Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05125-y
Background: Generation of insulin-producing cells (IPCs) from stem cells provides great hope for patients with diabetes mellitus (DM). Long non-coding RNAs (lncRNAs) ignited much interest regarding their role in determining the fate of stem cells. The lncRNAs MALAT1 and TUG1 have been reported to be interrelated with β-cell dysfunction and/or DM. However, their role during generation of IPCs from stem cells has not been adequately studied. Thus, the current study aimed to investigate the role of MALAT1 and TUG1 during differentiation of adipose tissue-derived mesenchymal stem cells (Ad-MSCs) towards IPCs. Methods: Ad-MSCs were isolated from rat epididymal fat pads, characterized and induced to differentiate towards IPCs. Assessment of differentiation was done by measuring expression levels of various β-cell-related markers using RT-qPCR, as well as morphological changes, and dithizone staining. Expression levels of MALAT1 and TUG1 were also measured by RT-qPCR. Several in-silico analyses were done using RNA–protein Association and Interaction Networks (RAIN) database. Results: MALAT1 and TUG1 expression levels were significantly increased during differentiation of Ad-MSCs into IPCs as compared to control uninduced cells. Furthermore, generated networks from RAIN database revealed an interplay between MALAT1 and TUG1, and between each of them with several common targets like GAS5, HOTAIR and TP53COR1. Conclusions: The current study portrays MALAT1 and TUG1 as novel interrelated molecular mediators and important regulatory nodes enhancing differentiation of Ad-MSCs towards IPCs. Their upregulation during differentiation can be interrelated with competitive endogenous RNA (ceRNA) networks, mediating various epigenetic modifications, orchestrating signaling pathways and overcoming cellular stress during reprogramming/differentiation.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05207-x
Background Dilated cardiomyopathy (DCM) is a progressive, intractable disease that leads to heart failure. Heart transplantation is the only curative treatment; however, access is limited by donor scarcity. Induced pluripotent stem cell (iPSC)-based therapies are attracting attention for DCM, but suitable large-animal models and robust preclinical data have been limited. Methods We generated multi-layered cardiovascular cell sheets from human iPSCs by combining cardiomyocytes with endothelial and stromal cells and overcoming stacking limits using interleaved gelatin hydrogel microspheres, yielding a thicker cardiac tissue-like construct (product code: IHJ-301). To enable rigorous testing in non-ischemic heart failure, we established a modified canine rapid-pacing heart failure model that maintains depressed function without mortality by continuing pacing at a slightly reduced rate after induction (Step-Down Pacing Heart Failure model). IHJ-301 was implanted epicardially onto the left ventricular surface via thoracotomy, and cardiac function was assessed by echocardiography and right-heart catheterization. Results After 4 weeks of rapid pacing (230±10 bpm), left ventricular ejection fraction (LVEF) was reduced from 77.8±1.1% (pre-pacing) to 44.9±1.9% (n=11) (0 W). Continued pacing at 210±10 bpm for additional 4 weeks resulted in no mortality and maintained depressed function (4 W LVEF 47.3±2.6%). IHJ-301 was implanted at 0 W. At 4 weeks post-implantation (4 W), all animals in the IHJ-301 group (n=5) showed greater functional improvement than sham (n=6). Absolute changes from 0 W to 4 W were: ΔLVEF (%) 9.38±1.47 vs. 1.90±0.34; Δfractional shortening (%) 4.84±0.75 vs. 0.97±0.18; stroke volume (mL/beat) 1.21±1.26 vs. −2.99±0.60; cardiac output (L/min) 0.19±0.19 vs. −0.58±0.12 (all p<0.05). Conclusions We established a non-ischemic large-animal heart failure model that sustains depressed function for one month, enabling clear therapeutic readouts. IHJ-301 significantly improved multiple parameters of cardiac function, providing preclinical evidence that IHJ-301 could offer a promising therapeutic option for DCM.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04780-x
Background Liver fibrosis is a crucial pathological stage in the progression of chronic liver diseases. Yiguanjian (YGJ), a Chinese herbal formula, exhibits anti-inflammatory, anti-fibrotic, and hepatoprotective effects. Extracellular vesicles from bone-marrow mesenchymal stem cells (BMSC-EVs) have shown potential in treating various disorders, including liver fibrosis. This study investigated the regulatory effects of EVs from YGJ-preconditioned BMSCs (YGJ-EVs) on TGF-β1-stimulated hepatic stellate cells (HSCs) and their therapeutic potential in a mouse model of liver fibrosis, with a focus on identifying the causative microRNA cargo. Methods YGJ-EVs and control EVs were isolated from BMSC culture supernatants and characterized via western blotting, transmission electron microscopy, and nanoparticle tracking analysis. Their cellular uptake in vitro and in vivo was evaluated using DIR labeling. To identify candidate miRNAs mediating YGJ-EV bioactivity, miRNA microarray analysis was conducted. To assess the effect of YGJ-EVs on liver fibrosis, TGF-β1-activated HSC cells were treated with YGJ-EVs or control-EVs for 24 h, and then the expression of proteins related to fibrotic activation (COL1-A1 and α-SMA), lysosomal biogenesis (LAMP1, TPP1, CTSD, and CTSB) mitophagy (p62, LC3, PINK1, and Parkin), and the Akt/AMPK/TFEB pathway was assessed. To determine whether miR-7045-5p is the causative factor, HSC cells transfected with miR-7045-5p were similarly analyzed. Results miRNA microarray analysis revealed miR-7045-5p upregulation in YGJ-EVs versus control EVs. In CCl4-treated mice, YGJ-EV-derived miR-7045-5p ameliorated the liver fibrosis, improved the hepatic function, and suppressed the HSC activation by inhibiting the Akt/AMPK/TFEB pathway. In vitro, miR-7045-5p overexpression attenuated TGF-β1-induced HSC activation. Conclusion YGJ increases miR-7045-5p abundance in BMSC-EVs. YGJ-EVs alleviate liver fibrosis by delivering the anti-fibrotic miRNA miR-7045-5p, which inhibits the Akt/AMPK/TFEB pathway, thereby promoting lysosomal biogenesis and mitophagy in HSCs.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04767-8
