Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05044-y
Tooth loss remains a major unmet clinical challenge, and current prosthetic approaches cannot restore the biological complexity, sensory function, or regenerative capacity of natural teeth. Recent progress in stem cell biology, developmental engineering, and regenerative biomaterials has opened new possibilities for biological tooth regeneration. This review integrates advances across three major research domains that together define the current landscape of translational regenerative dentistry. First, we discuss stem cell-based, scaffold-guided strategies for tooth regeneration. These approaches combine dental and nondental stem cells, including DPSCs, SCAPs, PDLSCs, SHED, and iPSC-derived lineages, with bioactive materials such as HA/TCP ceramics, dentin-derived extracellular matrix scaffolds, and natural or synthetic polymers to promote odontogenic differentiation, vascularization, and periodontal attachment. Second, we summarize emerging tooth organoid and bioengineered tooth germ technologies that recapitulate epithelial–mesenchymal interactions and enable controlled reconstruction of dentin–pulp and periodontal compartments for modeling human odontogenesis. Third, we highlight molecular regulation-driven therapeutic strategies, focusing on the modulation of Wnt, BMP, FGF, TGF-β, and USAG-1 pathways to stimulate endogenous tooth regeneration and correct developmental defects. Despite marked progress, challenges remain, including stable neurovascular integration, optimization of stem cell–material crosstalk, precise control of spatiotemporal signaling, and long-term functional stability in vivo. Finally, we outline future directions involving smart biomaterials, gene- and protein-based molecular targeting, organoid-guided regeneration, and iPSC-enabled personalized therapies, which may further accelerate the clinical translation of stem cell-based tooth regeneration.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03882-2
Background Periodontal tissue loss is the main reason for tooth mobility and loss caused by periodontal disease. Dental follicle stem cells (DFSCs) have significant therapeutic potential in periodontal regeneration, which maybe mainly depends on their potent immunomodulatory capacity. Consequently, this study aims to elucidate the impact of implanted xenogenous DFSCs on innate immune responses during early and late stages in the periodontal defect repair period. Methods To trace and investigate the immunomodulation mechanisms of DFSCs in vivo, DFSCs were engineered (E-DFSCs) using lentiviral vectors expressing CD63-enhanced green fluorescent protein (CD63-EGFP) and β-Actin-mCherry protein (ACTB-mCherry) to exhibit green and red fluorescence. The biological characteristics and functions of E-DFSCs were verified by proliferation, differentiation, and co-culture experiments in vitro. In vivo, the periodontal regeneration capacity of E-DFSCs was detected by implantation of murine periodontal defect model, and the response of innate immune cells was detected at the 1st, 3rd, and 5th days (early stage) and 4th week (late stage) after implantation. Results In vitro assessments showed that E-DFSCs retain similar properties to their non-engineered counterparts but exhibit enhanced macrophage immunomodulation capability. In mice models, four-week micro-CT and histological evaluations indicated that E-DFSCs have equivalent efficiency to DFSCs in periodontal defect regeneration. At the early stage of repair in mice periodontal defect, fluorescence tracking showed that implanted E-DFSCs might primarily activate endogenous cells through direct contact and indirect actions, and most of these cells are myeloperoxidase-positive neutrophils. Additionally, compared with the control group, the neutrophilic infiltration and conversion of N2-type were significantly increased in the E-DFSC group. At the late stage of defect regeneration, more M2-type
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025196
