Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed.Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group.Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.

Bioactive constituents and action mechanism of Xiaoyao San for treatment of non-alcoholic fatty liver disease

Xiaoyao San(XYS)is a classic Chinese medicine prescription.It is traditionally used to relieve syndrome of“liver stagnation and spleen deficiency”,a common syndrome type in traditional Chinese medicine,through soothing liver,tonifying spleen,and nourishing blood.Correspondingly,XYS has long application in the treatment of depression,dyspepsia and liver diseases.Given the rising of cutting-edge researches on XYS,there’s a significant need to diligently uncover the bioactive constituents and action mechanisms of XYS for treating non-alcoholic fatty liver disease accordingly.

Effects of Yigan Capsule on the expression of HMGB1,RAGE and NF-κB protein in rats with drug-induced liver injury

Objective:To study the effect of Yigan capsule on the expression of high mobility group protein B1(HMGB1),nuclear factor-B(NF-κB)and receptor for advanced glycation end products(RAGE)in anti-tuberculosis drug-induced liver injury(ATB-DILI),and to explore its protective effect and mechanism on ATB-DILI,so as to provide experimental basis for the clinical application of Yigan capsule.Methods:Twenty-four rats were divided into two groups.Except for the blank group(n=6),the other 18 rats were given isoniazid(INH)+rifampicin(RFP)(50 mg/kg.d)for 4 weeks.Then 18 rats were randomly divided into three groups(model group,low dose group of Yigan capsule and high dose group of Yigan capsule)according to 6 rats in each group.The blank group and the model group were given 0.9%sodium chloride solution by intragastric administration.The low dose group of Yigan capsule was 0.468 g/kg,and the high dose group of Yigan capsule was 1.872 g/kg[1].After 4 weeks,the pathological changes of liver were observed by HE staining.The contents of ALT,AST,ALP,γ-GT and TBIL were detected.The expression of HMGB1,NF-κBp65 and RAGE protein was detected by IHC.The expression levels of HMGB1,NF-κBp65,RAGE,TNF-αand IL-1βwere detected by WB.Result:HE staining showed that the structure of the liver in the model group was disordered,the liver cells showed swelling and fusion,the number of inflammatory cells increased and accompanied by punctate necrosis,while the above pathological changes in each treatment group of Yigan capsule were significantly improved.The contents of ALT,AST,ALP,γ-GT and TBIL in the model group were higher than those in the blank group(P<0.05).The contents of ALT,AST,ALP,γ-GT and TBIL in each treatment group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of TNF-αand IL-1βin the model group were increased(P<0.05),and the expression levels of HMGB1,NF-κBp65 and RAGE were increased(P<0.05).Compared with the model group,the expression levels of TNF-αand IL-1βin each treatment group of Yigan capsule decreased(P<0.05),and the expression of HMGB1,NF-κBp65 and RAGE decreased(P<0.05).Conclusion:Yigan capsule may inhibit the secretion of inflammatory factors through HMGB1/RAGE/NF-κBp65 signaling pathway,thus protecting ATB-DILI.

Contribution of gut microbiota to drug-induced liver injury

Drug-induced liver injury(DILI)is caused by various drugs with complex pathogenesis,and diverse clinical and pathological phenotypes.Drugs damage the liver directly through drug hepatotoxicity,or indirectly through drug-mediated oxidative stress,immune injury and inflammatory insult,which eventually lead to hepatocyte necrosis.Recent studies have found that the composition,relative content and distribution of gut microbiota in patients and animal models of DILI have changed significantly.It has been confirmed that gut microbial dysbiosis brings about intestinal barrier destruction and microorganisms translocation,and the alteration of microbial metabolites may cause or aggravate DILI.In addition,antibiotics,probiotics,and fecal microbiota transplantation are all emerging as prospective therapeutic methods for DILI by regulating the gut microbiota.In this review,we discussed how the altered gut microbiota participates in DILI.

Expert Consensus on the Diagnosis and Treatment of Anticancer Drug-Induced Interstitial Lung Disease

Drug-induced interstitial lung disease(DILD)is the most common pulmonary adverse event of anticancer drugs.In recent years,the incidence of anticancer DILD has gradually increased with the rapid development of novel anticancer agents.Due to the diverse clinical manifestations and the lack of specific diagnostic criteria,DILD is difficult to diagnose and may even become fatal if not treated properly.Herein,a multidisciplinary group of experts from oncology,respiratory,imaging,pharmacology,pathology,and radiology departments in China has reached the“expert consensus on the diagnosis and treatment of anticancer DILD”after several rounds of a comprehensive investigation.This consensus aims to improve the awareness of clinicians and provide recommendations for the early screening,diagnosis,and treatment of anticancer DILD.This consensus also emphasizes the importance of multidisciplinary collaboration while managing DILD.

