Utilizing multicompartmental restriction spectrum magnetic resonance imaging for liver fibrosis characterization in a mouse model.

BACKGROUND: Currently, an advanced imaging method may be necessary for magnetic resonance imaging (MRI) to diagnosis and quantify liver fibrosis (LF). PURPOSE: To evaluate the feasibility of the multicompartmental restriction spectrum imaging (RSI) model to characterize LF in a mouse model. METHODS: Thirty mice with carbon tetrachloride (CCl4)-induced LF and eight control mice were investigated using multi-b-value (ranging from 0 to 2000 s/mm2) diffusion-weighted imaging (DWI) on a 3T scanner. DWI data were processed using RSI model (2-5 compartments) with the Bayesian Information Criterion (BIC) determining the optimal model. Conventional ADC value and signal fraction of each compartment in the optimal RSI model were compared across groups. Receiver operating characteristics (ROC) curve analysis was performed to determine the diagnosis performances of different parameters, while Spearman correlation analysis was employed to investigate the correlation between different tissue compartments and the stage of LF. RESULTS: According to BIC results, a 4-compartment RSI model (RSI4) with optimal ADCs of 0.471 × 10-3, 1.653 × 10-3, 9.487 × 10-3, and > 30 × 10-3, was the optimal model to characterize LF. Significant differences in signal contribution fraction of the C1 and C3 compartments were observed between LF and control groups (P = 0.018 and 0.003, respectively). ROC analysis showed that RSI4-C3 was the most effective single diffusion parameter for characterizing LF (AUC = 0.876, P = 0.003). Furthermore, the combination of ADC values and RSI4-C3 value increased the diagnosis performance significantly (AUC = 0.894, P = 0.002). CONCLUSION: The 4-compartment RSI model has the potential to distinguish LF from the control group based on diffusion parameters. RSI4-C3 showed the highest diagnostic performance among all the parameters. The combination of ADC and RSI4-C3 values further improved the discrimination performance.

Deep Learning Based on ResNet-18 for Classification of Prostate Imaging-Reporting and Data System Category 3 Lesions.

RATIONALE AND OBJECTIVES: To explore the classification and prediction efficacy of the deep learning model for benign prostate lesions, non-clinically significant prostate cancer (non-csPCa) and clinically significant prostate cancer (csPCa) in Prostate Imaging-Reporting and Data System (PI-RADS) 3 lesions. MATERIALS AND METHODS: From January 2015 to December 2021, lesions diagnosed with PI-RADS 3 by multi-parametric MRI or bi-parametric MRI were retrospectively included. They were classified as benign prostate lesions, non-csPCa, and csPCa according to the pathological results. T2-weighted images of the lesions were divided into a training set and a test set according to 8:2. ResNet-18 was used for model training. All statistical analyses were performed using Python open-source libraries. The receiver operating characteristic curve (ROC) was used to evaluate the predictive effectiveness of the model. T-SNE was used for image semantic feature visualization. The class activation mapping was used to visualize the area focused by the model. RESULTS: A total of 428 benign prostate lesion images, 158 non-csPCa images and 273 csPCa images were included. The precision in predicting benign prostate disease, non-csPCa and csPCa were 0.882, 0.681 and 0.851, and the area under the ROC were 0.875, 0.89 and 0.929, respectively. Semantic feature analysis showed strong classification separability between csPCa and benign prostate lesions. The class activation map showed that the deep learning model can focus on the area of the prostate or the location of PI-RADS 3 lesions. CONCLUSION: Deep learning model with T2-weighted images based on ResNet-18 can realize accurate classification of PI-RADS 3 lesions.

Circular RNA DNAH14 molecular mechanism in an experimental model of hepatocellular carcinoma treated with Cobalt chloride to mimic the hypoxia-like response of transcatheter arterial chemoembolization.

