Exploring the relationship between malnutrition and the systemic immune-inflammation index in older inpatients: a study based on comprehensive geriatric assessment.

BACKGROUND: Malnutrition is a prevalent and major challenge among senior citizens, possibly due to the continual low-grade inflammatory state of the body. A novel inflammatory parameter, the systemic immune-inflammation index (SII), is highly valuable in evaluating and predicting the prognosis of a wide range of diseases. This study aims to explore the significance of the SII in assessing malnutrition in older inpatients. METHODS: This retrospective study included 500 senior hospitalized patients who met the inclusion and exclusion criteria from the Comprehensive Geriatric Assessment database of the First Hospital of Jilin University. The Mini-Nutritional Assessment (MNA) questionnaire was used to evaluate the nutritional status of patients. The SII was calculated using complete blood counts, and we performed natural logarithm transformation of the SII [ln(SII)]. Multivariable logistic regression analysis was used to identify the association between ln(SII) and malnutrition. To ensure the stability of the findings, a sensitivity analysis was conducted. RESULTS: The 500 patients had a mean age of 77.29 ± 9.85 years, and 68.6% were male. In accordance with the MNA, 30.4% of the patients were malnourished or at risk of malnutrition, and patients in this group had considerably greater levels of ln(SII) than patients with adequate nutrition (P < 0.001). The optimum ln(SII) cutoff value for patients with malnutrition or at risk of malnutrition was 6.46 (SII = 635.87) with 46.7% sensitivity and 80.2% specificity [95% CI: 0.613-0.721, AUC: 0.667, P < 0.001]. Multivariable logistic regression demonstrated that ln(SII) was an independent risk factor for the risk of malnutrition or malnutrition in older individuals (OR 3.984, 95% CI: 2.426-6.543, P < 0.001). Other metrics from the geriatric comprehensive assessment, including body mass index, calf circumference, fat ratio, activities of daily living and instrumental activities of daily living, and geriatric depression scale scores, were also independently correlated with nutritional status. CONCLUSIONS: According to our research, a high SII is an independent predictor of older inpatient malnutrition, and the SII aids in screening for malnutrition and may be a potential target for intervention. Comprehensive geriatric assessment parameters such as BMI, calf circumference, fat ratio, activities of daily living and depression were also linked to malnutrition.

Correlation analysis between body composition, serological indices and the risk of falls, and the receiver operating characteristic curve of different indexes for the risk of falls in older individuals.

Objective: This study assessed the risk factors for falls and evaluated the correlation between body composition, serological indices, and the risk of falls in older individuals. Method: This cross-sectional study included 387 individuals ≥60 years of age in the cadre ward of the First Hospital of Jilin University. The information used in this study was obtained from the comprehensive geriatric assessment database of the cadre ward. The body composition of the individuals was measured by bioelectrical impedance analysis using an InBody S10 device. We assessed fall risk using the fall risk assessment tool. Individuals with ≤2 points were placed in the low-risk group, those with 3-9 points were placed in the medium-risk group, and those with ≥10 points were placed in the high-risk group. Results: Differences in age, educational background, height, cognitive impairment, malnutrition, ability of daily living, depression, diastolic blood pressure, heart rate, intracellular water, total body moisture, water ratio, limb moisture (right and left, upper and lower), trunk moisture, fat-free weight, arm girth, body cell mass, skeletal muscle mass, limb muscle (right and left, upper and lower), appendicular skeletal muscle mass index (ASMI), sarcopenia, hemoglobin level, hematocrit level, aspartate aminotransferase level, albumin level, anemia, and hypoproteinemia were observed among the three groups (p < 0.001, p = 0.002, p = 0.006, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.008, p = 0.010). Ordinal logistic regression analysis showed that the probability of the fall risk increasing by one level was 1.902 times higher for each unit of decrease in educational background, respectively. In addition, the probability of the fall risk increasing by one level was 2.971, 3.732, 3.804, 1.690 and 2.155 times higher for each additional unit of age, cognitive impairment, lower limb edema, decreased skeletal muscle mass, and sarcopenia, respectively. Conclusion: Our findings suggest that educational background, age, cognitive impairment, lower limb edema, decreased skeletal muscle mass, and sarcopenia were associated with falls in older individuals. Body composition and serological indices can assist in the early identification of falls in the older people.

The prediction model of the short-term outcome in elderly heart failure patients.

