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Background and aim Psoriasis is a skin disorder that leads to chronic inflammation and keratinocyte hyperproliferation. Sericin extracted from Bombyx mori cocoon has been demonstrated to possess anti-inflammatory and antiproliferative properties, which makes it a viable candidate for psoriasis treatment. This study aimed to investigate the therapeutic effect of sericin on skin psoriasis at the cellular level. Experimental procedure Imiquimod-induced skin psoriasis was established in Sprague-Dawley rats. The rats with psoriasis were divided into 6 groups (n = 5), namely, one nontreatment control group and five groups that received different treatments: sericin (2.5%, 5%, and 10%), 0.1% betamethasone, 3 μg/ml calcitriol. The treatments were administered twice daily for 7 days, followed by skin sample collection. Epidermal improvement and protein expression were evaluated using histopathological and label-free proteomic approaches and immunohistochemistry. Results and conclusion Compared with other concentrations, 10% sericin had the desired effect of improving skin psoriasis as shown by reduced epidermal thickness, similar to the effects of betamethasone and calcitriol treatments. Anti-inflammatory activity was shown by decreased C–C motif chemokine 20 (CCL20) expression posttreatment. Proteomic observation revealed that sericin reduced cytokine production by Th17 cells by interfering with the JAK-STAT signaling pathway. Sericin treatment also resulted in a modulated immune response via upregulation of Galectin-3 (Lgals3) and downregulation of Sphingosine-1-phosphate lyase1 (Sgpl1). Sericin improved epithelial cell proliferation by upregulating Nucleoside diphosphate kinase B (Nme2). Therefore, the therapeutic effect of sericin on psoriasis correlated with a reduced immune response and attenuated epidermal proliferation, making sericin a promising approach for skin psoriasis treatment., Graphical abstract Image 1, Highlights • Sericin extracted from Bombyx mori cocoon ameliorates skin psoriasis. • Sericin modulated immune response and epithelial cell proliferation in skin-psoriasis rat model. • Sericin upregulated Lgals3 and downregulated Sgpl1 in immune system. • Downregulated Nme2 of skin psoriasis by sericin treatment reduces epithelial cell proliferation.

Adult Brugia malayi proteins with high potential as epidemiological markers, diagnostic and therapeutic targets, and/or vaccine candidates were revealed by using microfilaremic human sera and an immunoproteomic approach. They were HSP70, cytoplasmic intermediate filament protein, independent phosphoglycerate mutase, and enolase. Brugia malayi microfilaria-specific proteins that formed circulating immune complexes (ICs) were investigated. The IC-forming proteins were orthologues of hypothetical protein Bm1_12480, Pao retrotransposon peptidase family protein, uncoordinated protein 44, NAD-binding domain containing protein of the UDP-glucose/GDP-mannose dehydrogenase family which contained ankyrin repeat region, ZU5 domain with C-terminal death domain, C2 domain containing protein, and FLJ90013 protein of the eukaryotic membrane protein family. Antibodies to these proteins were not free in the microfilaremic sera, raising the possible role of the IC-forming proteins in an immune evasion mechanism of the circulating microfilariae to avoid antibody-mediated-host immunity. Moreover, detection of these ICs should be able to replace the inconvenient night blood sampling for microfilaria in an evaluation of efficacy of anti-microfilarial agents.

Drug-resistant strains of malaria parasites have emerged for most of antimalarial medications. A new chemotherapeutic compound is needed for malarial therapy. Antimalarial activity against both drug-sensitive and drug-resistant P. falciparum has been reported for an isocryptolepine derivative, 8-bromo-2-fluoro-5-methyl-5H-indolo[3,2-c]quinoline (ICL-M), which also showed less toxicity to human cells. ICL-M has indoloquinoline as a core structure and its mode of action remains unclear. Here, we explored the mechanisms of ICL-M in P. falciparum by assessing the stage-specific activity, time-dependent effect, a proteomic analysis and morphology. Since human topo II activity inhibition has been reported as a function of isocryptolepine derivatives, malarial topo II activity inhibition of ICL-M was also examined in this study. The ICL-M exhibited antimalarial activity against both the ring and trophozoite stages of P. falciparum. Our proteomics analysis revealed that a total of 112 P. falciparum proteins were differentially expressed after ICL-M exposure; among these, 58 and 54 proteins were upregulated and downregulated, respectively. Proteins localized in the food vacuole, nucleus, and cytoplasm showed quantitative alterations after ICL-M treatment. A bioinformatic analysis revealed that pathways associated with ribosomes, proteasomes, metabolic pathways, amino acid biosynthesis, oxidative phosphorylation, and carbon metabolism were significantly different in P. falciparum treated with ICL-M. Moreover, a loss of ribosomes was clearly observed by transmission electron microscopy in the ICL-M-treated P. falciparum. This finding is in agreement with the proteomics data, which revealed downregulated levels of ribosomal proteins following ICL-M treatment. Our results provide important information about the mechanisms by which ICL-M affects the malaria parasite, which may facilitate the drug development of isocryptolepine derivatives.