OBJECTIVEIt is revealed that circulating fibrocytes are elevated in patients/animals with cardiac fibrosis, and this review aims to provide an introduction to circulating fibrocytes and their role in cardiac fibrosis.

DATA SOURCESThis review is based on the data from 1994 to present obtained from PubMed. The search terms were "circulating fibrocytes " and "cardiac fibrosis ".

STUDY SELECTIONArticles and critical reviews, which are related to circulating fibrocytes and cardiac fibrosis, were selected.

RESULTSCirculating fibrocytes, which are derived from hematopoietic stem cells, represent a subset of peripheral blood mononuclear cells exhibiting mixed morphological and molecular characteristics of hematopoietic and mesenchymal cells (CD34+/CD45+/collagen I+). They can produce extracellular matrix and many cytokines. It is shown that circulating fibrocytes participate in many fibrotic diseases, including cardiac fibrosis. Evidence accumulated in recent years shows that aging individuals and patients with hypertension, heart failure, coronary heart disease, and atrial fibrillation have more circulating fibrocytes in peripheral blood and/or heart tissue, and this elevation of circulating fibrocytes is correlated with the degree of fibrosis in the hearts.

CONCLUSIONSCirculating fibrocytes are effector cells in cardiac fibrosis.

Coronary Disease ; pathology ; Fibroblasts ; physiology ; Fibrosis ; pathology ; Heart Failure ; pathology ; Humans ; Hypertension ; pathology ; Myocardium ; pathology

OBJECTIVETo explore the therapeutic effect and the hemorrheology change of berberine in new diagnosed patients with type 2 diabetes combining nonalcoholic fatty liver disease.

METHODSixty patients, in our department from March 2009 to March 2010, with type 2 diabetes and nonalcoholic fatty liver disease were randomly divided into two groups. One group was given berberine, another group was given Xuezhikang, both for 12 weeks. The indicators, include B-ultrasound of liver, triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), aspertate aminotransferase (AST), hemorrheology, were detected before and after treatment.

RESULTAfter treatment by berberine, B-ultrasound of liver were better than before, the effective rate was 70%, vs 73.3% after treatment by Xuezhikang. ALT, AST, TC, TG, LDL-L, hemorrheology (including the whole blood viscosity, whole blood viscosity, high cutting reduction of whole blood viscosity, plasma cutting reductive low viscosity, blood sedimentation, RBC deposited, fibrinogen) were significantly lower than before, however, HDL-L significantly increased (P<0.05). The therapeutic effect of xuezhikang was the same as berberine. The distance between the indicators of the two groups was no different.

CONCLUSIONBerberine can obviously improve the conditions of new diagnostic T2DM patients with nonalcoholic liver lesions, effectively reduce hemorrheology indicators, and has good application prospect.

Adult ; Alanine Transaminase ; blood ; Berberine ; therapeutic use ; Diabetes Mellitus, Type 2 ; blood ; diagnosis ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Fatty Liver ; blood ; diagnosis ; drug therapy ; Female ; Humans ; Lipoproteins, HDL ; blood ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; Treatment Outcome ; Triglycerides ; blood

OBJECTIVETo investigate the influence of aerosols on the expression of cyclin B(1), cyclin C and proliferating cell nuclear antigen (PCNA) in wound tissue healing of burned rat models.

METHODSSprague Dawley (SD) rats were inflicted as the deep partial thickness burn models. Rats were randomly divided into experimental group and control group. The experimental group were treated with aerosols. Samples were collected in 1 approximately 10 postburn days. Immunohistochemistry and image analysis methods were conducted to examine the expression of cyclin B(1), cyclin C and PCNA in both experimental and control groups.

