International Journal of Immunopathology and Pharmacology最新文献

{"title":"PD-L1 expression in breast invasive ductal carcinoma with incomplete pathological response to neoadjuvant chemotherapy","authors":"Ahmad Alhesa, Heyam A. Awad, Sarah Bloukh, Mahmoud Al-Balas, Mohammed El-Sadoni, Duaa Qattan, Bilal Azab, T. Saleh","doi":"10.1177/03946320221078433","DOIUrl":"https://doi.org/10.1177/03946320221078433","url":null,"abstract":"Objectives: To investigate the expression of programmed death-ligand 1 (PD-L1) in breast cancer in association with incomplete pathological response (PR) to neoadjuvant chemotherapy (NAC). Methods PD-L1 expression was evaluated using immunohistochemistry in post-operative, post-NAC samples of 60 patients (n = 60) diagnosed with breast invasive ductal carcinoma with incomplete PR to NAC, including 31 matched pre-NAC and post-NAC samples (n = 31). PD-L1 protein expression was assessed using three scoring approaches, including the tumor proportion score (TPS), the immune cell score (ICS), and the combined tumor and immune cell score (combined positive score, CPS) with a 1% cut-off. Results In the post-operative, post-NAC samples (n = 60), positive expression rate of PD-L1 was observed in 18.3% (11/60) of cases by TPS, 31.7% (19/60) by ICS, and 25% (15/60) by CPS. In matched samples, positive expression rate of PD-L1 was observed in 19.3% (6/31) of patients by TPS, 51.6% (16/31) by ICS, and 19.3% (6/31) by CPS in pre-NAC specimens, while it was observed in 22.6% (7/31) of matched post-NAC samples by TPS, 22.6% (7/31) by ICS, and 19.3% (6/31) by CPS. In the matched samples, there was a significant decrease in PD-L1 immunoexpression using ICS in post-NAC specimens (McNemar’s, p = 0.020), while no significant differences were found using TPS and CPS between pre- and post-NAC samples (p = 1.000, p = 0.617; respectively). PD-L1 immunoexpression determined by TPS or CPS was only significantly associated with ER status (p = 0.022, p = 0.021; respectively), but not with other clinicopathological variables. We could not establish a correlation between PD-L1 expression and the overall survival rate (p > 0.05). There were no significant differences in the tumor infiltrating lymphocytes count between the paired pre- and post-NAC samples (t = 0.581, p = 0.563 or Wilcoxon’s Signed Rank test; z = -0.625, p = 0.529). Conclusion Our findings indicate that PD-L1 protein expression in infiltrating immune cells was significantly reduced in breast tumors that developed incomplete PR following the exposure to NAC.","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44242925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated number of IL-21+ TFH and CD86+CD38+ B cells in blood of renal transplant recipients with AMR under conventional immuno-suppression.","authors":"Jing Liu, Tongyu Tang, Zhihui Qu, Li Wang, Rui Si, Haifeng Wang, Yanfang Jiang","doi":"10.1177/20587384211048027","DOIUrl":"10.1177/20587384211048027","url":null,"abstract":"<p><p>The objective of this study is to detect the number of different subsets of TFH and B cells in renal transplant recipients (RTR) with antibody-mediated acute rejection (AMR), acute rejection (AR), chronic rejection (CR), or transplant stable (TS). The present study was a prospective study. The numbers of ICOS +, PD-1+ and IL-21+ TFH, CD86+, CD38+, CD27+, and IgD- B cells in 21 patients with end-stage renal disease (ESRD) and post-transplant times were measured by flow cytometry. The level of serum IL-21 was detected by ELISA. The numbers of circulating CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+PD-1+, CD4+CXCR5+IL-21+ TFH, CD19+CD86+, and CD19 +CD86+CD38+ B cells as well as the level of serum IL-21 in the AMR, AR, and CR groups at post-transplantation were significantly higher than those at pre-transplantation. In contrast, the number of circulating CD19+CD27+IgD B cells was significantly increased in the TS groups in respect to the other groups. Moreover, the numbers of circulating CD4+CXCR5+IL-21+ TFH cells, CD19+CD86+CD38+ B cells as well as the level of serum IL-21 were positive related to the level of serum Cr while showing negative correlated with the values of eGFR in the AMR groups at post-transplantation for 4 and 12 weeks. Circulating TFH cells may be a biomarker in RTR with AMR, which can promote the differentiation of B cells into plasma cells by activating B cells, thereby promoting disease progression.