Journal of Biomedical Science最新文献

{"title":"Mitophagy is required to protect against excessive skeletal muscle atrophy following hindlimb immobilization.","authors":"Fasih A Rahman, Mackenzie Q Graham, Amanda M Adam, Emma S Juracic, A Russell Tupling, Joe Quadrilatero","doi":"10.1186/s12929-025-01118-w","DOIUrl":"10.1186/s12929-025-01118-w","url":null,"abstract":"<p><strong>Background: </strong>Skeletal muscle atrophy involves significant remodeling of fibers and is characterized by deficits in mitochondrial content and function. These changes are intimately connected to shifts in mitochondrial turnover, encompassing processes such as mitophagy and mitochondrial biogenesis. However, the role of these mitochondrial turnover processes in muscle atrophy remains poorly understood.</p><p><strong>Methods: </strong>We used a novel mitophagy reporter model, mt-Keima mice, to perform hindlimb immobilization and accurately measure mitophagy. A comprehensive set of analyses were conducted to investigate biochemical and molecular changes at the muscle and mitochondrial levels. We also performed image analyses to determine mitophagic flux. To further explore the role of mitophagy in immobilization-induced atrophy, we treated animals with N-acetylcysteine (NAC; 150 mg/kg/day) to modify reactive oxygen species (ROS) signaling and colchicine (0.4 mg/kg/day) to inhibit autophagy.</p><p><strong>Results: </strong>Our study revealed that hindlimb immobilization leads to muscle weakness and atrophy of fast-twitch muscle fibers (types IIA, IIX, and IIB), with recovery observed in IIA fibers following remobilization. This atrophy was accompanied by a significant increase in mitophagic flux. Additionally, immobilization induced notable mitochondrial dysfunction, as shown by diminished respiration, increased mitochondrial ROS, and greater whole muscle lipid peroxidation. Treatment of immobilized mice with NAC enhanced mitochondrial respiration and reduced ROS generation but suppressed mitophagic flux and intensified atrophy of type IIX and IIB fibers. Additionally, administration of colchicine to immobilized mice suppressed mitophagic flux, which also exacerbated atrophy of IIX and IIB fibers. Colchicine treatment led to significant reductions in mitochondrial function, accompanied by CASP9 and CASP3 activation.</p><p><strong>Conclusion: </strong>These findings emphasize the role of mitophagy in limiting excessive muscle atrophy during immobilization. Targeting mitophagy may offer new strategies to preserve muscle function during prolonged periods of immobilization.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"29"},"PeriodicalIF":9.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence of population heterogeneity in Klebsiella pneumoniae with a bla_OXA-232-harboring plasmid: carbapenem resistance, virulence, and fitness.","authors":"Yun Young Cho, Sun Ju Kim, Kwan Soo Ko","doi":"10.1186/s12929-024-01108-4","DOIUrl":"10.1186/s12929-024-01108-4","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate the population heterogeneity on carbapenem susceptibility in Klebsiella pneumoniae strains that acquired a bla_OXA-232-bearing ColE-type plasmid.</p><p><strong>Methods: </strong>A bla_OXA-232-bearing plasmid was electroporated into two carbapenem-susceptible K. pneumoniae strains. High- and low-carbapenem-resistant subpopulations were identified and isolated using patch plating. The strains were subsequently subcultured in antibiotic-free media, yielding two distinct populations: a stable, high-level carbapenem-resistant strains and a heterogeneous strains. Antibiotic susceptibility tests, time-killing assays, and population profiles were conducted, along with a competition assay was performed and the growth curve analysis. To assess virulence, we performed human serum resistance and Galleria mellonella infection assays, and measured the expression of virulence genes using qRT-PCR. Additionally, whole genome sequencing was carried out for further anaysis.</p><p><strong>Results: </strong>Introduction of pOXA-232 into carbapenem-susceptible K. pneumoniae strains resulted in two isogenic transformants with distinct resistance profiles: an unstable, high-level carbapenem-resistant (HCR), and highly virulent subpopulation; and a stable, low-level carbapenem-resistant (LCR), and low-virulence subpopulation. Whole genome and expression analyses revealed dysfunctionality of ompK36 in HCR subpopulations. Subculturing of HCR led to the re-emergence of heterogeneous populations with variations in carbapenem resistance and an additional compensatory mutation of 9,000 bp deletion in the genome. Thus, stable HCR strains featuring both mutations in ompK36 and compensatory mutations developed.</p><p><strong>Conclusion: </strong>This study demonstrated that underlying heterogeneity can promote the emergence of stable, high-level antibiotic resistance, even with the introduction of a plasmid carrying a low-level antibiotic resistance gene, such as bla_OXA-232. This highlights the critical need to closely monitor bacterial population dynamics.