Signal Integration of IFN-I and IFN-II With TLR4 Involves Sequential Recruitment of STAT1-Complexes and NFkB to Enhance Pro-inflammatory Transcription

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The role of autologous bone graft in surgical treatment of hypertrophic nonunion of midshaft clavicle fractures

AbstractBackgroundThis study was conducted to evaluate the results of treating hypertrophic nonunion of mid-shaft clavicle fracture with a limited contact dynamic compression plate (LC-DCP) without autologous cancellous bone graft.MethodsFrom 1995 to 2008, 51 cases of hypertrophic nonunion of mid-shaft clavicle fracture were managed with open reduction and internal fixation by LC-DCP without bone graft involvement. Of these 51 cases, 30 had nonunion after failure of initial surgical treatment (Group 1), and 21 had nonunion after failure of conservative treatment (Group 2). Preoperative and postoperative case management were the same for both groups, with the average follow-up period being 20.4 months (range 18–36). Our study evaluated the radiographic results and functional outcomes of these cases according to the quick disability of arm, shoulder, and hand score.ResultsAll 51 cases resulted in uneventful unions. There was no statistically significant difference between the two groups regarding patient demography, cause of injury, preoperative and postoperative functional scores, length of operation, union time, and duration of hospitalization (p>0.05).ConclusionLC-DCP fixation is an effective method for treating hypertrophic nonunion of mid-shaft clavicle fracture. Local bone graft is sufficient to achieve necessary union, and autologous bone graft from other sites of the body appears unnecessary

X-linked hyper-IgM syndrome with CD40LG mutation: Two case reports and literature review in Taiwanese patients

Hyper-IgM syndrome (HIGM) is a rare primary immunodeficiency disorder characterized by elevated or normal serum IgM and decreased IgG, IgA, and IgE due to defective immunoglobulin class switching. X-linked HIGM (XHIGM, HIGM1) is the most frequent type, is caused by mutations in the CD40 ligand gene, and is regarded as a combined T and B immunodeficiency. We report an 18-year-old male who was diagnosed initially with hypogammaglobulinemia in infancy, but developed repeated pneumonia, sepsis, cellulitis, perianal abscess, pericarditis, and bronchiectasis despite regular intravenous immunoglobulin replacement therapy. The patient died at age 18 years due to pneumonia and tension pneumothorax. Mutation analysis revealed CD40L gene mutation within Exon 5 at nucleotide position 476 (cDNA 476G > A). This nonsense mutation predicted a tryptophan codon (TGG) change to a stop codon (TGA) at position 140 (W140X), preventing CD40L protein expression. Sequence analysis in the family confirmed a de novo mutation. The second case of 6-month-old male infant presented as Pneumocystis jiroveci pneumonia and acute respiratory distress syndrome. Gene analysis of the CD40L gene revealed G to C substitution in Intron 4 (c.409 + 5G > C) and mother was a carrier. Hematopoietic stem cell transplantation, the only cure for XHIGM, was arranged in the second case

Neonauclea reticulata

In this study, we investigated whether the protective effects of Neonauclea reticulata water extract against ultraviolet B (UVB) irradiation in human skin fibroblast cell cultures (Hs68) are governed by its ability to protect against oxidative stress and expression of matrix metalloproteinases (MMPs). We found that Neonauclea reticulata extract exhibited DPPH scavenging activity and inhibited AAPH-induced haemolysis of erythrocytes in a dose- and time-dependent manner. We also found that pretreatment of fibroblasts with Neonauclea reticulata water extract resulted in markedly lower levels of MMP-1, -3, and -9 expressions. Furthermore, our results indicate that Neonauclea reticulata extract inhibits the expression of MMPs by inhibiting ERK, JNK, and p38 phosphorylation. Our results also demonstrate that treatment with Neonauclea reticulata extract protects against UVB-induced depletion of collagen. In addition, Neonauclea reticulata extract did not have a cytotoxic effect. These findings indicate that the antioxidant activity of Neonauclea reticulata extract resulted in inhibition of MMP-1, -3, and -9 expressions and in increased levels of collagen activity. Our results suggest that Neonauclea reticulata extract can protect against photoaging

Prognostic factors associated with the survival of oral and pharyngeal carcinoma in Taiwan

