Immunological Investigations最新文献

{"title":"In-Vitro and in-Vivo Evaluation of the Developed Curcumin-Cyclosporine-Loaded Nanoemulgel for the Management of Rheumatoid Arthritis.","authors":"Sankalp Gharat, Vivek Basudkar, Munira Momin","doi":"10.1080/08820139.2024.2301997","DOIUrl":"10.1080/08820139.2024.2301997","url":null,"abstract":"<p><strong>Background: </strong>Topical nanogel-based formulations have shown potential in the management of rheumatoid arthritis (RA). The aim of this research work was to explore the synergistic effect of Curcumin (CUR) and Cyclosporine (CYC) in combination via a topical route for the management of RA.</p><p><strong>Methods: </strong>The CUR+CYC loaded nanoemulsion was developed using the spontaneous emulsification technique and was subsequently incorporated into Carbopol® Ultrez 30-NF gel. The effect of the developed formulation on levels of proinflammatory cytokines (IL-6, TNF-α) and anti-inflammatory cytokine (IL-10) was evaluated using lipopolysaccharide (LPS) induced RAW 264.7 cell culture model. The anti-arthritic activity was evaluated in a Complete Freund's Adjuvant (CFA) induced arthritic rat model.</p><p><strong>Results: </strong>The optimized nanoemulgel (CUR + CYC NE gel) exhibited average globule size of 15.32 nm ±2.7 nm, poly-dispersity index of 0.181 ± 0.034 and zeta potential of -16.3 mV ± 0.9 mV. The cumulative drug release from ex-vivo diffusion studies on porcine ear skin was 99.189% ± 1.419% at the of 24 h and 99.177% ± 1.234% at the end of 18 h for CUR and CYC, respectively. The cell culture studies revealed that the formulation was able to significantly lower (<i>p</i> < .001) the levels of IL-6 and TNF-α, inhibited prostaglandin E2 (PGE2) while significantly elevating (<i>p</i> < .001) the levels of anti-inflammatory cytokine (IL-10). The gel was found to be non-irritating and showed the inhibition of paw edema and substantial reduction of arthritic symptoms in an arthritic rat model as compared to commercial and other conventional alternatives.</p><p><strong>Conclusion: </strong>This study highlights the potential of the developed nanoemulgel for the management of RA by enhancing the topical permeation of CUR and CYC.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"490-522"},"PeriodicalIF":2.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanomedicine at the Pulmonary Frontier: Immune-Centric Approaches for Respiratory Disease Treatment.","authors":"Jatinder Kaur, Akanksha Sharma, Gautam Passi, Piyush Dey, Akhil Khajuria, Hema Kumari Alajangi, Pradeep Kumar Jaiswal, Ravi Pratap Barnwal, Gurpal Singh","doi":"10.1080/08820139.2023.2298398","DOIUrl":"10.1080/08820139.2023.2298398","url":null,"abstract":"<p><p>Respiratory diseases (RD) are a group of common ailments with a rapidly increasing global prevalence, posing a significant threat to humanity, especially the elderly population, and imposing a substantial burden on society and the economy. RD represents an unmet medical need that requires the development of viable pharmacotherapies. While various promising strategies have been devised to advance potential treatments for RD, their implementation has been hindered by difficulties in drug delivery, particularly in critically ill patients. Nanotechnology offers innovative solutions for delivering medications to the inflamed organ sites, such as the lungs. Although this approach is enticing, delivering nanomedicine to the lungs presents complex challenges that require sophisticated techniques. In this context, we review the potential of novel nanomedicine-based immunomodulatory strategies that could offer therapeutic benefits in managing this pressing health condition.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"295-347"},"PeriodicalIF":2.