Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1

Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron- and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species (ROS) and inducing ferroptosis in activated hepatic stellate cells (HSCs). By using activity-based protein profiling (ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay (CETSA), we show that celastrol directly binds to peroxiredoxins (PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6, through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1 (HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2, PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.

Impairment of the autophagy-lysosomal pathway in Alzheimer's diseases: Pathogenic mechanisms and therapeutic potential

Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by memory loss and cognitive dysfunction. The accumulation of misfolded protein aggregates including amyloid beta (Aβ) peptides and microtubule associated protein tau (MAPT/tau) in neuronal cells are hallmarks of AD. So far, the exact underlying mechanisms for the aetiologies of AD have not been fully understood and the effective treatment for AD is limited. Autophagy is an evolutionarily conserved cellular catabolic process by which damaged cellular organelles and protein aggregates are degraded via lysosomes. Recently, there is accumulating evidence linking the impairment of the autophagy-lysosomal pathway with AD pathogenesis. Interestingly, the enhancement of autophagy to remove protein aggregates has been proposed as a promising therapeutic strategy for AD. Here, we first summarize the recent genetic, pathological and experimental studies regarding the impairment of the autophagy-lysosomal pathway in AD. We then describe the interplay between the autophagy-lysosomal pathway and two pathological proteins, Aβ and MAPT/tau, in AD. Finally, we discuss potential therapeutic strategies and small molecules that target the autophagy-lysosomal pathway for AD treatment both in animal models and in clinical trials. Overall, this article highlights the pivotal functions of the autophagy-lysosomal pathway in AD pathogenesis and potential druggable targets in the autophagy-lysosomal pathway for AD treatment.

E.faecium QH06 alleviates TNBS-induced colonic mucosal injury in rats / 南方医科大学学报

OBJECTIVE@#To investigate the effect of Enterococcus faecium QH06 on TNBS-induced ulcerative colitis (UC) in rats and explore the mechanisms in light of intestinal flora and intestinal immunity.@*METHODS@#Thirty-six male Wistar rats were randomized equally into control group, UC model group, and E.faecium QH06 intervention group. The rats in the latter two groups were subjected to colonic enema with 5% TNBS/ethanol to induce UC, followed by treatment with intragastric administration of distilled water or E.faecium QH06 at the dose of 0.21 g/kg. After 14 days of treatment, the rats were examined for colon pathologies with HE staining. The mRNA and protein expression levels of IL-4, IL-10, IL-12, and IFN-γ in the colon tissues were detected using RT-qPCR and ELISA, and the expression of TLR2 protein was detected with immunohistochemistry and ELISA. Illumina Miseq platform was used for sequencing analysis of the intestinal flora of the rats with bioinformatics analysis. The correlations of the parameters of the intestinal flora with the expression levels of TLR2 and cytokines were analyzed.@*RESULTS@#The rats with TNBS- induced UC showed obvious weight loss (P < 0.01) and severe colon tissue injury with high pathological scores (P < 0.01). The protein expression levels of IFN-γ, IL-12, and TLR2 (P < 0.01) and the mRNA expression levels of IFN-γ, IL-12 and IL-10 (P < 0.05) were significantly increased in the colon tissues of the rats with UC. Illumina Miseq sequence analysis showed that in UC rats, the Shannon index (P < 0.05) ACE (P < 0.01)and Chao (P < 0.05) index for the diversity of intestinal flora both decreased with a significantly increased abundance of Enterobacteriaceae (P < 0.01) and a lowered abundance of Burkholderiaceae (P < 0.05). Compared with the UC rats, the rats treated with E. faecium QH06 showed obvious body weight gain (P < 0.05), lessened colon injuries, lowered pathological score of the colon tissue (P < 0.05), decreased protein expressions of IFN- γ, IL- 12, and TLR2 and mRNA expressions of IFN- γ and IL-12 (P < 0.01 or 0.05), and increased protein expressions of IL- 4 (P < 0.05). The Shannon index ACE (P < 0.05) and Chao (P < 0.05) index of intestinal microflora were significantly increased, the abundance of Enterobacteriaceae was lowered and that of Burkholderiaceae and Rikenellaceae was increased in E.faecium QH06- treated rats (P < 0.01 or 0.05). Correlation analysis showed that IFN-γ was positively correlated with the abundance of Enterobacteriaceae, and IFN-γ was negatively correlated with the abundance of Prevotellaceae, Desulfovibrionaceae, norank_o_Mollicutes_RF39 and Clostridiales_vadinBB60_group; TLR2 was negatively correlated with Clostridiales_vadinBB60_group, norank_o_Mollicutes_RF39 and Prevotellaceae.@*CONCLUSION@#E.faecium QH06 can alleviate TNBS-induced colonic mucosal injury in rats, and its effect is mediated possibly by increasing the abundance of SCFA-producing bacteria such as Prevotellaceae and inhibiting abnormal immune responses mediated by TLR2.

