MedComm最新文献

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.

Melanoma is the most aggressive skin malignant tumor, typically exhibiting a high mutation burden and potentially harboring mutations in NRAS, BRAF, or NF1. To enhance survival rates, these driver alterations can achieve significant antitumor activity through targeted therapy. In the past decade, BRAF inhibitors combined with MEK inhibitors significantly improved the prognosis of BRAF mutation melanoma. Nevertheless, researchers have attempted various strategies to block the NRAS signaling pathway, NRAS mutation in melanoma is still considered to be untargetable. In recent years, MEK inhibitors like binimetinib and tunlametinib have displayed the efficacy for NRAS^mut melanoma, with tunlametinib being the first and only approved MEK inhibitor for advanced NRAS^mut melanoma. On the other hand, immune checkpoint inhibitors including PD-1/PD-L1 inhibitors and cytotoxic T-lymphocyte antigen 4 （CTLA-4） inhibitors changed the treatment landscape of advanced melanoma. In this review, we have summarized the current knowledge of molecular pathogenesis and classification of melanoma. Subsequently, we explored current and potential treatment approaches for melanoma, primarily encompassing BRAF inhibitors, MEK inhibitors, and immunotherapy, with a particular focus on their clinical relevance of development. Finally, the challenges in the treatment of melanoma, particularly in immunotherapy and targeted therapy, are summarized and discussed.

Myocardial ischemia-reperfusion (MIR) injury is a major cause of cardiac dysfunction, but the spatial heterogeneity of its underlying molecular programs remains unclear. In this study, we applied Visium spatial transcriptomics to generate gene expression maps of rat left ventricles after MIR and identified distinct regional features. The border zones were enriched with phagosome-related genes, incomplete infarct areas showed activation of MAPK, IL-17, and osteoclast differentiation pathways, while the infarct cores were characterized by ferroptosis and mitophagy-related genes. To further resolve the cellular basis, we integrated single-cell RNA sequencing with RCTD deconvolution and found immune cell infiltration in infarct zones, neutrophil enrichment in incomplete infarct areas, and smooth muscle cell predominance in border zones. Both spatial and single-cell analyses revealed altered expression of Piezo1, RyR2, MMP2, and SERCA2, which was further validated by Western blot and immunofluorescence co-staining with ACTN2. Pseudotime analysis demonstrated selective enrichment and dynamic activation of Piezo1 in specific cardiomyocyte subclusters. Functional validation using a hypoxia/reoxygenation model confirmed that reoxygenation induced marked intracellular Ca²⁺ accumulation, which was attenuated by the Piezo1 inhibitor GsMTx4. Together, these findings delineate the spatial heterogeneity of MIR injury, identify Piezo1 as a key mediator of Ca²⁺ dysregulation, and suggest Piezo1 as a potential therapeutic target for myocardial protection.

Since 2022, mpox epidemics have been sustaining and escalating over the world, posing a significant public health challenge. While significant progress has been made in diagnostic methodologies, prophylactic vaccines, and therapeutic interventions to mitigate monkeypox virus (MPXV) infection, scientific understanding of MPXV and related orthopoxviruses continues to evolve progressively. In order to keep pace with recent advancements, herein we review progress in mpox research from five key perspectives. This article first summarizes the latest epidemiological profiles, incorporating different viral lineages globally and in China, while highlighting their evolutionary history and distinct clinical characteristics. The virological profiles of MPXV shed light on its complete infectious lifecycle and the formation of distinct virus particle types. Clinically approved classical detection methods and emerging novel testing techniques are provided, establishing a framework for early diagnosis of mpox patients. The efficacy and safety of both licensed vaccines and those under development are analyzed to underscore their value in preventing mpox infection. Additionally, progress in approved and newly identified potential therapeutic agents is summarized and discussed, aiming to provide insights for further drug development and clinical treatment strategies.

Aberrant deposition of β-amyloid (Aβ) and hyperphosphorylated tau, along with neuroinflammation, are key drivers of Alzheimer's disease (AD) pathology. Here, we identify ramalin, a natural antioxidant, as a promising therapeutic agent that alleviates AD pathology by modulating β-site APP cleaving enzyme 1 (BACE1), histone deacetylase 6 (HDAC6), and the mitogen-activated protein kinases (MAPK) pathway. Ramalin reduced BACE1 protein levels, independently of its transcription, translation, or enzymatic activity, an effect mediated by inhibition of HDAC6. Consistently, HDAC6 knockout similarly decreased BACE1 levels, highlighting HDAC6 as a key regulator of BACE1. Ramalin further suppressed neuroinflammatory responses by downregulating inducible nitric oxide synthase (iNOS) and the NLR family pyrin domain containing 3 (NLRP3) inflammasome. In AD mouse models, ramalin treatment significantly attenuated neuroinflammation, Aβ plaque burden, and tau hyperphosphorylation, while improving cognitive performance. Notably, ramalin reversed Aβ oligomer-induced synaptic transmission impairment and restored synaptic vesicle recycling in hippocampal neurons. Transcriptomic analysis identified modulation of the MAPK pathway, with reduced phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) implicated in tau pathology. These findings establish ramalin as a disease-modifying intervention that provides neuroprotection through concurrent regulation of BACE1, HDAC6, and MAPK signaling pathway. Collectively, our findings highlight ramalin as a compelling disease-modifying candidate with the potential to drive a breakthrough approach targeting AD pathology.