Background With the global population aging, optimizing bone regeneration is becoming increasingly important for enhancing the quality of life among elderly individuals. Progenitor cell-based therapies, such as mesenchymal stromal cells and induced pluripotent stem cells for bone regeneration have shown challenges due to cellular senescence and the control of the differentiation processes remain significant hurdles. In particular, elevated expression of senescence markers may play a pivotal role in limiting bone regeneration. This systematic review examines how these senescence markers influence the efficacy of progenitor cell therapies and whether targeting them could improve outcomes. Methods We conducted a systematic literature review following the PRISMA guidelines, using the PubMed, Web of Science, Embase and Scopus with the algorithm of “bone regeneration AND senescence AND marker”. Data synthesis focused on human cell sources and specifically examined senescence markers related to bone regeneration. Results Studies using human cells were discussed in 101 papers. Based on our inclusion and exclusion criteria, 13 papers remained for our review on senescence markers in human cells within the context of bone regeneration and senescence, with and without interventional strategies. More than half of the cell sources in current aging-related studies are derived from bone marrow. Markers of aging relevant to bone regeneration include changes in cell size and morphology, increased levels of β-galactosidase (β-Gal) and Reactive Oxygen Species (ROS), and the presence of a senescence-associated secretory phenotype (SASP). Additionally, distinct senescence markers such as p16Ink4a, p21, and p53, and mitochondrial dysfunction were associated with reduced osteogenic potential and impaired regenerative capacity. Conclusion Bone marrow is the most common source of cells for studies of senescence. Cellular senescence characterized by elevated expression of specific markers was consistently shown to be negatively associated with osteogenic capacity and regenerative outcomes. The most common strategies to rejuvenate senescent cells include
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04578-x
Background Genomic studies have linked single nucleotide variants in the enhancer region of the leukemia inhibitory factor receptor (Lifr) gene to chromatin accessibility and the regulation of self-renewal in mouse embryonic stem cells (mESCs). However, the underlying mechanisms remain unclear. This study investigates the role of the transcription factor BTB and CNC homology 1 (BACH1) in regulating the Lifr enhancer and its impact on mESC pluripotency. Methods We performed RNA-sequencing (RNA-seq) to assess the impact of Bach1 knockout on gene expression in mESCs. Additionally, chromatin immunoprecipitation (ChIP), co-immunoprecipitation (co-IP), and luciferase reporter gene analysis were employed to investigate the mechanism by which BACH1 regulates Lifr expression. Results Genomic analyses identified BACH1 binding at the Lifr enhancer proximal to rs50454566 in mESCs. Integrated single-cell RNA sequencing (scRNA-seq) data revealed co-upregulation of Bach1 and Lifr in inner cell mass (ICM) cells. RNA-seq analyses demonstrated that Bach1 depletion attenuated Lifr expression and impeded LIFR-signal transducer and activator of transcription 3 (STAT3) signaling. Mechanistically, BACH1 recruited STAT3 to the Lifr enhancer, driving Lifr transcription and facilitating the LIFR-STAT3 signaling pathway, thereby enhancing mESC self-renewal. Conclusion Our findings demonstrate that BACH1 enhances Lifr enhancer activity by recruiting STAT3 and activates the LIFR-STAT3 signaling pathway by promoting the LIFR expression, thereby maintaining mESC self-renewal.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04764-x
Background Human hair follicle dermal sheath cup cells (DSCCs) hold promise as a cell source of regenerative medicine treatment for hair loss owing to their ability to secrete growth factors and/or signal pathway activators. The therapeutic effect of autologous DSCCs transplantation for male/female pattern hair loss (PHL) was demonstrated in a phase III equivalent clinical study. Intralesional inflammation has been implicated in the pathophysiology of various hair loss diseases, including PHL. As DSCCs possess mesenchymal stem/stromal cell (MSC)-like properties and MSCs are immunosuppressive, we investigated whether they exhibit immunoregulatory capabilities comparable to MSCs and developed an in vitro morphometric assay to predict this capability. Methods DSCCs were isolated via microdissection and propagated in vitro. Their conformity to MSC criteria was assessed based on cell surface antigen expression and differentiation potential. Furthermore, immunoregulatory capabilities were assessed by co-culturing DSCCs with anti-CD3/28 antibody-stimulated peripheral blood mononuclear cells (PBMCs) and examining the suppression mechanisms through pharmacological intervention. Multiple lots of DSCCs derived from various donors and manufacturing conditions were cultured and analyzed by phase-contrast microscopy to obtain their morphometric profiles. Parameters correlating with the expression levels of immunomodulatory factors were used to create a predictive model. Additional DSCC lots were manufactured to validate the predictive model. Results Similar to MSCs, cell differentiation assays revealed that DSCCs exhibited multipotency, and they did not express co-stimulatory molecules in response to immunogenic stimuli, suggesting low immunogenicity. Moreover, co-culture experiments with allogeneic PBMCs revealed that DSCCs reduced T cell proliferation (from 78 to 5%) and
