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MicroRNA (miRNA/miR), a type of non‑coding RNA molecule, is able to inhibit the expression of target genes at multiple stagess. There are 800‑1,000 known miRNAs in the human genome, which serve important roles in cell proliferation, differentiation, apoptosis and migration. Previous studies have demonstrated that the expression of miR‑21 is upregulated in numerous types of malignant tumor, and that miR‑21 participates in the occurrence and development of tumors via complex regulatory mechanisms. The present study aimed to investigate the association between miR‑21 expression, cell viability and apoptosis in a lung cancer cell line, and to elucidate the potential mechanisms. miR‑21 or small interfering RNA against miR‑21 were transfected into A549 non‑small cell lung cancer cells. The mRNA expression of miR‑21 was confirmed. Cell viability and apoptosis were examined using MTT and flow cytometric assays, respectively. The expression of certain apoptosis‑associated proteins was detected by western blotting. The results of the present study demonstrated that miR‑21 was able to increase the proliferation of A549 cells by inhibiting cellular apoptosis. miR‑21 inhibited apoptosis by modulating the activation of the phosphatidylinositol 3‑kinase/Rac‑α serine/threonine protein kinase (Akt) pathway in A549 cells. Correspondingly, inhibition of Akt decreased the apoptosis of A549 cells in miR‑21 siRNA‑treated cells. Therefore, the results of the present study demonstrated that miR‑21 increased cell viability by inhibiting apoptosis, through regulation of Akt activation. The present study demonstrated that miR‑21 may be involved in the progression of lung cancer and may be a novel therapeutic target for the disease. [ABSTRACT FROM AUTHOR]

The association between interleukin‑6 (IL‑6) and angiotensin II receptor 1 (AT1‑R) in modulating the progression of heart failure (HF) remains to be fully elucidated. The aim of the present study was to investigate the mechanism of IL‑6 and AT1‑R in a model of HF induced by surgery. Male Sprague‑Dawley rats were randomly divided into five groups, including sham surgery and vehicle groups. The animals were treated for 4 weeks via paraventricular nucleus infusion with either vehicle, losartan (LOS; 200 μg/day), IL‑6 (1 μg/day) or LOS and IL‑6 together (LOS+IL‑6). The rats with HF had higher levels of IL‑6, corticotropin‑releasing hormone (CRH) and norepinephrine (NE), and a lower level of neuronal nitric oxide synthase (nNOS), compared with the rats in the sham surgery group. Treatment with LOS attenuated the decrease in nNOS and the increases in IL‑6, CRH and NE; whereas treatment with IL‑6 facilitated the lower expression of nNOS and higher expression levels of IL‑6, CRH and NE. No differences in the expression levels of nNOS, CRH or NE were found between the LOS group and LOS+IL‑6 group. The results of the study demonstrated that IL‑6 contributed to the progression of HF via the AT1‑R pathway. [ABSTRACT FROM AUTHOR]

Human hepatocellular carcinoma (HCC) has been reported to be highly insensitive to conventional chemotherapy. In the current study, the Agilent Whole Human Genome Oligo Microarray (4x×44 K) was used in order to identify the differentially expressed genes between HCC and adjacent tissues, and the top 22 differentially expressed genes were confirmed through reverse transcription-quantitative polymerase chain reaction. Among the identified differences in gene expression, expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) was markedly higher in HCC tissue than in adjacent tissue. Previous studies have suggested that TNFRSF12A may serve a role in tumor growth and metastasis, thus in the current study, TNFRSF12A was knocked down in the SMMC7721 cell line through siRNA. This demonstrated that cells exhibited reduced reproductive and metastatic capacity ex vivo. Thus, the results of the current study suggest that TNFRSF12A may be a candidate therapeutic target for cancer including HCC, and additional genes that exhibited significantly different expression from normal adjacent tissues require further study. [ABSTRACT FROM AUTHOR]

