Clinical features and cardiovascular magnetic resonance characteristics in Danon disease.

AIMS: To investigate the clinical spectrum, cardiovascular magnetic resonance imaging (cMRI) characteristics, including T1 and extracellular volume fraction, and outcomes of Danon disease to facilitate further understanding of the phenotype of patients with Danon disease. MATERIALS AND METHODS: The study comprised six male patients 8-23 years old recruited to the study between 2014-2019. The clinical presentation, laboratory examinations, pathology/genetic analysis, electrocardiography (ECG), echocardiography, and cCMRI characteristics were summarised. RESULTS: Five out of six patients suffered from hypertrophic cardiomyopathy (HCM) phenotype of Danon disease, while one patient had dilated cardiomyopathy (DCM) phenotype. Left ventricular (LV) and left atrial (LA) function were impaired at strain measurement. Diffuse and focal late gadolinium enhancement (LGE) were observed separately in the LV walls of three patients and right ventricular (RV) insertion points of the remaining three patients. Furthermore, values for the native T1 (mean 1313.3 ms) and extracellular volume fraction (ECV; mean 39.17%) of three patients were increased. CONCLUSIONS: Both dilated and hypertrophic cardiomyopathy may be the phenotypes of Danon disease. Comprehensive cCMRI played a unique role in the diagnosis and grading severity and risk factors of Danon disease in vivo, especially by using robust quantitative strain analysis, T1 mapping, and further ECV calculation.

[Clinicopathological and molecular characteristics of Epstein-Barr virus associated gastric cancer: a single center large sample case investigation].

OBJECTIVE: Epstein-Barr virus associated gastric cancer (EBVaGC) is different from the traditional gastric cancer (Epstein-Barr virus non-associated gastric cancer, EBVnGC), and has unique clinicopathological features. This study investigated the largest single center cancer series so as to establish the clinicopathological and molecular characteristics of EBVaGC in China. METHODS: A retrospective analysis was conducted on EBVaGC and EBVnGC patients diagnosed at Peking University Cancer Hospital from 2003 to 2018 by comparing their clinicopathological features and prognosis. The gastric cancer (GC) dataset of public database was analyzed to obtain differentially expressed genes. The expression of important genes and their association with prognosis of GC were verified in GC tissues from our hospital. RESULTS: In this study, 3 241 GC patients were included, and a total of 163 EBVaGC (5.0%) patients were identified. Compared with EBVnGC, EBVaGC was higher in male and younger patients, and positively associated with remnant GC, poorly differentiated adenocarcinoma, and mixed type GC. EBVaGC was inversely related to lymph node metastasis. The 5-year survival rate of EBVnGC and EBVaGC was 59.6% and 63.2% respectively (P<0.05). In order to explore molecular features of EBVaGC, the Cancer Genome Atlas (TCGA) dataset was analyzed (n=240), and 7 404 significant differentially expressed genes were obtained, involving cell proliferation, apoptosis, invasion and metastasis. The down-regulated invasion/metastasis gene SALL4 and the up-regulated immune checkpoint gene PD-L1 were important molecular features of EBVaGC. Validation of these two genes in large GC series showed that the majority of the EBVaGC was SALL4 negative (1/92, 1.1%, lower than EBVnGC, 303/1 727, 17.5%), and that PD-L1 was mostly positive in EBVaGC (81/110, 73.6%, higher than EBVnGC, 649/2 350, 27.6%). GC patients with SALL4 negative and PD-L1 positive were often associated with better prognosis. CONCLUSION: EBVaGC is a unique subtype of GC with less metastasis and a good prognosis. It also has a distinct molecular background. The down-regulation of invasion/metastasis gene SALL4 and up-regulation of immune checkpoint gene PD-L1 are important molecular features.

Noninvasive induction of angiogenesis in tissues by external suction: sequential optimization for use in reconstructive surgery.

