Bioorthogonal Quinone Methide Decaging Enables Live-Cell Quantification of Tumor-Specific Immune Interactions.

Effective antitumor immunity hinges on the specific engagement between tumor and cytotoxic immune cells, especially cytotoxic T cells. Although investigating these intercellular interactions is crucial for characterizing immune responses and guiding immunotherapeutic applications, direct and quantitative detection of tumor-T cell interactions within a live-cell context remains challenging. We herein report a photocatalytic live-cell interaction labeling strategy (CAT-Cell) relying on the bioorthogonal decaging of quinone methide moieties for sensitive and selective investigation and quantification of tumor-T cell interactions. By developing quinone methide-derived probes optimized for capturing cell-cell interactions (CCIs), we demonstrated the capacity of CAT-Cell for detecting CCIs directed by various types of receptor-ligand pairs (e.g., CD40-CD40L, TCR-pMHC) and further quantified the strengths of tumor-T cell interactions that are crucial for evaluating the antitumor immune responses. We further applied CAT-Cell for ex vivo quantification of tumor-specific T cell interactions on splenocyte and solid tumor samples from mouse models. Finally, the broad compatibility and utility of CAT-Cell were demonstrated by integrating it with the antigen-specific targeting system as well as for tumor-natural killer cell interaction detection. By leveraging the bioorthogonal photocatalytic decaging chemistry on quinone methide, CAT-Cell provides a sensitive, tunable, universal, and noninvasive toolbox for unraveling and quantifying the crucial but delicate tumor-immune interactions under live-cell settings.

Polarized Th2 cells attenuate high-fat-diet induced obesity through the suppression of lipogenesis.

Immune cells, such as macrophages, B cells, neutrophils and T cell subsets, have been implicated in the context of obesity. However, the specific role of Th2 cells in adipose tissue function has remained elusive. Eight-week-old male CD3ε─/─ mice were randomly divided into two groups (≥ 5 mice per group): one received intravenous injection of Th2 cells isolated from LATY136F mice, while the other receiving PBS as a control. Both of groups were subjected to a high-fat diet (HFD). The adoptive transfer of polarized Th2 cells led to a significant reduction in obesity following a HFD. This reduction was accompanied by improvements in hepatic steatosis, glucose intolerance, and insulin resistance. Mechanistically, Th2 cell treatment promoted oxidative phosphorylation of adipocytes, thereby contributing to a reduction of lipid droplet accumulation. These findings suggest that Th2 cell therapy represents a novel approach for treating diet-induced obesity and other diseases involving lipid droplet accumulation disorders.

Association Between Peritoneal Carcinomatosis Index (PCI) Assessed by CT and Pathological Parameters and Short-Term Prognosis of Rectal Cancer.

Objective: The study aimed at explore the correlation between the CT-based Peritoneal Carcinomatosis Index (PCI) and pathological parameters of rectal cancer, as well as the correlation with short-term postoperative prognosis. Methods: A retrospective analysis was performed on 198 rectal cancer patients treated in our institution from January 2017 to December 2022. Based on preoperative CT-PCI, patients were classified into a normal and low CT-PCI groups. Baseline characteristics and short-term postoperative outcomes were compared between the two groups. Univariate and Multivariable logistic regression analyses were conducted to ascertain the independent risk factors for postoperative complications (Clavien-Dindo classification ≥ Grade II) following neoadjuvant treatment and radical rectal cancer surgery. Results: There were significant statistical differences between the two groups regarding age, ASA score, and surgical method (P < .05). Variations in overall postoperative complications and complications of Grade II or higher among patients with differing preoperative CT-PCI were statistically significant (P < .05). No significant statistical difference was found in the time to first liquid intake post-surgery between the preoperative low CT-PCI group and the normal CT-PCI group (P > .05); however, differences in the time to first flatus, duration of postoperative hospital stay, and total hospital expenditure were statistically meaningful (P < .05). Multivariate logistic regression revealed that CT-PCI (OR=2.254) was an influential factor for postoperative complications (Clavien-Dindo classification ≥ Grade II) (P < .05). The ROC curve demonstrated an AUC of 0.854 for CT-PCI in predicting postoperative complications (Clavien-Dindo classification ≥ Grade II). Conclusion: Preoperative CT-PCI may be utilized to evaluate the short-term prognosis of patients who undergo radical surgery for rectal cancer after neoadjuvant therapy. This evaluation assists in guiding clinical diagnostic and therapeutic decision-making, allowing for prompt interventions and enhancing short-term patient outcomes.