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"36 ","pages":"20587384211048027"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/76/50/10.1177_20587384211048027.PMC8755922.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39897235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal sperm morphology is associated with sensitization to inhaled allergens.","authors":"Rafał Adamczak,&nbsp;Natalia Ukleja-Sokołowska,&nbsp;Magdalena Pasińska,&nbsp;Joanna Zielińska,&nbsp;Mateusz Leśny,&nbsp;Mariusz Dubiel","doi":"10.1177/20587384211066718","DOIUrl":"https://doi.org/10.1177/20587384211066718","url":null,"abstract":"<p><strong>Background: </strong>Allergy is associated with the loss of tolerance of environmental antigens, combined with a pathological immune response. There were no studies up to date that would show whether the quality of semen decreases in people with allergic diseases.</p><p><strong>Material and methods: </strong>The research included men who reported to the Gynecological Outpatient Clinic due to reproductive difficulties, defined as the lack of pregnancy after one year of regular intercourse. Semen quality was assessed according to the World Health Organization (WHO) standard. All patients underwent skin prick tests with the most important inhalation allergens (such as hazel, silver birch, mugwort, rye, dog, cat, <i>Dermatophagoides farinae, Dermatophagoides pteronyssinus</i>, alder, <i>Alternaria alternata, Cladosporium herbarum</i>, and grass mix). The data was statistically analyzed.</p><p><strong>Results: </strong>Results of 52 patients aged 25-52 years (34.62 ± 4.96) were analyzed. The mean BMI (Body mass index) was 28.25 (+ -3.77). It was found that 38 men (73%) had increased body weight, and 14 men (26.9%) were obese (BMI > = 30). 13 patients were smokers (25%), and 24 patients (46%) had skin tests positive for at least one inhaled allergen. Sperm tail defects were statistically more significant in patients allergic to birch, rye, cat, alder, and grass. In patients allergic to <i>Alternaria alternata</i>, head defects were statistically more significant (<i>p</i> < .05). No association was found between allergy to house dust mites, mugwort, hazel, and dogs and the deterioration of semen.</p><p><strong>Conclusion: </strong>Allergy due to inhalation allergens had an influence on the quality of male semen. Further research is necessary to establish the immunological bases of this phenomenon.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"36 ","pages":"20587384211066718"},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9c/7a/10.1177_20587384211066718.PMC8743921.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39647129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single nucleotide polymorphism rs 2070874 at Interleukin-4 is associated with increased risk of type 1 diabetes mellitus independently of human leukocyte antigens","authors":"A. Osman, I. Brema, Alaa AlQurashi, A. Al-jurayyan, Benjamin Bradley, Muaawia Hamza","doi":"10.1177/03946320221090330","DOIUrl":"https://doi.org/10.1177/03946320221090330","url":null,"abstract":"Introduction Type 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of insulin-producing pancreatic beta (β-) cells. Previous studies suggested an imbalance between and pro- and anti-inflammatory cytokines exacerbates T1DM development. Objectives We aimed to test the hypothesis that patients with T1DM carry a higher frequency of regulatory genes associated with low levels of the anti-inflammatory cytokines interleukin-4 (IL-4), its receptor (IL-4R), and interleukin-10 (IL-10). Methods Accordingly, we compared