Transcatheter arterial chemoembolization (TACE) is the primary local treatment for patients with unresectable hepatocellular carcinoma (HCC). Numerous studies have demonstrated the pivotal role of circular RNAs (circRNAs) in TACE efficacy. This study aimed to investigate the function of circular RNA DNAH14 (circDNAH14) in TACE for HCC and to elucidate its molecular mechanisms. To simulate hypoxia conditions experienced during TACE, HCC cells were treated with cobalt chloride. The expression levels of circDNAH14, microRNA-508-3p (miR-508-3p), and Prothymosin Alpha (PTMA) were modulated via transfection for knockdown or overexpression. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays, flow cytometry, and Transwell assays, along with epithelial-mesenchymal transition (EMT) evaluations, were employed to assess cell proliferation, apoptosis, invasion, migration, and EMT. The results indicated that hypoxia treatment downregulated the expression of circDNAH14 and PTMA while upregulating miR-508-3p. Such treatment suppressed HCC cell proliferation, invasion, migration, and EMT, and induced apoptosis. Knockdown of circDNAH14 or PTMA intensified the suppressive effects of hypoxia on the malignant behaviors of HCC cells. Conversely, upregulation of miR-508-3p or PTMA mitigated the effects of circDNAH14 overexpression and knockdown, respectively. Mechanistically, circDNAH14 was found to competitively bind to miR-508-3p, thereby regulating PTMA expression. In vivo, nude mouse xenograft experiments demonstrated that circDNAH14 knockdown augmented the hypoxia-induced suppression of HCC tumor growth. In conclusion, circDNAH14 mitigates the suppressive effects of hypoxia on HCC, both in vitro and in vivo, by competitively binding to miR-508-3p and regulating PTMA expression.

The Role MicroRNA-135a in Suppressing Tumor Growth in Kidney Cancer Through the Regulation of Phosphoprotein Phosphatase2A and the Activation of the AKT and ERK1/2 Signaling Pathways.

Background: Kidney cancer is a frequently occurring malignant tumor in the urinary system, with rising morbidity and mortality rates in recent times. Developing new biomarkers and therapeutic targets is essential to improve the prognosis of patients affected by kidney cancer. In recent years, miRNAs' role in tumorigenesis and development has received growing attention. miRNAs constitute a group of small non-coding RNA molecules that regulate gene expression, affecting various biological processes, including cell proliferation, differentiation, and apoptosis. Of the many miRNAs, miR-135a plays a pivotal role in several cancers. Nevertheless, the precise mechanisms and functions concerning miR-135a in renal cancer remain incompletely understood. Therefore, this study aims to analyze the effects of miR-135a on renal cancer replication and migration and its possible mechanisms, and to provide new strategies for the diagnosis and treatment of renal cancer. Methods: Renal cell lines (ACHN, A498) with stable hyperexpression of miR-135a and reduced expression of miR-135a were constructed by lentivirus packaging. The changes of replication, clone formation and migration ability of overexpressed miR-135a and overexpressed miR-135a in ACHN and A498 renal cell lines were detected. The possible mechanism of miR-135a affecting the replication of kidney cancer was analyzed by target gene prediction, double luciferase test, Western blotting and subcutaneous tumorigenicity assay in nude mice. Results: Hyperexpression of miR-135a can inhibit kidney cancer replication, whereas miR-135a knockdown potentially enhances replication. However, neither hyperexpression nor knockdown of miR-135a affects the migration ability of kidney cancer cells. The protein expression of PP2A-B56-γ, PP2A-Cα and PP2A-Cß in renal cell line decreased after hyperexpression of miR-135a, while the protein expression of PP2A-B56-γ, PP2A-Cα and PP2A-Cß increased after knockdown of miR-135a. In addition, the protein expression of p-Akt and p-ERK1/2 proteins in kidney cancer cells after hyperexpression of miR-135a were down-regulated, while the protein expression of p-Akt and p-ERK1/2 were up-regulated in kidney cancer cells after knockdown of miR-135a. In subcutaneous tumor formation experiments in nude mice, tumor size within nude mice in the miR-135a group was significantly smaller than in the control group. Conclusion: MiR-135a could suppress the replication of kidney cancer by modulating PP2A and AKT, ERK1/2 signaling pathways.

