, and the serum level of HBV pgRNA was measured to investigate the possible causes of the difference in the prognosis of HBV-ACLF between the patients with different HBeAg statuses. The two-independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data. Results For the 108 patients with HBV-ACLF caused by drug withdrawal and recurrence, the HBeAg-positive group had an improvement rate of 49.1% and the HBeAg-negative group had an improvement rate of 74.5%. The HBeAg-negative group had a significantly higher improvement rate than the HBeAg-positive group ( χ 2 =2.811, P =0.006). The HBeAg-positive group had a significantly higher level of HBV DNA than the HBeAg-negative group on admission ( t =-3.138, P =0.002). For the 48 CHB patients who achieved virologic response after long-term antiviral therapy, the HBeAg-positive group had a significantly higher HBV pgRNA load than the HBeAg-negative group ( H =2.814, P =0.049). Conclusion Compared with the HBeAg-positive CHB patients, HBeAg-negative CHB patients have a significantly better improvement rate of HBV-ACLF caused by hepatitis recurrence after withdrawal of NUC antiviral therapy. The difference in baseline HBV pgRNA level may be associated with the difference in the prognosis of HBV-ACLF in patients with different HBeAg statuses.

8.
Journal of Clinical Hepatology ; (12): 532-536, 2022.
Article in Chinese | WPRIM | ID: wpr-922947

ABSTRACT

Objective To investigate the efficacy of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) and the treatment measures for poor response in previously untreated chronic hepatitis B (CHB) patients with high viral load. Methods A total of 165 CHB patients who received antiviral therapy and met the inclusion criteria in Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, from June 2016 to July 2021 were enrolled. The patients enrolled had a baseline HBV DNA level of > 6lg copies/ml and were previously untreated CHB patients who had used ETV or TDF for 48 weeks, and quantitative real-time PCR was used to measure HBV DNA. Virologic response rate was calculated after 48 weeks of treatment; a logistic regression analysis was used to investigate the influencing factors for the response of HBV DNA 40 U/L) at baseline, 89.2% (107/120) achieved an HBV DNA load of 30 years (77.8% vs 47.2%, 85.2% vs 66.7%). For the patients who did not achieve complete virologic response (HBV DNA ≥100 copies/mL) after 48 weeks of treatment, 87.9% (29/33) achieved complete virologic response after the original treatment regimen was prolonged for 48 weeks, and 100% (9/9) of the patients achieved complete virologic response after switching to or adding the first-line nucleos(t)ide analogues (NUCs) without cross-resistance sites with the original regimen for another 48 weeks. Conclusion The patients aged > 30 years should receive antiviral therapy as early as possible, regardless of viral load and ALT level, especially those with a family history of liver cirrhosis or hepatocellular carcinoma; the patients aged ≤30 years who have a normal ALT level and a high viral load should consider initiating antiviral therapy after providing informed consent. For the patients with poor response after 48 weeks of treatment, first-line NUCs without cross-resistance sites with the original regimen should be switched to or added in time.

9.
Journal of Clinical Hepatology ; (12): 1705-1709, 2022.
Article in Chinese | WPRIM | ID: wpr-941526

ABSTRACT

Chronic hepatitis B virus (HBV) infection is the main cause of viral hepatitis, liver cirrhosis, and primary liver cancer. At present, nucleos(t)ide analogues (NUC) and pegylated interferon α used in clinical practice cannot directly target covalently closed circular DNA, and it is difficult to achieve clinical cure of chronic hepatitis B patients; therefore, it is urgently needed to develop direct-acting antiviral agents targeting all stages of the HBV replication cycle. Capsid assembly modulator (CpAM) targets the assembly of viral capsids through various mechanisms, thereby exerting a direct-acting antiviral effect. Its combination with NUC should have a good synergistic antiviral effect, but the results of existing clinical trials have shown that chronic hepatitis B patients who received a limited course of antiviral therapy with CpAM and NUC all experienced off-therapy viral rebound. Based on the mechanism of action of these two types of drugs, this article provides a reasonable explanation for the above clinical trial results and points out that a longer course of antiviral therapy with CpAM and NUC may be needed in the future clinical trials with safe drug withdrawal as the end point of observation, so as to deplete or silence the pool of covalently closed circular DNA and increase the possibility of safe drug withdrawal in CHB patients. In addition, further studies are needed to explore antiviral therapeutic strategies with a combination of multiple targets.

