Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that catalyzes the conversion of heme to CO, biliverdin, and iron, which together protect cells from oxidative and inflammatory damage and play an important role in maintaining cell homeostasis. In recent years, HO-1 has also been found to have antiviral biological effects, and the induced expression of HO-1 inhibits the replication of various viruses such as hepatitis C virus, hepatitis B virus, human immunodeficiency virus, dengue virus, ebolavirus, influenza A virus, Zika virus, severe acute respiratory syndrome coronavirus 2, human respiratory syncytial virus, hepatitis A virus and enterovirus 71. The inhibitory effect of HO-1 on these viruses involves three mechanisms, including direct inhibition of virus replication by HO-1 and its downstream products, enhancement of type I interferon responses in host cell, and attenuation of inflammatory damage caused by viral infection. This review focuses on the recent advances in the antiviral effect of HO-1 and its mechanism, which is expected to provide evidence for HO-1 as a potential target for antiviral therapy.

Diabetic cardiomyopathy (DCM) is described as abnormalities of myocardial structure and function in diabetic patients without other well-established cardiovascular factors. Although multiple pathological mechanisms involving in this unique myocardial disorder, mitochondrial dysfunction may play an important role in its development of DCM. Recently, considerable progresses have suggested that mitochondrial biogenesis is a tightly controlled process initiating mitochondrial generation and maintaining mitochondrial function, appears to be associated with DCM. Nonetheless, an outlook on the mechanisms and clinical relevance of dysfunction in mitochondrial biogenesis among patients with DCM is not completely understood. In this review, hence, we will summarize the role of mitochondrial biogenesis dysfunction in the development of DCM, especially the molecular underlying mechanism concerning the signaling pathways beyond the stimulation and inhibition of mitochondrial biogenesis. Additionally, the evaluations and potential therapeutic strategies regarding mitochondrial biogenesis dysfunction in DCM is also presented.

Intervertebral disc degeneration is considered as a primary cause of clinical low back pain, however the molecular mechanism is not clear yet. Recently, researches on the molecular basis of intervertebral disc degeneration have become a hotspot. The special structure and biomechanics properties of the disc contribute to its propensity toward degeneration. Intervertebral disc degeneration is associated with the changes of the cytological behavior,including the increase in cell death and the degradation of extracellular matrix. However, the mechanism of cell death including cell apoptosis and autophagy in intervertebral disc degeneration remains unclear. Further study on the molecular mechanism of intervertebral disc degeneration is the foundation of improving and treating the intervertebral disc degeneration in the future. Although some progresses are made in the aspect of biological study, the biological environment of intervertebral disc itself is still a challenge for the development of biological treatment. This article is to review the latest advance on the biological characteristics of normal intervertebral disc and the cell death in the process of the intervertebral disc degeneration.
Animals ; Apoptosis ; Cell Death ; Extracellular Matrix ; metabolism ; Humans ; Intervertebral Disc ; cytology ; metabolism ; Intervertebral Disc Degeneration ; metabolism ; physiopathology

Objective To explore the effect of diabetes mellitus (DM) on biological behavior of epidermal keratinocyte in rats. Methods A total of 40 Sprague-Dawley rats were randomized into control group and streptozotocin (STZ) -induced diabetes group. Of each group, 10 rats were implemented with deep partial-thickness scalding. The re-epithelialization rate was observed at the 3rd, 7th, 14th and 21th post-burn day. Histological characteristics and thickness of epidermal tissue in both groups were observed. The adhesion rate, cell cycles, apoptosis rate and migration ability of keratinocyte were measured. The accumulation of advanced glycosylation end products (AGEs) of epidermal tissue was observed. Results The percentages of re-epithelialized area at the 7th, 14th and 21th post-burn day were much lower in DM group than in control group (P<0.05). In DM group, the epidermal thickness was reduced obviously with obscure multilayered epithelium and less amount of prickle cells; The adhesion rates of 12, 24 h after culturing keratinocyte and the percentage of G2/M phase cells were lower in DM group than in control group (P<0.05). However, apoptosis rate of keratinocyte was higher, the amount of migration cell was significantly less in DM group than in control group (both P<0.05). There were lots of AGEs accumulated in epidermal tissue in DM group, while there were hardly AGEs in control group. Conclusions Re-epithelization blocked exists on non-healing wound in DM rats, which is related with the impaired keratinocyte biological behavior. A large of AGEs accumulate in the epidermal tissue of DM rats, which may be a important reason to inhibit keratinocyte function in diabetic environment.