PD-1/PD-L1 inhibitor treatment and its impact on clinical imaging in non-small cell lung cancer: a systematic review and meta-analysis of immune-related adverse events.

Background: In the contemporary era of cancer treatment, lung cancer (LC) holds the unenviable position of being the primary contributor to cancer-induced mortality worldwide. Although immunotherapy has expanded the therapeutic landscape for metastatic non-small cell lung cancer (NSCLC), the advent of immune checkpoint inhibitors has been accompanied by a concomitant increase in immune-related adverse events (irAEs). Timely detection of irAEs is pivotal for efficacious management and enhanced patient outcomes. Diagnostic imaging, encompassing x-ray and CT scans, can facilitate the identification and supervision of irAEs, thereby ensuring the prompt recognition of associated patterns and alterations for expeditious treatment. Methods: The present inquiry undertook a systematic exploration of multiple databases, incorporating a diverse array of studies such as randomized controlled trials and observational analyses. Patient demographics, imaging outcomes, and risk of bias were extracted from the data. Meta-analysis was executed utilizing R Statistical Software, with the results of the risk of bias assessment summarized accordingly. Findings: The analysis unveiled a higher prevalence of irAEs in patients receiving first-line treatment for NSCLC compared to those receiving subsequent treatments, with a statistically significant distinction observed for both high- and low-grade irAEs (p < 0.001). Pneumonitis, thyroiditis, and colitis emerged as the most frequently reported irAEs, whereas hepatitis and pancolitis were less commonly documented. This investigation signifies a crucial advancement in elucidating the function of imaging in the treatment of NSCLC with PD-1/PD-L1 inhibitors and emphasizes the imperative for ongoing research in this domain.

Novel albumin-binding multifunctional probe for synergistic enhancement of FL/MR dual-modal imaging and photothermal therapy.

The fluorescence/magnetic resonance (FL/MR) dual-modal imaging could provide accurate tumor visualization to guide photothermal therapy (PTT) of cancer, which has attracted widespread attention from scientists. However, facile and effective strategies to synergistically enhance fluorescence intensity, MR contrast and photothermal efficacy have rarely been reported. This study presents a novel multifunctional probe Gd-EB-ICG (GI) for FL/MR dual-modal imaging-guided PTT of cancer. GIs can self-assemble with endogenous albumin to form drug-albumin complexes (GIAs), which exhibit excellent biocompatibility. Albumin can protect GIAs from the recognition and clearance by the mononuclear phagocytic system (MPS). High plasma concentration and long half-life allow GIAs to accumulate continuously in the tumor area through EPR effect and specific uptake of tumor. Because of the prolonged rotational correlation time (τR) of Gd chelates, GIAs exhibited superior MR contrast performance over GIs with more than 3 times enhancement of longitudinal relaxation efficiency (r1). The fluorescence quantum yield and photothermal conversion efficiency of GIAs was also significantly improved due to the constrained geometry, disrupted aggregation and enhanced photothermal stability. This simple and feasible strategy successfully resulted in a synergistic effect for FL/MR dual-modal imaging and photothermal therapy, which can cast a new light for the clinical translation of multifunctional probes.

Advances in application of novel magnetic resonance imaging technologies in liver disease diagnosis.

