Journal of Advanced Research最新文献

{"title":"The efferocytosis process in aging: Supporting evidence, mechanisms, and therapeutic prospects for age-related diseases","authors":"Meng Zhang ,&nbsp;Jin Wei ,&nbsp;Yu Sun ,&nbsp;Chang He ,&nbsp;Shiyin Ma ,&nbsp;Xudong Pan ,&nbsp;Xiaoyan Zhu","doi":"10.1016/j.jare.2024.03.008","DOIUrl":"10.1016/j.jare.2024.03.008","url":null,"abstract":"<div><h3>Background</h3><div>Aging is characterized by an ongoing struggle between the buildup of damage caused by a combination of external and internal factors. Aging has different effects on phagocytes, including impaired efferocytosis. A deficiency in efferocytosis can cause chronic inflammation, aging, and several other clinical disorders.</div></div><div><h3>Aim of review</h3><div>Our review underscores the possible feasibility and extensive scope of employing dual targets in various age-related diseases to reduce the occurrence and progression of age-related diseases, ultimately fostering healthy aging and increasing lifespan.</div><div>Key scientific concepts of review</div><div>Hence, the concurrent implementation of strategies aimed at augmenting efferocytic mechanisms and anti-aging treatments has the potential to serve as a potent intervention for extending the duration of a healthy lifespan. In this review, we comprehensively discuss the concept and physiological effects of efferocytosis. Subsequently, we investigated the association between efferocytosis and the hallmarks of aging. Finally, we discuss growing evidence regarding therapeutic interventions for age-related disorders, focusing on the physiological processes of aging and efferocytosis.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 31-49"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term and short-term cardiovascular disease mortality among patients of 21 non-metastatic cancers","authors":"Tianwang Guan ,&nbsp;Olivia Monteiro ,&nbsp;Dongting Chen ,&nbsp;Zehao Luo ,&nbsp;Kaiyi Chi ,&nbsp;Zhihao Li ,&nbsp;Yinglan Liang ,&nbsp;Zhenxing Lu ,&nbsp;Yanting Jiang ,&nbsp;Jinming Yang ,&nbsp;Wenrui Lin ,&nbsp;Min Yi ,&nbsp;Kang Zhang ,&nbsp;Caiwen Ou","doi":"10.1016/j.jare.2024.03.017","DOIUrl":"10.1016/j.jare.2024.03.017","url":null,"abstract":"<div><h3>Introduction</h3><div>Previous studies on cardiovascular disease (CVD) death risk in cancer patients mostly focused on overall cancer, age subgroups and single cancers.</div></div><div><h3>Objectives</h3><div>To assess the CVD death risk in non-metastatic cancer patients at 21 cancer sites.</div></div><div><h3>Methods</h3><div>A total of 1,672,561 non-metastatic cancer patients from Surveillance, Epidemiology, and End Results (SEER) datebase (1975–2018) were included in this population-based study, with a median follow-up of 12·7 years. The risk of CVD deaths was assessed using proportions, competing-risk regression, absolute excess risks (AERs), and standardized mortality ratios (SMRs).</div></div><div><h3>Results</h3><div>In patients with localized cancers, the proportion of CVD death and cumulative mortality from CVD in the high-competing risk group (14 of 21 unique cancers) surpassed that of primary neoplasm after cancer diagnosis. The SMRs and AERs of CVD were found higher in patients with non-metastatic cancer than the general US population (SMR 1·96 [95 %CI, 1·95-1·97]–19·85[95 %CI, 16·69-23·44]; AER 5·77–210·48), heart disease (SMR 1·94[95 %CI, 1·93-1·95]–19·25[95 %CI, 15·76-23·29]; AER 4·36–159·10) and cerebrovascular disease (SMR 2·05[95 %CI, 2·02-2·08]–24·71[95 %CI, 16·28-35·96]; AER 1·01–37·44) deaths. In the high-competing risk group, CVD-related SMR in patients with localized stage cancer increased with survival time but followed a reverse-dipper pattern in the low-competing risk group (7 of 21 cancers). The high-competing risk group had higher CVD-related death risks than the low-competing risk group.</div></div><div><h3>Conclusion</h3><div>The CVD death risk in patients with non-metastatic cancer varied by cancer stage, site and survival time. The risk of CVD mortality is higher in 14 out of 21 localized cancers (high-competing cancers). Targeted strategies for CVD management in non-metastatic cancer patients are needed.