International Journal of Immunopathology and Pharmacology最新文献

Objectives: The dysregulated immune response occurring upon COVID-19 infection can lead to tissue damage and organ failure. Different therapeutic strategies are needed to cope with the current and future outspread of COVID-19, including antiviral and anti-inflammatory agents. We describe the outcome of hospitalized patients treated with canakinumab and remdesivir plus the standard of care therapy. Methods: This observational study describes the outcome of the combination of canakinumab (450 mg for patients ≥40 and <60 kg, 600 mg for those ≥60 and <80 kg, or 750 mg for patients ≥80 kg) and 200 mg remdesivir intravenous infusion, plus standard of care (SOC), in 17 moderate-to-severe COVID-19 patients hospitalized in the "Annunziata" Hospital, Cosenza, Italy, between August and November 2021. Hematological markers, biochemical, and hemogasanalysis values at baseline versus day 7 of combination treatment were compared by paired t test after checking for normal distribution and correcting for multiple comparison. Results: The median age of patients was 64 years (range: 39-85), and the median hospitalization time (calculated on the 16 patients that were not transferred to intensive care unit) was of 12.5 days (range: 7-35 days); 15/17 patients (88%) did not experience complications. After 7 days of combination therapy, all the inflammatory parameters were significantly reduced with the exception of procalcitonin; moreover, hematological prognostic markers such neutrophil-to-lymphocyte ratio, CRP-to-lymphocyte ratio, and derived neutrophil-to-lymphocyte ratio reduced. Overall, 16/17 patients (94%) recovered after 14 days. Conclusions: Canakinumab and remdesivir treatment, in addition to SOC, in the early stage of moderate-to-severe COVID-19 showed promising outcomes in terms of safety and effectiveness potentially leading to a reduction in inflammatory and hematological prognostic markers after 7 days of treatment.

Background: Adult T-cell leukemia/lymphoma (ATL) is a lymphoid malignancy caused by HTLV-1 infection, with distinct geographical distribution. Despite advances in cancer treatment, the average survival rate of ATL is low. Conferone is a natural coumarin extracted from Ferula species with a wide range of pharmaceutical effects. In search for a novel chemotherapeutic agent, we investigated the cytotoxicity of conferone on ATL cells.

Methods: To obtain conferone, the methanolic extract of the roots of F. flabelliloba was subjected to silica gel column chromatography, followed by ¹H- and ¹³C-NMR to confirm its structure. For cytotoxicity assay, MT-2 cells were treated with different concentrations of conferone (2.5, 5, 10, 20, and 40 µM) for 24, 48, and 72 h, and viability was evaluated by a colorimetric assay using alamarBlue. Cell cycle was analyzed by PI staining and flow cytometry, and qPCR was used to study the expression of candidate genes.

Results and conclusion: Obtained findings indicated that conferone induced considerable cytotoxic effects on MT-2 cells in a time- and dose-dependent manner. In addition, accumulation of cells in the sub-G₁ phase of the cell cycle was detected upon conferone administration. Moreover, conferone reduced the expression of CDK6, c-MYC, CFLIP_L, and NF-κB (Rel-A) in MT-2 cells. Accordingly, conferone could be considered as a potent agent against ATL, although complementary investigations are required to define more precisely its mechanism of action.

Objective: Understand the progress of inflammation over time caused by multi-walled carbon nanotubes (MWCNT).

Methods: Two types of MWCNTs were administered to C57BL/6N mice via intraperitoneal administration at low and high doses (0.05 and 1.0 mg/mouse, respectively). Inflammation was evaluated until 6 months after administration based on cytokine levels and pathological observations. The abdominal cavity lavage fluid was collected and analyzed 1 week, 1, 3, and 6 month(s) after administration. IL-6 expression markedly increased 3 months after the administration of high-dose MWCNT-7.

Results: Notable inflammation was observed in the groups administered with one of the MWCNT, MWCNT-7. On the other hand, inflammation in another MWCNT-treated group was milder than that in the MWCNT-7-treated group. MWCNT-7 induced pronounced inflammation but did not induce tumor formation during the experimental period. Inflammation reaction is one of the most important biological responses to MWCNT.

Conclusion: Three months post-exposure becomes a turning point for the harmful effects of the intraperitoneally administered MWCNT-7.

Background: Hidradenitis suppurativa (HS) is a chronic auto-inflammatory skin condition characterized by nodules, abscesses, and fistulae in skin folds. The underlying pathogenesis of HS remains unclear, and effective therapeutic drugs are limited.

