JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Cell-Specific Signal Bias Shapes β3-Adrenoceptor Profibrotic Activation in Cardiac Fibroblasts","authors":"Ali H. Eid","doi":"10.1111/jcmm.71416","DOIUrl":"https://doi.org/10.1111/jcmm.71416","url":null,"abstract":"<p>Heart failure therapies have traditionally treated the myocardium as a functional whole. In doing so, we risk overlooking the fibroblast [<span>1</span>]. In this issue, Xu and colleagues show that β3-adrenergic receptor activation promotes a profibrotic phenotype in cardiac fibroblasts through β-arrestin2-mediated biased signalling [<span>2</span>]. The authors demonstrate that this pathway activates the JNK/c-Jun axis to upregulate TGF-β1, apparently independently of classical Gi protein coupling [<span>2</span>]. This discovery encourages us to rethink the cellular architecture of cardiac neurohormonal regulation. Sympathetic nervous system overdrive remains an important driver of adverse remodelling in failing hearts. We have long focused on β1-adrenergic receptor blockade as a central therapeutic strategy. The present findings suggest that we must also account for β3-adrenergic receptor signalling and its distinct cellular consequences [<span>3</span>].</p><p>The work of Xu and colleagues challenges the assumption that β3-adrenegic receptor signalling is uniformly cardioprotective [<span>2</span>]. For decades, pharmacologists have associated this receptor with Gi-dependent signalling, including pathways linked to nitric oxide synthase and negative inotropic effects [<span>4</span>]. We now see a change; the receptor behaves entirely differently in fibroblasts. By virtue of recruiting β-arrestin2, the β3-adrenoreceptor triggers a profibrotic cascade [<span>2, 5</span>]. This cell-specific signalling bias may help explain apparently conflicting observations surrounding β-adrenergic receptor biology [<span>5-8</span>]. Indeed, the timing of this report aligns well with the industry push towards biased ligands. The findings provide a mechanistic rationale for examining how a single receptor can exert different effects in a cell context-dependent manner. We must, therefore, recognize the fibroblast as an independent pharmacological context [<span>9</span>].</p><p>We must, however, confront a significant methodological limitation regarding the experimental model. The authors rely on receptor overexpression to stimulate β3-adrenoreceptor signalling [<span>2</span>]. This approach may alter receptor abundance, subcellular distribution, receptor stoichiometry and adaptor recruitment [<span>10</span>]. Physiological receptors reside predominantly on the cell surface, while overexpression may produce non-physiological receptor pools [<span>10</span>]. Thus, increased β-arrestin2 recruitment and subsequent downstream signalling could partly reflect receptor abundance rather than an intrinsic property of the receptor signalling mechanism. Furthermore, the study does not map G protein-coupled receptor kinase-dependent phosphorylation data. β-arrestin2 recruitment is influenced by receptor phosphorylation, conformation and cellular context [<span>11</span>]. Without mapping relevant phosphorylation sites, one cannot define the precise structural mechan","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 20","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71416","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose Mesenchymal Stem Cells Secreted Exosomal miR-26a-5p Ameliorate Renal Fibrosis via Inhibiting Glycolysis and Ferroptosis in Renal Interstitial Fibrosis","authors":"Chi Zhang,&nbsp;Rui Ge,&nbsp;Min Liu,&nbsp;Jianhuai Huang,&nbsp;Jingyu Cai,&nbsp;Tao Sun,&nbsp;Sheng Ge,&nbsp;Qiuchen Li,&nbsp;Yuanyuan Zhang","doi":"10.1111/jcmm.71369","DOIUrl":"10.1111/jcmm.71369","url":null,"abstract":"<p>Renal fibrosis, a defining feature of chronic kidney disease, involves a metabolic shift toward aerobic glycolysis and is frequently accompanied by ferroptosis, a form of iron-dependent cell death. This study investigated the therapeutic potential of adipose mesenchymal stem cell-derived exosomes (AMSC-exo) in renal fibrosis. Using a unilateral ureteral obstruction (UUO) mouse