SR-A deficiency reduces myocardial ischemia/reperfusion injury; involvement of increased microRNA-125b expression in macrophages

The macrophage scavenger receptor class A (SR-A) participates in the innate immune and inflammatory responses. This study examined the role of macrophage SR-A in myocardial ischemia/reperfusion (I/R) injury and hypoxia/reoxygenation (H/R)-induced cell damage. SR-A^?/? and WT mice were subjected to ischemia (45 min) followed by reperfusion for up to 7 days. SR-A^?/? mice showed smaller myocardial infarct size and better cardiac function than did WT I/R mice. SR-A deficiency attenuated I/R-induced myocardial apoptosis by preventing p53-mediated Bak-1 apoptotic signaling. The levels of microRNA-125b in SR-A^?/? heart were significantly greater than in WT myocardium. SR-A is predominantly expressed on macrophages. To investigate the role of SR-A macrophages in H/R-induced injury, we isolated peritoneal macrophages from SR-A deficient (SR-A^?/?) and wild type (WT) mice. Macrophages were subjected to hypoxia followed by reoxygenation. H/R markedly increased NF-κB binding activity as well as KC and MCP-1 production in WT macrophages but not in SR-A^?/? macrophages. H/R induced caspase-3/7 and -8 activities and cell death in WT macrophages, but not in SR-A^?/? macrophages. The levels of miR-125b in SR-A^?/? macrophages were significantly higher than in WT macrophages. Transfection of WT macrophages with miR-125b mimics attenuated H/R-induced caspase-3/7 and -8 activities and H/R-decreased viability, and prevented H/R-increased p-53, Bak-1 and Bax expression. The data suggest that SR-A deficiency attenuates myocardial I/R injury by targeting p53-mediated apoptotic signaling. SR-A^?/? macrophages contain high levels of miR-125b which may play a role in the protective effect of SR-A deficiency on myocardial I/R injury and H/R-induced cell damage.     

Overweight,hypertension and renal dysfunction in adulthood of neonatally overfed rats

Accelerated growth in early infancy has been associated with later cardiovascular and metabolic diseases. We investigated the influence of overnutrition during neonatal periods on the development of renal pathophysiological changes in adult offspring rats. Three or 10 male pups per mother were assigned to either the small litter (SL) or normal litter (NL) control groups during the first 21 days of life. The effects of early postnatal overnutrition on body weight, blood pressure and renal changes were determined at 3 and 6 months. Pups in the SL group weighed more than controls between 7 days and 6 months of age (P<.05). In the SL group, serum creatinine levels were higher at 3 and 6 months (P<.05), and at 6 months, blood pressure levels were higher than those of the controls (P<.05). The number of ED-1 positive macrophages in renal cortex and glomerulosclerosis index increased in the SL group at 3 and 6 months (P<.05). Additionally, cortical apoptotic cells increased in the SL group at 6 months (P<.05). Immunoblotting and immunohistochemistry showed that matrix metalloproteinase (MMP)-9 protein expressions decreased and tissue inhibitor of MMP-1, tumor necrosis factor-α, osteopontin and adiponectin expressions increased in the SL group at 3 months (P<.05). However, at 6 months, MMP-9 expression was elevated, and osteopontin expression remained elevated in the SL group (P<.05). Early postnatal overfeeding can lead to lasting overweight, hypertension and renal dysfunction and place a greater burden on the kidney.     

Focus: Allergic Diseases and Type II Immunity: Study of the Correlation between HRCT Semi-quantitative Scoring, Concentration of Alveolar Nitric Oxide,and Clinical-functional Parameters of Systemic Sclerosis-induced Interstitial Lung Disease