Human embryonic kidney (HEK) 293 cells are widely used for recombinant protein production because of their efficient posttranslational modification capabilities. However, their large-scale culture is often limited by metabolic stress and early apoptosis, leading to insufficient protein yields. In this study, we aim to increase protein expression through the coordinated modulation of metabolic and apoptotic pathways. Using CRISPR/Cas9 technology, we target and knockout the genes of ornithine decarboxylase antizyme 1 (OAZ1), which regulates polyamine metabolism, and caspase 8-associated protein 2 (CASP8AP2), an apoptosis-related protein. We successfully construct an OAZ1/CASP8AP2 double-knockout HEK293 cell line. Following transfection with the knockout vector and screening of single-cell clones, multiple levels of validation confirm the successful gene knockout. The results show that the double-knockout cells exhibit significantly reduced apoptosis rates. Furthermore, the production of recombinant secreted alkaline phosphatase (SEAP) and vitronectin (VN) increases by 2.1 folds and 2.9 folds, respectively, compared with those in wild-type cells. Metabolic profiling reveals that the cell cycle is arrested in the G1/G0 phase, accompanied by increased specific consumption and production rates of key metabolites. This study demonstrates that concurrent inhibition of apoptosis and optimization of metabolism effectively enhances recombinant protein production in HEK293 cells, suggesting a novel strategy for improving HEK293 cell-based expression.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026074
Tryptophan (Trp)-substituted antimicrobial peptides (AMPs) exhibit enhanced interactions with bacterial cell membranes, potentially improving their antimicrobial efficacy. Klebsiella pneumoniae (20.59% of 2054 ICU isolates) is resistant to multiple clinically used antibiotics and presents significant treatment challenges. In the present study, three Trp-modified peptides (I4W, L12W, and I1WL5W) are generated by substituting Ile or Leu residues in temporin-1CEb, a peptide derived from frog skin, with Trp at various sites to assess their antibacterial effects and mechanisms against K. pneumoniae. Compared with L12W, both I4W and I1WL5W display superior antimicrobial activity and lower cytotoxicity. Mechanistic studies reveal that AMPs exert antibacterial and bactericidal effects through bacterial surface charge neutralization, insertion into bacterial cell membranes, increase permeability of both the inner and outer membranes, and disruption of membrane integrity. Notably, I1WL5W exhibit the most potent membrane-disrupting activity. Assessment of the impact of Trp-containing peptides on bacterial biofilms reveals that these peptides not only inhibit exopolysaccharide production and biofilm formation but also degrade preformed biofilms. A murine lung infection model is established to investigate the therapeutic efficacy of I1WL5W against MDRKP 1203-induced lung infection in mice. Compared with the control treatment, treatment with I1WL5W results in reduced bacterial counts and levels of IL-6 and TNF-α in both the blood and lung tissues of MDRKP 1203-infected mice, and treatment with I1WL5W improves lung tissue structure. The present study provides valuable insights for designing Trp-containing peptides with potent antimicrobial properties by facilitating their penetration across bacterial membranes.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024087
The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of neointima formation in vascular restenosis. This study aims to explore the function of the long noncoding RNA H19 in neointima formation. A mouse carotid ligation model was established, and human vascular smooth muscle cells (VSMCs) were used as a cell model. lncRNA H19 overexpression promoted VSMC proliferation and migration. Moreover, miR-125a-3p potentially bound to lncRNA H19, and Fms-like tyrosine kinase-1 (FLT1) might be a direct target of miR-125a-3p in VSMCs. Upregulation of miR-125a-3p alleviated lncRNA H19-enhanced VSMC proliferation and migration. Furthermore, rescue experiments showed that enhanced expression of miR-125a-3p attenuated lncRNA H19-induced FLT1 expression in VSMCs. In addition, the overexpression of lncRNA H19 significantly exacerbated neointima formation in a mouse carotid ligation model. In summary, lncRNA H19 stimulates VSMC proliferation and migration by acting as a competing endogenous RNA (ceRNA) of miR-125a-3p. lncRNA H19 may be a therapeutic target for restenosis.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261603