10.
Journal of Clinical Hepatology ; (12): 1886-1891, 2022.
Article in Chinese | WPRIM | ID: wpr-941557

ABSTRACT

Nucleos(t)ide analogues (NUC) can inhibit the replication of hepatitis B virus (HBV) and effectively treat chronic hepatitis B (CHB), but they cannot completely eradicate HBV and cannot prevent the progression to hepatitis B cirrhosis and liver cancer in the context of a low viral load. In recent years, traditional Chinese medicine has been widely used in the treatment of CHB. This article elaborates on the application and mechanism of traditional Chinese medicine in inhibiting HBV replication, reducing the content of HBeAg, and delaying the progression to hepatitis B cirrhosis, and it is proposed that traditional Chinese medicine can improve the therapeutic effect of NUC in the treatment of CHB.

11.
Journal of Clinical Hepatology ; (12): 1268-1274, 2021.
Article in Chinese | WPRIM | ID: wpr-877314

ABSTRACT

Nucleos(t)ide analogues (NAs), which are widely used as the first-line anti-hepatitis B virus (HBV) drugs in clinical practice, can effectively inhibit the replication of HBV DNA, significantly slow down disease progression in chronic hepatitis B (CHB) patients, and reduce the development of end-stage liver diseases such as liver failure and liver cancer. However, for some CHB patients receiving first-line NAs for 48 weeks or longer, serum HBV DNA is still persistently or intermittently higher than the lower detection of limit of sensitive nucleic acid detection reagents. After discussion by the authors, low-level viremia (LLV) is defined as follows: persistent LLV refers to the condition in which CHB patients, who receive entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate for ≥48 weeks, test positive for HBV DNA by two consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of <2000 IU/ml; intermittent LLV refers to the condition in which patients test positive for HBV DNA intermittently by at least three consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of <2000 IU/ml. For the diagnosis of LLV, the issues of poor compliance and drug-resistant mutations should be excluded. LLV might be associated with the increased risk of progression to liver fibrosis or hepatocellular carcinoma in patients with liver cirrhosis under NA treatment, but there are still controversies over whether the original treatment regimen with NAs should be changed after the onset of LLV. This article summarizes the incidence rate of LLV under NA treatment and the influence of LLV on prognosis and analyzes the possible mechanisms of the osnet of LLV, so as to provide a reference for the management of LLV in patients treated with NAs.

