Biomedicines最新文献

{"title":"Interleukin-37 Suppresses the Function of Type 2 Follicular Helper T in Allergic Rhinitis.","authors":"Xi Luo, Yanhui Wen, Xiangqian Qiu, Lifeng Zhou, Qingxiang Zeng, Wenlong Liu","doi":"10.3390/biomedicines13051263","DOIUrl":"10.3390/biomedicines13051263","url":null,"abstract":"<p><p><b>Background:</b> Allergic rhinitis (AR) is triggered by immunoglobulin E (IgE)-mediated immune responses to airborne allergens. Recent studies highlight the pivotal role of T follicular helper 2 (Tfh2) cells in IgE production. Interleukin-37 (IL-37) has emerged as an intrinsic modulator of innate immunity and inflammatory processes. We aimed to investigate the regulatory effect of IL-37 on Tfh2 cells in the pathogenesis of AR. <b>Methods:</b> Blood samples were collected from AR patients and controls. The IL-37 levels and the frequency of Tfh2 cells were detected by enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. The isolated Tfh2 cells were cultured or cocultured with naive B cells. The regulatory effects of IL-37 on Tfh2/B cells were assessed using ELISA, quantitative real-time polymerase chain reaction (qRT-PCR). Mouse models of ovalbumin (OVA)-induced AR were established to explore the effect of IL-37 in vivo. <b>Results:</b> IL-37 suppressed the production of IL-4 and IL-21 by Tfh2 cells and downregulated C-X-C chemokine receptor type 5 (CXCR5) and B-cell lymphoma 6 protein (Bcl6) mRNA expression while upregulating B lymphocyte-induced maturation protein 1 (Blimp1) and signal transducers and activators of transduction5 (STAT5) mRNA. IL-37 decreased IgE production by B cells significantly, and the addition of anti-IL-18 receptor α alleviated this effect. In mouse models, IL-37 reduced nasal rubbing, sneezing, eosinophil counts, OVA-specific IgE, and Tfh2 proportions. <b>Conclusions:</b> IL-37 plays a crucial role in modulating Tfh2 cell responses in AR, suggesting a potential therapeutic target for this condition.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-Staged Sequential Management of Post-LASIK Ectasia: Under-Flap Corneal Cross-Linking for Stabilization Followed by Flap Surface Topography-Guided PRK for Visual Optimization.","authors":"Avi Wallerstein, Brandon Bellware, Mark Cohen, Pierre Demers, Mathieu Gauvin","doi":"10.3390/biomedicines13051258","DOIUrl":"10.3390/biomedicines13051258","url":null,"abstract":"<p><p><b>Background/Objectives</b>: To evaluate the efficacy, accuracy, safety, and long-term stability of topography-guided photorefractive keratectomy (TGPRK) in eyes where post-LASIK (PLE) ectasia progression was stabilized with under-flap corneal crosslinking (ufCXL). <b>Methods</b>: This retrospective interventional case series included six eyes from five patients with PLE after microkeratome LASIK. All eyes underwent ufCXL to halt ectatic progression. A shallow TGPRK enhancement was performed on the LASIK flap surface after corneal and refractive stability was confirmed (18 months median) post ufCXL Outcome measures included uncorrected and corrected distance visual acuity (UDVA, CDVA), spherical equivalent (SEQ), refractive astigmatism, keratometry, and corneal irregularity indices over a mean follow-up of 47 months. <b>Results</b>: ufCXL stabilized ectatic progression but left residual refractive errors, limiting UDVA. TGPRK performed subsequently significantly improved UDVA, from 0.38 to 0.10 LogMAR (<i>p</i> = 0.017), and increased the LASIK efficacy index from 0.46 to 0.83 (<i>p</i> = 0.0087). Refractive astigmatism was reduced in all eyes achieving a SEQ within ±1.00 D of the target. Long-term stability was maintained, with no ectasia progression, no change in SEQ, no change in corneal irregularity indices, and no increase in maximal keratometry. <b>Conclusions</b>: TGPRK performed in ufCXL stabilized corneas can safely correct residual refractive errors, resulting in significant and sustained improvements in both refractive and visual outcomes in PLE.