The inflorescences of Inula japonica Thunb. (Asteraceae) are a traditional Chinese medicine used for treating cough, phlegm, and vomiting. Sesquiterpenoid dimers, formed via Diels-Alder, hetero-Diels-Alder, [2+2] cycloaddition, or radical coupling, exhibit potent anti-inflammatory, neuroprotective, and antitumor activities. However, their low natural abundance and structural complexity hinder isolation and development. This study isolated six sesquiterpenoid dimers from the ethyl acetate fraction of a 90% ethanol extract of I. japonica using multiple chromatographic techniques. Their structures were elucidated by HRESIMS, NMR, IR, UV, and calculated NMR/ECD. Compounds 1 (inujaponolide T) and 3 (inujaponolide U) are new: a eudesmane-guaiane dimer and a 1,10-seco-eudesmane-guaiane dimer, respectively. The other four were identified as inujaponolide E (2), inujaponolide D (4), inujaponolide I (5), and japonicone X (6). In vitro anti-hepatocellular carcinoma activity was evaluated against HepG2 cells using MTT and colony formation assays. All compounds exhibited potent cytotoxicity with IC50 values of 2.61–13.94 μmol/L; compound 6 was most active (IC50 = 2.61 μmol/L). A preliminary structure-activity relationship indicated a positive correlation between the number of acetoxy substituents and antitumor activity. Compounds 1 and 3 inhibited cell viability and reduced colony formation in a dose-dependent manner. These findings expand the chemical diversity of I. japonica and provide a basis for developing these dimers as anti-hepatocellular carcinoma lead compounds.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05044-y
Tooth loss remains a major unmet clinical challenge, and current prosthetic approaches cannot restore the biological complexity, sensory function, or regenerative capacity of natural teeth. Recent progress in stem cell biology, developmental engineering, and regenerative biomaterials has opened new possibilities for biological tooth regeneration. This review integrates advances across three major research domains that together define the current landscape of translational regenerative dentistry. First, we discuss stem cell-based, scaffold-guided strategies for tooth regeneration. These approaches combine dental and nondental stem cells, including DPSCs, SCAPs, PDLSCs, SHED, and iPSC-derived lineages, with bioactive materials such as HA/TCP ceramics, dentin-derived extracellular matrix scaffolds, and natural or synthetic polymers to promote odontogenic differentiation, vascularization, and periodontal attachment. Second, we summarize emerging tooth organoid and bioengineered tooth germ technologies that recapitulate epithelial–mesenchymal interactions and enable controlled reconstruction of dentin–pulp and periodontal compartments for modeling human odontogenesis. Third, we highlight molecular regulation-driven therapeutic strategies, focusing on the modulation of Wnt, BMP, FGF, TGF-β, and USAG-1 pathways to stimulate endogenous tooth regeneration and correct developmental defects. Despite marked progress, challenges remain, including stable neurovascular integration, optimization of stem cell–material crosstalk, precise control of spatiotemporal signaling, and long-term functional stability in vivo. Finally, we outline future directions involving smart biomaterials, gene- and protein-based molecular targeting, organoid-guided regeneration, and iPSC-enabled personalized therapies, which may further accelerate the clinical translation of stem cell-based tooth regeneration.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025196
Human embryonic kidney (HEK) 293 cells are widely used for recombinant protein production because of their efficient posttranslational modification capabilities. However, their large-scale culture is often limited by metabolic stress and early apoptosis, leading to insufficient protein yields. In this study, we aim to increase protein expression through the coordinated modulation of metabolic and apoptotic pathways. Using CRISPR/Cas9 technology, we target and knockout the genes of ornithine decarboxylase antizyme 1 (OAZ1), which regulates polyamine metabolism, and caspase 8-associated protein 2 (CASP8AP2), an apoptosis-related protein. We successfully construct an OAZ1/CASP8AP2 double-knockout HEK293 cell line. Following transfection with the knockout vector and screening of single-cell clones, multiple levels of validation confirm the successful gene knockout. The results show that the double-knockout cells exhibit significantly reduced apoptosis rates. Furthermore, the production of recombinant secreted alkaline phosphatase (SEAP) and vitronectin (VN) increases by 2.1 folds and 2.9 folds, respectively, compared with those in wild-type cells. Metabolic profiling reveals that the cell cycle is arrested in the G1/G0 phase, accompanied by increased specific consumption and production rates of key metabolites. This study demonstrates that concurrent inhibition of apoptosis and optimization of metabolism effectively enhances recombinant protein production in HEK293 cells, suggesting a novel strategy for improving HEK293 cell-based expression.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026074
