Influence of shoe upper structure on shoe microclimate and human physiological characteristics during running.

BACKGROUND: Shoes upper has been shown to affect the shoe microclimate (temperature and humidity). However, the existing data on the correlation between the microclimate inside footwear and the body's physical factors is still quite limited. OBJECTIVE: This study examined whether shoes air permeability would influence foot microclimate and spatial characteristics of lower limb and body. METHODS: Twelve recreational male habitual runners were instructed to finish an 80 min experimental protocol, wearing two running shoes with different air permeability. RESULTS: Participants wearing CLOSED upper structure shoe exhibited higher in-shoe temperature and relative humidity. Although there was no significant difference, shank temperature and metabolism in OPEN upper structure shoes were lower. CONCLUSIONS: This indicates that the air permeability of shoes can modify the microclimate of the feet, potentially affecting the lower limb temperature. This study provides relevant information for the design and evaluation of footwear.

The triacylglycerol structures are key factors influencing lipid digestion in preterm formulas during in vitro digestion.

Preterm formulas are usually supplemented with medium-chain triacylglycerols (MCT) whereas breast milk contains more medium and long-chain triacylglycerols (MLCT). Different types of triacylglycerol (TAG) containing medium-chain fatty acids may influence lipid digestion. In this study, the digestive characteristics of breast milk and preterm formulas with different MCT contents were evaluated using a dynamic in vitro system simulating the gastrointestinal tract of preterm infants. The lipolysis products, including diacylglycerols, monoacylglycerols (MAGs), free fatty acids, and undigested TAGs, were analyzed. Formulas with MCT addition has significantly (P < 0.05) lower lipolysis degree (LD, 69.35%-71.28%) than breast milk (76.93%). Higher amounts of C8:0 and C10:0 were released in the formulas with MCT addition. Breast milk released more C18:1n-9, C18:2n-6, and MAG containing C16:0, whereas formulas released more free C16:0. The Pearson correlation heatmap showed that the LD value was significantly and positively (P < 0.05) related to the MLCT and sn-2 C16:0 content.

Adiponectin reduces apoptosis of diabetic cardiomyocytes by regulating miR-711/TLR4 axis.

OBJECTIVE: To investigate the regulation of adiponectin/miR-711 on TLR4/NF-κB-mediated inflammatory response and diabetic cardiomyocyte apoptosis. METHODS: Diabetes models were established using rats and H9c2 cardiomyocytes. qRT-PCR was used to detect adiponectin, miR-711, and TLR4. MTT, ß-galactosidase staining, and flow cytometry were utilized to assess cell viability, senescence, and apoptosis, respectively. The colorimetric method was used to measure caspase-3 activity, DCFH-DA probes to detect ROS, and western blotting to determine the protein levels of Bax, Bcl-2, TLR4, and p-NF-κB p65. ELISA was performed to measure the levels of adiponectin, ICAM-1, MCP-1, and IL-1ß. Dual-luciferase reporter system examined the targeting relationship between miR-711 and TLR4. H&E and TUNEL staining revealed myocardial structure and apoptosis, respectively. RESULTS: Adiponectin and miR-711 were underexpressed and TLR4/NF-κB signaling pathway was activated in high glucose-treated H9c2 cells. High glucose treatment reduced viability, provoked inflammatory response, and accelerated senescence and apoptosis in H9c2 cells. miR-711 could bind TLR4 mRNA and inactivate TLR4/NF-κB signaling. Adiponectin treatment increased miR-711 expression and blocked TLR4/NF-κB signaling. Adiponectin/miR-711 reduced myocardial inflammation and apoptosis in diabetic rats. CONCLUSION: Adiponectin inhibits inflammation and alleviates high glucose-induced cardiomyocyte apoptosis by blocking TLR4/NF-κB signaling pathway through miR-711.

miR-22 Suppresses EMT by Mediating Metabolic Reprogramming in Colorectal Cancer through Targeting MYC-Associated Factor X.

