Publications by authors named "Xiao-He Li"

26 Publications

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Diosmetin has therapeutic efficacy in colitis regulating gut microbiota, inflammation, and oxidative stress via the circ-Sirt1/Sirt1 axis.

Acta Pharmacol Sin 2021 Jul 14. Epub 2021 Jul 14.

The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350, China.

Diosmetin (3',5,7 -trihydroxy-4'-methoxy flavone) is a natural flavonoid compound in the citrus species, it exhibits a variety of pharmacological activities, but little is known of its effects on colitis. In this study we evaluated the therapeutic effects of diosmetin on mouse models of chronic and acute colitis. Chronic colitis was induced in mice by drinking water containing 3% dextran sulfate sodium (DSS) from D0 to D8, followed by administration of diosmetin (25, 50 mg · kg · d) for another 8 days. Acute colitis was induced by drinking water containing 5% DSS from D0 to D7, the mice concomitantly received diosmetin (25, 50 mg · kg · d) from D1 to D7. During the experiments, body weight and disease activity index (DAI) were assessed daily. After the mice were sacrificed, colon tissue and feces samples were collected, and colon length was measured. We showed that in both models, diosmetin administration significantly decreased DAI score and ameliorated microscopic colon tissue damage; increased the expression of tight junction proteins (occludin, claudin-1, and zonula occludens-1), and reduced the secretion of proinflammatory cytokines IL-1β, IL-6, TNF-α, and Cox-2 in colon tissue. We found that diosmetin administration remarkably inhibited colon oxidative damage by adjusting the levels of intracellular and mitochondrial reactive oxygen species, GSH-Px, SOD, MDA and GSH in colon tissue. The protection of diosmetin against intestinal epithelial barrier damage and oxidative stress were also observed in LPS-treated Caco-2 and IEC-6 cells in vitro. Furthermore, we demonstrated that diosmetin markedly increased the expression of Nrf2 and HO-1 and reduced the ratio of acetylated NF-κB and NF-κB by activating the circ-Sirt1/Sirt1 axis, which inhibited oxidative stress and inflammation in vivo and in vitro. Diosmetin reversed the effects of si-circSirt1 and si-Sirt1 in LPS-treated Caco-2 and IEC-6 cells. When the gut microbiota was analyzed in the mouse model of colitis, we found that diosmetin administration modulated the abundance of Bacteroidetes, Actinobacteria, Cyanobacteria and Firmicutes, which were crucial for inflammatory bowel disease. Our results have linked colitis to the circ-Sirt1/Sirt1 signaling pathway, which is activated by diosmetin. The results imply that diosmetin may be a novel candidate to alleviate DSS-induced colitis and can be a lead compound for future optimization and modification.
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http://dx.doi.org/10.1038/s41401-021-00726-0DOI Listing
July 2021

Exploration of The Function of Ginsenoside RD Attenuates Lipopolysaccharide-Induced Lung Injury: A Study of Network Pharmacology and Experimental Validation.

Shock 2021 Jun 24. Epub 2021 Jun 24.

Department of Thoracic Surgery, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin, 301800, P.R. China State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, P.R. China Department of Thoracic Surgery, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin,300192, P.R. China State Key Laboratory of Reliability and Intelligence of Electrical Equipment, Hebei University of Technology, Tianjin, 300401, P.R. China State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key, Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300353, P.R. China Department of Gastroenterology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin,300192, P.R. China.

Objective: Ginsenoside Rd (GSRd) displays a variety of pharmacological effects. However, the underlying role in acute lung injury (ALI) is not clear. In this study, the protective effect of GSRd on lipopolysaccharide (LPS)-induced ALI is investigated to explore the potential mechanisms.

Methods: GSRd-target-ALI-related gene set was constructed. And bioinformatics tools were used to discover the potential mechanism. We observed the survival of subjects for 72 hours. In addition, male BALB/c mice were intraperitoneal injected with GSRd (25 and 50 mg/kg) after received one intratracheal instillation of LPS. Inflammatory changes, oxidative stress, and phosphorylation were assessed to study the biological effects.

Results: A total of 245 interaction genes were collected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were enriched in immune-inflammatory system. Among them, PI3K-Akt signaling pathway was the highest-ranked pathway of inflammatory response. In vivo study, it was found that GSRd improved survival in endotoxemic mice and inhibited the major characteristic of ALI. And the p-PI3K and p-Akt expression was significantly decreased by GSRd treatment.

Conclusion: GSRd could protect mice against LPS-induced ALI effectively by inhibiting the PI3K-Akt signaling pathway.
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http://dx.doi.org/10.1097/SHK.0000000000001824DOI Listing
June 2021

Zc3h12d, a Novel of Hypomethylated and Immune-Related for Prognostic Marker of Lung Adenocarcinoma.

J Inflamm Res 2021 15;14:2389-2401. Epub 2021 Jun 15.

Department of Thoracic Surgery, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, 300192, People's Republic of China.

Background: Zc3h12d is a negative regulator which plays a crucial role in immune modulation. However, the role of zc3h12d in lung adenocarcinoma (LUAD) remains unclear. We aim to explore the prognostic of zc3h12d and investigate the relationship between zc3h12d expression and immune infiltration in LUAD.

Methods: TIMER site was used to analyze the expression of zc3h12d in LUAD. The zc3h12d protein levels in patient tissue samples were detected by immunohistochemistry staining assays. Meanwhile, based on UALCAN database and samples' data from our cohort, we explored the relationship of clinicopathological features and zc3h12d expression to determine the clinical effect of zc3h12d in LUAD. Several databases including GEPIA, Kaplan-Meier plotter and our samples' data were used to explore the prognostic value of zc3h12d in LUAD. Cox regression analysis was established to further evaluate the prognostic value of zc3h12d in LUAD. In addition, zc3h12d promoter methylation was analyzed by UALCAN database. Genetic alteration analysis was observed in the cBioPortal web. GO and KEGG analyses were conducted to elucidate the underlying mechanisms. Finally, the correlation between zc3h12d and tumor-infiltrating immune cells in LUAD was investigated by TIMER database. The B cells level was investigated by flow cytometry analysis of peripheral blood from our LUAD cohort.

