Hepatocellular carcinoma (HCC) poses a significant challenge to global health. Its pathophysiology involves interconnected processes, including cell proliferation, autophagy, and macrophage polarization. However, the role of Absent in Melanoma 2 (AIM2) in HCC remains elusive.
Methods
The expression of AIM2 in Huh-7 and Hep3B cell lines was manipulated and cell proliferation, autophagy, apoptosis, and migration/invasion, together with the polarization of M2 macrophages, were evaluated. The markers of autophagy pathway, LC3B, Beclin-1, and P62, underwent examination through Western blot analysis. An autophagy inhibitor, 3-MA, was used to measured the role of autophagy in HCC. Finally, the effect of AIM2 overexpression on HCC was further evaluated using a subcutaneous tumor model in nude mice.
Results
Our results established that AIM2 overexpression inhibits HCC cell proliferation, migration, and invasion while promoting apoptosis and autophagy. Conversely, knockdown of AIM2 engendered opposite effects. AIM2 overexpression was correlated with reduced M2 macrophage polarization. The autophagy inhibitor substantiated AIM2's role in autophagy and identified its downstream impact on cell proliferation, migration, invasion, and macrophage polarization. In the in vivo model, overexpression of AIM2 led to the inhibition of HCC tumor growth.
Conclusion
The findings underscore AIM2's crucial function in modulating major biological processes in HCC, pointing to its potential as a therapeutic target. This study inaugurally demonstrated that AIM2 activates autophagy and influences macrophage polarization, playing a role in liver cancer progression.
{"title":"Hepatocellular carcinoma and AIM2: Therapeutic potential through regulation of autophagy and macrophage polarization","authors":"Shuangshuang Xie, Cuiyun Wang, Xiaoyan Liu, Cheng Li, Jinhong Yu, Shumin Ma, Qiang Li, Wenjun Du","doi":"10.1002/iid3.70002","DOIUrl":"10.1002/iid3.70002","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) poses a significant challenge to global health. Its pathophysiology involves interconnected processes, including cell proliferation, autophagy, and macrophage polarization. However, the role of Absent in Melanoma 2 (AIM2) in HCC remains elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The expression of AIM2 in Huh-7 and Hep3B cell lines was manipulated and cell proliferation, autophagy, apoptosis, and migration/invasion, together with the polarization of M2 macrophages, were evaluated. The markers of autophagy pathway, LC3B, Beclin-1, and P62, underwent examination through Western blot analysis. An autophagy inhibitor, 3-MA, was used to measured the role of autophagy in HCC. Finally, the effect of AIM2 overexpression on HCC was further evaluated using a subcutaneous tumor model in nude mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results established that AIM2 overexpression inhibits HCC cell proliferation, migration, and invasion while promoting apoptosis and autophagy. Conversely, knockdown of AIM2 engendered opposite effects. AIM2 overexpression was correlated with reduced M2 macrophage polarization. The autophagy inhibitor substantiated AIM2's role in autophagy and identified its downstream impact on cell proliferation, migration, invasion, and macrophage polarization. In the in vivo model, overexpression of AIM2 led to the inhibition of HCC tumor growth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The findings underscore AIM2's crucial function in modulating major biological processes in HCC, pointing to its potential as a therapeutic target. This study inaugurally demonstrated that AIM2 activates autophagy and influences macrophage polarization, playing a role in liver cancer progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142106980","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}
Intestinal inflammation has various causes and leads to some inflammatory diseases, of which autophagy pathway dysfunction could be considered as one of them. Probiotics could have a positive effect on reducing inflammation by activating the autophagy pathway. To evaluate the precise effects of probiotics as preventive and therapeutic agents to control the symptoms of inflammatory diseases, we aimed to investigate the efficacy of Lactobacillus spp. in regulating the autophagy signaling pathway.
Methods
A quantitative real-time polymerase chain reaction assay was used to analyze the expression of autophagy genes involved in the formation of phagophores, autophagosomes, and autolysosomes after exposing the HT-29 cell line to sonicated pathogens and adding Lactobacillus spp. before, after, and simultaneously with inflammation. A cytokine assay was also accomplished to evaluate the interleukin (IL)-6 and IL-1β level following the probiotic treatment.
Results
Lactobacillus spp. generally increased autophagy gene expression and consumption of Lactobacillus spp. before, simultaneously, and after inflammation, ultimately leading to activate autophagy pathways. The proinflammatory cytokines including IL-6 and IL-1β decreased after probiotic treatment.
Conclusions
Our native probiotic Lactobacillus spp. showed beneficial effects on HT-29 cells by increasing autophagy gene expression and decreasing the proinflammatory cytokines production in all treatments. Therefore, this novel probiotic cocktail Lactobacillus spp. can prevent and treat inflammation-related diseases.