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet-Rich Plasma (PRP) in Reproductive Medicine: A Critical Review of PRP Therapy in Low-Reserve and Premature Ovarian Insufficiency.","authors":"Efthalia Moustakli, Anastasios Potiris, Athanasios Zikopoulos, Athanasios Zachariou, Spyridon Topis, Periklis Panagopoulos, Ekaterini Domali, Peter Drakakis, Sofoklis Stavros","doi":"10.3390/biomedicines13051257","DOIUrl":"10.3390/biomedicines13051257","url":null,"abstract":"<p><p><b>Background:</b> Intraovarian platelet-rich plasma (PRP) has emerged as a novel intervention at the intersection of reproductive medicine and regenerative biology. As women with diminished ovarian reserve (DOR), poor response to stimulation, or premature ovarian insufficiency (POI) seek fertility solutions, PRP provides a scientifically plausible-yet exploratory-strategy to restore or augment ovarian function. The proposed pathways include the stimulation of local stem cells, tissue remodeling, neoangiogenesis, and the potential reawakening of dormant follicles. <b>Methods:</b> This narrative review critically synthesizes the existing literature on intraovarian PRP therapy. It draws from published case series, pilot studies, and preclinical data to evaluate the biological rationale, clinical outcomes, and current limitations of PRP use in women with DOR and POI. <b>Results:</b> Early clinical findings, albeit limited to modest case series and pilot investigations, reveal promising outcomes such as improved ovarian reserve markers, menstrual restoration, and infrequent spontaneous pregnancies in women who had previously been unresponsive to treatment. However, the variability in preparation techniques, patient selection criteria, and outcome measures limits the generalizability of these results. <b>Conclusions:</b> While intraovarian PRP presents an exciting frontier in reproductive medicine, the absence of defined protocols, controlled trials, and long-term safety data underscores its experimental nature. Future research should focus on standardizing methodologies, conducting randomized controlled trials, and elucidating the molecular mechanisms underlying observed clinical effects to establish PRP's role in managing poor ovarian response and POI.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of Chick Early Amniotic Fluid in Mitigating Ionizing-Radiation-Induced Damage.","authors":"Ke Zhang, Hai Yang, Yueyue Wu, Yining Zhao, Wenxu Xin, Deshen Han, Ning Sun, Chao Ye","doi":"10.3390/biomedicines13051253","DOIUrl":"10.3390/biomedicines13051253","url":null,"abstract":"<p><p><b>Background:</b> Clinical data indicate that at least half of patients with malignancies receive radiotherapy. While radiotherapy effectively kills tumor cells, it is also associated with significant ionizing radiation (IR) damage. Moreover, the increasing emissions of nuclear pollutants raise concerns about the potential exposure of more individuals to the risks associated with IR. The Chinese term for amniotic fluid (AF) is rooted in the Yin-Yang theory of traditional Chinese medicine, where it symbolizes the inception of human life. Chick early AF (ceAF), a natural product, has shown promise in the field of regenerative medicine. There have been no studies investigating the potential efficacy of ceAF in the treatment of IR-induced damage. This study aims to assess the therapeutic potential of ceAF in alleviating IR-induced damage and elucidate its potential molecular mechanism. <b>Methods:</b> In vivo experiments were conducted on 8-week-old male C57BL/6J mice to investigate the effects of ceAF in a radiation injury model induced by whole-body irradiation with X-rays (6 Gy) for 5 min. The ceAF was extracted from chicken embryos aged 7-9 days. <b>Results:</b> We found that the supplementation of ceAF reduces mortality induced by IR, improves exercise capacity in IR mice, and reverses IR-induced skin damage. IR leads to varying degrees of volume atrophy and weight loss in the major internal organs of mice. However, ceAF intervention effectively mitigates IR-induced organ damage, with a notable impact on the spleen. The supplementation of ceAF enhances spleen hematopoietic and immune functions by reducing oxidative stress, alleviating inflammatory responses, and preventing splenic DNA damage from IR exposure, ultimately leading to an overall improvement in health. <b>Conclusions:</b> ceAF effectively alleviates body damage induced by IR, and our findings provide new perspectives and therapeutic strategies for mitigating IR-induced damage.