model and hypoxia-treated HK-2 cells, we assessed fibrosis, glycolysis, mitochondrial morphology, and ferroptosis. miRNA sequencing, dual-luciferase reporter assays, and transcriptome sequencing were performed to identify key exosomal miRNAs and downstream pathways. AMSC-exo significantly attenuated UUO-induced fibrosis and suppressed glycolysis and ferroptosis in tubular epithelial cells. miR-26a-5p was highly enriched in AMSC-exo and downregulated 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (Pfkfb3), a key regulator of glycolysis and ferroptosis. Knockdown of miR-26a-5p markedly weakened the renoprotective effects of AMSC-exo, whereas Pfkfb3 inhibition reversed the effects induced by miR-26a-5p deficiency. These findings indicate that AMSC-exo alleviate renal fibrosis by delivering miR-26a-5p to suppress Pfkfb3, thereby inhibiting glycolytic reprogramming and ferroptosis, and suggest the miR-26a-5p/Pfkfb3 axis as a potential therapeutic target for renal fibrosis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 20","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71369","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Limb-Threatening Ischemia Shows No Adaptability of Mitochondrial Function After Revascularisation","authors":"Fiona Speichinger,&nbsp;Alexandra Gratl,&nbsp;Ben Raude,&nbsp;Marco Arndt,&nbsp;Nina A. Hering,&nbsp;Andreas Greiner,&nbsp;Dominik Pesta,&nbsp;Christian Schineis,&nbsp;Jan Paul Frese","doi":"10.1111/jcmm.71383","DOIUrl":"https://doi.org/10.1111/jcmm.71383","url":null,"abstract":"<p>Peripheral arterial disease (PAD) impairs limb perfusion, leading to myopathy characterised by altered mitochondrial content and respiration. Because ischemic muscle appears to adapt differently across PAD stages, we examined stage-specific skeletal-muscle mitochondrial function before and after successful revascularisation. Muscle biopsies of gastrocnemius and vastus lateralis muscle were obtained from 32 patients—21 with intermittent claudication (IC) and 11 with chronic limb-threatening ischemia (CLTI)—before and 6 weeks after successful revascularisation. Mitochondrial respiration was assessed by high resolution respirometry (HRR). HRR results were normalised to citrate synthase activity (CSA) as a marker of mitochondrial content. Inter-individual variation was expressed as the gastrocnemius-to-vastus respiration ratio (‘GV ratio’). In the IC group, CSA-normalised mitochondrial respiration of gastrocnemius muscle was significantly reduced after revascularisation, paralleled by a significant decline in the GV ratio. In contrast, CLTI patients showed no significant pre- to postoperative change in CSA-normalised respiration or GV ratio, but mitochondrial content significantly improved by revascularisation. Mitochondrial respiration 6 weeks after successful revascularisation adapts only modestly in milder PAD stages such as IC, while more advanced stages (CLTI) display no functional adaptations. These findings suggest that mitochondrial adaptive capacity is stage-dependent and may require targeted therapeutic strategies beyond revascularisation alone, especially in CLTI.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 20","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Canine Distemper Virus-Induced Transcriptional Modulation of Canine Histiocytic Sarcoma Cells in an In Vitro Model of Tumour Zones","authors":"Thanaporn Asawapattanakul,&nbsp;Klaus Schughart,&nbsp;Robert Geffers,&nbsp;Maren von Köckritz-Blickwede,&nbsp;Federico Armando,&nbsp;Wolfgang Baumgärtner,&nbsp;Christina Puff","doi":"10.1111/jcmm.71409","DOIUrl":"https://doi.org/10.1111/jcmm.71409","url":null,"abstract":"<p>Canine distemper virus (Onderstepoort strain; CDVOnd) exhibits potential oncolytic properties. However, the detailed molecular mechanisms remain undetermined so far. This study investigated the influence of a CDVOnd infection and various culture conditions on gene expression patterns in canine histiocytic sarcoma (DH82) cells at different time points simulating different zones within a solid tumour. Persistently CDVOnd-infected DH82 cells and non-infected controls were cultured under standard conditions, 1% hypoxia, and starvation. Cells