Results: Zc3h12d expression was significantly higher in LUAD, compared with adjacent normal tissues. The clinical data from the UALCAN database demonstrated that zc3h12d expression was closely related with cancer stage and nodal metastasis. However, patient sample detection revealed that zc3h12d expression was closely related to pathological N (p = 0.0431) and grade (p = 0.004). Moreover, low zc3h12d expression was associated with poorer overall survival in LUAD. We analyzed the methylation level of zc3h12d in LUAD and found that the methylation levels of zc3h12d promoter in LUAD were significantly reduced. In addition, zc3h12d genetic alterations, including deep deletion, could be found in LUAD. GO and KEGG pathway analysis results indicated that zc3h12d has a certain value in immune infiltration. We investigated the expression of zc3h12d in tumor-immune interactions. It was found that zc3h12d might be associated with the immune infiltration and markers of infiltrating immune cells of LUAD. The results of patient sample detection confirmed that B cells level was significantly lower in the patients with low zc3h12d expression than those in the patients with high zc3h12d expression.

Conclusion: zc3h12d might be considered as a potential biomarker for determining prognosis and immune-related therapeutic target in LUAD.
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http://dx.doi.org/10.2147/JIR.S304278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214544PMC
June 2021

Three-dimensional digital measurement of the facet joint in normal and lumbar intervertebral disc herniation aged 13-18 years.

Asian J Surg 2021 Jun 19. Epub 2021 Jun 19.

Department of Physiatry, Changzhi People's Hospital, Changzhi, 046000, PR China. Electronic address:

Background: Lumbar facet joint is an important element of spinal "three-joint complex". Whether there is a relationship between strange structure of facet joint and adolescent lumbar disc herniation (ALDH) is nonetheless controversial, and the current research is mainly centered on adults.

Objective: To find out the normal lumbar facet joints between 13 and 18 years old to provide anatomical basis for early diagnosis and therapy of lumbar disc herniation.

Methods: CT imaging information of 32 sufferers with lumbar disc herniation aged from 13 to 18 years old in Inner Mongolia have been collected as the ALDH group, and 62 wholesome subjects in the equal period had been chosen as the normal group. Uncooked records of continuous scanning lumbar tomography pix were imported into MIMICS 21.0 for evaluation and size in DICOM format. The parameters include facet joint height, facet joint width, et al.

Results: 1. The left and right transverse angle of LS segment in the ALDH group were (52.41 ± 9.2) ° and (55.99 ± 10.91) ° (P < 0.05), and the differences were statistically significant. The right side is larger than the left side. 2. Facet joint thickness in L-L segment of the normal group was significantly higher than that of male (1.63 ± 0.32) mm than that of female (1.38 ± 0.25) mm; In 16-18 years old group, comparison of facet joint cross-sectional area was statistically significant (22.1 ± 3.04) mm in male than (18.92 ± 3.71) mm in female. 3. In comparison between normal and ALDH group, there was significant difference in L transverse angle (P < 0.05), L facet joint height and facet joint thickness (P < 0.05), LS facet joint thickness and transverse angle (P < 0.05).

Conclusion: When ALDH occurs in the LS segment, there is a substantial difference between the left and right sides of the transverse angle, and there is a difference in the thickness and the facet joint cross-sectional area between males and females, which is generally larger in males than in females. Facet joint height is larger, transverse angle of left and right is asymmetric, inferior articular process is larger, and facet joint thickness is smaller can indicate that lumbar disc herniation is effortless to occur.
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http://dx.doi.org/10.1016/j.asjsur.2021.05.028DOI Listing
June 2021

Comparison of patients hospitalized with COVID-19, H7N9 and H1N1.

Infect Dis Poverty 2020 Dec 2;9(1):163. Epub 2020 Dec 2.

Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China.

Background: There is an urgent need to better understand the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for that the coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. This paper was to differentiate COVID-19 from other respiratory infectious diseases such as avian-origin influenza A (H7N9) and influenza A (H1N1) virus infections.

Methods: We included patients who had been hospitalized with laboratory-confirmed infection by SARS-CoV-2 (n = 83), H7N9 (n = 36), H1N1 (n = 44) viruses. Clinical presentation, chest CT features, and progression of patients were compared. We used the Logistic regression model to explore the possible risk factors.

Results: Both COVID-19 and H7N9 patients had a longer duration of hospitalization than H1N1 patients (P < 0.01), a higher complication rate, and more severe cases than H1N1 patients. H7N9 patients had higher hospitalization-fatality ratio than COVID-19 patients (P = 0.01). H7N9 patients had similar patterns of lymphopenia, neutrophilia, elevated alanine aminotransferase, C-reactive protein, lactate dehydrogenase, and those seen in H1N1 patients, which were all significantly different from patients with COVID-19 (P < 0.01). Either H7N9 or H1N1 patients had more obvious symptoms, like fever, fatigue, yellow sputum, and myalgia than COVID-19 patients (P < 0.01). The mean duration of viral shedding was 9.5 days for SARS-CoV-2 vs 9.9 days for H7N9 (P = 0.78). For severe cases, the meantime from illness onset to severity was 8.0 days for COVID-19 vs 5.2 days for H7N9 (P < 0.01), the comorbidity of chronic heart disease was more common in the COVID-19 patients than H7N9 (P = 0.02). Multivariate analysis showed that chronic heart disease was a possible risk factor (OR > 1) for COVID-19, compared with H1N1 and H7N9.

Conclusions: The proportion of severe cases were higher for H7N9 and SARS-CoV-2 infections, compared with H1N1. The meantime from illness onset to severity was shorter for H7N9. Chronic heart disease was a possible risk factor for COVID-19.The comparison may provide the rationale for strategies of isolation and treatment of infected patients in the future.
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http://dx.doi.org/10.1186/s40249-020-00781-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707904PMC
December 2020

[Screening, identification and characterization of a broadspectrum antagonistic strain in banyan rhizosphere soil].

Ying Yong Sheng Tai Xue Bao 2019 Nov;30(11):3894-3902

College of Biological Science and Engineering, Jiangxi Agricultural University, Nanchang 330045, China.

