International Journal of Immunopathology and Pharmacology最新文献

{"title":"Revealing the potential of solute carrier family 31 (copper transporters), member 1: Insights into its role in bladder cancer progression and therapeutic implications.","authors":"Yun-Zhi Lin, Wei-Hui Liu, Yu-Peng Wu, Hai Cai, Qing-Shui Zheng, Yong Wei, Ning Xu, Xue-Yi Xue","doi":"10.1177/03946320241240706","DOIUrl":"10.1177/03946320241240706","url":null,"abstract":"<p><p><b>Introduction:</b> Bladder cancer represents a significant public health concern with diverse genetic alterations influencing disease onset, progression, and therapy response. In this study, we explore the multifaceted role of Solute Carrier Family 31 Member 1 (SLC31A1) in bladder cancer, a pivotal gene involved in copper homeostasis. <b>Methods:</b> Our research involved analyzing the SLC31A1 gene expression via RT-qPCR, promoter methylation via targeted bisulfite sequencing, and mutational status via Next Generation Sequencing (NGS) using the clinical samples sourced by the local bladder cancer patients. Later on, The Cancer Genome Atlas (TCGA) datasets were utilized for validation purposes. Moreover, prognostic significance, gene enrichment terms, and therapeutic drugs of SLC31A1 were also explored using KM Plotter, DAVID, and DrugBank databases. <b>Results:</b> We observed that SLC31A1 was significantly up-regulated at both the mRNA and protein levels in bladder cancer tissue samples, suggesting its potential involvement in bladder cancer development and progression. Furthermore, our investigation into the methylation status revealed that SLC31A1 was significantly hypomethylated in bladder cancer tissues, which may contribute to its overexpression. The ROC analysis of the SLC31A1 gene indicated promising diagnostic potential, emphasizing its relevance in distinguishing bladder cancer patients from normal individuals. However, it is crucial to consider other factors such as cancer stage, metastasis, and recurrence for a more accurate evaluation in the clinical context. Interestingly, mutational analysis of SLC31A1 demonstrated only benign mutations, indicating their unknown role in the SLC31A1 disruption. In addition to its diagnostic value, high SLC31A1 expression was associated with poorer overall survival (OS) in bladder cancer patients, shedding light on its prognostic relevance. Gene enrichment analysis indicated that SLC31A1 could influence metabolic and copper-related processes, further underscoring its role in bladder cancer. Lastly, we explored the DrugBank database to identify potential therapeutic agents capable of reducing SLC31A1 expression. Our findings unveiled six important drugs with the potential to target SLC31A1 as a treatment strategy. <b>Conclusion:</b> Our comprehensive investigation highlights SLC31A1 as a promising biomarker for bladder cancer development, progression, and therapy.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241240706"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11080779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855592","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":"Gemcitabine and synthesized silver nanoparticles impact on chemically induced hepatocellular carcinoma in male rats.","authors":"Mohamed R Mohamed, Soheir A Osman, Asmaa A Hassan, Amany I Raafat, Mahmoud M Refaat, Shadia A Fathy","doi":"10.1177/03946320241263352","DOIUrl":"10.1177/03946320241263352","url":null,"abstract":"<p><p><b>Objective:</b> Gemcitabine (GEM) is a deoxycytidine analog chemotherapeutic drug widely used to treat many cancers. Silver nanoparticles (AgNPs) are important nanomaterials used to treat many diseases. Using gamma radiation in nanoparticle preparation is a new eco-friendly method. This study aims to evaluate the efficiency of co-treating gemcitabine and silver nanoparticles in treating hepatocellular carcinoma. <b>Method:</b> The AgNPs were characterized using UV-visible spectroscopy, XRD, TEM, and EDX. The MTT cytotoxicity in vitro assay of gemcitabine, doxorubicin, and cyclophosphamide was assessed against Wi38 normal fibroblast and HepG2 HCC cell lines. After HCC development, rats received (10 µg/g b.wt.) of AgNPs three times a week for 4 weeks and/or GEM (5 mg/kg b.wt.) twice weekly for 4 weeks. Liver function enzymes were investigated. Cytochrome P450 and miR-21 genes were studied. Apoptosis was determined by using flow cytometry, and apoptotic modifications in signaling pathways were evaluated via Bcl-2, Bax, Caspase-9, and SMAD-4. <b>Results:</b> The co-treatment of GEM and AgNPs increased apoptosis by upregulating Bax and caspase 9 while diminishing Bcl2 and SMAD4. It also improved cytochrome P450 m-RNA relative expression. The results also proved the cooperation between GEM and AgNPs in deactivating miR21. The impact of AgNPs as an adjuvant treatment with GEM was recognized. <b>Conclusions:</b> The study showed that co-treating AgNPs and GEM can improve the efficiency of GEM alone in treating HCC. This is achieved by enhancing intrinsic and extrinsic apoptotic pathways while diminishing some drawbacks of using GEM alone.