{"title":"The preventive and therapeutic role of Lactobacillus spp. in in vitro model of inflammation via affecting autophagy signaling pathway","authors":"Fatemeh Haririzadeh Jouriani, Mahnaz Torfeh, Mahdi Torkamaneh, Amin Sepehr, Mahdi Rohani, Shadi Aghamohammad","doi":"10.1002/iid3.1336","DOIUrl":"10.1002/iid3.1336","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intestinal inflammation has various causes and leads to some inflammatory diseases, of which autophagy pathway dysfunction could be considered as one of them. Probiotics could have a positive effect on reducing inflammation by activating the autophagy pathway. To evaluate the precise effects of probiotics as preventive and therapeutic agents to control the symptoms of inflammatory diseases, we aimed to investigate the efficacy of <i>Lactobacillus</i> spp. in regulating the autophagy signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A quantitative real-time polymerase chain reaction assay was used to analyze the expression of autophagy genes involved in the formation of phagophores, autophagosomes, and autolysosomes after exposing the HT-29 cell line to sonicated pathogens and adding <i>Lactobacillus</i> spp. before, after, and simultaneously with inflammation. A cytokine assay was also accomplished to evaluate the interleukin (IL)-6 and IL-1β level following the probiotic treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>Lactobacillus</i> spp<i>.</i> generally increased autophagy gene expression and consumption of <i>Lactobacillus</i> spp. before, simultaneously, and after inflammation, ultimately leading to activate autophagy pathways. The proinflammatory cytokines including IL-6 and IL-1β decreased after probiotic treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our native probiotic <i>Lactobacillus</i> spp. showed beneficial effects on HT-29 cells by increasing autophagy gene expression and decreasing the proinflammatory cytokines production in all treatments. Therefore, this novel probiotic cocktail <i>Lactobacillus</i> spp. can prevent and treat inflammation-related diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.1336","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072613","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}
Jingwen Li, Qingmin Li, Wei Ma, Yongsheng Zhang, Xiaonan Li
Purpose
The aim of this study was to explore whether MAF bZIP transcription factor B (MAFB) might alleviate ulcerative colitis (UC) in dextran sulfate sodium (DSS)-induced mice and LPS-induced IEC-6 cells.
Methods
UC in vivo and in vitro model was established by using DSS and LPS, respectively. The mice body weight and disease activity index (DAI) score were recorded daily, and colon length was measured. Moreover, the permeability was evaluated utilizing a fluorescein isothiocyanate dextran (FITC-Dextran) probe. Histopathological changes of DSS-induced colitis mice was assessed utilizing H&E staining. Next, qRT-PCR was performed to detect IL-1β, IL-6, TNF-α, and IL-10 level in in vivo and in vitro. Furthermore, the level of MDA, SOD, CAT, and GSH were evaluated in colon tissues. Besides, the expressions of tight junction proteins and NF-κB pathway relative proteins were examined in colitis mice and IEC-6 cells using western blot, immunohistochemistry and immunofluorescence.
Results
MAFB level was downregulated in DSS-induced colitis mice. Moreover, the upregulation of MAFB protected mice from DSS-induced colitis by suppressing DSS-induced inflammation, oxidative stress, and intestinal barrier impairment. We also demonstrated that the upregulation of MAFB inactivated NF-κB pathway in DSS-caused colitis mice. Subsequently, we observed that MAFB upregulation could inhibit LPS-caused epithelial barrier impairment and inflammation in IEC-6 cells. Additionally, MAFB overexpression could suppress the activation of NF-κB pathway in IEC-6 cells.
Conclusion
The upregulation of MAFB could protect against UC via the suppression of inflammation and the intestinal barrier impairment through inhibiting the NF-κB pathway.
{"title":"Expression of MAF bZIP transcription factor B protects against ulcerative colitis through the inhibition of the NF-κB pathway","authors":"Jingwen Li, Qingmin Li, Wei Ma, Yongsheng Zhang, Xiaonan Li","doi":"10.1002/iid3.1372","DOIUrl":"10.1002/iid3.1372","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>The aim of this study was to explore whether MAF bZIP transcription factor B (MAFB) might alleviate ulcerative colitis (UC) in dextran sulfate sodium (DSS)-induced mice and LPS-induced IEC-6 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>UC in vivo and in vitro model was established by using DSS and LPS, respectively. The mice body weight and disease activity index (DAI) score were recorded daily, and colon length was measured. Moreover, the permeability was evaluated utilizing a fluorescein isothiocyanate dextran (FITC-Dextran) probe. Histopathological changes of DSS-induced colitis mice was assessed utilizing H&E staining. Next, qRT-PCR was performed to detect IL-1β, IL-6, TNF-α, and IL-10 level in in vivo and in vitro. Furthermore, the level of MDA, SOD, CAT, and GSH were evaluated in colon tissues. Besides, the expressions of tight junction proteins and NF-κB pathway relative proteins were examined in colitis mice and IEC-6 cells using western blot, immunohistochemistry and immunofluorescence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MAFB level was downregulated in DSS-induced colitis mice. Moreover, the upregulation of MAFB protected mice from DSS-induced colitis by suppressing DSS-induced inflammation, oxidative stress, and intestinal barrier impairment. We also demonstrated that the upregulation of MAFB inactivated NF-κB pathway in DSS-caused colitis mice. Subsequently, we observed that MAFB upregulation could inhibit LPS-caused epithelial barrier impairment and inflammation in IEC-6 cells. Additionally, MAFB overexpression could suppress the activation of NF-κB pathway in IEC-6 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The upregulation of MAFB could protect against UC via the suppression of inflammation and the intestinal barrier impairment through inhibiting the NF-κB pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.1372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017310","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}
Mohammad Hossein Eshaghi Ghalibaf, Mohammad Ehsan Taghavi zadeh Yazdi, Mona Mansourian, Nema Mohammadian Roshan, Mohammad Hossein Boskabady
Background
The inhalation of paraquat (PQ), one of the most widely used herbicides in the world, can result in lung injury. Curcuma longa (Cl) has long history in traditional and folk medicine for the treatment of a wide range of disorders including respiratory diseases.