The present study integrated microRNA (miRNA) and mRNA expression data obtained from atrial fibrillation (AF) tissues and healthy tissues, in order to identify miRNAs and target genes that may be important in the development of AF. The GSE28954 miRNA expression profile and GSE2240 mRNA gene expression profile were downloaded from the Gene Expression Omnibus. Differentially expressed miRNAs and genes (DEGs) in AF tissues, compared with in control samples, were identified and hierarchically clustered. Subsequently, differentially expressed miRNAs and DEGs were searched for in the miRecords database and TarBase, and were used to construct a regulatory network using Cytoscape. Finally, functional analysis of the miRNA-targeted genes was conducted. After data processing, 71 differentially expressed miRNAs and 390 DEGs were identified between AF and normal tissues. A total of 3,506 miRNA-mRNA pairs were selected, of which 372 were simultaneously predicted by both miRecords and TarBase, and were therefore used to construct the miRNA-mRNA regulatory network. Furthermore, 10 miRNAs and 12 targeted mRNAs were detected, which formed 14 interactive pairs. The miRNA-targeted genes were significantly enriched into 14 Gene Ontology (GO) categories, of which the most significant was gene expression regulation (GO 10468), which was associated with 7 miRNAs and 8 target genes. These results suggest that the screened miRNAs and target genes may be target molecules in AF development, and may be beneficial for the early diagnosis and future treatment of AF. [ABSTRACT FROM AUTHOR]

Carotid artery plaques are a leading cause of ischemic stroke, and carotid endarterectomy (CEA) is one of the major treatment approaches for this disease. Changes in cerebral metabolism following CEA remain unclear. The present study aimed to evaluate the effect of cerebral ammonia metabolism following CEA using 13N-labeled ammonia positron emission tomography (PET) in humans. A total of 20 patients were enrolled in the present study, with a mean age of 59.5 years, comprising 16 males and four females. Of these patients, eight underwent right CEA and 12 underwent left CEA. The rate of carotid artery stenosis was between 50-69% in six of the patients, between 70-99% in 11 of the patients and was at 100% (thrombosis) in three of the patients, measured by computerised tomography digital subtraction angiography prior to CEA. 13N-labeled ammonia (137 MBq) PET scanning was performed prior and subsequent to CEA surgery for each patient. The first ammonia PET scan was performed 1 day prior to CEA, while the second PET scan was performed 1-4 weeks following CEA. Following injection of 13N-labeled ammonia, static PET was acquired for 10 min. The region of interest (ROI), covering the major cerebral hemisphere, was selected and ammonia uptake in the ROI was determined in the ipsilateral and contralateral hemispheres. No hyperperfusion syndrome was observed in the patients subsequent to CEA. No significant change in cerebral hemisphere ammonia uptake was observed between the ipsilateral and contralateral hemispheres prior to (ratio =0.98; P>0.01) or following (ratio =1.09; P>0.01) CEA. Ammonia uptake in the ipsilateral and contralateral hemispheres was significantly reduced to 23.2 and 23.5%, respectively, following CEA. Using 13N-labeled ammonia PET to evaluate cerebral ammonia metabolism following CEA in patients with severe carotid artery stenosis, the present study demonstrated that uptake of ammonia in the ipsilateral and contralateral hemispheres was significantly reduced. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the effects of dietary trans fatty acids in mice. Following the administration of a 0.5/100 g diet of trans-9 octadecenoic acid (EA), trans-11 vaccenic acid (TVA) or cis-9, trans-11 conjugated linoleic acid (CLA) for 4 weeks, the body weights and the weights of the liver, testis and mediastinal adipose tissue (MAT) of the animals gradually decreased (P<0.05). The EA group exhibited the lowest levels of magnesium and triglycerides (P<0.05). CLA increased villus length (P<0.05), while EA and TVA decreased villus length (P<0.05). The TVA group exhibited the lowest levels of low-density lipoprotein and tumor necrosis factor-α (P<0.05). Taken together, EA, TVA and CLA affected the physiological conditions of mice differently. The potential effects of three well-known fatty acids, including trans-9 octadecenoic acid (EA), trans-11 vaccenic acid (TVA) and cis-9, trans-11 conjugated linoleic acid (CLA), in animals or humans remain to be elucidated. Therefore, in the present study, 32 animals were randomly divided intofour groups and administered a 0.5/100 g diet of EA, TVA or CLA for 4 weeks. The results demonstrated that the body weights and the weights of the liver, testis and mediastinal adipose tissue (MAT) of the animals gradually decreased (P<0.05). Blood was collected individually via the external jugular veins and the EA group exhibited the lowest levels of magnesium and triglycerides (P<0.05). CLA increased villus length (P<0.05), while EA and TVA decreased villus length (P<0.05). The TVA group exhibited the lowest levels of low-density lipoprotein and tumor necrosis factor-α (P<0.05). Taken together, EA, TVA and CLA affected the physiological conditions of mice differently and these may further our understanding of the various effects of these fatty acids on animals and humans. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small non-coding RNAs that inhibit the expression of target protein-coding genes, most often at the post-transcriptional level. miRNAs are often found to be misregulated in human cancer and they can act as potent oncogenes or tumor suppressor genes. In this study, we found that a germline mutation in the miR-125a coding region is associated with human gastric cancer. This mutation reduced the expression of mature miR-125a and alleviated its inhibitory effect on erythroblastic leukemia viral oncogene homolog 2 (ERBB2) gene expression and on gastric tumor cell proliferation. Thus, the data of this study suggested that this germline mutation in pri-miR-125a likely contributes to the genetic predisposition to gastric cancer by reducing the production of miR-125a, thereby interfering with the expression of miR-125a target genes. [ABSTRACT FROM AUTHOR]