frequencies of five different single nucleotide polymorphisms (SNPs) in T1DM patients and healthy controls who had been typed for HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes. Results The frequencies of rs2070874 (IL-4) alleles C and T differed between T1DM patients and controls (cp = 0.0065), as did their codominant (cp = 0.026) and recessive (cp = 0.015) models. Increased frequencies were observed in T1DM patients for HLA alleles: DRB1*03 (pc < 0.0013), DRB1*04 (cp = 0.0169), DQA1*03 (cp = 0.0222), DQA1*05 (cp < 0.0006), DQB1*02 (cp = 0.0005), and DQB1*06 (cp < 0.0005). And lower frequencies were observed for: DRB1*07 (cp = 0.0078), DRB1*11 (cp = 0.0013), DRB1*13 (cp < 0.0364), DRB1*15 (cp < 0.0013), DQA1*01 (cp < 0.0006), and DQA1*02 (cp = 0.0348). Certain DRB1: DQA1: DQB1 haplotypes showed greater frequencies, including, 03:05:02 (p < 0.0001) and 04:03:03 (p = 0.0017), whereas others showed lower frequencies, including, 07:02:02 (p = 0.0032), 11:05:03 (p = 0.0007), and 15:01:06 (p = 0.0002). Stratification for the above HLA haplotypes with rs2070874 C/C exhibited no significant differences between T1DM patients overall and controls. However, when stratified for the vulnerable HLA haplotype (03:05:02/04:03:03), young patients in whom T1DM began at ≤13 years had a higher frequency of the SNP (rs2070874 C/C); a gene associated with low IL-4 production (p < 0.024). Conclusion This study suggests that possession of the rs2070874 C/C genotype, which is associated with low production of IL-4, increases the risk of T1DM in young individuals carrying vulnerable HLA alleles/haplotypes.","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41917862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new indicator: The diagnostic value of CD8+T/B lymphocyte ratio in sepsis progression.","authors":"Yizhi Peng,&nbsp;Xiaofan Wang,&nbsp;Sheng Yin,&nbsp;Min Wang","doi":"10.1177/03946320221123164","DOIUrl":"https://doi.org/10.1177/03946320221123164","url":null,"abstract":"<p><strong>Objective: </strong>To reveal the value of single lymphocyte subpopulation and their ratios in the progression of sepsis.</p><p><strong>Methods: </strong>From January 2019 to March 2021, 39 sepsis patients, 16 septic shock patients, and 50 healthy volunteers were recruited in the Second Xiangya Hospital for this cross-sectional study. The absolute quantitation of CD4+T, CD8+T, B lymphocytes, and NK cells in peripheral blood were determined by flow cytometry. SPSS Software was used to analyze the results.</p><p><strong>Results: </strong>On the whole, the numbers of lymphocytes in the sepsis group and in the septic shock group were lower than that in the healthy control group. Surprisingly, the percentage of CD8+T lymphocytes in the septic shock group was slightly higher than that in the sepsis group. The percentage of B lymphocytes in the sepsis group was higher than that in the healthy control group. The AUC of CD8+T/B was 0.724, with the sensitivity and specificity being 75.00% and 71.79%, respectively.</p><p><strong>Conclusion: </strong>The immune expression pattern of patients with sepsis was not a simple decrease in the number of lymphocytes. The change in the ratios of lymphocyte subpopulation might be more meaningful along the development and progression of sepsis. The ratio of CD8+T/B could be used to diagnose the progression of sepsis and reduce the misdiagnosis rate to a certain extent.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"36 ","pages":"3946320221123164"},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8a/13/10.1177_03946320221123164.PMC9421217.