Aim
The aim of the present work was to evaluate the preventive effect of Cl on inhaled PQ-induced lung injury in rats.
Methods
Male Wistar rats were divided into 8 groups (n = 7), one group exposed to saline (control) and other groups exposed to PQ aerosol. Saline (PQ), Cl extract, (two doses), curcumin (Cu), pioglitazone (Pio), and the combination of Cl-L + Pio and dexamethasone (Dex) were administered during the exposure period to PQ. Total and differential white blood cell (WBC) counts, oxidant and antioxidant indicators in the bronchoalveolar lavage (BALF), interleukin (IL)-10, and tumor necrosis alpha (TNF-α) levels in the lung tissues, lung histologic lesions score, and air way responsiveness to methacholine were evaluated.
Results
WBC counts (Total and differential), malondialdehyde level, tracheal responsiveness (TR), IL-10, TNF-α and histopathological changes of the lung were markedly elevated but total thiol content and the activities of catalase and superoxide dismutase were decreased in the BALF in the PQ group. Both doses of Cl, Cu, Pio, Cl-L + Pio, and Dex markedly improved all measured variables in comparison with the PQ group.
Conclusion
CI, Pio, and Cl-L + Pio improved PQ-induced lung inflammation and oxidative damage comparable with the effects of Dex.
{"title":"Evaluation of the protective effect of Curcuma longa and PPARγ agonist, pioglitazone on paraquat-induced lung injury in rats","authors":"Mohammad Hossein Eshaghi Ghalibaf, Mohammad Ehsan Taghavi zadeh Yazdi, Mona Mansourian, Nema Mohammadian Roshan, Mohammad Hossein Boskabady","doi":"10.1002/iid3.70001","DOIUrl":"10.1002/iid3.70001","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The inhalation of paraquat (PQ), one of the most widely used herbicides in the world, can result in lung injury. <i>Curcuma longa</i> (Cl) has long history in traditional and folk medicine for the treatment of a wide range of disorders including respiratory diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The aim of the present work was to evaluate the preventive effect of Cl on inhaled PQ-induced lung injury in rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male Wistar rats were divided into 8 groups (<i>n</i> = 7), one group exposed to saline (control) and other groups exposed to PQ aerosol. Saline (PQ), Cl extract, (two doses), curcumin (Cu), pioglitazone (Pio), and the combination of Cl-L + Pio and dexamethasone (Dex) were administered during the exposure period to PQ. Total and differential white blood cell (WBC) counts, oxidant and antioxidant indicators in the bronchoalveolar lavage (BALF), interleukin (IL)-10, and tumor necrosis alpha (TNF-α) levels in the lung tissues, lung histologic lesions score, and air way responsiveness to methacholine were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>WBC counts (Total and differential), malondialdehyde level, tracheal responsiveness (TR), IL-10, TNF-α and histopathological changes of the lung were markedly elevated but total thiol content and the activities of catalase and superoxide dismutase were decreased in the BALF in the PQ group. Both doses of Cl, Cu, Pio, Cl-L + Pio, and Dex markedly improved all measured variables in comparison with the PQ group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CI, Pio, and Cl-L + Pio improved PQ-induced lung inflammation and oxidative damage comparable with the effects of Dex.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017309","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}
Chaofan Lu, Nan He, Lei Dou, Hongxia Yu, Mengtao Li, Xiaomei Leng, Xiaofeng Zeng
Objective
This study aimed to evaluate the clinical efficacy of belimumab in patients with early systemic lupus erythematosus (SLE), defined as having a disease duration of less than 6 months.
Methods
We retrospectively identified patients with SLE in the early stage who received belimumab and standard of care (belimumab group) or standard of care alone (control group) since September 2020. Propensity score matching (PSM) was used to reduce potential bias. The primary endpoint was lupus low disease activity status (LLDAS) at weeks 12 and 24. The secondary endpoints were remission and the proportion of glucocorticoid dose tapering to 7.5 mg/day. The efficacy of belimumab in patients with lupus nephritis was also assessed.