Colorectal cancer (CRC) is one of the most frequent gastrointestinal cancers. MicroRNAs (miRNAs) have been proved to be unusually expressed in CRC progression and thus alter multiple pathological processes in CRC cells. However, the specific roles and mechanisms of miR-22 in CRC have not been clearly reported. MicroRNA-22 (miR-22) and MYC-associated factor X (MAX) expressions were determined by RT-qPCR in CRC tissues and cells. The targeted regulatory effects of miR-22 and MAX were confirmed by luciferase reporter and coimmunoprecipitation assays. Also, gain- and loss-of-function and rescue experiments were used to elucidate the function and mechanism of miR-22 and MAX in CRC cells and the mouse xenograft model. We discovered that miR-22 was hypermethylated and downregulated, while MAX was upregulated in CRC. miR-22 markedly inhibited migration, invasion, glycolysis, and cancer stem cell transcription factors in CRC cells. In addition, it was found that miR-22 can directly target MAX. Additional functional experiments confirmed that MAX overexpression can rescue the effects of miR-22 on the behavior of CRC cells. This study suggested that miR-22, as a cancer suppressor, participates in CRC progression by targeting MAX, which might provide basic information for therapeutic targets for CRC.

Dynorphin/KOR inhibits neuronal autophagy by activating mTOR signaling pathway to prevent acute seizure epilepsy.

In previous studies, we found that dynorphin exerts antiepileptic effect by activating the kappa opioid receptor (KOR). However, the role of neuronal autophagy in dynorphin/KOR-mediated antiepileptic is still unclear. This study aimed to investigate the molecular mechanism of dynorphin's antiepileptic effect by inhibiting autophagy and reducing neuronal apoptosis. Here, a pilocarpine-induced rat model of epilepsy was established and hippocampal neurons were treated with Mg2+ -free exposed for epileptiform activity induction. The real-time polymerase chain reaction and Western blot analysis were used to evaluate messenger RNA and protein expression. The TdT-mediated dUTP-biotin nick end labeling staining and flow cytometry were used to analyze cell apoptosis in vivo and in vitro. Neuron cells viability was detected by Cell Counting Kit-8 assay. Immunofluorescent staining and green fluorescent protein-light chain 3 immunofluorescence were used to measure autophagy in vivo and in vitro. Results showed that overexpression of prodynorphin alleviated neuronal apoptosis, activated the mammalian target of rapamycin (mTOR) signaling pathway, and inhibited neuronal autophagy in epileptic rats. Dynorphin inhibited Mg2+ -free-induced seizure-like neuron apoptosis, partially reversing the effect of Mg2+ -free on the mTOR signaling pathway and seizure-like neuron autophagy. Further, using rapamycin, we found that dynorphin inhibited Mg2+ -free-induced seizure-like neuron autophagy and apoptosis by activating the mTOR signaling pathway. In conclusion, dynorphin inhibits autophagy by activating the mTOR signaling pathway and has a protective effect on epilepsy acute seizure and epilepsy-induced brain injury.

Inhibition of ANXA2 regulated by SRF attenuates the development of severe acute pancreatitis by inhibiting the NF-κB signaling pathway.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory process of the pancreas resulting from biliary obstruction or alcohol consumption. Approximately, 10-20% of AP can evolve into severe AP (SAP). In this study, we sought to explore the physiological roles of the transcription factor serum response factor (SRF), annexin A2 (ANXA2), and nuclear factor-kappaB (NF-κB) in SAP. METHODS: C57BL/6 mice and rat pancreatic acinar cells (AR42J) were used to establish an AP model in vivo and in vitro by cerulein with or without lipopolysaccharide (LPS). Production of pro-inflammatory cytokines (IL-1ß and TNF-α) were examined by ELISA and immunoblotting analysis. Hematoxylin and eosin (HE) staining and TUNEL staining were performed to evaluate pathological changes in the course of AP. Apoptosis was examined by flow cytometric and immunoblotting analysis. Molecular interactions were tested by dual luciferase reporter, ChIP, and Co-IP assays. RESULTS: ANXA2 was overexpressed in AP and correlated to the severity of AP. ANXA2 knockdown rescued pancreatic acinar cells against inflammation and apoptosis induced by cerulein with or without LPS. Mechanistic investigations revealed that SRF bound with the ANXA2 promoter region and repressed its expression. ANXA2 could activate the NF-κB signaling pathway by inducing the nuclear translocation of p50. SRF-mediated transcriptional repression of ANXA2-protected pancreatic acinar cells against AP-like injury through repressing the NF-κB signaling pathway. CONCLUSION: Our study highlighted a regulatory network consisting of SRF, ANXA2, and NF-κB that was involved in AP progression, possibly providing some novel targets for treating SAP.