were analysed on day 1 (short-term) and day 3 (prolonged exposure) using proliferation assays and RNA sequencing. The number of infected cells significantly decreased under altered compared to control conditions and decreased after prolonged compared to short-term exposure. Enrichment analysis revealed that persistent CDV infection, compared to non-infected controls, upregulated genes associated with immune processes and downregulated tissue developmental pathways, including angiogenesis across all conditions and time points. Compared to infected cells maintained under control conditions, hypoxia and starvation induced distinct, condition-dependent transcriptomic responses regardless of exposure duration. Hypoxia led to suppression of immune-related processes and promoted angiogenesis while starvation resulted in an opposite pattern. This suggests that CDV infection induces transcriptomic changes across all zones suggesting anti-tumour effects, while microenvironmental conditions might affect the efficacy of CDV-based virotherapy.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 20","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71409","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149177475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of Panax notoginseng Saponins in Skin Wound Repair: Mechanisms and Research Progress","authors":"Zhifeng Wang,&nbsp;Ting Shi,&nbsp;Daman Tian,&nbsp;Rui Li,&nbsp;Ting Yao,&nbsp;Junfeng Lan,&nbsp;Yujiang Xi,&nbsp;RuiRui Wang,&nbsp;Jian Wang","doi":"10.1111/jcmm.71381","DOIUrl":"https://doi.org/10.1111/jcmm.71381","url":null,"abstract":"<p>Skin wound repair involves four stages: haemostasis, inflammation, proliferation and remodelling. Refractory wounds feature prolonged healing cycles, severe scar hyperplasia and limited clinical therapeutic strategies. <i>Panax notoginseng</i> saponins (PNS), primarily the ginsenosides Rg1 and Rb1 monomers, display high safety and multitarget regulatory properties across the entire wound repair cycle. PNS modulates the inflammatory microenvironment and induces M2-type polarization of macrophages by inhibiting NF-κB, MAPK and other signalling pathways; activates the PI3K/AKT pathway to promote the proliferation and migration of keratinocytes and fibroblasts, and maintains the physiological ratio of collagen type I/III; and upregulates angiogenic factors, including VEGF and bFGF, improving local blood circulation to enhance angiogenesis. Meanwhile, it regulates collagen metabolism, blocks the TGF-β1/Smad2/3 scar-related pathway, and counteracts oxidative stress, thereby accelerating wound healing while inhibiting scar formation. In recent years, PNS has shown promising potential in acute trauma, diabetic foot ulcers, burns and scar repair. PLGA/chitosan nanocarriers, hydrogels, electrospun fibrous membranes and smart responsive delivery systems have effectively addressed limitations of traditional dosage forms, including low bioavailability, poor skin permeability and uneven drug release. Nevertheless, research gaps remains: unclear targets of core monomers r; ambiguous pathway interactions among monomers; and poorly understood crosstalk between signalling pathways; studies on the impacts of extraction processes on pharmacodynamic effects are lacking; and high-level clinical evidence is inadequate. Thus, PNS possesses substantial potential for treating refractory wounds because of its multi-component synergy and full-cycle regulation. Future research should focus on in-depth exploration of molecular mechanisms, standardization of extraction processes, optimization of smart delivery systems and implementation of high-quality clinical studies to promote the translation of active ingredients from traditional Chinese medicine into modern precision therapies.