MedComm最新文献

This study explored the microevolution of Shigella sonnei in China, focusing on 281 isolates exhibiting coresistance to ceftriaxone and azithromycin (cef^Razi^R) and 99 ONPG-negative isolates. Phylogenetic analysis revealed that waterborne outbreak strains, characterized by multidrug resistance (MDR) and cef^Razi^R, clustered within the predominant domestic lineage I. In contrast, sporadic MDR strains harboring a wider array of antimicrobial resistance (AMR) genes were primarily associated with lineage II. The cef^Razi^R phenotype in lineage I was mediated by an IncB/O/K/Z plasmid carrying bla_CTX-M-14, mphA, aac(3)-IId, dfrA17, aadA5, and sul1 genes. Lineage II strains acquired cef^Razi^R through a distinct IncFII plasmid possessing bla_CTX-M-15, ermB, and mphA genes, and additionally carried a separate IncB/O/K/Z plasmid backbone with bla_TEM-1, dfrA12, sul2, strA, strB, tet(A), and aac(3)-IId genes. Conversion to the ONPG-negative phenotype was linked to a deletion spanning approximately 10 kbp, which included two insertion sequences (IS1 and IS600), the mhpBAR operon, and the lacIZY operon. Genomic comparisons identified 66 SNPs and 9 accessory genes correlated with lineage II, and 23 SNPs with 9 accessory genes associated with ONPG-negative variants. Ongoing surveillance of S. sonnei epidemic clones is essential to elucidate their microevolution, track transmission, and assess public health implications.

Breast cancer is the most common cancer and the leading cause of cancer-related death among women worldwide. Advances in molecular biology, high-throughput sequencing, and integrative-omics have deepened the understanding of its heterogeneity by clarifying mechanisms linked to genetic susceptibility, epigenetic regulation, oncogenic signaling, and immune evasion. Although those developments have driven progress in targeted therapy and screening, concerns on drug resistance, toxicity, global inequities, and suboptimal risk stratification continue to limit outcomes. This review systematically summarizes current advances across four interconnected areas of breast cancer research and management, including molecular pathogenesis, targeted therapy, screening, and prevention. It describes key biological processes that shape tumor heterogeneity and examines targeted therapies, including endocrine agents, HER2-directed drugs, CDK4/6 and PI3K/AKT/mTOR inhibitors, antibody–drug conjugates, and immunotherapies, together with mechanisms of resistance and emerging treatment targets. It also evaluates evolving approaches in risk stratification and screening, highlighting progress in digital breast tomosynthesis, magnetic resonance imaging, contrast-enhanced mammography, and artificial intelligence-assisted interpretation. By integrating cutting-edge molecular insights with clinical advances, this review further highlights the expanding opportunities for personalized therapy and precision prevention. It outlines future directions linking multiomics and artificial intelligence to more equitable and effective breast cancer management.

Ischemic heart disease is one of the diseases with the highest morbidity and mortality in the world. The N⁷-methylguanosine (m⁷G) tRNA modifications are widely recognized as one of the most prevalent tRNA modifications. Nevertheless, there is still a lack of understanding regarding the roles and molecular mechanisms underlying the METTL1-mediated m⁷G tRNA modification in cardiac ischemia/reperfusion (I/R) injury. METTL1 and m⁷G tRNA modification were upregulated in mice with I/R injury hearts and the plasma of patients with acute myocardial infarction. Thus, we constructed METTL1 knockout mice and found that silencing METTL1 alleviates I/R. Mechanistically, tRNA sequencing, MeRIP-m⁷G-tRNA sequencing, and Ribosome profiling sequencing were used to clarify deficiency of METTL1 reduced the levels of m⁷G tRNA modifications and m⁷G-modified tRNAs, and consequently, downregulated the translation efficiency of ATPIF1 mRNA to restore the level of mitochondrial oxidative phosphorylation and suppress the increase of mitochondrial apoptosis. Moreover, cardiac-specific overexpression of ATPIF1 induced myocardial hypertrophy and inhibited the protective effect of silencing METTL1 on cardiac I/R injury. Collectively, m⁷G tRNA modifications regulate the translation efficiency of ATPIF1, which eventually mediates mitochondrial energy metabolism, apoptosis, and myocardial I/R injury. The findings uncover that interfering with METTL1 and ATPIF1 represents a novel therapeutic target in myocardial I/R injury.

Cancer and tissue regeneration pose great challenges to global health, as cancer treatment is impeded by tumor heterogeneity and therapy resistance, while regenerative medicine is constrained by donor shortages and difficulties in replicating native tissue structures. Organoids, as advanced three-dimensional multicellular structures derived from stem cells, have emerged as transformative tools in biomedical research. They recapitulate key aspects of native human tissue composition and functions, offering enhanced physiological relevance over traditional models. Therefore, this review aims to highlight the latest advancements in organoid technology within the fields of cancer research and regenerative medicine. We begin by discussing the fundamental aspects of organoid generation, characterization, and application. Furthermore, recent progress in both cancer-oriented and regeneration-focused organoids is summarized, with an emphasis on their applications in disease modeling, drug screening, mechanistic analysis, and precision medicine. Based on an extensive review of the literature, the current challenges and future directions in the development and application of organoid models are discussed. As organoid technology continues to evolve, it is anticipated that more high-quality studies will further advance medical science and foster innovation in personalized therapeutics.