Characterization of the first mitogenomes of the smallest fish in the world, Paedocypris progenetica, from peat swamp of Peninsular Malaysia, Selangor, and Perak

The two complete mitochondrial genomes (mitogenomes) of Paedocypris progenetica, the smallest fish in the world which belonged to the Cyprinidae family, were sequenced and assembled. The circular DNA molecules of mitogenomes P1-P. progenetica and S3-P. progenetica were 16,827 and 16,616 bp in length, respectively, and encoded 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and one control region. The gene arrangements of P. progenetica were identical to those of other Paedocypris species. BLAST and phylogenetic analyses revealed variations in the mitogenome sequences of two Paedocypris species from Perak and Selangor. The circular DNA molecule of P. progenetica yield a standard vertebrate gene arrangement and an overall nucleotide composition of A 33.0%, T 27.2%, C 23.5%, and G 15.5%. The overall AT content of this species was consistent with that of other species in other genera. The negative GC-skew and positive AT-skew of the control region in P. progenetica indicated rich genetic variability and AT nucleotide bias, respectively. The results of this study provide genomic variation information and enhance the understanding of the mitogenome of P. progenetica. They could later deliver highly valuable new insight into data for phylogenetic analysis and population genetics.

Synergistic effects of autophagy/mitophagy inhibitors and magnolol promote apoptosis and antitumor efficacy

Mitochondria as a signaling platform play crucial roles in deciding cell fate. Many classic anticancer agents are known to trigger cell death through induction of mitochondrial damage. Mitophagy, one selective autophagy, is the key mitochondrial quality control that effectively removes damaged mitochondria. However, the precise roles of mitophagy in tumorigenesis and anticancer agent treatment remain largely unclear. Here, we examined the functional implication of mitophagy in the anticancer properties of magnolol, a natural product isolated from herbal

Role of metabolic detoxification enzyme activity and knockdown resistance gene mutations in resistance of aedes albopictus to pyrethroid insecticides / 第二军医大学学报

[Abstract] Objective To explore the role of metabolic detoxification enzyme activity and knockdown resistance (kdr) gene mutations in the pyrethroid resistance of Aedes (Ae.) albopictus. Methods From Aug. to Sep. in 2017, the Ae. albopictus samples were collected in Qianfoshan Park, Jinan City, Shandong Province (JN), Shangmaojiabu, Hangzhou City, Zhejiang Province (HZ), Baoshan Sixth Village, Baoshan District, Shanghai (BS), Gongqing Forest Park, Yangpu District, Shanghai (YP), and Meilan District Residential Area, Haikou City, Hainan Province (HK). The above five field populations were all resistant to insecticide. The activities of metabolic detoxification enzymes (glutathione-S transferase [GST] and mixed function oxidase [MFO]) were detected and compared with the Ae. albopictus susceptible strain (JS). The contribution rates of activity changes of GST and MFO and kdr mutations (I1532 and F1534) in the resistance formation were analyzed by the classification and regression trees (CART). Results The baseline enzyme activities of GST and MFO in Ae. albopictus JS were both significantly higher than those in the BS and HK resistant populations (both P0.01). There were no significant difference in the activities of GST and MFO between the BS population unexposed and exposed to deltamethrin (P0.05). After exposure to permethrin of BS population, the activities of GST and MFO were significantly increased (P0.05, P0.01). After exposure to deltamethrin, the GST activity was not significantly changed in the HK population (P0.05), while the MFO activity was significantly increased (P0.01). However, after exposure to permethrin in the HK population, there were no significant changes in the GST and MFO activities (both P0.05). In the 5 field resistant populations exposed to deltamethrin and permethrin, the changes of GST and MFO activities were irregular compared with baseline of Ae. albopictus JS strain. CART analysis showed that in the resistance formation of Ae. albopictus against deltamethrin, the contribution rates of GST activity and kdr F1534 mutation were the greatest, followed by MFO activity, and the kdr I1532 mutation was the smallest. In the resistance formation of Ae. albopictus against permethrin, the kdr F1534 mutation had the highest contribution rate, followed by the GST and MFO activities, and the kdr I1532 mutation had no contribution. Conclusion The activity levels of metabolic detoxification enzymes (GST and MFO) are not suitable as single markers for detecting the resistance of Ae. albopictus to pyrethroids. The activity changes of metabolic detoxification enzymes and kdr mutations may be two synergistic mechanisms in the resistance formation of Ae. albopictus to pyrethroid insecticides.

