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This study was conducted to evaluate the effects of Allium hookeri (AH) leaves cultivated with different light-emitting diode (LED) intensities (L: low, 100 μmol/m 2 /s; M: medium, 150 μmol/m 2 /s; H: high, 200 μmol/m 2 /s). Alliin concentration increased as light intensity increased in AH and showed the highest level at LED-H condition. The anti-obesity and immunomodulatory properties of AH were evaluated in a cyclophosphamide (CPA)-induced immunosuppressed obese animal model. C57BL/6 J mice were randomly divided into control (CON), high-fat diet (HFD) control (CON-H), negative control (NC), positive control (PC, β-glucan, 50 mg/kg body weight (BW)), AH L, M, and H groups. The three kinds of AH extracts were orally administered to the mice at 300 mg/kg BW for 2 weeks. Except for CON and CON-H, all the other groups were intraperitoneally treated with CPA. Epididymal and abdominal fat weight decreased as LED intensity increased while spleen weight increased in the AH groups. Serum glucose decreased as LED intensity increased in the AH groups and H group showed the lowest level. Triglycerides, total, and LDL-cholesterol levels decreased while HDL-cholesterol level increased in the AH groups compared to the NC group. Moreover, AH effectively reduced serum ALT and AST levels and increased the total white blood cell count, particularly elevating lymphocyte and monocyte levels. Furthermore, NK cell activity was higher in the AH groups. These findings suggest that AH cultivated at optimal LED intensity could be used as a novel biomedicine and in pharmacotherapy to treat related diseases to improve public health without any toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Macrophages undergo activation in response to multiple stimuli, including pathogens, growth factors and natural products. The inflammatory response and oxidative stress play critical roles in such macrophage activation. Some natural products reportedly promote immunoregulatory effects and the control of macrophage activation. Caryocar villosum (Cv), a native amazon plant, contains compounds that are an important source of molecules capable of macrophage activation. Herein, we demonstrate the immunomodulatory effects of oil obtained from Caryocar villosum (CvO) on macrophages. Macrophages were treated with varying concentrations of CvO, and resulting cellular morphological and functional changes were evaluated, including the production of nitric oxide (NO), reactive oxygen species (ROS), cytokines and phagocytic activity. Treatment of cells with 50 and 100 μg/mL CvO induced morphological and physiological alterations in the macrophages, such as increased cell surface and phagocytic activity. Additionally, treatment increased the productions of inflammatory cytokines (INF-γ, TNF-α, IL-6) and anti-inflammatory cytokines (IL-17 and IL-10) by macrophages, and significantly decreased ROS levels. In conclusion, these data suggest that, due to molecular diversity, CvO promoted an immunomodulatory effect on macrophages, mediated by an increased production of cytokines, and inhibition of ROS generation and phagocytic activity. Thus, CvO presents potential as a therapeutic agent for the treatment of inflammatory and non-inflammatory diseases., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Edilene Oliveira da Silva reports financial support was provided by National Council for Scientific and Technological Development. Jose Luiz M Nascimento reports financial support was provided by Fundação de Amparo à Pesquisa no Estado do Pará. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Infectious diseases are a major threat to global health and cause millions of deaths every year, particularly in developing countries. The emergence of multidrug resistance challenges current antimicrobial treatments, inducing uncertainty in therapeutic protocols. New compounds are therefore necessary. A drug repurposing approach could play a critical role in developing new treatments used either alone or in combination with standard therapy regimens. Herein, we focused on cysteamine, an aminothiol endogenously synthesized by human cells during the degradation of coenzyme-A, which is a drug approved for the treatment of nephropathic cystinosis. Cysteamine influences many biological processes due to the presence of the highly reactive thiol group. This review provides an overview of cysteamine-mediated effects on different viruses, bacteria and parasites, with a particular focus on infections caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Mycobacterium tuberculosis, non-tuberculous mycobacteria (NTM), and Pseudomonas