EZH2: The roles in targeted therapy and mechanisms of resistance in breast cancer.

Drug resistance presents a formidable challenge in the realm of breast cancer therapy. Accumulating evidence suggests that enhancer of zeste homolog 2 (EZH2), a component of the polycomb repressive complex 2 (PRC2), may serve as a key regulator in controlling drug resistance. EZH2 overexpression has been observed in breast cancer and many other malignancies, showing a strong correlation with poor outcomes. This review aims to summarize the mechanisms by which EZH2 regulates drug resistance, with a specific focus on breast cancer, in order to provide a comprehensive understanding of the underlying molecular processes. Additionally, we will discuss the current strategies and outcomes of targeting EZH2 using both single agents and combination therapies, with the goal of offering improved guidance for the clinical treatment of breast cancer patients who have developed drug resistance.

Exosomes Derived from M2 Microglial Cells Modulated by 1070-nm Light Improve Cognition in an Alzheimer's Disease Mouse Model.

Near-infrared photobiomodulation has been identified as a potential strategy for Alzheimer's disease (AD). However, the mechanisms underlying this therapeutic effect remain poorly characterize. Herein, it is illustrate that 1070-nm light induces the morphological alteration of microglia from an M1 to M2 phenotype that secretes exosomes, which alleviates the ß-amyloid burden to improve cognitive function by ameliorating neuroinflammation and promoting neuronal dendritic spine plasticity. The results show that 4 J cm-2 1070-nm light at a 10-Hz frequency prompts microglia with an M1 inflammatory type to switch to an M2 anti-inflammatory type. This induces secretion of M2 microglial-derived exosomes containing miR-7670-3p, which targets activating transcription factor 6 (ATF6) during endoplasmic reticulum (ER) stress. Moreover, it is found that miR-7670-3p reduces ATF6 expression to further ameliorate ER stress, thus attenuating the inflammatory response and protecting dendritic spine integrity of neurons in the cortex and hippocampus of 5xFAD mice, ultimately leading to improvements in cognitive function. This study highlights the critical role of exosomes derive from 1070-nm light-modulated microglia in treating AD mice, which may provide a theoretical basis for the treatment of AD with the use of near-infrared photobiomodulation.

Azithromycin ameliorated cigarette smoke-induced airway epithelial barrier dysfunction by activating Nrf2/GCL/GSH signaling pathway.

BACKGROUND: Airway epithelium is the first barrier against environmental insults, and epithelial barrier dysfunction caused by cigarette smoke (CS) is particularly relevant to chronic obstructive pulmonary disease (COPD) progression. Our study was to determine whether Azithromycin (AZI) ameliorates CS-induced airway epithelial barrier dysfunction and the underlying mechanisms. METHODS: Primary bronchial epithelial cells (PBECs), human bronchial epithelial cells (HBECs), Sprague Dawley rats and nuclear factor erythroid 2-related factor 2 (Nrf2)-/- mice were pretreated with AZI and subsequently exposed to CS. Transepithelial electronic resistance (TEER), junction proteins as well as pro-inflammatory cytokines and apoptosis markers were examined to assess epithelial barrier dysfunction. Metabolomics study was applied to explore the underlying mechanism of AZI. RESULTS: CS-induced TEER decline and intercellular junction destruction, accompanied with inflammatory response and cell apoptosis in PBECs were restored by AZI dose-dependently, which were also observed in CS-exposed rats. Mechanistically, GSH metabolism pathway was identified as the top differentially impacted pathway and AZI treatment upregulated the activities of glutamate cysteine ligase (GCL) and the contents of metabolites in GSH metabolic pathway. Furthermore, AZI apparently reversed CS-induced Nrf2 suppression, and similar effects on airway epithelial barrier dysfunction were also found for Nrf2 agonist tert-butylhydroquinone and vitamin C. Finally, deletion of Nrf2 in both HBECs and C57BL/6N mice aggravated CS-induced GSH metabolism imbalance to disrupt airway epithelial barrier and partially deprived the effects of AZI. CONCLUSION: These findings suggest that the clinical benefits of AZI for COPD management are related with the protection of CS-induced airway epithelial barrier dysfunction via activating Nrf2/GCL/GSH pathway, providing potential therapeutic strategies for COPD.