Apoptosis-Inducing Effect of Ginsenoside Rh2 on Human Acute T Lymphoblastic Leukemia Jurkat Cells and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the apoptosis-inducing effect of Ginsenoside (Rh2) on human acute T lymphoblastic leukemia Jurkat cells and it mechamism.@*METHODS@#The effects of different concentration of Rh2 (0, 10 , 20, 40 and 80 µg/ml) on the proliferation activity of Jurkat cells were detected by methyl thiazolyl tetrazolium (MTT) method, and the semi-inhibitory concentration (IC) of Rh2 on Jurkat cells at 48 h was calculated. Microscopy and Hoechst 33258 fluorescence staining were used to observe the apoptosis of Jurkat cells treated with IC Rh2 for 48 h. And then, the cell experiment was divided into 4 groups: control, Rh2 (IC), PI3K inhibitor LY294002 (50 µmol/l) and Rh2 (IC) + LY294002 (50 µmol/l). After synchronous culture for 48 h, the apoptosis and cycle changes of Jurkat cells were detected by using PI single staining and Annexin V-FITC/PI double staining, respectively. Western blot was used to detect the expression level of apoptosis-related protein BAX, BCL-2, Cleaved-Caspasase 3, cell cycle-related protein Cyclin D1 and PI3K/AKT signaling pathway-related protein AKT and p-AKT.@*RESULTS@#Rh2 (10-80 µg/ml) inhibited the Jurkat cell proliferation in a dose-time dependent manner (r = 0.999, P＜0.01; r = 0.991; P＞0.05), accompanied by obvious morphological changes of apoptosis cells. Flow cytometry showed that compared with the control group, the cell apoptosis rate in Rh2 or LY294002 group significantly increased, and the cell cycle was mostly blocked in G0/G1 phase. However, the cell apoptosis and cell cycle block in Rh2+LY294002 group were more significant than that in Rh2 and LY294002 group. Western blot showed that compared with the control group, Rh2 significantly promoted the expression of BAX and Cleaved-Caspasase 3, inhibited the expression of BCL-2, Cyclin D1 and p-AKT, furthermore LY294002 significantly promoted this effect.@*CONCLUSION@#Rh2 can induce the apoptosis of Jurkat cells in time-dose dependent manner, moreover, Rh2 also can result in an obvious block of Jurkat cells at G0/G1, that may be closely related to a series of apoptotic signaling cascades mediated by Rh2 inhibiting PI3K/AKT pathway.

Ethyl acetate extract of Pleione bulbocodioides(Franch.)Rolfe induces apoptosis of human leukemia K562 and HL-60 cells through intrinsic mi-tochondrial apoptosis pathway / 中国病理生理杂志

AIM:To investigate the effects of ethyl acetate(EtOAc)extract of Pleione bulbocodioides (Franch.)Rolfe on proliferation and apoptosis of human leukemia K 562 and HL-60 cells and the possible apoptosis path-way.METHODS:Human leukemia cell lines were treated with EtOAc extract of Pleione bulbocodioides at different con-centrations.XTT method was used to evaluate the viability of K 562 cells and HL-60 cells.The cell growth inhibition was calculated by Trypan blue exclusion test.The percentage of apoptotic cells was determined by flow cytometry,and 4,,6-dia-midino-2-phenylindole(DAPI)was used to observe morphological changes of the cells.The cell cycle was observed by pro-pidium iodide(PI)staining.The protein expression of Bcl-2, Bax, cleaved poly(ADP-ribose)polymerase(PARP), cleaved caspase-3,cytochrome C and apoptosis-inducing factor(AIF)wase determined by Western blot.RESULTS:The cell viability and proliferation were inhibited by EtOAc extract of Pleione bulbocodioides with IC50of(42.14 ±2.54)mg/L for HL-60 cells and(51.28 ±3.12)mg/L for K562 cells at 24 h.The results of Annexin V-FITC/PI and DAPI staining showed that EtOAc extract of Pleione bulbocodioides induced cell apoptosis in a dose-dependent manner.The apoptotic rate was increased compared with control group(P<0.05).The G2phase increased with typical cell apoptosis-induced mor-phological changes.The levels of pro-apoptotic proteins Bax,cleaved PARP and cleaved caspase-3 were increased, while Bcl-2 was down-regulated(P<0.05).Cytochrome C and AIF in cytosol,characteristic proteins of intrinsic mitochondrial apoptosis pathway,also increased with the concentration of EtOAc extract of Pleione bulbocodioides increasing(P<0.05). CONCLUSION:EtOAc extract of Pleione bulbocodioides significantly inhibits cell proliferation and induces cell apoptosis in human leukemia cell lines HL-60 and K562 through intrinsic mitochondrial apoptosis pathway.