Liver disease is a major health concern globally, with high morbidity and mor-tality rates. Precise diagnosis and assessment are vital for guiding treatment approaches, predicting outcomes, and improving patient prognosis. Magnetic resonance imaging (MRI) is a non-invasive diagnostic technique that has been widely used for detecting liver disease. Recent advancements in MRI technology, such as diffusion weighted imaging, intravoxel incoherent motion, magnetic resonance elastography, chemical exchange saturation transfer, magnetic resonance spectroscopy, hyperpolarized MR, contrast-enhanced MRI, and ra-diomics, have significantly improved the accuracy and effectiveness of liver disease diagnosis. This review aims to discuss the progress in new MRI technologies for liver diagnosis. By summarizing current research findings, we aim to provide a comprehensive reference for researchers and clinicians to optimize the use of MRI in liver disease diagnosis and improve patient prognosis.

Corrigendum: Role and mechanism of DNA methylation and its inhibitors in hepatic fibrosis.

[This corrects the article DOI: 10.3389/fgene.2023.1124330.].

Retrospective Cohort Study of Shear-Wave Elastography and Computed Tomography Enterography in Crohn's Disease.

Distinguishing between inflammatory and fibrotic lesions drastically influences treatment decision-making regarding Crohn's disease. However, it is challenging to distinguish these two phenotypes before surgery. This study investigates the diagnostic yield of shear-wave elastography and computed tomography enterography to distinguish intestinal phenotypes in Crohn's disease. Thirty-seven patients (mean age, 29.51 ± 11.52; 31 men) were evaluated with average value of shear-wave elastography (Emean) and computed tomography enterography (CTE) scores. The results demonstrated that a positive correlation between the Emean and fibrosis (Spearman's r = 0.653, p = 0.000). The cut-off value for fibrotic lesions was 21.30 KPa (AUC: 0.877, sensitivity: 88.90%, specificity: 89.50%, 95% CI:0.755~0.999, p = 0.000). The CTE score showed a positive correlation with inflammation (Spearman's r = 0.479, p = 0.003), and a 4.5-point grading system was the optimal cut-off value for inflammatory lesions (AUC: 0.766, sensitivity: 73.70%, specificity: 77.80%, 95% CI: 0.596~0.936, p = 0.006). Combining these two metrics improved the diagnostic performance and specificity (AUC: 0.918, specificity: 94.70%, 95% CI: 0.806~1.000, p = 0.000). In conclusion, shear-wave elastography can be used to help detect fibrotic lesions and the computed tomography enterography score emerged as a feasible predictor of inflammatory lesions. The combination of these two imaging techniques is proposed to distinguish intestinal predominant phenotypes.

Inhibitory effects of Ganoderma lucidum triterpenoid on the growth and metastasis of hepatocellular carcinoma.

OBJECTIVE: To investigate the inhibitory effects and mechanisms of triterpenoids from Ganoderma lucidum (G. lucidum triterpenoids) on the growth and metastasis of hepatocellular carcinoma (HCC) both in vitro and in vivo. METHODS: In in-vitro experiments, the inhibitory effects of G. lucidum triterpenoids on human HCC SMMC-7721 cell lines were investigated by observing the proliferation, apoptosis, migration and invasion phenotypes of the cell line and assessing the cell cycles as well as the cell apoptosis and proliferation. In in-vivo experiments, nude mouse SMMC-7721 tumor models were established and divided into control group, treatment group A (low concentration group) and treatment group B (high concentration group) according to the treatment models received. Magnetic resonance imaging (MRI) was performed 3 times on each mouse model to calculate their tumor volumes. The liver and kidney functions of the models were evaluated. Tissues harvested from their solid organs were subjected to HE staining, and the tumor tissues were subjected to HE staining and immunohistochemical staining (E-cad, Ki-67, and Tunel), respectively. RESULTS: i. In in-vitro experiments, G. lucidum triterpenoids could inhibit the growth of human HCC SMMC-7721 cell lines via regulating their proliferation and apoptosis phenotype. ii. In in-vivo experiments, the comparison of tumor volumes of mouse models obtained from the second and third MIR scanning was found to be statistically significant between the control group and treatment group A (P<0.05); and statistically significant differences were also found in the tumor volumes from the second and third MRI scanning between the control group and treatment group B (P<0.05). iii. No significant acute injuries or adverse effects were observed in the liver or kidney of the nude mice. CONCLUSION: G. lucidum triterpenoids could inhibit the growth of tumor cells via blocking their proliferation, accelerating apoptosis, and inhibiting migration and invasion, without marked toxic effects on normal organs and tissues in the body.