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"22"},"PeriodicalIF":9.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-200c inhibition and catalase accelerate diabetic wound healing.","authors":"Marco D'Agostino, Sara Sileno, Daniela Lulli, Naomi De Luca, Claudia Scarponi, Massimo Teson, Alessio Torcinaro, Francesca De Santa, Corrado Cirielli, Sergio Furgiuele, Chris H Morrell, Elena Dellambra, Teresa Odorisio, Edward G Lakatta, Daniele Avitabile, M C Capogrossi, Alessandra Magenta","doi":"10.1186/s12929-024-01113-7","DOIUrl":"10.1186/s12929-024-01113-7","url":null,"abstract":"<p><strong>Background: </strong>Reactive oxygen species (ROS) are increased in diabetic conditions and play a causal role in diabetic foot ulcers (DFU). We previously showed that ROS up-regulate miR-200c expression, that in turns causes apoptosis, senescence, ROS upregulation and nitric oxide decrease, leading to endothelial disfunction.</p><p><strong>Methods: </strong>The aim of this study is to dissect miR-200c role in DFU and to explore the potential role of anti-miR-200c and antioxidant catalase (CAT) in promoting wound healing (WH). miR-200c inhibition and CAT treatment were performed either in immortalized keratinocytes (HaCaT) or in primary fibroblasts (FBs) and keratinocytes (KCs) deriving from diabetic patients (pts) undergoing amputations. Primary cells deriving from pts undergoing saphenectomies were used as controls. The miR-200c blockade was performed either via lentiviral particles bearing an anti-miR-200c sequence or locked nucleic acid (LNA) anti-miR-200c oligos. Equine CAT was administered on cell medium. The WH assay was performed in vivo on diabetic (db/db) mice by a topical treatment with CAT and LNA anti-miR-200c on wounds dissolved in a Pluronic gel mixture, administered every three days.</p><p><strong>Results: </strong>We found that miR-200c levels were increased by different stimuli known to induce ROS, such as ultraviolet radiation (UV), hydrogen peroxide (H₂O₂), and high glucose in HaCaT. miR-200c was also upregulated in skin biopsies, in FBs and KCs isolated from pts with DFU vs controls. Forced miR-200c expression induced ROS in both FBs and KCs, and CAT reduced it. miR-200c inhibition improved WH in HaCaT, both under basal conditions and after UV and H₂O₂ treatment, and the simultaneous treatment with CAT accelerated it. miR-200c inhibition accelerated WH in KCs of DFU pts, increasing its protein targets: sirtuin 1 (SIRT1), the transcription factors FOXO1 and ZEB1 and decreasing p66Shc phosphorylation at Ser-36, that is induced by ROS, and the co-treatment with CAT showed synergistic effects in reducing ROS and cytotoxicity. Interestingly, CAT treatment decreased miR-200c expression in FBs and KCs of DFU pts. Topical administration of anti-miR-200c and CAT in a WH model of diabetic mice accelerated closure.</p><p><strong>Conclusions: </strong>Anti-miR-200c and CAT could be considered a novel treatment for DFU and, possibly, for other types of non-diabetic skin ulcers.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"21"},"PeriodicalIF":9.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PEX11B palmitoylation couples peroxisomal dysfunction with Schwann cells fail in diabetic neuropathy.","authors":"Yu Mei Yang, Hang Bin Ma, Yue Xiong, Qian Wu, Xiu Kui Gao","doi":"10.1186/s12929-024-01115-5","DOIUrl":"10.1186/s12929-024-01115-5","url":null,"abstract":"<p><strong>Background: </strong>Diabetic neuropathy (DN) is a prevalent and painful complication of diabetes; however, the mechanisms underlying its pathogenesis remain unclear, and effective clinical treatments are lacking. This study aims to explore the role of peroxisomes in Schwann cells in DN.</p><p><strong>Methods: </strong>The abundance of peroxisomes in the sciatic nerves of mice or Schwann cells was analyzed using laser confocal super-resolution imaging and western blotting. The RFP-GFP-SKL (Ser-Lys-Leu) probe was utilized to assess pexophagy (peroxisomes autophagy) levels. To evaluate the palmitoylation of PEX11B, the acyl-resin assisted capture (acyl-RAC) assay and the Acyl-Biotin Exchange (ABE) assay were employed. Additionally, MR (Mendelian randomization) analysis was conducted to investigate the potential causal relationship between DN and MS (Multiple sclerosis).</p><p><strong>Results: </strong>There was a decrease in peroxisomal abundance in the sciatic nerves of diabetic mice, and palmitic acid (PA) induced a reduction in peroxisomal abundance by inhibiting peroxisomal biogenesis in Schwann cells. Mechanistically, PA induced the palmitoylation of PEX11B at C25 site, disrupting its self-interaction and impeding peroxisome elongation. Fenofibrate, a PPARα agonist, effectively rescued peroxisomal dysfunction caused by PA and restored the peroxisomal abundance in diabetic mice. Lastly, MR analysis indicates a notable causal influence of DN on MS, with its onset and progression intricately linked to peroxisomal dysfunction.