RESULTSThe expression of cyclin C in experimental group was detected in nucleus of skin basal cell on the second postburn day, increased evidently at the fifth days and sustained at high expression level up to the tenth days after treatment. The expression of cyclin C in experimental group was significantly higher than control group (P < 0.05). The expression of PCNA was first observed in skin basal cell nucleus and hair follicle cell nucleus in both experimental and control group on the third postburn day. The expression of PCNA increased evidently at the fifth days in experimental after treatment and that increased evidently at the seventh days in control group, which showed there were lots of active proliferation cell. And the difference of the expression of PCNA between experimental and control group was significant (P < 0.01). The expression of cyclin B(1) was detected in nucleus and cytoplasm of skin basal cell in both groups on the third postburn day, and no difference between the experimental and control group (P > 0.05).

CONCLUSIONSAerosols can up-regulate the expression of cyclin C and PCNA in skin basal cell nucleus. Therefore the aerosols can accelerate wound tissue healing.

Aerosols ; Animals ; Burns ; metabolism ; therapy ; Cyclin B ; biosynthesis ; Cyclin B1 ; Cyclin C ; Cyclins ; biosynthesis ; Disease Models, Animal ; Electric Stimulation Therapy ; methods ; Female ; Proliferating Cell Nuclear Antigen ; biosynthesis ; Rats ; Rats, Sprague-Dawley ; Wound Healing ; physiology

BACKGROUNDGenetic variations at the interleukin 28B (IL-28B) locus are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. The aim of this research was to evaluate the role of IL-28B single nucleotide polymorphism (SNP) variations in Chinese patients undergoing pegylated interferon-α plus ribavirin (PEG-IFN-α/RBV) treatment.

METHODSTo determine the effect of IL-28B variation on the response to HCV therapy, these variants were genotyped in a cohort of 220 patients who were chronically infected with HCV and received combined PEG-IFN-α/RBV therapy.

RESULTSThe proportions of rs12979860 CC, CT, and TT genotypes were 71.4%, 25.0%, and 3.6% respectively, in the sustained virological response (SVR) group; 15.8%, 60.5%, and 23.7% respectively, in the null virological response (NVR) group; and 38.1%, 52.4%, and 9.5% respectively, in the relapse (Rel) group (P < 0.05). Logistic regression analysis showed that, compared to those having the CC genotype, CT heterozygotes had an increased risk of NVR and Rel (OR = 10.95, 95%CI = 4.12-29.11, P = 1.5×10(-7) and OR = 3.93, 95%CI = 1.86-8.32, P = 2.1×10(-4) respectively). The RNA quantification assay showed that patients with genotype CC exhibited much higher levels of IL-28 expression than those with genotype CT or TT (P < 0.001).

CONCLUSIONSThe IL-28B SNP rs12979860 genotype was related to the effectiveness of HCV therapy: patients with the CC rs12979860 genotype had higher rates of SVR than those with the CT or TT genotype, and the CC genotype revealed a significantly higher level of IL-28 mRNA expression.

Adult ; Antiviral Agents ; therapeutic use ; Genotype ; Hepatitis C, Chronic ; drug therapy ; genetics ; Humans ; Interferon-alpha ; therapeutic use ; Interleukins ; genetics ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; genetics ; Ribavirin ; therapeutic use

BACKGROUNDMetabolic syndrome (MS) is a risk factor for stroke and thromboembolism event. Left atrial or LA appendage (LA/LAA) thrombus is a surrogate of potential stroke. The relationship between MS and atrial thrombus remains unclear. In this study, we sought to investigate the effect of MS on risk stratification of LA/LAA thrombus formation in patients with nonvalvular atrial fibrillation (NVAF).

METHODSThis cross-sectional study enrolled 294 consecutive NVAF patients without prior anticoagulant and lipid-lowering therapies. LA/LAA thrombus was determined by transesophageal echocardiography. Risk assessment of LA/LAA thrombus was performed using the CHADS2 , CHA2DS2 -VASc, MS, CHADS2 -MS, and CHA2DS2 -VASc-MS scores. Logistic regression analyses were performed to determine which factors were significantly related to LA/LAA thrombus. Odds ratio (OR) including 95% confidence interval was also calculated. The predictive powers of different scores for the risk of LA/LAA thrombus were represented by C-statistics and compared by receiver operating characteristic (ROC) analysis.