Comparisons of ankle arthrodesis with different internal fixation methods in the treatment of post-traumatic osteoarthritis.

BACKGROUND: The aim of this study was to explore the clinical efficacy of ankle arthrodesis with different internal fixation methods in the treatment of post-traumatic osteoarthritis. METHODS: We collected 85 patients with post-traumatic osteoarthritis who underwent different ankle arthrodesis between December 2015 and December 2020. The operation performance, complication rate, hindfoot alignment, talus tilt angle, visual analogue scale (VAS), and American Orthopedic Foot and Ankle Society (AOFAS) score were preoperatively and postoperatively evaluated. RESULTS: In an anterior approach, the locking plate-fixation exhibited a similarity in operation time, incision length, postoperative drainage, bone fusion, hindfoot alignment, and talus tilt angle with fibula support compression screw-fixation, but it was better in increasing postoperative AOFAS. The locking plate-fixation in the anterior approach had lower operation time, incision length, and postoperative drainage than that in the lateral approach. In addition, the lateral locking plate combined with posterolateral compression screw fixation (LLPPCSF) presented shorter bone fusion time, higher AOFAS score, and lower complication rate than either plate- or screw-fixation alone. CONCLUSION: Lateral locking plate fixation was better than fibula support compression screw fixation in relieving postoperative pain. Anterior locking plate fixation was more time-saving and less invasiveness than lateral locking plate fixation, but its application was limited in low degree of ankle deformation. LLPPCSF was the most effective in improving bone fusion and postoperative pain, considering an optimal option for the treatment of post-traumatic osteoarthritis.

Refracture-related bone transport of tibia: technical notes and preliminary clinical results in nineteen cases.

PURPOSE: Refracture is one of the main complications of bone transport, which brings additional physical and mental burden to surgeries and patients. We aimed to raise a new classification system of refracture-related bone transport based on the Simpson classification and to present our experience on treatment. METHODS: This retrospective analysis included 19 patients with refracture-related bone transport (average age of 37.7 years; 18 men). We developed a modified Simpson classification system to assist decision-making (conservative versus surgical). The ASAMI criteria were used to assess the outcomes at last follow-up. RESULTS: The mean follow-up was 12.3 ± 3.2 months. Complete union was achieved in all patients, with no reinfection. Based on the modified Simpson classification, refracture was Ia type (within regeneration area) in three cases, Ib (collapsed fracture at the regeneration area) in one case, Ic (stress fracture) in three cases, II (at the junction between the regenerate and original bone) in one case, III (at the docking site) in nine cases, and V (at distant site) in two cases. Refracture was managed conservatively in six cases and surgically in 13 cases. Average time to bone union was 2.8 ± 1.2 months in the conservative group versus 4.4 ± 1.4 months in the surgery group. Assessment at the final follow-up using the ASAMI criteria revealed excellent bone result in all patients, excellent functional results in six patients (31.6%), and good functional results in 13 patients. CONCLUSIONS: The modified Simpson classification could include refracture at the docking site and stress fracture in the regeneration zone and provide some guidance in determining the appropriate treatment strategy.

Combined therapy of prednisone and mTOR inhibitor sirolimus for treating retroperitoneal fibrosis.