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241263352"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753062","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":"A case report of primary Kaposiform hemangioendothelioma of the humerus.","authors":"Ye Wang, Zhenqi He, Hua Hao","doi":"10.1177/03946320241266914","DOIUrl":"10.1177/03946320241266914","url":null,"abstract":"<p><p>To examine the clinicopathological and immunohistochemical features of Kaposiform hemangioendothelioma (KHE) and discuss its differential diagnosis and prognosis. A patient with KHE was examined; the patient's clinical and histopathological features were observed, and the expression levels of CD31, CD34, ERG, D2-40, SMA, GLUT-1, and LANA-1 were assessed. The patient was a four-year-old child with primary KHE of the humerus. She was admitted to the hospital because of pain in the right elbow joint and limited movement for more than 2 years. Imaging revealed Langerhans cell histiocytosis. The child was not diagnosed with Kasabach-Merritt phenomenon (KMP). The tumor consists of multiple hemangiomatous nodules with infiltrative growth separated by fibrous connective tissue. The proliferating hemangiomatoid nodules consisted of crisscrossing short spindle-shaped cell bundles and erythrocyte-containing lacunar or crescentic vessels. Immunohistochemical staining showed that the tumor cells diffusely expressed CD31, CD34, ERG, and other vascular endothelium-derived markers; further, the tumor cells expressed neither GLUT-1 nor LANA-1. The patient's general condition improved after surgical resection. There was no tumor recurrence after more than 8 months of follow-up. Primary KHE of the humerus is a rare vasculogenic tumor. It presents with morphological features that require an accurate differential diagnosis.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":" ","pages":"3946320241266914"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11686642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731523","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":"Resection of extensive segments of inferior vena cava without reconstruction in the treatment of renal carcinoma with inferior vena cava tumor thrombus: A case report.","authors":"Kun Shang, Changjiu Li, Jun Chen, Ning Li, Huadong He","doi":"10.1177/03946320241272549","DOIUrl":"10.1177/03946320241272549","url":null,"abstract":"<p><p>We present a 55-year-old male patient with right renal carcinoma with long inferior vena cava (IVC) tumor thrombus who underwent robot-assisted laparoscopic radical nephrectomy with extensive IVC resection and left renal vein ligation. The patient had a history of hematuria only prior to admission. Our case involved resection of the entire abdominal segment of the IVC and left renal vein without reconstruction. Unfortunately, the patient passed away over a year after the surgery due to brain metastasis.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241272549"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894667","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":"Implication of IL-12A, IL-12B, IL-6, and TNF single-nucleotide polymorphisms in severity and susceptibility to COVID-19.","authors":"R Benmansour, M R Tagajdid, I A Lahlou, H Oumzil, H El Hamzaoui, S Fjouji, N Doghmi, A Houba, S Elkochri, R Aabi, H Elannaz, A Laraqui, B El Mchichi, N Touil, K Ennibi, A Bouhouche","doi":"10.1177/03946320241279893","DOIUrl":"10.1177/03946320241279893","url":null,"abstract":"<p><strong>Background: </strong>The Coronavirus Disease 2019 (COVID-19) pandemic has led to significant global morbidity and mortality. Understanding the genetic factors that influence disease outcomes can provide critical insights into pathogenesis and potential therapeutic targets.</p><p><strong>Objective: </strong>This study aimed to investigate the potential correlation between single nucleotide polymorphisms (SNPs) in <i>Interleukin 12 Subunit Alpha (IL-12A)</i>, <i>Interleukin 12 Subunit Beta (IL-12B)</i>, <i>Interleukin 6 (IL-6)</i>, and <i>Tumor Necrosis Factor (TNF)</i> genes and the severity as well as susceptibility to COVID-19 among Moroccan patients.