12.
Journal of Clinical Hepatology ; (12): 1793-1797., 2021.
Article in Chinese | WPRIM | ID: wpr-886332

ABSTRACT

ObjectiveTo investigate the population with an advantage of clinical cure previously treated with nucleos(t)ide analogues (NAs), and to provide more methods for clinicians in pursuing the clinical cure of hepatitis B. MethodsA total of 42 chronic hepatitis B patients with low-level HBsAg who received NAs treatment in Hebi Third People’s Hospital from October 2017 to October 2019 were enrolled as subjects and divided into combination treatment group (group A) and NA monotherapy group (group B). The 22 subjects in group A were treated with NAs combined with PEG-IFN antiviral therapy for 48 weeks, and some patients withdrew from PEG-IFN after 24 weeks and continued to receive NA monotherapy, while the 20 subjects in group B received NA antiviral therapy alone. Both groups were observed till week 48, and the five makers for hepatitis B were measured to evaluate clinical outcome. The t-test was used for comparison of continuous data between two groups, and the Fisher’s exact test was used for comparison of categorical data between two groups; a multivariate logistic regression analysis was used to perform a multivariate analysis. ResultsCompared with group B at the 48-week treatment endpoint, group A had significantly higher HBsAg clearance rate (45.5% vs 0, P<0.01) and HBsAg seroconversion rate (31.8% vs 0, P<0.01). The population with HBsAg <1000 IU/ml, <500 IU/ml, <100 IU/ml, and <10 IU/ml had an HBsAg clearance rate of 52.6%, 61.5%, 66.7%, and 100%, respectively, and the population with an HBsAg level of 500-1000 IU/ml, 100-500 IU/ml, 10-100 IU/ml, and <10 IU/ml had an HBsAg clearance rate of 33.3%, 50%, 40%, and 100%, respectively. The 4 patients with baseline HBsAg <10 IU/ml (accounting for 18.2% in group A) achieved clinical cure at week 12 of combined treatment, and after observation to week 48, 2 patients had an anti-HBs level of >100 IU/ml and 2 had an anti-HBs level of >1000 IU/ml. The multivariate logistic regression analysis of HBsAg clearance showed that age at the initiation of combined treatment affected HBsAg clearance (odds ratio [OR]=0.877, 95% confidence interval [CI]: 0.781-0.985, P=0.026), and most of the patients with HBsAg clearance had an age of 36-49 (44.20±4.49) years; baseline HBsAg level also had an impact on HBsAg clearance (OR=0.996, 95% CI: 0.992-1.000, P=0.050). ConclusionThe addition of interferon therapy in chronic hepatitis B patients with low-level HBsAg previously treated with NAs can significantly improve the clinical cure rate. The younger the age and the lower the HBsAg level, the shorter the duration of combined treatment. Age and baseline HBsAg level are more important than the duration and type of NA medication.

13.
Article in Chinese | WPRIM | ID: wpr-908758

ABSTRACT

Coronaviruses are dangerous human and animal pathogens.The newly identified coronavirus SARS-CoV-2 is the causative agent of COVID-19 outbreak,which is a real threat to human health and life.The world has been struggling with this epidemic for about a year,yet there are still no targeted drugs and effective treatments are very limited.Due to the long process of developing new drugs,reposition of existing ones is one of the best ways to deal with an epidemic of emergency infectious diseases.Among the existing drugs,there are candidates potentially able to inhibit the SARS-CoV-2 replication,and thus inhibit the infection of the virus.Some therapeutics target several proteins,and many diseases share molecular paths.In such cases,the use of existing pharmaceuticals for more than one purpose can reduce the time needed to design new drugs.The aim of this review was to analyze the key targets of viral infection and potential drugs acting on them,as well as to discuss various strategies and therapeutic approaches,including the possible use of natural products.We highlighted the approach based on increasing the involvement of human deaminases,particularly APOBEC deaminases in editing of SARS-CoV-2 RNA.This can reduce the cytosine content in the viral genome,leading to the loss of its integrity.We also indicated the nucleic acid technologies as potential approaches for COVID-19 treatment.Among numerous promising natural products,we pointed out curcumin and cannabidiol as good candidates for being anti-SARS-CoV-2 agents.

14.
Mem. Inst. Oswaldo Cruz ; 116: e210339, 2021. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1360593

ABSTRACT

BACKGROUND An increasing amount of research has led to the positioning of nucleoside diphosphate kinases (NDPK/NDK) as key metabolic enzymes among all organisms. They contribute to the maintenance the intracellular di- and tri- phosphate nucleoside homeostasis, but they also are involved in widely diverse processes such as gene regulation, apoptosis, signal transduction and many other regulatory roles. OBJETIVE Examine in depth the NDPKs of trypanosomatid parasites responsible for devastating human diseases (e.g., Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp.) which deserve special attention. METHODS The earliest and latest advances in the topic were explored, focusing on trypanosomatid NDPK features, multifunctionality and suitability as molecular drug targets. FINDINGS Trypanosomatid NDPKs appear to play functions different from their host counterparts. Evidences indicate that they would perform key roles in the parasite metabolism such as nucleotide homeostasis, drug resistance, DNA damage responses and gene regulation, as well as host-parasite interactions, infection, virulence and immune evasion, placing them as attractive pharmacological targets. MAIN CONCLUSIONS NDPKs are very interesting multifunctional enzymes. In the present review, the potential of trypanosomatid NDPKs was highlighted, raising awareness of their value not only with respect to parasite biology but also as molecular targets.