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 215-224"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of extracellular vesicles in non-alcoholic steatohepatitis: Emerging mechanisms, potential therapeutics and biomarkers","authors":"Qianrong Wang ,&nbsp;Xiangning Tang ,&nbsp;Yu Wang ,&nbsp;Danyi Zhang ,&nbsp;Xia Li ,&nbsp;Shanshan Liu","doi":"10.1016/j.jare.2024.03.009","DOIUrl":"10.1016/j.jare.2024.03.009","url":null,"abstract":"<div><div>Non-alcoholic steatohepatitis (NASH), an emerging global healthcare problem, has become the leading cause of liver transplantation in recent decades. No effective therapies in the clinic have been proven due to the incomplete understanding of the pathogenesis of NASH, and further studies are expected to continue to delve into the mechanisms of NASH. Extracellular vesicles (EVs), which are small lipid membrane vesicles carrying proteins, microRNAs and other molecules, have been identified to play a vital role in cell-to-cell communication and are involved in the development and progression of various diseases. In recent years, there has been increasing interest in the role of EVs in NASH. Many studies have revealed that EVs mediate important pathological processes in NASH, and the role of EVs in NASH is distinct and variable depending on their origin cells and target cells. This review outlines the emerging mechanisms of EVs in the development of NASH and the preclinical evidence related to stem cell-derived EVs as a potential therapeutic strategy for NASH. Moreover, possible strategies involving EVs as clinical diagnostic, staging and prognostic biomarkers for NASH are summarized.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 157-168"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles derived from Lactobacillus johnsonii promote gut barrier homeostasis by enhancing M2 macrophage polarization","authors":"Shiyu Tao ,&nbsp;Jinping Fan ,&nbsp;Jingjing Li ,&nbsp;Zhifeng Wu ,&nbsp;Yong Yao ,&nbsp;Zhenyu Wang ,&nbsp;Yujun Wu ,&nbsp;Xiangdong Liu ,&nbsp;Yingping Xiao ,&nbsp;Hong Wei","doi":"10.1016/j.jare.2024.03.011","DOIUrl":"10.1016/j.jare.2024.03.011","url":null,"abstract":"<div><h3>Introduction</h3><div>Diarrheic disease is a common intestinal health problem worldwide, causing great suffering to humans and animals. Precise manipulation strategies based on probiotics to combat diarrheic diseases have not been fully developed.</div></div><div><h3>Objectives</h3><div>The aim of this study was to investigate the molecular mechanisms by which probiotics manipulate macrophage against diarrheic disease.</div></div><div><h3>Methods</h3><div>Metagenome reveals gut microbiome profiles of healthy and diarrheic piglets. Fecal microbial transplantation (FMT) was employed to explore the causal relationship between gut microbes and diarrhea. The protective role of probiotics and their derived extracellular vesicles (EVs) was investigated in ETEC K88-infected mice. Macrophage depletion was performed to assess the role of macrophages in EVs against diarrhea. Execution of <em>in vitro</em> cell co-culture and transcriptome analyses elucidated the molecular mechanisms by which EVs modulate the macrophage and intestinal epithelial barrier.</div></div><div><h3>Results</h3><div><em>Escherichia coli</em> was enriched in weaned diarrheic piglets, while <em>Lactobacillus johnsonii</em> (<em>L. john</em>) showed a negative correlation with <em>Escherichia coli</em>. The transmission of diarrheic illness symptoms was achieved by transferring fecal microbiota, but not metabolites, from diarrheic pigs to germ-free (GF) mice. <em>L. john's</em> intervention prevented the transmission of disease phenotypes from diarrheic piglets to GF mice. <em>L. john</em> also reduces the gut inflammation induced by ETEC K88. The EVs secreted by <em>L. john</em> demonstrated enhanced efficacy in mitigating the adverse impacts induced by ETEC K88 through the modulation of macrophage phenotype. <em>In vitro</em> experiments have revealed that EVs activate M2 macrophages in a manner that shuts down ERK, thereby inhibiting NLRP3 activation in intestinal epithelial cells.</div></div><div><h3>Conclusion</h3><div>Our results reveal that intestinal microbiota drives the onset of diarrheic disease and that probiotic-derived EVs ameliorate diarrheic disease symptoms by modulating macrophage phenotypes. These findings can enhance the advancement of innovative therapeutic approaches for diarrheic conditions based on probiotic-derived EVs.