</p><p><strong>Patients and methods: </strong>Next-Generation sequencing (NGS) was conducted on 325 Moroccan participants, 207 patients with PCR-confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and 118 controls. Among these patients, 51% presented moderate to severe symptoms requiring hospitalization, while 49% were asymptomatic or experienced mild symptoms and did not require hospitalization. Statistical analysis was performed using codominant, dominant, and recessive logistic regression models to assess correlations with the severity and susceptibility to COVID-19 infection.</p><p><strong>Results: </strong>No association was found between SNPs of <i>IL-12A</i>, <i>IL-12B</i>, <i>IL-6</i> or <i>TNF</i> and COVID-19 severity and susceptibility. However, our results unveiled a noteworthy association with <i>IL-6</i> rs2069840, which exhibited a negative correlation (OR = 0.21, 95% CI = 0.07-0.69, <i>p</i> = .006), suggesting a protective effect against SARS-CoV-2 infection.</p><p><strong>Conclusion: </strong>Polymorphisms in <i>IL-12A</i>, <i>IL-12B</i>, <i>IL-6</i>, and <i>TNF</i> genes are not correlated to the severity and susceptibility of COVID-19.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241279893"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141496","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":"Is preexisting inflamed jaw marrow a \"hidden\" co-morbidity affecting outcomes of COVID-19 infections? - Clinical comparative study.","authors":"Johann Lechner, Robert E McMahon, Jerry E Bouquot, Florian Notter, Fabian Schick","doi":"10.1177/03946320241265265","DOIUrl":"10.1177/03946320241265265","url":null,"abstract":"<p><p><b>Introduction:</b> Exceedingly high levels of the chemokine CCL5/RANTES have been found in fatty degenerated osteonecrotic alveolar bone cavities (FDOJ) and aseptic ischemic osteolysis of the jaw (AIOJ) from toothless regions. Because CCL5/RANTES seems to have a prominent role in creating the COVID-19 \"cytokine storm\", some researchers have used the monoclonal antibody Leronlimab to block the CCR5 on inflammatory cells.<b>Objective:</b> Is preexisting FDOJ/AIOJ jaw marrow pathology a \"hidden\" co-morbidity affecting some COVID-19 infections? To what extent does the chronic CCL5/RANTES expression from preexisting FDOJ/AIOJ areas contribute to the progression of the acute cytokine storm in COVID-19 patients?<b>Methods:</b> Authors report on reducing the COVID-19 \"cytokine storm\" by treating infected patients through targeting the chemokine receptor 5 (CCR5) with Leronlimab and interrupting the activation of CCR5 by high CCL5/RANTES signaling, thus dysregulating the inflammatory phase of the viremia. Surgical removal of FDOJ/AIOJ lesions with high CCL5/RANTES from patients with inflammatory diseases may be classified as a co-morbid disease.<b>Results:</b> Both multiplex analysis of 249 FDOJ/AIOJ bone tissue samples as well as serum levels of CCL5/RANTES displayed exceedingly high levels in both specimens.<b>Discussion:</b> By the results the authors hypothesize that chronic CCL5/RANTES induction from FDOJ/AIOJ areas may sensitize CCR5 throughout the immune system, thus, enabling it to amplify its response when confronted with the virus. As conventional intraoral radiography does little to assess the quality of the alveolar bone, ultrasonography units are available to help dentists locate the FDOJ/AIOJ lesions in an office setting.<b>Conclusion:</b> The authors propose a new approach to containment of the COVID-19 cytokine storm by a prophylactic focus for future viral-related pandemics, which may be early surgical clean-up of CCL5/RANTES expression sources in the FDOJ/AIOJ areas, thus diminishing a possible pre-sensitization of CCR5. A more complete dental examination includes trans-alveolar ultrasono-graphy (TAU) for hidden FDOJ/AIOJ lesions.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241265265"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421448","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":"Proposal of pharmacophore model for HIV reverse transcriptase inhibitors: Combined mutational effect analysis, molecular dynamics, molecular docking and pharmacophore modeling study.","authors":"Azzeddine Annan, Noureddine Raiss, Sanae Lemrabet, Nezha Elomari, El Harti Elmir, Abdelkarim Filali-Maltouf, Leila Medraoui, Hicham Oumzil","doi":"10.1177/03946320241231465","DOIUrl":"10.1177/03946320241231465","url":null,"abstract":"<p><strong>Objectives: </strong>Antiretroviral therapy (ART) efficacy is jeopardized by the emergence of drug resistance mutations in HIV, compromising treatment effectiveness. This study aims to propose novel analogs of Effavirenz (EFV) as potential direct inhibitors of HIV reverse transcriptase, employing computer-aided drug design methodologies.