Regulation of Autophagy Machinery in Magnaporthe oryzae

Plant diseases cause substantial loss to crops all over the world, reducing the quality and quantity of agricultural goods significantly. One of the world’s most damaging plant diseases, rice blast poses a substantial threat to global food security. Magnaporthe oryzae causes rice blast disease, which challenges world food security by causing substantial damage in rice production annually. Autophagy is an evolutionarily conserved breakdown and recycling system in eukaryotes that regulate homeostasis, stress adaption, and programmed cell death. Recently, new studies found that the autophagy process plays a vital role in the pathogenicity of M. oryzae and the regulation mechanisms are gradually clarified. Here we present a brief summary of the recent advances, concentrating on the new findings of autophagy regulation mechanisms and summarize some autophagy-related techniques in rice blast fungus. This review will help readers to better understand the relationship between autophagy and the virulence of plant pathogenic fungi.     

Cell Development Enhanced Bionic Silk Hydrogel on Remodeling Immune Pathogenesis of Spinal Cord Injury via M2 Polarization of Microglial

Due to the complex spatial-temporal pathophysiology of spinal cord injury (SCI), effective modulation of SCI-specific inflammatory pathogenesis to achieve desirable therapeutic effects on functional recovery still remains challenging. Herein, cell-enhanced photocrosslinked silk fibroin hydrogels with extracellular matrix-mimicking cues of mechanical properties and RGD (Arg-Gly-Asp) signals are gelled in situ to fill the lesion site to modulate injury-induced neuroinflammation and promote neurite regrowth after SCI. The bionic hydrogel system provides biomimetic mechanical cues to promote neuronal differentiation of neural stem/progenitor cells (NPCs) and neurite growth by activating YAP nuclear expression. Importantly, favored by the strong capacity of silk fibroin hydrogels on macrophage/microglia recruitment, NPCs encapsulated hydrogel (NPCs@SFRGD0.1) effectively promotes recruited macrophages/microglia to M2 polarization in the lesion site by releasing S100A4 and thereby remodels the inflammatory microenvironment after SCI. Moreover, NPCs@SFRGD0.1 successfully reduces glial scar formation and accelerates corticospinal tract axon regrowth to improve locomotor recovery. Overall, this work contributes to illustrating the therapeutic mechanism of NPCs development based biomaterial therapies on modulating inflammatory microenvironment and this NPCs enhanced silk fibroin hydrogel provides a promising therapeutic strategy for SCI.     

Apple Allergy: The cDNA Sequence of the Major Allergen of Apple,Determined by Performing PCR with a Primer Based on the N-Terminal Amino Acid Sequence,is Highly Homologous to the Sequence of the Major Birch Pollen Allergen

Considering the known N-terminal amino acid sequence of the major apple allergen, a polymerase chain reaction (PCR) primer was selected to amplify cDNA encoding this protein. A single PCR product was obtained, cloned into Escherichia coli and subsequently sequenced. The missing 5′-end of the apple cDNA sequence was obtained by a 5′-RACE method. The cDNA sequence showed 72% identity with the coding region of one of the known isoforms of Bet v 1, the major allergen of birch pollen. The deduced amino acid sequence resulted in a 158-residue protein with a calculated molecular mass of 17·5 kDa and 63% amino acid sequence identity to Bet v 1. In addition, further protein alignments showed a high degree of identity with allergens from other tree pollens and some ‘pathogenesis-related proteins’ from food plants. According to international regulations the allergen was termed Mal d 1 for this protein, it being the first major allergen discovered and characterised in fruits of apple (Malus domestica).     

Atrial Fibrillation: Pathogenesis,Predisposing Factors,and Genetics

Atrial fibrillation (AF) is the most frequent arrhythmia managed in clinical practice, and it is linked to an increased risk of death, stroke, and peripheral embolism. The Global Burden of Disease shows that the estimated prevalence of AF is up to 33.5 million patients. So far, successful therapeutic techniques have been implemented, with a high health-care cost burden. As a result, identifying modifiable risk factors for AF and suitable preventive measures may play a significant role in enhancing community health and lowering health-care system expenditures. Several mechanisms, including electrical and structural remodeling of atrial tissue, have been proposed to contribute to the development of AF. This review article discusses the predisposing factors in AF including the different pathogenic mechanisms, sedentary lifestyle, and dietary habits, as well as the potential genetic burden.     