15.
Article in Chinese | WPRIM | ID: wpr-873166

ABSTRACT

Objective:To study the water soluble chemical constituents in rhizoma of Acorus tatarinowii and transformation pathway of nucleosides in the process of water extraction. Method:Compounds were isolated and purified by column chromatography on macroporous resin,Sephadex LH-20,ODS and preparative HPLC. Their structures were identified on the basis of physicochemical properties and spectral data. Nucleosides were identified from aqueous extract of A. tatarinowii,and their stability was investigated by HPLC. The possible transformation pathways of nucleosides in aqueous extract of A. tatarinowii were studied by nucleotide addition test. Result:Eleven compounds including four nucleosides,four phenylpropanoids,two alkaloids and a furfural were isolated,and identified as uridine(1),adenine(2),guanosine(3),adenosine(4),5-hydroxymethylfurfural(5),5-(hydroxymethyl)-1H-pyrrole-2-carboxaldehyde(6),(threo)1',2'-dihydroxyasarone(7),(erythro)1',2'-dihydroxyasarone(8),acoraminol A(9),acoraminol B(10),and tatarine A(11). The chromatographic peaks of compounds 1-4 and cytidine were identified from aqueous extract of A. tatarinowii by HPLC. After ultrasonic extraction for 0.5 h,the stability of nucleosides in water was poor. After ultrasonic extraction for 3 h or refluxing extraction for 0.5 h,the stability of nucleosides in water was good. Four transformation pathways including 5'-cytidylic acid→cytidine,uridine monophosphate→uridine,guanosine monophosphate,guanosine and adenosine-5'-monophosphate,adenosine 5'-diphosphate,adenosine 5'-triphosphorate,adenosine,adenine might exist in water extract of A. tatarinowii. Conclusion:Compounds 1-4 and 6 were isolated from the genus Acorus for the first time. These compounds further enriched the chemical constituents of A. tatarinowii. The stability and transformation pathway of nucleosides in A. tatarinowii provides reference data for the analysis of nucleosides in A. tatarinowii and other traditional Chinese medicine.

16.
Journal of Clinical Hepatology ; (12): 1358-1361, 2020.
Article in Chinese | WPRIM | ID: wpr-822190

ABSTRACT

Nucleos(t)ide analogues (NAs) are effective inhibitors for HBV replication and have become the preferred antiviral regimen for most patients with chronic hepatitis B (CHB). HBeAg seroconversion is an important index used to evaluate the durability and efficacy of antiviral therapy in HBeAg-positive CHB patients. The search for biomarkers that can predict HBeAg clearance or seroconversion after NAs treatment plays an important role in the selection of antiviral drugs, the adjustment of treatment regimens, and the achievement of individualized treatment. This article reviews the value of related markers, including HBV DNA, HBV RNA, anti-HBc, and HBcrAg, in predicting HBeAg clearance or seroconversion in CHB patients treated with NAs.