</p><p><strong>Conclusions: </strong>Targeting the peroxisomal biogenesis pathway may be an effective strategy for preventing and treating DN, underscoring the importance of addressing MS risk at the onset of DN.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"20"},"PeriodicalIF":9.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11818136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional hyaluronic acid-based biomimetic/pH-responsive hybrid nanostructured lipid carriers for treating bacterial sepsis.","authors":"Eman Elhassan, Calvin A Omolo, Mohammed A Gafar, Eman A Ismail, Usri H Ibrahim, Rene Khan, Mathieu Lesouhaitier, Paul Kubes, Thirumala Govender","doi":"10.1186/s12929-024-01114-6","DOIUrl":"10.1186/s12929-024-01114-6","url":null,"abstract":"<p><strong>Introduction: </strong>The application of biomimetic and stimuli-responsive nanocarriers displays considerable promise in improving the management of bacterial sepsis and overcoming antimicrobial resistance. Therefore, the study aimed to synthesize a novel hyaluronic acid-lysine conjugate (HA-Lys) and to utilize the attributes of the synthesized HA-Lys with Tocopherol succinate (TS) and Oleylamine (OLA) in the formulation of multifunctional biomimetic pH-responsive HNLCs loaded with vancomycin (VCM-HNLCs), to combat bacterial sepsis.</p><p><strong>Methods: </strong>A novel hyaluronic acid-lysine conjugate (HA-Lys) was synthesized and characterized using FTIR and ¹H NMR spectroscopy. Vancomycin-loaded hybrid nanosystems (VCM-HNLCs) were prepared through hot homogenization ultrasonication and evaluated for particle size, polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE%). In vitro biocompatibility was assessed via MTT assay and red blood cell hemolysis test. The binding affinity to TLR2 and TLR4 was measured using microscale thermophoresis (MST). Drug release was evaluated using the dialysis bag method. Antimicrobial activity against MRSA and efflux pump inhibition were also determined. Efficacy was demonstrated in an MRSA-induced sepsis mice model.</p><p><strong>Results: </strong>The VCM-HNLCs, produced via hot homogenization ultrasonication, exhibited particle size (PS), polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE%) of 110.77 ± 1.692 nm, 0.113 ± 0.022, - 2.92 ± 0.210 mV, and 76.27 ± 1.200%, respectively. In vitro, biocompatibility was proven by hemolysis and cytotoxicity studies. The VCM-HNLCs demonstrated targetability to human Toll-like receptors (TLR 2 and 4) as validated by microscale thermophoresis (MST). VCM-HNLCs showed a twofold reduction in MIC values at physiological pH compared to the bare VCM against S. aureus and MRSA for 48 h. While at pH 6.0, MIC values were reduced by fourfold in the first 24 h and by eightfold in the subsequent 48 and 72 h against tested strains. Furthermore, VCM-HNLCs showed inhibitory effects against MRSA efflux pumps, reactive oxygen species (ROS), and lipopolysaccharide (LPS)-induced hyperinflammation. In an MRSA-induced sepsis mice model, VCM-HNLCs demonstrated superior efficacy compared to free VCM, significantly eliminated bacteria and improved survival rates.</p><p><strong>Conclusions: </strong>Overall, these results highlight the potential of VCM-HNLCs as novel multifunctional nanocarriers to combat antimicrobial resistance (AMR) and enhance sepsis outcomes.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"19"},"PeriodicalIF":9.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the fundamentals for tremors: the frequency and amplitude coding in essential tremor.","authors":"Ming-Kai Pan","doi":"10.1186/s12929-024-01112-8","DOIUrl":"10.1186/s12929-024-01112-8","url":null,"abstract":"<p><p>Essential tremor (ET) is one of the most common movement disorders with heterogeneous pathogenesis involving both genetic and environmental factors, which often results in variable therapeutic outcomes. Despite the diverse etiology, ET is defined by a core symptom of action tremor, an involuntary rhythmic movement that can be mathematically characterized by two parameters: tremor frequency and tremor amplitude. Recent advances in neural dynamics and clinical electrophysiology have provided valuable insights to explain how tremor frequency and amplitude are generated within the central nervous system. This review summarizes both animal and clinical evidence, encompassing the kinematic features of tremors, circuitry dynamics, and the neuronal coding mechanisms for the two parameters. Neural population coding within the olivocerebellum is implicated in determining tremor frequency, while the cerebellar circuitry synchrony and cerebellar-thalamo-cortical interactions play key roles in regulating tremor amplitude. Novel therapeutic strategies aimed at tuning tremor frequency and amplitude are also discussed. These neural dynamic approaches target the conserved mechanisms across ET patients with varying etiologies, offering the potential to develop universally effective therapies for ET.