Mechanisms of liver injuries caused by traditional Chinese medicines

Drug-induced liver injury(DILI)is a common adverse drug reaction,which can even result in liver failure[1,2].The Chinese Medical Association issued the Guidelines for the Diagnosis and Treatment of DILI based on the Roussel Uclaf Causality Assessment Method(RUCAM)in 2015[3].A previous study reported that traditional Chinese medicines(TCMs),herbal and dietary supplements,and antituberculosis drugs were the main causes of DILI in China[4].Herb-induced liver injury(HILI)refers to liver injury caused by TCMs,natural drugs,and their related preparations[5].

Physcion increases the sensitivity of hepatocellular carcinoma to sorafenib through miRNA-370/PIM1 axis-regulated glycolysis

BACKGROUND Resistance to sorafenib has become a challenge in clinical treatment of hepatocellular carcinoma(HCC).Physcion is a common bioactive anthraquinone that has potential as an anticancer agent.AIM To study the effect of physcion on sensitizing HCC cells to sorafenib.METHODS Sorafenib-resistant HCC cells were established and treated with sorafenib and/or physcion.The cell viability,proliferation and apoptosis were measured by cell counting kit-8,colony formation,flow cytometry,and in vivo xenograft model.Glucose uptake,lactate acid production,extracellular acidification rate(ECAR),and oxygen consumption rate(OCR)were measured to analyze glycolysis.Expression of glycolysis-related regulators was assessed by western blotting.RESULTS The addition of physcion significantly enhanced the antitumor effects of sorafenib on sorafenib-resistant HCC cells,manifested by enhanced apoptosis and suppressed cell growth.The glucose uptake,lactate acid production,and ECAR were elevated,and OCR was suppressed by physcion treatment.The level of PIM1 was elevated and miR-370 was suppressed in sorafenib-resistant HCC cells compared with the parental cells,which was suppressed by physcion treatment.Inhibition of miR-370 notably reversed the effects of physcion on sorafenib-resistant HCC cells.CONCLUSION Our data indicated that physcion enhanced the sensitivity of HCC cells to sorafenib by enhancing miR-370 to suppress PIM1-promoted glycolysis.

Evaluation of a novel choanoid fluidized bed bioreactor for future bioartificial livers

AIM:To construct and evaluate the functionality of a choanoid-fluidized bed bioreactor(CFBB)based on microencapsulated immortalized human hepatocytes.METHODS:Encapsulated hepatocytes were placed in the constructed CFBB and circulated through Dulbecco’s Modified Eagle’s Medium(DMEM)for 12 h,and then through exchanged plasma for 6 h,and compared with encapsulated cells cultivated under static conditions in a spinner flask.Levels of alanine aminotransferase(ALT)and albumin were used to evaluate the CFBB during media circulation,whereas levels of ALT,total bilirubin(TBil),and albumin were used to evaluate it during plasma circulation.Mass transfer and hepatocyte injury were evaluated by comparing the results from the two experimental conditions.In addition,the viability and microstructure of encapsulated cells were observed in the different environments.RESULTS:The bioartificial liver model based on a CFBB was verified by in vitro experiments.The viability of encapsulated cells accounting for 84.6%±3.7%in CFBB plasma perfusion was higher than the 74.8%±3.1%in the static culture group(P<0.05)after 6 h.ALT release from cells was 29±3.5 U/L vs 40.6±3.2U/L at 12 h(P<0.01)in the CFBB medium circulation and static medium culture groups,respectively.Albumin secretion from cells was 234.2±27.8μg/1×107cells vs 167.8±29.3μg/1×107 cells at 6 h(P<0.01),274.4±34.6μg/1×107 cells vs 208.4±49.3μg/1×107 cells(P<0.05)at 12 h,in the two medium circulation/culture groups,respectively.Furthermore,ALT and TBil levels were 172.3±24.1 U/L vs 236.3±21.5 U/L(P<0.05),240.1±23.9μmol/L vs 241.9±31.4μmol/L(P>0.05)at 6 h in the CFBB plasma perfusion and static plasma culture groups,respectively.There was no significant difference in albumin concentration between the two experimental plasma groups at any time point.The microstructure of the encapsulated hepatocytes remained healthier in the CFBB group compared with the static culture group after 6 h of plasma perfusion.CONCLUSION:The CFBB can function as a bioartificial liver based on a bioreactor.The efficacy of this novel bioreactor is promising for the study of liver failure.