17.
Zhongguo Zhong Yao Za Zhi ; (24): 991-996, 2020.
Article in Chinese | WPRIM | ID: wpr-1008463

ABSTRACT

To investigate the effect of resolution components, such as Açaí oil, alcohol extract and water extract, on the temperature tendency animal behavior and intrinsic biochemical indexes, such ascyclic nucleotides and metabolic level, in mice with deficiency-heat and deficiency-cold syndrome, in order to study the characteristics of the cold and heat properties of each resolution component of Açaí and the material basis of cooling. KM mice were randomly divided into 12 groups, namely blank group, deficiency-heat model group, deficiency-heat+Açaí group, deficiency-heat+Açaí oil group, deficiency-heat+Açaí alcohol extract group, deficiency-heat+Açaí water extract group, deficiency-cold model group, deficiency-cold+Cinnamomi Cortex group, deficiency-cold+Açaí group, deficiency-cold+Açaí oil group, deficiency-cold+Açaí alcohol extract group, deficiency-cold+Açaí water extract group. The mice in deficiency-heat group were given thyroid tablet solution(160 mg·kg~(-1)), the mice in deficiency-cold group were given hydrocortisone solution(25 mg·kg~(-1)) through gastric perfusion every afternoon for 14 days, and each administration group was given the corresponding drug. The temperature tendency, cyclic nucleotides and metabolic level of animals were measured after the experiment. The Açaí alcohol extract was consistent with the Açaí powder, with a regulatory effect on the deficiency-heat model mice; Açaí oil and its water extract were consistent with Cinnamomi Cortex, with a regulatory effect on the deficiency-cold model mice. In this study, based on the parable theory of traditional Chinese medicine's properties and tastes, property of alcohol extract of Açaí was cool, while the property of oil and water extract were warm, the alcohol extract of Açaí was the material basis of Açaí cold medicine by the methods of homogeneous comparison and heterogeneous disproval.


Subject(s)
Animals , Mice , Ethanol , Euterpe/chemistry , Medicine, Chinese Traditional , Plant Extracts/pharmacology , Plant Oils/pharmacology , Random Allocation , Temperature , Water
18.
Zhongguo Zhong Yao Za Zhi ; (24): 1004-1010, 2020.
Article in Chinese | WPRIM | ID: wpr-1008465

ABSTRACT

The aim of this paper was to study the effect of Lepidium meyenii(Maca) on cyclic nucleotides, neurotransmitter levels and hypothalamic-pituitary-adrenal axis and immunization of deficiency-cold and deficiency-heat syndrome rats, in order to explore the cold and hot medicinal properties of Maca. SD rats were divided into blank group, deficiency-cold syndrome group, Cinnamomi Cortex of deficiency-cold syndrome(30 g·kg~(-1)) group, high and low-dose Maca groups(2.4, 1.2 g·kg~(-1)), deficiency-heat syndrome group, Phellodendri Chinensis Cortex(PCC) of deficiency-heat syndrome(5 g·kg~(-1)), and high and low-dose Maca groups(2.4, 1.2 g·kg~(-1)). The rats were treated with intramuscular injection of hydrocortisone(20 mg·kg~(-1)) or dexamethasone sodium phosphate(0.35 mg·kg~(-1)) for 21 days to set up the deficiency-cold and deficiency-heat model. The levels of cAMP, cGMP, NE, DA, 5-HT, CRH, ACTH, CORT and IgM, IgG, C3, C4 were detected by radio immunoassay. Both the high-dose Maca group and the low-dose Maca group can significantly improve the overall state and body weight of rats with deficiency-cold syndrome(P<0.01, P<0.05), significantly increasing cAMP, cAMP/cGMP, NE, DA, ACTH(P<0.01, P<0.001), and significantly decreasing 5-HT(P<0.01, P<0.001). However, high-dose and low-dose Maca groups could not improve the deficiency-heat syndrome, and the levels of cAMP, cGMP, cAMP/cGMP, NE, DA, 5-HT and ACTH were not statistically significant. Maca had a significant regulatory effect on CORT, IgM, IgG and C3 content of rats with deficiency-cold and deficiency-heat syndrome(P<0.01, P<0.05, P<0.001). Maca showed the same effect with Cinnamomi Cortex in adjusting the levels of deficiency-cold rats, but in opposition to Phellodendri Chinese Cortex. This paper confirmed that Maca was slightly warm based on its effect on cyclic nucleotide levels and neuro-endocrine-immune networks by the pharmacological experimental method.