Tryptophan (Trp)-substituted antimicrobial peptides (AMPs) exhibit enhanced interactions with bacterial cell membranes, potentially improving their antimicrobial efficacy. Klebsiella pneumoniae (20.59% of 2054 ICU isolates) is resistant to multiple clinically used antibiotics and presents significant treatment challenges. In the present study, three Trp-modified peptides (I4W, L12W, and I1WL5W) are generated by substituting Ile or Leu residues in temporin-1CEb, a peptide derived from frog skin, with Trp at various sites to assess their antibacterial effects and mechanisms against K. pneumoniae. Compared with L12W, both I4W and I1WL5W display superior antimicrobial activity and lower cytotoxicity. Mechanistic studies reveal that AMPs exert antibacterial and bactericidal effects through bacterial surface charge neutralization, insertion into bacterial cell membranes, increase permeability of both the inner and outer membranes, and disruption of membrane integrity. Notably, I1WL5W exhibit the most potent membrane-disrupting activity. Assessment of the impact of Trp-containing peptides on bacterial biofilms reveals that these peptides not only inhibit exopolysaccharide production and biofilm formation but also degrade preformed biofilms. A murine lung infection model is established to investigate the therapeutic efficacy of I1WL5W against MDRKP 1203-induced lung infection in mice. Compared with the control treatment, treatment with I1WL5W results in reduced bacterial counts and levels of IL-6 and TNF-α in both the blood and lung tissues of MDRKP 1203-infected mice, and treatment with I1WL5W improves lung tissue structure. The present study provides valuable insights for designing Trp-containing peptides with potent antimicrobial properties by facilitating their penetration across bacterial membranes.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21301
BACKGROUND: The pathogenesis of non-alcoholic fatty liver disease is closely associated with gut microbiota dysbiosis. In recent years, accumulating evidence has indicated that exercise may exert beneficial effects on host metabolic homeostasis by modulating the composition and function of the gut microbiota, thereby playing a positive role in the prevention and treatment of non-alcoholic fatty liver disease. OBJECTIVE: To systematically summarize current research progress on the interplay between gut microbiota and non-alcoholic fatty liver disease, to further elucidate the regulatory effects of exercise on gut microbiota, and to explore in depth the potential mechanisms by which exercise intervention may prevent or ameliorate non-alcoholic fatty liver disease via the "gut–liver axis." METHODS: Search terms included "non-alcoholic fatty liver disease," "gut microbiota," "exercise," "bile acid," "short-chain fatty acid," "lipopolysaccharide," "trimethylamine oxide," and "indole" in Chinese and English, respectively. China National Knowledge Infrastructure (CNKI), and WanFang Database were searched for relevant studies published up to March 2025. A total of 85 core studies were identified based on the inclusion and exclusion criteria. RESULTS AND CONCLUSION: (1) The composition of gut microbiota in patients with non-alcoholic fatty liver disease is significantly abnormal, with increased abundance of pro-inflammatory bacteria (such as Proteobacteria, Escherichia coli, and Streptococcus) and pathogenic bacteria (such as Enterobacteriaceae), while the abundance of anti-inflammatory and homeostatic bacteria (such as Ruminococcus and Faecalibacterium) is decreased. These adverse changes in microbial composition may promote the entry of metabolites into the liver by increasing intestinal permeability, activating inflammatory pathways, and increasing endogenous ethanol production, thereby driving the pathological progression of non-alcoholic fatty liver disease. (2) Modulating gut microbiota through probiotic supplementation or