</p><p><strong>Methods: </strong>Three key approaches were applied: a mutational profile study, molecular dynamics simulations, and pharmacophore development. The impact of mutations on the stability, flexibility, function, and affinity of target proteins, especially those associated with NRTI, was assessed. Molecular dynamics analysis identified G190E as a mutation significantly altering protein properties, potentially leading to therapeutic failure. Comparative analysis revealed that among six first-line antiretroviral drugs, EFV exhibited notably low affinity with viral reverse transcriptase, further reduced by the G190E mutation. Subsequently, a search for EFV-similar inhibitors yielded 12 promising molecules based on their affinity, forming the basis for generating a pharmacophore model.</p><p><strong>Results: </strong>Mutational analysis pinpointed G190E as a crucial mutation impacting protein properties, potentially undermining therapeutic efficacy. EFV demonstrated diminished affinity with viral reverse transcriptase, exacerbated by the G190E mutation. The search for EFV analogs identified 12 high-affinity molecules, culminating in a pharmacophore model elucidating key structural features crucial for potent inhibition.</p><p><strong>Conclusion: </strong>This study underscores the significance of EFV analogs as potential inhibitors of HIV reverse transcriptase. The findings highlight the impact of mutations on drug efficacy, particularly the detrimental effect of G190E. The generated pharmacophore model serves as a pivotal reference for future drug development efforts targeting HIV, providing essential structural insights for the design of potent inhibitors based on EFV analogs identified in vitro.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241231465"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10832406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139651911","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":"3-N-butylphthalide attenuates neuroinflammation in rotenone-induced Parkinson's disease models via the cGAS-STING pathway.","authors":"Yuqian Liu, Ruonan Duan, Peizheng Li, Bohan Zhang, Yiming Liu","doi":"10.1177/03946320241229041","DOIUrl":"10.1177/03946320241229041","url":null,"abstract":"<p><p>Neuroinflammation is crucial in the onset and progression of dopaminergic neuron loss in Parkinson's disease (PD). We aimed to determine whether 3-N-Butylphthalide (NBP) can protect against PD by inhibiting the cyclic GMP-AMP synthase (cGAS)<b>-</b>stimulator of interferon genes (STING) pathway and the inflammatory response of microglia. MitoSOX/MitoTracker/Hoechst staining was used to detect the levels of mitochondrial reactive oxygen species (ROS) in BV2 cells. Quantitative Real-Time Polymerase Chain Reaction was used to measure the levels of free cytoplasmic mitochondrial DNA (mtDNA) in BV2 cells and mouse brain tissues. Behavioral impairments were assessed using rotarod, T-maze, and balance beam tests. Dopaminergic neurons and microglia were observed using immunohistochemical staining. Expression levels of cGAS, STING, nuclear factor kappa-B (NfκB), phospho- NfκB (p-NfκB), inhibitor of NfκBα (IκBα), and phospho-IκBα (p-IκBα) proteins in the substantia nigra and striatum were detected using Western Blot. NBP decreased mitochondrial ROS levels in rotenone-treated BV2 cells. NBP alleviated behavioral impairments and protected against rotenone-induced microgliosis and damage to dopaminergic neurons in the substantia nigra and striatum of rotenone-induced PD mice. NBP decreased rotenone-induced mtDNA leakage and mitigated neuroinflammation by inhibiting cGAS-STING pathway activation. NBP exhibited a protective effect in rotenone-induced PD models by significantly inhibiting the cGAS-STING pathway. Moreover, NBP can alleviate neuroinflammation, and is a potential therapeutic drug for alleviating clinical symptoms and delaying the progression of PD. This study provided insights for the potential role of NBP in PD therapy, potentially mitigating neurodegeneration, and consequently improving the quality of life and lifespan of patients with PD. The limitations are that we have not confirmed the exact mechanism by which NBP decreases mtDNA leakage, and this study was unable to observe the actual clinical therapeutic effect, so further cohort studies are required for validation.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241229041"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10846052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693316","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":"Sestrin 2 protects human lens epithelial cells from oxidative stress and apoptosis induced by hydrogen peroxide by regulating the mTOR/Nrf2 pathway.","authors":"Xiao Tian, Jie Wei","doi":"10.1177/03946320241234741","DOIUrl":"10.1177/03946320241234741","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to explore the effect and potential mechanism of Sestrin 2 (SESN2) in human lens epithelial cells (HLECs).