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 545-563"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140173259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erianin serves as an NFATc1 inhibitor to prevent breast cancer-induced osteoclastogenesis and bone destruction","authors":"Jiehuang Zheng ,&nbsp;Weili He ,&nbsp;Yan Chen ,&nbsp;Lihong Li ,&nbsp;Qinghe Liang ,&nbsp;Wenqi Dai ,&nbsp;Ruopeng Li ,&nbsp;Fengsheng Chen ,&nbsp;Ziye Chen ,&nbsp;Yanhui Tan ,&nbsp;Xiaojuan Li","doi":"10.1016/j.jare.2024.03.021","DOIUrl":"10.1016/j.jare.2024.03.021","url":null,"abstract":"<div><h3>Introduction</h3><div>Breast cancer-related bone metastasis can lead to skeletal-related events (SREs), which decrease patient quality of life. Inhibition of osteoclastogenesis is a key treatment for SREs; however, the availability of clinical drugs remains limited, and all existing ones disrupt physiological bone formation, while exhibiting no effect on patient survival time.</div></div><div><h3>Objectives</h3><div>This study aimed to identify a novel osteoclast inhibitor for the treatment of breast cancer-induced SREs.</div></div><div><h3>Methods</h3><div>The MDA-MB-231 breast cancer cell-induced bone loss model was used to investigate the therapeutic effects of erianin <em>in vivo</em>. Then, we evaluated the inhibitory effects of erianin on osteoclastogenesis and signalling in bone marrow-derived macrophages (BMMs) induced by conditioned medium from MDA-MB-231 breast cancer cells (231 CM) and receptor activator of nuclear factor-κB ligand (RANKL) <em>in vitro</em>. Next, a Cellular Thermal Shift Assay and siRNA-mediate knockdown were performed, to investigate the target of erianin during osteoclast formation. The effects of erianin on human osteoclastogenesis were evaluated using CD14⁺ monocytes obtained from patients with breast cancer.</div></div><div><h3>Results</h3><div>Erianin effectively improved breast cancer cells-induced bone destruction at doses of 2 and 20 mg/kg/day <em>in vivo</em>, while suppressing osteoclastogenesis and the upregulation of SRC-NFATc1, INTEGRIN β3-MMP9 signals induced by 231 CM and RANKL <em>in vitro</em>. Furthermore, erianin interacted with NFATc1 but not SRC, and <em>Nfatc1</em> knockdown eliminated the inhibitory effects of erianin on osteoclastogenesis. Notably, lower expression of <em>NFATc1</em> positively correlated with longer survival in patients with cancer and a high risk of bone metastasis. We further revealed that 62.5–250 nM erianin suppresses NFATc1 and excessive osteoclastogenesis in CD14⁺ monocytes from patients with breast cancer.</div></div><div><h3>Conclusion</h3><div>Erianin acts as an NFATc1 inhibitor that attenuates breast cancer-induced osteoclastogenesis and bone destruction.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 399-411"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140332383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urolithin A inhibits breast cancer progression via activating TFEB-mediated mitophagy in tumor macrophages","authors":"Bowen Zheng ,&nbsp;Yuying Wang ,&nbsp;Baian Zhou ,&nbsp;Fengyuan Qian ,&nbsp;Diya Liu ,&nbsp;Danrong Ye ,&nbsp;Xiqian Zhou ,&nbsp;Lin Fang","doi":"10.1016/j.jare.2024.04.010","DOIUrl":"10.1016/j.jare.2024.04.010","url":null,"abstract":"<div><h3>Introduction</h3><div>Urolithin A (UA) is a naturally occurring compound that is converted from ellagitannin-like precursors in pomegranates and nuts by intestinal flora. Previous studies have found that UA exerts tumor-suppressive effects through antitumor cell proliferation and promotion of memory T-cell expansion, but its role in tumor-associated macrophages remains unknown.</div></div><div><h3>Objectives</h3><div>Our study aims to reveal how UA affects tumor macrophages and tumor cells to inhibit breast cancer progression.</div></div><div><h3>Methods</h3><div>Observe the effect of UA treatment on breast cancer progression though in vivo and in vitro experiments. Western blot and PCR assays were performed to discover that UA affects tumor macrophage autophagy and inflammation. Co-ip and Molecular docking were used to explore specific molecular mechanisms.