第4卷，第4期

Obesity is a chronic, complex disease, which is associated with several comorbidities, including diabetes mellitus, hypertension, and cardiovascular diseases. It is estimated that the prevalence of obesity among both adults and children nearly tripled between 1975 and 2016, highlighting a huge unmet treatment need. However, the currently available antiobesity drugs have serious side effects, which limit their long-term use. The finding that the newly-identified brain GDF15-GFRAL-RET receptor signaling complex is involved in stress/disease-induced anorexia will certainly impact our knowledge of body weight homeostasis under healthy and disease conditions. Based on this breakthrough, a new class of GFRAL/RET-based drugs is highly anticipated for the treatment of obesity, as well as cancer-induced cachexia.

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Advances in three-dimensional (3D) printing have increased feasibility towards the synthesis of living tissues. Known as 3D bioprinting, this technology involves the precise layering of cells, biologic scaffolds, and growth factors with the goal of creating bioidentical tissue for a variety of uses. Early successes have demonstrated distinct advantages over conventional tissue engineering strategies. Not surprisingly, there are current challenges to address before 3D bioprinting becomes clinically relevant. Here we provide an overview of 3D bioprinting technology and discuss key advances, clinical applications, and current limitations. While 3D bioprinting is a relatively novel tissue engineering strategy, it holds great potential to play a key role in personalized medicine.

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Glucose 6 phosphate dehydrogenase (G6PD) is a key and rate limiting enzyme in the pentose phosphate pathway (PPP). The physiological significance of enzyme is providing reduced energy to specific cells like erythrocyte by maintaining co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH). There are preponderance research findings that demonstrate the enzyme (G6PD) role in the energy balance, and it is associated with bloodrelated diseases and disorders, primarily the anemia resulted from G6PD deficiency. The X-linked genetic deficiency of G6PD and associated non-immune hemolytic anemia have been studied widely across the globe. Recent advancement in biology, more precisely neuroscience has revealed that G6PD is centrally involved in many neurological and neurodegenerative disorders. The neuroprotective role of the enzyme (G6PD) has also been established, as well as the potential of G6PD in oxidative damage and the Reactive Oxygen Species (ROS) produced in cerebral ischemia. Though G6PD deficiency remains a global health issue, however, a paradigm shift in research focusing the potential of the enzyme in neurological and neurodegenerative disorders will surely open a new avenue in diagnostics and enzyme therapeutics. Here, in this study, more emphasis was made on exploring the role of G6PD in neurological and inflammatory disorders as well as non-immune hemolytic anemia, thus providing diagnostic and therapeutic opportunities.

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Alveolar epithelial cells (AECs) injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis (PF). Nevertheless, the exact mechanisms regulating the regeneration of AECs post-injury still remain unclear. SMARCA4 is a part of the large ATP-dependent chromatin remodelling complex SWI/SNF, which is essential for kidney and heart fibrosis. We investigates SMARCA4 function in lung fibrosis by establishing PF mice model with bleomycin firstly and found that the expression of SMARCA4 was mainly enhanced in alveolar type II (ATII) cells. Moreover, we established an alveolar epithelium-specific SMARCA4-deleted SP-C-rtTA/ (tetO)₇-Cre/SMARCA4^f/fmice (SOSM4^Δ^/^Δ) model, as well as a new SMARCA4-deleted alveolar type II (ATII) -like mle-12 cell line. We found that the bleomycin-induced PF was more aggressive in SOSM4^Δ/Δ mice. Also, the proliferation of ATII cells was decreased with the loss of SMARCA4 in vivo and in vitro. In addition, we observed increased proliferation of ATII cells accompanied by abnormally high expression of SMARCA4 in human PF lung sections. These data uncovered the indispensable role of SMARCA4 in the proliferation of ATII cells, which might affect the progression of PF.

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Hepatocellular carcinoma (HCC) is one of the common lethal types of tumor all over the world. The lethality of HCC accounts for many reasons. One of them, the lack of reliable diagnostic markers at the early stage, in this context, serum miRNAs became promising diagnostic biomarkers. Herein, we aimed to identify the predictive value of two miRNAs (miR-122 and miR-224) in plasma of patients with HCC preceded by chronic HCV infection. Taqman miRNA assays specific for hsa-miR-122 and hsa-miR-224 were used to assess the expression levels of the chosen miRNAs in plasma samples collected from three groups; 40 patients with HCC related to HCV, 40 with CHC patients and 20 healthy volunteers. This study revealed that the mean plasma values of miRNA-122 were significantly lower among HCC group when compared to CHC and control groups (P < 0.001). Whereas, miR-224 mean plasma values were significantly higher among HCC group when compared to both CHC group and control group. Moreover, it was found that miR-122 can predict development of HCC at cut-off value <0.67 (RQ) and (AUC = 0.98, P < 0.001). As regards miR-224, it can predict development of HCC at cut-off value >1.2 (RQ) and (AUC = 0.93, P < 0.001), while the accuracy of AFP to diagnose HCC was (AUC:0.619; P = 0.06). In conclusion, the expression plasma of miR-122 and miR-224 could be used as noninvasive biomarkers for the early prediction of developing HCC at the early stage.

