Biomedicines最新文献

{"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}

{"title":"Significant Microvascular Abnormalities Present in Autonomic Nervous System Dysfunction: Results of a Cross-Sectional Study.","authors":"Sehreen Mumtaz, Karissa Arca, Vikas Majithia, William Cheshire, David Hodge, Florentina Berianu","doi":"10.3390/biomedicines13051242","DOIUrl":"10.3390/biomedicines13051242","url":null,"abstract":"<p><p><b>Purpose:</b> The prevalence and phenotype of capillaroscopic abnormalities in patients with autonomic nervous system dysfunction have not yet been investigated. Multiorgan involvement in dysautonomia entails abnormal vasoreactivity. We aim to correlate the diagnosis of autonomic dysfunction with certain clinical manifestations, which may provide prognostic or diagnostic information using a noninvasive technique, i.e., nailfold video capillaroscopy (NVC). <b>Methods:</b> Patients with autonomic nervous system dysfunction were recruited from rheumatology and neurology clinics with voluntary NVC procedures from 31 January 2024 to 10 January 2024, and a comparison with normal controls was performed. Additional recorded information include demographics and diagnoses of autonomic dysfunction types by autonomic testing, including, but not limited to, the following: reflex screen, sweat test, Valsalva maneuver, nerve fiber density, electromyography (EMG), serology, and history of autoimmune diseases. NVC was performed on a total of 27 patients. This study was approved by the Mayo Clinic Institutional Review Board. <b>Results:</b> The autonomic dysfunction group consisted of small-fiber neuropathy (37%), orthostatic hypotension (48%), autonomic neuropathy (30%), limited autonomic neuropathy (7%), postural orthostatic tachycardia syndrome (POTS) (7%), and connective tissue disease (7%), among other types. Patients with autonomic dysfunction had statistically significant increases in microhemorrhages, dilated capillaries, and ramifications when compared to controls. <b>Conclusions:</b> Autonomic dysfunction was associated with statistically significant microvascular abnormalities compared to normal controls with a distinct NVC pattern. There was a statistically significant correlation between age and BMI with microvascular abnormalities. Here, we demonstrate the diagnostic potential of NVC in autonomic dysfunction and advocate for further study of capillary structures in autonomic dysfunction.</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/PMC12108676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156543","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":"Targeting the <i>ZMYM2-ANXA9</i> Axis with <i>FLT3</i> Inhibitor G749 Overcomes Oxaliplatin Resistance in Colorectal Cancer.","authors":"Dezheng Lin, Yucheng Xu, Huanmiao Zhan, Yufan Liang, Riyun Liu, Jun Liu, Dandong Luo, Xiaochuan Chen, Jiawei Cai, Yifeng Zou","doi":"10.3390/biomedicines13051247","DOIUrl":"10.3390/biomedicines13051247","url":null,"abstract":"<p><p><b>Background:</b> Chemoresistance and tumor recurrence remain major obstacles in colorectal cancer (CRC) therapy. Elucidating the molecular mechanisms underlying treatment resistance is critical for improving therapeutic outcomes. <b>Methods</b>: We analyzed transcriptomic profiles from public datasets (TCGA and GSE39582) to identify differentially expressed genes associated with a poor response to neoadjuvant chemotherapy in CRC patients. Among 298 candidate genes, <i>ANXA9</i> emerged as significantly overexpressed in chemoresistant tumors and associated with a poor prognosis. These findings were further validated in an independent cohort of 146 Stage III CRC patients using immunohistochemistry and survival analysis. The expression of <i>ANXA9</i> was evaluated in oxaliplatin acquired-resistant CRC cell lines via qPCR and Western blot. Functional studies, including RNA interference, colony formation, apoptosis assays, and drug sensitivity testing, were performed in vitro and in vivo to assess the role of <i>ANXA9</i>. A high-throughput drug screen identified G749, a <i>FLT3</i> inhibitor, as a potential therapeutic agent. <b>Results:</b><i>ANXA9</i> expression was significantly elevated in non-responders to chemotherapy and oxaliplatin-resistant CRC cell lines. The knockdown of <i>ANXA9</i> reduced proliferation and