RESULTSLA/LAA thrombi were identified in 56 patients (19.0%). Logistic analysis showed that MS was the strongest risk factor for LA/LAA thrombus in NVAF patients (OR = 14.698, P < 0.001). ROC curve analyses revealed that the C-statistics of CHADS2 -MS and CHA2DS2 -VASc-MS was significantly higher than those of CHADS2 and CHA2DS2 -VASc scores (CHADS2 -MS vs. CHADS2 , 0.807 vs. 0.726, P = 0.0019). Furthermore, MS was helpful for identifying individuals with a high risk of LA/LAA thrombus in the population with a low risk of stroke (CHADS2 or CHA2DS2 -VASc score = 0).

CONCLUSIONSMS is associated with LA/LAA thrombus risk in patients with NVAF. In addition to the CHADS2 and CHA2DS2 -VASc scores, the CHADS2 -MS and CHA2DS2 -VASc-MS scores provide additional information on stroke risk assessment.

Aged ; Atrial Appendage ; pathology ; Atrial Fibrillation ; complications ; physiopathology ; Cross-Sectional Studies ; Female ; Humans ; Male ; Metabolic Syndrome ; complications ; physiopathology ; Middle Aged ; Multivariate Analysis ; ROC Curve ; Risk Factors ; Thrombosis ; etiology ; physiopathology

Objective To investigate the changing trend of platelet count (PLT) and related influencing factors in patients with hepatitis B virus-related chronic-on-acute liver failure (HBV-ACLF) after artificial liver support system (ALSS) therapy. Methods A total of 152 patients with HBV-ACLF who were hospitalized and treated in The Third Affiliated Hospital of Sun Yat-Sen University from January 2018 to November 2021 were included in the study, among whom 102 patients received plasma exchange (PE) and 50 patients received double plasma molecular absorption system combined with low-dose PE, and their clinical data and laboratory marker were measured. The independent samples t -test or the Mann-Whitney U test was used for the comparison of continuous data between two groups, and the chi-square test was used for the comparison of categorical data between two groups; a multivariate logistic regression analysis was used to investigate the risk factors for PLT > 50×10 9 /L after ALSS therapy; the receiver operating characteristic (ROC) curve was used to investigate the value of baseline PLT in predicting PLT > 50×10 9 /L after ALSS therapy. Results The patients were mostly middle-aged male adults; among the 152 patients, 70 (46.1%) had liver cirrhosis on admission, 114 (75.0%) received three sessions of ALSS therapy, and 88% had a baseline PLT count of > 50×10 9 /L. There was a significant reduction in PLT from baseline to after ALSS therapy (79.5±47.7 vs 112.5±64.1, t =4.965, P < 0.001), and at 1 week after treatment, PLT increased to the baseline level (97.2±50.7 vs 112.5±64.1, t =1.787, P =0.075). As for the change in PLT from baseline to 1 week after ALSS therapy, the liver cirrhosis group had a significantly greater reduction in PLT than the non-liver cirrhosis group ( U =1986.5, P =0.026), while there was no significant difference between different procedures of ALSS therapy and different sessions of treatment (3-5 sessions) (all P > 0.05). The multivariate logistic regression analysis showed that cirrhosis (odds ratio [ OR ]=3.097, 95% confidence interval [ CI ]: 1.255-7.645, P =0.014) and PLT > 50×10 9 /L at baseline ( OR =0.019, 95% CI : 0.002-0.154, P < 0.001) were independent risk factors for PLT > 50×10 9 /L after ALSS therapy. The ROC curve analysis of baseline PLT showed that PLT > 80.5×10 9 /L at baseline was the optimal cut-off value affecting PLT > 50×10 9 /L after treatment, with an area under the ROC curve of 0.818. Conclusion The influence of ALSS therapy on PLT is temporary, but cirrhotic patients have a weaker PLT generation ability than non-cirrhotic patients. PLT > 80.5×10 9 /L at baseline is the optimal cut-off value to reduce the risk of bleeding after ALSS therapy.

OBJECTIVETo study the effect and implication of nonmyeloablative donor specific bone marrow (DSBM) infusion on the immunoreaction of liver allotransplantation.