</div></div><div><h3>Results</h3><div>We observed that UA treatment could simultaneously inhibit harmful inflammatory factors, especially for InterleuKin-6 (IL-6) and tumor necrosis factor α (TNF-α), in both breast cancer cells and tumor-associated macrophages, thereby improving the tumor microenvironment and delaying tumor progression. Mechanistically, UA induced the key regulator of autophagy, transcription factor EB (TFEB), into the nucleus in a partially mTOR-dependent manner and inhibited the ubiquitination degradation of TFEB, which facilitated the clearance of damaged mitochondria via the mitophagy-lysosomal pathway in macrophages under tumor supernatant stress, and reduced the deleterious inflammatory factors induced by the release of nucleic acid from damaged mitochondria. Molecular docking and experimental studies suggest that UA block the recognition of TFEB by 1433 and induce TFEB nuclear localization. Notably, UA treatment demonstrated inhibitory effects on tumor progression in multiple breast cancer models.</div></div><div><h3>Conclusion</h3><div>Our study elucidated the anti-breast cancer effect of UA from the perspective of tumor-associated macrophages. Specifically, TFEB is a crucial downstream target in macrophages.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 125-138"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140776922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Calcium influx: An essential process by which α-Synuclein regulates morphology of erythrocytes” [J. Adv. Res. 62 (2024) 187–198]","authors":"Ying Yang ,&nbsp;Min Shi ,&nbsp;Xiaodan Liu ,&nbsp;Qiaoyun Zhu ,&nbsp;Zhi Xu ,&nbsp;Genliang Liu ,&nbsp;Tao Feng ,&nbsp;Tessandra Stewart ,&nbsp;Jing Zhang","doi":"10.1016/j.jare.2024.09.018","DOIUrl":"10.1016/j.jare.2024.09.018","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 581-583"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors affecting the intracytoplasmic sperm cell injection outcomes: A meta-analysis of porcine studies","authors":"Muhammad Ameen Jamal, Ali Husnain, Kaixiang Xu, Hong-Jiang Wei","doi":"10.1016/j.jare.2025.02.040","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.040","url":null,"abstract":"<h3>Background</h3>Intracytoplasmic sperm cell injection (ICSI) has the potential to produce gene-edited (GE) pigs for biomedical research, but its success is limited. The factors impeding ICSI in pigs are impractical <em>in-vivo</em> oocyte production, incomplete cytoplasmic maturation of <em>in-vitro</em> matured (IVM) oocytes, inefficient methods for sperm selection and membrane removal, abnormal sperm nucleus decondensation, substandard protocols for oocyte stimulation, suboptimal <em>in-vitro</em> culture (IVC) systems, and high embryonic/fetal losses.<h3>Aim of review</h3>The aim of this review is to investigate the effects of interventions in ICSI on oocyte activation, fertilization, cleavage, blastocyst, blastomere count, and live birth by means of robust statistical <em>meta</em>-analytical methods.<h3>Key scientific concepts of review</h3>A total of 61 studies published between 1905 ∼ 2024 met the inclusion criteria. The results of the <em>meta</em>-analysis suggested that manipulation in the IVM media did not improve oocyte developmental competency to blastocysts but increased the blastomere count, especially with the addition of thiol compounds. Consistently, manipulation with sperm was beneficial only for increasing the cleavage and blastomere count. Exogenous stimulation increased the relative risk (RR) for oocyte activation (10 %), fertilization (33 %), cleavage (18 %), and blastocyst formation (71 %) but did not affect the blastomere count. Chemical stimulation either pre- or post-ICSI was more beneficial than electrical stimulation. Manipulation of the culture increased the RR for oocyte activation (14 %) and fertilization (37 %) but did not benefit cleavage, blastocyst formation, or blastomere count. The subgroup analyses revealed that supplementation with thiol compounds was indeed beneficial. Our network <em>meta</em>-analysis also supported the findings of classical <em>meta</em>-analyses showing that cysteine, cysteamine, epidermal growth factor, amino acid supplementation in maturation and culture media, and Triton treatment of sperm improved blastocyst formation. The overall success rate of live births from total embryos transferred after ICSI was not greater than 2 %. Although, manipulations that were beneficial for ICSI outcomes were identified in this <em>meta</em>-analysis, however, areas where more robust data are needed to reach a conclusive decision are highlighted.