Distribution Characteristics and Influencing Factors of Bio-elements in the Human Hair of Uyghur Communities in an Oasis Area of Xinjiang, China.

Located in central Asia, Xinjiang is characterized as a diverse environment in China, consisting of vast deserts, dotted oases, and high mountains. Due to the combined effect of climate conditions under such a diverse environment, there are large differences in human activities, living styles, and eating habits in farmland and grazing pastures between Xinjiang and other regions of China. This study aimed to investigate the variations and mechanisms of elemental distribution in the hair of Uyghur communities among different ages and genders and under different land use backgrounds in an oasis region in Xinjiang. Hair samples from 524 residents from four traditional farmland areas and two grazing pasture areas in Bai Cheng County in Xinjiang were collected, and the levels of thirteen elements were analyzed. The results indicated that the average levels of Cu, Mg, Mn, Zn, Ni, Co, Pb, Fe, Ca, Cd, Cr, As, and Se in the hair of Uyghur communities were within the background levels of Chinese and global residents' hair. Overall, the levels of elements in the hair of women residents were higher than those of men residents. The levels of elements in the human hair of the middle-aged group were higher than those of child and older-aged groups. Elements Cr and Se in the hair of grazing pastures were higher than those of farmland areas. The levels of Cd, Pb, As, and Zn in the hair of farmland areas were higher than those of grazing pasture areas. The levels of Ca, Mg, Cu, and Fe in the hair of Uyghur communities were higher than those of other ethnic groups, while the toxic elements in the hair of residents in Bai Cheng were lower than those in other regions of China. Middle-aged people were exposed to higher levels of toxic elements in their daily activities compared to elderly and child groups. Also, adult groups need much more nutrients for their growth and intellectual development compared to child and elderly groups. The change in land use from grazing pastures to farmland increased the toxic trace element concentration levels in human hair. The significant differences in the overall concentration levels of elements in human hair among the different ethnic groups and regions can be attributed to the differences in lifestyles, cultural customs, dietary habits, and internal and external exposure routes.

Bioaccumulation characteristics, transfer model of heavy metals in soil-crop system and health assessment in plateau region, China.

This study investigated the bioaccumulation and transfer of heavy metals including Cd, Cr, Cu, Mn, Ni, Pb and Zn in soil-crop system in Lhasa, and assessed the health risks of the edible part of the crops. The results showed that the average values of Cd, Cr, Cu, Mn, Ni, Pb and Zn were 0.15, 44.55, 24.68, 532.40, 22.47, 38.18 and 73.99 mg kg-1 in natural soil, and 0.16, 46.93, 38.45, 559.13, 23.23, 40.03 and 83.29 mg kg-1 in cultivated soil, respectively. Highland barley and wheat had the strongest ability to accumulate Zn in grain, the BCF values were 0.24 and 0.27, respectively, significant differences in the distribution of metal contents in crop root, stem, leaf and grain were observed. Root presented larger accumulation capacity in most metals, Zn and Cu was easily transferred in the plant organs, most metals in this study presented difficult to migrate from root to grain. The transfer peak of most metals in soil-crop system appeared from stem to leaf. The concentrations of Cr and Mn in crop grains could be predicted according to the multiple linear regression models. THQ and HI values of heavy metals in edible parts of both highland barley and wheat were below the safety threshold of 1, indicating no detrimental effects posed to adults health. This study helps to understand the accumulation and transfer of heavy metals in soil-crop system in plateau region.

Exposure Routes and Health Risks Associated with Pesticide Application.