Effect of Implantable Electrical Nerve Stimulation on Cortical Dynamics in Patients With Herpes Zoster-Related Pain: A Prospective Pilot Study.

Implantable electrical nerve stimulation (ENS) can be used to treat neuropathic pain caused by herpes zoster. However, little is known about the cortical mechanism underlying neuromodulation therapy. Here, we recorded a 16-channel resting-state electroencephalogram after the application of spinal cord stimulation (n = 5) or peripheral nerve stimulation (n = 3). The neuromodulatory effect was compared between specific conditions (active ENS versus rest). To capture the cortical responses of ENS, spectral power and coherence analysis were performed. ENS therapy achieved satisfactory relief from pain with a mean visual analog scale score reduction of 5.9 ± 1.1. The spectral analysis indicated that theta and alpha oscillations increased significantly during active neuromodulation compared with the resting state. Furthermore, ENS administration significantly increased frontal-frontal coherence in the alpha band. Our findings demonstrate that, despite methodological differences, both spinal cord and peripheral nerve stimulation can induce cortical alpha oscillation changes in patients with zoster-related pain. The dynamic change may, in part, mediate the analgesic effect of ENS on herpes zoster-related pain.

The effect of arch-support insole on knee kinematics and kinetics during a stop-jump maneuver.

BACKGROUND: Anterior cruciate ligament injuries commonly occur during sports that involve sudden stops or direction changes. Although athletes often use arch-support insoles in competition and training, little is known about the effect of foot insoles on knee biomechanics and jump take-off performances. OBJECTIVE: This study aimed to investigate the effects of arch-support insoles on knee kinematics and kinetics during the stop-braking phase and the subsequent jump take-off performances. STUDY DESIGN: That is a quasi-experimental study, repeated-measures design. METHODS: Twenty male healthy recreational university basketball athletes performed stop-jump with maximum effort in both arch-support and flat insole conditions. Paired t -tests were performed on knee kinetics and kinematics and jump performance variables to determine whether there were significant differences between insole conditions. RESULTS: Wearing arch-support insoles experienced larger ground reaction forces (GRFs), loading rates of peak vertical and posterior GRFs, peak knee adduction and rotation moments, and knee flexion angular velocity than the flat insoles ( P < 0.05). CONCLUSIONS: The increased GRFs and knee loading in arch-support insoles are indicative of a higher risk of anterior cruciate ligament injuries. The findings could be insightful to the knee mechanics that are related to performance and injury potential during stop-jump maneuvers.

Knockdown of miR-92a suppresses the stemness of colorectal cancer cells via mediating SOCS3.

ABBREVIATIONS: CRC, cancer cell; CSCs, cancer stem cells; SOCS3, suppressor of cytokine signaling 3.

Sirtuin 6 regulates macrophage polarization to alleviate sepsis-induced acute respiratory distress syndrome via dual mechanisms dependent on and independent of autophagy.