Results
Out of 111 eligible patients, 16 patients in the belimumab group and 31 patients in the control group were identified by 1:2 PSM. At week 24, a significantly higher proportion of individuals achieved low disease activity state (LLDAS) in the belimumab group compared to the control group (56.3% vs. 19.4%, OR = 5.357, 95% CI = 1.417 to 20.260, p = 0.013). Furthermore, more patients in the belimumab group were reduced to low-dose glucocorticoid ( ≤ 7.5 mg/day) at week 24 (75.0% vs. 35.5%, OR = 5.182, 95%CI = 1.339 to 20.058, p = 0.017). Significant improvements in Patient Global Assessment scores were observed at Week 12 and 24 for those treated with belimumab compared to controls. In a subgroup analysis evaluating the efficacy of belimumab in patients with lupus nephritis, 42.9% of the seven individuals treated with belimumab achieved a complete renal response (CRR) by Week 24, and no instances of disease relapse were observed.
Conclusions
In SLE patients with a disease duration of less than 6 months, belimumab treatment can promote LLDAS achievement and reduce glucocorticoid dose, leading to a better prognosis. Introducing belimumab in the early stage of SLE may be a beneficial decision.
研究目的本研究旨在评估贝利木单抗对早期系统性红斑狼疮（SLE）患者的临床疗效：我们回顾性地确定了自2020年9月以来接受过贝利木单抗和标准疗法（贝利木单抗组）或单纯标准疗法（对照组）治疗的早期系统性红斑狼疮患者。采用倾向评分匹配法（PSM）减少潜在偏倚。主要终点是第12周和第24周的狼疮低疾病活动度状态（LLDAS）。次要终点是缓解率和糖皮质激素剂量减至7.5毫克/天的比例。此外，还评估了贝利木单抗对狼疮肾炎患者的疗效：在111名符合条件的患者中，通过1:2 PSM确定了16名贝利单抗组患者和31名对照组患者。第24周时，与对照组相比，贝利木单抗组达到低疾病活动状态（LLDAS）的比例明显更高（56.3%对19.4%，OR = 5.357，95% CI = 1.417对20.260，P = 0.013）。此外，更多的贝利木单抗组患者在第24周时减量使用低剂量糖皮质激素（≤ 7.5 mg/天）（75.0% vs. 35.5%，OR = 5.182，95%CI = 1.339 to 20.058，p = 0.017）。与对照组相比，接受贝利木单抗治疗的患者在第12周和第24周的 "患者总体评估 "评分均有显著改善。在一项评估贝利木单抗对狼疮肾炎患者疗效的亚组分析中，7名接受贝利木单抗治疗的患者中有42.9%在第24周时获得了完全肾脏反应（CRR），而且没有观察到疾病复发的情况：结论：对于病程少于6个月的系统性红斑狼疮患者，贝利木单抗治疗可促进LLDAS达标并减少糖皮质激素剂量，从而改善预后。在系统性红斑狼疮早期使用贝利木单抗可能是一个有益的决定。
{"title":"Belimumab in early systemic lupus erythematosus: A propensity score matching analysis","authors":"Chaofan Lu, Nan He, Lei Dou, Hongxia Yu, Mengtao Li, Xiaomei Leng, Xiaofeng Zeng","doi":"10.1002/iid3.1362","DOIUrl":"10.1002/iid3.1362","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to evaluate the clinical efficacy of belimumab in patients with early systemic lupus erythematosus (SLE), defined as having a disease duration of less than 6 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively identified patients with SLE in the early stage who received belimumab and standard of care (belimumab group) or standard of care alone (control group) since September 2020. Propensity score matching (PSM) was used to reduce potential bias. The primary endpoint was lupus low disease activity status (LLDAS) at weeks 12 and 24. The secondary endpoints were remission and the proportion of glucocorticoid dose tapering to 7.5 mg/day. The efficacy of belimumab in patients with lupus nephritis was also assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Out of 111 eligible patients, 16 patients in the belimumab group and 31 patients in the control group were identified by 1:2 PSM. At week 24, a significantly higher proportion of individuals achieved low disease activity state (LLDAS) in the belimumab group compared to the control group (56.3% vs. 19.4%, OR = 5.357, 95% CI = 1.417 to 20.260, <i>p</i> = 0.013). Furthermore, more patients in the belimumab group were reduced to low-dose glucocorticoid ( ≤ 7.5 mg/day) at week 24 (75.0% vs. 35.5%, OR = 5.182, 95%CI = 1.339 to 20.058, <i>p</i> = 0.017). Significant improvements in Patient Global Assessment scores were observed at Week 12 and 24 for those treated with belimumab compared to controls. In a subgroup analysis evaluating the efficacy of belimumab in patients with lupus nephritis, 42.9% of the seven individuals treated with belimumab achieved a complete renal response (CRR) by Week 24, and no instances of disease relapse were observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In SLE patients with a disease duration of less than 6 months, belimumab treatment can promote LLDAS achievement and reduce glucocorticoid dose, leading to a better prognosis. Introducing belimumab in the early stage of SLE may be a beneficial decision.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.1362","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017307","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}
Lupus nephritis (LN) is an autoimmune disease as a complication of systemic lupus erythematosus (SLE). LN is typically diagnosed through a combination of clinical evaluation as index scoring, and kidney biopsy as a more accurate but invasive examination. In the current study, we assessed serological markers including IFN-γ-inducible chemokines C-X-C motif chemokine ligand (CXCL)9, CXCL10, and CXCL11 in diagnosing LN.
