Anakinra treatment efficacy in reduction of inflammatory biomarkers in COVID-19 patients: A meta-analysis.

INTRODUCTION: Anakinra is being empirically considered for the treatment of COVID-19 patients. The aim is to assess the efficacy of anakinra treatment on inflammatory marker reduction, including c-reactive protein (CRP) concentrations, serum ferritin, and serum d-dimer levels. METHODS: Adhering to PRISMA 2020 statement guidelines, a systematic search was conducted across the following databases from December 2019 until January 10, 2022: PubMed/MEDLINE, Cochrane Central, Web of Science, Scopus, and EMBASE. The following keywords were employed: Anakinra, COVID*, SARS-CoV-2, inflammatory, CRP, D-dimer, Ferritin, hematological, laboratory, clinical, trials. The findings were collated and presented in a tabulated manner, and statistically analyzed using Review Manger 5.4 (Cochrane). RESULTS: In total, 2032 patients were included (881 in the anakinra and 1151 in the control/standard care group); 69.1% of them were males. Overall, the mean difference from admission until last follow-up in CRP values was -9.66, where notable reductions were seen in the anakinra group (SMD = -0.46, p < 0.00001, N = 655). Serum ferritin mean values were reduced by 1467.16 in the anakinra group (SMD = -0.31, p = 0.004, N = 537). D-dimer mean values were largely reduced by 4.04 in the anakinra group (SMD = -0.38, p = 0.0004, N = 375). CONCLUSION: This study finds that anakinra is potentially a strong candidate as an anti-inflammatory agent to reduce mortality in COVID-19 patients, specifically in patients with elevated inflammatory biomarkers.

Comparative Transcriptome Analysis between a Resistant and a Susceptible Wild Tomato Accession in Response to Phytophthora parasitica.

Phytophthora parasitica is one of the most widespread Phytophthora species, which is known to cause multiple diseases in tomato and is capable of infecting almost all plant parts. Our current understanding of tomato-Phytophthora parasitica interaction is very limited and currently nothing is known at the whole genome or transcriptome level. In this study, we have analyzed and compared the transcriptome of a resistant and a susceptible wild tomato accession in response to P. parasitica infection using the RNA-seq technology. We have identified 2657 and 3079 differentially expressed genes (DEGs) in treatment vs control comparison of resistant (Sp-R) and susceptible (Sp-S) samples respectively. Functional annotation of DEGs revealed substantial transcriptional reprogramming of diverse physiological and cellular processes, particularly the biotic stress responses in both Sp-R and Sp-S upon P. parasitica treatment. However, subtle expression differences among some core plant defense related genes were identified and their possible role in resistance development against P. parasitica is discussed. Our results revealed 1173 genes that were differentially expressed only in Sp-R accession upon P. parasitica inoculation. These exclusively found DEGs in Sp-R accession included some core plant defense genes, for example, several protease inhibitors, chitinases, defensin, PR-1, a downy mildew susceptibility factor, and so on, were all highly induced. Whereas, several R genes, WRKY transcriptions factors and a powdery mildew susceptibility gene (Mlo) were highly repressed during the resistance outcome. Analysis reported here lays out a strong foundation for future studies aimed at improving genetic resistance of tomato cultivars against to Phytopphthora species.

Cross-regulation of cytoskeleton and calcium signaling at plant-pathogen interface.

During plant-pathogen interactions, cytoskeleton and calcium signaling work independently as well as in coordination with each other for developing preformed and induced defense responses. A cell wall (CW) - plasma membrane (PM) - cytoskeleton (CS) continuum is maintained by coordination of cytoskeleton and calcium signaling. The current review is focused on the current knowledge of cytoskeleton­calcium cross-regulation during plant-pathogen interactions. Implications of recent technological developments in the existing toolkit that can address the outstanding questions of cytoskeleton­calcium coordination plant immunity are also discussed.

The PTI to ETI Continuum in Phytophthora-Plant Interactions.

Phytophthora species are notorious pathogens of several economically important crop plants. Several general elicitors, commonly referred to as Pathogen-Associated Molecular Patterns (PAMPs), from Phytophthora spp. have been identified that are recognized by the plant receptors to trigger induced defense responses in a process termed PAMP-triggered Immunity (PTI). Adapted Phytophthora pathogens have evolved multiple strategies to evade PTI. They can either modify or suppress their elicitors to avoid recognition by host and modulate host defense responses by deploying hundreds of effectors, which suppress host defense and physiological processes by modulating components involved in calcium and MAPK signaling, alternative splicing, RNA interference, vesicle trafficking, cell-to-cell trafficking, proteolysis and phytohormone signaling pathways. In incompatible interactions, resistant host plants perceive effector-induced modulations through resistance proteins and activate downstream components of defense responses in a quicker and more robust manner called effector-triggered-immunity (ETI). When pathogens overcome PTI-usually through effectors in the absence of R proteins-effectors-triggered susceptibility (ETS) ensues. Qualitatively, many of the downstream defense responses overlap between PTI and ETI. In general, these multiple phases of Phytophthora-plant interactions follow the PTI-ETS-ETI paradigm, initially proposed in the zigzag model of plant immunity. However, based on several examples, in Phytophthora-plant interactions, boundaries between these phases are not distinct but are rather blended pointing to a PTI-ETI continuum.

The Phytophthora RXLR Effector Avrblb2 Modulates Plant Immunity by Interfering With Ca2+ Signaling Pathway.

In plants, subcellular fluctuations in Ca2+ ion concentration are among the earliest responses to biotic and abiotic stresses. Calmodulin, which is a ubiquitous Ca2+ ion sensor in eukaryotes, plays a major role in translating these Ca2+ signatures to cellular responses by interacting with numerous proteins located in plasma membranes, cytoplasm, organelles and nuclei. In this report, we show that one of the Phytophthora RXLR effector, Avrblb2, interacts with calmodulin at the plasma membrane of the plant cells. Using deletion and single amino acid mutagenesis, we found that calmodulin binds to the effector domain of Avrblb2. In addition, we show that most known homologs of Avrblb2 in three different Phytophthora species interact with different isoforms of calmodulin. Type of amino acids at position 69 in Avrblb2, which determines Rbi-blb2 resistance protein-mediated defense responses, is not involved in the Avrblb2-calmodulin interaction. Using in planta functional analyses, we show that calmodulin binding to Avrblb2 is required for its recognition by Rpi-blb2 to incite hypersensitive response. These findings suggest that Avrblb2 by interacting with calmodulin interfere with plant defense associated Ca2+ signaling in plants.