D-mannose reduces adipogenesis by inhibiting the PI3K/AKT signaling pathway.

PURPOSE: To explore the effects and potential mechanisms of D-mannose on adipogenic differentiation of two kinds of representative mesenchymal stem cells (MSCs). METHODS: We cultured two kinds of representative MSCs, human adipose tissue-derived stromal cells (hADSCs) as well as human bone marrow mesenchymal stem cells (hBMSCs), with adipogenic-induced medium containing D-mannose or D-fructose as the control. Oil red O staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB) were used to detect whether D-mannose had effects on adipogenic differentiation of MSCs. RNA sequencing (RNA-seq) transcriptomic analysis was further used to explore the potential mechanisms of D-mannose on adipogenic differentiation of MSCs. After that, qRT-PCR and WB were used to verify the results of RNA-seq. Last, we removed bilateral ovaries of female rats to establish an estrogen deficiency obesity model, and gave D-mannose intragastric administration. One month later, the femurs of rats were sliced for oil red O staining, and the inhibitory effect of D-mannose on lipid formation in vivo was studied. RESULTS: Oil red O staining, qRT-PCR and WB in vitro demonstrated that D-mannose inhibited the adipogenic differentiation of both hADSCs and hBMSCs. Oil red O staining of femur sections proved that D-mannose was able to reduce in vivo adipogenesis. The results of RNA-seq transcriptomic analysis revealed that the adipogenesis-inhibition effects of D-mannose were performed by antagonizing the PI3K/AKT signaling pathway. Besides, qRT-PCR and WB further verified the results of RNA-seq. CONCLUSION: Our study indicated that D-mannose was able to reduce adipogenic differentiation of both hADSCs and hBMSCs by antagonizing the PI3K/AKT signaling pathway. D-mannose is expected to be a safe and effective treatment strategy for obesity.

MRI comparative study of diffuse midline glioma, H3 K27-altered and glioma in the midline without H3 K27-altered.

PURPOSE: The MRI features of Diffuse midline glioma, H3 K27-altered and glioma in the midline without H3 K27-altered were compared and analyzed, and the changes in the apparent diffusion coefficient (ADC) of the two groups were quantitatively analyzed. METHODS: The MRI images of 35 patients with Diffuse midline gliomas, H3 K27-altered and gliomas in the midline without H3 K27-altered were analyzed retrospectively. The location, edge, signal, peritumoral edema and enhancement characteristics of the lesions were observed, and the changes in ADC values were analyzed. RESULTS: In the H3 K27-altered group, 85.7% (12/14) of the tumors were located in the thalamus and brainstem compared with 28.6% (6/21) in the no H3 K27-altered group. In the H3 K27-altered group, for tumors only located in the midline area, only 14.3% (1/7) had irregular shapes and unclear boundaries, while for tumors also invaded the extramidline tissues 85.7% (6/7) had irregular shapes and unclear boundaries.The"basilar artery wrapped sign" was found in 6 patients with tumors located in the pons in the H3 K27-altered group, but none in the no H3 K27-altered group had this sign. In the H3 K27-altered group, only 14.3% (1/7) of the tumors confined to the midline area had small cystic degeneration and necrosis, while for tumors also invaded the extramidline tissues, 100% (7/7) of the tumors had cystic degeneration and necrosis, and the cystic degeneration and necrosis only located in the extramidline region of the tumor in 6 cases.A total of 78.6% (11/14) of tumors in the H3 K27-altered group showed mild to moderate enhancement, while 47.6% (10/21) of tumors in the no H3 K27-altered group showed mild to moderate enhancement. The average peritumoral edema index was 1.13 in the H3 K27-altered group and 1.75 in the no H3 K27-altered group. The average ADC value of tumor in the H3 K27-altered group was 7.83 × 10- 4 mm2/s, and the ratio to normal brain tissue was 0.844, while the values in the no H3 K27-altered group were 13.5 × 10- 4 mm2/s and 1.75, respectively. CONCLUSION: Compared with gliomas in the midline without H3 K27-altered, The MRI findings and ADC value of Diffuse midline gliomas, H3K27-altered have some characteristics, which can help improve the diagnosis and differential diagnosis.

Enhanced autophagy suppresses inflammation-mediated bone loss through ROCK1 signaling in bone marrow mesenchymal stem cells.