aeruginosa. Evidences for a potential use of cysteamine as a direct antimicrobial agent and/or a host-directed therapy, either alone or in combination with other antimicrobial drugs, are described., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The immunomodulatory imide drugs (IMiDs) thalidomide, lenalidomide and pomalidomide may exhibit therapeutic efficacy in the prostate. In lower urinary tract symptoms (LUTS), voiding and storage disorders may arise from benign prostate hyperplasia, or overactive bladder. While current therapeutic options target smooth muscle contraction or cell proliferation, side effects are mostly cardiovascular. Therefore, we investigated effects of IMiDs on human detrusor and porcine artery smooth muscle contraction, and growth-related functions in detrusor smooth muscle cells (HBdSMC)., Methods: Cell viability was assessed by CCK8, and apoptosis and cell death by flow cytometry in cultured HBdSMC. Contractions of human detrusor tissues and porcine interlobar and coronary arteries were induced by contractile agonists, or electric field stimulation (EFS) in the presence or absence of an IMID using an organ bath. Proliferation was assessed by EdU assay and colony formation, cytoskeletal organization by phalloidin staining, RESULTS: Depending on tissue type, IMiDs inhibited cholinergic contractions with varying degree, up to 50 %, while non-cholinergic contractions were inhibited up to 80 % and 60 % for U46619 and endothelin-1, respectively, and EFS-induced contractions up to 75 %. IMiDs reduced viable HBdSM cells in a time-dependent manner. Correspondingly, proliferation was reduced, without showing pro-apoptotic effects. In parallel, IMiDs induced cytoskeletal disorganization., Conclusions: IMiDs exhibit regulatory functions in various smooth muscle-rich tissues, and of cell proliferation in the lower urinary tract. This points to a novel drug class effect for IMiDs, in which the molecular mechanisms of action of IMiDs merit further consideration for the application in LUTS., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Thomas Kolben holds stock of Roche AG and a relative is employed at Bayer AG. The other authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Multiple myeloma is currently incurable, and the incidence rate is increasing year by year worldwide. Although in recent years the combined treatment plan based on proteasome inhibitors and immunomodulatory drugs has greatly improved the treatment effect of multiple myeloma, most patients still relapse and become resistant to current treatments. To solve this problem, scientists are committed to developing drugs with higher specificity, such as iberdomide, which is highly specific to ikaros and aiolos. This review aims to focus on the small molecular agents that are being researched/clinically used for the treatment of multiple myeloma, including the target mechanism, structure-activity relationship and application prospects of small molecular agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Sex differences in immune-mediated diseases are linked to the activity of estrogens on innate immunity cells, including macrophages. Tamoxifen (TAM) is a selective estrogen receptor modulator (SERM) used in estrogen receptor-alpha (ERα)-dependent breast cancers and off-target indications such as infections, although the immune activity of TAM and its active metabolite, 4-OH tamoxifen (4HT), is poorly characterized. Here, we aimed at investigating the endocrine and immune activity of these SERMs in macrophages. Using primary cultures of female mouse macrophages, we analyzed the expression of immune mediators and activation of effector functions in competition experiments with SERMs and 17β-estradiol (E2) or the bacterial endotoxin LPS. We observed that 4HT and TAM induce estrogen antagonist effects when used at nanomolar concentrations, while pharmacological concentrations that are reached by TAM in clinical settings regulate the expression of VEGFα and other immune activation genes by ERα- and G protein-coupled receptor 1 (GPER1)-independent mechanisms that involve NRF2 through PI3K/Akt-dependent mechanisms. Importantly, we observed that SERMs potentiate cell phagocytosis and modify the effects of LPS on the expression of inflammatory cytokines, such as TNFα and IL1β, with an overall increase in cell inflammatory phenotype, further sustained by potentiation of IL1β secretion through caspase-1 activation. Altogether, our data unravel a novel molecular mechanism and immune functions for TAM and 4HT, sustaining their repurposing in infective and other estrogen receptors-unrelated pathologies., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Ulcerative