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of CDK4/6 Inhibitors on Tumor Immune Microenvironment.","authors":"Jie Liu, Min Cheng, Jiamei Xu, Yue Liang, Beibei Yin, Jing Liang","doi":"10.1080/08820139.2024.2304565","DOIUrl":"10.1080/08820139.2024.2304565","url":null,"abstract":"<p><p>Cancer is an abnormal proliferation of cells that is stimulated by cyclin-dependent kinases (CDKs) and defective cell cycle regulation. The essential agent that drive the cell cycle, CDK4/6, would be activated by proliferative signals. Activated CDK4/6 results in the phosphorylation of the neuroblastoma protein (RB) and the release of the transcription factor E2F, which promotes the cell cycle progression. CDK4/6 inhibitor (CDK4/6i) has been currently a research focus, which inhibits the CDK4/6-RB-E2F axis, thereby reducing the cell cycle transition from G1 to S phase and mediating the cell cycle arrest. This action helps achieve an anti-tumor effect. Recent research has demonstrated that CDK4/6i, in addition to contributing to cell cycle arrest, is also essential for the interaction between the tumor cells and the host immune system, i.e., activating the immune system, strengthening the tumor antigen presentation, and reducing the number of regulatory T cells (Treg). Additionally, CDK4/6i would elevate the level of PD-L1, an immunosuppressive factor, in tumor cells, and CDK4/6i in combination with anti-PD-L1 therapy would more effectively reduce the tumor growth. Our results showed that CDK4/6i caused autophagy and senescence in tumor cells. Herein, the impact of CDK4/6i on the immune microenvironment of malignant tumors was mainly focused, as well as their interaction with immune checkpoint inhibitors in affecting anti-tumor immunity.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"437-449"},"PeriodicalIF":2.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139681049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter from the Editor and Introduction to the 2023 Thematic Issue","authors":"Adam J. Adler","doi":"10.1080/08820139.2024.2321685","DOIUrl":"https://doi.org/10.1080/08820139.2024.2321685","url":null,"abstract":"Published in Immunological Investigations: A Journal of Molecular and Cellular Immunology (Ahead of Print, 2024)","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":"2 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139919972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicles and the Immune System: From Immunological Function to Therapeutic Application","authors":"Aimin Jiang","doi":"10.1080/08820139.2024.2321684","DOIUrl":"https://doi.org/10.1080/08820139.2024.2321684","url":null,"abstract":"Published in Immunological Investigations: A Journal of Molecular and Cellular Immunology (Ahead of Print, 2024)","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":"41 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139919974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resistin - A Plausible Therapeutic Target in the Pathogenesis of Psoriasis.","authors":"Manupati Srikanth, Mahaboobkhan Rasool","doi":"10.1080/08820139.2023.2288836","DOIUrl":"10.1080/08820139.2023.2288836","url":null,"abstract":"<p><p>Resistin, a cytokine hormone predominantly secreted by adipose tissue, is elevated in various metabolic disorders such as obesity, type 2 diabetes, and cardiovascular disease. In addition to its involvement in metabolic regulation, resistin has been implicated in the pathogenesis of psoriasis, a chronic inflammatory skin disorder. Numerous studies have reported increased resistin levels in psoriatic skin lesions, suggesting a possible association between resistin and psoriasis. Recent studies have suggested the potential involvement of resistin in the development and progression of certain cancers. Resistin is overexpressed in breast, colorectal, and gastric cancers. This suggests that it may play a role in the development of these cancers, possibly by inducing inflammation and cell growth. The link between resistin and cancer raises the possibility of shared underlying mechanisms driving the pathogenesis of psoriasis. Chronic inflammation, one such mechanism, is a hallmark of psoriasis and cancer. Further research is needed to fully understand the relationship between resistin and psoriasis. Identifying potential therapeutic targets is crucial for effective management of psoriasis. By doing so, we may be able to develop more effective treatment options for individuals living with psoriasis and ultimately improve their quality of life. Ultimately, a more comprehensive understanding of the mechanisms underlying the impact of resistin on psoriasis is essential for advancing our knowledge and finding new ways to treat and manage this challenging condition.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"115-159"},"PeriodicalIF":2.