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 20","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71381","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149177479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic Co-Evolution of C-Reactive Protein and Albumin in Early Sepsis: A Group-Based Dual-Trajectory Analysis for Risk Stratification","authors":"Tengfei Chen,&nbsp;Shuwen Zhang,&nbsp;Maoyu Ding,&nbsp;Yumei Yang,&nbsp;Qinxiang Yang,&nbsp;Wei Guo,&nbsp;Xiaolong Xu,&nbsp;Qingquan Liu","doi":"10.1111/jcmm.71402","DOIUrl":"https://doi.org/10.1111/jcmm.71402","url":null,"abstract":"<p>The coupled evolution of inflammation and metabolic dysfunction during early sepsis is incompletely characterized. Although C-reactive protein (CRP) and albumin (ALB) are established markers of these processes, their joint longitudinal patterns have rarely been examined. We used group-based dual-trajectory modelling (GBDTM) to identify distinct coevolutionary patterns of CRP and ALB and to evaluate their associations with mortality in patients with sepsis. This retrospective observational study included patients admitted to the ICU of Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, between June 2014 and March 2025. All included adults met the Sepsis-3 criteria. Among 462 patients with sepsis, serial CRP and ALB measurements obtained on days 1, 3, 5, 7 and 14 after ICU admission were analysed using GBDTM. The selected three-class model showed acceptable classification quality (entropy = 0.80; class-specific average posterior probabilities [AvePPs] = 0.84–0.92) and identified slow-decreasing (79.65%), rapid-decreasing (10.39%) and increasing (9.96%) inflammatory phenotypes. The 28-day mortality rate was highest in the increasing group (52.2% vs. 32.6% and 33.3%; log-rank <i>p</i> = 0.034). In the fully adjusted Cox model, the increasing trajectory was associated with 28-day mortality (HR 1.943, 95% CI: 1.202–3.140; <i>p</i> = 0.007) and 60-day mortality (HR 1.946, 95% CI: 1.218–3.108; <i>p</i> = 0.005). Parsimonious models adjusted for age, sex, and SOFA or the Acute Physiology and Chronic Health Evaluation II (APACHE II) score yielded broadly similar estimates. Joint CRP-ALB trajectories identify clinically interpretable dynamic phenotypes during early sepsis. These findings support the joint trajectory as a hypothesis-generating, complementary phenotyping marker that requires external prospective validation.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 20","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149177478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of Platelet Caspase-1 and P-Selectin Over-Expression in Sickle Cell Disease Patients: An Involvement of NLRP3 Inflammasome?","authors":"Livia Claude,&nbsp;Frédéric Martino,&nbsp;Lydiane Mordier,&nbsp;Doris Célanie,&nbsp;Emmanuelle Bernit,&nbsp;Maryse Etienne-Julan,&nbsp;Benoît Tressières,&nbsp;Marc Romana,&nbsp;Véronique Baccini","doi":"10.1111/jcmm.71390","DOIUrl":"https://doi.org/10.1111/jcmm.71390","url":null,"abstract":"<p>Sickle cell disease (SCD) is characterized by hemolytic anaemia, painful vaso-occlusive crises, and chronic inflammation resulting partly from platelet activation. It has been shown that platelets express the nucleotide-binding domain leucine-rich repeat containing protein 3 (NLRP3) and the apoptosis-associated speck-like protein containing a CARD (ASC), forming the NLRP3 inflammasome, which controls activation of caspase-1 and cleavage of interleukin-1β (IL-1β). Bruton tyrosine kinase (BTK), known to activate the NLRP3 inflammasome, is also expressed in platelets. In SCD, platelets are activated and can secrete increased quantities of IL-1β, suggesting a possible activation of the NLRP3 inflammasome. Here, we assessed platelet P-selectin expression, caspase-1 activation, platelet–neutrophil aggregate formations by flow cytometry and BTK phosphorylation by Western blot in a cohort of 81 adult SCD patients at steady state condition (34 SC and 47 SS patients). We showed an increase in platelet activation in sickle patients and a high level of platelet–neutrophil aggregate in SS patients compared to healthy subjects (17 AA). We also demonstrated platelet caspase-1 activation in SCD patients and obtained data suggesting for the first time NLRP3 inflammasome activation in SC patients. Further studies are needed to understand the mechanism of caspase-1 activation and evaluate the potential therapeutic efficiency of Ibrutinib, a BTK inhibitor.