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03690-8
Background Cell- or tissue-based regenerative therapy is an attractive approach to treat heart failure. A tissue patch that can safely and effectively repair damaged heart muscle would greatly improve outcomes for patients with heart failure. In this study, we conducted a preclinical proof-of-concept analysis of the efficacy and safety of clinical-grade human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) patches. Methods A clinical-grade hiPSC line was established using peripheral blood mononuclear cells from a healthy volunteer that was homozygous for human leukocyte antigens. The hiPSCs were differentiated into cardiomyocytes. The obtained hiPSC-CMs were cultured on temperature-responsive culture dishes for patch fabrication. The cellular characteristics, safety, and efficacy of hiPSCs, hiPSC-CMs, and hiPSC-CM patches were analyzed. Results The hiPSC-CMs expressed cardiomyocyte-specific genes and proteins, and electrophysiological analyses revealed that hiPSC-CMs exhibit similar properties to human primary myocardial cells. In vitro and in vivo safety studies indicated that tumorigenic cells were absent. Moreover, whole-genome and exome sequencing revealed no genomic mutations. General toxicity tests also showed no adverse events posttransplantation. A porcine model of myocardial infarction demonstrated significantly improved cardiac function and angiogenesis in response to cytokine secretion from hiPSC-CM patches. No lethal arrhythmias were observed. Conclusions hiPSC-CM patches are promising for future translational research and may have clinical application potential for the treatment of heart failure.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03917-8
Background Intermediate cells are present in the early stages of human prostate development and adenocarcinoma. While primary cells isolated from benign human prostate tissues or tumors exhibit an intermediate phenotype in vitro, they cannot form tumors in vivo unless genetically modified. It is unclear about the stem cell properties and tumorigenicity of intermediate cells.
Methods We developed a customized medium to culture primary human intermediate prostate cells, which were transplanted into male immunodeficient NCG mice to examine tumorigenicity in vivo. We treated the cells with different concentrations of dihydrotestosterone (DHT) and enzalutamide in vitro and surgically castrated the mice after cell transplantation in vivo. Immunostaining, qRT-PCR, RNA sequencing, and western blotting were performed to characterize the cells in tissues and 2D and 3D cultures.
Results We found intermediate cells expressing AR+PSA+CK8+CK5+ in the luminal compartment of human prostate adenocarcinoma by immunostaining. We cultured the primary intermediate cells in vitro, which expressed luminal (AR+PSA+CK8+CK18+), basal (CK5+P63+), intermediate (IVL+), and stem cell (CK4+CK13+PSCA+SOX2+) markers. These cells resisted castration in vitro by upregulating the expression of AR, PSA, and proliferation markers KI67 and PCNA. The intermediate cells had high tumorigenicity in vivo, forming tumors in immunodeficient NCG mice in a month without any genetic modification or co-transplantation with embryonic urogenital sinus mesenchyme (UGSM) cells. We named these cells human castration-resistant intermediate prostate cancer stem cells or CriPCSCs and defined the xenograft model as patient primary cell-derived xenograft (PrDX). Human CriPCSCs resisted castration in vitro and
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-04044-0
The original article contains two errors which the authors wish to address: 1. On line 3 of page 3, the sentence should simply read, 'B1 and B2, which indicates complete […]', and the word '(Ref)' should be disregarded. 2. In Fig. 2C, the Y-axis label should instead read as 'Change in total motor score', and the word 'lower' should be disregarded.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026049
Esophageal squamous cell carcinoma (ESCC) represents a common malignancy of the digestive system. Circular RNAs (circRNAs) are a distinct class of single-stranded non-coding RNAs that are essential in the progression of various tumors given that they can act as microRNA (miRNA) sponges in a manner similar to that of mRNAs. In this study, circ_0006156 is screened to be highly expressed in ESCC tissues through high-throughput sequencing and quantitative real-time polymerase chain reaction. Subsequent in vitro and in vivo experiments are conducted to validate its biological functions. Furthermore, the regulatory relationships among circ_0006156, miR-202-5p, and TGFBR1 are investigated using RNA antisense purification, miRNA sequencing, RNA immunoprecipitation, fluorescence in situ hybridization, dual-luciferase reporter assay, and bioinformatics analyses. The results show significant overexpression of circ_0006156 in ESCC tissues, with relatively shorter overall survival observed in patients with high circ_0006156 expression. circ_0006156 is further identified to directly bind to miR-202-5p. miR-202-5p inhibits the proliferation, migration, and invasion of ESCC cells in vitro and partially rescues the effects induced by circ_0006156. Consistent results are reported by subcutaneous xenograft tumor experiments in nude mice. In addition, circ_0006156 is confirmed to act as an endogenous sponge for miR-202-5p, which results in a relieved suppression of its target gene TGFβR1. In summary, circ_0006156 can regulate TGFβR1 expression by sponging miR-202-5p, which may further activate the TGFβ/Smad pathway and promote ESCC progression. Collectively, circ_0006156 functions as a novel oncogenic RNA in ESCC and may serve as a potential tumor marker.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024141