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Mechanistic Target of Rapamycin Complex 1 Pathway Contributes to the Anti-Tumor Effect of Granulocyte-Macrophage-Colony-Stimulating Factor-Producing T Helper Cells in Mouse Colorectal Cancer.","authors":"Hongjian Zhou, Bin Jiang, Yuyuan Qian, Chao Ke","doi":"10.1080/08820139.2023.2290631","DOIUrl":"10.1080/08820139.2023.2290631","url":null,"abstract":"<p><strong>Introduction: </strong>The role of granulocyte-macrophage-colony-stimulating factor-producing T helper (ThGM) cells in colorectal cancer (CRC) development remains unclear. This study characterizes the function of ThGM cells in mouse CRC.</p><p><strong>Methods: </strong>Mouse CRC was induced by administrating azoxymethane and dextran sulfate sodium. The presence of ThGM cells in CRC tissues and the mechanistic target of rapamycin complex 1 (mTORC1) signaling in ThGM cells was detected by flow cytometry. The impact of mTORC1 signaling on ThGM cell function was determined by <i>in vitro</i> culture. The effect of ThGM cells on CRC development was evaluated by adoptive transfer assays.</p><p><strong>Results: </strong>ThGM cells, which expressed granulocyte-macrophage-colony-stimulating factor (GM-CSF), accumulated in CRC tissues. mTORC1 signaling is activated in CRC ThGM cells. mTORC1 inhibition by rapamycin suppressed ThGM cell differentiation and proliferation and resulted in the death of differentiating ThGM cells. mTORC1 inhibition in already differentiated ThGM cells did not induce significant cell death but decreased the expression of GM-CSF, interleukin-2, and tumor necrosis factor-alpha while impeding cell proliferation. Furthermore, mTORC1 inhibition diminished the effect of ThGM cells on driving macrophage polarization toward the M1 type, as evidenced by lower expression of pro-inflammatory cytokines, major histocompatibility complex class II molecule, and CD80 in macrophages after co-culture with rapamycin-treated ThGM cells. Lentivirus-mediated knockdown/overexpression of regulatory-associated protein of mTOR (Raptor) confirmed the essential role of mTORC1 in ThGM cell differentiation and function. Adoptively transferred ThGM cells suppressed CRC growth whereas mTORC1 inhibition abolished this effect.</p><p><strong>Conclusion: </strong>mTORC1 is essential for the anti-CRC activity of ThGM cells.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"261-280"},"PeriodicalIF":2.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Putative Effects of Neoadjuvant Chemotherapy on the Immune System of Advanced Epithelial Ovarian Carcinoma.","authors":"Yunyun Li, Xiaoling Gan, Fei Li, Lina Hu","doi":"10.1080/08820139.2023.2284885","DOIUrl":"10.1080/08820139.2023.2284885","url":null,"abstract":"<p><p>The epithelial ovarian carcinoma (EOC) is one of leading causes of cancer-related mortality in females. For some patients, complete resection cannot be achieved, thus neoadjuvant chemotherapy (NACT) following interval debulking surgery (IDS) could be an alternative choice. In general-held belief, cytotoxic chemotherapy is assumed to be immunosuppressive, because of its toxicity to dividing cells in the bone marrow and peripheral lymphoid tissues. However, increasing evidence highlighted that the anticancer activity of chemotherapy may also be related to its ability to act as an immune modulator. NACT not only changed the morphology of cancer cells, but also changed the transcriptomic and genomic profile of EOC, induced proliferation of cancer stem-like cells, gene mutation, and tumor-related adaptive immune response. This review will provide a comprehensive overview of recent studies evaluating the impact of NACT on cancer cells and immune system of advanced EOC and their relationship to clinical outcome. This information could help us understand the change of immune system during NACT, which might provide new strategies in future investigation of immuno-therapy for maintenance treatment of EOC.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"91-114"},"PeriodicalIF":2.