Role and mechanism of DNA methylation and its inhibitors in hepatic fibrosis.

Liver fibrosis is a repair response to injury caused by various chronic stimuli that continually act on the liver. Among them, the activation of hepatic stellate cells (HSCs) and their transformation into a myofibroblast phenotype is a key event leading to liver fibrosis, however the mechanism has not yet been elucidated. The molecular basis of HSC activation involves changes in the regulation of gene expression without changes in the genome sequence, namely, via epigenetic regulation. DNA methylation is a key focus of epigenetic research, as it affects the expression of fibrosis-related, metabolism-related, and tumor suppressor genes. Increasing studies have shown that DNA methylation is closely related to several physiological and pathological processes including HSC activation and liver fibrosis. This review aimed to discuss the mechanism of DNA methylation in the pathogenesis of liver fibrosis, explore DNA methylation inhibitors as potential therapies for liver fibrosis, and provide new insights on the prevention and clinical treatment of liver fibrosis.

Comparison of ZOOMit-DWI sequence and conventional DWI sequence in endometrial cancer. / ZOOMit-DWI序列和常规DWIåºåˆ—åœ¨å­å®«å† è†œç™Œä¸­çš„å¯¹æ¯”.

OBJECTIVES: Magnetic resonance diffusion-weighted imaging (DWI) has important clinical value in diagnosis and curative effect evaluation on endometrial carcinoma. How to improve the detection rate of endometrial small lesions by DWI is the research focus of MRI technology. This study aims to analyze the image quality of small field MRI ZOOMit-DWI sequence and conventional single-shot echo-planar imaging (SS-EPI) DWI sequence in the scanning of endometrial carcinoma, and to explore the clinical value of ZOOMit-DWI sequence. METHODS: A total of 37 patients with endometrial carcinoma diagnosed by operation and pathology in the Second Xiangya Hospital of Central South University from July 2019 to May 2021 were collected. All patients were scanned with MRI ZOOMit-DWI sequence and SS-EPI DWI sequence before operation. Two radiologists subjectively evaluated the anatomical details, artifacts, geometric deformation and focus definition of the 2 groups of DWI images. At the same time, the signal intensity were measured and the signal-to-noise ratio (SNR), contrast to noise ratio (CNR), and apparent diffusion coefficient (ADC) of the 2 DWI sequences were calculated for objective evaluation. The differences of subjective score, objective score and ADC value of the 2 DWI sequences were analyzed. RESULTS: The SNR of the ZOOMit-DWI group was significantly higher than that of the SS-EPI DWI group (301.96±141.85 vs 94.66±41.26), and the CNR of the ZOOMit-DWI group was significantly higher than that of the SS-EPI DWI group (185.05±105.45 vs 57.91±31.54, P<0.05). There was no significant difference in noise standard deviation between the ZOOMit-DWI group and the SS-EPI DWI group (P>0.05). The subjective score of anatomical detail and focus definition in the ZOOMit-DWI group was significantly higher than that of the SS-EPI DWI group (both P<0.05). The subjective score of artifacts and geometric deformation of ZOOMit-DWI group was significantly lower than that of the SS-EPI DWI group (both P<0.05). ADC had no significant difference between the ZOOMit-DWI group and the SS-EPI DWI group (P>0.05). CONCLUSIONS: The image quality of ZOOMit-DWI is significantly higher than that of conventional SS-EPI DWI. In the MRI DWI examination of endometrial carcinoma, ZOOMit-DWI can effectively reduce the geometric deformation and artifacts of the image, which is more conducive to clinical diagnosis and treatment.