BACKGROUND AIMS: Sepsis-induced acute respiratory distress syndrome (ARDS) can be mediated by an imbalance in macrophage polarization; however, the underlying mechanisms remain poorly understood. This study aimed to investigate the modulatory role of sirtuin 6 (SIRT6) in macrophage polarization during sepsis-induced ARDS. METHODS: A mouse ARDS model was established using cecal ligation and puncture. Isolated alveolar macrophages (AMs) and lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs) were adopted as in vitro models. Macrophage polarization was evaluated by measuring M1 and M2 macrophage percentages via flow cytometry and expression of specific markers. The expression of microtubule-associated light chain protein 3I/II and beclin-1 was detected for assessing macrophage autophagy. Binding between specificity protein 1 (SP1) and the target gene promoter was evaluated using a chromatin immunoprecipitation assay. RNA expression was analyzed by quantitative reverse transcription polymerase chain reaction and western blotting. RESULTS: Treatment with the SIRT6 activator UBCS039 significantly alleviated lung injury in the mouse ARDS model and enhanced autophagy and M2 polarization in isolated AMs. M2 polarization and autophagy in LPS-challenged BMDMs were also effectively promoted by UBCS039 treatment or SIRT6 overexpression. An adenosine monophosphate-activated protein kinase inhibitor (Compound C) or autophagy inhibitor (3-methyladenine) partially abrogated M2 polarization mediated by SIRT6 overexpression upon LPS exposure. SIRT6 induced autophagy and M2 polarization of BMDMs partially via its deacetylase activity. SIRT6 inhibited mammalian target of rapamycin transcription by modulating SP1 to promote BMDM M2 polarization, which was independent of autophagy. CONCLUSIONS: SIRT6 promotes M2 polarization of macrophages to alleviate sepsis-induced ARDS in an autophagy-dependent and -independent manner.

Naringin improves sepsis-induced intestinal injury by modulating macrophage polarization via PPARγ/miR-21 axis.

Naringin exhibited various pharmacological activities. However, its biological function and underlying mechanism in regulating macrophage polarization remain elusive. This study aimed to investigate the regulatory network between naringin and macrophage polarization in sepsis-induced intestinal injury. Cecal ligation and puncture (CLP) was used to establish the animal model of sepsis. Chromatin immunoprecipitation and a luciferase reporter assay were used to determine the interplay between peroxisome proliferator-activated receptor γ (PPARγ) and miR-21 promoter, as well as miR-21 and its target genes. Naringin enhanced the overall survival of septic mice and alleviated the CLP-induced inflammatory response and intestinal damage. This was accompanied by the increased expression of PPARγ in the intestines and the stimulation of ileal macrophages toward the M2 phenotype. Furthermore, in lipopolysaccharide-stimulated bone marrow-derived macrophages, naringin stimulated M2 polarization. Mechanistically, PPARγ inhibition attenuated the promotion of M2 polarization caused by naringin, and the naringin/PPARγ regulatory work was compromised by miR-21 inhibition. The present study suggested that naringin promoted M2 polarization via the PPARγ/miR-21 axis, thus relieving sepsis-induced intestinal injury. This study provides novel insights into the mechanism by which naringin alleviated sepsis-induced intestinal injury through regulation of macrophage polarization.

MiR-20b-5p modulates inflammation, apoptosis and angiogenesis in severe acute pancreatitis through autophagy by targeting AKT3.

BACKGROUND: Severe acute pancreatitis (SAP) is a common acute abdominal disease with high morbidity and mortality. However, the mechanism underlying SAP is still unclear. METHODS: Cerulean and LPS (Cer-LPS) was used to establish a rat model and an in vitro model of SAP. qRT-PCR, western blot and IHC were determined to analyse the expression of mRNA and proteins. IL-1ß, TNF-α and IL-6 levels were measured applying ELISA. H&E staining was determined to observe the pathological changes. Apoptosis was tested by AV-PI staining using flow cytometry. CCK8 assay was taken to detect cell viability. Cell migration was assessed by transwell assay. Tube formation assay was conducted to evaluate angiogenesis. Luciferase assay was used to detect relationship of miR-20b-5p and AKT3. RESULTS: MiR-20b-5p was lowly expressed in SAP models both in vivo and in vitro. Overexpression of miR-20b-5p restrained inflammation and apoptosis in Cer-LPS treated pancreatic acinar cells. Furthermore, miR-20b-5p promoted the angiogenesis of vascular endothelial cells, since the viability, migration and the capability of tube formation were increased by miR-20b-5p. Mechanically, miR-20b-5p directly targeted AKT3 to promote autophagy. Furthermore, miR-20b-5p could prevent the inflammation, apoptosis and enhance angiogenesis via enhancing autophagy, which was verified in vivo. CONCLUSION: This study demonstrated miR-20b-5p attenuates SAP through directly targeting AKT3 to regulate autophagy, subsequently inhibit inflammation and apoptosis, and promote angiogenesis. Our findings suggested a novel target of miR-20b-5p for the therapy of SAP.

