{"title":"Assessing the impact of e-cigarettes on human barrier systems: A systematic review","authors":"Gabriella Lupo , Carmelina Daniela Anfuso , Giuseppe Smecca , Alessia Cosentino , Aleksandra Agafonova , Chiara Prinzi , Rosario Junior Ferrauto , Stefano Turzo , Venerando Rapisarda , Caterina Ledda","doi":"10.1016/j.trsl.2025.01.001","DOIUrl":"10.1016/j.trsl.2025.01.001","url":null,"abstract":"<div><div>The use of e-cigarettes has grown rapidly in recent years, raising concerns about their impact on human health, particularly on critical physiological barriers such as the blood-brain barrier (BBB), alveolar-capillary barrier, and vascular systems. This systematic review evaluates the current literature on the effects of e-cigarette exposure on these barrier systems. E-cigarettes, regardless of nicotine content, have been shown to induce oxidative stress, inflammation, and disruption of tight junction proteins, leading to impaired barrier function. Key findings include compromised pulmonary function, increased vascular stiffness, and neuroinflammation. The review highlights potential long-term health risks associated with e-cigarette use, such as cardiovascular disease, neurodevelopmental disorders, and multi-organ fibrosis, and emphasizes the need for public health interventions to regulate e-cigarette use, especially in vulnerable populations like pregnant women and adolescents.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"277 ","pages":"Pages 39-63"},"PeriodicalIF":6.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mengmeng Liu , Yuanqing Yao , Fangyan Tan , Jing Wang , Rong Hu , Jianlin Du , Yonghong Jiang , Xin Yuan
{"title":"Sodium-glucose co-transporter 2 (SGLT-2) inhibitors ameliorate renal ischemia-reperfusion injury (IRI) by modulating autophagic processes","authors":"Mengmeng Liu , Yuanqing Yao , Fangyan Tan , Jing Wang , Rong Hu , Jianlin Du , Yonghong Jiang , Xin Yuan","doi":"10.1016/j.trsl.2024.12.006","DOIUrl":"10.1016/j.trsl.2024.12.006","url":null,"abstract":"<div><div>Renal ischemia-reperfusion injury (IRI) is a common clinical condition that currently lacks effective treatment options. Inhibitors targeting the sodium-glucose co-transporter-2 (SGLT-2), recognized for their role in managing hyperglycemia, have demonstrated efficacy in enhancing the health outcomes for diabetic patients grappling with chronic kidney disease. Nevertheless, the precise impact of SGLT-2 inhibitors on renal ischemia-reperfusion injury (IRI) and the corresponding transcriptomic alterations remain to be elucidated. In our research, we developed a model of IRI using male C57BL/6 mice by clamping the unilateral renal artery and administering empagliflozin Transcriptomic alterations were analyzed using RNA sequencing (RNA-Seq), complemented by proteomic analysis to investigate the effects of empagliflozin. Histological assessments revealed increased renal inflammatory cell infiltration, widespread renal tubular injury, and elevated autophagosomes formation in the IRI group compared to controls. These pathological changes were significantly attenuated following empagliflozin treatment. Besides, renal function impairment can be alleviated in empagliflozin-treated group. RNA-Seq analysis identified lysosomal autophagy as a key biological process in IRI mice. Empagliflozin exerted a renoprotective effect by downregulating lysosome-associated membrane proteins, primarily LAMP1, LAMP2, and LAMP4 (CD68), through the PI3K-Akt, MAPK, and mTOR signaling pathways, thereby inhibiting autophagic processes. In conclusion, this study highlights enhanced inflammation and disrupted metabolism as hallmark transcriptomic signatures of renal. Furthermore, it demonstrates the renoprotective effects of empagliflozin in alleviating renal IRI by modulating autophagic processes.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"277 ","pages":"Pages 27-38"},"PeriodicalIF":6.4,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shiao-Ying Chang , Min-Chun Liao , Kana N. Miyata , Yuchao Pang , Xin-Ping Zhao , Junzheng Peng , Alain Rivard , Julie R. Ingelfinger , John S.D. Chan , Shao-Ling Zhang
{"title":"Canagliflozin inhibits hedgehog interacting protein (Hhip) induction of tubulopathy in diabetic Akita mice","authors":"Shiao-Ying Chang , Min-Chun Liao , Kana N. Miyata , Yuchao Pang , Xin-Ping Zhao , Junzheng Peng , Alain Rivard , Julie R. Ingelfinger , John S.D. Chan , Shao-Ling Zhang","doi":"10.1016/j.trsl.2024.12.005","DOIUrl":"10.1016/j.trsl.2024.12.005","url":null,"abstract":"<div><div>Renal hedgehog interacting protein (Hhip) activates sodium-glucose cotransporter 2 (Sglt2) expression and promotes tubular senescence in murine diabetic kidney disease (DKD), yet its underlying mechanism(s) are poorly understood. Here we study the effect of the SGLT2 inhibitor, canagliflozin on tubulopathy (fibrosis and apoptosis) in Akita/<em>Hhip</em><sup>RPTC</sup>-transgenic (Tg) mice with overexpression of Hhip in their renal proximal tubular cells (RPTCs) and its relevant mechanisms. The DKD-tubulopathy with pronounced Sglt2 expression was aggravated in the kidney of Akita/<em>Hhip</em><sup>RPTC</sup>-Tg cf. Akita/non-Tg mice. A strong association was observed between Hhip and tubular senescence in Nephroseq from the Nakagawa chronic kidney disease study. Both <em>in vivo</em> and <em>in vitro</em>, excessive Hhip in RPTCs triggered RPTC senescence (polyploidization and cytoskeleton destabilization) and released extracellular vesicles (EVs) carrying Hhip (EVs<sup>Hhip</sup>), most of which were apoptotic bodies (ABs<sup>Hhip</sup>) or microvesicles (MVs<sup>Hhip</sup>) and little exosomes (EXOs<sup>Hhip</sup>). Further, Hhip stimulated β2-microglobulin, which further interacts with EVs<sup>Hhip</sup>, together facilitating RPTC turn-over from cellular senescence to fibrosis and/or apoptosis, ultimately leading to advanced tubulopathy. In contrast, canagliflozin administration offset the action of Hhip in RPTCs, thereby preventing DKD progression. In conclusion, canagliflozin prevented excessive Hhip-mediated tubulopathy, possibly via the inhibition of excessive Hhip carried by extracellular vehicles in DKD.