International Journal of Immunopathology and Pharmacology最新文献

{"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":"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":"Anti-astmatic effect of ROCK inhibitor, GSK429286 A, in experimentally induced allergic airway inflammation.","authors":"Eduard Gondáš, Jozef Mažerik, Matúš Dohál, Soňa Bálentová, Michal Pokusa, Daniela Vargová, Lukáš Smieško, Martina Šutovská, Marta Jošková, Soňa Fraňová","doi":"10.1177/03946320241282949","DOIUrl":"10.1177/03946320241282949","url":null,"abstract":"<p><strong>Background: </strong>Allergic asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness, inflammation and remodeling. ROCK inhibitors have now been shown to have the potential to alleviate these symptoms, although the specific effects of a new ROCK inhibitor, GSK429286 A, remain underexplored.</p><p><strong>Objective: </strong>The aim of this study was to evaluate the therapeutic effects of a novel ROCK inhibitor, GSK429286 A, which exhibits a high affinity for both ROCK1 and ROCK2 isoforms, on allergic asthma in a guinea pig model, focusing on its effects on airway hyperresponsiveness, inflammation, and remodeling.</p><p><strong>Methods: </strong>To induce allergic asthma, guinea pigs were sensitized with ovalbumin for 28 days, and in the middle of sensitization they were treated with different doses of the RoCK inhibitor, GSK429286 A. The study evaluated the effect of the administered doses on the reduction of airway hyperresponsiveness, by measuring specific airway resistance (sRaw), and the number of coughs after citric acid inhalation. We also monitored the anti-inflammatory effect by measuring levels of inflammatory cytokines, IL-2, IL-4, IL-5, IL-13, and remodeling markers, such as collagen deposition, and goblet cell hyperplasia. In addition, we monitored the possible anti-remodeling effect of GSK429286 A by histopathological examination.</p><p><strong>Results: </strong>The ROCK inhibitor, GSK429286 A, showed an effect on suppressing airway hyperresponsiveness by reducing sRaw and the number of coughs in treated guinea pigs compared to controls. Our investigated drug suppressed the release of key mediators of inflammation, including IL-2, IL-4, and IL-5, thus demonstrating the effect of this ROCK inhibitor on the suppression of inflammation in the airways. Finally, GSK429286 A reduced markers of airway remodeling such as collagen deposition and goblet cell hyperplasia.</p><p><strong>Conclusion: </strong>GSK429286 A, an inhibitor of the ROCK pathway, exhibits significant anti-inflammatory and antiremodeling effects in a guinea pig model of allergic asthma. Indeed, we demonstrate its effect on suppressing airway hyperreactivity and reducing cough frequency. These findings suggest that GSK429286 A may be a promising therapeutic agent for allergic asthma, although further studies are needed to investigate its long-term efficacy, underlying mechanisms, and optimal dosing strategy.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241282949"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298950","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":"Umbelliprenin improved anti-proliferative effects of ionizing radiation on adult T-cell leukemia/lymphoma cells via interaction with CDK6; an <i>in vitro</i> and <i>in silico</i> study.","authors":"Keyhan Ebrahimi, Ramin Bagheri, Hamid Gholamhosseinian, Mohammad Reza Keramati, Houshang Rafatpanah, Mehrdad Iranshahi, Fatemeh B Rassouli","doi":"10.1177/03946320241287873","DOIUrl":"10.1177/03946320241287873","url":null,"abstract":"<p><p>Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy with poor survival rates. The efficacy of radiotherapy in ATL needs enhancement with radiosensitizing agents. This study investigated whether umbelliprenin (UMB) could improve the therapeutic effects of ionizing radiation (IR) in ATL cells. UMB, a naturally occurring prenylated coumarin, exhibits anticancer properties and has shown synergistic effects when combined with chemotherapeutic drugs. Despite this promising profile, there is a notable lack of research on its potential combinatorial effects with IR, particularly for ATL treatment. UMB was extracted from <i>Ferula persica</i> using thin layer chromatography. MT-2 cells were treated with UMB alone and in combination with various doses of IR, and cell proliferation was assessed via alamarBlue assay. Flow cytometry with annexin V and PI staining was conducted, and candidate gene expression was analyzed by qPCR. <i>In silico</i> analysis involved identifying pathogenic targets of ATL, constructing protein-protein interaction (PPI) networks, and evaluating CDK6 expression in MT-2 cells. Molecular docking was used to determine the interaction between UMB and CDK6. The alamarBlue assay and flow cytometry showed that pretreating ATL cells with UMB significantly (<i>p</i> < .0001) enhanced anti-proliferative effects of IR. The combination index indicated a synergistic effect between UMB and IR. qPCR revealed significant (<i>p</i> < .0001) downregulation of <i>CD44, CDK6, c-MYC</i>, and <i>cFLIPL</i>, and overexpression of <i>cFLIPS</i>. Computational analysis identified CDK6 as a hub gene in the PPI network, and CDK6 overexpression was confirmed in MT-2 cells. Molecular docking revealed a favorable binding interaction between UMB and the ATP-binding site of CDK6, with a JAMDA score of -2.131, surpassing the control selonsertib. The current study provides evidence that UMB enhances the anti-proliferative effects of IR on ATL cells, and highlights the significance of targeting CDK6 in combinatorial approaches.