In reconstructive surgery, tissues are routinely transferred to repair a defect caused by trauma, cancer, chronic diseases, or congenital malformations; surgical transfer intrinsically impairs metabolic supply to tissues placing a risk of ischemia-related complications such as necrosis, impaired healing, or infection. Pre-surgical induction of angiogenesis in tissues (preconditioning) can limit postsurgical ischemic complications and improve outcomes, but very few preconditioning strategies have successfully been translated to clinical practice due to the invasiveness of most proposed approaches, their suboptimal effects, and their challenging regulatory approval. We optimized a method that adopts noninvasive external suction to precondition tissues through the induction of hypoxia-mediated angiogenesis. Using a sequential approach in a rodent model, we determined the parameters of application (frequency, suction levels, duration, and interfaces) that fine-tune the balance of enhanced angiogenesis, attenuation of hypoxic tissue damage, and length of treatment. The optimized repeated short-intermittent applications of intermediate suction induced a 1.7-fold increase in tissue vascular density after only 5 days of treatment (p < 0.05); foam interfaces showed the same effectiveness and caused less complications. In a second separate experiment, our model showed that the optimized technique significantly improves survival of transferred tissues. Here we demonstrate that noninvasive external suction can successfully, safely, and promptly enhance vascularity of soft tissues: these translational principles can help design effective preconditioning strategies, transform best clinical practice in surgery, and improve patient outcomes.

[An analysis of clinical features of celiac disease patients in different ethnic].

OBJECTIVE: To summarize the clinical features of different racial patients with celiac disease (CD) and analyze the disease prevalence, diagnosis and treatment in Chinese population. METHODS: All the patients were diagnosed as CD and enrolled in Beijing United Family Hospital between January 2005 and July 2015.Clinical data including nationality, age, symptoms, endoscopic and pathological findings, outcome were collected and compared in patients from different countries. RESULTS: A total of 87 patients were enrolled including 63 Caucasians, 18 Asian patients and 6 Middle East patients.The peak age of disease onset was 40-60 years old.Patients with typical symptoms such as chronic diarrhea and weight loss only accounted for 20.7%(18/87) and 9.2%(8/87) respectively.Some patients presented with nonspecific symptoms such as abdominal pain and bloating [32.2%(28/87)], even constipation [5.7%(5/87)].13.8%(12/87) patients were previously diagnosed as irritable bowel syndrome.The incidence of abdominal pain, bloating, diarrhea and constipation between Asians and Caucasians had no statistical significance (P>0.05); but the proportions of weight loss, growth retardation, iron deficiency anemia and dermatitis herpetiformis in Asian group were significantly higher than that in Caucasian group (P<0.05). IgA type of anti-gliadin antibody (AGA), endomysium antibody (EMA) and tissue transglutaminase antibody (tTGA) were dominant autoimmune antibodies in patients with CD, which accounted for 58.6%(51/87), 44.8%(39/87) and 36.8%(32/87) respectively.The endoscopy showed that the lesion of CD was mainly located in small intestine, with reducing severity from the proximal to the distal small intestine.The lesions of duodenal bulb and descending duodenum appeared more significant in Asian group.Accordingly pathological intestinal atrophy and the degree of intraepithelial lymphocytosis were more severe in Asian patients.All 87 cases took the gluten-free diet (GFD). Eighty-one cases received serological follow up and 8 with endoscopic intestinal biopsy.The celiac disease antibodies in 47 patients turned negative from 6-9 months after GFD treatment, while 34 patients turned negative from 12-18 months after GFD.All patients reported disease remission to some extent.After 1 year GFD treatment, the pathology of endoscopic intestinal biopsy in 8 patients showed significant improvement of villous atrophy and lymphocyte infiltration. CONCLUSIONS: CD patients with typical clinical manifestations are not the majority.Serological celiac disease antibodies (AGA, EMA and tTGA) have a high diagnostic value.GFD treatment is effective on majority of celiac patients.Clinical manifestations, endoscopy, intestinal pathology, and response to GFD in Chinese patients are not the same as Caucasians.Clinicians need to pay attention to the differential diagnosis.