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"54 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sweet regulation – The emerging immunoregulatory roles of hexoses","authors":"Junjie Xu ,&nbsp;Yuening Zhao ,&nbsp;Randall Tyler Mertens ,&nbsp;Yimin Ding ,&nbsp;Peng Xiao","doi":"10.1016/j.jare.2024.04.014","DOIUrl":"10.1016/j.jare.2024.04.014","url":null,"abstract":"<div><h3>Background</h3><div>It is widely acknowledged that dietary habits have profound impacts on human health and diseases. As the most important sweeteners and energy sources in human diets, hexoses take part in a broad range of physiopathological processes. In recent years, emerging evidence has uncovered the crucial roles of hexoses, such as glucose, fructose, mannose, and galactose, in controlling the differentiation or function of immune cells.</div></div><div><h3>Aim of Review</h3><div>Herein, we reviewed the latest research progresses in the hexose-mediated modulation of immune responses, provided in-depth analyses of the underlying mechanisms, and discussed the unresolved issues in this field.</div></div><div><h3>Key Scientific Concepts of Review</h3><div>Owing to their immunoregulatory effects, hexoses affect the onset and progression of various types of immune disorders, including inflammatory diseases, autoimmune diseases, and tumor immune evasion. Thus, targeting hexose metabolism is becoming a promising strategy for reversing immune abnormalities in diseases.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 361-379"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140604283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Punicalagin attenuates hyperuricemia via restoring hyperuricemia-induced renal and intestinal dysfunctions","authors":"Qing-qing Han ,&nbsp;Qi-dong Ren ,&nbsp;Xu Guo ,&nbsp;Mohamed A. Farag ,&nbsp;Yu-hong Zhang ,&nbsp;Meng-qi Zhang ,&nbsp;Ying-ying Chen ,&nbsp;Shu-tao Sun ,&nbsp;Jin-yue Sun ,&nbsp;Ning-yang Li ,&nbsp;Chao Liu","doi":"10.1016/j.jare.2024.03.029","DOIUrl":"10.1016/j.jare.2024.03.029","url":null,"abstract":"<div><h3>Introduction</h3><div>It is estimated that 90% of hyperuricemia cases are attributed to the inability to excrete uric acid (UA). The two main organs in charge of excreting UA are the kidney (70%) and intestine (30%). Previous studies have reported that punicalagin (PU) could protect against kidney and intestinal damages, which makes it a potential candidate for alleviating hyperuricemia. However, the effects and deeper action mechanisms of PU for managing hyperuricemia are still unknown.</div></div><div><h3>Objective</h3><div>To investigate the effect and action mechanisms of PU for ameliorating hyperuricemia.</div></div><div><h3>Methods</h3><div>The effects and action mechanisms of PU on hyperuricemia were assessed using a hyperuricemia mice model. Phenotypic parameters, metabolomics analysis, and 16S rRNA sequencing were applied to explore the effect and fundamental action mechanisms inside the kidney and intestine of PU for improving hyperuricemia.</div></div><div><h3>Results</h3><div>PU administration significantly decreased elevated serum uric acid (SUA) levels in hyperuricemia mice, and effectively alleviated the kidney and intestinal damage caused by hyperuricemia. In the kidney, PU down-regulated the expression of UA resorption protein URAT1 and GLUT9, while up-regulating the expression of UA excretion protein ABCG2 and OAT1 as mediated <em>via</em> the activation of MAKP/NF-κB in hyperuricemia mice. Additionally, PU attenuated renal glycometabolism disorder, which contributed to improving kidney dysfunction and inflammation. Similarly, PU increased UA excretion protein expression <em>via</em> inhibiting MAKP/NF-κB activation in the intestine of hyperuricemia mice. Furthermore, PU restored gut microbiota dysbiosis in hyperuricemia mice.</div></div><div><h3>Conclusion</h3><div>This research revealed the ameliorating impacts of PU on hyperuricemia by restoring kidney and intestine damage in hyperuricemia mice, and to be considered for the development of nutraceuticals used as UA-lowering agent.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 449-461"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140640594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}