Bone marrow mesenchymal stem cells (BMSCs) have strong proliferative ability and multi-directional differentiation potential. Osteoarthritis is a degenerative joint disease that is closely related to the loss of osteogenic differentiation function of BMSCs. Autophagy, plays a crucial role in the maintenance of cellular functions, but its regulatory mechanism during the osteogenic differentiation of BMSCs remains unclear. In this study, we analyzed the differential gene networks and pathways during BMSC osteogenesis using bioinformatics, and further validated the regulatory roles of autophagy during the osteogenic differentiation of BMSCs in inflammatory condition in vitro. We found that Tumor necrosis factor alpha (TNF-α) treatment led to actin cytoskeleton rearrangements and inhibited osteogenic differentiation in BMSCs. In addition, TNF-α enhanced Rho-associated protein kinase 1 (ROCK1) expression and decreased autophagy activation. ROCK1 knockdown reduced Endoplasmic Reticulum stress (ER stress) and promoted autophagy, resulting reversion of osteogenic differentiation in BMSCs under inflammatory condition. Rapamycin reversed the TNF-α-induced decrease in osteogenesis of BMSCs, assessed by alkaline phosphatase (ALP) activity and Alizarin staining. Autophagy treated with inhibitor 3-Methyladenine (3-MA) further increased TNF-α-induced osteogenesis inhibition of BMSCs. Collectively, these results indicate that ER stress and dysfunction of autophagy promote inflammation-induced bone loss through the activation of ROCK1 signaling in BMSCs.

Salivary Microbiome Variation in Early Childhood Caries of Children 3-6 Years of Age and Its Association With Iron Deficiency Anemia and Extrinsic Black Stain.

ECC is a common clinical manifestation of the oral cavity in childhood and Iron deficiency-anemia (IDA) is a high-risk factor but extrinsic black stain on the tooth surface is a protective factor for caries. There is limited information about oral microecological change in early children who suffer from ECC with IDA and extrinsic black stain (BS). This study enrolled 136 children aged 3-6 years. Dental caries and teeth BS were examined. Saliva was collected for 16S rRNA gene and fingertip blood were for Hemoglobin test. There are 93 ECC including 13 with IDA (IDA ECC) and 80 without IDA (NIDA ECC) and 43 caries free (CF) including 17 with BS (BSCF) and 26 without BS (NBS CF). Statistical analysis of microbiota data showed differences of the oral flora in different groups. The oral flora of the IDA ECC group had a high diversity, while the BSCF group had a low diversity. The bacterial genera Bacillus, Moraxella, and Rhodococcus were enriched in the IDA ECC while Neisseria was enriched in the NIDA ECC. Neisseria only exhibited high abundance in the BSCF, and the remaining genera exhibited high abundance in the NBSCF. Interestingly, the BSCF had the same trend as the NIDA ECC, and the opposite trend was observed with IDA ECC. We established random forest classifier using these biomarkers to predict disease outcomes. The random forest classifier achieved the best accuracy in predicting the outcome of caries, anemia and black stain using seven, one and eight biomarkers, respectively; and the accuracies of the classifiers were 93.35%, 94.62% and 95.23%, respectively. Our selected biomarkers can achieve good prediction, suggesting their potential clinical implications.

CCHE1 accelerated the initiation of oral squamous cell carcinoma through enhancing PAK2 expression by sponging miR-922.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a normal form of mouth cancer, comprising the majority of oral cancers. A large number of long non-coding RNAs (lncRNAs) have been reported due to their oncogenic function in cancers. Recent studies show that lncRNA CCHE1 is an oncogene in a wide range of cancers. Whether CCHE1 accelerates the progression of OSCC is still undiscovered. METHODS: The qRT-PCR analysis was used to determine CCHE1, miR-922, and PAK2 expression levels. CCK8 and colony formation assays were applied to evaluate OSCC cell proliferative ability. Transwell assay was performed to investigate the capability of cell migration and invasion. Cell apoptosis was assessed by flow cytometry analysis. The distribution of CCHE1 in OSCC cells was confirmed via subcellular fractionation assay. Luciferase reporter assay was used to verify the connection between miR-922 and CCHE1 or PAK2. RESULTS: qRT-PCR analysis identified the upregulation of CCHE1 in OSCC cells. Knockdown of CCHE1 curbed the proliferation, migration, and invasion and hastened the apoptosis in OSCC cell lines. Moreover, it was found that miR-922 could interact with CCHE1. Besides, PAK2 was identified as the target gene of miR-922 and its expression was negatively modulated by miR-922 and positively regulated by CCHE1. Restoration assay manifested that the suppressing influence of CCHE1 depletion on OSCC progression was rescued by amplified PAK2. CONCLUSIONS: CCHE1 increases the expression of PAK2 to promote the progression of OSCC by competitively binding to miR-922 in OSCC cells.