Novel albumin-binding photodynamic agent EB-Ppa for targeted fluorescent imaging guided tumour photodynamic therapy.

The targeted and novel albumin-binding strategy has been attractive in the field of cancer therapy. Herein, we have developed an organic small molecule-based photosensitizer, Evans Blue-Pyropheophorbide-alpha (EB-Ppa), to treat solid tumors with extremely high photodynamic therapeutic efficiency, which is stable in serum-containing aqueous media and can effectively accumulate in the tumor site due to the enhanced permeability and retention (EPR) effect. Particularly, after the photodynamic therapeutic treatment with EB-Ppa, all breast tumors (4T1 cell line) xenografted in nude mice shrink fast due to the singlet oxygen generated by EB-Ppa with laser irradiation. Furthermore, EB-Ppa shows negligible toxicity in major organs. These results demonstrate that EB-Ppa presents the great potential of photodynamic therapy for efficient tumor treatment.

CD151 and prostate cancer progression: A review of current literature.

Prostate cancer morbidity and mortality are increasing globally and in China, and the rate of metastasis is also rising, limiting the therapeutic effect and clinical prognosis of prostate cancer. CD151 is considered to be the first promoter of tumor metastasis in the tetraspanin superfamily. Previous research has linked CD151 to the progression of a number of malignancies, including prostate cancer. However, a recent study found that CD151 can inhibit the progression of prostate cancer. As a result, this paper examines existing research on CD151 and prostate cancer progression in order to clarify the relationship and provide a possible reference for future studies.

Non-alcoholic fatty liver disease and complications in type 1 and type 2 diabetes: A Mendelian randomization study.

AIM: To investigate the potential causal relationship between non-alcoholic fatty liver disease (NAFLD) and complications in type 1 diabetes (T1D) and type 2 diabetes (T2D). MATERIALS AND METHODS: Two-sample Mendelian randomization (MR) analysis was conducted to appraise after controlling for the confounding factors. Genetic instrument variables for NAFLD surrogated by chronically elevated serum alanine transferase were derived from a recent genome-wide association study. Diabetes-related complications, including diabetic ketoacidosis, nephropathy and retinopathy, were included as outcomes. Four complementary MR methods were used to test reliability. RESULTS: Genetically instrumented NAFLD showed a suggestive causal association with ketoacidosis in T1D (odds ratio [OR]: 1.574; 95% confidence interval [CI]: 1.076, 2.302; P = .019; false discovery rate [FDR] = 0.096) and a significant causal association with early-stage kidney disease in T1D (OR: 1.249; 95% CI: 1.089, 1.432; P = 1.457 × 10-3 , FDR = 0.015). Sensitivity analysis indicated low heterogeneity, low pleiotropy and high reliability of the causal estimates. However, the MR analyses failed to show a causal association between NAFLD and T1D retinopathy, T2D ketoacidosis, nephropathy and retinopathy. CONCLUSIONS: This study supports a causal effect of genetically driven chronic serum alanine aminotransferase-associated NAFLD on early-stage kidney disease in T1D and a suggestive causal effect on ketoacidosis in T1D. However, MR studies did not provide enough evidence to suggest that NAFLD independently increases the risk of retinopathy in T1D and of ketoacidosis, nephropathy and retinopathy in T2D.

Newly found variations of the right posterior portal vein identified radiologically in 1,003 Chinese patients: a cross-sectional study.

