Original Article
Jia Shao; Gang Deng; Guojun Wen; Xi Xie
Abstract
Background: CD8+ T cells play a crucial role in immune responses, and have significant potential in tumor immunotherapy. The JAK/STAT pathway is essential for cytokine signal transduction and is linked to immune escape. However, its role in mediating CD8+ T cell anti-tumor immunity in renal cancer is ...
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Background: CD8+ T cells play a crucial role in immune responses, and have significant potential in tumor immunotherapy. The JAK/STAT pathway is essential for cytokine signal transduction and is linked to immune escape. However, its role in mediating CD8+ T cell anti-tumor immunity in renal cancer is not fully understood.Objective: To study the mechanisms underlying CD8+ T cell-mediated anti-tumor immunity and propose new possibilities for immunotherapy in patients with renal cancer.Methods: CD8+ T cells from mouse spleens were sorted using immunomagnetic beads, and their purity was confirmed by flow cytometry. Proliferation was analyzed using CCK-8 and CFSE assays. Activation of CD8+ T cells was assessed through ELISA and Western blotting. The malignant properties of Renca cells were evaluated through flow cytometry, Calcein-AM/PI staining, wound healing, Transwell, Western blot, and immunofluorescence. A subcutaneous tumor model in nude mice was used to examine the role of JAK1/STAT1 pathway in vivo.Results: Inhibitors of JAK1 and STAT1 significantly reduced the proliferation and activation of CD8+ T cell. Co-culture with CD8+ T cells increased apoptosis and inhibited the proliferation, migration, and invasion of Renca cells. The effects were diminished by JAK1 and STAT1 inhibitors, confirming that CD8+ T cells exert antitumor effects through the JAK1/STAT1 pathway. In vivo, inhibition of this pathway reduced the anti-tumor effects of CD8+ T cells.Conclusion: Inhibitors of JAK1 and STAT1 weakened the antitumor effects of CD8+ T cells, suggesting that targeting this pathway could enhance CD8+ T cell-mediated immunity in renal cancer.
Original Article
Zhe Xue; Yuyan Guo; Fangyun Wang; Qinping Yang; Qiuhong Chen; Tingting Lin; Shunhe Lin
Abstract
Background: miR-196b-5p was found to be significantly reduced in endometriosis, but its function and the mechanisms involved remained unclear.Objective: To explore the effect of miR-196b-5p on manipulating macrophage phenotype and the underlying mechanisms in endometriosisMethods: The endometriosis mice ...
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Background: miR-196b-5p was found to be significantly reduced in endometriosis, but its function and the mechanisms involved remained unclear.Objective: To explore the effect of miR-196b-5p on manipulating macrophage phenotype and the underlying mechanisms in endometriosisMethods: The endometriosis mice and End1/E6E7 cells were used for in vivo and in vitro experiments, respectively. QRT-PCR was used to detect miR-196b-5p, suppressor of cytokine signaling 1 (SOCS1), high mobility group AT-Hook 1 (HMGA1), and CCL2 expressions. Western blot was used to detect SOCS1 and HMGA1 protein levels while luciferase reporter assay was performed to determine the interaction between miR-196b-5p and SOCS1/ HMGA1. ELISA was used to measure CCL2, IL-10, and IL-6 levels and immunohistochemical staining and flow cytometry were used to examine CD86 and CD206 expressions.Results: Significantly reduced levels of miR-196b-5p, and increased levels of SOCS1, HMGA1, and CCL2 were observed in the ectopic endometrium of mice with endometriosis. The miR-196b-5p mimic significantly reduced the lesion size, increased M1 macrophages, and decreased M2 macrophages in the ectopic endometrium of mice with endometriosis. End1/E6E7 cells transfected with miR196b-5p mimic significantly increased M1 macrophages, decreased M2 macrophages and reduced the migration in PMA-treated THP1 cells. Conversely, transfection with a miR-196b-5p inhibitor led to the opposite outcomes. miR-196b-5p targeted SOCS1/HMGA1, and miR-196b-5p inhibitor significantly up-regulated CCL2 and IL-10, and down-regulated IL-6 levels in End1/E6E7 cells. These effects were markedly reversed by si-SOCS1/si-HMGA1.Conclusion: miR-196b-5p elevates M1 macrophages and decreases M2 macrophages in endometriosis, possibly by targeting SOCS1/ HMGA1. This research may provide a novel insight into the pathological mechanisms of endometriosis.
Original Article
Adamu Imam Isa
Abstract
Background: Investigating the impacts of plant-based substances on the regulation of pro-inflammatory M1 and anti-inflammatory M2 cytokines could have significant implications for immune-related health conditions. Seven Persicaria plant species from sub-Saharan Africa were specifically selected for analysis, ...