Efficient generation of functional hepatocytelike cells from mouse liver progenitor cells via indirect co-culture with immortalized human hepatic stellate cells

BACKGROUND： Differentiation of liver progenitor cells（LPCs） to functional hepatocytes holds great potential to develop new strategies for hepatocyte transplantation and the screening of drug-induced cytotoxicity. However, reports on the efficient and convenient hepatic differentiation of LPCs to hepatocytes are few. The present study aims to investigate the possibility of generating functional hepatocytes from LPCs in an indirect co-culture system.METHODS： Mouse LPCs were co-cultured in Transwell plates with an immortalized human hepatic stellate cell line（HSCLi） we previously established. The morphology, expression of hepatic markers, and functions of mouse LPC-derived cells were monitored and compared with those of conventionally cultured LPCs. RESULTS： Co-culturing with HSC-Li cells induced differentiation of mouse LPCs into functional hepatocyte-like cells. The differentiated cells were morphologically transformed into hepatocyte-like cells 3 days after co-culture initiation. In addition, the differentiated cells expressed liver-specific genes and possessed hepatic functions, including glycogen storage, lowdensity lipoprotein uptake, albumin secretion, urea synthesis, and cytochrome P450 1A2 enzymatic activity.CONCLUSIONS： Our method, which employs indirect co-culture with HSC-Li cells, can efficiently induce the differentiation of LPCs into functional hepatocytes. This finding suggests that this co-culture system can be a useful method for the efficient generation of functional hepatocytes from LPCs.

Changes in Photosystem Ⅱ Activity and Leaf Reflectance Features of Several Subtropical Woody Plants Under Simulated SO2 Treatment

The effects of simulated SO2 treatment on the photosynthetic apparatus were investigated in five subtropical forest plants, namely Plnus massonlana Lamb., Schlma superba Gardn. et Champ., Castanopsls flssa （Champ. ex Benth.） Rehd. et Wils., Acmena acuminatissima （BI.） Merr et Perry, and Cryptocarya concinna Hance. After leaf sections had been immersed in 0, 20, 50, and 100 mmol/L NaHSO3 for 20 h, total chlorophyll （Chl） content, Chl a/b, maximal photochemical efficiency, and the photochemical quantum yields of photosystem Ⅱ of all five woody plants were reduced to different degrees, whereas lutein content （Chl base） was increased. Two protective mechanisms, namely the xanthophyll cycle （de-epoxidation） and an anti-oxidant system （1,1-diphenyl-2-picrylhydrazyl radical-scavenging capacity）, showed differences in the degree of modulation under simulated SO2 treatment. Compared with control （distilled water treatment）, the revised normalized difference vegetation index, a leaf reflectance index, was lowered with Increasing concentrations of NaHSO3. Cryptocarya conclnna, a dominant species in the late succession stage of subtropical forests in South China, exhibited less sensitivity to NaHSO3. Conversely, Pinus massonlana, the pioneer hellophyte species, was most susceptible to NaHSO3 treatment. It Is suggested that SO2 pollution may accelerate the succession of subtropical forest.