Pesticides play an important role in agricultural development. However, pesticide application can result in both acute and chronic human toxicities, and the adverse effects of pesticides on the environment and human health remain a serious problem. There is therefore a need to discuss the application methods for pesticides, the routes of pesticide exposure, and the health risks posed by pesticide application. The health problems related to pesticide application and exposure in developing countries are of particular concern. The purpose of this paper is to provide scientific information for policymakers in order to allow the development of proper pesticide application technics and methods to minimize pesticide exposure and the adverse health effects on both applicators and communities. Studies indicate that there are four main pesticide application methods, including hydraulic spraying, backpack spraying, basal trunk spraying, and aerial spraying. Pesticide application methods are mainly selected by considering the habits of target pests, the characteristics of target sites, and the properties of pesticides. Humans are directly exposed to pesticides in occupational, agricultural, and household activities and are indirectly exposed to pesticides via environmental media, including air, water, soil, and food. Human exposure to pesticides occurs mainly through dermal, oral, and respiratory routes. People who are directly and/or indirectly exposed to pesticides may contract acute toxicity effects and chronic diseases. Although no segment of the general population is completely protected against exposure to pesticides and their potentially serious health effects, a disproportionate burden is shouldered by people in developing countries. Both deterministic and probabilistic human health risk assessments have their advantages and disadvantages and both types of methods should be comprehensively implemented in research on exposure and human health risk assessment. Equipment for appropriate pesticide application is important for application efficiency to minimize the loss of spray solution as well as reduce pesticide residuals in the environment and adverse human health effects due to over-spraying and residues. Policymakers should implement various useful measures, such as integrated pest management (IPM) laws that prohibit the use of pesticides with high risks and the development of a national implementation plan (NIP) to reduce the adverse effects of pesticides on the environment and on human health.

Environmental monitoring and potential health risk assessment from Pymetrozine exposure among communities in typical rice-growing areas of China.

Pymetrozine is one of the most commonly used insecticides in China. This study was conducted to analyse Pymetrozine's potential exposures through various environmental routes beyond the treatment areas. The aim was to estimate the potential health risk for communities due to non-dietary exposures to Pymetrozine in soil and paddy water. Data on registration of pesticides in China, government reports, questionnaires, interviews and literature reviews as well as toxicological health investigations were evaluated to determine the hazard and dose-response characteristics of Pymetrozine. These were based on the US EPA exposure and human health risk assessment methods and exposure data from soil and paddy water samples collected between 10 and 20 m around the resident's location. The exposure doses from dermal contact through soil and paddy water were estimated. The potential cancer risk from the following exposure routes was evaluated: ingestion through soil; dermal contact exposure through soil; dermal contact exposure through paddy water. The potential total cancer risk for residents was estimated to be less than 1 × 10-6. These were relatively low and within the acceptable risk levels. The potential hazard quotient (HQ) from acute and lifetime exposure by dermal contact through paddy water and soil and acute and lifetime exposure by soil ingestion for residents was less than 1, indicating an acceptable risk level. This study suggested that there were negligible cancer risk and non-cancer risks based on ingestion and dermal contact routes of exposure to residents.

Natural dynamics and residues of pymetrozine for typical rice-growing areas of China.