Methods
A retrospective analysis was conducted on 160 SLE patients with and without LN. Fasting venous blood was collected from the study subjects for measuring serum levels of CXCL9, CXCL10, and CXCL11. The assessment of clinical disease activity in SLE was conducted using the SLE Disease Activity Index (SLEDAI)-2000 scoring system. LN disease activity was conducted using the Austin scoring system. LN was further confirmed following kidney biopsy, and data were compared by receiver operating characteristic (ROC) analysis.
Results
SLE patients with LN showed longer SLE duration, enhanced SLEDAI scores, lower serum anti-ds-DNA antibody levels when compared to SLE patients without LN. Specifically, these patients had significantly higher serum levels of CXCL9, CXCL10 and CXCL11. CXCL9, CXCL10, and CXCL11 showed positive correlation with SLE disease activity in SLE patients with LN. ROC analysis of CXCL9, CXCL10, and CXCL11 showed substantial enhancement of sensitivity and specificity for the diagnosis of LN in the patients with SLE.
Conclusions
Serum CXCL9, CXCL10, and CXCL11 levels may improve the sensitivity and specificity for the diagnosis of LN in SLE patients.
{"title":"Clinical significance of serum CXCL9, CXCL10, and CXCL11 in patients with lupus nephritis","authors":"Shuo Wang, Yanhui Cui","doi":"10.1002/iid3.1368","DOIUrl":"10.1002/iid3.1368","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Study Design</h3>\u0000 \u0000 <p>Lupus nephritis (LN) is an autoimmune disease as a complication of systemic lupus erythematosus (SLE). LN is typically diagnosed through a combination of clinical evaluation as index scoring, and kidney biopsy as a more accurate but invasive examination. In the current study, we assessed serological markers including IFN-γ-inducible chemokines C-X-C motif chemokine ligand (CXCL)9, CXCL10, and CXCL11 in diagnosing LN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective analysis was conducted on 160 SLE patients with and without LN. Fasting venous blood was collected from the study subjects for measuring serum levels of CXCL9, CXCL10, and CXCL11. The assessment of clinical disease activity in SLE was conducted using the SLE Disease Activity Index (SLEDAI)-2000 scoring system. LN disease activity was conducted using the Austin scoring system. LN was further confirmed following kidney biopsy, and data were compared by receiver operating characteristic (ROC) analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SLE patients with LN showed longer SLE duration, enhanced SLEDAI scores, lower serum anti-ds-DNA antibody levels when compared to SLE patients without LN. Specifically, these patients had significantly higher serum levels of CXCL9, CXCL10 and CXCL11. CXCL9, CXCL10, and CXCL11 showed positive correlation with SLE disease activity in SLE patients with LN. ROC analysis of CXCL9, CXCL10, and CXCL11 showed substantial enhancement of sensitivity and specificity for the diagnosis of LN in the patients with SLE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Serum CXCL9, CXCL10, and CXCL11 levels may improve the sensitivity and specificity for the diagnosis of LN in SLE patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.1368","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017308","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}
Fan Yang, Qinqin Zhang, Xi Wang, Yingbo Hu, Suiqing Chen
Background
Pulmonary fibrosis (PF) is a common clinically critical disease characterized by high morbidity and high mortality. Forsythiaside A (FA) is a phenylethanol glycoside component in Forsythia suspensa, which has anti-inflammatory, antioxidant, and antiviral activities. However, the effects of FA on bleomycin (BLM)-induced PF are unclear.
Purpose
The present study explored the role of FA in the amelioration of oxidative stress and apoptosis in BLM-induced PF as well as the possible underlying mechanisms, in vivo and in vitro.
Methods
Network pharmacology was used to collect the effects of FA on BLM-induced PF. Subsequently, further observation of the effects of FA on mice with PF by pulmonary pathological changes, transmission electron microscopy, real-time polymerase chain reaction, Western blot analysis, immunofluorescence, and immunohistochemistry. An in vitro model was constructed by inducing A549 with transforming growth factor beta-1 (TGF-β1) to observe the effect of FA on epithelial cell apoptosis.
Results
Network pharmacology predicted signaling pathways such as IL-17 signaling pathway and Relaxin signaling pathway. The results of in vivo studies showed that FA ameliorated BLM-induced PF through inhibition of fibrosis, modulation of apoptosis, and oxidative stress. In addition, FA promoted TGF-β1-induced apoptosis in A549 cells.
Conclusions
The results of our study suggested that FA could protect mice against BLM-induced PF by regulating oxidative stress and apoptosis as well as the Epithelial mesenchymal transition pathway.