Influences of Chinese herbal compound Qinghuayin on serum IL-10 ,NO , GAS and plasma MTL in animal model of chronic atrophic gastritis in rats / 西安交通大学学报(医学版)

Objective To explore the effects of Chinese herbal compound Qinghuayin on the pathological changes of gastric mucosa and interleukin-10 (IL-10) ,nitric oxide (NO) ,gasmn (GAS) and motilin (MTL) in the serum in the animal model of chronic atrophic gastritis (CAG ) in rats .Methods We divided 53 Wistar rats randomly into blank control group (n=8) and CAG model group (n=45) ,and the animal model of CAG in rats was replicated by combination of disease and syndrome .After confirming the sampled rat model was successful built , the other 40 CAG rats in CAG model group were divided into model group ,vitacoenzyme tablet group ,low-dosage TMC group ,medium-dosage TMC group ,and high-dosage TMC group (each group n=8) .With the corresponding drug intervention to different rats for 30 days , the rats were executed . Then their blood was drawn from the abdominal aorta and the gastric tissue was taken to analyze the changes of serum IL-10 ,NO ,GAS and MTL concentrations and gastric mucosa pathology . Results Compared with blank control group , model group had various degrees of gastric mucosa atrophy ; decreased concentrations of serum IL-10 and GAS ; increased NO and MTL ( P<0 .01 ) .Compared with model group,Qinghuayin could improve gastric mucosa pathology in different degrees and increase the concentrations of IL-10 and GAS . Decrease the concentrations of NO and MTL( P<0 .05 or P<0 .01 ) . What's more. The curative effect in high-dosage TMC group was better( P<0. 01 ). Conclusion Chinese herbal compound Qinghuayin can effectively regulate the lopsided expressions of serum IL-10 . NO .GAS and MTL and reverse the pathological and histological changes in the gastric mucosa of CAG rats .

Association between platelet-activating factor acetylhydrolase gene polymorphisms and gastrointestinal bleeding in children with Henoch-Schönlein purpura / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the association between the single nucleotide polymorphisms (SNPs) of the ninth exon Val279Phe of platelet-activating factor acetylhydrolase (PAF-AH) gene and gastrointestinal bleeding in children with Henoch-Schönlein purpura (HSP).</p><p><b>METHODS</b>A total 516 children with HSP were enrolled, among whom 182 had gastrointestinal bleeding and 334 had no gastrointestinal bleeding. PCR was used to investigate the distribution of genotypes and alleles in the SNPs of Val97Phe. The plasma PAF-AH activity was measured, as well as the levels of platelet-activating factor (PAF), granular membrane protein-140 (GMP-140), β-thromboglobulin (β-TG), and platelet factor 4 (PF4).</p><p><b>RESULTS</b>The Val279Phe genotype and allele frequencies were in Hardy-Weinberg equilibrium, and the homozygous genotype TT and heterozygotes accounted for 0.97% and 6.05% respectively. The gastrointestinal bleeding group had a significantly higher allele frequency than the control group (5.22% vs 3.33%; P<0.01). The HSP patients with GG genotype in the gastrointestinal bleeding group had significantly higher levels of plasma PAF and GMP-140 than those in the non-gastrointestinal bleeding group (P<0.05), while the non-gastrointestinal bleeding group had a significantly higher PAF-AH activity than the gastrointestinal bleeding group (P<0.05). There were no significant differences in β-TG and PF4 between the two groups (P>0.05).</p><p><b>CONCLUSIONS</b>Val279Phe gene polymorphisms in PAF-AH are associated with PAF-AH activity and PAF and GMP-140 levels and may be a risk factor for HSP with gastrointestinal bleeding.</p>

Analysis on the Countermeasures and the Investigation of the Current Situation of Medical Students'Humanistic Quality / 医学信息学杂志

The paper analyzes the current problems of medical students'humanistic quality and the causes,points out the necessity of strengthening the humanistic quality of medical students,and puts forward the countermeasures to be taken by libraries of medical colleges in the humanistic quality education for college students,including strengthening the construction of medical humanistic resources,doing well of medical humanistic reading guide and entrance education for new students,and strengthening reading promotion activities,etc.