Background: The anatomy of the right posterior portal vein (RPPV) plays an important role in planning hepatic resection, living transplantation and interventional radiological procedures, yet the incidence of variations of RPPV without a common trunk in Chinese persons is still unclear. Therefore, we conducted this study and discussed its clinical implications. Methods: A retrospective analysis of multidetector computed tomography (MDCT) scans was performed in 1,933 patients with various abdominal pathologies between September 28, 2018 through May 23, 2019. After excluding 930 patients, a total of 1,003 patients were included in this study. Variations of the RPPV without a common trunk were classified according to classification standards. Results: A total of 1,003 patients were included. RPPV without a common trunk was found in 216 (21.54%, 216/1,003) patients. Among them, we identified three variations of the origin from the right portal vein (RPV): first separate origin of P6, P7, or simultaneous separate origin of P6 and P7, and the incidences of these three variations were 1.50% (15/1,003), 6.58% (66/1,003) and 13.46% (135/1,003), respectively. Among 1,003 patients included in this study, 787 patients (78.46%, 787/1,003) showed that RPPV normally divided into P6 and P7 branches. Conclusions: Variations of the RPPV without a common trunk were not rare in Chinese population. Knowledge of this anatomic variation of the RPPV is extremely important for hepatic and transplant surgeons and interventional radiologists.

Mechanism and effect of stress granule formation in cancer and its potential roles in breast cancer therapy.

Stress granules are non-membranous cytoplasmic foci induced by various stress conditions. It is a protective strategy used by cells to suppress overall translation during stress. In cancer cells, it was thought that the formation of stress granules could protect them from apoptosis and induces resistance towards anti-cancer drugs or radiation treatment which makes the stress granules a potential target for cancer treatment. However, most of our understanding of stress granules are still in the stage of molecular and cell biology, and a transitional gap for its actual effect on clinical settings remains. In this review, we summarize the mechanism and effect of stress granules formation in cancer and try to illuminate its potential applications in cancer therapy, using breast cancer as an example.

Case Report: Treatment of Hypertrophic Cardiomyopathy With Stereotactic Body Radiotherapy.

Patients with hypertrophic cardiomyopathy (HCM), which is characterized by left ventricular hypertrophy, is usually treated with medications such as calcium channel blockers or beta-blockers and invasive treatments such as transcatheter alcohol septal ablation, percutaneous radiofrequency ablation, or heart transplantation. However, non-invasive methods have not been employed for the management of patients with HCM. A 71-year-old male who presented with occasional chest pain for approximately 2 months and had been diagnosed with HCM since he was 39 years old due to occasional fainting was treated with a novel method for HCM using stereotactic body radiotherapy (SBRT). The administration of 25 Gy of radiation as one fraction led to an improvement in his quality of life. No toxicity occurred during or immediately after the treatment. Our observations suggest that SBRT may be a reasonable treatment approach for patients with HCM who are not suitable for surgery.

Sodium Butyrate Pre-Treatment Enhance Differentiation of Bone Marrow Mesenchymal Stem Cells (BM-MSCs) into Hepatocytes and Improve Liver Injury.

OBJECTIVE: The treatment of liver failure by stem cell transplantation has attracted growing interest. Herein, we aim to explore the role of sodium butyrate (NaB) in the hepatic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) under liver-specific factors induction in vitro and vivo. MATERIALS & METHODS: We isolated BM-MSCs from the mononuclear cell fraction of rabbit bone marrow samples and identified the cells by Immunophenotypic analysis. We investigated the effects of different concentrations and induction conditions. The histone deacetylase inhibitor NaB induced hepatic differentiation of BM-MSCs under liverspecific factors induction in vitro. Morphological features, liver-specific gene and protein expression, and functional analyses in vitro and vivo were performed to evaluate the hepatic differentiation of BM-MSCs. RESULTS: Our results showed that pre-treated NaB inhibited the expression of the liverspecific protein in a dose-dependent manner. The induction efficiency of NaB with 24h pre-treatment was higher than that of NaB continuous intervention. 0.5 mM 24h NaB pre-treated cells can improve liver tissue damage in vivo. The liver ALB, AAT, and the serum TP were significantly increased, while the serum ALT was significantly reduced. CONCLUSION: Continuous NaB treatment can inhibit BM-MSCs proliferation in a dosedependent manner at a certain concentration range. 0.5 mM 24h pre-treatment of NaB enhanced differentiation of BM-MSCs into hepatocytes and improved liver injury in vitro and vivo.