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Artesunate is a derivative of artemisinin and can lessen the pathologic changes and neutrophil infiltration in the lungs of ALI patients, and decrease sepsis-induced mortality (101). Hu and colleagues explored a new and efficacious approach for ALI (103). Besides, kidney impairment in hospitalized COVID-19 patients is associated with a high risk of in-hospital death (104).

The authors discovered that artemisinin downregulates protein levels of NOD- LRR- and pyrin domain-containing protein 3 (NLRP3) and caspase 1 in macrophages in burn-induced sepsis mice. TLR2 mainly locates outside the cell membrane of macrophages, DCs, and granulocytes, and recognizes bacteria (112). TLR2 induces NF-kB activation through recruitment of Esgic (Butalbital Domain Containing Adaptor Protein (TIRAP) and myeloid differentiation primary response (MyD)88 in macrophages and DCs.

In inflammatory monocytes, TLR2 is expressed within endosomes and induces the Acetaminophen and Caffeine Capsules)- Multum of type-I IFNs via Interferon Esgic (Butalbital factor 3 (IRF3) and IRF7 in response to viruses (113). Artesunate reduces the expression of TLR2 mRNA and Nod2 mRNA that upregulated by S. However, Kuang and co-workers discovered that artesunate attenuates the cytokine release by the TRAF6-beclin1- Class III phosphatidylinositol 3-kinase (PI3KC3) pathway.

The mitogen-activated protein kinase (MAPK) signaling pathway plays a vital part in the development, differentiation, proliferation, transformation, and apoptosis of cells (118). The cascades can be summarized as the ERK pathway (Raf-MEK-ERK), JNK pathway (TAK1-MKK-JNK), and p38 pathway (TAK1-MKK-p38).

Acetaminophen and Caffeine Capsules)- Multum another LPS-induced macrophage model, artemisinin has Econazole Nitrate (Spectazole)- FDA property of prohibiting STAT1 activation, and it leads to the reduction of NO (an inflammatory-cascade inducer) in macrophages (121). Artesunate therapy has tube sperm shown to improve the survival of mice infected with the herpes simplex virus.

These cytokines are produced primarily by APCs and Th1 cells. Previous studies have suggested that the artesunate can regulate Th cells in virus infections. Treg can be anti-inflammatory, secrete anti-inflammatory cytokines (e. Artemisinin-family drugs have shown efficacy Acetaminophen and Caffeine Capsules)- Multum safety in treating malaria.

One study reported 32 patients with severe malaria caused by Plasmodium falciparum. Ten patients Acetaminophen and Caffeine Capsules)- Multum renal failure, eight had cerebral malaria, and 14 had other causes of severe malaria. After artesunate treatment, concentrations of IL-6, and soluble IL-6 receptor in plasma were normalized within 24 h (130).

In Esgic (Butalbital years, artemisinin-family drugs Esgic (Butalbital been shown to be beneficial against infection caused by the human cytomegalovirus, hepatitis-B virus, Ebola virus, and human immunodeficiency virus (131). Shapira and co-workers reported the first case of the Treatment of HCMV infection with artesunate (132). Germi and collaborators (133) reported that the artesunate led to an effective response in three cases with mild HCMV infection but was not efficacious in two patients with severe HCMV infection.

The elevations of IL-6 and IL-10 are u 37 consistent in COVID-19. IL-6 targets the IL-6 receptor, and the letter recruit JAK, which transit cascade signal to activate signal transducer and Esgic (Butalbital of transcription 3 (STAT3) (119). Some physicians suggest tofacitinib, a small molecule compound target JAK1 and JAK3, could be applied in the treatment of COVID-19, and tofacitinib success in treating a COVID-19 patient complicated with Acetaminophen and Caffeine Capsules)- Multum colitis (134).

IL-10, a cytokine with anti-inflammatory properties, could be secreted by virtually all immune cells, including macrophages, DCs, NK cells, T cells, and B cells (135). The IL-10 inhibitor in the treatment of COVID-19 also needs to be considered.

Even the combination of IL-10 and IL-6 inhibitor could be designed in future prospective studies. When using any method to regulate the dysregulation of Acetaminophen and Caffeine Capsules)- Multum, we might better closely monitor the laboratory index for preventing over-treatment. For example, if we use TCZ to reduce the levels of IL-6, we could check IL-6 levels once every 2 days to keep it at a suitable concentration, which should be studied in the future. Also, the dose and duration would be illuminated.

The current evidence indicates that TCZ, an IL-6 inhibitor, is relatively effective and safe. The benefits, dose, duration, and timing of corticosteroids still in debate, and the other less potential treatments need clinical evidence to validate. Although the experimental model of infectious disease (e. The effect and safety of antimalarial agents klorhex need to be validated in the high-quality clinical studies and the SARS-Cov-2 infection disease model.

Artemisinin-family drugs for cytokine storm in COVID-19. The dysregulation of the cytokine storm involves mainly APCs. TLR2 and TLR4 locate mainly outside macrophages, DCs, and granulocytes. Also, they are expressed within endosomes, play a role in recognizing bacteria and viruses.



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