The present study aimed to examine the status and clinical significance of cluster of differentiation (CD) 19+CD24highCD38high regulatory B cells (Bregs), serum interleukin (IL)‑10, serum transforming growth factor (TGF)‑β and IL‑10 receptor (IL‑10R) expression in peripheral blood from patients with systemic lupus erythematosus (SLE). A total of 56 patients with SLE and 35 healthy individuals were recruited to the present study. The SLE disease activity index (SLEDAI) was calculated, and other laboratory parameters were measured. Peripheral blood was collected from all participants. The frequency of CD19+CD24highCD38high Bregs and IL‑10R+ expression on circulating lymphocytes was examined by flow cytometry. The serum levels of IL‑10 and TGF‑β were measured using enzyme‑linked immunosorbent assay. The associations between these measurements and SLEDAI or other laboratory parameters were analyzed by correlation analysis. The percentage of CD19+CD24highCD38high Bregs and the serum levels of IL‑10 were significantly increased, whereas the expression of IL‑10R on circulating lymphocytes was markedly reduced in patients with SLE compared with in healthy controls. The serum levels of TGF‑β1 were not markedly different between the groups. In addition, these factors were correlated with other SLE laboratory parameters, and inter‑correlations were presented with different degrees of significance. The percentage of CD19+CD24highCD38high Bregs was positively correlated with the percentage of IL‑10R+ lymphocytes, mean fluorescence intensity (MFI) of IL‑10R+ lymphocytes and serum IL‑10 levels. In addition, the percentage of IL‑10R+ lymphocytes was positively correlated with its expression level (MFI), whereas serum TGF‑β1 levels were negatively correlated with serum IL‑10 levels. The present results indicated that expansion of CD19+CD24highCD38high Bregs, upregulation of IL‑10 and deficient lymphocyte‑associated IL‑10R may serve as novel SLE biomarkers. It may be hypothesized that deficient IL‑10R expression results in compensatory enhanced IL‑10 expression, expansion of Bregs, and/or compromised Breg and IL‑10 functions, thus contributing to SLE development. Therefore, targeting the ‘Bregs/IL‑10/IL‑10R’ system may provide a novel therapeutic approach for the treatment of SLE. [ABSTRACT FROM AUTHOR]

Oxidative stress induced by cadmium (Cd) is a common phenomenon that has been observed in numerous studies. However, the underlying mechanism remains unknown. Recently, exposure of PC-12 cells to Cd has been shown to activate autophagy, which acts as a temporary survival pathway under stressful conditions by delaying the occurrence of apoptosis. The present study investigated the impact of oxidative stress on Cd-induced autophagy in PC-12 cells. The results demonstrated that Cd-induced autophagy (following treatment with Cd for 4 h), increased the levels of intracellular reactive oxygen species (ROS), decreased the mitochondrial membrane potential and resulted in apoptosis. A treatment with chloroquine (CQ; an autophagic inhibitor) sensitized the PC-12 cells to Cd, due to the increased production of ROS, which was associated with the incapacity to reduce mitochondrial and cell death. N-acetyl-L-cysteine, an antioxidant agent, decreased Cd-induced autophagy and reduced intracellular ROS levels, but enhanced CQ-induced apoptotic cell death. These findings indicate that moderate levels of ROS are essential in the regulation of Cd-induced autophagy, which subsequently enhances cell survival. Thus, the results of the present study provide an insight for future investigation of Cd-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Autophagy is an evolutionarily conserved response that can be activated in response to heavy metal. Thus, the present study investigated the effect of autophagy on neurotoxic damage caused by cadmium (Cd) in rat cerebral cortical neurons. The results indicated that the viability of cortical neurons treated with Cd was markedly decreased in a dose- and time-dependent manner. The present study provided evidence that cortical neurons treated with Cd underwent autophagy: The conversion of microtubule-associated protein 1A/1B-light chain 3 (LC3) to LC3-II, an increase in the punctate distribution of endogenous LC3-II and the presence of autophagosomes were identified. Combined treatment with Cd and chloroquine, an autophagy inhibitor, reduced the amount of autophagocytosis and cell activity, whereas rapamycin, an autophagy inducer, reduced Cd-mediated cytotoxicity. Furthermore, it was found that beclin-1 and class III phosphoinositide 3 kinase (PI3K) levels were increased, while levels of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) were decreased after Cd treatment. LY294002, a specific inhibitor of PI3K, prevented the decline in Bcl-2 production and the increase in levels of beclin-1, class III PI3K and autophagy following Cd treatment. In conclusion, the results of the present study suggested that Cd can induce cytoprotective autophagy by activating the class III PI3K/beclin-1/Bcl-2 signaling pathway, and that the autophagy pathway can serve as a sensitive biomarker for nervous system injury after exposure to Cd. [ABSTRACT FROM AUTHOR]