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33445090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of STAT6 by intranasal allergens correlated with the development of eosinophilic chronic rhinosinusitis in a mouse model.","authors":"Hongqi Wei,&nbsp;Longjiang Xu,&nbsp;Peng Sun,&nbsp;Hongyu Xing,&nbsp;Zhengwen Zhu,&nbsp;Jisheng Liu","doi":"10.1177/03946320221109529","DOIUrl":"https://doi.org/10.1177/03946320221109529","url":null,"abstract":"<p><p>Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory disease characterized by prominent eosinophilic infiltration along with a T-helper-2 (Th2) response. It has been well documented that signal transducer and activator of transcription 6 (STAT6) is a nuclear transcription factor that mediates Th2-type immunity and is implicatory of STAT1 and STAT3 in the pathogenesis of allergic airway diseases. However, little is known about the association between STATs and ECRS. Here, we explored the relationship between STAT1, STAT3, and/or STAT6 and eosinophilic inflammation accompanied by Th2-type immunity in a mouse model of ECRS. An ovalbumin (OVA)-staphylococcal enterotoxin B (SEB)-induced ECRS murine model was first established. The mucosal histological alterations were determined using hematoxylin and eosin staining. The number of eosinophils in peripheral blood was measured using a blood cell analyzer. The cytokine (IL-4, IL-5, IL17 A and IFN-γ) expression levels in the sinonasal mucosa and total and OVA-specific IgE from serum were measured using ELISA. Then, the protein levels of STAT1, STAT3, STAT6, phosphorylated STAT1 (p-STAT1), p-STAT3, p-STAT6, T-box expressed in T-cells (T-bet), GATA binding protein 3 (GATA-3), and retinoic acid receptor-related orphan receptor γ (RORγt) in the sinonasal mucosa were examined by immunohistochemical staining or Western blotting. Local administration of OVA combined with SEB (OVA + SEB) induced multiple polyp-like lesions, accompanied by prominent eosinophilic infiltration in the sinonasal mucosa. The OVA- and OVA+SEB-treated groups showed significantly higher eosinophil counts from peripheral blood and total and OVA-specific IgE levels from serum than those in the PBS- and SEB-treated groups. The levels of p-STAT6 were markedly increased by OVA + SEB exposure, as well as GATA-3, IL-4, and IL-5, but did not affect STAT6, p-STAT1, p-STAT3, T-bet, RORγt, IFN-γ, or IL-17A. Furthermore, an eosinophil count in the sinonasal mucosa showed a positive correlation with the level of p-STAT6 in the ECRS mouse model. Signal transducer and activator of transcription 6 signaling could be activated in the OVA+SEB-induced ECRS model and might be a crucial signal transducer in the development of Th2-skewed ECRS.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":" ","pages":"3946320221109529"},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/04/aa/10.1177_03946320221109529.PMC9218454.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40122485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PM2.5 activated NLRP3 inflammasome and IL-1β release in MH-S cells by facilitating autophagy via activating Wnt5a.","authors":"Guanli Yuan,&nbsp;Yinfeng Liu,&nbsp;Zheng Wang,&nbsp;Xiaotong Wang,&nbsp;Zhuoxiao Han,&nbsp;Xixin Yan,&nbsp;Aihong Meng","doi":"10.1177/03946320221137464","DOIUrl":"https://doi.org/10.1177/03946320221137464","url":null,"abstract":"<p><p>Particulate matter 2.5 (PM2.5)-induced pulmonary inflammation is an important issue worldwide. NLRP3 inflammasome activation has been found to be involved in pulmonary inflammation development. However, whether PM2.5 induces pulmonary inflammation by activating the NLRP3 inflammasome has not yet been fully elucidated. This study researched whether PM2.5 induces the NLRP3 inflammasomes activation to trigger pulmonary inflammation.Mice and MH-S cells were exposed to PM2.5, BOX5, and Rapamycin. Hematoxylin and eosin staining was performed on the lung tissues of mice. M1 macrophage marker CD80 expression in the lung tissues of mice and LC3B expression in MH-S cells was detected by immunofluorescence. IL-1β level in the lavage fluid and MH-S cells were detected by enzyme-linked immunosorbent assay. Protein expression was detected by Western blot. Autophagy assay in MH-S cells was performed by LC3B-GFP punctae experiment.PM2.5 exposure induced the lung injury of mice and increased NLRP3, P62, Wnt5a, LC3BII/I, and CD80 expression and IL-1β release in the lung tissues. PM2.5 treatment increased NLRP3, pro-caspase-1, cleaved caspase-1, Pro-IL-1β, Pro-IL-18, P62, LC3BII/I, and Wnt5a expression, IL-1β release, and LC3B-GFP punctae in MH-S cells. However, BOX5 treatment counteracted this effect of PM2.5 on lung tissues of mice and MH-S cells. Rapamycin reversed the effect of BOX5 on PM2.5-induced lung tissues of mice and MH-S cells.PM2.5 activated the NLRP3 inflammasome and IL-1β release in MH-S cells by facilitating the autophagy via activating Wnt5a. The findings of this study provided a new clue for the treatment of pulmonary inflammation caused by PM2.5.