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"18"},"PeriodicalIF":9.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-initiating and metastasis-initiating cells of clear-cell renal cell carcinoma.","authors":"Dinh-Xuan Pham, Tien Hsu","doi":"10.1186/s12929-024-01111-9","DOIUrl":"10.1186/s12929-024-01111-9","url":null,"abstract":"<p><p>Clear-cell renal cell carcinoma (ccRCC) is the most common subtype of kidney malignancy. ccRCC is considered a major health concern worldwide because its numbers of incidences and deaths continue to rise and are predicted to continue rising in the foreseeable future. Therefore new strategy for early diagnosis and therapeutics for this disease is urgently needed. The discovery of cancer stem cells (CSCs) offers hope for early cancer detection and treatment. However, there has been no definitive identification of these cancer progenitors for ccRCC. A majority of ccRCC is characterized by the loss of the von Hippel-Lindau (VHL) tumor suppressor gene function. Recent advances in genome analyses of ccRCC indicate that in ccRCC, tumor-initiating cells (TICs) and metastasis-initiating cells (MICs) are two distinct groups of progenitors. MICs result from various genetic changes during subclonal evolution, while TICs reside in the stem of the ccRCC phylogenetic tree of clonal development. TICs likely originate from kidney tubule progenitor cells bearing VHL gene inactivation, including chromatin 3p loss. Recent studies also point to the importance of microenvironment reconstituted by the VHL-deficient kidney tubule cells in promoting ccRCC initiation and progression. These understandings should help define the progenitors of ccRCC and facilitate early detection and treatment of this disease.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"17"},"PeriodicalIF":9.0,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking precision medicine: clinical applications of integrating health records, genetics, and immunology through artificial intelligence.","authors":"Yi-Ming Chen, Tzu-Hung Hsiao, Ching-Heng Lin, Yang C Fann","doi":"10.1186/s12929-024-01110-w","DOIUrl":"10.1186/s12929-024-01110-w","url":null,"abstract":"<p><p>Artificial intelligence (AI) has emerged as a transformative force in precision medicine, revolutionizing the integration and analysis of health records, genetics, and immunology data. This comprehensive review explores the clinical applications of AI-driven analytics in unlocking personalized insights for patients with autoimmune rheumatic diseases. Through the synergistic approach of integrating AI across diverse data sets, clinicians gain a holistic view of patient health and potential risks. Machine learning models excel at identifying high-risk patients, predicting disease activity, and optimizing therapeutic strategies based on clinical, genomic, and immunological profiles. Deep learning techniques have significantly advanced variant calling, pathogenicity prediction, splicing analysis, and MHC-peptide binding predictions in genetics. AI-enabled immunology data analysis, including dimensionality reduction, cell population identification, and sample classification, provides unprecedented insights into complex immune responses. The review highlights real-world examples of AI-driven precision medicine platforms and clinical decision support tools in rheumatology. Evaluation of outcomes demonstrates the clinical benefits and impact of these approaches in revolutionizing patient care. However, challenges such as data quality, privacy, and clinician trust must be navigated for successful implementation. The future of precision medicine lies in the continued research, development, and clinical integration of AI-driven strategies to unlock personalized patient care and drive innovation in rheumatology.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"16"},"PeriodicalIF":9.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the G-quadruplex as a novel strategy for developing antibiotics against hypervirulent drug-resistant Staphylococcus aureus.","authors":"Maria Sultan, Maria Razzaq, Joohyun Lee, Shreyasi Das, Shrute Kannappan, Vinod Kumar Subramani, Wanki Yoo, Truc Kim, Hye-Ra Lee, Akhilesh K Chaurasia, Kyeong Kyu Kim","doi":"10.1186/s12929-024-01109-3","DOIUrl":"10.1186/s12929-024-01109-3","url":null,"abstract":"<p><strong>Background: </strong>The rapid emergence of multiple drug-resistant (MDR) bacterial pathogens and the lack of a novel antibiotic pipeline pose a serious threat to global healthcare. The limited number of established targets further restricts the identification of novel antibiotics to treat life-threatening MDR infections caused by Staphylococcus aureus strains. Therefore, novel targets for developing antibiotics are urgently required. In this study, we hypothesized that the G-quadruplex (G4)-binding ligands can be used as novel antibiotics as their binding can possibly downregulate/block the expression of vital genes.