Cholelithiasis is a common medical condition whose incidence rate is increasing yearly, while its pathogenesis has yet to be elucidated. The present study assessed the expression of Rho-kinase (ROCK) in gallbladder smooth muscles and its effect on the contractile function of gallbladder smooth muscles during gallstone formation. Thirty male guinea pigs were randomly divided into three groups: The control group, the gallstone model group and the fasudil interference group. The fasting volume (FV) and bile capacity of the gallbladder (FB) as well as the total cholesterol (TC) and triglyceride (TG) contents of the gallbladder bile were determined. In addition, the gallbladder was dissected to identify whether any gallstones had formed. Part of the gallbladder tissue specimens were used for immunohistochemical analysis of ROCK expression in gallbladder smooth muscles. The results showed that four guinea pigs in the model group and eight in the fasudil group displayed gallstone formation, while there was no gallstone formation in the control group. The FV and FB were significantly increased in the model and fasudil groups. Similarly, the TC and TG contents of gallbladder bile were increased in these groups. The positive expression rate of ROCK in gallbladder smooth muscles in the model and fasudil groups was significantly reduced compared with that in the control group (P<0.05). The results of the present study indicated that the reduction of ROCK expression in guinea pig gallbladder smooth muscles weakened gallbladder contraction and thereby promoted gallstone formation. [ABSTRACT FROM AUTHOR]

Baicalein (BA), one of the major bioactive flavonoids isolated from Scutellariae Radix, possesses various pharmacological activities. The present study aimed to investigate the protective effects of BA on tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity, and to investigate the potential mechanisms in LO2 cells. BA was demonstrated to possess protective properties against t-BHP injury in LO2 cells, as evidenced by MTT and lactate dehydrogenase assays. BA significantly prevented t-BHP-induced depolarization of mitochondrial membrane potential (MMP), decreased the percentage of apoptotic cells caused by t-BHP, and prevented intracellular reactive oxygen species (ROS) generation in LO2 cells. Furthermore, BA slightly triggered autophagy in LO2 cells, as evidenced by the elevation of LC3-II expression, while BA combined treatment with an autophagy inhibitor (chloroquine) or activator (rapamycin) did not alter the hepatoprotective properties. In conclusion, BA may possess a hepatoprotective effect against t-BHP-induced liver cell injury, dependent on ROS removal. Therefore, BA may represent a potential drug candidate in protecting hepatotoxicity. [ABSTRACT FROM AUTHOR]

Translocations are the most frequent structural aberration in the human genome. Carriers of balanced chromosome rearrangement exhibit an increased risk of abortion and/or a chromosomally‑unbalanced child. The present study reported a clinical and cytogenetic analysis of a child who exhibited typical trisomy 4p and monosomy 20q features, including intellectual disability, delayed speech, tall stature, seizures and facial dysmorphism. The karyotype of the proband exhibited 46, XY, add(20) (q13.3). The karyotype of the mother indicated a balanced translocation karyotype: 46, XX, t(4;20) (p15.2;q13.1). The array‑based comparative genomic hybridization (aCGH) analysis identified partial trisomy of the short arm of chromosome 4 and partial monosomy of distal 20q in the proband due to maternal balanced reciprocal translocation 4;20. The analysis of genotype/phenotype correlation demonstrated that fibroblast growth factor receptor 3 and msh homeobox 1 may be the important genes for 4p duplication, and that potassium voltage‑gated channel subfamily Q member 2, myelin transcription factor 1 and cholinergic receptor nicotinic α4 subunit may be the important genes for 20q deletion. To the best of our knowledge, the present study was the first to report an unbalanced translocation involving chromosomes 4p and 20q. The present study additionally demonstrated that aCGH analysis is able to reliably detect unbalanced submicroscopic chromosomal aberrations. [ABSTRACT FROM AUTHOR]