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"277 ","pages":"Pages 13-26"},"PeriodicalIF":6.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hao Chen , Qianchao Hu , Zhongshan Lu , Jie Zhao , Anxiong Liu , Zhongzhong Liu , Jun Luo , Qifa Ye , Zibiao Zhong
{"title":"Aldehyde dehydrogenase 2 attenuates renal injury through inhibiting CYP4A expression","authors":"Hao Chen , Qianchao Hu , Zhongshan Lu , Jie Zhao , Anxiong Liu , Zhongzhong Liu , Jun Luo , Qifa Ye , Zibiao Zhong","doi":"10.1016/j.trsl.2024.12.007","DOIUrl":"10.1016/j.trsl.2024.12.007","url":null,"abstract":"<div><div>Renal ischemia-reperfusion injury (IRI) is a prevalent clinical syndrome, yet its underlying pathogenesis remains largely unknown. Aldehyde dehydrogenase 2 (ALDH2), an enzyme responsible for detoxifying lipid aldehydes, has been suggested to play a protective role against IRI. In our study, we observed that Aldh2 knock-out C57BL/6 mice experienced more severe renal functional impairment following IRI. This was characterized by elevated levels of creatinine and blood urea nitrogen, as well as increased apoptosis. Proteomic analysis further revealed that ALDH2 deficiency significantly disrupted lipid metabolism, resulting in higher levels of the proinflammatory protein CYP4A and its metabolic byproduct, 20-HETE. This metabolic disruption exacerbated renal inflammation and triggered endoplasmic reticulum stress. However, we found that administration of the CYP4A inhibitor, HET0016, could ameliorate these effects. Mechanistically, we discovered that after IRI, ALDH2 translocates to the nucleus and interacts with nuclear receptor corepressor 1 (NCOR1) to repress <em>Cyp4a</em> transcription. ALDH2 specifically interacts with the N-terminal domain of NCOR1, which is responsible for its interaction with its E3 ligase SIAH2. This interaction inhibits the proteasome degradation of NCOR1, ultimately stabilizing the NCOR1 transcriptional repression complex. In summary, our research uncovers the role of ALDH2 in mitigating renal IRI by inhibiting 20-HETE synthesis through the transcriptional repression of <em>Cyp4a</em>.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"277 ","pages":"Pages 1-12"},"PeriodicalIF":6.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qing-Feng Huang , Ge-Fei Wang , Yi-Meng Zhang , Cong Zhang , Ying-Qi Ran , Jian-Zhong He , Geng Wang , Xiu-E Xu , Shao-Hong Wang , Jian-Yi Wu , En-Min Li , Li-Yan Xu
{"title":"Lympho-myeloid aggregate-infiltrating CD20+ B cells display a double-negative phenotype and correlate with poor prognosis in esophageal squamous cell carcinoma","authors":"Qing-Feng Huang , Ge-Fei Wang , Yi-Meng Zhang , Cong Zhang , Ying-Qi Ran , Jian-Zhong He , Geng Wang , Xiu-E Xu , Shao-Hong Wang , Jian-Yi Wu , En-Min Li , Li-Yan Xu","doi":"10.1016/j.trsl.2024.11.002","DOIUrl":"10.1016/j.trsl.2024.11.002","url":null,"abstract":"<div><div>According to morphological features, tumor-infiltrating B cells (TIL-Bs) can be classified as lympho-myeloid aggregates (LMAs) and tertiary lymphoid structures (TLSs). As a disease with high incidence and mortality, research on esophageal squamous cell carcinoma (ESCC) TIL-Bs is still unclear. Thus, we aimed to investigate the prognostic value and functional involvement of TIL-Bs in ESCC. Based on CD20 immunohistochemical staining of 147 ESCC samples, the TIL-Bs at different anatomic subregions (intra-tumor (T), invasive margin (IM) and peri-tumor (P)) were quantified and correlated with survival by Kaplan-Meier analyses. We found that LMAs were widely distributed throughout the whole section and were associated with poor prognosis, especially those located in the T subregion, which was contrary to the positive clinical significance of TLSs. Based on the number of LMAs and TLSs, a four-level immune type was constructed as an independent predictor for survival. Using multiplexed immunofluorescence (mIF) staining, we found that the main phenotype of infiltrating B cells in LMAs was CD20<sup>+</sup>IgD<sup>−</sup>CD27<sup>−</sup> double-negative (DN) B cells. DN B cells were abundant in ESCC tumor tissue, and their high expression was related to shortened overall survival time. Subsequently, we demonstrate a close relationship between DN B cells and regulatory T cells (Tregs) using single cell RNA-seq data, bulk RNA-seq data and flow cytometry, and verified the spatial proximity of DN B cells and Tregs by mIF staining. Trajectory analysis and flow cytometry revealed that DN B cells highly expressed genes involved in the antigen processing and presentation pathway, such as HLA-DR. The abundance of DN B cells and LMAs in ESCC provides novel potential targets for optimal immunotherapy against ESCC.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"275 ","pages":"Pages 48-61"},"PeriodicalIF":6.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}