Diabetic nephropathy (DN) is recognized as one of the primary causes of chronic kidney disease and end-stage renal disease. Vaccarin (VAC) confers favorable effects on cardiovascular and metabolic diseases, including type 2 diabetes mellitus (T2DM). Nonetheless, the potential role and mechanism of VAC in the etiology of DN have yet to be completely elucidated. In this study, a classical mouse model of T2DM is experimentally induced via a high-fat diet (HFD)/streptozocin (STZ) regimen. Renal histological changes are assessed via H&E staining. Masson staining and immunohistochemistry (IHC) are employed to assess renal fibrosis. RT-PCR is utilized to quantify the mRNA levels of renal fibrosis, oxidative stress and inflammation markers. The levels of malondialdehyde (MDA) and reactive oxygen species (ROS), as well as the content of glutathione peroxidase (GSH-Px), are measured. The protein expressions of collagen I, TGF-β1, α-SMA, E-cadherin, Nrf2, catalase, SOD3, SOD2, SOD1, p-ERK, p-EGFR (Y845), p-EGFR (Y1173), p-NFκB P65, t-ERK, t-EGFR and t-NFκB P65 are detected by western blot analysis. Our results reveal that VAC has a beneficial effect on DN mice by improving renal function and mitigating histological damage. This is achieved through its inhibition of renal fibrosis, inflammatory cytokine overproduction, and ROS generation. Moreover, VAC treatment effectively suppresses the process of epithelial-mesenchymal transition (EMT), a crucial characteristic of renal fibrosis, in high glucose (HG)-induced HK-2 cells. Network pharmacology analysis and molecular docking identify epidermal growth factor receptor (EGFR) as a potential target for VAC. Amino acid site mutations reveal that Lys-879, Ile-918, and Ala-920 of EGFR may mediate the direct binding of VAC to EGFR. In support of these findings, VAC reduces the phosphorylation levels of both EGFR and its downstream mediator, extracellular signal-regulated kinase 1/2 (ERK1/2), in diabetic kidneys and HG-treated HK-2 cells. Notably, blocking either EGFR or ERK1/2 yields renal benefits similar to those observed with VAC treatment. Therefore, this study reveals that VAC attenuates renal damage via inactivation of the EGFR/ERK1/2 signaling axis in T2DM patients.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025187
Chinese hamster ovary (CHO) cells are an extensively used platform for manufacturing biopharmaceuticals, and nearly 80% of recombinant protein is produced by CHO cell lines. Randomly incorporating genes of interest into the genome is a common method for the development of stable CHO cell lines in industry, but it is vulnerable to genetic instability, is difficult to predict productivity, and is accompanied by a time-consuming and laborious screening process. Nonetheless, highly productive clones isolated from a randomized pool often exhibit unfavorable properties including transgene copy number loss and epigenetic silencing over the lifespan of the culture, ultimately lowering transgene transcription and corresponding recombinant protein production, which referred to as production instability. Thus, this challenging situation underscores the urgent desire for a new strategy to satisfy ever-growing industrial production requirements. The lack of specificity of gene integration, which is often susceptible to genetic instability, causes production instability. Alternatively, in recent years, many investigators have shown that the bottleneck arising from traditional randomized cell line development can be overcome through site-specific integration to insert exogenous pieces of DNA into a precise location, which permits their predictable function, allows high levels of transgene expression and makes it possible to generate homogeneous clones with consistent productivity and stability. The transcription and expression activities of genes are influenced by chromatin structural properties and the environment surrounding the genome, and loci that are capable of facilitating high and stable transgene transcription and expression are termed 'hotspots'. Many significant upfront advances have been made to identify potential hotspots, and a number of promising genome loci have been reported, such as the Hprt, Ywhae, Hipp11, Rosa26, and C12orf35 loci. The C12orf35 gene is located on a telomeric region of chromosome 8 in CHO cells. It is widely known that telomeres are usually noncoding, repetitive sequences distributed at chromosome terminals that act as buffers for those coding sequences further behind and thus enable foreign gene expression without interrupting functional genes. Studies have demonstrated that the C12orf35 gene is a potential locus for the integration of foreign genes in mammalian cells and that disruption of C12orf35 gene expression leads to increased productivities and shorter recovery times during selection pressure in CHO cells. Although the C12orf35 gene has been partially researched in cell line development, very few publicly available reports have systematically validated site-specific integration in cell lines concerning the stability of transgene passage, transgene transcription and expression levels. A range of studies have successfully utilized site-specific recombinase or genome editing tools to incorporate exogenous genes into the desired site in the CHO genome. Clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR-Cas9), a leading gene editing tool, uses a guide RNA to target the DNA sequence with the Cas9 enzyme to induce cuts and allows easy, efficient and cost-effective edting. CRISPR-Cas9 has already been applied to mediate the insertion of targeted genes in mammalian cells, including CHO cells, for fundamental research. However, the adoption of this technology for industrial purposes remains to be investigated. Therefore, in this study, we sought to establish a CRISPR/Cas9-mediated site-specific integration strategy to overcome existing weaknesses and lay the foundation for the development of industrial rCHO cell lines.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.15.20261507