Molecular Pathogenesis of Glioblastoma in Adults and Future Perspectives: A Systematic Review

Glioblastoma (GBM) is the most common and malignant tumour of the central nervous system. Recent appreciation of the heterogeneity amongst these tumours not only changed the WHO classification approach, but also created the need for developing novel and personalised therapies. This systematic review aims to highlight recent advancements in understanding the molecular pathogenesis of the GBM and discuss related novel treatment targets. A systematic search of the literature in the PubMed library was performed following the PRISMA guidelines for molecular pathogenesis and therapeutic advances. Original and meta-analyses studies from the last ten years were reviewed using pre-determined search terms. The results included articles relevant to GBM development focusing on the aberrancy in cell signaling pathways and intracellular events. Theragnostic targets and vaccination to treat GBM were also explored. The molecular pathophysiology of GBM is complex. Our systematic review suggests targeting therapy at the stemness, p53 mediated pathways and immune modulation. Exciting novel immune therapy involving dendritic cell vaccines, B-cell vaccines and viral vectors may be the future of treating GBM.     

The Pathogenesis of Cardiac Fibrosis: A Review of Recent Progress

Fibrosis is defined as the excessive deposition of extracellular matrix (ECM) proteins in the interstitium. It is an essential pathological response to chronic inflammation. ECM protein deposition is initially protective and is critical for wound healing and tissue regeneration. However, pathological cardiac remodeling in excessive and continuous tissue damage with subsequent ECM deposition results in a distorted organ architecture and significantly impacts cardiac function. In this review, we summarized and discussed the histologic features of cardiac fibrosis with the signaling factors that control it. We evaluated the origin and characteristic markers of cardiac fibroblasts. We also discussed lymphatic vessels, which have become more important in recent years to improve cardiac fibrosis.     

Identification of Pathogenicity-Related Genes in Biofilm-Defective Acidovorax citrulli by Transposon Tn5 Mutagenesis

Biofilm formation is important for virulence of a large number of plant pathogenic bacteria. Indeed, some virulence genes have been found to be involved in the formation of biofilm in bacterial fruit blotch pathogen Acidovorax citrulli. However, some virulent strains of A. citrulli were unable to format biofilm, indicating the complexity between biofilm formation and virulence. In this study, virulence-related genes were identified in the biofilm-defective strain A1 of A. citrulli by using Tn5 insertion, pathogenicity test, and high-efficiency thermal asymmetric interlaced PCR (hiTAIL-PCR). Results from this study indicated that 22 out of the obtained 301 mutants significantly decreased the virulence of strain A1 compared to the wild-type. Furthermore, sequence analysis indicated that the obtained 22 mutants were due to the insertion of Tn5 into eight genes, including Aave 4244 (cation diffusion facilitator family transporter), Aave 4286 (hypothetical protein), Aave 4189 (alpha/beta hydrolase fold), Aave 1911 (IMP dehydrogenase/GMP reductase domain), Aave 4383 (bacterial export proteins, family 1), Aave 4256 (Hsp70 protein), Aave 0003 (histidine kinase, DNA gyrase B, and HSP90-like ATPase), and Aave 2428 (pyridoxal-phosphate dependent enzyme). Furthermore, the growth of mutant Aave 2428 was unaffected and even increased by the change in incubation temperature, NaCl concentration and the pH of the LB broth, indicating that this gene may be directly involved in the bacterial virulence. Overall, the determination of the eight pathogenicity-related genes in strain A1 will be helpful to elucidate the pathogenesis of biofilm-defective A. citrulli.     