fecal microbiota transplantation can effectively reduce transaminase levels and chronic inflammation in patients with non-alcoholic fatty liver disease, suggesting that gut microbiota may be an important target for the prevention and treatment of non-alcoholic fatty liver disease. (3) Exercise can regulate gut microbiota composition, increase the abundance of beneficial bacteria, reduce the abundance of pro-inflammatory bacteria, and promote the activation of key metabolic pathways, thereby improving host metabolic health. However, current research on the effects of exercise on gut microbiota in patients with non-alcoholic fatty liver disease remains relatively limited, especially the effects and mechanisms of different exercise types, intensities, and durations on gut microbiota and host metabolism are still unclear. (4) Exercise may regulate gut microbiota and increase short-chain fatty acid production to activate G protein-coupled receptors 41/43 and AMP-activated protein kinase pathways, inhibit histone deacetylase activity, thereby reducing hepatic fat accumulation, alleviating liver inflammation, and decreasing insulin resistance; exercise may regulate the gut microbiota-bile acid axis to improve bile acid metabolism, thereby mediating the farnesoid X receptor/G protein-coupled bile acid receptor 5 signaling pathway to prevent and treat non-alcoholic fatty liver disease; exercise may reshape gut microbiota to reduce the abundance of lipopolysaccharide-containing Gram-negative bacteria and improve intestinal barrier function to reduce lipopolysaccharide production and translocation, preventing and treating non-alcoholic fatty liver disease; exercise may regulate gut microbiota composition to enhance the synthesis of indole and its derivatives, while inhibiting the production of ethanol and trimethylamine oxide, thereby enhancing liver metabolic capacity, improving intestinal barrier function, and reducing liver inflammation, playing a positive role in the prevention and treatment of non-alcoholic fatty liver disease.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21320
BACKGROUND: Xanthohumol is a natural polyphenol that exhibits biological activities such as antioxidant and anti-inflammatory properties. Recently, it has been found to potentially improve lipid metabolism disorders. As an aerobic exercise, swimming can effectively regulate body energy metabolism and reduce hepatic fat accumulation. However, the intervention effect and mechanism of their combined application on metabolic associated fatty liver disease remain unclear. OBJECTIVE: To investigate the effect of xanthohumol combined with swimming on the ferroptosis pathway mediated by nuclear factor erythroid 2-related factor 2 in rats with metabolic associated fatty liver disease. METHODS: Rats were randomly divided into seven groups: control group, model group, exercise group, low-, medium-, and high-dose xanthohumol, and combination groups, with 12 rats in each group. The rats in control group were fed with normal feed, while the rats in other groups were used to prepare metabolic associated fatty liver disease models. Rats in the exercise and combination groups received swimming training once a day, 6 days per week, for a total of 8 weeks. Rats in other groups were raised quietly. Rats in the low-, medium-, and high-dose xanthohumol groups were intragastrically administered 2 mL of 25, 50, and 100 mg/(kg·d) xanthohumol, respectively; rats in the combination group were intragastrically administered 2 mL of 100 mg/(kg·d) xanthohumol while undergoing swimming training; other groups were intragastrically administered 2 mL of 0.3% sodium carboxymethyl cellulose, for a total of 8 weeks. After treatment, serum alanine aminotransferase, aspartate aminotransferase, and free fatty acid levels were measured; hepatic lipid accumulation was observed by hematoxylin-eosin staining; hepatic malondialdehyde and reduced glutathione levels were detected according to kit instructions; hepatic ferrous ion content was measured by microassay; Western blot was used to detect the protein expression of nuclear factor erythroid 2-related factor 2, Kelch-like ECH-associated protein 1, and glutathione peroxidase 4 in liver tissue; RT-qPCR was used to detect the mRNA levels of ferroptosis-related genes (glutathione peroxidase 4, solute carrier family 7 member 11, ferritin heavy chain 1, ferroportin 1, and cationic transport regulator-like protein 