Neuroinflammatory Triangle Presenting Novel Pharmacological Targets for Ischemic Brain Injury

Ischemic stroke is one of the leading causes of morbidity and mortality globally. Hundreds of clinical trials have proven ineffective in bringing forth a definitive and effective treatment for ischemic stroke, except a myopic class of thrombolytic drugs. That, too, has little to do with treating long-term post-stroke disabilities. These studies proposed diverse options to treat stroke, ranging from neurotropic interpolation to venting antioxidant activity, from blocking specific receptors to obstructing functional capacity of ion channels, and more recently the utilization of neuroprotective substances. However, state of the art knowledge suggests that more pragmatic focus in finding effective therapeutic remedy for stroke might be targeting intricate intracellular signaling pathways of the ‘neuroinflammatory triangle’: ROS burst, inflammatory cytokines, and BBB disruption. Experimental evidence reviewed here supports the notion that allowing neuroprotective mechanisms to advance, while limiting neuroinflammatory cascades, will help confine post-stroke damage and disabilities.

Arsenene-mediated multiple independently targeted reactive oxygen species burst for cancer therapy

The modulation of intracellular reactive oxygen species (ROS) levels is crucial for cellular homeostasis and determination of cellular fate. A sublethal level of ROS sustains cell proliferation, differentiation and promotes tumor metastasis, while a drastic ROS burst directly induces apoptosis. Herein, surface-oxidized arsenene nanosheets (As/AsxOy NSs) with type II heterojunction are fabricated with efficient ·O2− and 1O2 production and glutathione consumption through prolonging the lifetime of photo-excited electron-hole pairs. Moreover, the portion of AsxOy with oxygen vacancies not only catalyzes a Fenton-like reaction, generating ·OH and O2 from H2O2, but also inactivates main anti-oxidants to cut off the “retreat routes” of ROS. After polydopamine (PDA) and cancer cell membrane (M) coating, the engineered As/AsxOy@PDA@M NSs serve as an intelligent theranostic platform with active tumor targeting and long-term blood circulation. Given its narrow-band-gap-enabled in vivo fluorescence imaging properties, As/AsxOy@PDA@M NSs could be applied as an imaging-guided non-invasive and real-time nanomedicine for cancer therapy.

Identification of Riptortus pedestris Salivary Proteins and Their Roles in Inducing Plant Defenses

The bean bug, Riptortus pedestris (Fabricius), is one of the most important soybean pests. It damages soybean leaves and pods with its piercing-sucking mouthparts, causing staygreen-like syndromes in the infested crops. During the feeding process, R. pedestris secretes a mixture of salivary proteins, which play critical roles in the insect–plant interactions and may be responsible for staygreen-like syndromes. The present study aimed to identify the major salivary proteins in R. pedestris saliva by transcriptomic and proteomic approaches, and to screen the proteins that potentially induced plant defense responses. Altogether, 136 salivary proteins were identified, and a majority of them were involved in hydrolase and binding. Additionally, R. pedestris saliva contained abundant bug-specific proteins with unknown function. Transient expression of salivary proteins in Nicotiana benthamiana leaves identified that RpSP10.3, RpSP13.4, RpSP13.8, RpSP17.8, and RpSP10.2 were capable of inducing cell death, reactive oxygen species (ROS) burst, and hormone signal changes, indicating the potential roles of these proteins in eliciting plant defenses. Our results will shed more light on the molecular mechanisms underlying the plant–insect interactions and are useful for pest management.

Flg22-induced Ca2+ increases undergo desensitization and resensitization

The flagellin epitope flg22, a pathogen-associated molecular pattern (PAMP), binds to the receptor-like kinase FLAGELLIN SENSING2 (FLS2), and triggers Ca2+ influx across the plasma membrane (PM). The flg22-induced increases in cytosolic Ca2+ concentration ([Ca2+]i) (FICA) play a crucial role in plant innate immunity. It’s well established that the receptor FLS2 and the key downstream component, reactive oxygen species (ROS) burst, undergoes sensitivity adaptation after flg22 stimulation, referred to as desensitization and resensitization, to prevent over responses to pathogens. However, whether FICA also mount adaptation mechanisms to ensure appropriate and efficient responses against pathogens remains poorly understood. Here, we carried out detailed analyses of [Ca2+]i increases upon two successive flg22 treatments, recorded and characterized, for the first time, rapid desensitization but slow resensitization of FICA in Arabidopsis thaliana. Pharmacological analyses showed that the rapid desensitization might be synergistically regulated by ligand-induced FLS2 endocytosis as well as the PM depolarization. The recovery of desensitized FICA might require to de novo FLS2 protein synthesis. FICA resensitization appeared significantly slower than FLS2 protein recovery, suggesting additional regulatory mechanisms of other components, such as flg22-related Ca2+ permeable channels. Taken together, we have carefully defined the FICA sensitivity adaptation, which will facilitate further molecular and genetic dissection of the Ca2+-mediated adaptive mechanisms in PAMP-triggered immunity.

The Pleiades are a cluster of fungal effectors that inhibit host defenses

Biotrophic plant pathogens secrete effector proteins to manipulate the host physiology. Effectors suppress defenses and induce an environment favorable to disease development. Sequence-based prediction of effector function is impeded by their rapid evolution rate. In the maize pathogen Ustilago maydis, effector-coding genes frequently organize in clusters. Here we describe the functional characterization of the pleiades, a cluster of ten effector genes, by analyzing the micro- and macroscopic phenotype of the cluster deletion and expressing these proteins in planta. Deletion of the pleiades leads to strongly impaired virulence and accumulation of reactive oxygen species (ROS) in infected tissue. Eight of the Pleiades suppress the production of ROS upon perception of pathogen associated molecular patterns (PAMPs). Although functionally redundant, the Pleiades target different host components. The paralogs Taygeta1 and Merope1 suppress ROS production in either the cytoplasm or nucleus, respectively. Merope1 targets and promotes the auto-ubiquitination activity of RFI2, a conserved family of E3 ligases that regulates the production of PAMP-triggered ROS burst in plants.

Potential Association of Reactive Oxygen Species With Male Sterility in Peach

Male sterility is an important agronomic trait for hybrid vigor utilization and hybrid seed production, but its underlying mechanisms remain to be uncovered. Here, we investigated the mechanisms of male sterility in peach using a combined cytology, physiology, and molecular approach. Cytological features of male sterility include deformed microspores and tapetum cells along with absence of pollen grains. Microspores had smaller nucleus at the mononuclear stage and were compressed into belts and subsequently disappeared in the anther cavity, whereas tapetum cells were swollen and vacuolated, with a delayed degradation to flowering time. Male sterile anthers had an ROS burst and lower levels of major antioxidants, which may cause abnormal development of microspores and tapetum, leading to male sterility in peach. In addition, the male sterility appears to be cytoplasmic in peach, which could be due to sequence variation in the mitochondrial genome. Our results are helpful for further investigation of the genetic mechanisms underlying male sterility in peach.