The clinical utility of mesenchymal stem cells (MSCs) is often limited by pulmonary entrapment and poor systemic distribution, particularly in diseases constrained by physiological barriers such as rheumatoid arthritis (RA), where joint accessibility restricts therapeutic efficacy. This study systematically compares the immunomodulatory capacity and inflammation-targeting potential of human gingiva-derived MSCs (GMSCs) and their extracellular vesicles (GMSC-EVs) in vivo. Using an experimental RA model, we demonstrate that GMSC-EVs exhibit superior tropism to inflamed joints compared to GMSCs, resulting in significantly greater amelioration of disease severity, including reduced joint swelling, bone destruction, and balanced pathogenic T-cell responses. Mechanistically, we identify C-C chemokine receptor type 2 (CCR2) as the critical molecular driver of this targeted homing. Genetic ablation of CCR2 via CRISPR-Cas9/sgRNA knockdown abolishes both the joint-specific accumulation of GMSC-EVs and their therapeutic efficacy. These findings elucidate the molecular basis for GMSC-EVs tropism to arthritic lesions and establish CCR2 as a pivotal target for developing precision-engineered EVs therapies with enhanced specificity for RA treatment.

Organoid technology has become among the most popular technologies in recent years, due to their three-dimensional and physiologically enriching models that closely mimic the structure and function of human organs. Herein, this review details the in-depth methodology, updated to date, for the efficient cultivation of organoids. Emphasizing liver organoids, both hepatocyte and cholangiocyte derived, and other abdominal organ systems, such as gut, kidney, and pancreas, we explore the technological challenges researchers are facing nowadays, including how to optimize nutrient delivery, maintain cellular diversity, achieve scalability in the organoid culture system, and high-throughput applications. Addressing those biological and technological complexities, this review aimed at equipping new researchers with practical insights and standardized protocols that will help improve reproducibility and success rates in organoid culture and expand their applications. Furthermore, we discuss current limitations and barriers to clinical translation, highlight key knowledge gaps, and outline emerging innovations, including bioengineering, microfluidic systems, and genetic manipulation, expected to further enhance disease modeling, personalized medicine, and regenerative therapies. Finally, we provide perspective on next-generation technologies that expedite organoid-based discovery and development.

Li W, Yang C, Cheng Z, et al., “Gallium complex K6 inhibits colorectal cancer by increasing ROS levels to induce DNA damage and enhance phosphatase and tensin homolog activity.” MedComm. (2024);5:e665. doi: 10.1002/mco2.665

In the process of checking the raw data [1], the authors noticed an inadvertent mistake occurring in Figure 3B that needed to be corrected after the online publication of the article. In paragraph 3 of the “Results” section, the image data for SW620 cells following treatment with L-OHP (8 µM) orK6 (8 µM) for 2 h in Figure 3B was incorrect and has been replaced with the correct images. The corrected result is shown below.

The authors apologize for this error and declare that this correction does not affect the description, interpretation, or conclusions.

1. Li W, Yang C, Cheng Z, et al., “Gallium complex K6 inhibits colorectal cancer by increasing ROS levels to induce DNA damage and enhance phosphatase and tensin homolog activity.” MedComm (2020). 2024 Jul 24;5(8):e665. https://doi.org/10.1002/mco2.665.

Reproductive toxicity testing is essential for evaluating whether xenobiotics, including pharmaceuticals, environmental chemicals, or ionizing radiation, adversely affect reproductive function. However, conventional assessments rely on mating outcomes or histopathology, which are labor-intensive, variable, and require large numbers of animals. Acrosin, a serine protease encoded by the Acr gene and localized in the acrosome of spermatozoa, plays a critical role in sperm penetration of the zona pellucida. To exploit this germ cell-specific expression, we generated a genetically engineered mouse model in which the Luciferase (Luc) reporter gene is driven by the Acr promoter. This Acr-Luc knock-in (KI) model enables longitudinal and quantitative imaging of spermatogenesis using bioluminescence. We demonstrate that this platform captures radiation-induced impairments in male fertility in real time, eliminating the need for terminal analyses. By allowing repeated evaluation within the same individuals, our approach reduces interindividual variability and enables a substantial reduction in animal use, aligning with the “Reduction” principle of the 3Rs. Moreover, it reveals both the onset and recovery phases of spermatogenic disruption with high temporal resolution. The Acr-Luc KI model provides a reliable preclinical platform for reproductive toxicity testing and offers broad utility for studies in reproductive biology, toxicology, and oncofertility research.

Immunomodulatory therapies demonstrate variable efficacy in sepsis, suggesting biological heterogeneity inadequately captured by current stratification approaches. Although lymphopenia predicts mortality, functional thresholds and their interaction with inflammation remain poorly characterized. We investigated whether integrating lymphocyte status with systemic inflammation defines sepsis endotypes with differential treatment responsiveness. We retrospectively profiled 714 patients within 24 h using lymphocyte subsets and inflammatory biomarkers. Restricted cubic spline analysis revealed nonlinear associations between lymphocyte counts and mortality (p < 0.01), with steep risk increases at lower counts. Risk optimization identified critical thresholds at 374 cells/µL (total T cells), 340 cells/µL (CD4⁺), and 157 cells/µL (CD8⁺). Principal component analysis of inflammatory markers combined with lymphocyte stratification classified patients into four discrete endotypes with markedly divergent 28-day survival (55%–58% vs. 82–87%, p < 0.001). Patients with immunosuppressed/hypo-inflammatory endotype had higher survival among those who received corticosteroids (CD4⁺-depleted: 84.4% vs. 75.6%, p < 0.001; T-cell-depleted: 78.7% vs. 72.3%, p = 0.006), whereas hyperinflammatory endotypes showed no such association. Integration of publicly available single-cell (GSE167363) and bulk transcriptomics (GSE65682) datasets yielded a 15-gene T-cell dysfunction signature with external validation (CNP0004962, area under the curve [AUC] 0.76–0.85). These observational findings suggest that immune-inflammatory co-profiling identifies biologically distinct sepsis subgroups with differential treatment associations, generating testable hypotheses for prospective validation through endotype-guided trials.

The authors apologize for this error.