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beating Heart Coronary Artery Bypass Grafting with Preemptive Impella^™ 5.5 Assist Device in Ischemic Cardiomyopathy.","authors":"Francesco Cabrucci, Massimo Baudo, Yoshiyuki Yamashita, Amanda Yakobitis, Courtney Murray, Gianluca Torregrossa","doi":"10.3390/biomedicines13051259","DOIUrl":"10.3390/biomedicines13051259","url":null,"abstract":"<p><p><b>Background:</b> Choosing the best surgical approach for coronary revascularization in patients with ischemic cardiomyopathy and low EF is complex. Several strategies have been adopted, including on- and off-pump CABG, the use of IABP, and the combination of ECMO or even LVAD with CABG. Recently, the Impella 5.5 micro-axial pump has been used as perioperative temporary left ventricular support in CABG patients. This study aims to report a series of CABG procedures performed with Impella assistance, highlighting its potential benefits in high-risk surgery cases. <b>Methods:</b> Between January 2023 and December 2024, seven consecutive patients underwent on-pump beating CABG with planned central Impella 5.5 support via a 10 mm graft in the ascending aorta. This study focused on assessing perioperative outcomes in patients with reduced ventricular dysfunction (ejection fraction [EF] < 35%) undergoing CABG with Impella-assisted support. <b>Results:</b> Seven patients were included in the study, with a median age of 70 [IQR 57-74.7], and six were male. Hypertension was present in all patients, diabetes in six, and COPD in two, and two were in dialysis. The median preoperative EF was 20% [IQR, 18-29%], and the median STS PROM was 5.5 [IQR: 2.9-8.9]. One patient had preoperative IABP support. Four patients required intraoperative transfusions, but all remained hemodynamically stable upon OR exit. The Impella was removed after an average of 5.6 ± 2.1 days. One patient underwent surgical revision for bleeding. No strokes, myocardial infarctions, repeat revascularizations, or mortality occurred postoperatively. The median postoperative hospital stay was 21 [IQR, 17.5-22] days, with a discharge EF of 38% [IQR 33.5-38%]. One patient died 6 months after the procedure due to sepsis caused by a gangrenous diabetic leg. <b>Conclusions:</b> This initial experience using Impella 5.5 support in CABG patients with reduced EF demonstrated its feasibility in selected cases. The Impella provided effective circulatory support, ensuring stable hemodynamics throughout the postoperative stay without complications.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ML210 Antagonizes ABCB1- Not ABCG2-Mediated Multidrug Resistance in Colorectal Cancer.","authors":"Yan-Chi Li, Yu-Meng Xiong, Ze-Ping Long, Yi-Ping Huang, Yu-Bin Shu, Ke He, Hong-Yan Sun, Zhi Shi","doi":"10.3390/biomedicines13051245","DOIUrl":"10.3390/biomedicines13051245","url":null,"abstract":"<p><p><b>Objectives:</b> ABCB1-mediated multidrug resistance (MDR) compromises chemotherapy efficacy in colorectal cancer (CRC). Despite decades of research, no selective ABCB1 inhibitor has achieved clinical success. This study investigates ML210 as a novel ABCB1-specific inhibitor to reverse ABCB1-driven MDR. <b>Methods:</b> Cytotoxicity assays (MTT) were performed on ABCB1-overexpressing HCT-8/V and ABCG2-overexpressing S1-M1-80 CRC cells. Drug accumulation (doxorubicin/mitoxantrone) was quantified via flow cytometry, and cell cycle effects were analyzed using propidium iodide staining. Molecular docking utilized the ABCB1 crystal structure. <b>Results:</b> ML210 selectively reversed ABCB1-mediated resistance to doxorubicin and vincristine in HCT-8/V cells, enhancing intracellular drug accumulation without affecting ABCG2 activity. It induced cell cycle arrest in ABCB1-overexpressing cells and did not alter ABCB1 protein expression. Molecular docking revealed stable binding of ML210 within the ABCB1 substrate pocket through hydrophobic interactions and hydrogen bonding. <b>Conclusions:</b> ML210 is a selective ABCB1 inhibitor that circumvents MDR via direct transport blockade, offering a targeted strategy against ABCB1-mediated chemoresistance in CRC. Its specificity for ABCB1 over ABCG2 highlights potential clinical advantages.