Expression and prognostic significance of CBX2 in colorectal cancer: database mining for CBX family members in malignancies and vitro analyses.

BACKGROUND: The Chromobox (CBX) domain protein family, a core component of polycomb repressive complexes 1, is involved in transcriptional repression, cell differentiation, and program development by binding to methylated histone tails. Each CBX family member plays a distinct role in various biological processes through their own specific chromatin domains, due to differences in conserved sequences of the CBX proteins. It has been demonstrated that colorectal cancer (CRC) is a multiple-step biological evolutionary process, whereas the roles of the CBX family in CRC remain largely unclear. METHODS: In the present study, the expression and prognostic significance of the CBX family in CRC were systematically analyzed through a series of online databases, including Cancer Cell Line Encyclopedia (CCLE), Oncomine, Human Protein Atlas (HPA), and Gene Expression Profiling Interactive Analysis (GEPIA). For in vitro verification, we performed cell cloning, flow cytometry and transwell experiments to verify the proliferation and invasion ability of CRC cells after knocking down CBX2. RESULTS: Most CBX proteins were found to be highly expressed in CRC, but only the elevated expression of CBX2 could be associated with poor prognosis in patients with CRC. Further examination of the role of CBX2 in CRC was performed through several in vitro experiments. CBX2 was overexpressed in CRC cell lines via the CCLE database and the results were verified by RT-qPCR. Moreover, the knockdown of CBX2 significantly suppressed CRC cell proliferation and invasion. Furthermore, the downregulation of CBX2 was found to promote CRC cell apoptosis. CONCLUSIONS: Based on these findings, CBX2 may function as an oncogene and potential prognostic biomarker. Thus, the association between the abnormal expression of CBX2 and the initiation of CRC deserves further exploration.

Long Non-coding RNA FENDRR Modulates Autophagy Through Epigenetic Suppression of ATG7 via Binding PRC2 in Acute Pancreatitis.

Acute pancreatitis (AP) is an inflammatory, complicated pancreatic disease, carrying significant morbidity and mortality. However, the molecular and cellular mechanisms involved in AP pathogenesis remain to be elucidated. Here, we explore the role of FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) in AP progression. Caerulein with or without LPS- induced or taurolithocholic acid 3-sulfate (TLC-S)-induced AP mouse models and cell models were performed for the validation of FENDRR expression in vivo and in vitro, respectively. Histopathological examinations of pancreatic tissues were performed to evaluate the severity of AP. Transmission electron microscopy was utilized to visualize the autophagic vacuoles. siRNA specifically targeting FENDRR was further applied. Flow cytometry was employed to assess cell apoptosis. ELISA, immunoflureoscence, and western blotting analysis were also performed to determine the levels of inflammatory cytokines and autophagy activity. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays were carried out to reveal the epigenetic regulation of FENDRR on ATG7. Additionally, silencing FENDRR was also verified in AP mouse models. Higher FENDRR and impaired autophagy were displayed in both AP mouse models and cell models. FENDRR knockdown dramatically attenuated caerulein- or TLC-S-induced AR42J cells apoptosis and autophagy suppression. Further mechanistic experiments implied that the action of FENDRR is moderately attributable to its repression of ATG7 via direct interaction with the epigenetic repressor PRC2. Moreover, the silencing of FENDRR significantly induced the promotion of ATG7, thus alleviating the development of AP in vivo. Our study highlights FENDRR as a novel target that may contribute to AP progression, suggesting a therapeutic target for AP treatment.