Rhizosphere soil samples were collected from an ancient banyan tree grown in the Wanli period of Ming Dynasty in Ji'an City, Jiangxi Province. Twenty-three kinds of indicator bacteria were used to screen soil actinomycetes by cylinder-plate method and mycelium growth rate method. A broad-spectrum antagonistic strain AHF-20 with stable passage was obtained. According to the morphological observation, physiological and biochemical tests, and molecular biological identification, the antagonistic strain was identified as Streptomyces. We examined the antibacterial active substance of the strain. The results showed that the fermentation products of Streptomyces AHF-20 had antagonistic effects on all the 23 test indicator bacteria. The antibacterial ability was stable, tolerant to temperature, light, ultraviolet, acid and alkali. Antibacterial activity still existed after heating at 121 ℃ for 20 min. The fermentation product was extracted with n-butanol according to the polarity of the active substance. The obtained crude n-butanol extract was diluted to 1 μg·mL, which still had inhibitory effect for Escherichia coli. The results indicated that it has well utilization potential for biocontrol and developing new microbial drug.
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http://dx.doi.org/10.13287/j.1001-9332.201911.037DOI Listing
November 2019

Effects of l-arginine on endometrial estrogen receptor α/β and progesterone receptor expression in nutrient-restricted sheep.

Theriogenology 2019 Oct 25;138:137-144. Epub 2019 Jul 25.

Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address:

This study aimed to determine the effects of l-arginine (L-Arg) supplementation on steroid hormone receptors in non-pregnant ovine endometrium. All experimental ewes were randomly assigned to either a control group (n = 6), a nutrient-restricted group (n = 6), or an L-Arg supplemented nutrient-restricted group (n = 6). The effects of L-Arg on estrogen receptor α/β (ERα/β) and progesterone receptor (PGR) expression in the ovine endometrium were assessed. Our results showed that levels of ERβ and PGR expression were significantly increased by nutrient restriction, but L-Arg counteracted the effect of nutrient restriction on ERβ and PGR expression (p < 0.05). Also, expression of endometrial ERα was substantially increased (p < 0.05) by L-Arg supplementation. Furthermore, ERα/β and PGR were mainly detected in the endometrial luminal epithelium and glandular epithelium. Therefore, we isolated and identified endometrial epithelial cells (EECs) from sheep. Different concentrations of L-Arg were added to investigate the effects on ERα/β and PGR in EECs. The expression levels of endothelial nitric oxide synthase, ERβ, and PGR were significantly increased in response to low-concentration (200 μmol) L-Arg supplementation, which subsequently decreased with a high concentration (800 μmol) (p < 0.05). Otherwise, ERα expression was remarkably increased at both L-Arg concentrations in EECs (p < 0.05). Overall, the results indicated that L-Arg performed crucial roles in the regulation of ovine steroid hormone receptor expression in the endometrium. The results of this study provide a theoretical basis and technical means for the normal function of endometrium in response to low nutrient levels.
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http://dx.doi.org/10.1016/j.theriogenology.2019.07.018DOI Listing
October 2019

Three-dimensional digitizing and anatomic study of lumbar vertebral canal and pedicle in children.

Wideochir Inne Tech Maloinwazyjne 2018 Dec 8;13(4):518-524. Epub 2018 Aug 8.

Teaching and Researching Institute of Human Anatomy, School of Basic Medicine, Hohhot, China.

Introduction: Spinal pedicle screw internal fixation has been widely used in adult spine injury fixation. Due to being in a period of continuous growth and development, the spine of children at different ages shows different characteristics from adults in terms of anatomy, physiological function, and biomechanics. Furthermore, because the pedicle of children is small, has large anatomic variation, and has complex adjacent relationships, the surgical risk is extremely high. How to improve the screwing accuracy is the key to the success of children's pedicle internal fixation. Therefore, applying the concept of digitized and individualized screwing will be of great significance to children's pedicle screwing.

Aim: To investigate the morphologies, development patterns, and aging characteristics of the lumbar vertebral pedicle (LVP) in children aged 6-11 years, and to provide a theoretical basis for screw implantation and related biomechanical studies.

Material And Methods: A total of 60 children aged 6-11 years were selected for the intergroup measurement and statistical analysis of their lumbar diameter, pedicle diameter, screw canal length (SCL), etc.

Results: Generally, the vertebral foramen diameter (ID), sagittal diameter (SD), pedicle width (PW), and SCL as well as the pedicle height (PH) exhibited an increasing trend with age and increasing vertebral sequence among children aged 6-11 years.

Conclusions: By observing the LVP in children using 3D digital reconstruction technology, the morphology of the spinal canal and pedicles at different lumbar segments showed obvious development patterns, and the best treatment protocol should be selected according to the LVP characteristics in clinical applications.
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http://dx.doi.org/10.5114/wiitm.2018.77554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280084PMC
December 2018

Follistatin-Like 1 Promotes Bleomycin-Induced Pulmonary Fibrosis through the Transforming Growth Factor Beta 1/Mitogen-Activated Protein Kinase Signaling Pathway.

Chin Med J (Engl) 2018 Aug;131(16):1917-1925

Department of Respiratory Disease, Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Capital Medical University; Department of Respiratory Disease, Capital Medical University, Beijing 100020, China.

Background: Follistatin-like 1 (FSTL1) is a novel profibrogenic factor that induces pulmonary fibrosis (PF) through the transforming growth factor-beta 1 (TGF-β1)/Smad signaling. Little is known about its effects on PF through the non-Smad signaling, like the mitogen-activated protein kinase (MAPK) pathway. Therefore, this study aimed to investigate the role of FSTL1 in PF through the MAPK signaling pathway and its mechanisms in lung fibrogenesis.

Methods: PF was induced in Fstl1and wild-type (WT) C57BL/6 mice with bleomycin. After 14 days, the mice were sacrificed, and lung tissues were stained with hematoxylin and eosin; the hydroxyproline content was measured to confirm PF. The mRNA and protein level of FSTL1 and the change of MAPK phosphorylation were measured by quantitative polymerase chain reaction and Western blotting. The effect of Fstl1 deficiency on fibroblasts differentiation was measured by Western blotting and cell immunofluorescence. MAPK signaling activation was measured by Western blotting in Fstl1 and WT fibroblasts treated with recombinant human FSTL1 protein. We pretreated mouse lung fibroblast cells with inhibitors of the extracellular signal-regulated kinase (ERK), p38, and Jun N-terminal kinase (JNK) signaling and analyzed their differentiation, proliferation, migration, and invasion by Western blotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis, and transwell assays. The Student's t-test was used to compare the differences between two groups.