Pymetrozine has replaced toxic organophosphate pesticides previously used for controlling pests of rice crops in China. Existing data on its environmental behavior are usually related to studies on artificial plots that do not adequately address the natural dynamics and residues in actual field conditions. Therefore, studies under field conditions were carried out to investigate the natural dynamics and residues of pymetrozine in two typical rice-growing areas in China - Hunan and Guangxi provinces. Samples of paddy soil and water were collected in relation to spraying events in the study areas. The quick, easy, cheap, effective, rugged and safe (QuEChERS) method was used to extract pymetrozine residues from the samples by a Waters ACQUITY UPLC (Milford, MA, USA) system interfaced with a triple-quadrupole mass spectrometer (Xevo TQ-D, Waters Corp., USA). The initial deposition of pymetrozine in paddy soils was higher than in paddy waters in both areas. The decay of pymetrozine followed an exponential trend consistent with the first order kinetics. The half-life of pymetrozine in paddy water was determined to be 3.0 and 3.8 days, whereas the half-life in soil was 3.8 and 3.5 days in the Guangxi and Hunan samples, respectively. The decline rates of pymetrozine in paddy soil and paddy water in this field study were faster than those conducted under non-field conditions reported in previous studies. Compared to other pesticides used in China as reported in previous studies, the environmental persistence of pymetrozine in both paddy water and soils in Guangxi and Hunan provinces is very low. This has important implications for the use of pymetrozine in agricultural systems globally.

Association of selenium, arsenic, and other trace elements in drinking water and urine in residents of the plateau region in China.

Drinking water is considered to be an important exposure pathway for humans to ingest trace elements; human urine samples are widely accepted as biometric substrates that can reflect human exposure to trace elements. The current study aimed at investigating the concentrations of trace elements including selenium (Se), arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) in drinking water and human urine in plateau region of China, determining the association among trace elements in drinking water and urine, and analyzing their associations with age and gender. The results showed that the majority of trace element concentrations were in the range of the World Health Organization (WHO 2011) guideline values, in both urine samples of male and female, and the median values were descending in the order: Zn > Cu > As > Se > Cr > Ni > Mn > Pb > Cd > Co. Selenium contributed to the excretion of As, Cr, Cu, Cd, and Zn in human body, group of 31-40 years appeared to present the greatest excretion ability in most of the trace elements. Weak positive correlations were observed between age and Mn in female urine samples, and negative correlations were observed between age and Se, As, Co, and Cu in male urine samples and between age and Co in female urine samples, respectively. Significant positive correlation was observed in As between drinking water and the whole human urine. In the same family, female seemed to show higher proportions of urinary As levels than male. This study will provide elementary information regarding trace element levels in drinking water and human urine in residents in plateau region of China and is helpful to provide reference for dietary nutrient trace element intake and effective control for local resident.

Comprehensive pharmacogenomics characterization of temozolomide response in gliomas.

Recent developments in pharmacogenomics have created opportunities for predicting temozolomide response in gliomas. Temozolomide is the main first-line alkylating chemotherapeutic drug together with radiotherapy as standard treatments of high-risk gliomas after surgery. However, there are great individual differences in temozolomide response. Besides the heterogeneity of gliomas, pharmacogenomics relevant genetic polymorphisms can not only affect pharmacokinetics of temozolomide but also change anti-tumor effects of temozolomide. This review will summarize pharmacogenomic studies of temozolomide in gliomas which can lay the foundation to personalized chemotherapy.

Comparison of characteristics, water quality and health risk assessment of trace elements in surface water and groundwater in China.

Water quality is closely associated with human health and socio-economic sustainable development. With the increasingly intensive anthropogenic activities, pollutants especially trace elements, enter water aquatic system and cause harm to humans. This study conducted the first systematic comparison on the pollution status of surface water and groundwater in China. Water quality and health risk assessment of 12 trace elements were evaluated according to the water quality index (WQI), hazard quotient (HQ), hazard index (HI), and carcinogenic risk (CR). The results showed that the average values of trace elements in the majority of surface water were higher than those in groundwater. The WQI values demonstrated that 86.02% of surface water and 83.11% of groundwater were suitable for drinking water. Arsenic served as the predominant pollutant and contributed significantly to cause the non­carcinogenic risk on human health in both surface water and groundwater, children were more vulnerable to the adverse effects than adults. In surface water, the priority non-carcinogenic risk sites were mainly distributed in Anning River, Taizi River, Middle reaches of Huai River and Jilin section of Songhua River. For groundwater, the high-risk sites were located in Huhhot Basin, Kuitun, Jianghan Plain, Datong Basin and Yucheng County. Arsenic posed potential carcinogenic risk to local resident in some water sites, and it presented higher in groundwater than surface water. More concerns should be paid on Songhua, Yangtze and Huai River Basins, in addition, Pearl, Southeast Coastal, Southwest and Northwest River Basins still need attention. The future work should be carried out more extensive range of the water sites and long-term monitoring in China. In particular, more attention should be dedicated to assess high As water bodies.

