Pkd2 Mesenteric Vessels Exhibit a Primary Defect in Endothelium-Dependent Vasodilatation Restored by Rosiglitazone

Patients with autosomal dominant polycystic kidney disease have a high prevalence of hypertension and structural vascular abnormalities, such as intracranial aneurysms. Hypertension can develop in childhood and often precedes a significant reduction in the glomerular filtration rate. The major aim of this study was to investigate whether a primary endothelial defect or a vascular smooth muscle (VSM) defect was present in murine polycystic kidney disease (Pkd)2 heterozygous mesenteric vessels before the development of renal failure or hypertension. Using pressure myography, we observed a marked defect in ACh-stimulated endothelium-dependent vasodilatation in Pkd2 arterioles. In contrast, Pkd2 vessels responded normally to sodium nitroprusside, phenylephrine, KCl, and pressure, indicating unaltered VSM-dependent responses. Pretreatment with the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone significantly restored ACh-dependent vasodilation in Pkd2 mice. Isolated heterozygous Pkd2 endothelial cells displayed normal ACh-stimulated Ca2+ and nitric oxide production. However, isolated Pkd2 heterozygous VSM cells displayed basal increases in superoxide and sodium nitroprusside-stimulated peroxynitrite formation, which were both suppressed by rosiglitazone. Furthermore, we observed a defective response of Pkd2 mesenteric venules to ACh in vivo, which was more marked after ischemia-reperfusion injury. In conclusion, the results of our study suggest that the defect in vasodilatation in Pkd2 heterozygous vessels is primarily due to a reduction in nitric bioavailability secondary to increased vascular oxidative stress. The ability of rosiglitazone to correct this phenotype suggests that this defect is potentially reversible in patients with autosomal dominant polycystic kidney disease

Transglutaminase inhibition ameliorates experimental diabetic nephropathy

Diabetic nephropathy is characterized by excessive extracellular matrix accumulation resulting in renal scarring and end-stage renal disease. Previous studies have suggested that transglutaminase type 2, by formation of its protein crosslink product epsilon-(gamma-glutamyl)lysine, alters extracellular matrix homeostasis, causing basement membrane thickening and expansion of the mesangium and interstitium. To determine whether transglutaminase inhibition can slow the progression of chronic experimental diabetic nephropathy over an extended treatment period, the inhibitor NTU281 was given to uninephrectomized streptozotocin-induced diabetic rats for up to 8 months. Effective transglutaminase inhibition significantly reversed the increased serum creatinine and albuminuria in the diabetic rats. These improvements were accompanied by a fivefold decrease in glomerulosclerosis and a sixfold reduction in tubulointerstitial scarring. This was associated with reductions in collagen IV accumulation by 4 months, along with reductions in collagens I and III by 8 months. This inhibition also decreased the number of myofibroblasts, suggesting that tissue transglutaminase may play a role in myofibroblast transformation. Our study suggests that transglutaminase inhibition ameliorates the progression of experimental diabetic nephropathy and can be considered for clinical application

Directional Selection from Host Plants Is a Major Force Driving Host Specificity in Magnaporthe Species

One major threat to global food security that requires immediate attention, is the increasing incidence of host shift and host expansion in growing number of pathogenic fungi and emergence of new pathogens. The threat is more alarming because, yield quality and quantity improvement efforts are encouraging the cultivation of uniform plants with low genetic diversity that are increasingly susceptible to emerging pathogens. However, the influence of host genome differentiation on pathogen genome differentiation and its contribution to emergence and adaptability is still obscure. Here, we compared genome sequence of 6 isolates of Magnaporthe species obtained from three different host plants. We demonstrated the evolutionary relationship between Magnaporthe species and the influence of host differentiation on pathogens. Phylogenetic analysis showed that evolution of pathogen directly corresponds with host divergence, suggesting that host-pathogen interaction has led to co-evolution. Furthermore, we identified an asymmetric selection pressure on Magnaporthe species. Oryza sativa-infecting isolates showed higher directional selection from host and subsequently tends to lower the genetic diversity in its genome. We concluded that, frequent gene loss or gain, new transposon acquisition and sequence divergence are host adaptability mechanisms for Magnaporthe species, and this coevolution processes is greatly driven by directional selection from host plants

Global knowledge mapping and emerging research trends in the microbiome and asthma: A bibliometric and visualized analysis using VOSviewer and CiteSpace

Background: Numerous prior studies have extensively highlighted the significance of the microbiome in association with asthma. While several studies have concentrated on the asthma microbiome in previous research, there is currently a lack of publications that employ bibliometric methods to assess this area. Methods: In this study, the Web of Science Core Collection database was utilized as the data source, and the SCI-EXPANDED index was employed to ensure that the retrieved data were comprehensive and accurate. All original research articles and review articles related to the correlation between asthma and the microbiome were systematically searched from the inception of the database until June 20, 2023. These articles were subsequently visualized and analyzed using VOSviewer and CiteSpace software. Results: A total of 1366 relevant publications were acquired, indicating a consistent annual increase in global publications in the field. The United States and China emerged as the top two contributors to international publications. Among prolific authors, Susan V. Lynch achieved the highest publication record, with Hans Bisgaard and Jakob Stokholm sharing the second position. The majority of publications concentrated on allergy-related and microbiome areas, with a few comprehensive journals standing out. Journals with 40 or more publications included the Journal of Allergy and Clinical Immunology, Allergy, Frontiers in Immunology, and PLOS One. The top 5 cited journals were the Journal of Allergy and Clinical Immunology, PLOS One, American Journal of Respiratory and Critical Care Medicine, Clinical and Experimental Allergy, and Nature. Upon analyzing keywords, high-frequency terms, such as asthma, gut microbiota, microbiome, children, childhood asthma, allergy, risk, exposure, inflammation, diversity, and chain fatty acids emerged as representative terms in the field. Conclusion: This study systematically presented a comprehensive overview of the literature regarding the association between asthma and the microbiome over the last two decades. Through a bibliometric perspective, the findings may assist researchers with a better understanding of the essential information in the field