Results: Fstl1 deficiency attenuated phosphorylation of the ERK, p38, and JNK signaling in bleomycin-induced fibrotic lung tissue 14 days after injury (0.67 ± 0.05 vs. 1.22 ± 0.03, t = 14.92, P = 0.0001; 0.41 ± 0.01 vs. 1.15 ± 0.07; t = 11.19; P = 0.0004; and 0.41 ± 0.01 vs. 1.07 ± 0.07, t = 8.92, P = 0.0009; respectively), compared with WT lungs at the same time and in primary lung fibroblasts (0.82 ± 0.01 vs. 1.01 ± 0.04, t = 4.06, P = 0.0150; 1.04 ± 0.03 vs. 1.24 ± 0.03, t = 4.44, P = 0.0100; and 0.76 ± 0.05 vs. 0.99 ± 0.05, t = 4.48, P = 0.0100; respectively), compared with TGF-β1-stimulated WT group. Recombinant human FSTL1 protein in lung fibroblasts enhanced TGF-β1-mediated phosphorylation of the ERK (1.19 ± 0.08 vs. 0.55 ± 0.04, t = 6.99, P = 0.0020), p38 (1.18 ± 0.04 vs. 0.66 ± 0.03, t = 11.20, P = 0.0020), and JNK (1.11 ± 0.01 vs. 0.84 ± 0.04, t = 6.53, P = 0.0030), compared with the TGF-β1-stimulated WT group. Fstl1-deficient fibroblasts showed reduced alpha-smooth muscle actin (α-SMA) expression (0.70 ± 0.06 vs. 1.28 ± 0.11, t = 4.65, P = 0.0035, compared with the untreated WT group; 1.40 ± 0.05 vs. 1.76 ± 0.02, t = 6.31, P = 0.0007; compared with the TGF-β1-treated WT group). Compared with the corresponding condition in the control group, the TGF-β1/FSTL1-mediated α-SMA expression was significantly suppressed by pretreatment with an inhibitor of p38 (0.73 ± 0.01 vs. 1.13 ± 0.10, t = 3.92, P = 0.0078) and JNK (0.78 ± 0.03 vs. 1.08 ± 0.06, t = 4.40, P = 0.0046) signaling. The proliferation of mouse lung fibroblast cells (MLgs) significantly decreased after treatment of an inhibitor of p38 (0.30 ± 0.01 vs. 0.46 ± 0.03, t = 4.64, P = 0.0009), JNK (0.30 ± 0.01 vs. 0.49 ± 0.01, t = 12.84, P = 0.0001), and Smad2/3 (0.18 ± 0.02 vs. 0.46 ± 0.02, t = 12.69, P = 0.0001) signaling compared with the dimethylsulfoxide group. The migration and invasion cells of MLgs significantly decreased in medium pretreated with an inhibitor of p38 (70.17 ± 3.28 vs. 116.30 ± 7.11, t = 5.89, P = 0.0042 for the migratory cells; 19.87 ± 0.84 vs. 32.70 ± 0.95, t = 10.14, P = 0.0005 for the invasive cells), JNK (72.30 ± 3.85 vs. 116.30 ± 7.11, t = 5.44, P = 0.0056 for the migratory cells; 18.03 ± 0.94 vs. 32.70 ± 0.95, t = 11.00, P = 0.0004 for the invasive cells), and Smad2/3 (64.76 ± 1.41 vs. 116.30 ± 7.11, t = 7.11, P = 0.0021 for the migratory cells; 18.03 ± 0.94 vs. 32.70 ± 0.95, t = 13.29, P = 0.0002 for the invasive cells) signaling compared with the corresponding condition in the dimethylsulfoxide group.

Conclusion: FSTL1 affects lung fibroblast differentiation, proliferation, migration, and invasion through p38 and JNK signaling, and in this way, it might influence the development of PF.
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http://dx.doi.org/10.4103/0366-6999.238151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085847PMC
August 2018

Effects of l-arginine on endometrial microvessel density in nutrient-restricted Hu sheep.

Theriogenology 2018 Oct 19;119:252-258. Epub 2018 Jul 19.

Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address:

Nutrient deficiency in ruminants can lead to estrus cycle disorders, a decreased pregnancy rate, and reduce birth weight. l-arginine (L-Arg), an important amino acid, can improve uterine homeostasis in pregnant sheep and prevent intrauterine growth restriction (IUGR). However, most studies of L-Arg have been conducted on pregnant sheep and few have reported the effects of L-Arg on microvessel density (MVD) in the non-pregnant ovine endometrium. The processes of normal uterine cyclical development and implantation are dependent on a balanced of endometrial MVD. In this study, female Hu sheep were randomly assigned to either a control group (n = 6), a nutrient-restricted group (n = 6), or an L-Arg supplemented nutrient-restricted group (n = 6). The effects of L-Arg on MVD in ovine endometrium were then studied. Our results showed that ovine endometrial MVD was significantly increased by nutrient restriction, but L-Arg counteracted the effect of nutrient restriction on MVD (P < 0.05). Levels of angiogenic growth factors (including VEGFA, VEGFR2, and FGF2) had significant increases (P < 0.05) in endometrium of nutrient restriction on sheep, but that L-Arg supplementation substantially decreased (P < 0.05) their expressions in nutrient restriction sheep. Furthermore, oxidative stress caused by nutrient restriction was also alleviated by L-Arg supplementation in the ovine endometrium. Overall, the results suggested that L-Arg has crucial roles in maintaining the balance of endometrial MVD and angiogenic growth factors, and increasing anti-oxidation capability in the endometrium of nutrient-restricted sheep. This study will provide a theoretical basis and technical means for the normal development of endometrial microvessels in low nutrition level.
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http://dx.doi.org/10.1016/j.theriogenology.2018.07.017DOI Listing
October 2018

Parthenolide attenuated bleomycin-induced pulmonary fibrosis via the NF-κB/Snail signaling pathway.

Respir Res 2018 06 5;19(1):111. Epub 2018 Jun 5.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China.