OBJECTIVES: Retroperitoneal fibrosis (RPF) is a rare autoimmune disease with fibrous tissue growth and inflammation in retroperitoneum. Its current treatments involve long-term uptake of glucocorticoids (e.g., prednisone) for controlling inflammation; however, side effects are common. We strived for an improved therapy for fibrosis remission while reducing side effects. METHODS: We surveyed gene-disease-drug databases and discovered that mammalian target of rapamycin (mTOR) was a key signalling protein in RPF and the mTOR inhibitor compound sirolimus affected many RPF pathways. We designed a therapy combining a gradual reduction of prednisone with a long-term, stable dosage of sirolimus. We then implemented a single-arm clinical trial and assessed the effects in eight RPF patients at 0, 12 and 48 weeks of treatment by measuring fibrous tissue mass by CT, markers of inflammation and kidney functions by lab tests, immune cell profiles by flow cytometry and plasma inflammatory proteins by Olink proteomics. RESULTS: With the combined therapy, fibrous tissue shrunk about by half, markers of acute inflammation reduced by 70% and most patients with abnormal kidney functions had them restored to normal range. Molecularly, fibrosis-related T cell subsets, including TH2, TH17 and circulating TFH cells, were reduced and tumour necrosis factor and related cytokines restored to healthy levels. No severe long-term side effects were observed. CONCLUSIONS: Our combined therapy resulted in significant fibrosis remission and an overall regression of the immune system towards healthy states, while achieving good tolerance. We concluded that this new therapy had the potential to replace the steroid monotherapy for treating RPF.

Subcortical structures associated with childhood trauma and perceived stress in schizophrenia.

BACKGROUND: Childhood trauma influences the clinical features of schizophrenia. In this study, we examined how childhood trauma and perceived stress are associated with clinical manifestations and subcortical gray matter volumes (GMVs) in patients with schizophrenia. METHODS: We recruited 127 patients with schizophrenia and 83 healthy controls for assessment of early childhood trauma, perceived stress, and clinical symptoms. With structural brain imaging, we identified the GMVs of subcortical structures and examined the relationships between childhood trauma, perceived stress, clinical symptoms, and subcortical GMVs. RESULTS: Compared to controls, patients with schizophrenia showed higher levels of childhood trauma and perceived stress. Patients with schizophrenia showed significantly smaller amygdala and hippocampus GMVs as well as total cortical GMVs than age-matched controls. Childhood trauma score was significantly correlated with the severity of clinical symptoms, depression, perceived stress, and amygdala GMVs. Perceived stress was significantly correlated with clinical symptoms, depression, and hippocampus and amygdala GMVs. Further, the association between childhood trauma (emotional neglect) and stress coping ability was mediated by right amygdala GMV in patients with schizophrenia. CONCLUSIONS: Patients with schizophrenia had more exposure to early-life trauma and poorer stress coping. Both childhood trauma and perceived stress were associated with smaller amygdala volumes. The relationship between early-life trauma and perceived stress was mediated by right amygdala GMV in patients with schizophrenia. These findings together suggest the long-term effects of childhood trauma on perceived stress and the subcortical volumetric correlates of the effects in schizophrenia.

Adiponectin overexpression promotes fracture healing through regulating the osteogenesis and adipogenesis balance in osteoporotic mice.

INTRODUCTION: Osteoporosis invariably manifests as loss of bone, which is replaced by adipose tissue; this can easily lead to fractures, accompanied by delayed and poor healing. Adiponectin (APN) balances osteogenesis and adipogenesis in bone marrow mesenchymal stem cells (BMSCs). Therefore, this study explored whether adiponectin promotes bone fracture healing by regulating the balance between osteogenesis and adipogenesis. MATERIALS AND METHODS: We used adenovirus overexpression vectors carrying APN (Ad-APN-GFP) to treat ovariectomized (OVX) mouse BMSCs and osteoporotic bone fractures to investigate the role of APN in bone microenvironment metabolism in osteoporotic fractures. We subsequently established an OVX mice and bone fracture model using Ad-APN-GFP treatment to investigate whether APN could promote bone fracture healing in osteoporotic mice. RESULTS: The experimental results showed that APN is a critical molecule in diverse differentiation directions in OVX mouse BMSCs, with pro-osteogenesis and anti-adipogenesis properties. Importantly, our study revealed that Ad-APN-GFP treatment facilitates bone generation and healing around the osteoporotic fracture ends. Moreover, we identified that Sirt1 and Wnt signaling were closely related to the pro-osteogenesis and anti-adipogenesis commitment of APN in OVX mouse BMSCs and femoral tissues. CONCLUSION: We demonstrated that APN overexpression facilitates bone fracture healing in osteoporosis. Furthermore, APN overexpression promoted bone formation in OVX mouse BMSCs and bone fracture ends by regulating the balance between osteogenesis and adipogenesis both in vitro and in vivo.