Death-associated protein-3, DAP-3, correlates with preoperative chemotherapy effectiveness and prognosis of gastric cancer patients following perioperative chemotherapy and radical gastrectomy.

BACKGROUND: DAP3 is a member of the death-associated protein (DAP) family and is characterised by proapoptotic function. It is involved in both exogenous and endogenous apoptotic pathways. In our previous studies, apoptotic level was found to be correlated with the effectiveness of preoperative chemotherapy. The effectiveness of preoperative chemotherapy was also associated with the overall effectiveness of the combined therapy and prognosis. The present study aimed to investigate the role of DAP3 in the evaluation of preoperative chemotherapy effectiveness and its ability to predict prognosis in gastric cancer. METHODS: Quantitative PCR and immunohistochemistry staining were performed in 87 patients who received combined therapy. Knockdown of DAP3 was conducted in gastric cancer cell lines to investigate its impact on cell growth, migration, adhesion and invasion. Tolerance to chemotherapy agents was determined by assessing apoptosis and caspase-3. RESULTS: Higher DAP3 expression in gastric tumours was correlated with better prognosis. Knockdown of DAP3 expression promoted cell migration and enhanced resistance to chemotherapy by inhibiting apoptosis. CONCLUSION: DAP3 is a potential molecular marker for response to preoperative chemotherapy and for predicting prognosis in gastric cancer patients treated with neoadjuvant chemotherapy and gastrectomy.

An endurance-enhancing effect of peanut meal protein hydrolysate in mice: possible involvement of a specific peanut peptide.

To improve the functional properties of peanut meal protein for wide utilization, hydrolysis was conducted by alcalase. Compared with saline and peanut meal protein, intragastric administration of low molecular weight (<1 kD) peanut meal peptide (PPH I) could significantly prolong swimming time, increase levels of blood sugar, non-esterified fatty acids (NEFA) and liver glycogen and decrease blood lactate content in mice. Levels of Pro, Leu, Val and His in low molecular weight peanut meal peptides were higher significantly than those in other peanut meal protein hydrolysates. Hydrophobic amino acids, such as Pro, Tyr and His, could perhaps capture free radical and increase antioxidant capacity of peanut peptide and retard fatigue induced by free radical. After separation by HPLC, a primary peptide P1, Pro-Glu-Ile-Glu-Val, was sequenced. Its N-terminal was Val, and it was rich in antioxidant amino acid, Pro and Ile. Levels of plasma glucose, NEFA and liver glycogen in PPH I group were higher than those in mice intragastric administration with peptide P1, and the swimming time is longer in PPH I group than in P1 group. So, the high content of P1 was one of the reason why PPH I had high endurance-enhancing capacity.

[Neoadjuvant immunotherapy ushers in a new era of gastric cancer treatment].

Recent advances in tumor immunology have made immunotherapy a new direction for neoadjuvant treatment of gastric cancer. Multiple clinical trials have confirmed that combining immunotherapy with chemotherapy and targeted therapy in the neoadjuvant treatment of gastric cancer can effectively improve treatment response and prolong patient survival time. This article aims to comment on the application of immunotherapy in the neoadjuvant treatment of gastric cancer, exploring its mechanisms, integration strategies with traditional treatments, safety, and personalized precision therapy in the hope of providing new insights and directions for the field of gastric cancer treatment.

Origin of giant enhancement of phase contrast in electron holography of modulation-doped n-type GaN.

The electron optical phase contrast probed by electron holography at n-n+ GaN doping steps is found to exhibit a giant enhancement, in sharp contrast to the always smaller than expected phase contrast reported for p-n junctions. We unravel the physical origin of the giant enhancement by combining off-axis electron holography data with self-consistent electrostatic potential calculations. The predominant contribution to the phase contrast is shown to arise from the doping dependent screening length of the surface Fermi-level pinning, which is induced by FIB-implanted carbon point defects below the outer amorphous shell. The contribution of the built-in potential is negligible for modulation doping and only relevant for large built-in potentials at e.g. p-n junctions. This work provides a quantitative approach to so-called dead layers at TEM lamellas.