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 20","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71390","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149177476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treadmill Exercise Can Modulate the Inflammatory Microenvironment and Promote Regeneration After Compressive Spinal Cord Injury in Female Mice","authors":"Anne Caroline Rodrigues dos Santos Cavalcante,&nbsp;Renata Pereira Laurindo,&nbsp;Luiza dos Santos Heringer,&nbsp;Anna Lecticia Martinez Martinez Toledo,&nbsp;Gabriela Sena Souza,&nbsp;Gabriel Fidalgo Queiroz da Silva,&nbsp;Ana Carolina Campos dos Santos,&nbsp;Morgana Teixeira Lima Castelo Branco,&nbsp;Ana Maria Blanco Martinez,&nbsp;Suelen Adriani Marques","doi":"10.1111/jcmm.71351","DOIUrl":"https://doi.org/10.1111/jcmm.71351","url":null,"abstract":"<p>Traumatic spinal cord injury (SCI) leads to severe sensorimotor impairments and reduced quality of life. Physical rehabilitation has emerged as a key therapeutic strategy to improve function and mitigate complications such as muscle atrophy and joint contractures, partly through modulation of the inflammatory microenvironment. This study investigated the effects of a structured exercise protocol on inflammation, neuroplasticity and sensorimotor recovery following compressive SCI in mice. Female C57BL/6 mice (8–12 weeks) were subjected to extradural spinal cord compression and divided into three groups: SHAM (laminectomy only), SCI (injury without treatment) and TMT (injury plus treadmill training). The TMT protocol began 7 days post-injury and continued until 56 days, with sessions performed three times per week. Functional assessments were conducted weekly, followed by electroneuromyography at 56 days and biochemical and morphological analyses after euthanasia. The TMT group demonstrated significantly improved locomotor performance and nociceptive response compared to the SCI group. Electroneuromyography revealed higher compound muscle action potential amplitudes in TMT and SHAM groups (<i>p</i> &lt; 0.001). Additionally, TMT reduced muscle atrophy (<i>p</i> &lt; 0.05) and increased neuromuscular junction density. Bladder wall thickness in TMT animals resembled SHAM and differed from SCI (<i>p</i> &lt; 0.001), suggesting reduced inflammation. At the molecular level, TMT increased anti-inflammatory cytokines and reduced pro-inflammatory markers, alongside enhanced M2 microglial polarisation, decreased astrocyte reactivity and reduced apoptosis. Imaging analyses confirmed reduced lesion spread and fibrosis. These findings indicate that phase-adjusted exercise promotes functional recovery, neuromuscular plasticity and tissue preservation after SCI.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 20","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149177460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to Editor on Collagen-Rich Extracellular Matrix and Postoperative Angiogenesis in Moyamoya Disease: The Need for Phenotype-Stratified Transcriptomic Analysis","authors":"Emaan Rani,&nbsp;Mirza Faaz Baig","doi":"10.1111/jcmm.71400","DOIUrl":"10.1111/jcmm.71400","url":null,"abstract":"&lt;p&gt;We have read the article titled ‘Transcriptomic Profiling Associates Collagen-Rich Extracellular Matrix With Postoperative Angiogenesis in Moyamoya Disease’ by Chen et al. with great interest [&lt;span&gt;1&lt;/span&gt;]. The authors deserve praise for their creative application of transcriptome-wide RNA sequencing to temporal muscle tissue to uncover the crucial role of extracellular matrix (ECM) remodelling and collagen deposition in postoperative collateral vessel formation after indirect revascularization. A few drawbacks should be mentioned, however.