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SARS-CoV-2: destiny in water environments along with sewer surveillance as an first forewarning system.
Microglia safeguard the CNS against injuries and pathogens, and in the presence of certain harmful stimuli are capable of inducing a disease-dependent inflammatory response. When exposed to anti-inflammatory cytokines, however, these cells possess the ability to switch from an inflammatory to an immunosuppressive phenotype. Cancer cells exploit this property to evade the immune system, and elicit an anti-inflammatory microenvironment that facilitates tumor attachment and growth.

The tumor-supportive biological processes that are activated in microglia cells in response to anti-inflammatory cytokines released from cancer cells were explored with mass spectrometry and proteomic technologies.

Serum-depleted and non-depleted human microglia cells (HMC3) were treated with a cocktail of IL-4, IL-13, IL-10, TGFβ, and CCL2. The cellular protein extracts were analyzed by LC-MS/MS. Using functional annotation clustering tools, statistically significant proteins that displayed a change in abundance between cytokinment-dependent biological mechanisms.Viral encephalitis is a major cause of morbidity and mortality, but the manifestation of disease varies greatly between individuals even in response to the same virus. Microglia are professional antigen presenting cells that reside in the central nervous system (CNS) parenchyma that are poised to respond to viral insults. However, the role of microglia in initiating and coordinating the antiviral response is not completely understood. Utilizing Theiler's murine encephalomyelitis virus (TMEV), a neurotropic picornavirus, and PLX5622, a small molecule inhibitor of colony-stimulating factor 1 receptor (CSF1R) signaling that can deplete microglia in the CNS; we investigated the role of the CSF1R-microglia axis in neurotropic picornavirus infection of C57BL/6J and SJL/J mice. These mouse strains differ in their ability to clear TMEV and exhibit different neurological disease in response to TMEV infection. CSF1R antagonism in C57BL/6J mice, which normally clear TMEV in the CNS, led to acute fatal encephalitis. In contrast, CSF1R antagonism in SJL/J mice, which normally develop a chronic CNS TMEV infection, did not result in acute encephalitis, but exacerbated TMEV-induced demyelination. Immunologically, inhibition of CSF1R in C57BL/6J mice reduced major histocompatibility complex II expression in microglia, decreased the proportion of regulatory T cells in the CNS, and upregulated proinflammatory pathways in CNS T cells. Acute CSF1R inhibition in SJL/J mice had no effect on microglial MHC-II expression and upregulated anti-inflammatory pathways in CNS T cells, however chronic CSF1R inhibition resulted in broad immunosuppression. Our results demonstrate strain-specific effects of the CSF1R-microglia axis in the context of neurotropic viral infection as well as inherent differences in microglial antigen presentation and subsequent T cell crosstalk that contribute to susceptibility to neurotropic picornavirus infection.The occurrence of allergic diseases induced by aeroallergens has increased in the past decades. Among inhalant allergens, mites remain the important causal agent of allergic diseases. Storage mites- Tyrophagus putrescentiae are found in stored products or domestic environments. Major allergen Tyr-p3 plays a significant role in triggering IgE-mediated hypersensitivity. However, its effects on pulmonary inflammation, internalization, and activation in human epithelium remain elusive. Protease-activated receptors (PARs) are activated upon cleavage by proteases. A549 cells were used as an epithelial model to examine the PAR activation by Tyr-p3 and therapeutic potential of PAR-2 antagonist (GB88) in allergic responses. Selleckchem ALK inhibitor Enzymatic properties and allergen localization of Tyr-p3 were performed. The release of inflammatory mediators, phosphorylation of mitogen-activated protein kinase (MAPK), and cell junction disruptions were evaluated after Tyr-p3 challenge. Enzymatic properties determined by substrate digestion andd by treatment of GB88 or SBTI. Further, GB88 treatment down-regulated the nTyr-p3-induced PAR-2 expression in allergic patients with asthma or rhinitis. Tight junction and adherens junction were disrupted in epithelial cells by nTyr-p3 exposure; however, this effect was avoided by GB88. Immunostaining with frozen sections of the mite body showed the presence of Tyr-p3 throughout the intestinal digestive system, especially in the hindgut around the excretion site. In conclusion, our findings suggest that Tyr-p3 from domestic mites leads to disruption of the airway epithelial barrier after inhalation. Proteolytic activity of Tyr-p3 causes the PAR-2 mRNA expression, thus leading to the release of numerous inflammatory mediators. Antagonism of PAR2 activity suggests GB88 as the therapeutic potential for anti-inflammation medicine, especially in allergy development triggered by protease allergens.Interfering with the ability of pathogenic bacteria to import glucose may represent a new promising antibacterial strategy, especially for the treatment of infections occurring in diabetic and other hyperglycemic patients. Such patients are particularly susceptible to infections caused by a variety of bacteria, among which opportunistic pathogens like Pseudomonas aeruginosa. In P. aeruginosa, glucose can be directly imported into the cytoplasm or after its periplasmic oxidation into gluconate and 2-ketogluconate (2-KG). We recently demonstrated that a P. aeruginosa mutant lacking the 2-KG transporter KguT is less virulent than its kguT + parental strain in an insect infection model, pointing to 2-KG branch of glucose