Background: Parthenolide (PTL) is a natural molecule isolated from Tanacetum parthenium that exhibits excellent anti-inflammatory and antitumor activities. Pulmonary fibrosis (PF), especially idiopathic pulmonary fibrosis (IPF), is a chronic lung disease that lacks a proven effective therapy. The present study evaluated the therapeutic effect of PTL on PF.

Methods: Serum-starved primary lung fibroblasts and HFL1 cells were treated with different doses of PTL, and cell viability and the migration rate were measured. Western blot analysis and a dual-luciferase assay were used to analyze the epithelial-mesenchymal transition (EMT)-related transcription factors influenced by PTL treatment in A549 cells and primary lung epithelial cells. Mice with bleomycin (BLM)-induced pulmonary fibrosis were treated with different doses of intragastric PTL, and pathological changes were evaluated using Hematoxylin-eosin (H&E) staining and immunohistochemical analysis.

Results: Our results demonstrated that PTL reduced the cell viability and migration rate of lung fibroblasts and inhibited the expression of EMT-related transcription factors in lung epithelial cells. In vivo studies demonstrated that PTL attenuated BLM-induced pulmonary fibrosis and improved the body weight and pathological changes of BLM-treated mice. We further demonstrated that PTL attenuated BLM-induced PF primarily via inhibition of the NF-κB/Snail signaling pathway.

Conclusion: These findings suggest that PTL inhibits EMT and attenuates BLM-induced PF via the NF-κB/Snail signaling pathway. PTL is a worthwhile candidate compound for pulmonary fibrosis therapy.
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http://dx.doi.org/10.1186/s12931-018-0806-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989384PMC
June 2018

Gut microbiota profiles in treatment-naïve children with attention deficit hyperactivity disorder.

Behav Brain Res 2018 07 23;347:408-413. Epub 2018 Mar 23.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China. Electronic address:

Backgrounds: Although increasing evidence suggests a role for the gut microbiota in neurodevelopment, the actual structure and composition of microbiota in children with attention-deficit/hyperactivity disorder (ADHD) remain unclear.

Methods: Thus, the present study aimed to define the characteristics of gut microbiota in treatment-naive children with ADHD and to assess their relationship with the severity of ADHD symptoms. High-throughput pyrosequencing was used to investigate the microbiota composition in fecal matter from 51 children with ADHD and 32 healthy controls (HC).

Results: An operational taxonomical unit (OTU)-level analysis revealed a significant decrease in the fractional representation of Faecalibacterium in children with ADHD compared to HC. In individuals with ADHD, the abundance of Faecalibacterium was negatively associated with parental reports of ADHD symptoms. However, there was no significant difference in alpha diversity between the ADHD and control groups.

Conclusions: This present findings support the involvement of microbiota alteration in psychiatric diseases and Faecalibacterium may represent a potential novel marker of gut microbiota in ADHD. Future studies are needed to validate these findings and to elucidate the temporal and causal relationships between these variables.
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http://dx.doi.org/10.1016/j.bbr.2018.03.036DOI Listing
July 2018

Doxycycline attenuates paraquat-induced pulmonary fibrosis by downregulating the TGF-β signaling pathway.

J Thorac Dis 2017 Nov;9(11):4376-4386

State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 300071, China.

Background: Paraquat (PQ) is a highly efficient herbicide that remains widely used in agriculture. However, the inappropriate application of this herbicide may cause multiple organ injuries including pulmonary injury. In this study, we report that doxycycline (Doxy) treats PQ-induced pulmonary fibrosis (PF).

Methods: Mice with PQ-induced PF were treated with different doses of Doxy by intragastric administration. Human lung cancer cell line A549 pre-treated with TGF-β1 (5 ng/mL) were treated with Doxy hydrochloride (3.4 µM).

Results: PF was observed from day 28 in PQ-treated group and Doxy treatments significantly reduced pulmonary coefficient, histopathological score and collagen content in a dose-dependent manner. Doxy can inhibit the expression levels of plasma inflammation cytokines at day 28 after modeling and reduced inflammatory response at early stage of PQ-induced lung injury. Immunohistochemical staining assay and proteomic analysis indicated that Doxy could restore ectopic epithelial-mesenchymal transition (EMT) induced by PQ-treatment by regulating numerous TGF-β signaling related proteins.

Conclusions: The findings suggest that Doxy can restore the balance of epithelial-mesenchymal cells and attenuate PQ-induced PF by downregulating the TGF-β signaling pathway.
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http://dx.doi.org/10.21037/jtd.2017.10.42DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5720967PMC
November 2017

HBcrAg Identifies Patients Failing to Achieve HBeAg Seroconversion Treated with Pegylated Interferon Alfa-2b.

Chin Med J (Engl) 2016 09;129(18):2212-9

Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People's Hospital, Beijing 100044, China.

Background: We aimed to evaluate the usefulness of serum hepatitis B virus core-related antigens (HBcrAg) for predicting hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B patients treated with conventional interferon (IFN) alfa-2b or pegylated IFN.

Methods: Fifty-eight patients were enrolled: 29 for the training group and 29 for the validating group. HBcrAg was measured at baseline, week 12, end of the treatment, and 12- and 24-week follow-ups. Sixteen patients in the training group were enrolled in the long-term follow-up (LTFU), during which time the dynamics of the HBcrAg was monitored.

Results: The serum HBcrAg level gradually declined during treatment among the HBeAg seroconversion patients of the training group (from baseline, week 12, end of the treatment, 12-week follow-up to 24-week follow-up were 110,245 kU/ml, 3760 kU/ml, 7410 kU/ml, 715 kU/ml, 200 kU/ml, respectively). HBcrAg <19,565 kU/ml at week 24, HBcrAg <34,225 kU/ml at 12-week follow-up, and HBcrAg decrease ≥0.565 log10kU/ml from the baseline to the end of treatment (EOT) had negative predictive values (NPVs) of 100% for HBeAg seroconversion at the end of follow-up, whereas the positive predictive values (PPVs) were 30.77%, 26.67%, and 25.00%, respectively. The patients with HBeAg seroconversion at the end of 24-week follow-up remained in seroconversion during the LTFU, during which time their serum HBcrAg levels steadily declined or even became undetectable, ranging from 0 to 2.1 kU/ml.