Introduction: The correlation between alveolar nitric oxide (CANO) and the severity of interstitial lung disease (ILD) evaluated by high resolution computed tomography (HRCT) has not been well demonstrated. Methods: It was a perspective and observational study, including patients with diagnosed systemic sclerosis (SSc). They performed lung function testing (LFT), exhaled nitric oxide (NO) measurements, exercise testing, chest X-ray, and HRCT. Study patients were divided into SSc with ILD (SSc-ILD+) or without ILD (SSc-ILD-). SSC-ILD+ patients were revisited after 6 months and 12 months to complete the study. Results: Thirty-one control subjects and 74 patients with SSc (33 SSc-ILD- and 41 SSc-ILD+) were included. Forty-one SSc-ILD+ patients were followed-up at 6 months and 12 months. Lung functional parameters of patients with SSc-ILD+ were lower than that of SSc-ILD- patients. The level of CANO was significantly higher in SSc-ILD+ than SSc-ILD- patients (8.6 ± 2.5 vs 4.2 ± 1.3 ppb and P<0.01). Warrick and Goldin scores of patients with SSc-ILD+ were respectively 16.5 ± 5.2 and 12.7 ± 4.3. Warrick scores were reduced after 6 and 12 months of follow-up vs at inclusion (12.4 ± 4.3 and 9.1 ± 3.2 vs 16.5 ± 5.2; P<0.05, P<0.01, and P<0.05; respectively). ΔWarrick and ΔGoldin scores were significantly and inversely correlated with ΔFVC, ΔTLC, ΔTLCO, ΔVO₂ max; that was also correlated with ΔCANO (R= 0.783, P<0.01 and R= 0.719 and P<0.05). Conclusion: CANO is a relevant biomarker for the diagnosis of ILD in patients with SSc, especially in combination with HRCT.     

The impact of cytomegalovirus infection on clinical severity and outcomes in kidney transplant recipients with Pneumocystis jirovecii pneumonia

Cytomegalovirus (CMV) infection is associated with Pneumocystis jirovecii pneumonia (PJP) in kidney transplant recipients (KTRs), but its impact on clinical severity and outcomes in KTRs with PJP is unknown. We reviewed 1994 medical records of KTRs from January 1997 to March 2019. PJP or CMV infection was diagnosed by polymerase chain reaction or culturing using blood or respiratory specimens. We divided patients into PJP and PJP+CMV groups, and evaluated the clinical severity and outcomes. Fifty two patients had PJP (2.6%) in the whole study cohort. Among patients with PJP, 38 (73.1%) had PJP alone and 14 (26.9%) had combined PJP and CMV co-infection. The PJP+CMV group showed worse laboratory findings (serum albumin and C-reactive protein, P = 0.010 for both) and higher requirement of continuous renal replacement therapy than the PJP group (P = 0.050). The pneumonia severity was worse in the PJP+CMV group than in the PJP group (P < 0.05), and CMV infection was a high risk factor of pneumonia severity (odds ratio 16.0; P = 0.002). The graft function was worse in the PJP+CMV group (P < 0.001), and the incidence of graft failure was higher in the PJP+CMV group than in the PJP group (85.7% vs 36.8%; P < 0.001). Mortality was double in the PJP+CMV group than in the PJP group, but not statistically significant (21.4% vs 10.5%; P = 0.370). Our results show that approximately one in four patients with PJP after kidney transplantation develops CMV with increased clinical severity and risk of graft failure. The possibility of increased clinical severity and worse clinical outcomes by CMV co-infection should be considered in KTRs with PJP.     

Simultaneous Inhibition of Ethylene Biosynthesis and Binding Using AVG and 1-MCP in Two Rose Cultivars with Different Sensitivities to Ethylene

Journal of Plant Growth Regulation - The primary factors that determine the longevity of cut roses are variable and depend on a cultivar’s sensitivity to ethylene. The vase life of...     

Cryptic and extensive hybridization between ancient lineages of American crows

Most species and therefore most hybrid zones have historically been defined using phenotypic characters. However, both speciation and hybridization can occur with negligible morphological differentiation. Recently developed genomic tools provide the means to better understand cryptic speciation and hybridization. The Northwestern Crow (Corvus caurinus) and American Crow (Corvus brachyrhynchos) are continuously distributed sister taxa that lack reliable traditional characters for identification. In this first population genomic study of Northwestern and American crows, we use genomic SNPs (nuDNA) and mtDNA to investigate the degree of genetic differentiation between these crows and the extent to which they may hybridize. Our results indicate that American and Northwestern crows have distinct evolutionary histories, supported by two nuDNA ancestry clusters and two 1.1%‐divergent mtDNA clades dating to the late Pleistocene, when glacial advances may have isolated crow populations in separate refugia. We document extensive hybridization, with geographic overlap of mtDNA clades and admixture of nuDNA across >900 km of western Washington and western British Columbia. This broad hybrid zone consists of late‐generation hybrids and backcrosses, but not recent (e.g., F1) hybrids. Nuclear DNA and mtDNA clines had concordant widths and were both centred in southwestern British Columbia, farther north than previously postulated. Overall, our results suggest a history of reticulate evolution in American and Northwestern crows, perhaps due to recurring neutral expansion(s) from Pleistocene glacial refugia followed by lineage fusion(s). However, we do not rule out a contributing role for more recent potential drivers of hybridization, such as expansion into human‐modified habitats.     

