High mobility group box-1 protein (HMGB1) has recently been shown as a crucial late mediator of inflammation and sepsis, and is involved in mediating multi-organ functional lesions, including acute lung, liver, and intestine injuries. As a delayed inflammatory cytokine, HMGB1 provides a wider therapeutic time window for clinical intervention. HMGB1 has been proven to be a promising therapeutic target to prevent the development of multiple organ dysfunction syndrome in experimental models of severe sepsis. The pharmacological strategies include neutralization of antibodies or specific HMGB1 antagonists, suppression of HMGB1 secretion (ethyl pyruvate, agonists for alpha7-nicotinic acetylcholine receptors), and down-regulation of HMGB1 expression (sodium butyrate, signaling inhibitors for Janus kinase/signal transducer and activator of transcription).
HMGB1 Protein ; antagonists & inhibitors ; biosynthesis ; physiology ; Humans ; Multiple Organ Failure ; immunology ; metabolism ; prevention & control ; Sepsis ; immunology ; metabolism ; therapy

0.05).Conclusion MSCs could derive to cardiomyocyte-like cells after induction and incubation for 4 weeks in vitro,of which Ca~(2+)/CaMKⅡ is similar to the normal cardiomyocytes cells.

Burns ; complications ; diagnosis ; prevention & control ; Humans ; Sepsis ; diagnosis ; etiology ; prevention & control

Adenocarcinoma ; diagnosis ; genetics ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; genetics ; Carcinoma, Squamous Cell ; diagnosis ; genetics ; Cyclin-Dependent Kinase Inhibitor p16 ; blood ; metabolism ; DNA Methylation ; Genes, p16 ; Humans ; Lung Neoplasms ; diagnosis ; genetics ; Tumor Suppressor Proteins ; blood ; metabolism

Adult ; Herpes Zoster ; etiology ; Herpesvirus 3, Human ; genetics ; Humans ; Male ; Middle Aged ; Mutation

Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Molecular Docking Simulation ; Molecular Structure ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; Quinazolinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

Male infertility is a worldwide problem, and about 15% of the cases are associated with spermatogenesis-related gene mutation. The mammalian gene UBE2B is the homolog of the RAD6 gene of yeast, belonging to the ubiquitin proteasome system and playing an important role in spermatogenesis. Mice lacking the UBE2B gene are infertile, with reduced sperm motility, increased morphologically abnormal sperm, and inhibited meiosis of spermatogonia. Accumulated evidence shows that UBE2B gene mutants and single nucleotide polymorphisms are associated with male infertility. This article reviews the relation between the UBE2B gene and male infertility, offering some theoretical evidence for the diagnosis and treatment of male infertility.
Animals ; Asthenozoospermia ; genetics ; Humans ; Infertility, Male ; genetics ; Male ; Meiosis ; Mice ; Mutation ; Polymorphism, Single Nucleotide ; Spermatogenesis ; genetics ; Ubiquitin-Conjugating Enzymes ; genetics

ObjectiveTo study the imaging characteristics of SPN of adenocarcinoma (ASPNs) on 18F-FDG PET/CT.MethodsThe morphological and metabolic features of 35 ASPNs on FDG PET/CT were retrospectively reviewed.SUVmax (SUV) was measured and ΔSUVmax was calculated according to ΔSUVmax =(SUVmax on delay imaging - SUVmax on early imaging)/SUVmax on early imaging × 100％.Statistical analysis was performed by software SPSS 11.5 using t-test,analysis of variance and Fisher exact test.Results( 1 ) Fifteen ASPNs (42.86％,15/35) presented as nodular pattern on FDG PET imaging,while 20 (57.14％,20/35) as lamellar,cloudy or ill-defined patterns.The SUVmax of these ASPNs followed a descending order of nodular,lamellar,cloudy and ill:defined on both early and delay imaging (F =30.696 and 24.758,both P＜0.001).(2)There were 54.29％ (19/35) ASPNs with SUVmax ≥2.5 and 45.71％ (16/35) ASPNs with SUVmax ＜2.5.(3) Of 35 ASPNs,24(68.57％ ) were solid nodules and 11(31.43％) were ground glass nodules with SUVmax =4.54 ±2.69 and 1.30±0.87,respectively (t =-5.234,P ＜O.001 ).(4) The SUVmax of ASPNs on delay FDG imaging (4.22 ±3.52) was significantly higher than that on early imaging (3.49 ±2.72) (t =-4.021,P ＜0.001 ).However,SUVmax was dependent on SUVmax on the early imaging:when SUVmax ≥2.5,ΔSUVmax was positive in 94.74％ (18/19) of ASPNs; while SUVmax ＜2.5,ΔSUVmax was positive in 56.25％ (9/16) of ASPNs (P =0.013).(5) Of 31 ASPNs with cell differentiation data,there were 10/17 well-differentiated ASPNs and 13/14 poorly-differentiated ASPNs with positive ΔSUVmax ( P =0.045 ).The average SUVmax of well-differentiated ASPNs was significantly lower than that of poorly-differentiated ASPNs ( 1.70 ± 1.51 vs 4.91 ± 2.69,t =- 3.951,P ＜ 0.001 ).Conclusions The morphological and metabolic features of ASPNs are diversified.It is common for ASPN to present with SUVmax ＜ 2.5.ΔSUVmax may be helpful for differentiating malignant from benign SPNs.