Sexual satisfaction and its associated factors among individuals with hearing disability / 中华男科学杂志

<p><b>Objective</b>To investigate sexual satisfaction (SS) and the factors associated with decreased SS among individuals with hearing disability.</p><p><b>METHODS</b>We conducted an investigation on SS among 439 individuals (268 males and 171 females, aged ≥18 yr) with hearing disability using a general information questionnaire, Center for Epidemiologic Studies Depression Scale, Social Support Rating Scale, and a self-report on SS. We identified the factors of decreased SS by multivariate ordinal logistic regression analysis.</p><p><b>RESULTS</b>Totally 76 (17.3%) of the hearing-disability individuals investigated were dissatisfied with their sexual life. SS reduction was significantly correlated with the status of being single (OR=1.72), grade-1 or -2 disability (OR=1.78), physical diseases (OR=2.46), depression (OR=6.61), or inadequate subjective social support (OR=3.28).</p><p><b>CONCLUSIONS</b>SS of hearing-disability persons is relatively low, which can be improved by treating physical diseases, promoting mental health, and providing psycho-social support.</p>

Single nucleotide polymorphism of CYP3A4 intron 2 and its influence on CYP3A4 mRNA expression and liver enzymatic activity in human liver / 华中科技大学学报（医学）（英德文版）

In adult liver, CYP3A4 plays an important role in the metabolism of a wide range of endogenous and exogenous compounds. To investigate whether there is a single nucleotide polymorphism (SNP) of CYP3A4 intron 2 in the liver and its effects on the mRNA expression and enzymatic activity of CYP3A4, genomic DNA was extracted from 96 liver tissue samples obtained from patients who had undergone liver surgery. An SNP of CYP3A4 intron 2 was identified by polymerase chain reaction (PCR)-single-strand confirmation polymorphism and DNA sequencing. The mRNA expression of CYP3A4 was determined by the fluorescence quantitative PCR technique. The enzymatic activity of CYP3A4 was measured using erythromycin and testosterone as probe substrates. Twelve patients were found to have the SNP/T4127G CYP3A4 within intron 2. The mRNA levels of CYP3A4 in wild-type and SNP/T4127G samples were 2.62±1.09 and 2.79±1.63, respectively (P>0.05). Erythromycin N-demethylase activity in wild-type and SNP/T4127G samples were 121.2±32.8 and 124.7±61.6 nmol·mg(-1)·min(-1), respectively (P>0.05). The activity of testosterone 6β-hydroxylase was significantly different between wild-type (648±173 pmol·mg(-1)·min(-1)) and SNP/T4127G samples (540±196 pmol·mg(-1)·min(-1); P<0.05). In conclusion, the SNP/T4127G of CYP3A4 intron 2 exists in the liver. This SNP does not affect the mRNA expression of CYP3A4 but significantly decreases the hepatic microsomal testosterone 6β-hydroxylase activity of CYP3A4. Furthermore, this study indicates that the appropriate selection of probe substrates is very important in studying the relationship between the genotype and phenotype of CYP3A4.

Femoral offset and its relationship to femoral neck-shaft angle and torsion angle / Desplazamiento femoral y su relación con el ángulo cuello-diáfisis femoral y el ángulo de torsión

The aims to study the femoral offset and its relationship to femoral neck-shaft angle and torsion angle. One hundred paired (50 males and 50 females) Chinese femurs were used to measure the femoral offset, femoral neck-shaft angle and torsion angle. The data were analyzed by SPSS software. Femoral offsets were male right 44.40±4.56 mm, left 42.70±4.95 mm; female right 39.90±6.00 mm, left 38.90±6.18 mm. Femoral torsion angles were male right 6.02±10.85°, left 7.08±9.30°; female right 10.02±11.69, ° left 6.02±10.85°. Neck-shaft angles were male right 131.80±4.36°, left 134.00±4.78°; female right 132.10±5.94°, left 132.80±4.93°. There were no sexual differences in the two femoral angles (P>0.05) while there was a significant sexual difference in the femoral offset (P<0.01). The differences between left and right femoral offset and neck-shaft angle were significant (P<0.01). Clinically, our results indicate that FO could be obtained using the regression equation when the torsion angle and/or neck-shaft angle is measured.