enhanced oxaliplatin sensitivity. G749 was found to suppress <i>ANXA9</i> expression in a dose-dependent manner and inhibit CRC cell growth in vitro and in patient-derived organoids. In a CRC xenograft mouse model, G749 reduced the tumor burden without observable toxicity. Mechanistically, we identified <i>ZMYM2</i> as a transcriptional regulator of <i>ANXA9</i>. ChIP-qPCR confirmed <i>ZMYM2</i> binding to the <i>ANXA9</i> promoter, especially in resistant cells. Silencing <i>ZMYM2</i> suppressed tumor cell growth and restored chemosensitivity. <b>Conclusions:</b> The <i>ZMYM2-ANXA9</i> signaling axis drives chemoresistance and tumor progression in CRC. <i>FLT3</i> inhibition by G749 effectively downregulates <i>ANXA9</i> and sensitizes tumors to chemotherapy, highlighting a novel therapeutic approach for chemoresistant CRC.</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/PMC12108716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156495","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":"The Potential Role of SP-G and PLUNC in Tumor Pathogenesis and Wound Healing in the Human Larynx.","authors":"Aurelius Scheer, Lars Bräuer, Markus Eckstein, Heinrich Iro, Friedrich Paulsen, Fabian Garreis, Martin Schicht, Antoniu-Oreste Gostian","doi":"10.3390/biomedicines13051240","DOIUrl":"10.3390/biomedicines13051240","url":null,"abstract":"<p><p><b>Background:</b> Immunological and rheological properties are important factors of the surfactant protein (SP) family, whose impact on tumorigenesis is not yet known, although some SPs have been identified as tumor marker candidates for various malignancies. This study describes the detection of the two surfactant family proteins SP-G and PLUNC in healthy glottis, the presence of SP-G in glottic cancer, and the in vitro tissue regeneration potential of SP-G and PLUNC on epithelial cells. <b>Methods:</b> The expression and distribution of SP-G and PLUNC were investigated immunohistochemically in squamous cell carcinomas of the vocal folds. The expression of both proteins was analyzed by Western blot in micro-dissected healthy vocal fold mucosa from body donors. The hypopharyngeal squamous carcinoma cell line (FaDu) was used as an in vitro model for wound healing experiments with Electric cell-substrate impedance sensing (ECIS). <b>Results:</b> The results show the presence of SP-G and PLUNC in epithelial cells of the healthy vocal folds and the submucosal glands of the vestibular folds. SP-G was detected in squamous cell carcinomas of the vocal folds. SP-G and PLUNC show accelerated wound healing of FaDu cells in vitro. <b>Conclusions:</b> SP-G and PLUNC were first detected in the vocal fold of the human larynx. SP-G shows a distinct presence in glottic carcinoma, whose relevance needs to be determined in future studies. SP-G and PLUNC exhibit a positive influence on the repair mechanisms of epithelial lesions of the glottis. The data presented form the basis for follow-up studies focusing on the impact of SP-G in glottic cancer development and the potentially meaningful clinical effect of SP-G and PLUNC on tissue repair of the human vocal fold.</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/PMC12108585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156512","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":"HD-OCT Angiography and SD-OCT in Patients with Mild or No Clinically Apparent Diabetic Retinopathy.","authors":"Maja Vinković, Andrijana Kopić, Tvrtka Benašić, Dubravka Biuk, Ivanka Maduna, Stela Vujosevic","doi":"10.3390/biomedicines13051251","DOIUrl":"10.3390/biomedicines13051251","url":null,"abstract":"<p><p><b>Purpose:</b> To analyze the retinal and choriocapillaris changes in diabetic patients with no or with early signs of diabetic retinopathy using high-definition (HD) angio optical coherence tomography angiography (OCTA) software and spectral-domain (SD) OCT. <b>Methods:</b> A total of 112 eyes (54 eyes from 27 diabetic patients and 58 eyes from 29 control subjects) were included in this retrospective cross-sectional study of healthy and diabetic adults. Retinal microvascular changes were assessed by using HD-OCTA software to calculate vascular density (VD) and foveal avascular zone (FAZ). SD-OCT was used to assess retinal thickness and volume in parafovea as well as ganglion cell complex (GCC) parameters. <b>Results:</b> The VD-whole image was significantly higher in the healthy control group (MW z = 1109.5, <i>p</i> = 0.012; <i>t</i> = 2.611, <i>p</i> = 0.010). Also, VD-parafovea was significantly higher in the healthy subjects (MW z = 1053.5, <i>p</i> = 0.004; <i>t</i> = 3.207, <i>p</i> = 0.002). GCC focal loss volume (FLV) was significantly decreased in diabetic patients (<i>p</i> = 0.051). Non-flow FAZ did not show a statistically significant difference between groups, although the FAZ was larger in the diabetic patients. <b>Conclusions:</b> Diabetic patients with no or early signs of diabetic retinopathy have decreased VD compared to healthy individuals. They also present retinal changes at the GCC that are correlated with initial neurodegeneration. HD-OCTA and SD-OCT can detect vascular changes and structural signs of retinal neurodegeneration before clinically apparent diabetic retinopathy. Potentially, these methods may offer new biomarkers for monitoring disease progression and visual prognosis.</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/PMC12109522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156104","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":"New Insights into the Diagnosis and Treatment of Hepatocellular Carcinoma.","authors":"Chengbo Li, Bingjiu Lu, Baocheng Deng","doi":"10.3390/biomedicines13051244","DOIUrl":"10.3390/biomedicines13051244","url":null,"abstract":"<p><p>Hepatocellular carcinoma remains one of the leading contributors to global cancer mortality, frequently stemming from chronic liver conditions, such as viral hepatitis, non-alcoholic fatty liver disease, and alcohol-induced cirrhosis. While antiviral treatments have made significant strides, the rising prevalence of hepatocellular carcinoma linked to non-infectious causes underscores the pressing demand for more effective diagnostic tools and therapeutic interventions. Advances in imaging and liquid biopsy technologies have facilitated early detection and diagnosis, and treatment strategies are diversifying to include immune checkpoint inhibitors, tyrosine kinase inhibitors, and interventional therapies. Translational therapies for advanced hepatocellular carcinoma have improved surgical opportunities and patient survival. Artificial intelligence has played a transformative role in the diagnosis and treatment of hepatocellular carcinoma, in terms of image analysis, histopathologic classification, drug development, and targeted therapy. The future of hepatocellular carcinoma treatment lies in precision oncology and the collaboration of multidisciplinary teams, as well as in early detection. The ultimate goal is to keep patients alive longer and reduce the global burden of this complex malignancy.</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/PMC12109435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156312","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":"Systemic Ozone Therapy Improves Oral Hard and Soft Tissue Healing in Medication-Related Osteonecrosis of the Jaw (MRONJ): A Study in Senescent Female Rats.","authors":"Leonardo Alan Delanora, Tiburtino José de Lima Neto, Tiago Esgalha da Rocha, Glauco Rodrigues Carmo Silveira, Liran Levin, Jamil Awad Shibli, Edilson Ervolino, Carlos Fernando Mourão, Leonardo P Faverani","doi":"10.3390/biomedicines13051248","DOIUrl":"10.3390/biomedicines13051248","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Medication-related osteonecrosis of the jaw (MRONJ) is a challenging condition often associated with bisphosphonate use, leading to impaired bone healing and difficult clinical management. Given the lack of predictable therapeutic options, this study investigated the effects of systemic ozone therapy on MRONJ healing. This study aimed to analyze the effects of systemic ozone therapy on oral hard and soft tissue healing in senescent rats with medication-related osteonecrosis of the jaw (MRONJ) induced by antiresorptive therapy. <b>Methods</b>: Twenty-eight senescent Wistar rats, aged eighteen months and weighing ~350 g, were used for this study. The animals were divided into four groups. The negative control (SAL) group received saline applications, while the control-treated (SAL+OZ) group received saline applications and ozone therapy (0.7 mg/kg). The MRONJ (ZOL) group