1). RESULTS AND CONCLUSION: Compared with the exercise group and high-dose xanthohumol group, the combination group showed lower serum alanine aminotransferase, aspartate aminotransferase, and free fatty acid levels, improved liver morphology, decreased hepatic malondialdehyde level, increased reduced glutathione level, decreased hepatic ferrous ion content, increased protein expression of nuclear factor erythroid 2-related factor 2 (nuclear) and glutathione peroxidase 4, decreased protein expression of Kelch-like ECH-associated protein 1, increased mRNA levels of glutathione peroxidase 4, solute carrier family 7 member 11, ferritin heavy chain 1, and ferroportin 1, and decreased mRNA level of cationic transport regulator-like protein 1 (P < 0.05). These findings suggest that xanthohumol combined with swimming may improve hepatic injury in rats with metabolic associated fatty liver disease by regulating the ferroptosis pathway mediated by nuclear factor erythroid 2-related factor 2.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21361
BACKGROUND: Stem cells have the potential for self-renewal and multi-directional differentiation, which can enhance tissue repair through direct differentiation or paracrine and immunomodulatory microenvironments. Acupuncture can promote the proliferation and differentiation of stem cells through multi-pathway synergy, which expands the application range of acupuncture. OBJECTIVE: To review the types of stem cells and their differentiation potential, and to explore the role and mechanism of acupuncture in promoting stem cell proliferation and differentiation. METHODS: Articles published before March 2025 were searched in PubMed and CNKI databases using English search terms 'Electroacupuncture, Acupuncture, Neural stem cells, Bone marrow mesenchymal stem cells, Adipose mesenchymal stem cells' and Chinese search terms '电针, 针刺, 神经干细胞, 骨髓间充质干细胞, 脂肪间充质干细胞'. Literature related to acupuncture promoting stem cell proliferation and differentiation was included, while irrelevant content was excluded. Finally, 76 articles were selected for analysis. RESULTS AND CONCLUSION: (1) Stem cells belong to the category of kidney essence, and stem cells and kidney essence play a synergistic role, which can be used to guide the treatment of diseases with kidney essence deficiency, explaining modern medicine with traditional Chinese medicine theory. (2) Acupuncture can activate multiple signaling pathways and regulate growth factor expression to promote the proliferation and differentiation of endogenous or exogenous stem cells, providing new ideas for clinical treatment. (3) Although acupuncture plays an important role in stem cell proliferation and differentiation, it also faces many challenges in application; the establishment of stem cell engineering standards and the innovative development of acupuncture therapy are the primary prerequisites for in-depth exploration of the combined mechanism of acupuncture and stem cell therapy, ensuring the stability and efficiency of treatment effects.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026026
Epstein-Barr virus (EBV) is now recognized as the definitive environmental driver of multiple sclerosis (MS), shifting the conceptual landscape of this autoimmune disorder to an infection-triggered model. In this review, we systematically evaluate the multidimensional evidence linking EBV to MS. This evidence ranges from epidemiological associations and the identification of mimotopes to emerging therapeutic strategies. We also discuss the broader implications of infection-driven immune dysregulation for autoimmune research. This pathogenic link is underpinned by molecular mimicry, where immune responses against the viral protein EBNA1 cross-react with the central nervous system (CNS) protein GlialCAM. Beyond this initial insult, EBV reprograms B cells to survive and proliferate abnormally, creating a compartmentalized viral reservoir within the CNS that sustains chronic neuroinflammation. These mechanistic insights catalyze a transition from broad immunosuppression to precision therapies targeting the EBV-MS axis, including CNS-penetrant kinase inhibitors and EBV-specific CAR-T cells. By integrating etiological discovery with mechanism-based intervention, the EBV-MS paradigm serves as a blueprint for transforming idiopathic autoimmune diseases into mechanistically tractable conditions with actionable therapeutic targets.