utilization as a possible target for anti-Pseudomonas drugs. In this work, we devised an experimental protocol to find specific inhibitors of the 2-KG pathway of P. aeruginosa glucose utilization and applied it to the screening of the Prestwick Chemical Library. By exploiting mutants lacking genes involved in the transport of glucose derivatives in the primary screening and in the secondary assays, we could identify sanguinarine as an inhibitor of 2-KG utilization. We also demonstrated that sanguinarine does not prevent 2-KG formation by gluconate oxidation or its transport, suggesting that either KguD or KguK is the target of sanguinarine in P. Aeruginosa.Mitochondrial antiviral signaling protein (MAVS) functions as a "switch" in the immune signal transduction against most RNA viruses. Upon viral infection, MAVS forms prion-like aggregates by receiving the cytosolic RNA sensor retinoic acid-inducible gene I-activated signaling and further activates/switches on the type I interferon signaling. While under resting state, MAVS is prevented from spontaneously aggregating to switch off the signal transduction and maintain immune homeostasis. Due to the dual role in antiviral signal transduction and immune homeostasis, MAVS has emerged as the central regulation target by both viruses and hosts. Recently, researchers show increasing interest in viral evasion strategies and immune homeostasis regulations targeting MAVS, especially focusing on the post-translational modifications of MAVS, such as ubiquitination and phosphorylation. This review summarizes the regulations of MAVS in antiviral innate immune signaling transduction and immune homeostasis maintenance.As a structural, catalytic, and signaling component, zinc is necessary for the growth and development of plants, animals, and microorganisms. Zinc is also essential for the growth of pathogenic microorganisms and is involved in their metabolism as well as the regulation of various virulence factors. Additionally, zinc is necessary for infection and colonization of pathogenic microorganisms in the host. Upon infection in healthy organisms, the host sequesters zinc both intracellularly and extracellularly to enhance the immune response and prevent the proliferation and infection of the pathogen. Intracellularly, the host manipulates zinc levels through Zrt/Irt-like protein (ZIP)/ZnT family proteins and various zinc storage proteins. Extracellularly, members of the S100 protein family, such as calgranulin C, sequester zinc to inhibit microbial growth. In the face of these nutritional limitations, bacteria rely on an efficient zinc transport system to maintain zinc supplementation for proliferation and disruption of the host defense system to establish infection. Here, we summarize the strategies for zinc uptake in conditional pathogenic Pseudomonas aeruginosa, including known zinc uptake systems (ZnuABC, HmtA, and ZrmABCD) and the zinc uptake regulator (Zur). In addition, other potential zinc uptake pathways were analyzed. This review systematically summarizes the process of zinc uptake by P. aeruginosa to provide guidance for the development of new drug targets.Merkel cell polyomavirus (MCPyV) infection causes near-ubiquitous, asymptomatic infection in the skin, but occasionally leads to an aggressive skin cancer called Merkel cell carcinoma (MCC). Epidemiological evidence suggests that poorly controlled MCPyV infection may be a precursor to MCPyV-associated MCC. Clearer understanding of host responses that normally control MCPyV infection could inform prophylactic measures in at-risk groups. Similarly, the presence of MCPyV in most MCCs could imbue them with vulnerabilities that-if better characterized-could yield targeted intervention solutions for metastatic MCC cases. In this review, we discuss recent developments in elucidating the interplay between host cells and MCPyV within the context of viral infection and MCC oncogenesis. We also propose a model in which insufficient restriction of MCPyV infection in aging and chronically UV-damaged skin causes unbridled viral replication that licenses MCC tumorigenesis.Copper (Cu) is an important trace element with a two-sided effect on the growth performance of animals, which depends on the timing and dosage of Cu addition, etc. The purpose of this study was to determine the effects of oral copper sulfate (CuSO4, 350 ppm) on growth performance, cecal morphology, and its microflora of chickens (n = 60) after 30, 60, and 90 days. The results showed that after 90 days of copper exposure, the chickens lost weight, the cecum mucosa was detached, and vacuolation and inflammatory infiltration occurred at the base of the lamina propria. In addition, using the 16S rDNA sequencing method, we observed that copper exposure changed the richness and diversity of intestinal microorganisms. At the phylum level, Proteobacteria and Actinobacteria both significantly increased, while Bacteroidetes significantly decreased in the Cu group compared with control check (CK) group. At the genus level, the relative abundance of Rikenellaceae_RC9_gut_group decreased significantly, while Ruminococcaceae_UCG-014, Lachnoclostridium, and [Eubacterium]_coprostanoligenes_group increased significantly after copper exposure, and the change in microflora was most significant at 90 days. Moreover, the relevance of genus-level bacteria was altered. PICRUST analysis revealed potential metabolic changes associated with copper exposure, such as Staphylococcus aureus infection and metabolic disorders of nutrients. To sum up, these data show that subchronic copper exposure not only affects the growth and development of chickens but also causes the imbalance of intestinal microflora, which may further induce metabolic disorders in chickens.
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