Long non-coding RNA APDC plays important regulatory roles in metabolism of bone and adipose tissues.

The long noncoding RNA (lncR) ANRIL in the human genome is an established genetic risk factor for atherosclerosis, periodontitis, diabetes, and cancer. However, the regulatory role of lncR-ANRIL in bone and adipose tissue metabolism remains unclear. To elucidate the function of lncRNA ANRIL in a mouse model, we investigated its ortholog, AK148321 (referred to as lncR-APDC), located on chr4 of the mouse genome, which is hypothesized to have similar biological functions to ANRIL. We initially revealed that lncR-APDC in mouse bone marrow cells (BMSCs) and lncR-ANRIL in human osteoblasts (hFOBs) are both increased during early osteogenesis. Subsequently, we examined the osteogenesis, adipogenesis, osteoclastogenesis function with lncR-APDC deletion/overexpression cell models. In vivo, we compared the phenotypic differences in bone and adipose tissue between APDC-KO and wild-type mice. Our findings demonstrated that lncR-APDC deficiency impaired osteogenesis while promoting adipogenesis and osteoclastogenesis. Conversely, the overexpression of lncR-APDC stimulated osteogenesis, but impaired adipogenesis and osteoclastogenesis. Furthermore, KDM6B was downregulated with lncR-APDC deficiency and upregulated with overexpression. Through binding-site analysis, we identified miR-99a as a potential target of lncR-APDC. The results suggest that lncR-APDC exerts its osteogenic function via miR-99a/KDM6B/Hox pathways. Additionally, osteoclasto-osteogenic imbalance was mediated by lncR-APDC through MAPK/p38 and TLR4/MyD88 activation. These findings highlight the pivotal role of lncR-APDC as a key regulator in bone and fat tissue metabolism. It shows potential therapeutic for addressing imbalances in osteogenesis, adipogenesis, and osteoclastogenesis.

A Systematic Review and Meta-Analysis of Complications among Various Reduction Malarplasty.

BACKGROUND: Reduction malarplasty is one of the most common aesthetic procedures to improve a wide bizygomatic width and a prominent zygomatic body. Although there are various kinds of modifications, any method is imperfect, while some complications may occur. The purpose of this review was to compare kinds of complications of reduction malarplasty to provide certain suggestions for clinical application. METHODS: A comprehensive computerized search of scientific literature was performed via the PubMed, Web of Science, and Library of Congress databases, involved in articles from January 1st, 1983 to February 28th, 2022. The outcomes were extracted and analyzed by 3 independent authors, including patient demographics, diagnoses, surgical techniques, postoperative outcomes, and complications. RESULTS: A total of 29 studies covering 6611 patients were included according to the inclusion and exclusion criteria. The L-shaped osteotomy may obtain a better effect when someone has both zygomatic body and arch protrusion. In the view of complications, our conclusion suggested that L-shaped osteotomy without bony resection reduced the zygomatic complex effectively with the lowest incidence of postoperative complications (0.02%). But the amount of bone resection is limited. If increasing bone resection is necessary, L-shaped osteotomy with long arm bony resection and L-shaped osteotomy with short arm bony resection are both preferable choices with lowest incidence of structural and functional complications, respectively. CONCLUSION: L-shaped osteotomy may obtain a better effect when a patient has both zygomatic body and arch protrusion. L-shaped osteotomy without bony resection reduced the zygomatic complex effectively with the lowest incidence of postoperative complications. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Antigen-Specific T Cell Detection via Photocatalytic Proximity Cell Labeling (PhoXCELL).