Influence of heel design on lower extremity biomechanics and comfort perception in overground running.

The study investigated whether an alteration of the shoe heel curvature would influence lower extremity biomechanics and comfort perception in running. Twenty recreational habitual rearfoot strikers performed five running trials in running shoes with three different heel curvature designs (short-parallel, long-parallel and oblique curvatures). Synchronised force plate and motion capturing systems were used to collect three-dimensional lower extremity joint kinetics and kinematics, followed by subjective comfort perception on the 15 cm Visual Analogue Scale. The results showed that participants wearing oblique and long-parallel curvature shoes exhibited larger initial frontal shoe-ground angle (p= 0.003, p= 0.016) and ankle inversion angle (p= 0.008, p= 0.032) as well as higher maximum sagittal foot slap velocity (p= 0.041, p = 0.011) compared with a short-parallel curvature shoe. When wearing the short-parallel curvature shoe, participants had better rearfoot stability perception than the oblique curvature shoes (p = 0.028). These results suggest that the short parallel curvature shoes had better motion control and stability perception than the other two curvature conditions. However, the design of heel curvature seems to have minimal influence on the cushioning related variables in running.

Cytochrome C Oxidase Assembly Factor 1 Homolog Predicts Poor Prognosis and Promotes Cell Proliferation in Colorectal Cancer by Regulating PI3K/AKT Signaling.

PURPOSE: Colorectal cancer (CRC) is one of the most common malignancies in the world. The prognosis of advanced CRC is still poor. The purpose of this study was to identify a gene expression profile associated with CRC that may contribute to the early diagnosis of CRC and improve patient prognosis. PATIENTS AND METHODS: Five pairs of CRC tissues and paracancerous tissues were used to identify causative genes using microarray assays. The prognostic value of Cytochrome C Oxidase Assembly Factor 1 Homolog (COA1) in CRC was assessed in 90 CRC patients. Loss-of-function assays, cell proliferation assays using Celigo and MTT, colony formation assays, a subcutaneous xenograft mouse model, and apoptosis assays were used to define the effects of downregulation of COA1 in CRC cells in vitro and in vivo. The underlying molecular mechanisms of COA1 in CRC were also investigated. RESULTS: The causative gene COA1 was identified through microarray analysis. COA1 expression in CRC was notably associated with pathologic differentiation, tumor size, and tumor depth. COA1 expression may act as an independent prognostic factor for overall survival of CRC. Knockdown of COA1 inhibited the proliferation of CRC cells in vitro and the tumorigenicity of CRC cells in vivo. Decreased COA1 expression induced apoptosis of CRC cells. Based on the microarray assay results comparing HCT116 cells transfected with lentivirus encoding anti-COA1 shRNA or negative control shRNA, ingenuity pathway analysis (IPA) revealed that the PI3K/AKT signaling pathway was significantly enriched. Moreover, CCND1, mTOR, AKT1, and MDM2 were identified as the downstream genes of COA1. CONCLUSION: These findings demonstrate that COA1 promotes CRC cell proliferation and inhibits apoptosis by regulating the PI3K/AKT signaling pathway. Our results implicate COA1 as a potential oncogene involved in tumor growth and progression of CRC.

Relation between blood glucose and the prognosis of severe coronavirus disease 2019. / 血糖与重型2019å† çŠ¶ç— æ¯’ç— é¢„åŽçš„å ³ç³».