El objetivo fue estudiar el desplazamiento femoral y su relación con el ángulo cuello-diáfisis femoral y el ángulo de torsión. Se utilizaron 100 pares de fémures (50 hombres y 50 mujeres) y se tomaron las medidas del desplazamiento femoral, ángulo cuello-diáfisis femoral y ángulo de torsión. Los datos fueron analizados con el software SPSS. El desplazamiento femoral en los hombres fue 44,40±4,56 mm en el lado derecho y 42,70±4,95 mm en el lado izquierdo, y en las mujeres, fue de 39,90±6,00 mm y 38,90±6,18 mm para el lado derecho e izquierdo, respectivamente. El ángulo de torsión femoral del lado derecho en los hombres fue 6,02±10,85° y 7,08±9,30° del izquierdo; mientras que en las mujeres, fue de 10,02±11,69° y 6,02±10,85° para el lado derecho e izquierdo, respectivamente. Los ángulos cuello-diáfisis fueron 131,80±4,36° en el lado derecho, y 134,00±4,78° en el izquierdo, para los hombres, mientras que en las mujeres fueron de 132,10±5,94° en el lado derecho y 132,80±4,93° en el izquierdo. No hubo diferencias según sexo en los dos ángulos femorales (P>0,05), mientras que si hubo una diferencia significativa en el desplazamiento femoral (P<0,01). Las diferencias entre el desplazamiento femoral izquierdo y derecho, y el ángulo cuello-diáfisis fueron significativas (P<0,01). Clínicamente, nuestros resultados indican que el desplazamiento femoral podría obtenerse utilizando la ecuación de regresión cuando se mide el ángulo de torsión o el ángulo cuello-diáfisis.

Effects of Kaixin Jieyu Decoction () on behavior, monoamine neurotransmitter levels, and serotonin receptor subtype expression in the brain of a rat depression model / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine the mechanisms underlying the anti-depressant effects of Kaixin Jieyu Decoction (, KJD) by investigating the effects of KJD on behavior, monoamine neurotransmitter levels, and serotonin (5-HT) receptor subtype expression in the brain in a rat model of depression.</p><p><b>METHODS</b>The rat depression model was established using chronic unpredictable mild stress (CUMS). Forty-eight Sprague Dawley rats were randomly divided into control, depression model (CUMS), CUMS+KJD (7.7 g/kg(-1)·d(-1) of crude drug), and CUMS+fluoxetine (2.4 mg/kg(-1)·d(-1)) groups (n=12 in each group), and the treatments lasted for 21 days. We regularly evaluated body weight, sucrose consumption, and horizontal and vertical activity scores in open-field tests. The content of the monoamine neurotransmitters 5-HT, norepinephrine (NE), and dopamine (DA) and the DA metabolite homovanillic acid in the cerebral cortex, and 5-HT1A and 5-HT2A receptor mRNA in the cerebral cortex and the hippocampus, were determined respectively by high-performance liquid chromatography-coularray electrochemical detector and real-time polymerase chain reaction.</p><p><b>RESULTS</b>Compared with the control group, CUMS rats showed a variety of depression-like behavioral changes, including a significant reduction in body weight, sucrose consumption, and horizontal and vertical activity scores in open-field tests (P<0.05 or P<0.01), and a significant decrease in 5-HT and NE levels and 5-HT2A receptor mRNA expression. In contrast, they showed a significant increase in 5-HT1A receptor mRNA expression in the cerebral cortex. In the hippocampus, 5-HT1A receptor mRNA expression was lower whereas 5-HT2A receptor mRNA expression was higher than in the control group (P<0.05 or P<0.01). Treatment with KJD or fluoxetine partially attenuated these changes (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>KJD could normalize the levels of 5-HT and NE and adjust the balance of 5-HT1A and 5-HT2A receptor expression in rat cerebrum, and this may be one of mechanisms of antidepressant effects of KJD.</p>