</p><p><strong>Methods: </strong>To test this, first we screened the antibiotic properties of representative G4-binding ligands against hypervirulent and MDR S. aureus USA300 and determined the in vitro and in vivo antibacterial activity; and proposed the mechanism of action by applying various microbiological, infection, microscopic, and biophysicochemical techniques.</p><p><strong>Results: </strong>Herein, among screened G4-binding ligands, N-methyl mesoporphyrin IX (NMM) showed the highest antibacterial activity against S. aureus USA300. NMM exhibited a minimum inhibitory concentration (MIC) of 5 μM against S. aureus USA300, impacting cell division and the cell wall by repressing the expressions of genes in the division cell wall (dcw) gene cluster. Genome-wide bioinformatics analysis of G4 motifs and their mapping on S. aureus genome, identified the presence of G4-motif in the promoter of mraZ, a conserved master regulator of the dcw cluster regulating the coordinated cell division and cell wall synthesis. Physicochemical assessments using UV-visible, circular dichroism, and nuclear magnetic resonance spectroscopy confirmed that the G4-motif present in the mraZ promoter formed an intramolecular parallel G4 structure, interacting with NMM. In vivo reporter followed by coupled in vitro transcription/translation (IVT) assays confirmed the role of mraZ G4 as a target interacting NMM to impose extreme antibacterial activity against both the gram-positive and -negative bacteria. In-cell and in vivo validation of NMM using RAW264.7 cells and Galleria mellonella; respectively, demonstrated that NMM exhibited superior antibiotic activity compared to well-established antibiotics, with no observed cytotoxicity.</p><p><strong>Conclusions: </strong>In summary, the current study identified NMM as a broad-spectrum potent antibacterial agent and elucidated its plausible mechanism of action primarily by targeting G4-motif in the mraZ promoter of the dcw gene cluster.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"15"},"PeriodicalIF":9.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Data Artifacts Glossary: a community-based repository for bias on health datasets.","authors":"Rodrigo R Gameiro, Naira Link Woite, Christopher M Sauer, Sicheng Hao, Chrystinne Oliveira Fernandes, Anna E Premo, Alice Rangel Teixeira, Isabelle Resli, An-Kwok Ian Wong, Leo Anthony Celi","doi":"10.1186/s12929-024-01106-6","DOIUrl":"10.1186/s12929-024-01106-6","url":null,"abstract":"<p><strong>Background: </strong>The deployment of Artificial Intelligence (AI) in healthcare has the potential to transform patient care through improved diagnostics, personalized treatment plans, and more efficient resource management. However, the effectiveness and fairness of AI are critically dependent on the data it learns from. Biased datasets can lead to AI outputs that perpetuate disparities, particularly affecting social minorities and marginalized groups.</p><p><strong>Objective: </strong>This paper introduces the \"Data Artifacts Glossary\", a dynamic, open-source framework designed to systematically document and update potential biases in healthcare datasets. The aim is to provide a comprehensive tool that enhances the transparency and accuracy of AI applications in healthcare and contributes to understanding and addressing health inequities.</p><p><strong>Methods: </strong>Utilizing a methodology inspired by the Delphi method, a diverse team of experts conducted iterative rounds of discussions and literature reviews. The team synthesized insights to develop a comprehensive list of bias categories and designed the glossary's structure. The Data Artifacts Glossary was piloted using the MIMIC-IV dataset to validate its utility and structure.</p><p><strong>Results: </strong>The Data Artifacts Glossary adopts a collaborative approach modeled on successful open-source projects like Linux and Python. Hosted on GitHub, it utilizes robust version control and collaborative features, allowing stakeholders from diverse backgrounds to contribute. Through a rigorous peer review process managed by community members, the glossary ensures the continual refinement and accuracy of its contents. The implementation of the Data Artifacts Glossary with the MIMIC-IV dataset illustrates its utility. It categorizes biases, and facilitates their identification and understanding.</p><p><strong>Conclusion: </strong>The Data Artifacts Glossary serves as a vital resource for enhancing the integrity of AI applications in healthcare by providing a mechanism to recognize and mitigate dataset biases before they impact AI outputs. It not only aids in avoiding bias in model development but also contributes to understanding and addressing the root causes of health disparities.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"14"},"PeriodicalIF":9.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}