As influencing factors of genesis and progression in several types of human tumor, microRNAs (miRs) serves roles in the regulation of tumor cell viability, migration, and apoptosis. The present research aimed to investigate the association between the function of miR‑100‑5p and renal cell carcinoma (RCC). miR‑100‑5p expression was determined in RCC tissue and paired normal tissue samples using reverse transcription‑quantitative polymerase chain reaction. To assess the effects of miR‑100‑5p on cell viability, migration and apoptosis, multiple methods were used, including scratch wound assays, MTT assays, and flow cytometry. It was demonstrated that miR‑100‑5p was significantly upregulated in RCC tissue compared with in normal adjacent tissue samples. Furthermore, the viability and migration of 786‑O and, ACHN cells tranfected with miR‑100‑5p was significantly increased compared with the negative control group. In addition, miR‑100‑5p‑transfected 786‑O and ACHN cells demonstrated significantly reduced cellular apoptotic rates compared with the negative control group. To the best of our knowledge, the present study is the first to report an association between miR‑100‑5p and RCC. The results of the current study suggest that tumor oncogene miR‑100‑5p could be used as a diagnostic biomarker for RCC. [ABSTRACT FROM AUTHOR]

The molecular mechanisms underlying protection and pathogenesis in spinal degenerative diseases remain unclear. Tumor necrosis factor-α (TNF-α) has been demonstrated to induce apoptosis of inte rvertebral disc (IVD) cells during IVD degeneration, and 17β-estradiol (17β-E2) has a protective effect against IVD cell apoptosis. However, the underlying molecular mechanism by which 17β-E2 protects nucleus pulposus (NP) cells remains to be investigated. The aim of the present study was to evaluate whether 17β-E2 modulates apoptosis of human NP cells induced by TNF-α. In addition, the concentration-response effect of 17β-E2 on human NP cells was investigated. Human NP cells were cultured in complete medium, which was replaced every three days until the culture was ~80% confluent. Cells were treated with 100 ng/ml TNF-α for 48 h, with or without pretreatment with various concentrations of 17β-E2, and ICI 182,780, for 30 min. Morphologic alterations characteristic of apoptosis were observed by inverted phase-contrast microscopy and Hoechst 33258 staining; the apoptosis rate was analyzed by flow cytometry. A Cell Counting kit-8 assay was used to assess cell proliferation. Furthermore, caspase-3 activity was determined and proteins associated with apoptosis were analyzed by western blotting. The level of apoptosis and caspase-3 activity in human NP cells increased, whereas proliferation and the expression of poly ADP-ribose polymerase decreased following TNF-α treatment. These effects of TNF-α were abolished by pretreatment with 17β-E2 in a concentration-dependent manner. The results of the present study indicated that 17β-E2 serves a critical role in the survival of degenerative human NP cells. [ABSTRACT FROM AUTHOR]

Renal fibrosis is the final common pathway of all progressive renal disease. Excessive and chronic activation of the Wnt/β‑catenin signaling pathway results in chronic kidney disease (CKD) progression. To mimic CKD, the present study used 5/6‑nephrectomized rats, and alterations in kidney histology, expression of β‑catenin and renal cell apoptosis were assessed. In addition, mesangial cells were cultured in vitro and transfected with β‑catenin siRNA to evaluate the effect of blocking Wnt/β‑catenin signaling on cell apoptosis and the expression of markers of renal fibrosis. The results demonstrated that CKD rat kidney tissues exhibited moderate renal fibrosis and significantly increased expression levels of β‑catenin and apoptosis associated proteins compared with sham‑operated rats. In vitro, silencing of β‑catenin by siRNA attenuated tumor necrosis factor‑α‑induced apoptosis and decreased mRNA expression levels of various markers of fibrosis, including fibronectin, transforming growth factor‑β, and collagen I, III and IV. In conclusion, inhibition of Wnt/β‑catenin signaling by β‑catenin silencing attenuated apoptosis and expression of fibrosis‑associated markers in renal cells. The present study suggested that the Wnt/β‑catenin signaling pathway may serve as a potential treatment strategy for renal fibrotic disorders. [ABSTRACT FROM AUTHOR]

