Journal of Advanced Research最新文献

{"title":"Small-molecule targeting BCAT1-mediated BCAA metabolism inhibits the activation of SHOC2-RAS-ERK to induce apoptosis of Triple-negative breast cancer cells","authors":"Ling Huang, Guanjun Li, Ying Zhang, Ruishen Zhuge, Shijie Qin, Jinjun Qian, Ruixing Chen, Yin Kwan Wong, Huan Tang, Peili Wang, Wei Xiao, Jigang Wang","doi":"10.1016/j.jare.2024.10.021","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.021","url":null,"abstract":"<h3>Introduction</h3>Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer with the worst prognosis. Exploring novel carcinogenic factors and therapeutic drugs for TNBC remains a focus to improve prognosis. Branched-chain amino acid transaminase 1 (BCAT1), a crucial enzyme in branched-chain amino acid (BCAA) metabolism, has been linked to various tumor developments, but its carcinogenic function and mechanism in TNBC remain unclear. Eupalinolide B (EB) is a naturally-derived small-molecule with anti-tumor activity, but its role in TNBC remains unknown.<h3>Objectives</h3>By exploring the targets and pharmacological mechanisms of EB in inhibiting TNBC, this study aimed to discover novel therapeutic targets and potential inhibitors for TNBC, and elucidate novel pathogenic mechanisms of TNBC.<h3>Methods</h3>The inhibitory effect of EB on TNBC was investigated using mouse models and cellular phenotypic experiments. Activity-based protein profiling (ABPP) technology, pull down-WB, CETSA-WB and MST were utilized to discover and validate the targets of EB. The oncogenic role of BCAT1 was determined through clinical data analysis and biochemical experiments. To elucidate the mechanism by which EB inhibited TNBC, many methods, including but not limited to HPLC and proteomic sequencing were used.<h3>Results</h3>We found that EB significantly inhibited TNBC progression. We identified BCAT1 as the direct target of EB and confirmed that BCAT1 was critical for TNBC development. EB inhibited BCAT1-involved BCAA metabolism to reduce the synthesis of BCAAs (including Leu, Ile, and Val), thereby inhibiting SHOC2 (a Leu-rich repeat protein) expression and the downstream SHOC2-participating RAS-ERK signaling pathway, ultimately leading to apoptosis of TNBC cells.<h3>Conclusion</h3>Collectively, this study not only elucidates the oncogenic role of BCAT1 and its downstream SHOC2-RAS-ERK signaling axis in TNBC progression but also opens up avenues for potential therapies targeting BCAT1 or BCAA metabolism (using EB alone or in combination with its inhibitor candesartan) for TNBC treatment.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"61 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519534","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":"Multiple roles of p53 in cancer development: Regulation of tumor microenvironment, m6A modification and diverse cell death mechanisms","authors":"Xiangyu Wang, Jianhua Yang, Wanting Yang, Haiyang Sheng, Buyun Jia, Peng Cheng, Shanshan Xu, Xinhui Hong, Chuanwei Jiang, Yinfeng Yang, Ziyin Wu, Jinghui Wang","doi":"10.1016/j.jare.2024.10.026","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.026","url":null,"abstract":"<h3>Background</h3>The protein p53, encoded by the most frequently mutated gene TP53 in human cancers, has diverse functions in tumor suppression. As a best known transcription factor, p53 can regulate various fundamental cellular responses, ranging from the cell-cycle arrest, DNA repair, senescence to the programmed cell death (PCD), which includes autophagy, apoptosis, ferroptosis, cuproptosis, pyroptosis and disulfidoptosis. Accumulating evidence has indicated that the tumor microenvironment (TME), N⁶-methyladenosine (m⁶A) modification and diverse PCD are important for the progression, proliferation and metastases of cancers.<h3>Aim of review</h3>This paper aims to systematically and comprehensively summarize the multiple roles of p53 in the development of cancers from the regulation of TME, m⁶A Modification and diverse PCD.<h3>Key scientific concepts of review</h3>TME, a crucial local homeostasis environment, influences every step of tumorigenesis and metastasis. m⁶A, the most prevalent and abundant endogenous modification in eukaryotic RNAs, plays an essential role in various biological processes, containing the progression of cancers. Additionally, PCD is an evolutionarily conserved mechanism of cell suicide and a common process in living organisms. Some forms of PCD contribute to the occurrence and development of cancer. However, the complex roles of p53 within the TME, m⁶A modification and diverse PCD mechanisms are still not completely understood. Presently, the function roles of p53 including the wild-type and mutant p53 in different context are summarized. Additionally, the interaction between the cancer immunity, cancer cell death and RNA m⁶A methylation and the p53 regulation during the development and progress of cancers were discussed. Moreover, the key molecular mechanisms by which p53 participates in the regulation of TME, m⁶A and diverse PCD are also explored. All the findings will facilitate the development of novel therapeutic approaches.