colitis (UC) is a gastrointestinal inflammatory disease with a multifactorial pathophysiology. This study aims to investigate the immunomodulatory effect of Portulaca oleracea leaf ethanolic extract (POE) on acetic acid (AA)-induced UC in mice. Experimental animals received oral doses of POE (200 mg/kg for 7 days) after an induction of colitis by intrarectal AA administration. In mice with AA-induced UC treated with POE, the results revealed a significant modulation in body weight and colon length. Moreover, treatment with POE downregulated the interleukin 1, 6, and 17, tumor necrosis factor-alpha, gamma interferon, and nuclear factor-kappa B levels compared with the colitis group. Furthermore, POE markedly inhibited histological damage, decreased myeloperoxidase activity and reduced fecal calprotectin level compared with the colitis group. These data are consistent with the reduction in total bacterial content in the colon. Taken together, treatment with POE may reduce colonic inflammation by alleviating the immune response and inhibiting the severity of colitis. The HPLC analysis of POE resulted in the identification of seven medicinal compounds comprising two phenolic acids (ferulic and caffeic acids) and five flavonoids (kaempferol, quercetin, rutin, narenginin and hesperidin). Subsequent analysis of POE by GC-MS revealed ten phytocomponents; the major percentages were hexadecenoic acid, methyl ester (29.8119%), α-linolenic acid (25.8431%), 16-octadecenoic acid, methyl ester (15.1578%) and α-tocopherol (10.7848%). Delta-lactams and alkanes were the minor components. Such natural plant-derived substances and their probable synergistic action appear to contribute to a promising therapeutic protocol for colitis., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The study aimed, by integrating transcriptomics and metabolomics, to reveal novel biomarkers caused by overdosed acetaminophen (APAP) and liver protection substances procured by pre-administration of ginseng shoots extract (GSE). Totally 4918 genes and 127 metabolites were identified as differentially expressed genes and differential metabolites, respectively. According to KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment, such pathways as primary bile acid biosynthesis, bile secretion, retinol metabolism, histidine and several other amino-related metabolism were significantly altered by GSE and disturbed by subsequent overdosed APAP at the transcriptomic as well as metabolomic levels. Fifteen key biomarker metabolites related to these pathways were up-regulated in APAP-treated vs GSE-pretreated liver tissues, and were reported exerting anti-oxidant, anti-inflammatory, anti-apoptotic and/or immunomodulate functions, three of which even possessed direct hepatoprotection effects. Twenty five vital unigenes modulating these metabolites were further verified by correlation analysis and expression levels of fifteen of them were examined by qRT-PCR. Our findings indicate that GSE may be an effective dietary supplement for preventing the liver damage caused by the overdosed APAP., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

HIV infection and the prolonged use of antiretroviral therapy (ART) contribute to persistent inflammation and immune deregulation in people living with HIV/AIDS (PLWHA). Propolis is a bee product with plenty of biological properties, including immunomodulatory and anti-inflammatory action. This work aimed to evaluate possible changes in the immune/inflammatory response in PLWHA under ART after propolis intake. Asymptomatic PLWHA were double-blindly randomized into parallel groups receiving propolis (500 mg/day, n = 20) for 3 months or placebo (n = 20). Plasma cytokines (TNF-α, IL-2, IL-4, IL-6, IL-10 and IL17) were evaluated by cytometric bead array; cytokine production by PBMC (IFN-γ, IL-5, IL-17, IL-10, IL-1β, IL-18, and IL-33) was assessed by ELISA; gene expression (T-bet, GATA-3, RORγt and Foxp3) was determined by RT-qPCR, and cell proliferation was analysed by flow cytometry using CFSE staining. The average of gender, age, CD4 + /CD8 + T cell count, time of diagnosis and treatment were similar in both groups. No differences were observed in cytokine levels nor in inflammasome activation. However, Pearson's correlation showed that IL-10 was directly correlated to CD4 + T cell count and inversely to IFN-γ after treatment with propolis. Foxp3 expression and lymphocyte proliferation increased in the propolis group. Data suggested that daily propolis consumption may improve the immune response and decrease the inflammatory status in asymptomatic PLWHA under ART., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)