To study the pharmacokinetic characteristics and absolute bioavailability of α-asarone through dry powder inhalation in rats, and compare with that through oral administration and intravenous injection. A HPLC method was established for the determination of α-asarone in rat plasma to detect the changes in plasma concentrations of α-asarone through dry powder inhalation (20 mg · kg(-1)), oral administration (80 mg · kg(-1)) and intravenous injection (20 mg · kg(-1)) in rats. DAS 2.0 software was used to calculate the pharmacokinetic parameters. The absolute bioavailability of α-asarone was calculated according to AUC(0-t)) of administration routes and administration doses. According to the results, α-asarone showed good linear relations (r = 0. 999 4) at concentrations between 0.282-14.1 mg · L(-1), with the limit of detection (LOD) at 0.212 mg · L(-1). Through dry powder inhalation, oral administration and intravenous injection of α-asarone, the metabolic processes of α-asarone in rats conformed to one, two and three compartment models respectively, with the elimination half-life of (95.48 ± 48.28), (64.34 ± 27.59), (66.99 ± 29.76) min. According to the bioavailability formula, the absolute bioavailability of α-asarone through dry powder inhalation and oral administration were 78.32% and 33. 60%, respectively. This study showed that significant increase in elimination half-life and absolute bioavailability of α-asarone through dry powder inhalation, which lays a theoretical foundation for preparing α-asarone dry powder inhalers.
Administration, Inhalation ; Animals ; Anisoles ; administration & dosage ; blood ; pharmacokinetics ; Biological Availability ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; pharmacokinetics ; Half-Life ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effects of Shadu Cao Mixture (SDCM, traditional Chinese medicine) on immune functions of immunosuppression mice.

METHODSFifty BALB/C mice were randomly divided into blank control group, model group, SDCM low-dose, middle-dose and high-dose group. Except the blank control group, other groups were intraperitoneal injected with cyclophosphamide (40 mg/kg) to establish immunosuppression mice model. The blank control group and model group received gavage administration with nonnal saline, while the other groups received gavage administration with different doses of SDCM (10, 20, 40 m/kg for 15 days) respectively. The number of leukocytes and serum levels of interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in peripheral blood, spleen index, and the function of NK cells were measured.

RESULTSCompared with the model group , SDCM increased the number of leukocytes and serum concentrations of IL-2, TNF-α and IFN-γ in peripheral blood and improved the spleen index and the function of NK cells significantly (P < 0.05-0.01).

CONCLUSIONSDCM could remarkably enhance the immune functions of immunosuppression mice induced by cyclophosphamide.

Animals ; Cyclophosphamide ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Immunosuppression ; Interferon-gamma ; blood ; Interleukin-2 ; blood ; Killer Cells, Natural ; immunology ; Mice ; Mice, Inbred BALB C ; Spleen ; immunology ; Tumor Necrosis Factor-alpha ; blood

The aim of this study was to investigate the clinical characteristics and prognosis of acute erythroleukemia (AEL, AML-M6). The clinical features and results of morphologic, immunophenotypic, cytogenetic and molecular biologic detections were retrospectively analyzed in 13 cases of AEL from 305 acute leukemia patients hospitalized between October 2007 and October 2012. The results showed that the expression of erythroid and non-erythroid cells increased at the same time. The myeloid antigens mainly expressed CD13/CD33/CD117/CD34, while the erythroid antigens expressed Gly and CD71. The karyotypic detection indicated that there were 1 case with normal karyotype, 3 cases with simple karyotypic abnormality and 2 cases with complex karyotypic abnormality, the other cases were not detected. The molecular biological detection found that the poor prognosis gene existed in 5 cases [38.5% (5/13)], including 3 cases with MLL-MLL fusion gene, 1 case with MLL mutation, and 1 cases with NRAS gene mutation, the abnormal genes were not detected in remainder 8 cases. After chemotherapy with decitabine, the complete remission (CR) rate achieved 53.5% (7/13), partial remission (DR) rate achieved 15.4% (2/13). Finally, 8 patients received allo-HSCT, the median overall survival (OS) was 20.7 months, 3 year survival rate was 79%, 3 year disease-free survival rate was 78%. It is concluded that the acute erythroleukemia is a rare subtype of AML, which is transformed from MDS and has harmful genes and poor prognosis. Allo-HSCT and treatment with decitabine may enhance the survival rate of AEL.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Humans ; Karyotyping ; Leukemia, Erythroblastic, Acute ; diagnosis ; genetics ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; Young Adult

OBJECTIVETo observe the clinical significance of postoperative personalized antithrombotic therapy for patients with hemophilic arthritis (HA) patients after arthroplasty.

METHODSFrom September 2005 to October 2013, 11 cases of arthroplasty for hemophilic arthritis in hip and knee total operation 14 times,including 1 case of double knees (calculated as one operation), operation in left knees 6 times, operation in right knees 5 times, 2 in hip. All the patients were male and the age ranged from 23 to 57 years old,with an average of (36.1 ± 11.0) years old; the average weight was (64.1 ± 8.9) kg. All the patients were preoperatively diagnosed and classified as hemophilic arthritis with the radiological images and laboratory tests. According to the function of joints, the risk of postoperative venous thromboembolism (VTE), and dynamic observation of Factor VIII:C (FVIII:C) activity, patients were treated with personalized antithrombus by adjusting the dosage of recombinant human coagulation factor VIII (Kogenate FS). All the patients were orderly divided into postoperatively distal joints moving group and none-moving group to observe the coagulation function.