Regulation of Light Energy Utilization and Distribution of Photosynthesis in Five Subtropical Woody Plants

The adaptations and responses of photosynthesis to long- and short-term growth light gradient treatments were investigated in five subtropical forest plants, namely Pinus massoniana Lamb., Schima superba Gardn. et Champ., Castanopsis flssa （Champ. ex Benth.） Rehd. et Wils., Acmena acuminatissima （BI.） Merr et Perry, and Cryptocarya concinna Hance. With diurnal changes in sunlight and air temperature, the de-epoxidation state and lutein content in the five woody plants under three light Intensities first increased and then decreased during the day. However, maximal photochemical efficiency （FvFm; where Fm is the maximum fluorescence yield and Fv Is variable fluorescence） and the photochemical quantum yields of photosystem （PS）Ⅱ （φPSⅡ） of the species examined changed in the opposite manner, with those in plants grown under 100% natural light changing the most. After long-term treatment （21 months）, anti-oxidant capacity （1,1-diphenyl-2-picrylhydrazyl radical （DPPH.）-scavenging capacity） and utilization of excitation energy showed differences in modulation by different light intensities. It was shown that A. acuminatissima and C. concinna, as dominant species in the late succession stage of a subtropical forest in Dinghu mountain, South China, were better able to adapt to different light environments. However, P. massonlana, the pioneer species of this forest, exhibited less adaptation to low light intensity and was definitely eliminated by the forest succession process.

Cost-effectiveness analysis of the prevention of mother-to-child transmission of HIV

Background:The number of HIV-positive pregnant women accounted for about 10% of China’s total over the past few years in Liangshan Prefecture, Sichuan province in China. Although cost-effectiveness of the PMTCT of HIV have been evaluated in other previous studies, no specific study has been conducted in Liangshan prefecture, nor has the expenses paid individually by HIV-positive pregnant women been included. The purpose of this study was to evaluate both the short-term and long-term cost-effectiveness of PMTCT of HIV in Liangshan Prefecture from the social perspective.Methods:From December 2018 to January 2019, individual expenses and the other costs were collected: individual expenses of 133 recruited HIV-positive pregnant women registered in the National Information System of Prevention of Mother-to-Child Transmission of HIV, Syphilis, and HBV, and the other costs from local maternal and child healthcare hospitals, Centers for Disease Control and Prevention, and general hospitals. The costs, the number of pediatric infections averted from being HIV infected were analyzed. And, Life years gained by pediatric infections averted were calculated by using a life table. Besides, Direct benefit was calculated through a Markov mode. Furthermore, One-way sensitivity analysis was conducted for key variables affecting the benefit–cost ratio.Results:The estimated number of pediatric infections averted was 164.The total cost was USD 114.1 million, including direct medical costs, direct non-medical costs, and indirect costs, which were USD 54.2 million, USD 53.4 million, and USD 6.5 million, respectively. 630.6 person-years discounted to 2017 were gained at a 3% annual rate, and cost per life year gained was USD 1809.50. Direct benefits were USD 198.4 million, indirect benefits USD 82.5 million, and the benefit–cost ratio was 1.5. The sensitivity analysis showed that if PMTCT costs hypothetically ranged from USD 85.6 million to USD 142.6 million, benefit–cost ratio would vary from 1.0 to 2.3.Conclusions:PMTCT of HIV in Liangshan Prefecture was very cost-effective. It was a great economic burden of PMTCT on HIV-positive pregnant women and their families to take individual expenses. Therefore, it could be suggested that individual expenses should be covered as much as possible by different types of financing.

Levels of vaccination coverage among HIV-exposed children in China: a retrospective study

Background:Vaccination is crucial for human immunodeficiency virus(HlV)-exposed children because of their increased risk of morbidity and mortality from various vaccine-preventable diseases.However,studies have shown that they are at high risk of incomplete vaccination.Although China has developed prevention of mother-to-child transmission(PMTCT)of HIV programs substantially over the past decades,few studies have investigated the immunization levels of Chinese HIV-exposed children.Therefore,we aimed to evaluate vaccination coverage and its associated factors among HIV-exposed children in China during 2016-2018.