METHODSOrthotopic liver transplantation model was used in this study. Groups were set as follows: Group I, syngeneic control (Wistar-to-Wistar); Group II, acute rejection (SD-to-Wistar); Group III, acute rejection treated with cyclosporine A (CsA) by intramuscular injection (SD-to-Wistar+CsA); Group IV, bone marrow infusion at 7 d pretransplantation followed by short-term CsA treatment (SD-to-Wistar+DSBM); Another group of short-term CsA treatment preoperatively without bone marrow infusion was also set as control. General characteristics and survival time were observed. Histological grades of rejection were determined by pathological examination. IL-2 and IFN-gamma level in peripheral blood and donor liver were detected respectively by Enzyme-Linked Immuno-Sorbent Assay (ELISA) and Western blot. Chimerism of donor cells was measured by PCR for a male-specific marker (Y-chromosome-specific sequence, Sry).

RESULTSNo signs of rejection were found in Group I. Acute rejection occurred in both Group II and the short-term CsA treated group. All the recipients died at (9-15) d posttransplantation with a median survival time of (10.7+/-0.5) d and (11.2+/-2.4) d, respectively. Only mild rejection could be seen in Group III. In Group IV, 4 out of 6 recipients had long-term survival (>100 d), the histological grade of rejection was significantly lower than that of Group II, so did the expression level of IL-2 and IFN-gamma in both peripheral blood and grafted liver. Y-chromosome-specific sequence (Sry) of male SD rats could be detected in the bone marrow, spleen and thymus of female recipients at 15 d after bone marrow infusion.

CONCLUSIONMild preconditioning nonmyeloablative donor specific bone marrow infusion can enhance chimerism formation in recipients, alleviate the rejection of liver allotransplantation and prolong survival of liver allotransplantation.

Animals ; Bone Marrow Transplantation ; immunology ; methods ; Graft Rejection ; etiology ; immunology ; prevention & control ; Liver Transplantation ; adverse effects ; immunology ; Male ; Rats ; Rats, Inbred Strains ; Rats, Wistar ; Transplantation, Homologous ; adverse effects ; immunology ; Treatment Outcome

OBJECTIVETo investigate the regular pattern of the distribution of skin epidermal stem cells (ESCs) in the different parts of a healthy human body, and to evaluate the feasibility of the identification of ESCs by P63 and CD29 with single and double labeling.

METHODSFull-thickness skin samples from 21 parts (including scalp, dorsum of foot, sole of foot, pubic region, and scrotum) of 5 healthy persons were harvested for the study. Immunohistochemistry method with biotin-streptavidin-horseradish peroxidase (SP) was employed with P63 and CD29 as the first antibody to carry out single and double labeling. The staining results were subjected to image analysis. The distribution of the ESCs in the skin from the above parts was observed and expressed as positive unit (PU) value.

RESULTSIt was found by P63 single labeling and P63 and CD29 double labeling that the PU value in the dorsum of foot was the lowest while that in the scalp was the highest among all the parts of a healthy body. It was also found by CD29 single labeling that the PU value in the dorsum of foot was the lowest [(11.9 +/- 1.5)%] while highest in the scalp [(29.1 +/- 5.0)%]. The PU value in the hairy region of a human body was evidently higher than that in the non-hairy region (P < 0.01), when examined by P63 and CD29 single and double labeling. But there was no difference in the PU values between the trunk and limbs by means of P63 and CD29 single and double labeling (P > 0.05).

CONCLUSIONThere are more ESCs in the skin from the scalp, mons pubis and scrotum than other parts of the body. Single P63 or CD29 labeling exhibits higher sensitivity but lower specificity in the identification of ESCs. While the double labeling method exhibits higher specificity but lower sensitivity. Above all, it seems that the double labeling may be a simple and effective method for the identification of ESCs.

Epithelial Cells ; cytology ; Humans ; Immunohistochemistry ; Integrin beta1 ; Male ; Skin ; cytology ; Stem Cells

OBJECTIVETo investigate the effect of combined CsA and FK506 with 5-FU on hepatocellular carcinoma rats.