Asymptotic almost periodicity of C-semigroups

Let {T(t)}t≥0 be a C-semigroup on a Banach space X with generator A. We will investigate the asymptotic almost periodicity of {T(t)} via the Hille-Yosida space of its generator

Magnetic nanoparticles enhance the cellular immune response of dendritic cell tumor vaccines by realizing the cytoplasmic delivery of tumor antigens

Abstract Dendritic cells (DCs)‐based tumor vaccines have the advantages of high safety and rapid activation of T cells, and have been approved for clinical tumor treatment. However, the conventional DC vaccines have some severe problems, such as poor activation of DCs in vitro, low level of antigen presentation, reduced cell viability, and difficulty in targeting lymph nodes in vivo, resulting in poor clinical therapeutic effects. In this research, magnetic nanoparticles Fe3O4@Ca/MnCO3 were prepared and used to actively and efficiently deliver antigens to the cytoplasm of DCs, promote antigen cross‐presentation and DC activation, and finally enhance the cellular immune response of DC vaccines. The results show that the magnetic nanoparticles can actively and quickly deliver antigens to the cytoplasm of DCs by regulating the magnetic field, and achieve cross‐presentation of antigens. At the same time, the nanoparticles degradation product Mn2+ enhanced immune stimulation through the interferon gene stimulating protein (STING) pathway, and another degradation product Ca2+ ultimately promoted cellular immune response by increasing autophagy. The DC vaccine constructed with the magnetic nanoparticles can more effectively migrate to the lymph nodes, promote the proliferation of CD8+ T cells, prolong the time of immune memory, and produce higher antibody levels. Compared with traditional DC vaccines, cytoplasmic antigen delivery with the magnetic nanoparticles provides a new idea for the construction of novel DC vaccines

Inhibition of miR-34a-5p alleviates hypoxia-reoxygenation injury by enhancing autophagy in steatotic hepatocytes

Hypoxia-reoxygenation (H/R) injury in steatotic hepatocytes has been implicated in liver dysfunction after liver transplantation. MicroRNAs (miRs) play important roles in regulating several cell biology mechanisms related to H/R injury. However, the role of miRs in regulating H/R injury in steatotic hepatocytes is still unclear. We established an in vitro model for studying H/R injury in steatotic hepatocytes and identified miR-34a-5p as a miR that was substantially upregulated in steatotic hepatocytes under H/R challenge. MiR-34a-5p expression was modified by transfecting miR-34a-5p mimic and inhibitor into H/R-challenged steatotic hepatocytes. We found that inhibition of miR-34a-5p alleviated H/R-induced apoptosis and promoted post-H/R proliferation in steatotic hepatocytes. Whereas, overexpression of miR-34a-5p augmented H/R-induced apoptosis and prohibited post-H/R proliferation. By examining autophagy, our data demonstrated that miR-34a-5p suppressed autophagy in H/R-challenged steatotic hepatocytes, induction of autophagy partially rescued the exaggeration of H/R injury induced by miR-34a-5p mimic, while inhibition of autophagy impaired the protection of the miR-34a-5p inhibitor against H/R injury. In conclusion, miR-34a-5p is crucial in exaggerating H/R injury, likely by suppressing autophagy in steatotic hepatocytes. Inhibition of miR-34a may be a promising strategy to protect steatotic hepatocytes against H/R-injury

Effect of Al2O3 addition on the non-isothermal crystallization kinetics and long-term stability of BCABS sealing glass for IT-SOFCs

Abstract Owing to adjustable thermal expansion performance, BaO–CaO–Al2O3–B2O3–SiO2 (BCABS) glass has a promising commercialization prospect for intermediate temperature-solid oxide fuel cells (IT-SOFCs) sealing. Herein, Al2O3 with two different contents was added into the same glass formulation, referred to as A and B glass, respectively. In terms of the non-isothermal crystallization kinetic behavior, the effect of Al2O3 as the unique intermediate was innovatively studied on the long-term performance of BCABS sealing glass. After the heat treatment at 1023 K for 100 h, the change of the network structure and the expansion coefficient of the glass were characterized. The results showed that the addition of Al2O3 as a network forming body could enhance the structure of glass, and increase the activation energy for glass transition, which could effectively inhibit the crystallization ability of sealing glass. Therefore, the B glass with the higher Al2O3 content showed the better long-term sealing ability, which was greatly beneficial for IT-SOFCs sealing