{"title":"Forsythiaside A ameliorates bleomycin-induced pulmonary fibrosis by inhibiting oxidative stress and apoptosis","authors":"Fan Yang, Qinqin Zhang, Xi Wang, Yingbo Hu, Suiqing Chen","doi":"10.1002/iid3.70006","DOIUrl":"10.1002/iid3.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pulmonary fibrosis (PF) is a common clinically critical disease characterized by high morbidity and high mortality. Forsythiaside A (FA) is a phenylethanol glycoside component in <i>Forsythia suspensa</i>, which has anti-inflammatory, antioxidant, and antiviral activities. However, the effects of FA on bleomycin (BLM)-induced PF are unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>The present study explored the role of FA in the amelioration of oxidative stress and apoptosis in BLM-induced PF as well as the possible underlying mechanisms, in vivo and in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Network pharmacology was used to collect the effects of FA on BLM-induced PF. Subsequently, further observation of the effects of FA on mice with PF by pulmonary pathological changes, transmission electron microscopy, real-time polymerase chain reaction, Western blot analysis, immunofluorescence, and immunohistochemistry. An in vitro model was constructed by inducing A549 with transforming growth factor beta-1 (TGF-β1) to observe the effect of FA on epithelial cell apoptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Network pharmacology predicted signaling pathways such as IL-17 signaling pathway and Relaxin signaling pathway. The results of in vivo studies showed that FA ameliorated BLM-induced PF through inhibition of fibrosis, modulation of apoptosis, and oxidative stress. In addition, FA promoted TGF-β1-induced apoptosis in A549 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results of our study suggested that FA could protect mice against BLM-induced PF by regulating oxidative stress and apoptosis as well as the Epithelial mesenchymal transition pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017311","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}
Oxidative stress (OS) plays a major role in the progress of hypoxic-ischemic brain damage (HIBD). This study aimed to investigate OS-related genes and their underlying molecular mechanisms in neonatal HIBD.
Methods
Microarray data sets were acquired from the Gene Expression Omnibus (GEO) database to screen the differentially expressed genes (DEGs) between control samples and HIBD samples. OS-related genes were drawn from GeneCards and OS-DEGs in HIBD were obtained by intersecting with the DEGs. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were conducted to determine the underlying mechanisms and functions of OS-DEGs in HIBD. Moreover, the hub genes were screened using the protein−protein interaction network and identified in the GSE144456 data set. CIBERSORT was then performed to evaluate the expression of immunocytes in each sample and perform a correlation analysis of the optimal OS-DEGs and immunocytes. Finally, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed to validate the expression levels of the optimal OS-DEGs.
Results
In total, 93 OS-DEGs were identified. GO, KEGG, and GSEA enrichment analyses indicated that these genes were predominantly enriched in OS and inflammation. Four OS-related biomarker genes (Jun, Fos, Tlr2, and Atf3) were identified and verified. CIBERSORT analysis revealed the dysregulation of six types of immune cells in the HIBD group. Moreover, 47 drugs that might target four OS-related biomarker genes were screened. Eventually, RT-qPCR and immunohistochemistry results for rat samples further validated the expression levels of Fos, Tlr2, and Atf3.
Conclusions
Fos, Tlr2 and Atf3 are potential OS-related biomarkers of HIBD progression. The mechanisms of OS are associated with those of neonatal HIBD.
{"title":"Identification and analysis of oxidative stress-related genes in hypoxic-ischemic brain damage using bioinformatics and experimental verification","authors":"Ni Jin, Sha Sha, Yanghao Ruan, Ying Ouyang","doi":"10.1002/iid3.70000","DOIUrl":"10.1002/iid3.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Oxidative stress (OS) plays a major role in the progress of hypoxic-ischemic brain damage (HIBD). This study aimed to investigate OS-related genes and their underlying molecular mechanisms in neonatal HIBD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Microarray data sets were acquired from the Gene Expression Omnibus (GEO) database to screen the differentially expressed genes (DEGs) between control samples and HIBD samples. OS-related genes were drawn from GeneCards and OS-DEGs in HIBD were obtained by intersecting with the DEGs. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were conducted to determine the underlying mechanisms and functions of OS-DEGs in HIBD. Moreover, the hub genes were screened using the protein−protein interaction network and identified in the GSE144456 data set. CIBERSORT was then performed to evaluate the expression of immunocytes in each sample and perform a correlation analysis of the optimal OS-DEGs and immunocytes. Finally, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed to validate the expression levels of the optimal OS-DEGs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 93 OS-DEGs were identified. GO, KEGG, and GSEA enrichment analyses indicated that these genes were predominantly enriched in OS and inflammation. Four OS-related biomarker genes (Jun, Fos, Tlr2, and Atf3) were identified and verified. CIBERSORT analysis revealed the dysregulation of six types of immune cells in the HIBD group. Moreover, 47 drugs that might target four OS-related biomarker genes were screened. Eventually, RT-qPCR and immunohistochemistry results for rat samples further validated the expression levels of Fos, Tlr2, and Atf3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Fos, Tlr2 and Atf3 are potential OS-related biomarkers of HIBD progression. The mechanisms of OS are associated with those of neonatal HIBD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017312","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}
In mammals, amino acid metabolism has evolved to control immune responses. Tryptophan (Trp) is the rarest essential amino acid found in food and its metabolism has evolved to be a primary regulatory node in the control of immune responses. Celiac disease (CeD) is a developed immunological condition caused by gluten intolerance and is linked to chronic small intestine enteropathy in genetically predisposed individuals. Dendritic cells (DCs), serving as the bridge between innate and adaptive immunities, can influence immunological responses in CeD through phenotypic alterations.