OBJECTIVES: To describe the clinical characteristics and outcomes of severely ill patients with coronavirus disease 2019, and to investigate the relationship between plasma glucose level and the prognosis of severely ill patients with coronavirus disease 2019. METHODS: We enrolled 52 severely ill patients with coronavirus disease 2019. Among them, 12 cases progressed to critical illness. The clinical and biochemical characteristics of severely and critically ill patients were compared. RESULTS: Compared with the severely ill patients, critically ill patients had higher white blood cell and neutrophil counts, as well as higher levels of D-dimer, IL-6 and C-reactive protein (all P<0.05). Before treatment, the fasting plasma glucose (FPG) levels were significantly higher in the critically ill patient's group [(10.23±3.71) mmol/L] compared to those in the severely ill patients [(7.12±3.35) mmol/L, P<0.05]. After adjusting for age, gender, and course of the disease, fasting blood glucose at admission (OR=1.308, 95% CI 1.066 to 1.606, P=0.01) and hyperglycemia at admission (OR=29.198, 95% CI 2.903 to 293.639, P=0.004) were closely related to whether severely ill patients progressed to critical patients with coronavirus disease 2019. In our study, 15 (34.8%) of the severely ill and 10 (83.3%) critically ill patients received the steroid treatment. Compared with the severely ill patients, the FPG levels in critically ill patients were higher (P<0.05). CONCLUSIONS: Fasting hyperglycemia at admission is a significant predictor for the prognosis of severely ill patients with coronavirus disease 2019. Closely monitoring and the optimal management of hyperglycemia may improve the prognosis of patients with coronavirus disease 2019.

Elevated expression of minichromosome maintenance 3 indicates poor outcomes and promotes G1/S cell cycle progression, proliferation, migration and invasion in colorectal cancer.

BACKGROUND: The minichromosome maintenance (MCM) family, a core component of DNA replication, is involved in cell cycle process. Abnormal proliferation has been identified as a crucial process in the evolution of colorectal cancer (CRC). However, the roles of the MCM family in CRC remain largely unknown. METHODS: Here, the expression, prognostic significance and functions of the MCM family in CRC were systematically analyzed through a series of online databases including CCLE, Oncomine, HPA, cBioPortal and cancerSEA. RESULTS: We found all MCM family members were highly expressed in CRC, but only elevation of MCM3 expression was associated with poor prognosis of patients with CRC. Further in vitro and in vivo experiments were performed to examine the role of MCM3 in CRC. Analysis of CCLE database and qRT-PCR assay confirmed that MCM3 was overexpressed in CRC cell lines. Moreover, knockdown of MCM3 significantly suppressed transition of G1 to S phase in CRC cells. Furthermore, down-regulation of MCM3 inhibited CRC cell proliferation, migration, invasion and promoted apoptosis. CONCLUSION: These findings reveal that MCM3 may function as an oncogene and a potential prognosis biomarker. Thus, the association between abnormal expression of MCM3 and the initiation of CRC deserves further exploration.

miR-375 Inhibits Autophagy and Further Promotes Inflammation and Apoptosis of Acinar Cells by Targeting ATG7.

OBJECTIVES: MicroRNAs have been considered to be closely related with the development of severe acute pancreatitis (SAP), and microRNA-375 (miR-375) was believed to be a marker of SAP. We aim to investigate the role of miR-375 in regulating SP. METHODS: Cerulein and lipopolysaccharide were used to establish the models of SAP. AR42J cell line was chosen for study in vitro. Flow cytometry was applied for assessing apoptosis. The contents of inflammatory factors were detected with related enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction assays. Hematoxylin and eosin staining was applied to observe the pathological changes of pancreatic tissues. Immunohistochemistry analysis was conducted for investigating the expression of light chain 3. RESULTS: The level of miR-375 in pancreatitis tissues and cell lines was upregulated. Overexpression of miR-375 promoted inflammation and the apoptosis of acinar cells through inhibiting autophagy. The binding site between miR-375 and ATG7 was identified, and miR-375 could directly regulate the ATG7. microRNA-375 suppressed autophagy and promoted inflammation and the apoptosis of acinar cells via targeting ATG7. CONCLUSIONS: We proved that miR-375 could inhibit autophagy and promote inflammation and the apoptosis of acinar cells through regulating ATG7. This study first proves that miR-375 modulates the development of SAP through targeting ATG7.