Periodontal tissue engineering with stem cells from the periodontal ligament of human retained deciduous teeth.

BACKGROUND AND OBJECTIVE: Periodontal ligament stem cells from human permanent teeth (PePDLSCs) have been investigated extensively in periodontal tissue engineering and regeneration. However, little knowledge is available on the periodontal ligament stem cells from human retained deciduous teeth (DePDLSCs). This study evaluated the potential of DePDLSCs in periodontal tissue regeneration. MATERIAL AND METHODS: DePDLSCs were isolated and purified by limited dilution. The characteristics of DePDLSCs were evaluated and compared with PePDLSCs both in vitro and in vivo. RESULTS: DePDLSCs presented a higher proliferation rate and colony-forming capacity than PePDLSCs in vitro. During the osteogenic induction, alkaline phosphatase (ALP) activity, mineralized matrix formation and expression of mineralization-related genes, including runt-related transcription factor 2 (RUNX2), ALP, collagen type I (COLI) and osteocalcin (OCN) were significantly enhanced in DePDLSCs compared with PePDLSCs. Furthermore, DePDLSC cell sheets showed a stronger synthesis of collagen type I in the extracellular matrix than did PePDLSC cell sheets. After in vivo transplantation, DePDLSC cell sheets recombined with human dentin blocks were able to generate new cementum/periodontal ligament-like tissues. CONCLUSION: Our findings suggest that DePDLSCs can be used as a promising candidate for periodontal tissue engineering.

CaFeFeNbO6 - an iron-based double double perovskite.

Ordering of cations is important for controlling properties of ABO3 perovskites, and CaFeFeNbO6 is the first example of an Fe-based AA'BB'O6 double double perovskite, with Ca2+/Fe2+ ordered on A-site columns, and Fe3+/Nb5+ at the octahedral B-sites. Substantial (37%) antisite disorder of the latter cations leads to spin glassy magnetism below a freezing transition at 12 K. The CaMnFeNbO6 analogue also shows substantial cation disorder and spin glassy behaviour. Comparison of synthesis pressures for ordered materials based on different A-site transition metals, suggests that pressures of at least 14-18 GPa will be required to discover the expected plethora of double double perovskites based on A' cations smaller than Mn2+.

Kinase D-interacting Substrate of 220 kDa Is Overexpressed in Gastric Cancer and Associated With Local Invasion.

BACKGROUND/AIM: Kinase D-interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning protein (ARMS), is a transmembrane scaffold protein. Deregulated Kidins220 has been observed in various malignancies including melanoma, glioma, neuroblastoma, prostate cancer, pancreatic cancer, and ovarian cancer. MATERIALS AND METHODS: In the current study, Kidins220 expression was determined at transcript and protein levels. A Kidins220 knockdown cell model was established to identify its role in cellular functions including cell cycle, proliferation, and invasion. Cell signalling was analysed by protein array and the TCGA gastric cancer cohort. RESULTS: Kidins220 transcript levels were significantly increased in gastric tumours, compared with adjacent normal tissues. More advanced tumours (TNMIII and TNMIV) exhibited higher protein levels of Kidins220 compared with early-stage tumours (TNMI and TNMII). Increased expression of Kidins220 in gastric cancer was associated with poorer overall survival. Loss of Kidins220 promoted cell invasion and adhesion of gastric cancer and correlated to epithelial-mesenchymal transition (EMT) and matrix metalloproteinase (MMP) signalling. Knockdown of Kidins220 promoted proliferation of gastric cancer cells with an increased population at the G2/M phase. CONCLUSION: Our study identified increased expression of Kidins220 in gastric cancer, which is associated with disease progression and poor prognosis. However, Kidins220 presented an inhibitory effect on the proliferation, invasion, and adhesion through a regulation of EMT, MMP and cell cycle.

ALCAM, Activated Leukocyte Cell Adhesion Molecule, in Clinical Gastric Cancer and Patient's Response to Chemotherapies.