The present study aimed to screen several differentially expressed genes (DEGs) and differentially expressed microRNAs (miRNAs) for two types of mesenchymal stem cell (MSC) differentiation. Bone morphogenetic protein 6 (BMP-6) and dexamethasone were used to induce MSCs towards osteoblastic differentiation or adipocytic differentiation. The t-test in the Bioconductor bioinformatics software tool was used to screen DEGs and differentially expressed miRNAs in the two samples. Subsequent gene ontology (GO) and pathway analyses on the DEGs were performed using the GO and Kyoto Encyclopedia of Genes and Genomes databases, respectively; potential target genes for the screened miRNAs were predicted using the TargetScan database. In addition, an interaction network between the DEGs and miRNAs was constructed. Numerous DEGs and miRNAs were screened during osteoblastic and adipocytic differentiation of MSCs. Important pathways, such as glutathione metabolism, pathogenic Escherichia coli infection and Parkinson's disease, and GO terms, including cytoskeletal protein binding and phospholipase inhibitor activity, were enriched in the screened DEGs from MSCs undergoing osteogenic differentiation and adipocytic differentiation. miRNAs, including miRNA (miR)-382 and miR-203, and DEGs, including neuronal growth regulator 1 (NEGR1), phosphatidic acid phosphatase 2B (PPAP2B), platelet-derived growth factor receptor alpha (PDGFRA), interleukin 6 signal transducer (IL6ST) and sortilin 1 (SORT1), were demonstrated to be involved in osteoblastic differentiation. In addition, the downregulated miRNAs (including miR-495, miR-376a and miR-543), the upregulated miR-106a, the upregulated DEGs, including enabled homolog (ENAH), polypeptide N-acetylgalactosaminyltransferase 1 and acyl-CoA synthetase long-chain family member 1, and the downregulated repulsive guidance molecule family member B and semaphorin SEMA7A were demonstrated to be involved in adipocytic differentiation. The results of the present study suggested that miRNAs (miR-203 and miR-382) and DEGs (NEGR1, PPAP2B, PDGFRA, IL6ST and SORT1) may serve pivotal functions in the osteoblastic differentiation of MSCs, whereas miR-495, which is also involved in osteoblast differentiation and had four targets, including NEGR1, miR-376a, miR-543 and ENAH may have crucial roles in adipocytic differentiation of MSCs. [ABSTRACT FROM AUTHOR]

Hypertrophic scars (HS) area fibroproliferative disorder of the skin, which causes aesthetic and functional impairment. However, the molecular pathogenesis of this disease remains largely unknown and currently no efficient treatment exists. MicroRNAs (miRNAs) are involved in a variety of pathophysiological processes, however the role of miRNAs in HS development remains unclear. To investigate the miRNA expression signature of HS, microarray analysis was performed and 152 miRNAs were observed to be differentially expressed in HS tissue compared with normal skin tissues. Of the miRNAs identified, miRNA-21 (miR-21) was significantly increased in HS tissues and hypertrophic scar fibroblasts (HSFBs) as determined by reverse transcription-quantitative polymerase chain reaction analysis. It was also observed that, when miR-21 in HSFBs was blocked through use of an antagomir, the phenotype of fibrotic fibroblasts in vitro was reversed, as demonstrated by growth inhibition, induction of apoptosis and suppressed expression of fibrosis-associated genes collagen type I ɑ 1 chain (COL1A1), COL1A2 and fibronectin. Furthermore, miR-21 antagomir administration significantly reduced the severity of HS formation and decreased collagen deposition in a rabbit ear HS model. The total scar area and scar elevation index were calculated and were demonstrated to be significantly decreased in the treatment group compared with control rabbits. These results indicated that the miR-21 antagomir has a therapeutic effect on HS and suggests that targeting miRNAs may be a successful and novel therapeutic strategy in the treatment of fibrotic diseases that are difficult to treat with existing methods. [ABSTRACT FROM AUTHOR]