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"31 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519575","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":"Plasma proteomic profiles reveal proteins and three characteristic patterns associated with osteoporosis: A prospective cohort study","authors":"Yi Zheng, Jincheng Li, Yucan Li, Jiacheng Wang, Chen Suo, Yanfeng Jiang, Li Jin, Kelin Xu, Xingdong Chen","doi":"10.1016/j.jare.2024.10.019","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.019","url":null,"abstract":"<h3>Introduction</h3>Exploration of plasma proteins associated with osteoporosis can offer insights into its pathological development, identify novel biomarkers for screening high-risk populations, and facilitate the discovery of effective therapeutic targets.<h3>Objectives</h3>The present study aimed to identify potential proteins associated with osteoporosis and to explore the underlying mechanisms from a proteomic perspective.<h3>Methods</h3>The study included 42,325 participants without osteoporosis in the UK Biobank (UKB), of whom 1,477 developed osteoporosis during the follow-up. We used Cox regression and Mendelian randomization analysis to examine the association between plasma proteins and osteoporosis. Machine learning was utilized to explore proteins with strong predictive power for osteoporosis risk.<h3>Results</h3>Of 2,919 plasma proteins, we identified 134 significantly associated with osteoporosis, with sclerostin (SOST), adiponectin (ADIPOQ), and creatine kinase B-type (CKB) exhibiting strong associations. Twelve of these proteins showed significant associations with bone mineral density (BMD) T-score at the femoral neck, lumbar spine, and total body. Mendelian randomization further supported causal relationships between 17 plasma proteins and osteoporosis. Moreover, follitropin subunit beta (FSHB), SOST, and ADIPOQ demonstrated high importance in predictive modeling. Utilizing a predictive model built with 10 proteins, we achieved relatively accurate prediction of osteoporosis onset up to 5 years in advance (AUC = 0.803). Finally, we identified three osteoporosis-related protein modules associated with immunity, lipid metabolism, and follicle-stimulating hormone (FSH) regulation from a network perspective, elucidating their mediating roles between various risk factors (smoking, sleep, physical activity, polygenic risk score (PRS), and menopause) and osteoporosis.<h3>Conclusion</h3>We identified several proteins associated with osteoporosis and highlighted the role of plasma proteins in influencing its progression through three primary pathways: immunity, lipid metabolism, and FSH regulation. This provides further insights into the distinct molecular patterns and pathogenesis of bone loss and may contribute to strengthening early diagnosis and long-term monitoring of the condition.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"26 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520224","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":"Chromosome-scale assembly with improved annotation provides insights into breed-wide genomic structure and diversity in domestic cats","authors":"Yuki Matsumoto, Claire Yik-Lok Chung, Sachiko Isobe, Mika Sakamoto, Xiao Lin, Ting-Fung Chan, Hideki Hirakawa, Genki Ishihara, Hon-Ming Lam, Shinobu Nakayama, Shigemi Sasamoto, Yasuhiro Tanizawa, Akiko Watanabe, Kei Watanabe, Masaru Yagura, Yoshihito Niimura, Yasukazu Nakamura","doi":"10.1016/j.jare.2024.10.023","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.023","url":null,"abstract":"<h3>Introduction</h3>Comprehensive genomic resources offer insights into biological features, including traits/disease-related genetic loci. The current reference genome assembly for the domestic cat (<em>Felis catus</em>), Felis_Catus_9.0 (felCat9), derived from sequences of the Abyssinian cat, may inadequately represent the general cat population, limiting the extent of deducible genetic variations.<h3>Objectives</h3>The goal was to develop Anicom American Shorthair 1.0 (AnAms1.0), a reference-grade chromosome-scale cat genome assembly.<h3>Methods</h3>In contrast to prior assemblies relying on Abyssinian cat sequences, AnAms1.0 was constructed from the sequences of the phylogenetically distant and more popular American Shorthair breed, which is related to more breeds than the Abyssinian cat. By combining advanced genomics technologies, including PacBio long-read sequencing and Hi-C- and optical mapping data-based sequence scaffolding, we compared AnAms1.0 to existing Felidae genome assemblies (20 scaffolds, scaffolds N50 &gt; 150 Mbp). Homology-based and <em>ab initio</em> gene annotation through Iso-Seq and RNA-seq was used to identify new coding genes and structural variations.