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138176103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A State-of-the-Art Review on the Recent Advances of Mesenchymal Stem Cell Therapeutic Application in Systematic Lupus Erythematosus.","authors":"Farshid Karimi, Babak Nejati, Fatemeh Rahimi, Vahid Alivirdiloo, Iraj Alipourfard, Ali Aghighi, Alireza Raji-Amirhasani, Majid Eslami, Ali Babaeizad, Farhood Ghazi, Akram Firouzi Amandi, Mehdi Dadashpour","doi":"10.1080/08820139.2023.2289066","DOIUrl":"10.1080/08820139.2023.2289066","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is an autoimmune disease with an unknown etiology that has widespread clinical and immunological manifestations. Despite the increase in knowledge about the pathogenesis process and the increase in treatment options, however, the treatments fail in half of the cases. Therefore, there is still a need for research on new therapies. Mesenchymal stem cells (MSCs) are powerful regulators of the immune system and can reduce the symptoms of systemic lupus erythematosus. This study aimed to review the mechanisms of immune system modulation by MSCs and the role of these cells in the treatment of SLE. MSCs suppress T lymphocytes through various mechanisms, including the production of transforming growth factor-beta (TGF-B), prostaglandin E2 (PGE2), nitric oxide (NO), and indolamine 2 and 3-oxygenase (IDO). In addition, MSCs inhibit the production of their autoantibodies by inhibiting the differentiation of lymphocytes. The production of autoantibodies against nuclear antigens is an important feature of SLE. On the other hand, MSCs inhibit antigen delivery by antigen-presenting cells (APCs) to T lymphocytes. Studies in animal models have shown the effectiveness of these cells in treating SLE. However, few studies have been performed on the effectiveness of this treatment in humans. It can be expected that new treatment strategies for SLE will be introduced in the future, given the promising results of MSCs application.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"160-184"},"PeriodicalIF":2.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138459725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Live-Cell Imaging Quantifies Changes in Function and Metabolic NADH Autofluorescence During Macrophage-Mediated Phagocytosis of Tumor Cells.","authors":"Shelby N Bess, Matthew J Igoe, Timothy J Muldoon","doi":"10.1080/08820139.2023.2284369","DOIUrl":"10.1080/08820139.2023.2284369","url":null,"abstract":"<p><strong>Background: </strong>The immune system has evolved to detect foreign antigens and deliver coordinated responses, while minimizing \"friendly fire.\" Until recently, studies investigating the behavior of immune cells were limited to static <i>in vitro</i> measurements. Although static measurements allow for real-time imaging, results are often difficult to translate to an <i>in vivo</i> setting. Multiphoton microscopy is an emerging method to capture spatial information on subcellular events and characterize the local microenvironment. Previous studies have shown that multiphoton microscopy can monitor changes in single-cell macrophage heterogeneity during differentiation. Therefore, there is a need to use multiphoton microscopy to monitor molecular interactions during immunological activities like phagocytosis. Here we investigate the correlation between phagocytic function and changes in endogenous optical reporters during phagocytosis.</p><p><strong>Methods: </strong><i>In vitro</i> autofluorescence imaging of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) was used to detect metabolic changes in macrophages during phagocytosis. More specifically, optical redox ratio, mean NADH fluorescence lifetime and ratio of free to protein-bound NADH were used to quantify changes in metabolism.</p><p><strong>Results: </strong>Results show that IFN-<i>γ</i> (M1) macrophages showed decreased optical redox ratios and mean NADH lifetime while phagocytosing immunogenic cancer cells compared to metastatic cells. To validate phagocytic function, a fluorescence microscopy-based protocol using a pH-sensitive fluorescent probe was used. Results indicate that M0 and M1 macrophages show similar trends in phagocytic potential.</p><p><strong>Conclusion: </strong>Overall, this work demonstrates that <i>in vitro</i> multiphoton imaging can be used to longitudinally track changes in phagocytosis and endogenous metabolic cofactors.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"210-223"},"PeriodicalIF":2.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10959688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}