This study reports the fabrication and in vitro evaluation of carrier-free self-assembled nanoparticles (SSD-CBD) composed of saikosaponin D (SSD) and cannabidiol (CBD) at a 3:1 mass ratio via nano co-precipitation. Assembly mechanisms were probed using XPS, FTIR, and 1H-1H NOESY, revealing hydrogen bonding and hydrophobic interactions as principal driving forces. Physicochemical characterization by TEM and DLS confirmed a stable nanoscale architecture. The formulation exhibited pH-responsive release, preferentially discharging payload in tumor microenvironment (pH 6.8) while retaining stability at physiological pH 7.4. In HepG2 hepatocellular carcinoma cells, SSD and CBD displayed synergy with a combination index (CI) of 0.79. MTT assays, Annexin V-FITC/PI flow cytometry, and caspase activity measurements demonstrated that SSD-CBD nanoparticles induce apoptosis via the mitochondrial pathway. The carrier-free strategy addresses CBD's poor aqueous solubility and instability, simultaneously improving delivery efficiency and enabling precise synergistic drug co-administration. These findings provide an experimental foundation for intelligent nanomedicine development based on SSD. However, in vivo pharmacokinetics, tissue distribution, tumor accumulation, and potential hepatotoxicity of SSD in nanoformulation remain unresolved. Future work should focus on surface engineering (e.g., PEGylation or targeting ligand modification) to enhance stability and tumor targeting, integration of immunomodulatory components, and scalable GMP-compliant manufacturing with comprehensive quality control.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.15.20261504
This study establishes an integrated strategy for rapid screening of pancreatic lipase (PPL) inhibitors from Rheum palmatum and elucidates their anti-obesity mechanisms. Fe3O4@SiO2@PPL magnetic nanoparticles were synthesized via chemical co-precipitation, Stöber method, and cross-linking, and characterized by FTIR, SEM, and XRD. Ligand fishing from a 30% ethanol extract specifically captured four compounds: chrysophanol-8-O-β-D-glucopyranoside, aloe-emodin, rhein, and chrysophanol. In vitro enzyme assays confirmed that chrysophanol and aloe-emodin exhibited potent PPL inhibition with IC50 values of 67.03 and 85.86 µmol/L, respectively. Molecular docking revealed that these active components form hydrogen bonds and hydrophobic interactions with key amino acid residues of PPL, consistent with experimental inhibition. Network pharmacology identified 150 overlapping targets between the active compounds and obesity, with five core targets: EGFR, AKT1, SRC, HSP90AA1, and BCL2. Pathway enrichment analysis highlighted the HIF-1 signaling pathway and lipid and atherosclerosis pathway as principal mechanisms. The developed 'material screening–computational validation–network prediction' platform offers a robust tool for high-throughput discovery of natural PPL inhibitors and provides methodological reference for multi-target mechanistic studies of traditional Chinese medicine.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261621
This bibliometric investigation systematically maps the research landscape and emerging frontiers of sinomenine, an alkaloid derived from Sinomenium acutum, Diploclisia chinensis, and S. scutum. A comprehensive search of CNKI and Web of Science yielded 710 Chinese and 471 English publications, which were screened via NoteExpress and analyzed using Excel, CiteSpace, and VOSviewer. Publication trends, national distribution, institutional and author networks, and keyword co-occurrence were visualized. China dominates the field, with international attention rising annually. Core research teams have formed, yet collaboration remains largely intra-institutional or regional, with minimal cross-regional integration. Both Chinese and English literature converge on sinomenine's anti-arthritis pharmacological mechanisms, while Chinese studies additionally emphasize extraction, quality standards, and formulation development. The analysis identifies three future breakthrough dimensions: multi-omics-driven integration employing spatial transcriptomics and single-cell sequencing to dissect the drug-host-microbiome network; precision medicine-oriented drug delivery innovations, including microenvironment-responsive nanocarriers and smart hydrogels for targeted controlled release; and clinical expansion into neurodegenerative diseases and organ fibrosis with internationally compliant trials. Establishing a synergistic 'discovery-formulation-clinical validation' framework is recommended to accelerate sinomenine's translation from traditional herbal component to modern precision therapeutic, offering a paradigm for traditional Chinese medicine internationalization.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261609