Bioaccumulation and translocation of trace elements in soil-irrigation water-wheat in arid agricultural areas of Xin Jiang, China.

Pollution resulting from toxic trace elements is an increasing concern around the world especially in developing countries such as China. Rapid industrialisation, urbanisation and agricultural development are the dominant sources of anthropogenic contamination contributed to an increased potential toxicity of trace elements in the irrigation water-soil-food chain. Xin Jiang in China is a reserved cultivated land development area that could provide the most extensive strategic support for food production and arable land security in China. Thus, it is crucial to investigate the bioaccumulation and translocation of trace elements in order to assess the ecological and human health risks in the traditional oasis system of the agricultural areas in Bay Cheng County, Xin Jiang. This study analysed the levels of trace elements in different layers of the soil, the irrigation water and the wheat plants, and the relationships among them. The results indicated that cadmium (Cd) and chromium (Cr) were the primary pollutants in soils and wheats respectively, and they fell into the serious pollution category. However, no trace elements over the pollution limits were detected in irrigation water. The maximum values of trace elements appeared in the soil layers at 5-10 cm and 10-15 cm. The pollution levels of trace elements in the soil layers were found at 0-5 cm and 0-20 cm, which were higher than those at 20-80 cm. In wheat, high amounts of absorption for Se, Cr, Zn and Cu, but low for Pb were detected in different parts of a plant. The roots of wheats were more eco-toxic to Cd, Co and Pb than other tissues, indicating that roots were more effective at absorbing Cd, Co and Pb, as these metals are usually toxic in the soil. Se, Cu and Zn showed a higher ability of being transferred from soils to the edible parts of crops. The bio-transfer factors of Zn, Mo, Cu, Mg and Mn were considerably higher than those of other elements. The average cancer risk of As, Cd, Co, Ni and TCR in wheat grains exceeded the safety reference limit (1 × 10-4). For the exposed population, Cr in wheat was the major contributor to total cancer risk. The average values of HQ of Cr, Mn and As, and total non-cancer risk index exceeded the corresponding effective safe reference doses (HQ > 1).

Serum ERK1/2 proteins fluctuating with HBV infection report frequency of viral-specific CD8+ T cells and predict IFNα therapeutic effect in chronic hepatitis B patients.

Chronic hepatitis B (CHB) is a life-threatening disease caused by HBV infection. Our previous work proved that activation of ERK1/2 and STAT3 signaling was involved in HBV tolerance. We herein investigated clinical significances of serum ERK1/2 and STAT3 proteins in CHB. Results showed that ERK1/2 and STAT3 were fluctuated with natural history of CHB. In addition, STAT3 was found to be positively correlated to the elevation of ALT, AST and GGT, while ERK1 was negatively correlated to decreases of TP and ALB. Also, there was a positive correlation between the anti-HBc antibody and ERK1, ERK2 or STAT3 in HBeAg-negative patients. Strikingly, serum ERK1 and ERK2 could reflect level of HBsAg-specific CD8+ T cells. A model composed with baseline ERK1 and ERK2 levels had a high accuracy to predict the effect of IFNα treatment. In conclusion, serum ERK1, ERK2 and STAT3 could serve as novel biomarkers in chronic HBV infections.

La protein contributes to cells proliferation and migration and serves as a potential therapeutic target for hepatocellular carcinoma.