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":" ","pages":"3946320221137464"},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c4/88/10.1177_03946320221137464.PMC9647284.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40672611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers of inflammation and left ventricular remodelling in psoriasis patients treated with infliximab.","authors":"Helga Midtbø,&nbsp;Ester Kringeland,&nbsp;Eva Gerdts,&nbsp;Per Magne Ueland,&nbsp;Klaus Meyer,&nbsp;Anja Linde,&nbsp;Arve Ulvik,&nbsp;Roland Jonsson,&nbsp;Kåre Steinar Tveit","doi":"10.1177/03946320221111131","DOIUrl":"https://doi.org/10.1177/03946320221111131","url":null,"abstract":"<p><p><b>Objective:</b> Psoriasis is an immune mediated disorder associated with T cell activation and cardiovascular disease (CVD). We explored the association of inflammation with left ventricular (LV) remodelling in psoriasis patients receiving treatment with the tumour necrosis factor-α (TNF-α) blocker infliximab. <b>Methods:</b> Psoriasis patients (<i>n</i> = 47, age 47 ± 14 years, 66% men) and 99 control subjects without psoriasis (age 47 ± 11 years, 72% men) were examined by echocardiography in a cross-sectional study. LV remodelling was assessed by LV mass index for height in the allometric power of 2.7. Serum concentrations of C-reactive protein (CRP), serum amyloid A (SAA), neopterin, kynurenine:tryptophan ratio (KTR) and the pyridoxic acid ratio (PAr) index were measured. <b>Results:</b> Serum concentration of neopterin (<i>p</i> = .007) was higher in psoriasis patients, while the other inflammatory biomarkers had similar levels. LV mass index was lower in patients than controls (35.6 ± 9.6 g/m^2.7 vs. 40.3 ± 9.8 g/m^2.7, <i>p</i> = .008). In the total study population, serum SAA (β = 0.18, <i>p</i> = .02), KTR (β = 0.20, <i>p</i> = .02) and the PAr index (β = 0.26, <i>p</i> = .002) were all associated with higher LV mass index independent of age, sex, body mass index, hypertension, smoking, renal function and psoriasis. Also in psoriasis patients, higher SAA level (β = 0.34, <i>p</i> = .02), KTR (β = 0.32, <i>p</i> = .02) and the PAr index (β = 0.29, <i>p</i> = .05) were associated with higher LV mass index independent of body mass index, hypertension and diabetes. <b>Conclusion:</b> Higher levels of the inflammatory biomarkers SAA, KTR and the PAr index were associated with greater LV mass index in psoriasis patients, indicating a role of chronic inflammation in LV remodelling evident even during treatment with TNF-α blockers.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":" ","pages":"3946320221111131"},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/20/16/10.1177_03946320221111131.PMC9379959.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40699940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evodiamine suppresses the progression of non-small cell lung carcinoma via endoplasmic reticulum stress-mediated apoptosis pathway in vivo and in vitro","authors":"Yu-ting Li, Yuming Wang, Xiaoqun Wang, Lulu Jin, Lu Yang, Jinli Zhu, Hongwu Wang, Fang Zheng, H. Cui, Xiaojiang Li, Yingjie Jia","doi":"10.1177/03946320221086079","DOIUrl":"https://doi.org/10.1177/03946320221086079","url":null,"abstract":"Background Evodiamine (EVO) is one of the major components isolated from Evodia rutaecarpa (Juss.). Recent studies have shown that EVO has an anti-cancer effect. However, the pharmacological mechanism by which