Conclusions: Effective antiviral treatment can decrease HBcrAg levels in the serum. The NPVs of HBcrAg for predicting HBeAg seroconversion at 24-week follow-up was 100%, but the PPVs were not satisfactory (all <31%). The serum HBcrAg levels of the patients with HBeAg seroconversion at the end of the 24-week follow-up steadily declined or even became undetectable during the LTFU.
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http://dx.doi.org/10.4103/0366-6999.189904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5022343PMC
September 2016

[Formula method of medicated diet based on medicinal property combination patterns].

Zhongguo Zhong Yao Za Zhi 2014 Jul;39(13):2392-5

To propose a formula method of medicated diet based on medicinal property combination patterns in this paper under the context of lack of innovation in medicated diets. By analyzing the property combination patterns of traditional Chinese medicine and commonly used foods recorded in the pharmacopoeia, medicated diet formulae were optimized by using the greedy algorithm, with the property combination patterns of classical formulae based on the syndrome differentiation and treatment. In this paper, the Baihu Rensheng decoction, which is a classical formula for treating lung and stomach heat-derived diabetes, was taken for example in the formula design. As a result, totally 18 medicated diet formulae were developed and proved to be rational in the analysis on traditional Chinese medicines and nutriology. This method expands the way of thinking for personalized diet therapies and provides theoretical basis the industrial development and clinical application of medicated diets.
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July 2014

[Study on prescription combination and design method based on dichotomy and greedy algorithm].

Zhongguo Zhong Yao Za Zhi 2014 Jul;39(13):2386-8

The prescription combinations of traditional Chinese medicine (TCM) focuses on the taste and channel tropism, the Qi movement, as well as the compatibility according to multiple combination principles and medicinal property and flavor combination of several traditional Chinese medicines. With the in-depth study on the prescription compatibility, researchers have realized that the medicinal property theory is the core of TCM combinations. However, there is no definite method for combinations based on medicinal properties. In this paper, the authors put forward an method for designing prescription combinations based on bipartite graph and the greedy algorithm. With the medicinal property combinations of Siweilurong Pills for example, the authors proved this method could provide ideas for quickly choosing herbal medicines for prescription combinations, and discussed the prospect of this method in substituting previous and endangered herbal medicines and banned medicinal materials.
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July 2014

[Effects of controlled ovarian hyperstimulation on mitochondria copy number and functions in murine oocytes].

Zhonghua Fu Chan Ke Za Zhi 2013 Nov;48(11):858-61

Reproductive Medical Center, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

Objective: To investigate the effect of whether controlled ovarian hyperstimulation (COH) on mitochondrial DNA (mtDNA) copy number, mitochondrial function, distribution, the level of reactive oxygen species (ROS) in oocytes and the mechanism of oocyte loss in COH.

Methods: Matured murine oocytes were classified into COH group and natural cycles (NC) group. The copies of mtDNA, the magnitude of mitochondrial membrane potential (Δφm) and oocyte adenosine triphosphate (ATP) content, pattern of mitochondrial distribution, and ROS levels were evaluated by realtime PCR, immunofluorescence and fluorescence-luciferase mensuration.

Results: The copies of mtDNA, the levels of Δφm, and ATP content in oocytes between COH and NC groups showed statistical difference [(1.15 ± 0.01)×10(5), 0.34 ± 0.03 and (241 ± 20) fmol/oocyte (COH)] versus [(2.15 ± 0.19)×10(5), 0.82 ± 0.07 and (325 ± 11) fmol/oocyte (NC)], respectively(P < 0.05). However, there were no significant differences in the rate of evenly distributed mitochondria and the level of ROS in oocytes from COH and NC [(76.5% (78/102) in COH versus 82.1% (69/84)]; 1.07 ± 0.07 in COH versus 0.93 ± 0.08 in NC (P > 0.05).

Conclusion: It was indicated that non-physiological COH treatments inhibit mtDNA replication, alter mitochondrial function, which might partly be involved in the low development potential of COH oocyte.
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November 2013

[Suppression of mitochondrial oxidative phosphorylation on in vitro maturation, fertilization and developmental competence of oocytes].

Beijing Da Xue Xue Bao Yi Xue Ban 2013 Dec;45(6):864-8

Reproductive Health Center, Second Affiliated Hospital of Wenzhou Medical University, Zhejiang Wenzhou 325000, China.

Objective: To investigate the roles of mitochondrial oxidative phosphorylation (OXPHOS) capacity in oocyte maturation, fertilization and embryo development.

Methods: Carbonyl cyanide p- (tri-fluromethoxy) phenyl-hydrazone (FCCP), a metabolic inhibitor of mitochondria, was introduced into culture medium. The integrity of spindle and chromosome alignment, reactive oxygen species (ROS) levels, and rates of maturation, germinal vesicle breakdown, fertilization and blastulation were assessed in vitro.

Results: Significant decreases were detected in the percentages of oocytes with nuclear maturation, normal spindle formation and chromosome alignment, ROS levels and capable for blastocyst formation between oocytes treated with FCCP and non-treated (control group), 55.8%, 37.9%, 0.67 and 57.9% (FCCP 10 nmol/L group), 47.3%,34.7%, 0.59 and 41.8% (FCCP 100 nmol/L group) versus 62.9%, 61.9%,0.94 and 68.3% (control group) respectively, P<0.05. However, No significant differences were found in the rates of GVBD and fertilization in oocytes from the FCCP treated and the control.

Conclusion: Inhibition of mitochondrial metabolic capacity resulted in decreased the percentages of oocytes with nuclear maturation, normal spindle formation and chromosome alignment, ROS levels and capable for blastocyst formation. But the treatment of FCCP did not affect the rate of fertilization.
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December 2013

Impaired elastin deposition in Fstl1-/- lung allograft under the renal capsule.

PLoS One 2013 25;8(11):e81368. Epub 2013 Nov 25.

College of Life Sciences, Nankai University, Tianjin, China ; School of Pharmaceutical Science, Jiangnan University, Wuxi, China.