Research progress on chemical constituents and pharmacological activities of Amomum longiligulare T.L.Wu

In order to develop and utilize the tropical medicinal resource Amomum(A.)longiligulare T.L.Wu more reasonably and effectively,this paper summarizes the research progress in chemical constituents and pharmacological activities of A.longiligulare by consulting the literatures,so as to provide a certain theoretical basis for exploring its material basis.The chemical constituents of A.longiligulare mainly include volatile oil,diphenylheptane and flavonoids,which have good efficacy in anti-peptic ulcer,as well as antioxidant,analgesic and other pharmacological activities.This paper briefly discusses the reasons for the differences in the composition of volatile oil studied by different scholars.By summarizing its pharmacological activities,it is found that its various pharmacological activities may be the basis of its anti-peptic ulcer.

Research Progress on Chemical Constituents and Pharmacological Effects of Celosia L.

Celosia L. is richly distributed in China and there are about 60 species in the world. The chemical constituents of Celosia L. include flavonoids, triterpenoid saponins, steroids, organic acids, and cyclic peptides. Which have a variety of effects such as antimicrobial, hepatoprotective and antitumour. To provide a scientific foundation for the subsequent phase of research and development for Celosia L., 30 years of pertinent global literature is summarized, analyzed, and categorized. An overview of 75 chemical constituents, pharmacological activities, and clinical applications is provided.

Phoenix dactylifera:traditional uses,chemical constituents,nutritional benefit and therapeutic effects

Phoenix dactylifera(Fam:Arecaceae)is originated from the Mesopotamia.The date fruit,was eaten fresh,in various processed forms and dried.The fruits were used traditionally as general tonic,for the treatment of liver diseases,memory disturbances,fever,inflammation,paralysis,loss of consciousness,nervous disorders and consumed by pregnant women before and after delivery.However,all parts of the plant were used for some purpose.Dates fruits were considered a complete diet and a very important item of food,with plenty of vitamins and minerals.It contained a wide range of secondary metabolites.It possessed many pharmacological effects included anticancer,antidiabetic,anti-inflammatory,antimicrobial,antiparasitic,antioxidant,anti-toxin,cardiovascular,hypolipidemic,gastrointestinal,immunomodullatory,neural,hepato and reno-protective,reproductive and wound healing effects.This review highlighted the chemical constituents,nutritional and pharmacological effects of Phoenix dactylifera.

Drug-induced entero-colitis due to interleukin-17 inhibitor use;capsule endoscopic findings and pathological characteristics:A case report

BACKGROUND Interleukin-17(IL-17)inhibitors are known to cause exacerbation or new onset of inflammatory bowel disease upon administration.However,few reports have described characteristic endoscopic and histopathologic findings,and no small intestinal lesions have been reported so far.CASE SUMMARY A woman in her 60s with psoriasis was administered ixekizumab(IXE),an anti-IL-17A antibody,for the treatment of psoriasis.Twenty months after commencing treatment,the patient visited our hospital because of persistent diarrhea.Blood tests performed at the time of the visit revealed severe inflammation,and colonoscopy revealed multiple round ulcers throughout the colon.A tissue biopsy of the ulcer revealed infiltration of inflammatory cells and granuloma-like findings in the submucosal layer.Capsule endoscopy revealed multiple jejunal erosions.After the withdrawal of IXE,the symptoms gradually improved,and ulcer reduction and scarring of the colon were endoscopically confirmed.CONCLUSION To the best of our knowledge,17 reports have documented IL-17 inhibitorinduced entero-colitis with endoscopic images,endoscopic findings,and pathological characteristics,including the present case.Nine of these cases showed diffuse loss of vascular pattern,coarse mucosa/ulcer formation in the left colon,and endoscopic findings similar to those of ulcerative colitis.In the remaining eight cases,discontinuous erosions and ulcerations from the terminal ileum to the rectum were seen,with endoscopic findings similar to those of Crohn’s disease.In this case,the findings were confirmed by capsule endoscopy,which has not been previously reported.