BACKGROUND/AIM: Activated leukocyte cell adhesion molecule (ALCAM/CD166), a member of the immunoglobulin superfamily, has been shown to regulate cell adhesion through both homotypic and heterotypic interactions. In cancer, it might be involved in disease progression and chemotherapy drug resistance. The present study explored the clinical and prognostic significance of ALCAM in gastric cancer and its impact on patient's responses to neoadjuvant chemotherapies and cancer cells' response to chemodrugs in vitro. MATERIALS AND METHODS: Two independent cohorts were included to evaluate the link between ALCAM and the clinical outcomes and pathological factors of the patients. The gastric cancer cell lines HGC27 and AGS were used to generate ALCAM knockdown cell models. The cytotoxicity of chemotherapy drugs was examined using ALCAM knockdown cell models. RESULTS: Patients with gastric cancer who had high levels of ALCAM transcripts showed a significantly shorter overall survival in both cohorts (p=0.043 and 0.006, respectively). Patients who resisted to neoadjuvant chemotherapy had marginally higher levels of ALCAM than those responded (p=0.056). Patients with low levels of ALCAM expression and resisted to neoadjuvant chemotherapy had the worst clinical outcome with a significantly shorter overall survival (p=0.004) and disease-free survival (p=0.006), whereas such results did not appear in high ALCAM expression patients. ALCAM knockdown cells were more sensitive to Cisplatin, Oxaliplatin and 5-Fluorouracil compared with their respective control cells. CONCLUSION: ALCAM acts as a negative prognostic indicator in patients with gastric cancer and high levels of ALCAM expression result in increased chemotherapy drug resistance.

The trophic effect of cholecystokinin on the pancreas declines in rats on total parenteral nutrition.

Total parenteral nutrition (TPN) results in atrophy of the pancreas, while cholecystokinin (CCK) can significantly stimulate the exocrine pancreas in rodents. This study was designed to examine whether CCK may improve the atrophy of the pancreas in rats on TPN treatment. Forty-eight Sprague-Dawley rats were divided into orally fed and TPN groups and were infused with CCK at a dose of 5 µg/kg/h or the CCK-receptor antagonist devazepide at a dose of 200 µg/kg/h for 10 days. Infusion of CCK caused hypercholecystokininemia (hyperCCKemia) and decreased the atrophy of the pancreas resulting from TPN. The hyperplastic response to CCK in orally fed rats was decreased in the rats given TPN. Devazepide did not influence the pancreatic variables. This study further confirmed that CCK stimulates the exocrine pancreas and decreases the atrophy of the exocrine pancreas resulting from TPN. Our present findings suggest that the trophic effect of CCK on the exocrine pancreas declines in TPN.

Clinical use of internal distraction osteogenesis in the rehabilitation of gunshot injuries of the mandible.

Rehabilitation of gunshot injuries that require combined reconstruction of bone and soft tissue poses a considerable challenge. We describe three cases of rehabilitation for mandibular defects and deformities caused by gunshot injuries. After debridement, three kinds of internal distractors were used. The bony transport discs were distracted about 10-22mm, and the new bone formed well in the distracted gaps. There was no evidence of infection during the consolidation period or follow up. Aesthetic appearance was also pleasing after treatment. Internal distraction osteogenesis after debridement might be a practical way of synchronously reconstructing bony and soft tissue after mandibular gunshot injuries.

Effects of ischemic postconditioning on reperfusion injury in rat liver grafts after orthotopic liver transplantation.

