Protective effect of L-citrulline against acute gastric mucosal lesions induced by ischemia-reperfusion in rats

The present study investigated the protective effect of L-citrulline on gastric mucosal injury induced by ischemia-reperfusion (IR) in rats. Under anesthesia, the celiac artery was clamped for 30 min, and then the clamp was removed for 60 min reperfusion. Sixty minutes before ischemia, L-citrulline was administered intragastrically at doses of 300, 600, and 900 mg/kg. After the experiment, the stomachs were removed for biochemical and histological examinations. Pretreatment with L-citrulline (300, 600, and 900 mg/kg) significantly ameliorated the gastric damage caused by IR. Moreover, L-citrulline prevented the production of lipid peroxidation and inhibited the increase of myeloperoxidase activity. The elevation in total nitric oxide synthase (NOS) activity, inducible NOS activity, and inducible NOS protein expression as well as the decrease in constitutive NOS activity and gastric mucus level in the gastric mucosa induced by IR were significantly prevented. However, the protective effect mediated by L-citrulline was significantly antagonized by coadministration of L-nitroarginine methyl ester (10 mg/kg, s.c.). These results suggest that part of the mechanism of gastric protection by L-citrulline might be through inhibiting neutrophil infiltration and preserving gastric mucus synthesis and secretion in rats, functions that are closely related to the maintenance of constitutive NOS activity.     

Exposure to Odors of Rivals Enhances Sexual Motivation in Male Giant Pandas

Males will alter their mating behavior to cope with the presence of their competitors. Even exposure to odors from potential competitors can greatly increase male ejaculate expenditure in a variety of animals including insects, fishes, birds and rodents. Major efforts have been made to examine males'' plastic responses to sperm competition and its fitness benefits. However, the effects of competitor absence on male''s sexual motivation and behaviors remain unclear, which has been proposed to be one of the causes for the poor sexual performance of some captive mammals. This study revealed that sexual motivation can be greatly enhanced in captive male giant pandas (Ailuropoda melanoleuca) by exposure to chemosensory cues from either one or three conspecifics males. It had been shown that potential rivals'' odors increased males'' chemosensory investigation behavior, as well as their observing, following and sniffing behaviors towards estrous females. Behaviors changed regardless of the number of rivals (one or three). Our results demonstrate the effects of potential competition on male giant pandas'' sexual motivation and behavioral coping strategy. We anticipate that our research will provide a fresh insight into the mechanisms underlying poor sexual performance in male captive mammals, and valuable information for the practical management and ex situ conservation of endangered species.     

Screening and Identification of the Binding Peptides of Mycoplasma genitalium Protein of Adhesion

International Journal of Peptide Research and Therapeutics - Mycoplasma genitalium protein of adhesion (MgPa) is a vital membrane protein, which plays an important role in mediating the adhesion...     

Targeted Next-Generation Sequencing Reveals Novel USH2A Mutations Associated with Diverse Disease Phenotypes: Implications for Clinical and Molecular Diagnosis

USH2A mutations have been implicated in the disease etiology of several inherited diseases, including Usher syndrome type 2 (USH2), nonsyndromic retinitis pigmentosa (RP), and nonsyndromic deafness. The complex genetic and phenotypic spectrums relevant to USH2A defects make it difficult to manage patients with such mutations. In the present study, we aim to determine the genetic etiology and to characterize the correlated clinical phenotypes for three Chinese pedigrees with nonsyndromic RP, one with RP sine pigmento (RPSP), and one with USH2. Family histories and clinical details for all included patients were reviewed. Ophthalmic examinations included best corrected visual acuities, visual field measurements, funduscopy, and electroretinography. Targeted next-generation sequencing (NGS) was applied using two sequence capture arrays to reveal the disease causative mutations for each family. Genotype-phenotype correlations were also annotated. Seven USH2A mutations, including four missense substitutions (p.P2762A, p.G3320C, p.R3719H, and p.G4763R), two splice site variants (c.8223+1G>A and c.8559-2T>C), and a nonsense mutation (p.Y3745*), were identified as disease causative in the five investigated families, of which three reported to have consanguineous marriage. Among all seven mutations, six were novel, and one was recurrent. Two homozygous missense mutations (p.P2762A and p.G3320C) were found in one individual family suggesting a potential double hit effect. Significant phenotypic divergences were revealed among the five families. Three families of the five families were affected with early, moderated, or late onset RP, one with RPSP, and the other one with USH2. Our study expands the genotypic and phenotypic variability relevant to USH2A mutations, which would help with a clear insight into the complex genetic and phenotypic spectrums relevant to USH2A defects, and is complementary for a better management of patients with such mutations. We have also demonstrated that a targeted NGS approach is a valuable tool for the genetic diagnosis of USH2 and RP.     

Willingness to Participate in HIV Therapeutic Vaccine Trials among HIV-Infected Patients on ART in China

Background

More and more HIV therapeutic vaccines will enter clinical trials; however, little is known about the willingness to participate (WTP) in HIV therapeutic vaccine trials among HIV-positive individuals.

Objective

To investigate the WTP in HIV therapeutic vaccine trials among Chinese HIV-infected patients.

Methods

We conducted a cross-sectional survey on HIV-positive inpatients and outpatients at Shanghai Public Health Center. A total of 447 participants were recruited into this study. Following an introduction with general information on HIV therapeutic vaccine and its potential effectiveness and side effects, each participant completed a questionnaire in a self-administered form. The questionnaires covered demographics, high-risk behaviors, clinical characteristics and willingness to participate in HIV therapeutic vaccine trial.

