Background/Aims: This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results: One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.

Objective : To investigate the antidepressant effects and the underlying mechanisms of tetrahydrocurcumin(THC) and its nanoparticle formulation(THCN). Methods : Forty-six male ICR mice were randomly divided into Con group, LPS group, THC group, THCN group and SER group. A mouse depression model was established by intraperitoneal administration of LPS. The anxiety and depression-like behaviors of mice were evaluated by open field test(OFT) and forced swimming test(FST). Myelin staining was applied to assess the extent of demyelination in the prefrontal cortex of the mice. The prefrontal cortex and hippocampus were further examined for the expression levels of glial fibrillary acidic protein(GFAP) and Toll-like receptor 4(TLR4) through quantitative immunofluorescence assays. Results : Compared with the Con group, the LPS group showed increased anxiety-like and depressive-like behaviors in both the long-term and short-term experiments(P<0.05); the degree of demyelination increased in the LPS group of the long-term experiment(P<0.01); the expression of GFAP was reduced in the LPS group of the short-term experiment(P<0.01), while the expression of TLR4 increased(P<0.05); the expression of TLR4 decreased in the THC group(P<0.01); the expression of GFAP in the prefrontal cortex of the THCN group was reduced(P<0.01), while the expression of TLR4 increased(P<0.05). Compared with the LPS group, the THC group showed reduced depressive-like behaviors in the long-term experiment(P<0.05), while the anxiety-like and depressive-like behaviors of the THCN group and the SER group were reduced(P<0.05), and the anxiety-like and depressive-like behaviors of the THC group and the THCN group were reduced in the short-term experiment(P<0.05); the degree of demyelination was reduced in the THC group, THCN group and SER group in the long-term experiment(P<0.05); the expression of GFAP increased in the THC group of the short-term experiment(P<0.05), while the expression of TLR4 was reduced(P<0.05), and the expression of GFAP increased in the THCN group(P<0.05). Compared with the THC group, the THCN group and the SER group showed reduced anxiety-like behaviors in the long-term experiment(P<0.05); the expression of GFAP in the prefrontal cortex of the THCN group was reduced in the short-term experiment(P<0.05), while the expression of TLR4 in the hippocampal DG area increased in the short-term experiment(P<0.01). Conclusion Tetrahydrocurcumin and its nanoparticle formulation both exert significant ameliorative effects on depression-like behaviors and demyelination in mice induced by lipopolysaccharide. The antidepressant mechanism of THC appears to be mediated through the down-regulation of TLR4 and the up-regulation of GFAP. The mechanism underlying the antidepressant action of THCN seems predominantly focused on the enhancement of GFAP expression.

In this work,a rapid and label-free sensing platform was designed for visual detection of p53 gene.The rolling circle amplification(RCA)process of the assay platform was activated by p53 gene to produce long DNA-wires,which could bound with berberine hydrochloride(BBH)and further enhanced its fluorescence.This method showed high sensitivity with a low detection limit of 5.63 pmol/L,and high specificity toward p53 gene over other interference materials,even for single-base mutation gene.The method could realize the visual detection of targets under the illumination of a UV lamp.In addition,the designed fluorescence detection platform was successfully applied to p53 gene analysis in 10% fetal bovine serum samples,and the relative standard deviation and the recoveries were 0.1% -1.2% and 99.5% -104.7%,respectively.This approach had satisfactory characteristics,such as low cost,label-free,rapidity,high sensitivity,good selectivity and anti-interference ability,and reliable detection capability for complex practical samples,demonstrating a promising prospect in the diagnosis and treatment of diseases,especially for cancer.

Objective:To dry fresh Ginseng Radix et Rhizoma using different drying conditions; To investigate the effects of different drying conditions on the drying characteristics and medicinal quality of Ginseng Radix et Rhizoma.Methods:With moisture, powder color, extract, total polysaccharide and ginsenoside contents of Rg 1, Re, Rf, Rb 1, Rc, Rb 2 and Rd as indexes, the drying characteristics of Ginseng Radix et Rhizoma were studied based on Weibull function model, and the quality of Ginseng Radix et Rhizoma after drying was evaluated by entropy weight-TOPSIS model. Results:The drying method for Ginseng Radix et Rhizoma from its origin can be achieved by controlling the relative humidity of the drying medium to 50%, drying at 70 ℃ for 24 h, and then reducing the drying temperature to 60 ℃ until the moisture content was below 12.0%. This method could achieve high drying efficiency and produce high-quality Ginseng Radix et Rhizoma.Conclusions:The drying process of Ginseng Radix et Rhizoma is a falling rate process controlled by internal moisture diffusion. The drying rate of fresh Ginseng Radix et Rhizoma is affected by temperature and humidity. There is a certain correlation between the color of powder and the content of moisture, alcohol-soluble extractives and ginsenosides.