BACKGROUND: High mobility group box 1 protein (HMGB1) is a highly conserved, ubiquitous protein in the nuclei and cytoplasm of nearly all cell types. HMGB1 is secreted into the extracellular milieu and acts as a proinflammatory cytokine. In this article we reviewed briefly the cellular immune response mediated by HMGB1 in inflammation and sepsis. METHODS: This systemic review is mainly based on our own work and other related reports. RESULTS: HMGB1 can actively affect the immune functions of many types of cells including T lymphocytes, regulatory T cells (Tregs), dendritic cells (DCs), macrophages, and natural killer cells (NK cells). Various cellular responses can be mediated by HMGB1 which binds to cell-surface receptors [e.g., the receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)2, and TLR4]. Anti-HMGB1 treatment, such as anti-HMGB1 polyclonal or monoclonal antibodies, inhibitors (e.g., ethyl pyruvate) and antagonists (e.g., A box), can protect against sepsis lethality and give a wider window for the treatment opportunity. CONCLUSION: HMGB1 is an attractive target for the development of new therapeutic strategies in the treatment of patients with septic complications.

Objective: To observe the clinical effect of Zheng's Jin Gou Diao Yu (gold-hook-fishing) acupuncture method versus ordinary acupuncture on superficial fascia for treating neck type cervical spondylopathy in Kyrgyz. Methods:A total of 64 Kyrgyz patients conforming to the diagnostic criteria of neck type cervical spondylopathy were included. The patients were randomized into a Zheng's Jin Gou Diao Yu (gold-hook-fishing) acupuncture group and a conventional acupuncture group, with 32 cases in each group. Patients in the Zheng's Jin Gou Diao Yu (gold-hook-fishing) acupuncture group were treated with Zheng's Jin Gou Diao Yu (gold-hook-fishing) acupuncture method to stimulate the superficial fascia, the stimulation sites were primarily located at bilateral sides of the cervical vertebra as well as the trigger points in shoulder-neck region; patients in the conventional acupuncture group were punctured at the same acupoints, with twirling reducing method, and the depth of insertion was determined by the treated region. Patients in both groups received treatment every day for a succession of 5 d as a course, with a 2-day interval between 2 courses, and the whole treatment lasted for 3 courses. After 3 courses of treatment, the McGill pain questionnaire (MPQ) and neck disability index (NDI) were measured to compare the clinical effect between the two groups. Results: After treatment, scores of MPQ and NDI scale dropped when compared with those before treatment, and the differences showed statistical significance (allP<0.05); scores of MPQ and NDI in the Jin Gou Diao Yu (gold-hook-fishing) acupuncture group were substantially lower than those in the conventional acupuncture group, and the differences showed statistical significance (allP<0.05). The total effective rate was 96.9％ in the Jin Gou Diao Yu (gold-hook-fishing) acupuncture group and the cured rate was 78.1％, which were higher than 81.3％ and 40.6％ in the conventional acupuncture group, and the differences showed statistical significance (bothP<0.05). Conclusion: Zheng's Jin Gou Diao Yu (gold-hook-fishing) acupuncture method by stimulating superficial fascia to treat cervical spondylopathy in Kyrgyz can produce a better clinical effect than conventional acupuncture treatment, and is effective in improving pain and stiffness in patients, and thus is worth clinical popularization.