Lung alveolar development in late gestation is a process important to postnatal survival. Follistatin-like 1 (Fstl1) is a matricellular protein of the Bmp antagonist class, which is involved in the differentiation/maturation of alveolar epithelial cells during saccular stage of lung development. This study investigates the role of Fstl1 on elastin deposition in mesenchyme and subsequent secondary septation in the late gestation stage of terminal saccular formation. To this aim, we modified the renal capsule allograft model for lung organ culture by grafting diced E15.5 distal lung underneath the renal capsule of syngeneic host and cultured up to 7 days. The saccular development of the diced lung allografts, as indicated by the morphology, epithelial and vascular developments, occurred in a manner similar to that in utero. Fstl1 deficiency caused atelectatic phenotype companied by impaired epithelial differentiation in D3 Fstl1(-/-) lung allografts, which is similar to that of E18.5 Fstl1(-/-) lungs, supporting the role of Fstl1 during saccular stage. Inhibition of Bmp signaling by intraperitoneal injection of dorsomorphin in the host mice rescued the pulmonary atelectasis of D3 Fstl1(-/-) allografts. Furthermore, a marked reduction in elastin expression and deposition was observed in walls of air sacs of E18.5 Fstl1(-/-) lungs and at the tips of the developing alveolar septae of D7 Fstl1(-/-) allografts. Thus, in addition to its role on alveolar epithelium, Fstl1 is crucial for elastin expression and deposition in mesenchyme during lung alveologenesis. Our data demonstrates that the modified renal capsule allograft model for lung organ culture is a robust and efficient technique to increase our understanding of saccular stage of lung development.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0081368PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839892PMC
August 2014

[Integration sites in HCC biopsy].

Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2010 Oct;24(5):386-8

The Surgical Department of The First Clinical College of GuangDong Medical College, ZhanJiang 524023, China.

Objective: To compare the performance of Inverse-PCR, Alu-PCR and Cassette-ligation-mediated PCR (CLM-PCR) in HBV DNA integration sites identification.

Methods: One HCC biopsy was obtained from surgically resected sample. The patient was positive for serum hepatitis B surface antigen (HBsAg). The genomic DNA was purified by the standard phenol/chloroform extraction and ethanol precipitation method. Seperated set of primers were designed to amplify the HBV DNA integration region by means of 3 different PCR methods respectively. The PCR products were analyzed by electrophoresis, then cloned to PMD18-T vector for DNA sequencing. The sequence alignment was performed under Blast software.

Results: 7 bands and 22 sequencing results was obtained from IPCR and 3 integration sites was identified. Alu-PCR provided 12 bands and 32 sequencing results, and CLM-PCR showed 12 bands and 4 sequencing results. No integration site was identified from the latter two.

Conclusion: IPCR compared with another two methods showed a reliable capacity in HBV DNA integration site identification.
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October 2010

Anatomical study of position of the rib head for placing anterior vertebral body screws in a chinese population.

Orthopedics 2010 Dec 1;33(12):884. Epub 2010 Dec 1.

Department of Anatomy, Southern Medical University, Guangzhou, Guangdong Province, P.R. China.

In this study, the variability of rib head position in a Chinese population in terms of the spinal canal and vertebral body was analyzed using computed tomography (CT). Images from transverse CT scan of the T4 to T12 vertebral bodies of 30 normal individuals were 3-dimensionally reconstructed, and analyzed for measurement of parameters that define the relative anatomic position of the rib head. We have found that the distance between the anterior border of the rib head and the posterior margin of the vertebral body, posterior safe angle, and the distance between the most inferior border of the rib head and inferior end plate in the sagittal plane gradually decrease. However, the distance between the anterior boarder of the rib head and the anterior margin of the vertebral body, transverse dimension, anterior safe angle, and the distance between the most inferior border of the rib head and superior end plate in the sagittal plane gradually increase from T4 to T12. This indicates that the position of the rib head is oriented from a more anterior position to a more posterior position and from a more superior position to a more inferior position as the number of the vertebra increases, which is different from what has been reported from western populations. Our study has identified useful parameters to define the position of the rib head, and provides a comprehensive reference guide for accurate and safe instrumentation of vertebral body screws in treating related spine diseases.
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http://dx.doi.org/10.3928/01477447-20101021-03DOI Listing
December 2010

[Construction and application of a genechip method for detection of hepatitis B virus lamivudine-resistant mutants and basal core promotor/Pre-C mutants].

Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2009 Aug;23(4):309-12

Infection Department, Shenzhen Disanrenmin Hospital of Guangdong Medical College, Shenzhen 518020, China

Objective: The objective of this research is to construct a clinic-usable genechip method for detection of hepatitis B virus lamivudine-resistant mutants and basal core promotor/Pre-C mutants, compare this method with DNA sequencing to investigate this genechip's character (sensity, specificity, stability and practicability in clinic) and apply it in clinic.

Methods: This genechip detection method can detect the DNA and 8 mutative site of HBV, include 3 lamivudine-resistant mutation site(No. 180, 204, 207 site in DNA polymerase gene), 5 HBeAg escape-related mutation site (nt 1896, 1899, 1862, 1764,1762 site in BCP/Pre-C region).The results of genechip method was verified by DNA sequencing.

Results: In detecting HBV DNA, the results of genechip were agree with 100% of the results of DNA sequencing. In detecting HBV mutants, 251 sites (in 32 samples, 256 sites) showed the same results using both methods, and only 5 sites were not completely match (P > 0.05). In these 5 sites, genechip methods got multi-infection results, but sequencing got single-infection results.

Conclusion: These results suggest that genechip method has the same positive rate and almost these same specificity with DNA sequencing method, and is better than DNA sequencing method in detecting multi-infected HBV strains. [Key words]
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August 2009

[High throughput detection of drug-resistance gene mutations in HBV using MALDI-TOF mass spectrometry].

Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2008 Oct;22(5):351-3

Shenzhen Donghu Hospital, Shenzhen 548020, China.

Objective: To develop a high-throughput clinical method on drug-resistance gene mutations of HBV using MALDI-TOF-MS.

Method: Using MassArray Assay Design software designed the iPLEX primers and followed the iPLEX instruction for amplification, SAP reaction, primer extenction, desalination, dispensing, MALDI-TOF-MS screening and data analysis of the gene mutation locus. 138 serum samples of chronic HBV patients with single drug-resistance or multiple drug-resistance on Lamivudin, adefovi, Entecavir were detected.