CYP450 enzyme inhibition of berberine in pooled human liver microsomes by cocktail probe drugs / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of CYP450 enzyme inhibition of berberine in pooled human liver microsomes by cocktail probe drugs.</p><p><b>METHOD</b>Cocktail probe drugs method has been established, an LC-MS/MS analytical method has been established to determine the five probes of midazolam, phenacetin, dextromethorphan, tolbutamide, chlorzoxazone and the internal standard was benzhydramine to evaluate the effect of CYP450 activity following administration of berberine in pooled human liver microsomes.</p><p><b>RESULT</b>Compared with control group, the pharmacokinetics of midazolam, phenacetin and tolbutamide were no significant differences, but the pharmacokinetics of chlorzoxazone was significantly decreased. There were no significant differences for the pharmacokinetics of dextromethorphan when the concentration of berberine was 50 microg x L(-1). The pharmacokinetics of dextromethorphan was significantly decreased when the concentration of berberine was exceed 200 microg x L(-1).</p><p><b>CONCLUSION</b>Berberine has no influence on the activities of CYP3A4, CYP1A2 and CYP2C19 below 2 000 microg x L(-1), but can inhibit the activity of CYP2E1 and CYP2D6 in concentration-dependent.</p>

Prevalence of celiac disease in children with chronic diarrhea in China / 中华儿科杂志

<p><b>OBJECTIVES</b>To investigate the prevalence of celiac disease in children with chronic diarrhea in China.</p><p><b>METHODS</b>Inpatients of the pediatric hospitals in Shanghai, Jinan, Wuhan and Chengdu who were diagnosed as chronic diarrhea were recruited from Jan. 2005 to Dec. 2008. Their clinical history, physical examination and laboratory data were collected. The SPSS version 11.5 statistical package for Microsoft Windows was used for statistical analysis.</p><p><b>RESULTS</b>Data of 199 patients and finally enrolled 118 hospitalized chronic diarrhea inpatients during the observation period were collected and 14 (12%) of the chronic diarrhea patients were suspected as having celiac disease and in one the diagnosis of celiac disease was confirmed. Gluten-free diet (GFD) treatment was effective. M/F: 12/2, the age ranged from 6 months to 12 years; 43% (6/14) had malnutrition, 29% (4/14) had anemia, villous atrophy was found in 4 patients by endoscopy. Duodenal biopsies revealed stage I in 1, stage II in 2, stage IIIa in 7, stage IIIb in 3 and stage IIIc in 1 patient according to the modified Marsh classification.</p><p><b>CONCLUSION</b>This study was the first time to report the research of celiac disease in children with chronic diarrhea in China. The percentage of suspicious celiac disease patients was 12% (14/118) in children and one was confirmed. CD exists in China. Chinese pediatricians should pay attention to the disease.</p>

Complementary and alternative medicine among Singapore cancer patients

<p><b>INTRODUCTION</b>This study evaluates determinants, expectations, association with quality of life (QOL) and doctor's awareness of Complementary and Alternative Medicine (CAM) use in Singapore cancer patients.</p><p><b>MATERIAL AND METHODS</b>We interviewed 316 patients visiting the Cancer Centre of the National University Hospital on behaviour, attitudes and expectations towards CAM and assessed QOL via Euroqol Questionnaire (EQ-5D). Medical information was obtained from oncologists.</p><p><b>RESULTS</b>One hundred and seventy-three patients (55%) reported CAM use after cancer diagnosis. Chinese ethnicity, tertiary education, age <65 years and previous CAM use were independent predictors of CAM use. Fifty-one per cent of CAM users informed their doctors about their use and 15% of doctors reported to be aware of CAM use in these patients. Thirty-seven per cent believed CAM to be equally or more effective than conventional cancer therapies and 78% expected at least basic knowledge about CAM from their oncologists. Twenty-fi ve per cent of patients reported concurrent use of oral CAM and chemotherapy, of which oncologists were unaware in 86% of cases. CAM users had higher EuroQol utility scores than non-CAM users (0.79 versus 0.73, respectively, P = 0.03), in particularly those aged >or=65 years and those with stage IV disease.</p><p><b>CONCLUSION</b>Singapore cancer patients show high prevalence of CAM use, high expectations regarding its effectiveness and doctors' knowledge on CAM and many use it concurrently with chemotherapy or radiotherapy. Since oncologists are generally unaware of CAM use in their patients, doctor-patient communication on CAM use needs to be improved. The association of CAM use and higher QOL scores in some subgroups deserves further exploration.</p>