Osteosarcoma Pathogenesis Leads the Way to New Target Treatments

Osteosarcoma (OS) is a rare condition with very poor prognosis in a metastatic setting. Basic research has enabled a better understanding of OS pathogenesis and the discovery of new potential therapeutic targets. Phase I and II clinical trials are already ongoing, with some promising results for these patients. This article reviews OS pathogenesis and new potential therapeutic targets.     

Cutting Edge of the Pathogenesis of Atopic Dermatitis: Sphingomyelin Deacylase,the Enzyme Involved in Its Ceramide Deficiency,Plays a Pivotal Role

Atopic dermatitis (AD) is characterized clinically by severe dry skin and functionally by both a cutaneous barrier disruption and an impaired water-holding capacity in the stratum corneum (SC) even in the nonlesional skin. The combination of the disrupted barrier and water-holding functions in nonlesional skin is closely linked to the disease severity of AD, which suggests that the barrier abnormality as well as the water deficiency are elicited as a result of the induced dermatitis and subsequently trigger the recurrence of dermatitis. These functional abnormalities of the SC are mainly attributable to significantly decreased levels of total ceramides and the altered ceramide profile in the SC. Clinical studies using a synthetic pseudo-ceramide (pCer) that can function as a natural ceramide have indicated the superior clinical efficacy of pCer and, more importantly, have shown that the ceramide deficiency rather than changes in the ceramide profile in the SC of AD patients plays a central role in the pathogenesis of AD. Clinical studies of infants with AD have shown that the barrier disruption due to the ceramide deficiency is not inherent and is essentially dependent on postinflammatory events in those infants. Consistently, the recovery of trans-epidermal water loss after tape-stripping occurs at a significantly slower rate only at 1 day post-tape-stripping in AD skin compared with healthy control (HC) skin. This resembles the recovery pattern observed in Niemann–Pick disease, which is caused by an acid sphingomyelinase (aSMase) deficiency. Further, comparison of ceramide levels in the SC between before and after tape-stripping revealed that whereas ceramide levels in HC skin are significantly upregulated at 4 days post-tape-stripping, their ceramide levels remain substantially unchanged at 4 days post-tape-stripping. Taken together, the sum of these findings strongly suggests that an impaired homeostasis of a ceramide-generating process may be associated with these abnormalities. We have discovered a novel enzyme, sphingomyelin (SM) deacylase, which cleaves the N-acyl linkage of SM and glucosylceramide (GCer). The activity of SM deacylase is significantly increased in AD lesional epidermis as well as in the involved and uninvolved SC of AD skin, but not in the skin of patients with contact dermatitis or chronic eczema, compared with HC skin. SM deacylase competes with aSMase and β-glucocerebrosidase (BGCase) to hydrolyze their common substrates, SM and GCer, to yield their lysoforms sphingosylphosphorylcholine (SPC) and glucosylsphingosine (GSP), respectively, instead of ceramide. Consistently, those reaction products (SPC and GSP) accumulate to a greater extent in the involved and uninvolved SC of AD skin compared with chronic eczema or contact dermatitis skin as well as HC skin. Successive chromatographies were used to purify SM deacylase to homogeneity with a single band of ≈43 kDa and with an enrichment of >14,000-fold. Analysis of a protein spot with SM deacylase activity separated by 2D-SDS-PAGE using MALDI-TOF MS/MS allowed its amino acid sequence to be determined and to identify it as the β-subunit of acid ceramidase (aCDase), an enzyme consisting of α- and β-subunits linked by amino-bonds and a single S-S bond. Western blotting of samples treated with 2-mercaptoethanol revealed that whereas recombinant human aCDase was recognized by antibodies to the α-subunit at ≈56 and ≈13 kDa and the β-subunit at ≈43 kDa, the purified SM deacylase was detectable only by the antibody to the β-subunit at ≈43 kDa. Breaking the S-S bond of recombinant human aCDase with dithiothreitol elicited the activity of SM deacylase with an apparent size of ≈40 kDa upon gel chromatography in contrast to aCDase activity with an apparent size of ≈50 kDa in untreated recombinant human aCDase. These results provide new insights into the essential role of SM deacylase as the β-subunit aCDase that causes the ceramide deficiency in AD skin.