Prospects for the therapeutic development of umbilical cord blood-derived mesenchymal stem cells

Umbilical cord blood (UCB) is a primitive and abundant source of mesenchymal stem cells (MSCs). UCB-derived MSCs have a broad and efficient therapeutic capacity to treat various diseases and disorders. Despite the high latent self-renewal and differentiation capacity of these cells, the safety, efficacy, and yield of MSCs expanded for ex vivo clinical applications remains a concern. However, immunomodulatory effects have emerged in various disease models, exhibiting specific mechanisms of action, such as cell migration and homing, angiogenesis, anti-apoptosis, proliferation, anti-cancer, anti-fibrosis, anti-inflammation and tissue regeneration. Herein, we review the current literature pertaining to the UCB-derived MSC application as potential treatment strategies, and discuss the concerns regarding the safety and mass production issues in future applications.     

Synthesis of double-layered rotavirus-like particles using internal ribosome entry site vector system in stably-transformed <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

We established a bicistronic expression system using an encephalomyocarditis virus (EMCV)-derived internal ribosomal entry site (IRES) element to generate stably transformed Drosophila melanogaster Schneider 2 (S2) cells expressing human rotavirus Wa capsid proteins, VP2 and VP6, for the synthesis of VP2/6 double-layered virus-like particle (DVLP). The EMCV-derived IRES permitted bicistronic translation of recombinant VP6. Recombinant VP2 and VP6 were detected in extracellular fractions of stably transformed S2 cells. A wheel-like DVLP (diam ~ 50–55 nm) with short spikes was produced from the extracellular fraction of stably transformed S2 cells. A bicistronic expression system using an EMCV-derived IRES element can thus be used to express two proteins of interest in stably transformed S2 cells. The bi-or tri-cistronic expression of recombinant VP2/6/7 using stably transformed S2 cells can also be used to produce rotavirus VLPs.     

Xylitol does not inhibit xylose fermentation by engineered <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> expressing <Emphasis Type="Italic">xylA</Emphasis> as severely as it inhibits xylose isomerase reaction in vitro

Efficient fermentation of xylose, which is abundant in hydrolysates of lignocellulosic biomass, is essential for producing cellulosic biofuels economically. While heterologous expression of xylose isomerase in Saccharomyces cerevisiae has been proposed as a strategy to engineer this yeast for xylose fermentation, only a few xylose isomerase genes from fungi and bacteria have been functionally expressed in S. cerevisiae. We cloned two bacterial xylose isomerase genes from anaerobic bacteria (Bacteroides stercoris HJ-15 and Bifidobacterium longum MG1) and introduced them into S. cerevisiae. While the transformant with xylA from B. longum could not assimilate xylose, the transformant with xylA from B. stercoris was able to grow on xylose. This result suggests that the xylose isomerase (BsXI) from B. stercoris is functionally expressed in S. cerevisiae. The engineered S. cerevisiae strain with BsXI consumed xylose and produced ethanol with a good yield (0.31 g/g) under anaerobic conditions. Interestingly, significant amounts of xylitol (0.23 g xylitol/g xylose) were still accumulated during xylose fermentation even though the introduced BsXI might not cause redox imbalance. We investigated the potential inhibitory effects of the accumulated xylitol on xylose fermentation. Although xylitol inhibited in vitro BsXI activity significantly (K _I = 5.1 ± 1.15 mM), only small decreases (less than 10%) in xylose consumption and ethanol production rates were observed when xylitol was added into the fermentation medium. These results suggest that xylitol accumulation does not inhibit xylose fermentation by engineered S. cerevisiae expressing xylA as severely as it inhibits the xylose isomerase reaction in vitro.