Results

The overall willingness to participate in HIV therapeutic vaccine trials was 91.5%. Interestingly, multivariate logistic regression analyses demonstrated that the willingness was higher for those sexually infected by HIV (odds ratio [OR]: 4.36; 95% confidence interval [CI]: 1.53–12.41), diagnosed as HIV-1 infection for greater than 5 years (OR: 7.12, 95% CI: 1.83–27.76), and with the presence of infectious complications (OR: 2.75; 95% CI: 1.02–7.45). The primary reason for participation was to delay or reduce antiretroviral treatment (ART) and to avoid ART side effects (76.6%), and then followed by delaying disease progression (74.9%), increasing immune response to suppress opportunistic infections (57.7%) and preventing the development of drug resistance (37.1%). Reasons for unwillingness to participate mainly included concern for safety (37.0%), lack of knowledge on therapeutic vaccine (33.3%), and satisfaction with ART effectiveness (22.2%).

Conclusions

The WTP in HIV therapeutic vaccine trials was high among HIV-infected Chinese patients. HIV⁺ subjects who acquired infection through sexual contact and who were diagnosed for more than 5 years may represent a good candidate population for enrollment in therapeutic vaccine trials.     

Outcomes of Bronchial Artery Embolization for Life-Threatening Hemoptysis Secondary to Tuberculosis

Objective

To appraise the immediate and long-term outcomes of bronchial arterial embolization for life-threatening hemoptysis secondary to tuberculosis.

Methods

112 patients with life-threatening hemoptysis due to tuberculosis underwent bronchial artery embolization from January 2004 to February 2014. Life-threatening hemoptysis was defined as expectoration of at least 400 ml of blood in 24 hour. The median follow-up is 20 months, ranging from 2 to 52 months.

Results

The hemoptysis control rate was 86.6% at 14 days, 84.8% at 30 days, 78.6% at 240 days, 75.9% at 360 days, respectively. None of these characteristics, including gender, age and tuberculosis status, was significantly associated with immediate control of bleeding. Patients with active tuberculosis had a significantly longer recurrence-free duration than did patients with inactive tuberculosis (P = 0.040), which was further confirmed by Cox regression hazards model (P = 0.046). There was no spinal cord complication or mortality related to bronchial artery embolization. The most common complication was transient chest pain.

Conclusion

Bronchial arterial embolization is an effective and safe technique in the management of life-threatening hemoptysis secondary to tuberculosis. Active tuberculosis may be associated with a lower rate of recurrence of hemoptysis.     

In-Depth Investigation of Archival and Prospectively Collected Samples Reveals No Evidence for XMRV Infection in Prostate Cancer

XMRV, or xenotropic murine leukemia virus (MLV)-related virus, is a novel gammaretrovirus originally identified in studies that analyzed tissue from prostate cancer patients in 2006 and blood from patients with chronic fatigue syndrome (CFS) in 2009. However, a large number of subsequent studies failed to confirm a link between XMRV infection and CFS or prostate cancer. On the contrary, recent evidence indicates that XMRV is a contaminant originating from the recombination of two mouse endogenous retroviruses during passaging of a prostate tumor xenograft (CWR22) in mice, generating laboratory-derived cell lines that are XMRV-infected. To confirm or refute an association between XMRV and prostate cancer, we analyzed prostate cancer tissues and plasma from a prospectively collected cohort of 39 patients as well as archival RNA and prostate tissue from the original 2006 study. Despite comprehensive microarray, PCR, FISH, and serological testing, XMRV was not detected in any of the newly collected samples or in archival tissue, although archival RNA remained XMRV-positive. Notably, archival VP62 prostate tissue, from which the prototype XMRV strain was derived, tested negative for XMRV on re-analysis. Analysis of viral genomic and human mitochondrial sequences revealed that all previously characterized XMRV strains are identical and that the archival RNA had been contaminated by an XMRV-infected laboratory cell line. These findings reveal no association between XMRV and prostate cancer, and underscore the conclusion that XMRV is not a naturally acquired human infection.     

Inhibition of myeloid differentiation 1 specifically in colon with antisense oligonucleotide exacerbates dextran sodium sulfate-induced colitis

Myeloid differentiation 1 (MD-1), also known as lymphocyte antigen 86 (Ly86), is a soluble protein homologous to MD-2 and forms a complex with radioprotective 105 (RP105). RP105/MD-1 complex negatively regulates toll-like receptor 4 (TLR4) signaling and is involved in several immune disorders. However, the precise role of MD-1 in inflammatory bowel diseases (IBD) remains poorly understood. To further investigate the involvement of MD-1 in IBD, we inhibited MD-1 in colon with antisense oligonucleotide (AS-ODN) and assessed the effect of MD-1 inhibition on dextran sodium sulfate (DSS)-induced colitis. We discovered that MD-1 protein expression was remarkably decreased in both patients with ulcerative colitis and mice with DSS-induced colitis. For the first time, we showed that oral administration of MD-1 AS-ODN to mice significantly suppressed the MD-1 protein levels in colon rather than systemic tissues. Subsequently, we found that MD-1 AS-ODN treated mice were more susceptible to DSS-induced colitis based on loss of body weight, colon length, histological scores, and disease activity index. MD-1 inhibition also significantly enhanced inflammatory cytokines production such as IL-6 and IL-1β in colons. Finally, mice treated with MD-1 AS-ODN exhibited increased messenger RNA levels of TLR4 and MyD88 after DSS exposure and showed enhanced nuclear factor (NF)-κB activation compared with the control. Taken together, specifically suppression of MD-1 in colon tissues with AS-ODN exacerbates DSS-induced experimental colitis in mice, which is possibly related to activation of TLR4/NF-κB signaling.     

An Entropy-based gene selection method for cancer classification using microarray data

Background  

Accurate diagnosis of cancer subtypes remains a challenging problem. Building classifiers based on gene expression data is a promising approach; yet the selection of non-redundant but relevant genes is difficult.