Calcium oxalate stones account for >80% of urinary stones, however the mechanisms underlying their formation remains to be elucidated. Hyperoxaluria serves an important role in the pathophysiological process of stone formation. In the present study, differences in the miRNA expression profiles between experimental hyperoxaluric rats and normal rats were analyzed, in order to identify target genes and signaling pathways involved in the pathogenesis of hyperoxaluria. Ethylene glycol and ammonium chloride was fed to male hyperoxaluric rats (EXP) and normal age-matched male rats (CON). The oxalate concentration in the urine of each experimental rat was collected every 24 h and measured on day 14. Three rats exhibiting the highest concentrations were selected for microarray analysis. Microarray analysis was performed to evaluate differences in the expression of microRNA (miRNA) in the kidney tissues from EXP and CON groups, and miRNAs that exhibited a >2-fold or a <0.5-fold alteration in expression between these groups were screened for differential expression patterns according to the threshold P-values. Reverse transcription-quantitative polymerase chain reaction analysis was employed to confirm the microarray results. In order to predict the potential role of miRNAs in pathophysiological processes, gene ontology (GO), pathway and target prediction analyses were conducted. A total of 28 miRNAs were observed to be differentially expressed (>2-fold change) between EXP and CON groups. Among these miRNAs, 20 were upregulated and 8 were downregulated. GO and pathway analyses revealed that the insulin resistance and phosphatidylinositol-bisphosphonate 3-kinase/AKT serine threonine kinase signaling pathways were potentially associated with miRNA regulation in this setting. In conclusion, the results of the present study identified differentially expressed miRNAs in hyperoxaluric rats, and provided a novel perspective for the role of miRNAs in the formation of calcium oxalate stones. [ABSTRACT FROM AUTHOR]

The aim of the present study was to report on a family with pathologically and genetically diagnosed autosomal dominant inherited centronuclear myopathy (CNM). In addition, this study aimed to investigate the clinical, pathological and molecular genetic characteristics of the disease. This pedigree was traced back three generations, four patients underwent neurological examination, two patients underwent muscle biopsy, and eight family members were subjected to dynamin 2 (DNM2) gene mutation analysis. DNM2 mutations were detected in seven family members, of which four patients exhibited DNM2 mutation-specific clinical and pathological features. Lower extremity weakness was the predominant symptom of these patients, however, proximal and distal lower extremity involvement was inconsistent. All patients exhibited marked systematic muscle atrophy and various degrees of facial muscle involvement. The patients presented the typical pathological changes of CNM, and their muscle tissues were heavily replaced by adipose tissue, with clustered distribution of muscle fibers as another notable feature. DNM2-CNM patients of this pedigree exhibited heterogeneous clinical and pathological features, providing a basis for further molecular genetic analysis. [ABSTRACT FROM AUTHOR]