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Background: Investigating the impacts of plant-based substances on the regulation of pro-inflammatory M1 and anti-inflammatory M2 cytokines could have significant implications for immune-related health conditions. Seven Persicaria plant species from sub-Saharan Africa were specifically selected for analysis, based on their traditional use in treating inflammation.Objective: To investigate the inhibitory effects of methanol leaf extracts from selected plants on enzymes involved in chronic inflammation.Methods: The inhibition of nitric oxide production, acetylcholinesterase activity, and 15-lipoxygenase activity was assessed using the Griess reagent method, Ellman’s colorimetric method, and the ferrous oxidation-xylenol orange assay. The quantity of M1/M2 cytokines released was quantified using a flow cytometerResults: At a concentration of 50 µg/mL, the methanol extracts of P. limbata exhibited the highest NO inhibition (97.67%), followed by P. nepalensis (93.06%) and P. setosula (92.78%). The NO inhibition caused by the plant extracts was correlated directly with the decrease in NO release by the LPS-stimulated macrophages. Furthermore, the pro-inflammatory enzyme assays indicated that the methanol extracts of P. setosula exhibited the highest enzyme inhibitory activity (LOX 89.59%, AChE 72.12 %). This was followed by P. limbata (with 92.76% for LOX and 56.93% for AChE) and P. nepalensis (with 88.16% for LOX and 47.17% for AChE). Cytokine assays revealed that the extracts of P. limbata had significant dose-dependent suppressive effects on IFN-γ and TNF-α expression while promoting the secretion of IL-2, IL-4, IL-6, and IL-10.Conclusion: Extracts of P. limbata contain immunomodulatory compounds that could be further explored as potential remedies to target the molecular drivers of chronic inflammation.
Original Article
Sengul Aksakal; Selim Gorgun
Abstract
Background: The development of a cytokine storm in Coronavirus Disease 2019 (COVID-19) infection can make the disease fatal. We hypothesize that this excessive cytokine production impairs mucosal healing. IL-17 and IL-22 are cytokines that play a key role in protecting and regenerating mucosal tissues. ...
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Background: The development of a cytokine storm in Coronavirus Disease 2019 (COVID-19) infection can make the disease fatal. We hypothesize that this excessive cytokine production impairs mucosal healing. IL-17 and IL-22 are cytokines that play a key role in protecting and regenerating mucosal tissues. IL-17 and IL-22 support each other, and the imbalance between them plays a role in the pathogenesis of many rheumatologic diseases.Objective: To investigate whether COVID-19 severity is related to IL17, IL-22, and the IL-17/IL-22 ratio.Methods: The study was planned prospectively and included 69 patients with active COVID-19 infection. Three groups were created: patients with upper respiratory tract infection, pneumonia, and cytokine storm. Blood samples were taken from the patients upon their first admission and serum levels of IL-17 and IL-22 were measured using the enzyme-linked immunosorbent assay (ELISA). We assessed the relationship between IL17, IL22, IL17/ IL22 ratio, clinical and lung involvement by comparing them with the healthy group.Results: The levels of IL-17 were significantly higher in COVID-19 patients with upper respiratory tract infection compared to the control group (p=0.027). IL17/IL-22 ratio significantly increased in patients with cytokine storm compared to the healthy controls (p=0.027). Serum levels of IL-22 were negatively correlated with the CO-RADS score (r=-0.31, p=0.004), while IL-17/IL-22 ratio was positively correlated with the CO-RADS score (r=0.29, p=0.008). Conclusion: Levels of IL-17, IL-22, and IL-17/IL-22 may provide valuable insights into the progression of COVID-19.
Original Article
Ruiping Li; Wei Song; Donglan Mei
Abstract
Background: Severe chronic obstructive pulmonary disease (COPD) patients with pulmonary infections face higher morbidity and mortality.Objective: To investigate mononuclear cell membrane CD14 as a prognostic marker for their outcome.Methods: A total of 311 participants were included: 122 in the coinfection ...