Result: The HBV gene mutation platform was successfully developed and applied on the high-throughput dectection of clinical serum samples. It was also a high throughput assay which could be used to detect for more than 138 samples once. The MALDI-TOF-MS technology and the DNA sequencing simultaneously examine 33 samples, in which result of 10 sample is inconsistent, the including 2 samples by MALDI-TOF-MS technology has not tested, 1 sample has 2 inconsistent mutations.

Conclusion: Detection of HBV gene mutations using MALDI-TOF-MS is highly-sensitive, highly-accurate, high-throughput, fast achieved and suitable to use in the diagnosis and monitoring of HBV.
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October 2008

[Detection of cryptosporidium infection among AIDS patients in Guangdong and Yunnan].

Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2008 Oct;22(5):339-41

Shenzhen Donghu Hospital, Shenzhen 518020, China.

Objective: To investigate the infection of Cryptosporidium and its epidemiological characteristics in AIDS patients of Southern China.

Methods: Stool samples colleted from AIDS confirmed patients. The samples were detected for oocyst of Cryptosporidium by acid fast bacteria stain and indirect fluorescent antibody stain respectively, CD4 count was detected by Flow Cytometry.

Results: 212 samples of fresh stool obtained from the AIDS patients who live in Guangdong and Yunnan province. The total infection rate of Cryptosporidium in AIDS patients was 4.25% (9/212), the infectious rate of oocyst in the group of 50- 59-years-old was significantly higher than those in 30-39 (P < 0.01); the infectious rate of oocyst in patients with antiretroviral therapy (ART) was also significantly lower (P = 0.0000); we found the patients coinfected with Cryptosporidium with CD4 count all below 100 cells/microl. However, there were no any difference between the infectious rate to the patient's gender, areas and stool shape.

Conclusion: AIDS patients infected by Cryptosporidium are not rare in southern China, and the infectious rate was lower than western country. Patients received ART could decrease the infectious rate of Cryptosporidium, Cryptosporidium always happen in patient whose CD4 count was very low (< 100 cells/microl).
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October 2008

Decline of serum HBV DNA and no change apportioned by the same hepatic parenchyma cell volume from hepatic fibrosis stage 1 to stage 4 during the natural history of chronic hepatitis B.

Intervirology 2008 24;51(4):235-40. Epub 2008 Sep 24.

Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, Shipai, Guangzhou, PR China.

During the initial phase of chronic hepatitis B virus (HBV) infection, serum HBV DNA levels are high. Contrarily, fibrosis, cirrhosis and hepatocellular carcinoma have been found in patients with lower serum HBV DNA levels. The aim of this study is to clarify HBV DNA level dynamics of serum apportioned by the same hepatic parenchyma cell volume (HPCV) in hepatic fibrosis stages 1-4 during the natural history of chronic hepatitis B. Serum HBV DNA levels were evaluated by real-time polymerase chain reaction. Further, serum HBV DNA levels were apportioned by and compared with the same HPCV in hepatic fibrosis stages 1-4, respectively. Serum HBV DNA levels were 8.91 x 10(6) +/- 4.37 x 10(1), 8.13 x 10(6) +/- 7.41 x 10(1), 9.55 x 10(5) +/- 1.02 x 10(2), and 4.07 x 10(5) +/- 7.24 x 10(1) copies/ml, respectively; there were differences among hepatic fibrosis stages 1-4 (p < 0.021-0.000). However, serum HBV DNA levels apportioned by the same volume of hepatic parenchyma cells in hepatic fibrosis stages 1-4 were 3.47 x 10(10) +/- 8.71 x 10(2), 1.02 x 10(11) +/- 9.55 x 10(2), 1.41 x 10(10) +/- 2.57 x 10(3), and 3.72 x 10(10) +/- 3.02 x 10(3) with HPCV proportions 65.9, 62.7, 58.9, and 53.3%, respectively; there were no differences among hepatic fibrosis stages 1-4 (p > 0.203-0.967).Following the progression of hepatic fibrosis from stage 1 to 4, ongoing decline of HPCV is responsible for a declining trend of serum HBV DNA levels.
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http://dx.doi.org/10.1159/000156482DOI Listing
December 2008

Etiological investigation of fatal liver failure during the course of chronic hepatitis B in southeast China.

J Gastroenterol 2006 Apr;41(4):347-51

Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-Sen University, Shipai, Guangzhou 510630, P. R. China.

Background: The purpose of this study was to clarify the relationships between patients who had fatal liver failure during the course of chronic hepatitis B and those who were also superinfected with hepatitis A, C, D, or E virus, as well as their hepatitis B virus e system status, so that suitable measures could be adopted to decrease the mortality of patients with chronic hepatitis B.

Methods: This study detected superinfections of hepatitis A, C, D, or E virus and the hepatitis B virus e system status in cases of fatal liver failure during the course of chronic hepatitis B by enzyme-lined immunosorbent assay.

Results: The frequency of superinfections of hepatitis A, C, D, and E virus was 1.4% (4/282), 6.4% (18/282), 1.8% (5/282), and 28.4% (80/282), respectively, overall, 37.9% (107/282). Hepatitis E was prominent and steady in superinfection rates during the past 12 years. In 62.1% (175/282) of patients, the causes of fatal liver failure were not clear. The serological status frequency of HBeAg(+) and anti-HBe(-), HBeAg(-) and anti-HBe(-), and HBeAg(-) and anti-HBe(+) was 20.6% (22/107), 23.4% (25/107), and 56.1% (60/107), respectively, in the group with superinfections of hepatitis A, C, D, or E virus and 31.4% (55/175), 21.1% (37/175), and 47.4% (83/175), respectively, in the group in which causes were not clear. The serological status HBeAg(+) and anti-HBe(-) was more frequent in the group in which causes were not clear than in the group with superinfections of hepatitis A, C, D, or E virus (P < 0.05). Statistically, there were no differences (P > 0.05) between the serological status HBeAg(-), anti-HBe(-) and HBeAg(-), anti-HBe(+) between the two groups.

Conclusions: These results suggest that superinfection (107/282) is an important factor in fatal liver failure. The mortality of chronic hepatitis B can be decreased by strict food sanitation and the use of safe blood products. There were no significant relationships between hepatitis B e antigen seroconversion and fatal liver failure during the course of chronic hepatitis B.
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http://dx.doi.org/10.1007/s00535-005-1781-yDOI Listing
April 2006
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