Quantitative detection and characterization of antigen-specific T cells are crucial to our understanding of immune responses as well as the development of new immunotherapies. Herein, we report a spatiotemporally resolved method for the detection and quantification of cell-cell interactions via Photocatalytic proXimity CELl Labeling (PhoXCELL). The biocompatible photosensitizer dibromofluorescein (DBF) was leveraged and optimized as a nongenetic alternative of enzymatic approaches for efficient generation of singlet oxygen upon photoirradiation (520 nm) on the cell surface, which allowed the subsequent labeling of nearby oxidized proteins with primary aliphatic amine-based probes. We demonstrated that DBF-functionalized dendritic cells (DCs) could spatiotemporally label interacting T cells in immune synapses via rapid photoirradiation with quantitatively discriminated interaction strength, which revealed distinct gene signatures for T cells that strongly interact with antigen-pulsed DCs. Furthermore, we employed PhoXCELL to simultaneously detect tumor antigen-specific CD8+ as well as CD4+ T cells from tumor-infiltrating lymphocytes and draining lymph nodes in murine tumor models, enabling PhoXCELL as a powerful platform to identify antigen-specific T cells in T cell receptor (TCR)-relevant personal immunotherapy.

MicroRNA-1298-5p inhibits cell proliferation and the invasiveness of bladder cancer cells via down-regulation of connexin 43.

MicroRNA (miR)-1298 is widely down-regulated in a variety of malignant tumors, which facilitates cell proliferation, invasiveness, and migration. However, the specific biological function of miR-1298 in bladder cancer (BC) is still unknown. Connexin 43 (Cx43) is often up-regulated in tumors. Identifying miRNAs that target Cx43 in the setting of BC will help to develop Cx43-based therapies for BC. In this study, the results demonstrated that the expression levels of miR-1298 and Cx43 were significantly down-regulated and up-regulated, respectively, in BC tissues. Overexpression of miR-1298 inhibited cell proliferation, migration, and invasiveness in two BC cell lines as determined using MTT assays, cell cycle assays, colony formation assays, Transwell assays, gelatin zymography, and Western blot. In addition, we found that miR-1298 decreased Cx43 expression by directly targeting the 3'-UTR. Further, we observed that the promotion of BC cell proliferation, migration, and invasiveness from Cx43 on could be partially attenuated by overexpressing miR-1298. Moreover, the protein expression of p-ERK was ameliorated after transfection with overexpressed-miR-1298. Knockdown of Cx43 reversed the promotion of cell migration and invasiveness due to decreased expression of miR-1298. All of the data from our study indicate that miR-1298 could be a diagnostic marker of BC and a potential therapeutic agent via inhibiting Cx43.

Enzyme-Mediated Intercellular Proximity Labeling for Detecting Cell-Cell Interactions.

Cell-cell interactions and communications play fundamental roles in life processes but remain largely uncharacterized. We developed an enzyme-mediated proximity cell labeling (EXCELL) strategy as a general method to detect and record cell-cell interactions under living conditions. EXCELL relies on an evolved Staphylococcus aureus transpeptidase sortase A variant (mgSrtA) capable of promiscuous labeling of various cell surface proteins containing a monoglycine residue at the N-terminus. Displaying mgSrtA on the surface of a cell of interest allows the labeling and detection of interacting cells in a proximity-dependent fashion.

Upregulated LASP-1 correlates with a malignant phenotype and its potential therapeutic role in human cholangiocarcinoma.

