Peptidome analysis reveals the involvement of endogenous peptides in mouse pancreatic dysfunction with aging

Type 2 diabetes (T2D) is a glucose regulation disorder that has significantly enhanced mortality and the global disease burden. The prevalence of T2D has increased worldwide and is higher in the elderly. The function of pancreatic islets decreases with age, which is one important reason for the occurrence of diabetes in the elderly. Recently, peptidome analysis has attracted attention. However, the role of age-related peptides in pancreatic dysfunction has not been investigated extensively. Here, we conducted a comparison of endogenous peptides between pancreas from adult and aging mice by liquid chromatography tandem mass spectrometry (LC-MS/MS). A total of 2,089 peptides originating from 1,280 protein precursors were identified, of which 232 were upregulated and 183 were downregulated in the aging mice (fold change ≥ 2 and p < 0.05), suggesting that the expression of pancreatic peptides in mice varied with age. The molecular weight of most peptides was <3.0 kDa, and the isoelectric point distribution had a bimodal characteristic. Further analysis of cleavage site patterns indicated that proteases cleaved pancreatic proteins according to their rules. Moreover, Gene Ontology and pathway analyses showed that the differentially expressed peptides potentially had specific effects on pancreatic dysfunction. Some differential peptides were located within the domains of precursor proteins that were closely associated with the development of diabetes. We believe that our research may advance the current understanding of pancreas-derived peptides and that certain peptides may be involved in the etiology of diabetes.     

Spectrum structures and biological functions of 8-mers in the human genome

The spectra of k-mer frequencies can reveal the structures and evolution of genome sequences. We confirmed that the trimodal spectrum of 8-mers in human genome sequences is distinguished only by CG2, CG1 and CG0 8-mer sets, containing 2,1 or 0 CpG, respectively. This phenomenon is called independent selection law. The three types of CG 8-mers were considered as different functional elements. We conjectured that (1) nucleosome binding motifs are mainly characterized by CG1 8-mers and (2) the core structural units of CpG island sequences are predominantly characterized by CG2 8-mers. To validate our conjectures, nucleosome occupied sequences and CGI sequences were extracted, then the sequence parameters were constructed through the information of the three CG 8-mer sets respectively. ROC analysis showed that CG1 8-mers are more preference in nucleosome occupied segments (AUC > 0.7) and CG2 8-mers are more preference in CGI sequences (AUC > 0.99). This validates our conjecture in principle.     

Emergence of Cryptosporidium hominis Monkey Genotype II and Novel Subtype Family Ik in the Squirrel Monkey (Saimiri sciureus) in China

A single Cryptosporidium isolate from a squirrel monkey with no clinical symptoms was obtained from a zoo in Ya’an city, China, and was genotyped by PCR amplification and DNA sequencing of the small-subunit ribosomal RNA (SSU rRNA), 70-kDa heat shock protein (HSP70), Cryptosporidium oocyst wall protein, and actin genes. This multilocus genetic characterization determined that the isolate was Cryptosporidium hominis, but carried 2, 10, and 6 nucleotide differences in the SSU rRNA, HSP70, and actin loci, respectively, which is comparable to the variations at these loci between C. hominis and the previously reported monkey genotype (2, 3, and 3 nucleotide differences). Phylogenetic studies, based on neighbor-joining and maximum likelihood methods, showed that the isolate identified in the current study had a distinctly discordant taxonomic status, distinct from known C. hominis and also from the monkey genotype, with respect to the three loci. Restriction fragment length polymorphisms of the SSU rRNA gene obtained from this study were similar to those of known C. hominis but clearly differentiated from the monkey genotype. Further subtyping was performed by sequence analysis of the gene encoding the 60-kDa glycoprotein (gp60). Maximum homology of only 88.3% to C. hominis subtype IdA10G4 was observed for the current isolate, and phylogenetic analysis demonstrated that this particular isolate belonged to a novel C. hominis subtype family, IkA7G4. This study is the first to report C. hominis infection in the squirrel monkey and, based on the observed genetic characteristics, confirms a new C. hominis genotype, monkey genotype II. Thus, these results provide novel insights into genotypic variation in C. hominis.     