<h3>Results</h3>AnAms1.0 demonstrated superior contiguity and accuracy than existing Felidae genome assemblies. Using AnAms1.0, we identified over 1.5 thousand structural variations and 29 million repetitions compared to felCat9. Additionally, we identified &gt; 1,800 novel protein-coding genes and structural variants. Notably, olfactory receptor structural variants and cardiomyopathy-related variants were identified.<h3>Conclusion</h3>AnAms1.0 facilitates the discovery of novel genes related to normal and disease phenotypes in domestic cats. The analyzed data are publicly accessible on Cats-I (<span><span>https://cat.annotation.jp/</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>), which we established as a platform for accumulating and sharing genomic resources to discover novel genetic traits and advance veterinary medicine.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"10 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520222","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":"Tailoring obeticholic acid activity by iridium(III) complex conjugation to develop a farnesoid X receptor probe","authors":"Dou Niu, Xiaolei Wu, Yuxin Zhang, Xueliang Wang, Daniel Shiu-Hin Chan, Shaozhen Jing, Chun-Yuen Wong, Wanhe Wang, Chung-Hang Leung","doi":"10.1016/j.jare.2024.10.028","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.028","url":null,"abstract":"<h3>Introduction</h3>The farnesoid X receptor (FXR) is a crucial regulator in the intestine, maintaining bile acid homeostasis. Inhibiting intestinal FXR shows promise in managing inflammatory bowel and liver diseases by reducing bile acid accumulation. Additionally, changes in FXR expression could serve as a potential biomarker for intestinal diseases. Therefore, developing an imaging probe for FXR holds significant potential for the early detection, simultaneous treatment, and monitoring of FXR-related diseases.<h3>Objectives</h3>The study aimed to develop a bioimaging probe for FXR by conjugating obeticholic acid (OCA), an FXR agonist, to an iridium(III) complex, and to investigate its application for targeting FXR in intestinal cells.<h3>Methods</h3>OCA was conjugated to an iridium(III) complex to generate the novel complex <strong>1</strong>. The effect of complex <strong>1</strong> on FXR activity, nuclear translocation, and downstream targets was investigated in intestinal epithelial cells using various biochemical and cellular assays. Additionally, the photophysical properties of complex <strong>1</strong> were assessed for FXR imaging.<h3>Results</h3>Complex <strong>1</strong> retained the desirable photophysical properties for monitoring FXR in intestinal cells while reversing OCA’s activity from agonistic to antagonistic. It disrupted FXR-RXR heterodimerization, inhibited FXR nuclear translocation, and downregulated downstream targets responsible for bile acid absorption, transport, and metabolism in intestinal epithelial cells.<h3>Conclusion</h3>The study successfully developed an imaging probe and modulator of FXR by conjugating OCA to an iridium(III) complex. Complex <strong>1</strong> retained the favorable photophysical properties of the iridium(III) complex, while reversing OCA’s activity from agonistic to antagonistic. The findings highlight the exciting application of using metals to tailor the activity of nuclear receptor modulators in living systems.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"3 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520223","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":"Impaired stemness in aging periodontal ligament stem cells is mediated by the progerin/endoplasmic reticulum stress/p53 axis","authors":"Xige Zhang, Yazheng Wang, Jinjin Wang, Yang Zhang, Rui Li, Xiaoyu Wang, Xiaotong Ge, Qingyuan Ye, Jiyun Ji, Dongdong Fei, Qintao Wang","doi":"10.1016/j.jare.2024.10.029","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.029","url":null,"abstract":"<h3>Introduction</h3>Decreased periodontal ligament stem cells (PDLSCs) stemness is a key factor in age-related alveolar bone loss. Endoplasmic reticulum (ER) stress is closely related to age-related diseases and the mesenchymal stem cell (MSC) stemness. However, the role of ER stress in regulating the stemness of senescent PDLSCs and its potential mechanism remain unclear.<h3>Objectives</h3>To investigate the detailed effect and mechanism of ER stress on impaired stemness in old periodontal ligament stem cells (OPDLSCs).<h3>Methods</h3>The level of ER stress of Young PDLSCs (YPDLSCs) and OPDLSCs were detected, and ER stress was regulated to observe its effect on PDLSCs stemness. The expression levels of ER stress sensors (protein kinase R-like ER kinase (PERK), activating transcription factor 6 (ATF6), inositol requiring enzyme 1 (IRE1)) were upregulated in YPDLSCs and downregulated in OPDLSCs by transfection experiments to verify the detailed unfolded protein response (UPR) pathway. Mechanismly, the regulatory effect of UPR pathway on p53/p21 pathway was explored. Further study was performed to investigated the important role of progerin accumulation during aging process on ER stress, UPR and p53/p21 pathway.