Subject(s)
Animals , Rats , Drugs, Chinese Herbal/pharmacology , Endocrine System/drug effects , Hypothalamo-Hypophyseal System , Immune System/drug effects , Lepidium/chemistry , Medicine, Chinese Traditional , Nervous System/drug effects , Neurotransmitter Agents , Nucleotides, Cyclic , Pituitary-Adrenal System , Plant Extracts/pharmacology , Rats, Sprague-Dawley , Temperature
19.
Article in Chinese | WPRIM | ID: wpr-733898

ABSTRACT

Objective To investigate the effects of cisplatin on the expression of nucleotide - binding oligomerization domain-like receptor(NOD) 1 and 2 in human osteosarcoma SaOS-2 cell line,and to explore the mechanism of cisplatin in the treatment of human osteosarcoma. Methods CCK-8 assay,real-time quantitative reverse transcription polymerase chain reaction ( qRT - PCR ) and immumofluorescence methods were used to determine the growth survival rate and expression levels of NOD1 and NOD2 in osteosarcoma SaOS -2 cell line treated with cisplatin (0,5,10,20 μmol/L,named group S0,group S5,group S10,group S20,respectively) for 24, 48,72 hours. Results After treatment with cisplatin for 48 h or 72 h,the growth survival rates of SaOS-2 cells were significantly decreased in group S5 than those in group S0(65. 53% vs. 100. 00%;46. 43% vs. 100. 00%,χ2=8. 64,73. 97,all P<0. 01). Moreover,after treatment with cisplatin for 24 h,48 h or 72 h,the growth survival rates of SaOS-2 cells were significantly decreased in group S10 or group S20 than those in group S0(80. 60% vs. 100. 00% , 42. 94 vs. 100. 00% ,27. 90% vs. 100. 00% ;62. 54% vs. 100. 00% ,33. 09% vs. 100. 00% ,22. 95% vs. 100. 00% , χ2=20. 99,79. 72,112. 50;45. 40,67. 56,125. 20,all P<0. 01),and the growth survival rates were significantly lower in group S20 than those in group S5(62. 54% vs. 93. 78% ,33. 09% vs. 65. 53% ,22. 95% vs. 46. 43% ,χ2= 28. 47,21. 78,11. 71,all P <0. 01). The expression levels of NOD1 mRNA and NOD2 mRNA in group S5 were significantly increased at 48 h or 72 h than those at 24 h,and were higher than group S0 when treated with 5μmol/L cisplatin[(3. 64 ± 0. 44) vs. (4. 47 ± 1. 22) vs. (1. 79 ± 0. 44) vs (1. 00 ± 0. 00);(6. 88 ± 2. 79) vs. (6. 86 ± 2. 40) vs (2. 29 ± 0. 70) vs. (1. 00 ± 0. 00),F=29. 12,24. 11,all P<0. 01]. And the expression levels of NOD1 protein had an increased tendency after 48 h or 72 h treatment with 5μmol/L cisplatin. Furthermore,the expression level of NOD1 mRNA was positively correlated with NOD2 mRNA(n=36,r=0. 92,P<0. 01). Conclusion Cisplatin can elevate the function of osteosarcoma cell in a dose - and time - dependent manners, cisplatin may act as a efficient drug to cure osteosarcoma desease,which may be related to NOD1 and NOD2 signal pathway.

20.
Journal of Clinical Hepatology ; (12): 734-736, 2019.
Article in Chinese | WPRIM | ID: wpr-778789

ABSTRACT

Recently, Choi et al. published a real-world study in JAMA Oncology, which showed that there was a significant difference between the entecavir group and the tenofovir disoproxil fumarate group in reducing the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. This result is inconsistent with the common point of view in antiviral therapy for CHB and has aroused a heated discussion in the academic world. The editorial simultaneously published in JAMA Oncology pointed out that the study by Choi et al. has certain clinical significance, but there are still many confounding factors which need to be further clarified, and therefore, the regimen of antiviral therapy for CHB patients cannot be changed based on this result. With reference to this result, this article analyzes the key influencing factors for the risk of HCC in CHB patients receiving long-term antiviral therapy with NAs.

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