Prevalence of Post-Stroke Cognitive Impairment in China: A Community-Based,Cross-Sectional Study

International hospital-based studies have indicated a high risk of cognitive impairment after stroke, evidence from community-based studies in China is scarce. To determine the prevalence of post-stroke cognitive impairment (PSCI) and its subtypes in stroke survivors residing in selected rural and urban Chinese communities, we conducted a community-based, cross-sectional study in 599 patients accounting for 48% of all stroke survivors registered in the 4 communities, who had suffered confirmed strokes and had undergone cognitive assessments via the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and Hachinski Ischemia Scale (HIS). Detection of PSCI was based on scores in these neuropsychological scales. Factors potentially impacting on occurrence of PSCI were explored by comparing demographic characteristics, stroke features, and cardiovascular risk factors between patients with and without PSCI. The overall prevalence of PSCI was 80.97% (95%CI: 77.82%-84.11%), while that of non-dementia PSCI (PSCI-ND) and post-stroke vascular dementia (PSD) was 48.91% (95%CI: 44.91%-52.92%) and 32.05% (95%CI: 28.32%-35.79%), respectively. Prior stroke and complications during the acute phase were independent risk factors for PSCI. The risk of recurrent stroke survivors having PSCI was 2.7 times higher than for first-episode survivors, and it was 3 times higher for those with complications during the acute phase than for those without. The higher prevalence of PSCI in this study compared with previous Chinese studies was possibly due to the combined effects of including rural stroke survivors, a longer period from stroke onset, and different assessment methods. There is an urgent need to recognize and prevent PSCI in stroke patients, especially those with recurrent stroke and complications during the acute phase.     

Comparing the effects of atamestane, toremifene and tamoxifen alone and in combination, on bone, serum lipids and uterus in ovariectomized rats

Complete estrogen blockade remains under investigation as a means to optimize anti-estrogen therapy in breast cancer thus both the efficacy and end-organ toxicities are of interest with combinations. We hypothesized that a steroidal aromatase inhibitor (AI) atamestane (ATA) alone, and in combination with the anti-estrogens tamoxifen (TAM) or toremifene (TOR) would have beneficial effects in ovariectomized (OVX) rats on key end-organ functions including bone and lipid metabolism and on the endometrium. Significant positive effects on bone were noted with ATA, TOR, TAM, ATA + TOR, or ATA + TAM. TOR, TAM, ATA + TOR, or ATA + TAM caused significant decreases in serum cholesterol and low-density lipoprotein cholesterol whereas ATA had no effect. Uterine weight and epithelium lining height were not increased by ATA but were by TOR and TAM. No significant differences were found in the key parameters outlined above between OVX rats given TOR and ATA + TOR, or TAM and ATA + TAM. Our data show that ATA in combination with TOR or TAM is equivalent to TOR or TAM alone in terms of end-organ effects within a range of clinically relevant doses. Further studies of combinations of AIs with anti-estrogens on end-organ function are merited.     

Correlations between Clinical Features and Mortality in Patients with Vibrio vulnificus Infection

Vibrio vulnificus is a common gram-negative bacterium, which might cause morbidity and mortality in patients following consumption of seafood or exposure to seawater in Southeast China. We retrospectively analyzed clinical data of patients with laboratory confirmed V. vulnificus infection. Twenty one patients were divided into a survival group and a non-surviving (or death) group according to their clinical outcome. Clinical data and measurements were statistically analyzed. Four patients (19.05%) died and five patients gave positive cultures from bile fluid, and 16 other patients gave positive culture from blood or blisters. Ten patients (47.62%) had an underlying liver disease and marine-related events were found in sixteen patients (76.2%). Patients with heavy drinking habits might be at increased mortality (p = 0.028). Clinical manifestations of cellulitis (47.6%), septic shock (42.9%) and multiple organ failure (28.6%) were statistically significant when comparing survivors and non-survivors (p = 0.035, p = 0.021 and p = 0.003, respectively). The laboratory results, including hemoglobin < 9.0 g/L (p = 0.012), platelets < 2.0×10⁹ /L, prothrombin time activity (PTA) <20%, decreased serum creatinine and increased urea nitrogen were statistically significant (p = 0.012, p = 0.003, p = 0.028 and p = 0.028, respectively). Patients may be at a higher risk of mortality under situations where they have a history of habitual heavy alcoholic drink consumption (p = 0.028, OR = 22.5, 95%CI 1.5–335.3), accompanied with cellulitis, shock, multiple organ failure, and laboratory examinations that are complicated by decreased platelets, hemoglobin and significantly prolonged prothrombin time (PT).