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective Management of Chronic Low Back Pain in the Elderly: A One-Year Cohort Study of Oxygen-Ozone Therapy Under CT Guidance Combined with Alpha Lipoic Acid, Palmitoylethanolamide, and Myrrh.","authors":"Matteo Bonetti, Michele Frigerio, Gian Maria Ottaviani, Giannantonio Pellicanò, Alessio Zambello, Mario Muto, Francesco Carinci, Federico Maffezzoni","doi":"10.3390/biomedicines13051250","DOIUrl":"10.3390/biomedicines13051250","url":null,"abstract":"<p><p><b>Background and Objective:</b> This observational study aimed to evaluate the clinical efficacy of combined oxygen-ozone (O₂-O₃) therapy under CT guidance with the oral administration of alpha-lipoic acid (ALA), palmitoylethanolamine (PEA), and myrrh in elderly patients suffering from chronic low back pain (LBP). Given the rising prevalence of degenerative spinal diseases in older adults, this study addresses the need for effective, minimally invasive treatment options. <b>Methods:</b> A total of 276 patients aged 65 to 92 years, with chronic unilateral or bilateral LBP, underwent CT-guided paravertebral infiltrations with an O₂-O₃ gas mixture. This treatment was complemented with a 30-day regimen of ALA (800 mg/day), PEA (600 mg/day), and myrrh (200 mg/day). Clinical outcomes were assessed at one month and one year post-treatment using the Visual Analog Scale (VAS) and the modified McNab method. <b>Results</b>: At one month, 32.94% of patients reported an excellent improvement, with the mean VAS score dropping from 8.17 to 2.81. At the one-year follow-up, 68.15% cumulatively experienced positive outcomes, with 17.78% reporting the complete resolution of pain. In this occasion, the mean VAS score was 3.57. <b>Conclusions:</b> The study demonstrates that the combination of oxygen-ozone therapy and oral ALA, PEA, and myrrh is a promising alternative for managing chronic low back pain in the elderly, leading to significant pain reduction and improved quality of life. Findings emphasize the need for further research to validate these results and explore the long-term benefits.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics-Guided Experimental Validation Identifies NQO1 as a Senescence-Ferroptosis Hub in Liver Fibrosis.","authors":"Xinying Zhang, Chunmeng Fu, Ziyue Yang, Yue Tan, Huan Li, Xiangqian Zhang, Mengru Chen, Fang Peng, Ning Li","doi":"10.3390/biomedicines13051249","DOIUrl":"10.3390/biomedicines13051249","url":null,"abstract":"<p><p><b>Background:</b> As a pivotal point for the development of liver diseases, liver fibrosis (LF) is closely associated with cellular senescence and ferroptosis. However, there is a lack of effective markers that accurately predict LF status. This study aims to identify key genes involved in LF through bioinformatics analysis and experimental validation. <b>Methods:</b> We used bioinformatics analysis of Gene Expression Omnibus (GEO) data to investigate the gene functions, prognostic value, and immune associations of characteristic genes in LF. Functional enrichment analysis of DEGs was performed using GO and KEGG. Immune cell types and their proportions were estimated with CIBERSORTx. In addition, we analyzed the role of NQO1 in LF using IHC, WB, PCR, and flow cytometry. <b>Results:</b> Bioinformatics analysis identified 10 hub genes, including <i>AR, CDKN1A, GJA1, CTSB, HIF1A, HMGB1, NQO1, PARP1, PTEN</i>, and <i>TXN</i>. Among them, <i>NQO1</i> was strongly correlated with immune cell activity. Experimental validation confirmed that NQO1 is upregulated and promotes αSMA and COL1A1 expression in hepatic stellate cells (HSCs). Knockdown of <i>NQO1</i> significantly affected the proliferation of HSCs. <b>Conclusions:</b> NQO1 plays a critical role in HSC senescence and ferroptosis, promoting HSC activation and contributing to LF progression. Our findings suggest that NQO1 may serve as a potential biomarker for LF.