Patients with essential hypertension undergo endothelial dysfunction, particularly in the conduit arteries. Cilostazol, a type III phosphodiesterase inhibitor, serves a role in the inhibition of platelet aggregation and it is widely used in the treatment of peripheral vascular diseases. Previous studies have suggested that cilostazol suppresses endothelial dysfunction; however, it remains unknown whether cilostazol protects the endothelial function in essential hypertension. The aim of the present study was to investigate whether, and how, cilostazol suppresses angiotensin II (angII)-induced endothelial dysfunction. Human umbilical vein endothelial cells (HUVECs) and Sprague Dawley rats were exposed to angII and treated with cilostazol. Endothelial cell apoptosis and function, nitric oxide and superoxide production, phosphorylation (p) of Akt, and caspase-3 protein expression levels were investigated. AngII exposure resulted in the apoptosis of endothelial cells in vitro and in vivo. In vitro, cilostazol significantly suppressed the angII-induced apoptosis of HUVECs; however, this effect was reduced in the presence of LY294002, a phosphoinositide 3 kinase (PI3K) inhibitor. Furthermore, cilostazol suppressed the angII-induced p-Akt downregulation and cleaved caspase-3 upregulation. These effects were also alleviated by LY294002. In vivo, cilostazol suppressed the angII-induced endothelial cell apoptosis and dysfunction. Cilostazol was also demonstrated to partially reduced the angII-induced increase in superoxide production. The results of the present study suggested that cilostazol suppresses endothelial apoptosis and dysfunction by modulating the PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the role of arginase (Arg) in pulmonary arterial hypertension (PAH). In vitro, human pulmonary artery smooth muscle cells (HPASMCs) were cultured under hypoxic conditions with, or without, the Arg inhibitor, S-(2-boronoethyl)-l-cysteine (BEC), for 48 h, following which the proliferation of the HPASMCs was determined using MTT and cell counting assays. For the in vivo investigation, 30 male rats were randomly divided into the following three groups (n=10 per group): i) control group, ii) PAH group and iii) BEC group, in which the right ventricle systolic pressure (RVSP) of the rats was assessed. The levels of cyclin D1, cyclin-dependent kinase (CDK)4 and p27 were measured in vitro and in vivo. The phosphorylation levels of Akt and extracellular-related kinase (ERK) were also measured in HPASMCs. In vitro, compared with the hypoxia group, Arg inhibition reduced HPASMC proliferation and reduced the expression levels of cyclin D1, CDK4, phosphorylated (p-)Akt and p-ERK. By contrast, Arg inhibition increased the expression of p27. In vivo, compared with the control group, the expression levels of cyclin D1 and CDK4 were reduced in the PAH group, however, the expression of p27 and the RVSP increased. In the BEC group, the opposite effects were observed. Therefore, it was suggested that Arg inhibition may reduce the RVSP of PAH rats and reduce HPASMC proliferation by decreasing the expression levels of cyclin D1 and CDK4, increasing the expression of p27, and partly reducing the phosphorylation of Akt and ERK. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify the molecular events that distinguish serrated colorectal carcinoma (SCRC) from conventional colorectal carcinoma (CCRC) through differential gene expression, pathway and protein-protein interaction (PPI) network analysis. The GSE4045 and GSE8671 microarray datasets were downloaded from the Gene Expression Omnibus database. We identified the genes that are differentially expressed between SCRC and normal colon tissues, CCRC and healthy tissues, and between SCRC and CCRC using Student's t-tests and Benjamini-Hochberg (BH) multiple testing corrections. The differentially expressed genes (DEGs) were then mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and their enrichment for specific pathways was investigated using the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool with a significance threshold of 0.1. Analysis of the potential interactions between the protein products of 220 DEGs (between CCRC and SCRC) was performed by constructing a PPI network using data from the high performance RDF database (P<0.1). The interaction between pathways was also analyzed in CCRC based on the PPI network. Our study identified thousands of genes differentially expressed in SCRC and CCRC compared to healthy tissues. The DEGs in SCRC and CCRC were enriched in cell cycle, DNA replication, and base excision repair pathways. The proteasome pathway was significantly enriched in SCRC but not in CCRC after BH adjustment. The PPI network showed that tumour necrosis factor receptor-associated factor 6 (TRAF6) and atrophin 1 (ATN1) were the most central genes in the network, with respective degrees of node predicted at 90 and 88. In conclusion, the preoteasome pathway was shown to be specifically enriched in SCRC. Furthermore, TRAF6 and ATN1 may be promising biomarkers for the distinction between serrated and conventional CRC. [ABSTRACT FROM AUTHOR]

The present study aimed to examine potential biomarkers for the diagnosis of endometriosis. A plasma-based proteomic approach, including 2-dimentional electrophoresis and mass spectrometry, was used. Samples were obtained from patients with (n=15) and without (n=15) endometriosis, or from mice with surgically induced endometriosis. Seven spots corresponding to six differentially expressed proteins were identified in the human plasma samples. However, only haptoglobin (Hp) was identified to be significantly decreased in the plasma levels of patients with endometriosis (P<0.05) and in mice with surgically induced endometriosis (P<0.05). The results demonstrated that Hp was downregulated in females with endometriosis, and it therefore, may be a useful diagnostic tool as a biomarker of endometriosis. [ABSTRACT FROM AUTHOR]

ArfGAP with SH3 domain, ankyrin repeat and PH domain 3 (ASAP3), previously known as ACAP4, DDEFL1 and UPLC1, is considered to be an important regulator in cancer cell migration/invasion and actin based cytoskeletal remodeling. However, the underlying mechanisms through which ASAP3 mediates these processes are not well elucidated. This study reported that in certain types of cancer cells, loss of ASAP3 suppressed cell migration/invasion, in part by destabilizing γ-actin-1 (ACTG1), a cytoskeletal protein considered to be an integral component of the cell migratory machinery, essential for the rearrangement of the dynamic cytoskeletal networks and important in diseases, such as brain malformation, hearing loss and cancer development. The data, for the first time, link ASAP3 with ACTG1 in the regulation of cytoskeletal maintenance and cell motility. [ABSTRACT FROM AUTHOR]

A correction to the article "Clinical, pathological and genetic characteristics of autosomal dominant inherited dynamin 2 centronuclear myopathy" in the 2016 issue is presented.