LIM and SH3 protein 1 (LASP-1) is demonstrated to play a key role in occurrence and development of tumors. However, the expression and function of LASP-1 in cholangiocarcinoma (CCA) remain largely unexplored. This study aimed to investigate the effect of regulated LASP-1 expression on migration, invasion, proliferation, and apoptosis of CCA cells and on tumorigenesis in vivo, and to examine clinico-oncological correlates of LASP-1 expression. Expression of LASP-1 by immunohistochemistry was evaluated in CCA tissue samples. HCCC-9810 and RBE cells were transfected with the LASP-1 small interfering RNA (siRNA), and the effect of knocking down LASP-1 gene expression on cell migration, invasion, proliferation, and apoptosis were examined by wound healing, transwell assays, CCK-8 assays, colony formation, and flow cytometry assays, respectively. Xenograft tumor model was used to validate the effect of downregulated LASP-1 in vivo. Our results demonstrated that LASP-1 was over-expressed in CCA tissues, positively correlating with larger tumors, poor histological differentiation, lymph node metastasis, advanced TNM stage, and poor prognosis in CCA patients (P < 0.05). Downregulation of LASP-1 in HCCC-9810 and RBE cell lines significantly increased cell apoptosis and suppressed cell migration, invasion, and proliferation in vitro and tumorigenesis in vivo. Our results indicate that LASP-1 may essentially involve in the metastasis and growth of CCA and clinical significance of LASP-1 may reside in function as a biomarker to predict prognosis and as a promising therapeutic strategy for CCA patients by the inhibition of LASP-1 expression.

Magnolol inhibits growth of gallbladder cancer cells through the p53 pathway.

Magnolol, the major active compound found in Magnolia officinalis has a wide range of clinical applications due to its anti-inflammation and anti-oxidation effects. This study investigated the effects of magnolol on the growth of human gallbladder carcinoma (GBC) cell lines. The results indicated that magnolol could significantly inhibit the growth of GBC cell lines in a dose- and time-dependent manner. Magnolol also blocked cell cycle progression at G0 /G1 phase and induced mitochondrial-related apoptosis by upregulating p53 and p21 protein levels and by downregulating cyclin D1, CDC25A, and Cdk2 protein levels. When cells were pretreated with a p53 inhibitor (pifithrin-a), followed by magnolol treatment, pifithrin-a blocked magnolol-induced apoptosis and G0 /G1 arrest. In vivo, magnolol suppressed tumor growth and activated the same mechanisms as were activated in vitro. In conclusion, our study is the first to report that magnolol has an inhibitory effect on the growth of GBC cells and that this compound may have potential as a novel therapeutic agent for the treatment of GBC.

Two-micron thulium laser resection of the distal ureter and bladder cuff during nephroureterectomy for upper urinary tract urothelial carcinoma.

The thulium laser (Tm-laser) technique has been used in the management of many urologic conditions. The present study aimed to evaluate the use of this technique for distal ureter and bladder cuff (DUBC) excision during nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC). Fifty-eight patients with UUT-UC who underwent radical nephroureterectomy were included in this retrospective study. DUBC was managed by open excision in 24 cases, by transurethral electrosurgery in 17 cases, and by transurethral Tm-laser in 17 cases. Perioperative measures and oncologic outcomes were compared among the three groups. Furthermore, 11 human ureteral segments were collected to measure the burst pressure and show physical pressure tolerance, and six ureteral segments were assessed histologically to investigate the sealing effect. Operative time and hospital stay were significantly longer, and intraoperative blood loss was significantly greater in the open excision group than in the electrosurgery and Tm-laser groups (P < 0.05 for all). There were no significant differences in these parameters between the electrosurgery and Tm-laser groups. In addition, there were no significant differences in the incidences of bladder tumors and retroperitoneal recurrence of urothelial carcinoma among the three groups. The coagulation time and resection time were significantly shorter in the Tm-laser group than in the electrosurgery group. The mean burst pressure did not differ significantly between the tissues sealed by electrosurgery and by Tm-laser. Histopathological analyses showed that distal ureters were completely sealed by both electrosurgery and Tm-laser. The Tm-laser technique is superior to open excision and comparable to transurethral electrosurgery in the management of DUBC during nephroureterectomy for UUT-UC, offering an alternative treatment option for this condition.

SIRT1 activation promotes bone repair by enhancing the coupling of type H vessel formation and osteogenesis.