AIM: The effects of ischemic postconditioning (IPostC) on ischemia reperfusion (IR) injury of liver grafts was examined in rats after orthotopic liver transplantation (OLT). METHODS: Male Wistar rats were used as donors and recipients to establish a liver transplantation model. The animals were randomly divided into four groups: sham-operated (SO, n = 6), IR (n = 6), IPostC1 (n = 6) and IPostC2 (n = 6). IPostC was achieved by several intermittent interruptions of blood flow in the early phase of reperfusion. Several parameters of hepatic damage, oxidative stress, neutrophil infiltration and the expression of TNF-alpha and MIP-2 were detected as well as microscopic examination. Nitric oxide release and liver NO synthases (endothelial NO synthase and inducible NO synthase) expression were also measured. RESULTS: We observed that a significant reduction in alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase values in two IPostC groups when compared with IR group. The increases in hepatic malondialdehyde, and decreases in superoxide dismutase and reduced glutathione levels after orthotopic liver transplantation were significantly inhibited by IPostC. IR induced increase in hepatic myeloperoxidase content, TNF-alpha and MIP-2 expression were also lowered by IPostC. The increases in NO content and NOS protein expression were much more prominent in IPostC treated groups. Animals treated with IPostC presented minimal hemorrhage and reduced signs of liver injury. There was no significant difference between two IPostC treated groups. CONCLUSIONS: IPostC provided significant protection against IR injury to liver grafts. The protective effect of IPostC is closely related to the NO production following the increase in endothelial and inducible NO synthases expression and the suppression of tumor necrosis factor-alpha and macrophage inflammatory protein-2 overproduction.

Counting-based cell-free DNA screening test fails to identify triploidy-A case report.

Although noninvasive prenatal testing (NIPT) is a good test with high sensitivity and specificity for trisomy 21, 18, and 13, it remains a screening test and cannot be used for diagnostic purposes. It is important to consider the outcomes of this test and interpret the results and offer consultation accordingly.

Membrane progestin receptor beta (mPR-beta): a protein related to cumulus expansion that is involved in in vitro maturation of pig cumulus-oocyte complexes.

A new group of putative membrane receptors have now been isolated from fish and other vertebrates, including human. These proteins are classified into three groups known as membrane progestin receptor alpha, beta and gamma (mPR-alpha, -beta and -gamma). In the present study we have investigated the role of mPR-beta in regulating in vitro maturation (IVM) of pig cumulus-oocyte complexes (COCs). RT-PCR and Western blot analysis indicated that COCs contain transcripts and proteins for mPR-beta. The levels of both transcripts and proteins increased between 0 and 20h IVM, but then decreased between 20 and 44h. The luteinizing hormone (LH) and follicle-stimulating hormone (FSH) did not affect mPR-beta expression during IVM. Immunofluorescence analysis indicated that the mPR-beta was localized in the plasma membrane of cumulus cell. However, in mouse embryonic fibroblasts (MEFs), mPR-beta was detected at the endoplasmic reticulum (ER) rather than the plasma membrane. Cumulus expansion was impaired significantly (P<0.05) when COCs were incubated in maturation medium containing 10% (v/v) anti-mPR-beta serum during IVM. Bioinformatics analysis predicted that mPR-beta had an ER retention motif and an endocytosis internalization motif. These results suggest that the mPR-beta is a molecule related to cumulus expansion and it might function by regulation of exocytosis. In conclusion, this is the first description of the expression patterns and subcellular localization of mPR-beta in COCs and might shed light on the function of the protein.

Effect of silencing microRNA-508 by STTM on melanogenesis in alpaca (Vicugna pacos).

It has been demonstrated that microRNAs (miRNAs) play important roles in the regulation of melanogenesis and hair color in mammals. Short tandem target mimic (STTM) has been used to effectively block small RNA functions in plants and animals. We previously showed that miR508-3p plays a functional role in regulating melanogenesis in alpaca melanocytes by directly targeting microphthalmia (MITF). To verify the effect of miR-508-3p function on melanogenesis in alpaca melanocytes, miR-508-3p was blocked using STTM technology in the present research. miR508-3p was predicted to target the gene encoding SRY-box6 (SOX6) by bioinformatics. The luciferase reporter assay indicated that miR508-3p regulates SRY-box6 (SOX6) expression by targeting its 3'UTR. Here, STTM-miR508-3p overexpression in alpaca melanocytes blocked the expression of miR-508-3p and up-regulated SOX6 expression at both the mRNA and protein levels, resulting in increasing the expression of key melanogenic genes, including cAMP responsive element (CRE) binding protein (CREB), MITF, tyrosinase (TYR) and tyrosinase-related protein 1 and 2 (TYRP1 and TYRP2). STTM-miR508-3p overexpression in melanocytes also resulted in increased melanin production, including total alkali soluble melanogenesis (ASM), eumelanogenesis (EM) and pheomelanogenesis (PM). Additionally, we identified melanin granules in alpaca melanocytes transfected with STTM-miR508-3p under Fontana-Masson staining. These results suggest that STTM-miR508-3p could up-regulate melanogenesis by effectively blocking miR508-3p.