AIM: La protein is a multifunctional RNA-binding protein involved in RNA metabolism that has been reported to promote the growth of some solid tumors. However, potential role of La in hepatocellular carcinoma (HCC) has not been fully elucidated. This study aimed to investigate the expression of La and its function in HCC. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis were conducted to detect the expression levels of La mRNA and protein in HCC cells and tissues. The proliferation capability of cells was clarified by Cell Counting Kit-8 and clone formation assays. Wound healing assay was carried out to assess cell migration ability. Related protein expressions were also analyzed by western blot. RESULTS: Analysis of our clinical samples showed that La mRNA and protein expression of HCC tissues was higher than those of corresponding adjacent tissues, consistent with the result of microarray datasets from Oncomine database. La was also significantly overexpressed in eight HCC cells, compared with normal hepatocytes. According to in vitro experiments, we demonstrated that knockdown of La inhibited HCC cell proliferation and migration. CONCLUSIONS: Our results revealed that La expression is elevated both at the RNA and protein levels in HCC. Highly expressed La significantly promotes tumorigenesis of HCC, suggesting that La may be a potential therapeutic target for the treatment of HCC.

Concentration, Spatial Distribution, Contamination Degree and Human Health Risk Assessment of Heavy Metals in Urban Soils across China between 2003 and 2019-A Systematic Review.

This study provides an overview of the studies of heavy metal pollution regarding As, Cd, Cr, Hg, Pb, Cu, Zn and Ni in the urban soils throughout 71 cities of China, based on data from online literature, during the period 2003-2019. The concentrations, spatial distributions, contamination degrees and health risks of heavy metals in the urban soils were evaluated. The results demonstrated that the mean values of eight heavy metals all exceeded the soil background values in China, and the kriging interpolation method showed that the hot-spot cities with heavy metal contamination in urban soils were mainly concentrated in the southwest, southcentral, southeast coast, northcentral and northwest regions of China. The geoaccumulation index (Igeo) indicated that Hg and Cd were at moderate contamination levels and that the levels of the other six metals did not appear contamination. The pollution index (PI) showed that Cd and Hg reached high contamination levels, and the other metals reached moderate contamination levels. The integrated pollution index (IPI) and potential ecological risk index (PRI) indicated that the integral urban soils in the study areas ranked high contamination levels and moderate ecological risk degree, respectively, and Cd and Hg should be labeled as priority metals for control in the urban soils around China. The human health risk assessments for the heavy metals indicated that ingestion was the dominant exposure pathway for having adverse effects on human health. The mean Hazard index (HI) values of eight heavy metals all showed that adverse effects on human health were unlikely, and the mean carcinogenic (CR) values of As, Cr and Ni for children and adults all suggested an acceptable carcinogenic risk to human beings. In addition, children exposed to these heavy metals faced more serious non-carcinogenic and carcinogenic health threats compared to adults. The results could provide valuable information for demanding the better control of heavy metal pollution and mitigation of the adverse effects on residents by environmental regulators in national urban regions.

Study on the structure optimization and anti-hepatitis B virus activity of novel human La protein inhibitor HBSC11.

In our previous study, Methyl pyrazolo[1,5-a] pyridine-2-carboxylate (HBSC11) was shown to combine with La protein, which conferred anti-hepatitis B virus (HBV) effects. The purpose of this study was to optimize, synthesize, and evaluate the anti-HBV activity of HBSC11. The methyl group of HBSC11 was substituted with hydrophobic, hydrophilic, and tricyclic groups to generate novel HBV inhibitors with desirable potency. On in vitro evaluation, several derivatives exhibited good anti-HBV activity compared with control. In particular, compound 5a reduced the level of HBV antigen by approximately 50%, which was similar to the activity of entecavir. In a mouse model, 5a showed 98.9% inhibition rate for HBV DNA, 57.4% for HBsAg, and 46.4% for HBeAg; the corresponding rates in the control group were 90.8, 3.8, and 9.8%, respectively. In addition, prediction of binding modes and physicochemical properties showed that 5a formed hydrogen bonds with La protein and conformed well to the Lipinski's rule of five. Our results suggest that 5a is a potential new anti-HBV drug.