<p>Abstract</p> <p>Background</p> <p>In Taiwan, a distinct ethnic group variation in incidence and mortality rates has been suggested for most carcinomas. Our aim is to identify the role of prognostic factors associated with the survival of oral and pharyngeal carcinoma in Taiwan.</p> <p>Methods</p> <p>Taiwan Cancer Registry records of 9039 subjects diagnosed with oral and pharyngeal carcinoma were analyzed. The population was divided into three ethnic groups by residence, which were Taiwanese aborigines, Hakka and Hokkien communities. Five-year survival rates were estimated by Kaplan-Meier methods. Ethnic curves differed significantly by log-rank test; therefore separate models for Taiwanese aborigines, Hakka and Hokkien were carried out. The Cox multivariate proportional hazards model was used to examine the role of prognostic factors on ethnic survival.</p> <p>Results</p> <p>The five-year survival rates of oral and pharyngeal carcinoma were significantly poorer for Hokkien community (53.9%) and Taiwanese aborigines community (58.1%) compared with Hakka community (60.5%). The adjusted hazard ratio of Taiwanese aborigines versus Hakka was 1.07 (95%CI, 0.86–1.33) for oral and pharyngeal carcinoma mortality, and 1.16 (95%CI, 1.01–1.33) for Hokkien versus Hakka. Males had significantly poor prognosis than females. Subjects with tongue and/or mouth carcinoma presented the worst prognosis, whereas lip carcinoma had the best prognosis. Subjects with verrucous carcinoma had better survival than squamous cell carcinoma. Prognosis was the worst in elderly subjects, and subjects who underwent surgery had the highest survival rate.</p> <p>Conclusion</p> <p>Our study presented that predictive variables in oral and pharyngeal carcinoma survival have been: ethnic groups, period of diagnosis, gender, diagnostic age, anatomic site, morphologic type, and therapy.</p

Clinical characteristics and risk behavior as a function of HIV status among heroin users enrolled in methadone treatment in northern Taiwan

<p>Abstract</p> <p>Background</p> <p>Methadone treatment was introduced in Taiwan in 2006 as a harm-reduction program in response to the human immunodeficiency virus (HIV), which is endemic among Taiwanese heroin users. The present study was aimed at examining the clinical and behavioral characteristics of methadone patients in northern Taiwan according to their HIV status.</p> <p>Methods</p> <p>The study was conducted at four methadone clinics. Participants were patients who had undergone methadone treatment at the clinics and who voluntarily signed a consent form. Between August and November 2008, each participant completed a face-to-face interview that included questions on demographics, risk behavior, quality of life, and psychiatric symptoms. Data on HIV and hepatitis C virus (HCV) infections, methadone dosage, and morphine in the urine were retrieved from patient files on the clinical premises, with permission of the participants.</p> <p>Results</p> <p>Of 576 participants, 71 were HIV positive, and 514 had hepatitis C. There were significant differences between the HIV-positive and HIV-negative groups on source of treatment payment, HCV infection, urine test results, methadone dosage, and treatment duration. The results indicate that HIV-negative heroin users were more likely to have sexual intercourse and not use condoms during the 6 months prior to the study. A substantial percent of the sample reported anxiety (21.0%), depression (27.2%), memory loss (32.7%), attempted suicide (32.7%), and administration of psychiatric medications (16.1%). There were no significant differences between the HIV-positive and HIV-negative patients on psychiatric symptoms or quality of life.</p> <p>Conclusions</p> <p>HIV-positive IDUs were comorbid with HCV, indicating the need to refer both HIV- and HCV-infected individuals for treatment in methadone clinics. Currently, there is a gap between psychiatric/psychosocial services and patient symptoms, and more integrated medical services should be provided to heroin-using populations.</p

Improvement of Carbon Tetrachloride-Induced Acute Hepatic Failure by Transplantation of Induced Pluripotent Stem Cells without Reprogramming Factor c-Myc

The only curative treatment for hepatic failure is liver transplantation. Unfortunately, this treatment has several major limitations, as for example donor organ shortage. A previous report demonstrated that transplantation of induced pluripotent stem cells without reprogramming factor c-Myc (3-genes iPSCs) attenuates thioacetamide-induced hepatic failure with minimal incidence of tumorigenicity. In this study, we investigated whether 3-genes iPSC transplantation is capable of rescuing carbon tetrachloride (CCl4)-induced fulminant hepatic failure and hepatic encephalopathy in mice. Firstly, we demonstrated that 3-genes iPSCs possess the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that exhibit biological functions and express various hepatic specific markers. 3-genes iPSCs also exhibited several antioxidant enzymes that prevented CCl4-induced reactive oxygen species production and cell death. Intraperitoneal transplantation of either 3-genes iPSCs or 3-genes iPSC-Heps significantly reduced hepatic necrotic areas, improved hepatic functions, and survival rate in CCl4-treated mice. CCl4-induced hepatic encephalopathy was also improved by 3-genes iPSC transplantation. Hoechst staining confirmed the successful engraftment of both 3-genes iPSCs and 3-genes iPSC-Heps, indicating the homing properties of these cells. The most pronounced hepatoprotective effect of iPSCs appeared to originate from the highest antioxidant activity of 3-gene iPSCs among all transplanted cells. In summary, our findings demonstrated that 3-genes iPSCs serve as an available cell source for the treatment of an experimental model of acute liver diseases

4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

<p>Abstract</p> <p>Background</p> <p>The crude extract of the fruit bearing plant, <it>Physalis peruviana </it>(golden berry), demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown.</p> <p>Methods</p> <p>Herein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug.</p> <p>Results</p> <p>It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (<it>p </it>< 0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4βHWE in both dose- and time-dependent manners (<it>p </it>< 0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC₅₀) of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub-G₁accumulation and slight arrest at the G₂/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G₂/M arrest for H1299 cells treated with 5 μg/mL for 24 h.</p> <p>Conclusions</p> <p>In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.</p