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structured Early Follow-Up in Head and Neck Squamous Cell Carcinomas: A Retrospective Cohort Study.","authors":"Philipp Dittmann, Bernhard Lehnert, Friedrich Ihler, Chia-Jung Busch, Markus Blaurock","doi":"10.3390/biomedicines13051246","DOIUrl":"10.3390/biomedicines13051246","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The various head and neck squamous cell carcinoma (HNSCC) subtypes are among the most common cancers globally, with significant recurrence rates within the first two years post-treatment. Despite advancements in treatment, structured early follow-up remains crucial for timely diagnosis and effective salvage treatment. <b>Methods</b>: This retrospective study examines the impact of implementing a structured initial restaging between three and six months after the conclusion of initial treatment. The study population included 532 patients treated with curative intent at the University Medicine of Greifswald, Germany, between 2010 and 2019. Patients were divided into two groups: standard follow-up (SF) and adapted follow-up (AF). The AF group received standardized post-treatment restaging, including imaging and panendoscopy or PET-CT exams. <b>Results</b>: We found a trend towards earlier diagnosis and a reduction in recurrences, although these differences were not statistically significant. Secondary cancers were observed more frequently in the AF group, significantly affecting overall survival. <b>Conclusions</b>: Our cohort supports structured initial cancer follow-up in HNSCC. Although not significant, an initial multimodal exam after treatment was well tolerated and showed a trend toward earlier diagnosis.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renalase Overexpression-Mediated Excessive Metabolism of Peripheral Dopamine, DOPAL Accumulation, and α-Synuclein Aggregation in Baroreflex Afferents Contribute to Neuronal Degeneration and Autonomic Dysfunction.","authors":"Xue Xiong, Yin-Zhi Xu, Yan Zhang, Hong-Fei Zhang, Tian-Min Dou, Xing-Yu Li, Zhao-Yuan Xu, Chang-Peng Cui, Xue-Lian Li, Bai-Yan Li","doi":"10.3390/biomedicines13051243","DOIUrl":"10.3390/biomedicines13051243","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Increasing evidence reveals the likely peripheral etiology of Parkinson's disease; however, the mechanistic insight into α-Synuclein aggregation in the periphery remains unclear. This study aimed to explore the effect of abnormal expression of renalase on dopamine metabolism, toxic DOPAL generation, and subsequently, α-Synuclein aggregation. <b>Methods</b>: Blood pressure (BP) was monitored while changing the body position of rats; the serum level of renalase was detected by ELISA; the mRNA/protein of renalase and α-Synuclein were determined by qRT-PCR/Western blot; DOPAL was measured using HPLC; renalase distribution was explored by immunostaining; cell viability and ultrastructure were examined by TUNEL and electron microscopy, respectively. <b>Results</b>: The results showed that, in PD model rats, the serum level of renalase was increased time-dependently with up-regulated renalase gene/protein expression in the nodose ganglia, nucleus tractus solitarius, and heart; a reduced dopamine content was also detected by the renalase overexpression in PC12 cells. Strikingly, up-regulated renalase and orthostatic BP changes were observed before the behavioral changes in the model rats. Meanwhile, the levels of DOPAL and α-Synuclein were increased time-dependently. Intriguingly, the low molecular weight of α-Synuclein declined coordinately with the increase in the higher molecular weight of α-Synuclein. Clear ultrastructure damage at the cellular level supported the notion of molecular findings. Notably, the α-Synuclein aggregation-induced impairment of the axonal transport function predates neuronal degeneration mediated by renalase overexpression. <b>Conclusions</b>: Our results demonstrate that abnormal peripheral dopamine metabolism mediated by overexpressed renalase promotes the DOPAL-induced α-Synuclein and leads to baroreflex afferent neuronal degeneration and early autonomic failure.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}