RESULTSThe enrolled patients had no postoperative complication of VTE and pulmonary embolism (PE). The APTT and D-2 were different between two groups in the postoperative early stage. Length of hospital day was shorter in the moving group than none-moving group.

CONCLUSIONBecause of the self-coagulation disorder, patients with HA tended to bleed. However it doesn't mean that there is no risk of postoperative thrombosis. Therefore,it's important to determine how to control the balance between postoperative antithrombus, hemostasis,and coagulation factor replacement therapy after arthroplasty for HA. Postoperative moving has proved helpful for HA, especially in reducing the risk of hemostasis and shortening the time in hospital.

Adult ; Arthritis ; surgery ; Arthroplasty ; adverse effects ; Factor XIII ; metabolism ; Hemophilia A ; complications ; Hemostasis ; Humans ; Male ; Middle Aged ; Postoperative Complications ; prevention & control ; Thrombosis ; prevention & control ; Young Adult

OBJECTIVETo investigate the anti-proliferative effects of curcumol, an herbal extract from curcuma, in human hepatocarcinoma HepG2 cells, and its possible molecular mechanism.

METHODThe effects of curcumol on human hepatocarcinoma cells were assessed in vitro. Proliferation of HepG2 cells treated with various concentration (2.5-10 mg x L(-1)) of curcumol was determined using the MTT assay and the distribution of cell cycle of HepG2 cells was analyzed using the FCM technique. Expression of 14 cell cycle regulation-related genes were assessed by TaqMan real-time polymerase chain reaction (RT-PCR) method and Western blot.

RESULTCurcumol significantly inhibited the proliferation of HepG2 cells and induced G1 phase arrest in a dose- and time-dependent manner. The mRNA levels of pRB1, cyclin D1, CDK2, CDK8 and p27KIP1 were elevated, while cyclin A1 decreased, in both of the low (25 mg x L(-1)) and the high dose (100 mg x L(-1)) treatment of curcumol. There were no significant changes in the expression of either cyclin E1 or CDK4. The expression of p53 and its target genes p21WAF1 and Wip1 protein were increased.

CONCLUSIONCurcumol can inhibit the proliferation of HepG2 cells in vitro and induce G1 arrest of cell cycle through mechanisms activating p53 and pRB pathways that involve genes of cyclin A1, CDK2, CDK8, p21WAF1 and p27KIP1.

Carcinoma, Hepatocellular ; drug therapy ; physiopathology ; Cell Division ; drug effects ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Hep G2 Cells ; Humans ; Liver Neoplasms ; drug therapy ; physiopathology ; Sesquiterpenes ; pharmacology

OBJECTIVETo evaluate the value of serum brain natriuretic peptide (BNP) in the diagnosis of hyperthyroid heart disease in children.

METHODSFifty-eight children with hyperthyroidism were assigned to two groups according to their cardiac functions: hyperthyroid heart disease (n=28) and hyperthyroidism alone (n=30). Thirty healthy children served as the control group. Serum BNP level, left ventricular ejection fraction (LVEE) and E/A ratio were measured before and after treatment. The diagnostic value of BNP was evaluated in children with hyperthyroid heart disease.

RESULTSThe serum BNP level in the hyperthyroid heart disease and the hyperthyroidism alone groups before treatment was significantly higher than that in the control group (P<0.05), while the LVEF and the E/A ratio were significantly lower than those in the control group (P<0.05). Serum BNP level was positively correlated with the TT3 (r=0.801, P<0.05) and TT4 levels (r=0.578, P<0.05) and negatively with the LVEF (r=-0.48, P<0.05) and the E/A ratio (r=-0.35, P<0.05) in the hyperthyroid heart disease group. The serum BNP, TT3 and TT4 levels in the hyperthyroid heart disease and the hyperthyroidism alone groups were reduced and the LVEF and the E/A ratio increased significantly three months after treatment (P<0.05). When serum BNP level of >323.62 pg/mL was proposed as a cutoff point, the sensitivity, specificity, positive predictive value and negative predictive value were 92.86%, 90.00%, 89.66% and 93.10% respectively for the diagnosis of hyperthyroid heart disease.

CONCLUSIONSBNP may serve as a reliable marker for the diagnosis of hyperthyroid heart disease in children. Serum BNP level along with the LVEF and the E/A ratio may be useful in the evaluation of the severity and the cardiac function in children with this disease.

Child ; Child, Preschool ; Female ; Heart Diseases ; blood ; diagnosis ; Humans ; Hyperthyroidism ; blood ; complications ; Male ; Natriuretic Peptide, Brain ; blood ; Thyroid Hormones ; blood ; Ventricular Function, Left