Methods: We acquired mRNA expression profiles from the Gene Expression Omnibus (GEO) database and conducted differential expression analysis between control and HS samples using R software. Four machine learning algorithms (SVM, RF, ANN, and lasso) and WCGNA were utilized to identify feature genes. GO, KEGG, Metascape, and GSVA were utilized for the enrichment analysis. CIBERSORT and ssGSEA were employed to analyze immune infiltration.

Results: A total of 29 DEGs were identified, with the majority showing up-regulation in HS. Enrichment analysis revealed their involvement in immune responses and cytokine activities. KEGG analysis highlighted pathways such as IL-17 signaling, rheumatoid arthritis, and TNF signaling in HS. Immune infiltration analysis revealed the predominant presence of neutrophils, monocytes, and CD8 T cells. Machine learning algorithms and WCGNA identified KYNU as a feature gene associated with HS. We have also identified 59 potential drugs for HS based on the DEGs. Additionally, ceRNA network analysis identified the MUC19_hsa-miR-382-5p_KYNU pathway as a potential regulatory pathway.

Conclusions: KYNU emerged as a feature gene associated with HS, and the ceRNA network analysis identified the MUC19_hsa-miR-382-5p_KYNU pathway as a potential regulator.

Objectives: Sclareol (SCL) is a natural diterpene with anti-inflammation and antioxidant properties. This study aimed to assess the hepatoprotective effects of SCL in diabetic mice. Methods: SCL (10 mg/kg) was administered intragastrically to C57BL/6 mice with streptozotocin-induced diabetes daily for 5 weeks to evaluate its beneficial effects in liver injury. Body and liver weight and blood glucose levels were measured. Liver histopathology, fibrosis, and lipid accumulation were evaluated using hematoxylin and eosin, Masson's trichrome, and Oil Red O staining, respectively. Serum hepatic enzyme and lipid levels were measured using an automatic biochemical analyzer. Hepatocellular apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Oxidative stress markers and reactive oxygen species (ROS) were measured using appropriate assay kits. The effects of sclareol on inflammation and lipid metabolism was evaluated by enzyme-linked immunosorbent assay (ELISA), immunohistochemical analysis, and Western blot assays. Results: SCL significantly decreased serum liver enzymes and lipids levels, and alleviated adipogenesis and fibrosis. Moreover, the protein levels of acetyl-CoA carboxylase and sterol response element-binding protein 1 were downregulated, whereas the expression of carnitine palmitoyl transferase 1 was upregulated. SCL increased the antioxidant activity, and decreased ROS levels. SCL alleviated hepatic mitochondrial damage. Furthermore, SCL inhibited Kupffer cell infiltration and reduced serum inflammatory cytokine levels. SCL significantly downregulated the protein expression of nuclear factor-kappa B (NF-κB) P65, NOD-like receptor protein 3 (NLRP3), caspase 1, and interleukin-1β. Conclusions: Our findings suggest that SCL improves diabetes-induced liver injury by alleviating the NF-κB/NLRP3-mediated inflammation and lipid metabolism disorder.

Introduction: Aberrant epithelial-mesenchymal transition (EMT) and migration frequently occur during tumour progression. BML-111, an analogue of lipoxin A₄, has been implicated in inflammation in cancer research. Methods: 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, western blot, Reverse Transcription Polymerase Chain Reaction (RT-PCR), transwell assay, immunofluorescence, and immunohistochemistry were conducted in this study. Results: In vitro experiments revealed that BML-111 inhibited EMT and migration in CoCl₂-stimulated MCF-7 cells. These effects were achieved by inhibiting MMP-2 and MMP-9, which are downregulated by 5-lipoxygenase (5-LOX). Moreover, BML-111 inhibited EMT and migration of breast cancer cells in BALB/c nude mice inoculated with MCF-7 cells. Conclusion: Our results suggest that BML-111 may be a potential therapeutic drug for breast cancer and that blocking the 5-LOX pathway could be a possible approach for mining effective drug targets.