Study on the chemical constituents and antitumor activity of galangal

Objective:The main chemical components of galangal(Alpinia officinarum Hance)are flavonoids and diarylheptanes.In the previous work,the total heptane and total flavonoid components of galangal were isolated.In this paper,the two components were separated.The monomeric compound was purified and its cytotoxic activity was determined.Methods:Silica gel column chromatography,ODS column chromatography,preparative thin layer chromatography,preparative and semi-preparative HPLC methods were used to separate and purify the total heptane components and total flavonoid components of galangal.Structures of compounds were identified by 1H-NMR,13C-NMR modern spectroscopic techniques combined with literature.The cytotoxic activity of the isolated compounds against MDA-MB-231(breast cancer),HepG-2(liver cancer)and MKN-45(gastric cancer)cells was tested by CCK-8 method.Results:Six compounds were isolated from the total heptane fractions of galangal,and three compounds were isolated from the total flavonoids of galangal.Their structures were identified as:5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenylheptan-3-one(1),(E)-7-(4-hydr-oxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one(2),5-hydroxy-1,7-diphenylheptan-3-one(3)7-(4-hydroxyphenyl)-5-methoxy-1-phenylheptan-3-one(4),(E)-7-(4-hydroxyphenyl)-1-phenylhept-4-en-3-one(5),(E)-1,7-diphenylhept-4-en-3-one(6),pinocembrin(7),galangin(8),3-O-methylgalangin(9).Conclusion:Compounds 1-6 were isolated from the total heptane components of galangal,and compounds 7-9 were isolated from the total flavonoids of galangal.The results of CCK-8 showed that compounds 2,3,5,6,7 and 8 had weak antitumor activity.

Chemical Constituents from Ethnic Medicine Laportea bulbifera

[Objectives]This study was conducted to study the chemical constituents from Laportea bulbifera. [Methods] The 60% ethanol extract from L. bulbifera was isolated and purified by silica, Sephadex LH-20, ODS, semi-preparative HPLC and recrystallization. Their chemical structures were elucidated by physicochemical properties and spectroscopic methods. [Results] These compounds were determined as kaempferol-3-O-α-L-(3-O-acetyl)-rhamnoside-7-O-α-L-rhamnoside(1), sutchuenoside A(2), kaempferol-3-O-[β-D-glucopyranosyl-(1→3)]-α-L-(4-O-acetyl)-rhamnopyranoside-7-O-α-L-rhamnopyranoside(3). Compounds 1-3 are isolated from genus Laportea for the first time. Compound 3 is a new compound. [Conclusions] This study lays a foundation for improving the quality standard of L. bulbifera and the development and utilization of its resources.

Contributions of annual and semiannual tidal constituents to chart datum in the China seas and adjacent waters

Global uniform chart datum(CD)surface construction is the basic upon which to realize various vertical datums transformation,and is of great importance for geospatial data expression under the same vertical datum.Generally,the CD level is computed by developing the function between tidal constituents’harmonic constants and time,i.e.,the lowest astronomical tide is taken as the lowest predicted tide level by adopting the major constituents over a 19-a period.The CD surface prescribed in China is the theoretical lowest tide(TLT)and is calculated using 13 tidal constituents,i.e.,short-period(Q_(1),O_(1),P_(1),K_(1),N_(2),M_(2),S_(2),K_(2),M_(4),MS_(4)and M_(6))and long-period(Sa and Ssa)tidal constituents.Although the accuracy in determining short-period tidal constituents has improved gradually,the long-period tide has not been studied thoroughly owing to nonstationary and temporal variations.Previous studies have intended to evaluate the effect of Sa and Ssa tides in the determination of the TLT level for the purpose of determining a more accurate CD surface for the China seas and adjacent waters.Here,the parameters of long-period tidal correction and long-period tidal correction rate were treated as the effect of both Sa and Ssa on the TLT,and the TOPEX/Poseidon and Jason series satellite altimetry data ranged from October 1992 to April 2022 were adopted to analyze the contribution of long-period tidal constituents.Results showed that the average long-period correction value is 10.10 cm(range from 8.57 cm to 14.98 cm),and that the average long-period tidal contribution rate is 14.56%(range from 9.09%to 23.97%)in the China seas and adjacent waters.Finally,data from 82 tide gauge station with at least a 1-a record of hourly observations were compared with satellite-derived result.We concluded that the long-period tidal contribution should not be neglected in TLT construction.Furthermore,to reduce tidal datum uncertainty,accurate extraction of long-period tidal constituents should receive closer attentions.