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241287873"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308841","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":"The senomorphic impact of astaxanthin on irradiated rat spleen: STING, TLR4 and mTOR contributed pathway.","authors":"Maha M Aziz, Marwa M El-Sheikh, Marwa A Mohamed, Sahar S Abdelrahman, Mai H Mekkawy","doi":"10.1177/03946320241297342","DOIUrl":"10.1177/03946320241297342","url":null,"abstract":"<p><strong>Objectives: </strong>Exposure of spleen tissues to ionizing radiation during radiotherapy can induce cellular stress and immune-dysfunction leading to cellular senescence.</p><p><strong>Introduction: </strong>The process of a cancerous development is facilitated by the accumulation of senescent cells. This justifies the incorporation of anti-senescent medications during splenic irradiation (SI).</p><p><strong>Methods: </strong>In this study senescence was induced in the spleen of male albino rats by radiation exposure (5Gy-single whole body gamma-irradiation) then after 2 weeks, oral astaxanthin regimen was started once daily in a dose of 25 mg/kg for 7 consecutive days. Concurrent control groups were carried out.</p><p><strong>Results: </strong>the present data reflected that irradiation provoked an increase in the oxidative stress biomarkers (nitric oxide, lipid peroxidation and total reactive oxygen species levels)and the inflammatory biomarkers (Myeloperoxidase and interleukin-6). In addition irradiation led to the over expression of stimulator of interferon genes (cGAS-STING), mammalian target of rapamycin (mTOR) and Toll-like receptor 4 (TLR4) along with the lactate dehydrogenase (LDH), cyclin-dependent kinase inhibitor 1 (p21) cyclin-dependent kinase inhibitor 2A (p16) increment with elevation of tumor suppressor protein (p53) level. However, reduced glutathione contents and catalase activity were reduced post irradiation in spleen tissues, all these changes reflecting induction of cellular senescence. Astaxanthin treatment showed an improvement in the antioxidant/oxidative stress balance, inflammatory biomarkers, histopathological examination and immunohistochemical expressions of the tested proteins in the irradiated rats.</p><p><strong>Conclusion: </strong>the current findings offer a new insight into the senomorphic effect of astaxanthin following radiation-induced spleen senescence via STING, mTOR, and TLR4 signalling pathways.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241297342"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548389","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":"Enzyme ChE, cholinergic therapy and molecular docking: Significant considerations and future perspectives.","authors":"Snežana M Jovičić","doi":"10.1177/03946320241289013","DOIUrl":"10.1177/03946320241289013","url":null,"abstract":"<p><p>Enzyme Che plays an essential role in cholinergic and non-cholinergic functions. It is present in the fertilized/unfertilized eggs and sperm of different species. Inclusion criteria for data collection from electronic databases NCBI and Google Scholar are enzyme AChE/BChE, cholinergic therapy, genomic organization and gene transcription, enzyme structure, biogenesis, transport, processing and localization, molecular signaling and biological function, polymorphism and influencing factors. Enzyme Che acts as a signaling receptor during hematopoiesis, protein adhesion, amyloid fiber formation, neurite outgrowth, bone development, and maturation, explaining the activity out of synaptic neurotransmission. Polymorphism in the Che genes correlates to various diseases and diverse drug responses. In particular, change accompanies cancer, neurodegenerative, and cardiovascular disease. Literature knowledge indicates the importance of Che inhibitors that influence biochemical and molecular pathways in disease treatment, genomic organization, gene transcription, structure, biogenesis, transport, processing, and localization of Che enzyme. Enzyme Che polymorphism changes indicate the possibility of efficient and new inhibitor drug target mechanisms in diverse research areas.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241289013"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376172","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}