&lt;/p&gt;&lt;p&gt;First, all the paediatric and adult patients with Moyamoya disease (MMD) are grouped together in the study cohort without stratification by clinical disease stage (e.g., Suzuki stage or hemodynamic stage) or age-dependent angiogenic ability. In addition, as a natural trait of paediatric patients they have a much higher ‘native’ capacity for neoangiogenesis and collateral development than adult patients, irrespective of whether ECM is expressed. In addition, the endogenously generated differential angiogenic signals are associated with advanced disease stage and severe basal hypoperfusion. The collagen-rich transcriptomic signature could be confounded by an age-specific baseline angiogenic response or a drive towards ischemia in patients rather than a shared mechanism of surgical success, as the analysis of a mixed cohort lacks control of stage progression and age. As shown in Related Article, indirect revascularization efficacy is intrinsic to the exquisite balance between disease stage progression and age-associated neoangiogenesis potential, suggesting that different patient subsets have different collateral formation [&lt;span&gt;2&lt;/span&gt;]. Future studies are needed to study age-matched groups (paediatric and adult separately) and to correct multi-variable transcriptomic models for pre-operative Suzuki staging and cerebrovascular reserve baseline.&lt;/p&gt;&lt;p&gt;Secondly, the investigation does not include a comparison or control group that underwent the direct bypass procedure or a combined bypass procedure (e.g., STA-MCA bypass with encephaloduroarteriomyosynangiosis [EDAMS]). Direct bypass restores hemodynamic function immediately, changing the shear stress and metabolic function in adjacent tissues. Indirect bypass, on the other hand, is completely vascularized by tissue-level angiogenesis. The results from this study cannot be generalised across different bypass techniques because of the absence of a comparative tissue sample for combined or direct bypass. As outlined previously in Related Article, the clinical and angiographic results of any combined bypass surgery are significantly different from those of any standalone indirect procedure, as is the local tissue perfusion pressures [&lt;span&gt;3&lt;/span&gt;]. The addition of tissue controls from patients that have combined direct–indirect bypass would allow to separate the expression patterns of ECM molecules that are direct–indirect bypass specific from those th","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 19","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Casticin From Sanse Powder- In Vitro Release Medium Inhibits FAK/PI3K/AKT Phosphorylation Reducing Synovial Senescence and Alleviates Inflammation in Knee Osteoarthritis","authors":"Jiangyu Liu,&nbsp;Peng Wu,&nbsp;Rui Jiang,&nbsp;Lishi Jie,&nbsp;Lei Shi,&nbsp;Houyu Fu,&nbsp;Yibao Wei,&nbsp;Deren Liu,&nbsp;Peimin Wang,&nbsp;Songjiang Yin,&nbsp;Jun Mao","doi":"10.1111/jcmm.71391","DOIUrl":"10.1111/jcmm.71391","url":null,"abstract":"<p>Sanse Powder (SSP) has been shown to be effective in the clinical treatment of knee osteoarthritis (KOA), although its active components and underlying mechanisms remain unclear. In this study, we collected the in vitro release medium of SSP (SSP-IVRM) using an in vitro release test and evaluated its pharmacological effects in a KOA rat model. Ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) was used to identify active constituents in SSP-IVRM, while network pharmacology and molecular docking were applied to screen key compounds and molecular targets. In vivo and in vitro experiments using histological staining and molecular biology techniques were performed to investigate the effects of casticin (CAS), a major component of SSP-IVRM, on KOA-related synovitis. UHPLC–MS/MS identified CAS, monocerin, and chlorogenic acid as major components. Network pharmacology and molecular docking associated these compounds with PI3K signalling and cellular senescence. CAS significantly improved synovial pathology, reduced pro-inflammatory cytokines and chemokines, modulated fibrosis- and senescence-related genes and proteins, and decreased synovial fibroblast senescence. Transcriptomic analysis further implicated cell adhesion and the PI3K–AKT pathway. Additional experiments demonstrated that CAS alleviates KOA-related inflammation and cellular senescence by inhibiting FAK/PI3K/AKT phosphorylation. These findings indicate that CAS in SSP-IVRM reduces synovial fibroblast senescence and inflammation through inhibition of the FAK/PI3K/AKT signalling pathway, thereby exerting therapeutic effects against KOA.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 19","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}