Objective
This review aims to highlight the connection between Trp metabolism and tolerogenic DCs, and the significance of this interaction in the pathogenesis of CeD.
Results
It is been recognized that various DC subtypes contribute to the pathogenesis of CeD. Tolerogenic DCs, in particular, are instrumental in inducing immune tolerance, leading to T-reg differentiation that helps maintain intestinal immune tolerance against inflammatory responses in CeD patients and those with other autoimmune disorders. T-regs, a subset of T-cells, play a crucial role in maintaining intestinal immunological homeostasis by regulating the activities of other immune cells. Notably, Trp metabolism, essential for T-reg function, facilitates T-reg differentiation through microbiota-mediated degradation and the kynurenine pathway.
Conclusion
Therefore, alterations in Trp metabolism could potentially influence the immune response in CeD, affecting both the development of the disease and the persistence of symptoms despite adherence to a gluten-free diet.
背景：在哺乳动物中，氨基酸代谢的进化是为了控制免疫反应。色氨酸（Trp）是食物中最稀有的必需氨基酸，其代谢进化为控制免疫反应的主要调节节点。乳糜泻（Celiac disease，CeD）是一种由麸质不耐受引起的发达免疫学疾病，与遗传易感人群的慢性小肠肠病有关。树突状细胞（DC）是先天性免疫和适应性免疫之间的桥梁，可通过表型改变影响乳糜泻患者的免疫反应：本综述旨在强调 Trp 代谢与耐受性 DC 之间的联系，以及这种相互作用在 CeD 发病机制中的意义：结果：人们已经认识到，不同亚型的DC对CeD的发病机制起着不同的作用。耐受性直流细胞尤其有助于诱导免疫耐受，导致T-调节分化，从而帮助维持肠道免疫耐受，抵御CeD患者和其他自身免疫性疾病患者的炎症反应。T-regs 是 T 细胞的一个亚群，通过调节其他免疫细胞的活动，在维持肠道免疫平衡方面发挥着至关重要的作用。值得注意的是，Trp 代谢对 T-reg 的功能至关重要，它通过微生物群介导的降解和犬尿氨酸途径促进 T-reg 的分化：因此，Trp代谢的改变可能会影响CeD的免疫反应，从而影响疾病的发展以及在坚持无麸质饮食后症状的持续存在。
{"title":"The role of tryptophan metabolism and tolerogenic dendritic cells in maintaining immune tolerance: Insights into celiac disease pathogenesis","authors":"Fatemeh Asgari, Mahdi Khodadoust, Abdolrahim Nikzamir, Somayeh Jahani-Sherafat, Mostafa Rezaei Tavirani, Mohammad Rostami-Nejad","doi":"10.1002/iid3.1354","DOIUrl":"10.1002/iid3.1354","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In mammals, amino acid metabolism has evolved to control immune responses. Tryptophan (Trp) is the rarest essential amino acid found in food and its metabolism has evolved to be a primary regulatory node in the control of immune responses. Celiac disease (CeD) is a developed immunological condition caused by gluten intolerance and is linked to chronic small intestine enteropathy in genetically predisposed individuals. Dendritic cells (DCs), serving as the bridge between innate and adaptive immunities, can influence immunological responses in CeD through phenotypic alterations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This review aims to highlight the connection between Trp metabolism and tolerogenic DCs, and the significance of this interaction in the pathogenesis of CeD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>It is been recognized that various DC subtypes contribute to the pathogenesis of CeD. Tolerogenic DCs, in particular, are instrumental in inducing immune tolerance, leading to T-reg differentiation that helps maintain intestinal immune tolerance against inflammatory responses in CeD patients and those with other autoimmune disorders. T-regs, a subset of T-cells, play a crucial role in maintaining intestinal immunological homeostasis by regulating the activities of other immune cells. Notably, Trp metabolism, essential for T-reg function, facilitates T-reg differentiation through microbiota-mediated degradation and the kynurenine pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Therefore, alterations in Trp metabolism could potentially influence the immune response in CeD, affecting both the development of the disease and the persistence of symptoms despite adherence to a gluten-free diet.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.1354","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987887","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}
Elijah K. Oladipo, Olanrewaju D. Oyelakin, Abdulsamad O. Aiyelabegan, Elizabeth O. Olajide, Victoria O. Olatayo, Kaothar P. Owolabi, Yewande B. Shittu, Rhoda O. Olugbodi, Hezekiah A. Ajala, Raji A. Rukayat, Deborah O. Olayiwola, Boluwatife A. Irewolede, Esther M. Jimah, Julius K. Oloke, Taiwo O. Ojo, Olumide F. Ajani, Bamidele A. Iwalokun, Olatunji M. Kolawole, Olumuyiwa E. Ariyo, Daniel A. Adediran, Seun E. Olufemi, Helen Onyeaka
Background
Messenger RNA (mRNA) vaccines emerged as a powerful tool in the fight against infections. Unlike traditional vaccines, this unique type of vaccine elicits robust and persistent innate and humoral immune response with a unique host cell-mediated pathogen gene expression and antigen presentation.