</p><p><strong>Methods: </strong>To mimic the oxidative stress environment, SAR01/04 cells were treated with 200 μM hydrogen peroxide (H₂O₂) for 24 h. Cell viability and apoptosis were checked by cell counting kit-8 and flow cytometry. Western blot was taken to check the protein changes of SESN2, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), mechanistic target of rapamycin (mTOR), phosphorylated (p)-mTOR, ribosomal protein S6 kinase B1 (p70S6K), p-p70S6K, and nuclear factor erythroid 2-related factor 2 (Nrf2). Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and reactive oxygen species (ROS) were detected via the corresponding reagent kit. The levels of interleukin (IL)-1β, IL-18, and tumor necrosis factor (TNF)-α were measured using enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>SESN2 was down-regulated in cataract lens tissue and up-regulated in SAR01/04 cells treated with H₂O₂. Under treatment of H₂O₂, up-regulation of SESN2 improved cell viability, enhanced the activity of SOD and CAT, inhibited cell apoptosis, and reduced the levels of MDA, ROS, IL-1β, IL-18, and TNF-α, while down-regulation of SESN2 caused the contrary effects. Further bioinformatics analysis suggested that SESN2 regulated the mTOR signaling pathway. Treatment of H₂O₂ inhibited p-mTOR and p-p70S6K protein expression, while overexpression of SESN2 increased p-mTOR and p-p70S6K protein expression in the H₂O₂ group and down-regulation of SESN2 further decreased p-mTOR and p-p70S6K protein expression in the H₂O₂ group. Additionally, H₂O₂ increased Nrf2 protein expression, and overexpression of SESN2 further increased Nrf2 protein expression in the H₂O₂ group. Importantly, rapamycin (an inhibitor of mTOR signaling pathway) and knockdown of Nrf2 reversed the promotive effects of SESN2 on cell viability and the inhibitive effects of SESN2 on cell apoptosis, oxidative stress, and inflammatory reaction.</p><p><strong>Conclusion: </strong>SESN2 protected HLECs damage induced by H₂O₂, which was related to the activation of mTOR/Nrf2 pathway.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241234741"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913799","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":"Adverse reactions of immune checkpoint inhibitors combined with angiogenesis inhibitors: A pharmacovigilance analysis of drug-drug interactions.","authors":"Xiayang Ren, Lei Deng, Xin Dong, Ying Bai, Guohui Li, Yanfeng Wang","doi":"10.1177/03946320241305390","DOIUrl":"10.1177/03946320241305390","url":null,"abstract":"<p><p>The combination of immune checkpoint inhibitors (ICIs) and angiogenesis inhibitors (AGIs) is widely used in cancer treatment; however, drug-drug reactions (DDIs) remain unknown. We aimed to identify interaction signals for the concomitant use of ICIs and AGIs. Data were obtained from the US FDA Adverse Event Reporting System (FAERS) from January 1, 2015, to December 31, 2023. Disproportionality analysis was used for data mining by calculating the reporting odds ratio (ROR) and 95% confidence interval (95% CI). Adjusted RORs were analysed using logistic regression analysis, considering age, sex and reporting year. Further confirmation was assessed via additive and multiplicative models. We identified 75,936 reports on ICIs combined with AGIs. Significant interaction signals were observed for hepatobiliary disorders (RORcrude: 5.25, 95% CI: 5.07-5.44, RORadj: 5.01, 95% CI: 4.82-5.22, additive models: 0.2323), investigations (RORcrude: 1.66, 95% CI: 1.62-1.70, RORadj: 1.63, 95% CI: 1.58-1.67, additive models: 0.2187, multiplicative models: 1.1265), renal and urinary disorders (RORcrude: 1.87, 95% CI: 1.80-1.95, RORadj: 1.72, 95% CI: 1.64-1.79, additive models: 0.3239, multiplicative models: 1.1799) and vascular disorders (RORcrude: 1.94, 95% CI: 1.87-2.02, RORadj: 1.87, 95% CI: 1.80-1.95, additive models: 0.5823, multiplicative models: 1.5676). Subset data analysis showed positive interaction signals for PDL-1/CTLA-4 inhibitors + AGI in hepatobiliary disorders, PD-1 inhibitors + AGI in investigations, or PD-1/PDL-1 inhibitors + AGI in renal and urinary/ vascular disorders. Based on FAERS data, four systemic disorders were identified as having DDIs related to the combined use of ICIs and AGIs. Pre-clinical trials are required to explore the mechanisms underlying these interactions.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241305390"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808319","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}