Patient compliance with antimicrobial drugs: A Chinese survey.

BACKGROUND: Antimicrobial therapy is among the mainstream treatment modalities employed in clinical settings. Antimicrobial sensitivity of the pathogen and patient compliance are key determinants of the efficacy of antimicrobial therapy. OBJECTIVE: In this study, we sought to investigate the factors that affect patient compliance to antimicrobial therapy in a Chinese teaching hospital to enhance patient compliance and to prevent abuse and misuse of antibiotics by patients. METHODS: A questionnaire survey was conducted among patients willing to answer all the questions who were prescribed antimicrobial drugs orally, and for whom at least half of the duration of therapy was not under the supervision of a doctor or nurse. Data analyses were performed using Kruskal-Wallis test and multivariate logistic regression. RESULTS: A total of 720 patients participated in the survey; of these, 714 patients provided complete data and were included in the analysis. Up to 86.97% of patients showed noncompliance to antimicrobial therapy (total compliance score < 8), whereas 13.03% of patients showed good compliance (total compliance score = 8). On multivariate analyses, understanding of the treatment was an important factor associated with compliance. CONCLUSIONS: A range of factors were associated with compliance to antimicrobial therapy, including understanding of the treatment, gender, age, home address, education level, and family income.

Alteration of microRNA profiles by a novel inhibitor of human La protein in HBV-transformed human hepatoma cells.

A pyrazolopyridine HBSC11 was previously identified as a novel inhibitor of human La protein with anti-hepatitis B virus (HBV) activity. However, the underlying mechanism(s) of HBV inhibition by HBSC11 remains unclear. This study aimed to examine the regulation of microRNA (miRNA) by HBSC11 in HBV-transformed human hepatoma HepG2.2.15 cells using microarray and quantitative real-time PCR. Target genes of the differentially expressed miRNAs were predicted and subjected to bioinformatics analysis. Results showed that HBSC11 significantly upregulated the expression of miR-3912-5p, miR-6793-5p, and miR-7159-5p in HepG2.2.15 cells. Target genes of the three miRNAs were mainly involved in the regulation of nucleic acid-templated transcription, negative regulation of gene expression, nucleic acid binding transcription factor activity and regulation of phosphorylation. In addition, target genes were enriched in certain regulatory pathways related to HBV infection and HBV-associated disease progression, such as the transforming growth factor (TGF)-ß, Wnt, and p53 signaling. Our study demonstrates the involvement of miR-3912-5p, miR-6793-5p, and miR-7159-5p and the potential modulation of specific pathways (TGF-ß, Wnt, and p53 signaling) in HBSC11-mediated inhibition of HBV replication. This study provides insight into the molecular mechanism of the action of HBSC11 against HBV infection and will support the development of antiviral drugs targeting La protein.

New anti-hepatitis B virus drugs under development and evaluation.

PURPOSE OF REVIEW: Although available therapies can effectively inhibit hepatitis B virus (HBV) replication in patients with active chronic hepatitis B (CHB) infection, therapeutic efficacy is limited because of potential drug resistance, and an inability to mediate viral clearance and to rectify immune impairment in CHB patients. This review will summarize the state-of-the-art for anti-HBV drugs and focus on potential drugs and targets under development and evaluation. RECENT FINDINGS: New developing drugs are evaluated for their antiviral effects in the areas of interference with the viral replication cycle, elimination of covalently closed circular DNA, modulation of host immunity and identification of the La protein and its regulator casein kinase as possible targets for the development of anti-HBV therapies. SUMMARY: These novel compounds and targets have showed great inhibitory effects on HBV replication in vitro and in animal models. Several novel therapies are promising in early clinical trials. Potentially, combination of newly developing and current antiviral drugs may cure CHB in the clinic.