Puerarin, a principal isoflavone from Pueraria lobata, exhibits anti-migraine activity but suffers from poor oral bioavailability and limited blood-brain barrier penetration. This study reports a puerarin-loaded chitosan-modified β-cyclodextrin supramolecular gel (Pur@CS-β-CD Gel) for intranasal delivery. Formulation optimization employed single-factor experiments and Box-Behnken design-response surface methodology (BBD-RSM). The optimal formulation comprised CS-β-CD and sodium carboxymethylcellulose at a mass ratio of 1:9, total polymer concentration 2.6%, and puerarin 40 mg. The resulting gel displayed a three-dimensional porous architecture, pH 6.5, favorable stability, and a biphasic in vitro release profile: 82.75% cumulative release within 4 h followed by sustained release. No nasal mucosal irritation was observed. In a chronic migraine rat model induced by nitroglycerin, Pur@CS-β-CD Gel significantly ameliorated behavioral deficits, reduced brain levels of calcitonin gene-related peptide (CGRP) and interleukin-1β (IL-1β), and elevated 5-hydroxytryptamine (5-HT). These pharmacodynamic outcomes are consistent with interruption of trigeminovascular CGRP release, modulation of serotonergic neurotransmission, and attenuation of IL-1β-mediated nociceptive sensitization. The study acknowledges limitations: the animal model only partially recapitulates clinical migraine heterogeneity; long-term safety and immunogenicity of repeated dosing remain unassessed; and direct quantification of brain puerarin concentration was not performed, leaving brain-targeting efficiency unproven. Nonetheless, the optimized gel offers a feasible, non-invasive nasal delivery platform with preliminary anti-migraine efficacy, warranting further pharmacokinetic and mechanistic validation.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05125-y
Diabetes mellitus (DM) affects approximately 589 million individuals globally, with Egypt among the ten most affected nations. Stem cell-based therapies, particularly adipose tissue-derived mesenchymal stem cells (Ad-MSCs), offer a promising route for generating insulin-producing cells (IPCs). Long non-coding RNAs (lncRNAs) have emerged as critical regulators of stem cell fate. This study investigates the roles of MALAT1 and TUG1 during Ad-MSC differentiation into IPCs. Ad-MSCs were isolated from rat epididymal fat pads, characterized, and induced to differentiate. Differentiation was assessed via RT-qPCR for β-cell markers, morphological changes, and dithizone staining. MALAT1 and TUG1 expression was quantified by RT-qPCR. In-silico analyses utilized the RNA–protein Association and Interaction Networks (RAIN) database. Results demonstrate that MALAT1 and TUG1 expression significantly increased during differentiation compared to uninduced controls. Network analysis revealed interplay between MALAT1 and TUG1, and their common targets including GAS5, HOTAIR, and TP53COR1. These findings position MALAT1 and TUG1 as novel interrelated molecular mediators and regulatory nodes enhancing IPC generation from Ad-MSCs. Their upregulation may involve competitive endogenous RNA (ceRNA) networks, epigenetic modifications, signaling pathway orchestration, and cellular stress mitigation during reprogramming. This study provides a foundation for dissecting molecular mechanisms underlying β-cell lineage specification, with implications for improving stem cell-based diabetes therapies.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05207-x
Dilated cardiomyopathy (DCM) is a progressive, intractable disease leading to heart failure, with heart transplantation as the only curative option, limited by donor scarcity. Induced pluripotent stem cell (iPSC)-based therapies are promising but lack robust large-animal preclinical data. We generated multi-layered cardiovascular cell sheets (IHJ-301) from human iPSCs by combining cardiomyocytes with endothelial and stromal cells, using interleaved gelatin hydrogel microspheres to overcome stacking limits, yielding a thicker cardiac tissue-like construct. To test in non-ischemic heart failure, we established a modified canine rapid-pacing model (Step-Down Pacing Heart Failure) that maintains depressed function without mortality by continuing pacing at a slightly reduced rate after induction. IHJ-301 was implanted epicardially onto the left ventricular surface via thoracotomy. After 4 weeks of rapid pacing (230±10 bpm), left ventricular ejection fraction (LVEF) fell from 77.8±1.1% to 44.9±1.9% (n=11). Continued pacing at 210±10 bpm for 4 weeks caused no mortality and maintained depressed function (4-week LVEF 47.3±2.6%). At 4 weeks post-implantation, IHJ-301-treated animals (n=5) showed significantly greater improvements than sham (n=6): ΔLVEF 9.38±1.47% vs. 1.90±0.34%; Δfractional shortening 4.84±0.75% vs. 0.97±0.18%; stroke volume change 1.21±1.26 vs. -2.99±0.60 mL/beat; cardiac output change 0.19±0.19 vs. -0.58±0.12 L/min (all p<0.05). This non-ischemic large-animal model sustains depressed function for one month, enabling clear therapeutic readouts. IHJ-301 significantly improved multiple cardiac function parameters, providing preclinical evidence for its potential in DCM therapy.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026049
Esophageal squamous cell carcinoma (ESCC) represents a common malignancy of the digestive system. Circular RNAs (circRNAs) are a distinct class of single-stranded non-coding RNAs that are essential in the progression of various tumors given that they can act as microRNA (miRNA) sponges in a manner similar to that of mRNAs. In this study, circ_0006156 is screened to be highly expressed in ESCC tissues through high-throughput sequencing and quantitative real-time polymerase chain reaction. Subsequent in vitro and in vivo experiments are conducted to validate its biological functions. Furthermore, the regulatory relationships among circ_0006156, miR-202-5p, and TGFBR1 are investigated using RNA antisense purification, miRNA sequencing, RNA immunoprecipitation, fluorescence in situ hybridization, dual-luciferase reporter assay, and bioinformatics analyses. The results show significant overexpression of circ_0006156 in ESCC tissues, with relatively shorter overall survival observed in patients with high circ_0006156 expression. circ_0006156 is further identified to directly bind to miR-202-5p. miR-202-5p inhibits the proliferation, migration, and invasion of ESCC cells in vitro and partially rescues the effects induced by circ_0006156. Consistent results are reported by subcutaneous xenograft tumor experiments in nude mice. In addition, circ_0006156 is confirmed to act as an endogenous sponge for miR-202-5p, which results in a relieved suppression of its target gene TGFβR1. In summary, circ_0006156 can regulate TGFβR1 expression by sponging miR-202-5p, which may further activate the TGFβ/Smad pathway and promote ESCC progression. Collectively, circ_0006156 functions as a novel oncogenic RNA in ESCC and may serve as a potential tumor marker.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21253