Effect and mechanism of emodin on cholestatic hepatitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the therapeutic effect and mechanism of emodin on cholestatic hepatitis.</p><p><b>METHODS</b>Rats were divided into 5 groups: 1 group was untreated, the other 4 groups were treated with alpha-naphthylisothiocyanate (ANIT), ANIT and emodin, ANIT and ursodeoxycholic acid, or ANIT and dexamethasone, respectively. At 24 h, 48 h and 72 h after the treatment, NF-kappa B, early growth response factor-1 (Egr-1), cytokine-induced neutrophil chemoattractant 1 (CINC-1), macrophage inflammatory protein 2 (MIP-2), intercellular adhesion molecule 1 (ICAM-1),tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) were assayed by immunohistochemistry, real-time PCR , western-blot and ELISA. The level of malondialdehyde (MDA), superoxide Dismutase(SOD) and myeloperoxidase (MPO) were assayed by thiobarbituric acid method, xanthine oxidase method and colorimetric method, respectively.</p><p><b>RESULTS</b>(1) Compared to the controls, emodin had a notable effect on total bilirubin (TB), direct bilirubin (DB), alanine aminotransferase (ALT) at all time points (all P less than 0.05). Compared to ursodeoxycholic acid, emodin had a notable effect on TB and DB at 24 h after the treatments, however, after 48 h, emodin had a notable effect only on TB (all P less than 0.05). Compared to Dexamethasone, emodin had a notable effect on TB at 48 h time point, and it had a notable effect on ALT at all time points (all P less than 0.05). (2) The nuclei NF-kappa B p65 staining was significantly increased at 24 h and 48 h after ANIT treatment (all P less than 0.05), and emodin treatment could block the increase (all P less than 0.05). (3) Egr-1 mRNA level was not affected by emodin treatment (P more than 0.05); levels of CINC-1, MIP-2 mRNA and ICAM-1 protein were significantly decreased after emodin treatment (all P less than 0.05). (4) The levels of TNF alpha and IL-6 were decreased after emodin treatment(all P less than 0.05). (5) The levels of MDA at all time points and MPO at 24 h, 48 h time points were notably down-regulated by emodin treatment, while the level of SOD was markedly elevated at all time points after emodin treatment (all P less than 0.05).</p><p><b>CONCLUSIONS</b>Emodin treatment can reduce the levels of TB, DB and ALT in ANIT induced-cholestatic hepatitis. The effect may be due to inhibition of NF-kappa B signal pathway.</p>

Effects of silencing connective tissue growth factor on rat transforming growth factor beta/Smads signal / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effects of small interfering RNA targeting connective tissue growth factor (CTGF) on rat transforming growth factor beta (TGF beta)/Smads signal pathway.</p><p><b>METHODS</b>Chemically synthetic siRNA targeting CTGF was transfected into HSC T6 and then they were injected into rat livers through their intraportal veins. At the same time these rats also received CCl4 subcutaneously every three days for 6 consecutive weeks. Untreated HSC T6 or/and rats with random siRNA treatment served as controls. Total RNA or/and protein in HSC T6 and rat hepatic tissues were extracted. The expressions of CTGF and TGF beta 1, Smad2, 3 and 7 genes were detected by reverse transcription-polymerase chain reaction (RT-PCR) and/or Western blot.</p><p><b>RESULTS</b>CTGF siRNA significantly reduced the expression of CTGF protein in HSC T6. At 48 h after CTGF siRNA treatment, the down-regulation of CTGF protein was the most significant, up to 94%+/-4% (t=46.196, P less than 0.01), but the expressions of TGF beta 1, Smad2, 3 and 7 mRNA showed no differences in HSC T6 compared with the blank controls. Six weeks after CCl4 injections, prominent up-regulations were observed in the gene expressions of CTGF and TGF beta 1 in saline control or siRNA-treated rat livers. Administering CTGF siRNA for six weeks markedly attenuated the induction of CTGF and TGF beta 1 genes; the expressions of CTGF and TGF beta 1 protein decreased by 95%+/-2% (F=21.234, P less than 0.01) and 74%+/-8% (F=13.464, P less than 0.05), respectively, whereas Smad2, 7 protein expressions were not affected.</p><p><b>CONCLUSION</b>Silencing the CTGF gene can suppress the TGF beta /Smads signal pathway in rat livers.</p>