Bone repair is intricately correlated with vascular regeneration, especially of type H vessels. Sirtuin 1 (SIRT1) expression is closely associated with endothelial function and vascular regeneration; however, the role of SIRT1 in enhancing the coupling of type H vessel formation with osteogenesis to promote bone repair needs to be investigated. A co-culture system combining human umbilical vein endothelial cells and osteoblasts was constructed, and a SIRT1 agonist was used to evaluate the effects of SIRT1 activity. The angiogenic and osteogenic capacities of the co-culture system were examined using short interfering RNA. Mouse models with bone defects in the femur or mandible were established to explore changes in type H vessel formation and bone repair following modulated SIRT1 activity. SIRT1 activation augmented the angiogenic and osteogenic capacities of the co-culture system by activating the PI3K/AKT/FOXO1 signalling pathway and did not significantly regulate osteoblast differentiation. Inhibition of the PI3K/AKT/FOXO1 pathway attenuated SIRT1-mediated effects. The SIRT1 activity in bone defects was positively correlated with the formation of type H vessels and bone repair in vivo, whereas SIRT1 inhibition substantially weakened vascular and bone formation. Thus, SIRT1 is crucial to the coupling of type H vessels with osteogenesis during bone repair.

The role of zinc finger proteins in the fate determination of mesenchymal stem cells during osteogenic and adipogenic differentiation.

Zinc finger proteins (ZFPs) constitute a crucial group of transcription factors widely present in various organisms. They act as transcription factors, nucleases, and RNA-binding proteins, playing significant roles in cell differentiation, growth, and development. With extensive research on ZFPs, their roles in the determination of mesenchymal stem cells (MSCs) fate during osteogenic and adipogenic differentiation processes have become increasingly clear. ZFP521, for instance, is identified as an inhibitor of the Wnt signaling pathway and RUNX2's transcriptional activity, effectively suppressing osteogenic differentiation. Moreover, ZFP217 contributes to the inhibition of adipogenic differentiation by reducing the M6A level of the cell cycle regulator cyclin D1 (CCND1). In addition, other ZFPs can also influence the fate of mesenchymal stem cells (MSCs) during osteogenic and adipogenic differentiation through various signaling pathways, transcription factors, and epigenetic controls, participating in the subsequent differentiation and maturation of precursor cells. Given the prevalent occurrence of osteoporosis, obesity, and related metabolic disorders, a comprehensive understanding of the regulatory mechanisms balancing bone and fat metabolism is essential, with a particular focus on the fate determination of MSCs in osteogenic and adipogenic differentiation. In this review, we provide a detailed summary of how zinc finger proteins influence the osteogenic and adipogenic differentiation of MSCs through different signaling pathways, transcription factors, and epigenetic mechanisms. Additionally, we outline the regulatory mechanisms of ZFPs in controlling osteogenic and adipogenic differentiation based on various stages of MSC differentiation.

Mesenchymal stem cells in craniofacial reconstruction: a comprehensive review.

Craniofacial reconstruction faces many challenges, including high complexity, strong specificity, severe injury, irregular and complex wounds, and high risk of bleeding. Traditionally, the "gold standard" for treating craniofacial bone defects has been tissue transplantation, which involves the transplantation of bone, cartilage, skin, and other tissues from other parts of the body. However, the shape of craniofacial bone and cartilage structures varies greatly and is distinctly different from ordinary long bones. Craniofacial bones originate from the neural crest, while long bones originate from the mesoderm. These factors contribute to the poor effectiveness of tissue transplantation in repairing craniofacial defects. Autologous mesenchymal stem cell transplantation exhibits excellent pluripotency, low immunogenicity, and minimally invasive properties, and is considered a potential alternative to tissue transplantation for treating craniofacial defects. Researchers have found that both craniofacial-specific mesenchymal stem cells and mesenchymal stem cells from other parts of the body have significant effects on the restoration and reconstruction of craniofacial bones, cartilage, wounds, and adipose tissue. In addition, the continuous development and application of tissue engineering technology provide new ideas for craniofacial repair. With the continuous exploration of mesenchymal stem cells by researchers and the continuous development of tissue engineering technology, the use of autologous mesenchymal stem cell transplantation for craniofacial reconstruction has gradually been accepted and promoted. This article will review the applications of various types of mesenchymal stem cells and related tissue engineering in craniofacial repair and reconstruction.