Methods
This offers a novel approach to combat poxviridae infections. From the genome of vaccinia and Mpox viruses, three key genes (E8L, E7R, and H3L) responsible for virus attachment and virulence were selected and employed for designing the candidate mRNA vaccine against vaccinia and Mpox viral infection. Various bioinformatics tools were employed to generate (B cell, CTL, and HTL) epitopes, of which 28 antigenic and immunogenic epitopes were selected and are linked to form the mRNA vaccine construct. Additional components, including a 5′ cap, 5′ UTR, adjuvant, 3′ UTR, and poly(A) tail, were incorporated to enhance stability and effectiveness. Safety measures such as testing for human homology and in silico immune simulations were implemented to avoid autoimmunity and to mimics the immune response of human host to the designed mRNA vaccine, respectively. The mRNA vaccine's binding affinity was evaluated by docking it with TLR-2, TLR-3, TLR-4, and TLR-9 receptors which are subsequently followed by molecular dynamics simulations for the highest binding one to predict the stability of the binding complex.
Results
With a 73% population coverage, the mRNA vaccine looks promising, boasting a molecular weight of 198 kDa and a molecular formula of C8901H13609N2431O2611S48 and it is said to be antigenic, nontoxic and nonallergic, making it safe and effective in preventing infections with Mpox and vaccinia viruses, in comparison with other insilico-designed vaccine for vaccinia and Mpox viruses.
Conclusions
However, further validation through in vivo and in vitro techniques is underway to fully assess its potential.
{"title":"Exploring computational approaches to design mRNA Vaccine against vaccinia and Mpox viruses","authors":"Elijah K. Oladipo, Olanrewaju D. Oyelakin, Abdulsamad O. Aiyelabegan, Elizabeth O. Olajide, Victoria O. Olatayo, Kaothar P. Owolabi, Yewande B. Shittu, Rhoda O. Olugbodi, Hezekiah A. Ajala, Raji A. Rukayat, Deborah O. Olayiwola, Boluwatife A. Irewolede, Esther M. Jimah, Julius K. Oloke, Taiwo O. Ojo, Olumide F. Ajani, Bamidele A. Iwalokun, Olatunji M. Kolawole, Olumuyiwa E. Ariyo, Daniel A. Adediran, Seun E. Olufemi, Helen Onyeaka","doi":"10.1002/iid3.1360","DOIUrl":"10.1002/iid3.1360","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Messenger RNA (mRNA) vaccines emerged as a powerful tool in the fight against infections. Unlike traditional vaccines, this unique type of vaccine elicits robust and persistent innate and humoral immune response with a unique host cell-mediated pathogen gene expression and antigen presentation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This offers a novel approach to combat poxviridae infections. From the genome of vaccinia and Mpox viruses, three key genes (E8L, E7R, and H3L) responsible for virus attachment and virulence were selected and employed for designing the candidate mRNA vaccine against vaccinia and Mpox viral infection. Various bioinformatics tools were employed to generate (B cell, CTL, and HTL) epitopes, of which 28 antigenic and immunogenic epitopes were selected and are linked to form the mRNA vaccine construct. Additional components, including a 5′ cap, 5′ UTR, adjuvant, 3′ UTR, and poly(A) tail, were incorporated to enhance stability and effectiveness. Safety measures such as testing for human homology and in silico immune simulations were implemented to avoid autoimmunity and to mimics the immune response of human host to the designed mRNA vaccine, respectively. The mRNA vaccine's binding affinity was evaluated by docking it with TLR-2, TLR-3, TLR-4, and TLR-9 receptors which are subsequently followed by molecular dynamics simulations for the highest binding one to predict the stability of the binding complex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>With a 73% population coverage, the mRNA vaccine looks promising, boasting a molecular weight of 198 kDa and a molecular formula of C<sub>8901</sub>H<sub>13609</sub>N<sub>2431</sub>O<sub>2611</sub>S<sub>48</sub> and it is said to be antigenic, nontoxic and nonallergic, making it safe and effective in preventing infections with Mpox and vaccinia viruses, in comparison with other insilico-designed vaccine for vaccinia and Mpox viruses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>However, further validation through in vivo and in vitro techniques is underway to fully assess its potential.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.1360","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987886","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}
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