BACKGROUND: Muscular atrophy is a pathological process characterized by the progressive decline in muscle mass and function, which severely affects patients' quality of life. In recent years, the role of mitophagy, as an important mitochondrial quality control mechanism for maintaining intracellular homeostasis, has attracted significant attention in the context of muscle atrophy. Drosophila, as a classical model organism, has become a crucial tool for studying the connection between muscle atrophy and mitophagy mechanism due to its conserved muscle functional structure and straightforward genetic manipulation. OBJECTIVE: To review the molecular mechanism of mitophagy dysfunction in muscular atrophy and to summarize the research progress of relevant Drosophila models in this field, with the aim of providing new insights and directions for the study of the pathological mechanism and the development of therapeutic strategies for muscular atrophy. METHODS: PubMed and China National Knowledge Infrastructure databases were searched using keywords including 'skeletal muscle, muscle regenerate, denervation muscle atrophy, muscle atrophy, sarcopenia, drosophila, drosophila melanogaster, mitophagy, mitochondrial dysfunction' and 'muscle atrophy, skeletal muscle, muscle regeneration, sarcopenia, denervation muscle atrophy, Drosophila, mitophagy, mitochondrial dysfunction'. The search period was from January 2001 to February 2025. After screening, 68 articles were included for review. RESULTS AND CONCLUSION: Studies using Drosophila models indicate that mitophagy plays a critical role in the development of muscle atrophy. Mitophagy dysfunction leads to the accumulation of damaged mitochondria in muscle cells, triggering oxidative stress, energy metabolism disorders, and inducing myocyte apoptosis, thereby exacerbating muscle atrophy. Furthermore, Drosophila models have shown great advantages in screening potential therapeutic targets and identifying intervention strategies, providing new avenues for mechanistic research and therapeutic development for muscle atrophy. By summarizing the findings from Drosophila models, this review emphasizes the strategy of treating muscle atrophy by modulating mitophagy mechanisms, highlights the unique advantages of Drosophila models in studying the molecular mechanisms of mitophagy and muscle atrophy, and suggests that future research should integrate translational medicine, high-throughput molecular screening, and multi-omics approaches to further explore unknown molecular mechanisms and new therapeutic targets.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21418
BACKGROUND: Clinically, due to the special anatomical characteristics and internal trabecular bone distribution of the scaphoid, the treatment effect of fractures is generally poor, often leading to nonunion and ischemic necrosis, which in turn causes wrist arthritis and loss of function. OBJECTIVE: To scan scaphoid specimens using Micro CT technology, analyze their internal microstructure characteristics, measure the trabecular bone microstructure parameters in each region, and discover regional differences in scaphoid trabecular bone, aiming to provide a scientific basis for the prevention, treatment, and fracture mechanism research of scaphoid fractures. METHODS: Bilateral scaphoid bones (10 cases) from 5 adult cadaver specimens were scanned by Micro CT. By selecting and reconstructing trabecular bone in three regions of interest (tubercle, waist, and body), the internal micromorphological characteristics of the scaphoid were observed in detail, and the differences in trabecular bone microstructure parameters among regions were measured and compared. RESULTS AND CONCLUSION: (1) Micro CT images showed that the cortical bone on the surface of the scaphoid was relatively thin, and the interior was filled with complex trabecular bone microstructure; the lamellar trabecular bone near the cortical bone was relatively dense, extending inward into rod-like trabecular bone. From sagittal, coronal, and transverse sections, the trabecular bone distribution in the waist was relatively sparse, while that in the body and tubercle was denser. (2) There were significant differences in bone volume fraction, bone surface area, bone surface area to tissue volume ratio, trabecular separation, trabecular number, trabecular connectivity, trabecular connection density, fractal dimension, bone mineral density, and bone mineral content of the scaphoid tubercle between left and right sides (P < 0.05). There were no significant differences in the trabecular bone microstructure parameters of the waist and body between left and right sides (P > 0.05). (3) There were significant differences in bone volume, bone volume fraction, bone surface area, bone surface area to tissue volume ratio, bone surface area to bone volume ratio, bone mineral density, and bone mineral content between the body and the tubercle/waist (P < 0.05). There was a significant difference in