MiR-378 promotes the cell proliferation of non-small cell lung cancer by inhibiting FOXG1.

OBJECTIVE: To identify the functioning mode of miR-378 on non-small cell lung cancer (NSCLC) and provide therapeutic targets for NSCLC. PATIENTS AND METHODS: Expression levels of miR-378 in human NSCLC tissue samples and NSCLC-derived cell lines were measured by using quantitative Real-time polymerase chain reaction (PCR). Cell proliferation capacity was assessed by methyl thiazolyl tetrazolium (MTT) assay and colony formation assay. Cell apoptosis and cell cycle distribution were identified by flow cytometry. Downstream target gene was confirmed by using luciferase and Western blotting assays. RESULTS: MiR-378 was significantly elevated in NSCLC tissues when compared with para-carcinoma tissues (n=42). Decreased-miR-378 could attenuate cell proliferation capacity, as well as promoted cell apoptosis and induced cell cycle arrest at G0/G1 phase. FOXG1 was chosen as the target gene of miR-378 by bioinformatics analysis and luciferase reporter assay. Moreover, restoration of miR-378 could impair the tumor suppression role of downregulated-miR-378 on NSCLC growth. CONCLUSIONS: Decreased-miR-378 exerted tumor-suppressive effects on NSCLC growth via targeting FOXG1 in vitro, which provided an innovative and candidate target for diagnosis and treatment of NSCLC.

Autophagy attenuates the oxidative stress-induced apoptosis of Mc3T3-E1 osteoblasts.

OBJECTIVE: The oxidative stress-induced osteoblast apoptosis plays an important role in the pathological process of osteoporosis, but the roles of autophagy in oxidative stress and apoptosis of osteoblasts remain unclear. This study aimed to observe the role of autophagy in oxidative stress injury of osteoblasts and the relationship between autophagy and apoptosis. MATERIALS AND METHODS: Mc3T3-E1 cells were stimulated with different concentrations (0.1, 0.5, and 1 mM) of hydrogen peroxide. The cell viability was detected via cell counting kit 8 (CCK8) at different time points (0, 2, 6, 8, and 12 h), the apoptosis was detected via Western blotting and flow cytometry, and the autophagy was detected via macrophage-derived chemokine (MDC) and transmission electron microscope. The changes in expression of autophagy-associated protein, Beclin1, and LC3II/I ratio, were detected via Western blotting. Moreover, the intracellular reactive oxygen species (ROS) level and extracellular superoxide dismutase (SOD) level were observed using the autophagy regulators, rapamycin (Rap) and 3-methyladenine (3-MA), so as to clarify the interaction between autophagy and cellular oxidation. RESULTS: Hydrogen peroxide-induced apoptosis and autophagy of osteoblasts were in dose- and time-dependent manners; the hydrogen peroxide inhibitors could inhibit the autophagy level, and autophagy inhibitor (3-MA) could significantly enhance the hydrogen peroxide-induced ROS level and apoptosis rate in cells. Besides, Western blotting confirmed that the cleaved caspase-3 and cleaved poly adenosine diphosphate ribose polymerase (PARP) proteins were increased. The autophagy inducer (Rap) partially inhibited the hydrogen peroxide-induced oxidative stress and apoptosis. CONCLUSIONS: Autophagy inhibits the oxidative stress-mediated apoptosis of osteoblasts, which is a potential target for the osteoporosis treatment.