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Background: Severe chronic obstructive pulmonary disease (COPD) patients with pulmonary infections face higher morbidity and mortality.Objective: To investigate mononuclear cell membrane CD14 as a prognostic marker for their outcome.Methods: A total of 311 participants were included: 122 in the coinfection group, 127 in the severe COPD group, and 62 in the control group. The patients in the coinfection group were categorized into survival (n=106) and death (n=16) groups based on hospitalization prognosis. The CD14%, CD14MFI, and CD14IND values were compared between the groups. Death risk factors were assessed by COPD grading, FEV1% pred, FEV1/FVC, CD14%, CD14MFI, and CD14IND. Correlations between CD14 parameters and mortality, COPD grade, FEV1%pred, and FEV1/FVC were analyzed. The critical value for CD14IND to predict patient death was determined and survival rates were compared between the high and the low-risk groups.Results: CD14% values were significantly lower in the COPD and co-infection groups than in the control groups (p<0.05). The survival group showed a steady increase in mCD14 expression, while the death group showed fluctuating low levels. Low value of CD14% was identified as a risk factor for death and correlated with mortality and COPD severity (p<0.001). CD14IND≤74.36 predicted death with 91.22% sensitivity and 95.51% specificity. The high-risk group had a significantly lower 30-day survival rate (68.42%) compared with the low-risk group (95.24%) (log-rank χ2=10.067, p=0.002).Conclusion: The CD14 parameters of mononuclear cell membranes prove to be promising markers for predicting prognosis and death in severe COPD patients with lung infection.
Original Article
Ali Fotouhi; Maryam Hosseini; Ali Aghebati-Maleki; Mohammad Sadegh Soltani-Zangbar; Sara Parsania; Amirhossein Mardi; Leili Aghebati-Maleki
Abstract
Background: Osteoarthritis (OA) is the most common joint disease worldwide. Routine treatment options are limited, and total knee replacement surgeries often come with complications. In recent years, the use of biologics, such as Wharton’s jelly (Wj) derived from the umbilical cord (UC), has gained ...
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Background: Osteoarthritis (OA) is the most common joint disease worldwide. Routine treatment options are limited, and total knee replacement surgeries often come with complications. In recent years, the use of biologics, such as Wharton’s jelly (Wj) derived from the umbilical cord (UC), has gained popularity. While mesenchymal stem cells (MSCs) derived from Wj show promise in restoring articular cartilage, they also have some limitations. Recent studies have indicated that exosomes isolated from acellular Wj may offer advantages under certain conditions.Objective: To investigate the anti-inflammatory properties of exosomes isolated from Wj in synoviocytes.Methods: Decellularization of Wj was performed using sterile umbilical cords obtained from patients. Next, the exosomes were isolated from Wj using ultracentrifugation. After characterizing the exosomes, they were co-cultured with inflammatory synovial fibroblast cells (HIG-82) for 24 hours. Then, the gene expression levels and protein contents of some important inflammatory mediators including metalloproteinase-13 (MMP-13), cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS) were measured in the cells using real-time PCR and ELISA tests, respectively.Results: The expression levels of MMP-13, COX-2, and iNOS genes were significantly reduced in the cultured cells treated with exosomes compared to untreated cells. Moreover, the content of MMP-13, COX-2, and iNOS proteins were significantly lower in the supernatant of the cultured cells compared to the control.Conclusion: Wj-derived exosomes exhibit notable anti-inflammatory properties, which can help mitigate inflammation in the synovial environment of joints. However, further research is required to fully understand their benefits and potential applications in treating osteoarthritis.
Case Report
Qitao Ren; Ying Jin; Guangxin Zhou; Qiaoxiang Yin; Ping Liu; Yanjie Cao; Yongmin Bi
Abstract
IgG4-related disease (IgG4-RD) is a multi-organ inflammatory immune-mediated illness caused by IgG4-secreting plasma cells infiltrating the tissue. This condition usually affects elderly men. A 90-year-old Chinese male was diagnosed with IgG4-RD based on the new 2019 ACR/EULAR classification criteria, ...
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IgG4-related disease (IgG4-RD) is a multi-organ inflammatory immune-mediated illness caused by IgG4-secreting plasma cells infiltrating the tissue. This condition usually affects elderly men. A 90-year-old Chinese male was diagnosed with IgG4-RD based on the new 2019 ACR/EULAR classification criteria, as he had multiple organ involvement. After receiving treatment with glucocorticoids, leflunomide, and gamma-globulin, the patient’s clinical symptoms significantly improved, confirming the accuracy of the diagnosis. The patient had an 18-year medical history during which the disease progressively worsened due to delayed diagnosis and treatment. Although the relevant symptoms were alleviated with appropriate medication, the overall treatment process encountered challenges. Due to the patient’s relative lack of adrenocortical function, he experienced symptoms such as nausea, exhaustion, and loss of appetite during the hormone reduction process. Therefore, timely intervention is especially crucial to address the side effects of hormone therapy.
Letter To The Editor
Ali Saffaei; Jafar Amani; Jafar Salimian; Gholamhossein Alishiri; Hassan Abolghasemi
