International immunopharmacology
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Int. Immunopharmacol. · Dec 2020
ReviewToll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets.
Cytokine storm generates during various systemic acute infections, including sepsis and current pandemic called COVID-19 (severe) causing devastating inflammatory conditions, which include multi-organ failure or multi-organ dysfunction syndrome (MODS) and death of the patient. Toll-like receptors (TLRs) are one of the major pattern recognition receptors (PRRs) expressed by immune cells as well as non-immune cells, including neurons, which play a crucial role in generating cytokine storm. They recognize microbial-associated molecular patterns (MAMPs, expressed by pathogens) and damage or death-associate molecular patterns (DAMPs; released and/expressed by damaged/killed host cells). ⋯ This state-of-the-art review describes the importance of TLR signaling in the onset of the sepsis-associated cytokine storm and discusses various host-derived endogenous negative regulators of TLR signaling pathways. The subject is very important as there is a vast array of genes and processes implicated in these negative feedback mechanisms. These molecules and mechanisms can be targeted for developing novel therapeutic drugs for cytokine storm-associated diseases, including sepsis, severe COVID-19, and other inflammatory diseases, where TLR-signaling plays a significant role.
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Int. Immunopharmacol. · Dec 2020
Association between tumor mutation burden and immune infiltration in ovarian cancer.
It remains unclear whether the tumor mutation burden (TMB) or a TMB-related signature could be prognostic indicators in ovarian cancer (OC), as potential correlations with immune infiltrates and immunotherapy responsiveness remains poorly understood. ⋯ We examined the prognostic value of TMB and its potential association with immune cell infiltration and immunotherapy responsiveness in OC. A TMB-related prognostic signature consisting of 8 genes was developed and verified, which might be a promising prognostic signature for the prognosis of OC patients.
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Int. Immunopharmacol. · Dec 2020
Puerarin alleviates vincristine-induced neuropathic pain and neuroinflammation via inhibition of nuclear factor-κB and activation of the TGF-β/Smad pathway in rats.
Chemotherapy-induced neuropathic pain harms the quality of life patients. Vincristine is an often used chemotherapeutic drug that evokes neuralgia via inflammation. Puerarin (Pue) extracted from Puerariae Lobatae Radix has analgesic and anti-inflammatory effects; however, its possible effect and mechanism in vincristine (Vin)-induced neuropathic pain has not been investigated. ⋯ Immunofluorescence staining further demonstrated that Pue decreased the NF-κBp65 protein. Our findings imply that Pue relieved chemotherapy-induced neuropathic pain might be attributable to the suppression of inflammation cytokines. The anti-inflammation action of Pue might be associated with the activation of the TGF-β/Smad pathway, a novel mechanism exploring its prophylactic effect in vincristine-induced neuropathic pain.