EVO impacts cancer is still poorly understood. Objectives This study focused on asking the anti-cancer effect of EVO in human non-small cell lung carcinoma (NSCLC), and in particular to investigate whether EVO acts via modulating the endoplasmic reticulum stress (ERS)-mediated apoptosis pathway. Materials and Methods A Lewis lung carcinoma (LLC) tumor-bearing mouse model was treated with low-dose EVO (5 mg/kg) and high-dose EVO (10 mg/kg) intraperitoneally for 14 d. The effects of EVO on tumor growth, apoptosis, and ERS were assessed. In addition, NSCLC A549 and LLC cells were treated with EVO in vitro. The effects of EVO on cell proliferation, apoptosis, and ERS were investigated. Finally, 4-phenylbutyric acid (4-PBA), an ERS inhibitor, was used to validate whether EVO induced apoptosis of NSCLC cells by modulating ERS. Results EVO treatment significantly inhibited tumor growth in LLC tumor-bearing mice. H&E staining indicated that EVO treatment reduced the number of tumor cells and the nucleo-plasmic ratio. Immunostaining showed that EVO treatment significantly decreased the expression of Ki-67. TUNEL staining revealed that EVO induced apoptosis in the tumor. Likewise, EVO treatment up-regulated the expression of apoptosis-related genes and proteins and increased activation of the ERS pathway in the tumor. Additionally, EVO inhibited cell proliferation and increased cell apoptotic rates in A549 and LLC cells. EVO also increased the expression levels of genes and proteins associated with ERS-mediated apoptosis pathway in vitro. The effects of EVO on apoptosis were abolished by 4-PBA treatment. Conclusions Our study demonstrated that EVO suppresses the progression of NSCLC by modulating the ERS-mediated apoptosis pathway.","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44226776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IP-10 and complement activation as friend or foe in COVID-19","authors":"Saowalak Bunprakob, Pasin Hemachudha, Chanida Ruchisrisarod, Thirawat Supharatpariyakorn, T. Hemachudha","doi":"10.1177/03946320221096202","DOIUrl":"https://doi.org/10.1177/03946320221096202","url":null,"abstract":"Introduction The Innate immune system senses danger signals of COVID-19 infection and produce an orchestration of cellular, complement and cytokines cascades. These led to the approach using immunosuppressive agents. It is intriguing whether certain biomarkers can aid the proper administration of such drugs. Methods Plasma specimens of 58 COVID-19 patients with differing severity, from very mild illness (group A), mild (group B), moderate (group C), and severe/critical illness (group D) were assayed for cyto-chemokines and terminal complement complex (SC5b-9) during the course of diseases. None received anti-IL-6 therapy, there was no mortality in this cohort. Results IP-10 and RANTES levels were dominant cytokines. IP-10 levels increased significantly in all groups when compared between pre-nadir and nadir phases (group A, p =0.428; group B =0.034; group C =0.159; group D <0.001) and in groups B and D when compared between nadir and recovery phases (p <0.001). RANTES levels were elevated in all groups across all phases with no significant differences. SC5b-9 levels increased significantly as compared to healthy controls [pre-nadir- group A versus healthy, p =0.122; group B-D versus healthy, p =0.021); nadir-group A versus healthy, p =0.003; group B-D versus healthy, p <0.001; recovery phase (p <0.001)] but not between groups A and B-D at pre-nadir (p=0.606). Conclusion The absence of significant pro-inflammatory responses and early elevation of IP-10 levels and complement activation may be favorable and necessary for viral elimination in COVID-19 patients. Expression of distinct cyto-chemokines during each clinical phase may be useful for guiding proper therapeutic interventions on alleviating thrombo-inflammation responses to COVID-19 infection.","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45538333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}