Research progress on effective chemical constituents of Sijunzi Decoction and mechanism of prevention and treatment of digestive system diseases

Sijunzi Decoction,as one of the classic Chinese traditional prescriptions,has been used clinically by major physicians since the Song Dynasty.This article reviewed and sorted out the literature on the effective chemistry of Sijunzi Decoction and the mechanism of its prevention and treatment of digestive system diseases.At present,its effective chemical components are derived from the saponins and flavonoids in ginseng and licorice,and are effective for gastrointestinal mucosal injury diseases and malignant digestive system.Digestive system diseases such as tumors,functional gastrointestinal diseases,non-alcoholic fatty liver,acute liver injury,and liver failure show a multi-path,multi-target effect mechanism.This article reviews the effective chemical components and research of Sijunzi Decoction and the related mechanisms of prevention and treatment of digestive system diseases,and provides valuable clues for the follow-up research of Sijunzi Decoction.

Chemical constituents and pharmacological activities of Salvia miltiorrhiza

Salvia miltiorrhiza Bunge(S.miltiorrhiza),a perennial plant of the genus Salvia,is widely used in traditional folklore medicine.Previous chemical research on this plant contains diterpenoid quinones,phenolic acids,polysaccharides and other compounds.The pharmacological investigation of S.miltiorrhiza has shown that it has various pharmacological activities,such as cardiovascular system protection,anti-inflammatory,anti-oxidant,anti-tumor,liver protection,and neuroprotection activities.This research tends to give an overview of the main chemical constituents and pharmacological effects of S.miltiorrhiza,aiming to reveal its potential value and provide reference for its further development.

Study on Chemical Constituents from Phellodendron chinense

[Objectives]To isolate and identify chemical constituents from Phellodendron chinense.[Methods]Compounds were isolated by silica gel,Sephadex LH-20,and ODS column chromatography,and their structures were determined by means of the spectral analysis and physicochemical properties.[Results]Eleven compounds were isolated and identified as berberine(1),obaculactone(2),shihulimonin A(3),N-p-coumaroyltyramine(4),1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxy-propyl)-2-methoxyphenoxy]-propane-1,3-diol(5),phellodendrine(6),magnoflorine(7),palmatine(8),jatrorrhizine(9),columbamine(10),and obacunone(11).[Conclusions]Compounds 3 and 5 were isolated from Phellodendron for the first time,and compound 4 was isolated from this plant for the first time.

Improvement of (Eruca sativa Mill) yield, oil, chemical constituents and antioxidant activity utilizing a by-product of yeast production (CMS) with zinc and boron under salinity stress conditions

The impact of low-quality irrigation water on plant development has garnered significant attention from researchers. In light of this, two field experiments were conducted to evaluate the performance, yield, oil production and composition, as well as active constituents of Rocket(Eruca sativa Mill) cultivated in calcareous soil under saline water irrigation. Foliar sprays containing condensed molasses soluble(CMS), zinc(Zn), and boron(B) alone or in combination were used for irrigation. The data obtained from measuring various parameters of Rocket following foliar spraying with CMS, Zn, B or their combinations demonstrated that most treatments resulted in a significant increase in these parameters. The highest values for most measurements were observed when foliar application included all three components(CMS + Zn + B), resulting in a seed yield of 184.6 g/m2and an oil content of 675.3 kg/ha. Compared to the control group, the macronutrient content of N, P, K, Mg, and Ca increased by 34.4%, 56%, 42%, 45%, and 39% respectively in the seeds treated with these components.Furthermore, carbohydrates, proteins, phenolics flavonoids, and antioxidants showed increases of 24%, 34%,21%, 43%, and 28% respectively compared to the control group. Gas-liquid chromatography analysis identified ten components present in the seed oil characterized by higher unsaturated fatty acids ranging from 81.28% to92.28% and lower saturated fatty acids ranging from 6.72% to 8.21%. Therefore, foliar spray application including CMS, zinc, and boron can help alleviate salinity effects on Rocket plants grown under saline water irrigation conditions while improving growth, yield, oil production, and nutritional content such as total carbohydrates, proteins, and macronutrients levels.

The main chemical constituents from Piper amalago: A review of its phytochemistry

Piper amalago(P.amalago)is a traditional medicine in Brazil for the treatment of leishmanial.Owing to its rare occurrence and potent pharmacological activities,efforts have been devoted to the identification of its diverse constituents,especially terpenoids.Researchers have found that the major constituents of P.amalago were amides,monoterpenes,norisoprenoids,sesquiterpenes,aliphatic hydrocarbons and aromatic hydrocarbons.The amides show anxiolytic,anti-inflammatory,antileishmanial and antinociceptive activity.This review summarizes the research progress of the structural diversity and pharmacological activities of P.amalago.