received Zoledronate, an intravenous antiresorptive drug (100 μg/kg), and the MRONJ-treated (ZOL+OZ) group received zoledronate application and was treated with systemic ozone therapy (0.7 mg/kg). All rats underwent molar extraction in the third week of the experiment and were euthanized in the seventh week of the experiment. The mandibles were resected, reduced, and prepared for microtomographic analysis, histopathological/histometric analysis, and immunohistochemistry. <b>Results</b>: The ZOL group presented characteristics of vitreous, non-vital, and dense bone, poor vascularization, and high values of inflammation markers compatible with MRONJ. In contrast, the ZOL+OZ group exhibited improvement in alveolar bone and soft tissue healing, a decrease in nonvital bone area, and modulation of local inflammation. <b>Conclusions</b>: It can be concluded that Ozone therapy improved oral hard and soft tissue healing of MRONJ in senescent female rats subjected to antiresorptive drugs and might be considered for future clinical applications.</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/PMC12108863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156435","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":"In Vitro Evaluation of the PMN Reaction on a Collagen-Based Purified Reconstituted Bilayer Matrix (PRBM) Using the Autologous Blood Concentrate PRF.","authors":"Eva Dohle, Hongyu Zuo, Büşra Bayrak, Anja Heselich, Birgit Schäfer, Robert Sader, Shahram Ghanaati","doi":"10.3390/biomedicines13051239","DOIUrl":"10.3390/biomedicines13051239","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The body's reaction after the implantation of a biomaterial is a non-specific inflammatory response that is mainly initiated via the recruitment of polymorphonuclear cells (PMNs) to the implant site secreting cytokines and growth factors, followed by activation of monocytes/macrophages, finally leading to wound healing. The wound healing process is dependent on the priming of the PMNs that can be guided towards an inflammatory or a regenerative phenotype with the associated characteristic PMN cytokine profiles. Since the collagen-based Purified Reconstituted Bilayer Matrix (PRBM) triggers the wound healing process at the implant site in vivo, it is hypothesized that this positive effect might be due to a material-mediated priming of the PMNs towards the regenerative phenotype. With the use of the blood concentrate platelet-rich fibrin (PRF) containing high concentrations of leukocytes, including PMNs, the natural environment of the body after the implantation of a material can be mimicked in vitro. The aim of the present study was to characterize the phenotype of native blood-derived PMNs within PRF in response to the PRBM. <b>Methods</b>: PMNs within PRF gained from different relative centrifugal forces were characterized in a first step before PRF was combined with the PRBM for 4 h. Supernatants were harvested to analyze the phenotype of the PMNs via the evaluation of eight different cytokines using the ELISA. <b>Results</b>: Analysis of the PMN phenotype could assess cytokines commonly associated with neutrophils of the proinflammatory phenotype, such as TNFα, IL15, and IL1, as lower in supernatants when PRF was incubated in the presence of the PRBM and compared to the control PRF. On the other hand, cytokines related to the PMN regenerative phenotype, like TGFβ and IL10, could be detected as higher when PRF was incubated in the presence of the PRBM. <b>Conclusions</b>: This might suggest that PRBM significantly activates and primes neutrophils to the regenerative phenotype, leading to the resolution of inflammation. This might trigger the process of wound healing and tissue regeneration, making the PRBM a beneficial material for therapeutic applications.