<h3>Results</h3>Decreased stemness and ER stress activation were found in OPDLSCs. ER stress activation resulted in decreased stemness of YPDLSCs, while ER stress inhibition rescued compromised stemness of OPDLSCs. Mechanismly, ATF6 pathway regulated the OPDLSC stemness via the p53/p21 signaling as confirmed by transfection assay. Further study showed that progerin was accumulated in PDLSCs and progerin overexpression could resulted in ER stress activation, activating the ATF6/p53/p21 axis, leading to decreased stemness of aging PDLSCs.<h3>Conclusions</h3>Progerin accumulation during the aging process can lead to ER stress activation, which can suppress OPDLSC stemness via the ATF6/p53/p21 axis.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"12 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519536","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":"Dihydrokoumine, a dual-target analgesic with reduced side effects isolated from a traditional Chinese medicine","authors":"Dian Liu, Jixia Wang, Tao Hou, Yan Zhang, Han Zhou, Yaopeng Zhao, Liangliang Zhou, Cuiyan Cao, Yanfang Liu, Xinmiao Liang","doi":"10.1016/j.jare.2024.10.011","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.011","url":null,"abstract":"<h3>Introduction</h3>Opioids are the most common antinociceptive drugs, but long-term administration causes serious adverse side effects. <em>Gelsemium elegans</em> Benth. is traditionally used as an analgesic agent and mainly contains indole alkaloids with structures different from those in common opioids, indicating distinct pharmacological properties. This work aims to find a new analgesic from <em>Gelsemium elegans</em> Benth. and evaluate it <em>in vitro</em> and <em>in vivo</em>.<h3>Methods</h3>Dihydrokoumine was purified from <em>Gelsemium elegans</em> Benth. Binding to mu opioid receptor (MOR), M3 receptor (M3R) and other 15 G protein-coupled receptors were evaluated <em>in vitro</em> combined with molecular docking analysis. Analgesic efficacy and side effects were measured <em>in vivo</em> using hot-plate, formalin paw, and rotarod tests in mice. Cytotoxicity, acute toxicity in mice and pharmacokinetics were assessed.<h3>Results</h3>A MOR agonist, dihydrokoumine, was first identified from <em>Gelsemium elegans</em> Benth. Further investigations showed that dihydrokoumine exhibited selective partial agonist action on the MOR and antagonist action on the M3R among other 15 GPCRs. In <em>in vivo</em> mouse models, dihydrokoumine could relieve acute pain and chronic inflammatory pain without drug tolerance and sedative side effects. Additionally, we observed a good safety profile and favorable pharmacokinetic properties.<h3>Conclusion</h3>A MOR partial agonist/M3R antagonist analgesic with reduced side effects was isolated from a traditional Chinese medicine. This study bestows dihydrokoumine as a new dual-target analgesic and as a potential lead compound in pain management.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"1 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489284","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":"Neural and molecular investigation into the paraventricular thalamus for chronic restraint stress induced depressive-like behaviors","authors":"Yong He, Yikun Ren, Xiangyu Chen, Yue Wang, Heming Yu, Junchao Cai, Peng Wang, Yi Ren, Peng Xie","doi":"10.1016/j.jare.2024.10.025","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.025","url":null,"abstract":"<h3>Introduction</h3>Disturbance of neural circuits and chronic stress contribute to depression onset. Given the crucial role of paraventricular nucleus of thalamus (PVT) in emotional behaviors, however, the specific neural and molecular mechanism of PVT in depression still unclear.<h3>Objective</h3>Our study aim to explore the neural and molecular mechanism of PVT in depression.<h3>Methods</h3>In the present study, we utilize behavioral tests,chemogenetics, RNA-sequence, molecular profiling and pharmacological approaches to investigate the role of PVT in depression.<h3>Results</h3>We observed that CamkIIα neurons in PVT were inactivated by chronic restraint stress (CRS) with reduced c-Fos positive neurons. Activation of PVT^CamkIIα neurons displayed antidepressant-like effect in both naive and CRS mice, whereas inhibition or ablation of these neurons is sufficient to trigger depressive-like behaviors. Moreover, we found that activating PVT → Nucleus accumbens (NAc) circuit attenuated depressive-like behaviors induced by CRS, while inhibiting this circuit directly caused behavioral deficits in mice. Intriguingly, artificially enhancing PVT → Central amygdala (CeA) pathway failed to alleviate depressive-like behaviors. Importantly, increased expression of neuropeptide Y (NPY) and depressive-like behaviors induced by CRS could be ameliorated via antidepressant treatment, manipulation of PVT^CamkIIα neurons (or PVT → NAc circuit) and NPY inhibitor.<h3>Conclusion</h3>Taken together, our study uncovered that PVT regulated depressive-like behaviors via PVT → NAc circuit together with NPY, thus shedding light on potential target for preventing depression and promoting clinical translation.