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This study was performed for investigation the relationship between variants of MTP gene polymorphism and the development of NAFLD in patients with and without MS. The study was included 174 NAFLD patients (106 with MS and 68 without MS), and 141 healthy control subjects. The 493 G/T polymorphism of MTP gene was evaluated by PCR-RFLP method. The frequency of MTP TT genotype and T allele were significantly higher in NAFLD patients when compared to healthy controls. Moreover, a significant association in MTP gene polymorphism was observed in NAFLD patients with MS compared to NAFLD patients without MS and controls. Our study suggested that MTP 493 G/T gene polymorphism may act as susceptibility biomarker for NAFLD and MS.

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Cartilage injuries caused by arthritis or trauma pose formidable challenges for effective clinical management due to the limited intrinsic proliferative capability of chondrocytes. Autologous stem cell-based therapies and transgene-enhanced cartilage tissue engineering may open new avenues for the treatment of cartilage injuries. Bone morphogenetic protein 2 (BMP2) induces effective chondrogenesis of mesenchymal stem cells (MSCs) and can thus be explored as a potential therapeutic agent for cartilage defect repair. However, BMP2 also induces robust endochondral ossification. Although the precise mechanisms through which BMP2 governs the divergence of chondrogenesis and osteogenesis remain to be fully understood, blocking endochondral ossification during BMP2-induced cartilage formation may have practical significance for cartilage tissue engineering. Here, we investigate the role of Sox9-donwregulated Smad7 in BMP2-induced chondrogenic differentiation of MSCs. We find that overexpression of Sox9 leads to a decrease in BMP2-induced Smad7 expression in MSCs. Sox9 inhibits BMP2-induced expression of osteopontin while enhancing the expression of chondrogenic marker Col2a1 in MSCs. Forced expression of Sox9 in MSCs promotes BMP2-induced chondrogenesis and suppresses BMP2-induced endochondral ossification. Constitutive Smad7 expression inhibits BMP2-induced chondrogenesis in stem cell implantation assay. Mouse limb explant assay reveals that Sox9 expands BMP2-stimulated chondrocyte proliferating zone while Smad7 promotes BMP2-intitated hypertrophic zone of the growth plate. Cell cycle analysis indicates that Smad7 induces significant early apoptosis in BMP2-stimulated MSCs. Taken together, our results strongly suggest that Sox9 may facilitate BMP2-induced chondrogenesis by downregulating Smad7, which can be exploited for effective cartilage tissue engineering.

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Breast cancer is the most common invasive cancer in women worldwide. Sirtuin 1 (SIRT1) has recently been shown to have implications in regulating cancer cell growth and apoptosis. SIRT1 regulates Forkhead box O3a (FOXO3a) by both inhibiting FOXO3-induced apoptosis and potentiating the ability of FOXO3a to resist oxidative stress. Matrix metalloproteinase 2 (MMP2) participates in tumor invasion and metastasis by degrading extracellular matrix. SIRT1 up regulates MMP2 expression by its deacetylation activity. This study aimed to investigate the expression of SIRT1, FOXO3a and MMP2 in breast tissues of women with breast cancer. In addition, the effect of SIRT1 inhibition on both FOXO3a and MMP2 expression in breast cancer (MCF-7) cells was assessed. The expression levels of SIRT1, FOXO3a and MMP2 in the breast tissues were determined by real-time PCR in 60 patients with malignant tumor and in 24 patients with benign tumors. After SIRT1 inhibition, protein levels of SIRT1 and FOXO3a were assessed by Western Blot and levels of MMP2 by ELISA in MCF-7 cells. The expression levels of SIRT1, FOXO3a and MMP2 were significantly higher in breast cancer tissues compared to in benign breast tumor and adjacent normal tissues. SIRT1, MMP2 and FOXO3a expression were associated directly with each other. SIRT1 inhibition suppresses MMP2 and FOXO3a expression compared to control MCF7. Sirtinol (SIRT1 inhibitor) effectively induced inhibition of MMP2 and FOXO3a expression in MCF-7 cells, indicating the promising therapeutic strategy of targeting SIRT1 for breast cancer.

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