</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/PMC12109348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156286","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":"The Chemokine (C-C Motif) Receptor 1 Antagonist BX471 Improves Fluid Resuscitation in Rat Models of Hemorrhagic Shock.","authors":"Elizabeth A Cook, Ololade Ogunsina, Xianlong Gao, Matthias Majetschak","doi":"10.3390/biomedicines13051241","DOIUrl":"10.3390/biomedicines13051241","url":null,"abstract":"<p><p><b>Background/Objectives</b>: We reported previously that antagonists at chemokine receptors CCR2 and CCR3 have fluid-sparing effects during resuscitation from hemorrhagic shock. Because CCR1 shares several chemokine ligands with CCR2/3, we tested whether the CCR1 antagonist BX471 also reduces fluid requirements to maintain hemodynamics. <b>Methods</b>: Sprague Dawley rats were hemorrhaged for 30 min, followed by fluid resuscitation to maintain blood pressure for 60 min (series 1) and 180 min (series 2). Series 1: Animals received vehicle (n = 5), 0.05 μmol/kg (n = 5), or 0.5 μmol/kg (n = 4) BX471 at t = 30 min. Series 2: Animals received vehicle (n = 8) or 0.5 μmol/kg (n = 7) BX471 at t = 30 min. Hemodynamics, fluid requirements, blood gases, and lactate were monitored. Serum concentrations of CCR1 ligands (CCL3/4/5/7) were determined at baseline and at the conclusion of the experiments. Tissue (small/large intestine, lung) wet/dry (W/D) weight ratios, lung myeloperoxidase activity, and a panel of inflammation markers in tissue extracts were measured. <b>Results</b>: All animals could be resuscitated to target blood pressures. Series 1: A total of 0.5 μmol/kg BX471 reduced fluid requirements by more than 60% (<i>p</i> < 0.05 vs. vehicle and 0.05 μmol/kg BX471). Series 2: Systemic CCL3/5/7 levels increased during the experiment (<i>p</i> < 0.05). BX471-treatment reduced fluid requirements by more than 60% (<i>p</i> < 0.05) and prevented increases in CCL3/7. W/D ratios of large intestine and of the sum of all tissues were lower with BX471 treatment (<i>p</i> < 0.05). BX471-treatment reduced TNFα and IL6 concentrations in large intestine extracts (<i>p</i> < 0.05). <b>Conclusions</b>: Our findings suggest CCR1 as a new therapeutic target to reduce fluid requirements during resuscitation from hemorrhagic shock.</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/PMC12109411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156498","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":"Cardiac Amyloidosis: A Narrative Review of Diagnostic Advances and Emerging Therapies.","authors":"Dana Emilia Movila, Alexandru Catalin Motofelea, Dragos Cozma, Oana Albai, Alexandra Christa Sima, Minodora Andor, Tudor Ciocarlie, Simona Ruxanda Dragan","doi":"10.3390/biomedicines13051230","DOIUrl":"10.3390/biomedicines13051230","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Cardiac amyloidosis (CA) is an underdiagnosed and potentially life-threatening infiltrative cardiomyopathy characterized by the extracellular deposition of misfolded amyloid fibrils in cardiac tissue. It is most commonly associated with light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis, either hereditary or wild-type. The disease often presents with non-specific symptoms, leading to delayed diagnosis and treatment. This study aims to provide a comprehensive overview of the pathophysiology, diagnostic strategies, and current therapeutic approaches for cardiac amyloidosis, with a focus on improving early detection and clinical outcomes. <b>Methods</b>: A narrative review was conducted using databases such as PubMed and Scopus, covering the period from September 2016 to March 2025. Keywords such as \"cardiac amyloidosis\", \"cardiac amyloidosis from transthyretin\", \"cardiomyopathy\", \"transthyretin\", \"immunoglobulin light-chain amyloidosis\", and \"familial amyloidosis\" were used. Relevant clinical trials and guideline-based management recommendations were also included. <b>Results</b>: This review highlights that non-invasive imaging modalities and serum biomarker analyses are key to reducing diagnostic delays. New therapeutic developments, including gene-editing technologies and RNA-based therapies, show promise in early trials. Multidisciplinary management and increased awareness are crucial for timely diagnosis and treatment optimization. <b>Conclusions</b>: The early recognition of cardiac amyloidosis remains a major clinical challenge. Advances in non-invasive diagnostics and emerging disease-modifying therapies are transforming the prognosis of affected patients. Continued research and heightened clinical suspicion are essential to improve outcomes in this complex and heterogeneous disease.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156218","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}