COVID-19-related liver injury:Focus on genetic and drug-induced perspectives

BACKGROUND Empirical use of potentially hepatotoxic drugs in the management of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection is considered as one of the major etiopathogenetic factors for liver injury.Recent evidence has shown that an underlying genetic factor may also occur.Hence,it is important to understand the host genetics and iatrogenic-based mechanisms for liver dysfunction to make timely remedial measures.AIM To investigate drug-induced and genetic perspectives for the development of coronavirus disease 2019(COVID-19)-related liver injury.METHODS Reference Citation Analysis,PubMed,Google Scholar and China National Knowledge Infrastructure were searched by employing the relevant MeSH keywords and pertaining data of the duration,site and type of study,sample size with any subgroups and drug-induced liver injury outcome.Genetic aspects were extracted from the most current pertinent publications.RESULTS In all studies,the hepatic specific aminotransferase and other biochemical indices were more than their prescribed upper normal limit in COVID-19 patients and were found to be significantly related with the gravity of disease,hospital stay,number of COVID-19 treatment drugs and worse clinical outcomes.In addition,membrane bound O-acyltransferase domain containing 7 rs641738,rs11385942 G>GA at chromosome 3 gene cluster and rs657152 C>A at ABO blood locus was significantly associated with severity of livery injury in admitted SARS-CoV-2 patients.CONCLUSION Hepatic dysfunction in SARS-CoV-2 infection could be the result of individual drugs or due to drug-drug interactions and may be in a subset of patients with a geneticpropensity. Thus, serial estimation of hepatic indices in hospitalized SARS-CoV-2 patients shouldbe done to make timely corrective actions for iatrogenic causes to avoid clinical deterioration.Additional molecular and translational research is warranted in this regard.

Drug-induced sarcoidosis-like reaction three months after BNT162b2 mRNA COVID-19 vaccination:A case report and review of literature

BACKGROUND A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment(S)5.CASE SUMMARY Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(EOB-MRI)revealed the nodule in S5 with a defect at the hepatobiliary phase,hyperintensity on diffusion weighted imaging(DWI)and hypointensity on apparent diffusion coefficient(ADC)map.Contrast-enhanced computed tomography revealed hypervascularity at the early phase,and delayed contrast-enhancement was observed at the late phase.Contrast-enhanced ultrasound(US)revealed incomplete defect at the late vascular phase.Inflammatory liver tumor,lymphoproliferative disease,intrahepatic cholangiocarcinoma(small duct type)and bile duct adenoma were suspected through the imaging studies.US guided biopsy,however,showed a noncaseating hepatic sarcoid-like epithelioid granuloma(HSEG),and histopathological analysis disclosed spindle shaped epithelioid cells harboring Langhans-type multinucleated giant cells.One month after admission,EOB-MRI signaled the disappearance of the defect at the hepatobiliary phase,of hyperintensity on DWI,of hypointensity on ADC map,and no stain at the early phase.CONCLUSION That the patient had received BNT162b2 messenger RNA(mRNA)coronavirus disease 2019 vaccination 3 mo before the occurrence of HSEG,and that its disappearance was confirmed 4 mo after mRNA vaccination suggested that the drug-induced sarcoidosis-like reaction(DISR)might be induced by the mRNA vaccination.Fortunately,rechallenge of drug-induced DISR with the third mRNA vaccination was not confirmed.

Chemical Constituents from Roots of Semiaquilegia adoxoides

Semiaquilegia adoxoides ( DC. ) Makino ( Chinese name ''Tian-Kui-Zi'' ) , theonly species of genus Semiaquilegia, belongs to the Ranunculaceae family. As a perennial herbaceousplant, both the aerial parts and the roots are used in traditional Chinese medicine for differentmedications. The roots are often used to treat inflammation, snake bite, bruises and injuries,tonsillitis, mastitis, scrofula, and cancer for their antibacterial, anti-inflammatory, andantineoplastic activities. The aerial parts are used for the treatment of mastitis, bruises, andheart diseases, such as endomyocarditis. The medicinal usage of this plant prompted us toinvestigate its chemical constituents. As a result, nine compounds 1-9 ( see Figure 1) were isolatedfrom the roots of S. adoxoides. Among them, compounds 1-7 and 9 were isolated from the genusSemiaquilegia for the first time.