trabecular thickness between the body and the tubercle (P < 0.05). There were significant differences in trabecular separation and fractal dimension among the body, tubercle, and waist (P < 0.05). There were significant differences in trabecular number, trabecular connectivity, and trabecular connection density between the waist and the tubercle/body (P < 0.05). There were no significant differences in tissue volume and degree of anisotropy among the body, tubercle, and waist (P > 0.05). (4) The results showed that the trabecular bone microstructure parameters of the scaphoid had regional differences, among which the waist had lower bone density and strength, making it the most prone to fracture. This finding provides a theoretical basis for understanding the fracture mechanism of the scaphoid from the perspective of trabecular bone microstructure. At the same time, the trabecular bone structure characteristics of different parts of the scaphoid revealed in this study also provide a theoretical basis for designing targeted internal fixation instruments.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21520
BACKGROUND: 10-Hydroxy-2-decenoic acid (10-HDA) exhibits potent anti-inflammatory, antioxidant, and immunomodulatory effects, but its role in regulating bone metabolism remains unclear. OBJECTIVE: To investigate the regulatory effects and potential mechanisms of 10-HDA in bone remodeling. METHODS: Rat bone marrow mesenchymal stem cells (BMSCs) were cultured with different concentrations of 10-HDA (0, 0.5, 1, 2, 4 mmol/L); cytoskeletal staining, live/dead staining, and CCK-8 assay were used to assess cell morphology, viability, and proliferation. For osteogenic differentiation, BMSCs were cultured with 10-HDA (0, 0.5, 1, 2 mmol/L) and osteogenic induction; alkaline phosphatase (ALP) and alizarin red staining were performed, and osteogenic-related protein expression was analyzed by western blot and immunofluorescence. Mouse bone marrow mononuclear cells were induced to differentiate into macrophages and cultured in osteoclast differentiation medium with different concentrations of 10-HDA (0, 0.5, 1, 2 mmol/L); tartrate-resistant acid phosphatase (TRAP) and F-actin staining were used to detect osteoclast formation. BMSCs were serum-starved for 6 h and then cultured normally, divided into control, 10-HDA, 10-HDA+AS1842856 (FOXO1 inhibitor), and 10-HDA+EX-527 (SIRT1 inhibitor) groups; 10-HDA concentration was 0.5 mmol/L. Western blot and immunofluorescence were used to analyze SIRT1/FOXO1 pathway activation and expression of autophagy- and osteogenesis-related proteins. BMSCs were divided into control, H2O2, and H2O2+10-HDA groups; 10-HDA concentration was 0.5 mmol/L; after H2O2 treatment for 24 h, corresponding drug interventions were applied; after osteogenic induction, ALP and alizarin red staining were performed. BMSCs were divided into five groups: control, H2O2, H2O2+10-HDA, H2O2+10-HDA+AS1842856, and H2O2+10-HDA+EX-527; 10-HDA concentration was 0.5 mmol/L; after H2O2 treatment for 24 h, corresponding drug interventions were applied; western blot was used to detect SIRT1/FOXO1 signaling pathway and antioxidant-related protein expression; TUNEL and β-galactosidase staining were used to assess apoptosis and senescence. RESULTS AND CONCLUSION: Cytoskeletal staining, live/dead staining, and CCK-8 assay showed that 0.5, 1, 2 mmol/L 10-HDA promoted proliferation of rat BMSCs; these three concentrations were selected for subsequent experiments. ALP, alizarin red staining, western blot, and immunofluorescence analysis showed that 0.5 mmol/L 10-HDA promoted osteogenic differentiation and mineralization of rat BMSCs and increased osteogenic-related protein expression. TRAP and F-actin staining showed that 0.5 mmol/L 10-HDA significantly inhibited osteoclast formation. Western blot and immunofluorescence showed that 10-HDA activated the SIRT1/FOXO1 signaling pathway, promoted FOXO1 deacetylation and nuclear translocation, and upregulated autophagy-related proteins and antioxidant enzymes. ALP and alizarin red staining showed that under oxidative stress, 10-HDA promoted osteogenic differentiation and mineralization of rat BMSCs. Western blot showed that under oxidative stress, 10-HDA enhanced the antioxidant capacity of rat BMSCs by activating the SIRT1/FOXO1 signaling pathway. TUNEL and β-galactosidase staining showed that under oxidative stress, 10-HDA reduced apoptosis and senescence of rat BMSCs via activation of the SIRT1/FOXO1 signaling pathway. These findings indicate that 10-HDA enhances autophagy and antioxidant capacity through regulation of the SIRT1/FOXO1 signaling pathway, thereby promoting osteogenic differentiation.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026117
SGLT2 inhibitor (SGLT2i)-induced diabetic hyperketonemia is a life-threatening acute complication of diabetes. While celastrol has been reported to have beneficial effects on obesity, its potential role in ketogenesis remains unclear. In this study, celastrol administration significantly attenuates the fasting-induced increase in blood β-hydroxybutyrate levels. Moreover, a 7-day course of celastrol (1 mg/kg/day) leads to reductions in body weight and fat mass. Mechanistically, celastrol specifically downregulates HMGCS2 expression and suppresses hepatic ketogenesis through the inhibition of PPARα expression in the short term (≤ 2 days). However, after prolonged treatment for 7 days, celastrol modulates both PPARα and serum free fatty acid (FFA) levels. Furthermore, the anti-ketogenic effect of celastrol is abolished in Pparα⁻/⁻ mice. Importantly, celastrol effectively ameliorates SGLT2i-induced hyperketonemia. In summary, celastrol curbs hepatic ketone overproduction in a PPARα-dependent manner, indicating its protective potential against SGLT2i-induced hyperketonemia.