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"17 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487540","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":"Roles of oral and gut microbiota in acute myocardial infarction","authors":"Yu-Lin Li, Bo-Yan Chen, Ze-Hao Feng, Lu-Jun Zhou, Ting Liu, Wen-Zhen Lin, Hong Zhu, Shuo Xu, Xue-Bing Bai, Xiao-Qian Meng, Jun Zhang, Yan Liu, Jun Pu, Meng Jiang, Sheng-Zhong Duan","doi":"10.1016/j.jare.2024.10.009","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.009","url":null,"abstract":"<h3>Introduction</h3>The significance of oral/gut microbiota in acute myocardial infarction (AMI) has been increasingly appreciated. However, correlations between oral/gut microbiota and AMI parameter, as well as the key microbiota that may have a crucial function in this process, remain unclear.<h3>Objectives</h3>To investigate the composition and structure of oral and gut microbiota associated with AMI and explore the roles of specific bacterial species in the progression of AMI.<h3>Methods</h3>We conducted a case-control study with 37 AMI patients and 36 controls. Oral and gut sample were collected and sequenced. Using correlation analysis, we combined bioinformatics data with AMI clinical parameters and obtained heatmaps of correlation coefficients. Additionally, we used antibiotics to eliminate the gut microbiota of C57BL/6J mice, followed by the transplantation of selected bacteria to verify the gut colonization of oral bacteria and their impact on AMI.<h3>Results</h3>The component of oral and gut microbiota of AMI group showed significant alterations when compared to the control group. 17 salivary genera, 21 subgingival genera, and 8 gut genera in AMI group substantially differed from those in control group. Additionally, 19 genera from saliva, 19 genera from subgingival plaque, and 11 genera from feces substantially correlated with AMI clinical parameters. Orally administrated S.o (<em>Streptococcus oralis</em> subsp. <em>dentisani</em>), S.p (<em>Streptococcus parasanguinis</em>), and S.s (<em>Streptococcus salivarius</em>) were able to colonize in the gut and exacerbate myocardial infarction.<h3>Conclusion</h3>There is a strong correlation between oral/gut microbiota and AMI. <em>Streptococcus</em> spp. is capable to transmit from oral to gut and exacerbate myocardial infarction in mice. Monitoring and control of specific oral microbiota may be an effective new strategy for improving the therapy of AMI.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"67 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487108","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":"Regulatory balance between ear rot resistance and grain yield and their breeding applications in maize and other crops","authors":"Zechao Yin, Xun Wei, Yanyong Cao, Zhenying Dong, Yan Long, Xiangyuan Wan","doi":"10.1016/j.jare.2024.10.024","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.024","url":null,"abstract":"<h3>Background</h3>Fungi are prevalent pathogens that cause substantial yield losses of major crops. Ear rot (ER), which is primarily induced by <em>Fusarium</em> or <em>Aspergillus</em> species, poses a significant challenge to maize production worldwide. ER resistance is regulated by several small effect quantitative trait loci (QTLs). To date, only a few ER-related genes have been identified that impede molecular breeding efforts to breed ER-resistant maize varieties.<h3>Aim</h3><strong><em>of review:</em></strong> Our aim here is to explore the research progress and mine genic resources related to ER resistance, and to propose a regulatory model elucidating the ER-resistant mechanism in maize as well as a trade-off model illustrating how crops balance fungal resistance and grain yield.<strong><em>Key Scientific Concepts of Review:</em></strong> This review presents a comprehensive bibliometric analysis of the research history and current trends in the genetic and molecular regulation underlying ER resistance in maize. Moreover, we analyzed and discovered the genic resources by identifying 162 environmentally stable loci (ESLs) from various independent forward genetics studies as well as 1391 conservatively differentially expressed genes (DEGs) that respond to <em>Fusarium</em> or <em>Aspergillus</em> infection through multi-omics data analysis. Additionally, this review discusses the syntenies found among maize ER, wheat <em>Fusarium</em> <!-- -->head blight (FHB), and rice Bakanae<!-- --> <!-- -->disease (RBD) resistance-related loci, along with the significant overlap between fungal resistance loci and reported yield-related loci, thus providing valuable insights into the regulatory mechanisms underlying the trade-offs between yield and defense in crops.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"25 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487105","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}