METHODSA syngeneic rat model of hepatocellular carcinoma was used. Control group (A) underwent 4 ml 5% GS. Treatment group was divided into 3 groups namely, group B: only 5-FU and 5% GS; group C: 5-FU, CsA and 5% GS; group D: 5-FU, FK506 and 5%GS. Cell cycle, apoptosis, necrosis and mitochondrial transmembrane potential were measured by flow cytometry, laser scanning confocal microscopy, and electron transmission microscopy. Statistical analysis was performed by SPSS 10.0 for Windows software. Statistical comparisons were made with ANOVA followed by Dunnett's T3 or LSD test.

RESULTSCompared to the control group, the percentage of apoptotic cells including trifle necrotic cells was significantly higher, and among the treatment group, group D was the highest, and group C was higher than group B. In the treatment group, cell cycle of hepatoma cells was mainly arrested at S phase, but in group D, G0/G1 phase cells were significantly decreased and S phase cells significantly increased. Compared to the control group, mitochondrial transmembrane potential was significantly decreased in the treatment group, among with, group B was the lowest, group C was higher than group D. Morphological changes demonstrated by electron microscopy included dispersed nuclear chromatin, loss of nucleoli, membrane bleeding, cell shrinkage, typical apoptotic bodies and marked swelling of mitochondria in the treatment group. In the control group, however, they were characterized by normal cell ultrastructure.

CONCLUSIONSThe present study reveals that 5-FU combined with CsA or FK506 demonstrated a synergistic effect on hepatocellular carcinoma rats. For FK506, the powerful mutual effect is related to the increase of tumor cell's quantity in S phase. Both CsA and FK506 can provide protection on mitochondrial transmembrane potential reduction against hepatoma cells damage from 5-FU.

Animals ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; drug therapy ; Cyclosporine ; administration & dosage ; Fluorouracil ; administration & dosage ; pharmacology ; Liver Neoplasms ; drug therapy ; Male ; Membrane Potentials ; drug effects ; Mitochondria ; drug effects ; physiology ; Necrosis ; Rats ; Rats, Wistar ; Tacrolimus ; administration & dosage

OBJECTIVETo investigate the role of focal adhesion kinase (FAK) in adhesion and migration of hepatic stellate cells (HSC).

METHODSTwo recombinant plasmids expressing short hairpin RNAs (shRNAs) targeting FAK were constructed and one plasmid substantially suppressing FAK expression in HSC was selected. Real-time PCR and Western blot were used to detect the knockdown effects of FAK gene. After 48-hour treatment with FAK shRNA, toluidine blue colorimetric assay was used to detect the cell adhesion. Wound-healing assay and improved Boyden double-chamber were used to detect the cell migration induced by FN.

RESULTSThe recombinant plasmid expressing FAK shRNA was successfully constructed and transfected into HSC. Compared with the controls, the expression of FAK mRNA and protein in HSC treated with FAK shRNA was markedly down-regulated by 76.82% and 72.53%, respectively. The expression of p-FAK (Tyr397) protein was also decreased by 62.71% 48 h posttransfection. The adhesion of HSC was inhibited by 58.69% at 48 h after shRNA transfection. FAK gene silencing could also dramatically inhibit FN-stimulated HSC migration, and the cell migration distance and the cell number of crossing membrane were decreased by 58.27% and 83.70%, respectively.

CONCLUSIONSFAK gene silencing suppresses adhesion and migration of HSC, and FAK may be a potential target for novel anti-fibrosis therapies.

Animals ; Blotting, Western ; Cell Adhesion ; Cell Line ; Cell Movement ; Down-Regulation ; Fibronectins ; Focal Adhesion Kinase 1 ; genetics ; metabolism ; Genetic Vectors ; Hepatic Stellate Cells ; cytology ; enzymology ; Liver Cirrhosis ; pathology ; prevention & control ; Plasmids ; genetics ; Polymerase Chain Reaction ; RNA Interference ; RNA, Messenger ; genetics ; metabolism ; Rats ; Transfection