Processing for deodorization is widely used in the production of animal-derived Chinese medicinal materials. In this study, Heracles Neo ultra-fast gas-phase electronic nose combined with chemometrics was employed to analyze the overall odor difference of Cervi Cornu Pantotrichum(focusing on that derived from Cervus nippon Temminck in this study) before and after processing. The results showed that the electronic nose effectively distinguished between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. HS-GC-MS was used to identify and quantify the volatile components in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum, and 35 and 37 volatile components were detected in the medicinal materials and decoction pieces, respectively. The medicinal materials and decoction pieces contained 28 common volatile components contributing to the odor of Cervi Cornu Pantotrichum. The odor activity value(OAV) of each volatile component was calculated based on the olfactory threshold and relative content. The results showed that there were 17 key odor substances such as isovaleraldehyde, 2-methylbutanal, isobutyraldehyde, hexanal, and methanethiol in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. All of them had bad odor and were the main source of the odor of Cervi Cornu Pantotrichum. The results of principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) showed that there were significant differences in volatile components between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. Based on the thresholds of P<0.05 and Variable Importance in Projection(VIP)>1, 21 differential volatile odor components were screened out. Among them, isopentanol, isovaleraldehyde, 2-methylbutanal, n-nonanal, and dimethylamine were the key differential odor compounds between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. The odor compounds and their relative content reduced, and some flavor substances such as esters were produced after processing with wine, which was the main reason for the reduction of the odor after processing of Cervi Cornu Pantotrichum.
Odorants/analysis* ; Electronic Nose ; Gas Chromatography-Mass Spectrometry/methods* ; Animals ; Volatile Organic Compounds/analysis* ; Deer ; Drugs, Chinese Herbal/chemistry*

This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

Background/Aims: This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results: One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.

OBJECTIVE: To investigate the therapeutic potential of pseudolaric acid B (PAB) on non-alcoholic fatty liver disease (NAFLD) and its underlying molecular mechanism in vitro and in vivo. METHODS: Eight-week-old male C57BL/6J mice (n=32) were fed either a normal chow diet (NCD) or a high-fat diet (HFD) for 8 weeks. The HFD mice were divided into 3 groups according to a simple random method, including HFD, PAB low-dose [10 mg/(kg·d), PAB-L], and PAB high-dose [20 mg/(kg·d), PAB-H] groups. After 8 weeks of treatment, glucose metabolism and insulin resistance were assessed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Biochemical assays were used to measure the serum and cellular levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). White adipose tissue (WAT), brown adipose tissue (BAT) and liver tissue were subjected to hematoxylin and eosin (H&E) staining or Oil Red O staining to observe the alterations in adipose tissue and liver injury. PharmMapper and DisGeNet were used to predict the NAFLD-related PAB targets. Peroxisome proliferator-activated receptor alpha (PPARα) pathway involvement was suggested by Kyoto Encyclopedia of Genes and Genomes (KEGG) and search tool Retrieval of Interacting Genes (STRING) analyses. Luciferase reporter assay, cellular thermal shift assay (CETSA), and drug affinity responsive target stability assay (DARTS) were conducted to confirm direct binding of PAB with PPARα. Molecular dynamics simulations were applied to further validate target engagement. RT-qPCR and Western blot were performed to assess the downstream genes and proteins expression, and validated by PPARα inhibitor MK886. RESULTS: PAB significantly reduced serum TC, TG, LDL-C, AST, and ALT levels, and increased HDL-C level in HFD mice (P<0.01). Target prediction analysis indicated a significant correlation between PAB and PPARα pathway. PAB direct target binding with PPARα was confirmed through luciferase reporter assay, CETSA, and DARTS (P<0.05 or P<0.01). The target engagement between PAB and PPARα protein was further confirmed by molecular dynamics simulations and the top 3 amino acid residues, LEU321, MET355, and PHE273 showed the most significant changes in mutational energy. Subsequently, PAB upregulated the genes expressions involved in lipid metabolism and mitochondrial biogenesis downstream of PPARα (P<0.05 or P<0.01). Significantly, the PPARα inhibitor MK886 effectively reversed the lipid-lowering and PPARα activation properties of PAB (P<0.05 or P<0.01). CONCLUSION PAB mitigates lipid accumulation, ameliorates liver damage, and improves mitochondrial biogenesis by binding with PPARα, thus presenting a potential candidate for pharmaceutical development in the treatment of NAFLD.
Animals ; PPAR alpha/metabolism* ; Non-alcoholic Fatty Liver Disease/pathology* ; Male ; Mice, Inbred C57BL ; Lipid Metabolism/drug effects* ; Diterpenes/therapeutic use* ; Organelle Biogenesis ; Diet, High-Fat ; Humans ; Mice ; Liver/metabolism* ; Insulin Resistance ; Mitochondria/metabolism* ; Molecular Docking Simulation

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Background/Aims: This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results: One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.