Resveratrol (Res) has anti-inflammation and antiosteoporosis functions. We evaluated the effect of Res on osteoclast differentiation by releasing inflammatory cytokines from osteoclast precursor RAW 264.7 cells stimulated by lipopolysaccharide (LPS). In the study, LPS (1 ng/L) was used to induce the Raw 264.7 inflammatory injury model in vitro. A total of 25 ng/mL M-CSF + 30 ng/mL RANKL or plus 1 μg/L LPS was used to induce osteoclastogenesis in the experiments. We utilized the Cell Counting Kit-8 assay to measure the relative cell survival of RAW 264.7 cells. Then, enzyme-linked immunosorbent assays were utilized to measure the abundance of inflammatory markers, such as interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and IL-6. Subsequently, Western blot analysis was applied to assess the abundance of phosphorylated transforming growth factor beta-activated kinase 1 (P-TAK1) protein, TNF receptor-associated factor 6 (TRAF6), nuclear factor-κB inhibitor protein (IκB), phosphorylated IκB-α (P-IκB-α), and nuclear factor κB65 (NF-κB65). mRNA expression levels of miR-181a-5p, TRAF6, specific gene calcitonin receptor (CTR), activated T nuclear factor 1 (NFATC1), cathepsin K (CTSK), and matrix metalloproteinase (MMP)-9 were determined via a real-time polymerase chain reaction. Osteoclast bone resorption function was determined. Finally, tartrate-resistant acid phosphatase (TRAP) staining was performed.The results found that Compared with the model group, the degrees of expressions of supernatant inflammatory factors TNF-α, IL-1β, and IL-6 were substantially attenuated in the Res treatment group (p < 0.05). Furthermore, the extent of miR-181a-5p expression in the RAW 264.7 cells significantly increased, whereas P-IκB-α, P-TAK1, NF-κB65, and TRAF6 expressions significantly decreased in the Res treatment group as opposed to the model group (p < 0.05). The CTR, NFATC1, MMP-9, CTSK, and TRAP mRNA expression levels were substantially reduced during osteoclast differentiation and bone resorption in the Res treatment group.The results suggest that Res can reduce the RAW 264.7 cell differentiation into osteoclasts and relieve LPS-stimulated osteoporosis, and the underlying mechanism may be associated with the Res-inhibited activity of the TRAF6/TAK1 pathway through the increased miR-181a-5p expression.

Objective: The objective of this study was to evaluate the magnitude and durability of the anti-nucleocapsid-IgG antibody titer in healthcare workers previously infected with SARS-CoV-2 for a period of 12 months.Methods: This study examined blood samples for SARS-CoV-2-specific IgG collected periodically from 120 healthcare workers previously infected with SARS-CoV-2 (confirmed by RT-PCR) and followed longitudinally up to 12 months from their enrolment into the study.Results: The median anti-N-IgG antibody level identified at 3 months was 23.7 CO-index (IQR: 9.13-50.27) and increased to 32.9 CO-index (IQR: 11.8-84.4) at 6 months. At 9 months, the median anti-N-IgG antibody level started to wane in the subsequent time and was dropped to 14 CO-index (IQR: 3.4-37.6) and declined further to 9.8 CO-index at 12 months (IQR: 2.8-9.8). When classified by age groups, the only statistically significant difference in anti-N-IgG between the two age groups (≤30 years and >30 years) was identified at 12 month time point (median difference 8.06, p = 0.035). Spearman correlation coefficient was negatively associated between anti-N-IgG and time interval (r = -0.255, p = 0.000) but was not statistically significant with age of a patient (p > 0.05).Conclusions: In conclusion, SARS-CoV-2 antibody levels started declining after 6 months but remained detectable in the majority of patients up to 12 months.

Acetaldehyde dehydrogenases (ALDH) 1B1 is associated with a poor prognosis in pancreatic cancer, colorectal cancer, and osteosarcoma. Overexpression of ALDH also impairs tumor immunity. However, it is unclear how ALDH1B1 is associated with patient prognosis and immune infiltration in different cancer types. This is an original research based on bioinformatics analysis. In this study, we investigated the expression and prognostic value of ALDH1B1 in pan-cancer specimens using several databases, including GEPIA2 and Kaplan-Meier Plotter. The GEPIA2 and TIMER2 databases were used to explore correlations between ALDH1B1 expression and immune infiltration in cancers, especially head and neck squamous cell carcinoma (HNSC) and stomach adenocarcinoma (STAD). Finally, the expression of ALDH1B1 was validated by qPCR and immunohistochemistry. The expression of ALDH1B1 differed in most cancers compared to normal tissue controls. ALDH1B1 has an important impact on the prognosis different cancer types, and the high expression of ALDH1B1 is inversely associated with survival in patients with HNSC. A significant positive correlation was identified between ALDH1B1 expression in HNSC and immune infiltration. The poor prognosis associated with high expression of ALDH1B1 may be related to the promotion of M2 polarization of tumor-associated macrophages. Furthermore, markers of immune cell infiltration, such as exhausted T cells and regulatory T cells showed different patterns of ALDH1B1-associated immune infiltration. ALDH1B1 can serve as a prognostic biomarker in pan-cancer types and is correlated with immune infiltration.