This study was designed to investigate the effect of the comprehensive geriatric assessment on the short-term prognosis of the elderly heart failure patients (EHFP), analyze the relevant risk factors, and construct an effective risk prediction model. According to the selection and exclusion criteria, 617 patients were filtered from 800 patients from the cadre ward database of the first Hospital of Jilin University. The EHFP were randomly divided into the model group (432 cases) and the validation group (185 cases). A retrospective study on the general clinical data of patients in the model group was conducted to analyze the risk factors associated with the short-term outcomes of EHFP. Based on the risk factors, the risk prediction model was established and validated through the validation group. In the model group, the following independent risk factors were identified for the short-term outcomes in EHFP in the light of univariate logistic and cox regression analysis: female (ß = 0.989, OR = 1.277, 95% CI: 1.090-1.847, P = 0.024), age (65-75 years, ß = 0.654, OR = 2.320, 95% CI: 1.135-3.136, P = 0.012; 75-85 years, ß = 1.123, OR = 3.159, 95% CI: 1.532-5.189, P = 0.001; age > 85 years old, ß = 1.513, OR = 4.895, 95% CI: 1.866-979, P = 0.001), frailty (ß = 1.015, OR = 2.761, 95% CI: 1.097-6.945, P = 0.031), malnutrition (ß = 1.271, OR = 3.560, 95% CI: 1.122-11.325, P = 0.002), and EF≦40% (ß = 1.250, OR = 3.498, 95% CI: 1.898-6.447, P = 0.001). The simple risk prediction score was set up in line with the five risk factors, including range (1-7), the area under ROC curve (0.771, 95% CI: 0.723-0.819), and H-L test (P = 0.393), so patients were divided into the low-risk group (1-3) and the high-risk group (4-8). As a result, the number of EHFP in the high-risk group was significantly much more than that in the low-risk group (70.1% versus 29.9%, P < 0.001). Besides, the area under ROC curve (0.758, 95% CI: 0.682-0.835) and H-L test (P = 0.669) of the validation group indicated that this model could be a promising prediction model for the short-term outcomes of EHFP. Female, age, frailty, malnutrition, and EF ≦ 40% are independent risk factors for short-term outcomes of EHFP. The risk prediction model based on the five risk factors provided compelling clinic predictive value for the short-term prognosis of EHFP.

The role of comprehensive geriatric assessment in the identification of different nutritional status in geriatric patients: a real-world, cross-sectional study.

Background: Malnutrition is an often unrecognized problem, but it is common in older patients and leads to adverse outcomes. Aims: The purpose of this study is to analyze the prevalence of the risk of undernutrition in elderly patients and the correlation between CGA and nutritional status, and to determine the nutritional status of elderly patients. Methods: This is a real-world cross-sectional study of continuously enrolled elderly patients aged 65 years or older with a complete CGA database. CGA inventory was prepared by compiling and screening general information, body composition and blood biochemical results. MNA was also conducted for each elderly patient to screen for malnutrition. A multivariable logistic regression analysis was used to determine the association between the CGA and nutritional assessment. Result: The average age of the 211 selected elderly patients (160 men and 51 women) was 79.60 ± 9.24 years, and their ages ranged from 65 to 96 years. After controlling for confounders, patients with a history of PUD (OR = 2.353, p = 0.044), increased ADLs & IADLs scores (OR = 1.051, p = 0.042) or GDS scores (OR = 6.078, p < 0.001) may increase the incidence of the risk of undernutrition respectively, while an increase in BMI (OR = 0.858, p = 0.032) may lower the incidence of malnutrition risk. In addition, increased ADLs & IADLs scores (OR = 1.096, p = 0.002) or GDS scores (OR = 11.228, p < 0.001) may increase the incidence of undernutrition. However, increased MMSE (OR = 0.705, p < 0.001), BMI (OR = 0.762, p = 0.034), UAC (OR = 0.765, p = 0.048) and CC (OR = 0.721, p = 0.003) may decrease the incidence of undernutrition, respectively. Conclusion: The study found that the prevalence of risk of undernutrition in elderly patients was the highest. Risk of undernutrition was independently associated with peptic ulcer disease, ADLs & IADLs, GDS and BMI. However, we found that when the nutritional status reached the level of undernutrition, it was related to more factors, including ADLs & IADLs, MMSE, GDS, BMI, UAC and CC. Determining the level of malnutrition through CGA may help to prevent and intervene malnutrition as early as possible.

The relationship between Comprehensive Geriatric Assessment parameters and depression in elderly patients.

Background: Depression is common and serious among elderly patients. The treatment of elderly depression is often delayed owing to insufficient diagnosis, which eventually leads to adverse consequences. Aims: To explore the association between the parameters of the Comprehensive Geriatric Assessment and depression in elderly patients. Methods: A cross-sectional study of 211 outpatients and inpatients aged ≥ 65 years from the Comprehensive Geriatric Assessment database was conducted. A Comprehensive Geriatric Assessment inventory was prepared by compiling and screening general characteristics, chronic diseases (cardiovascular disease, diabetes, and peptic ulcer disease), nutritional status, daily living ability, anthropometric measurements (body mass index (BMI), upper arm circumference, and calf circumference), and blood biochemical indicators (hemoglobin, albumin, prealbumin, triglycerides, and low-density lipoprotein cholesterol). The Geriatric Depression Scale was also conducted for each elderly patient to screen for depression. A multivariable logistic regression analysis was used to determine the association between the parameters of the Comprehensive Geriatric Assessment and geriatric depression. Results: There were 63 patients in the depression group with a median age of 84.00 years, and 148 patients in the non-depression group with a median age of 78.50 years. After controlling for confounders, the risk of depression in elderly patients with cardiovascular diseases was 6.011 times higher than that in those without cardiovascular diseases (p < 0.001); and the risk of depression in elderly patients with peptic ulcer diseases was 4.352 times higher than that in those without peptic ulcer diseases (p < 0.001); the risk of depression in elderly patients decreased by 22.6% for each 1-point increase in the Mini Nutritional Assessment (p < 0.001). The risk of depression in elderly patients decreased by 19.9% for each 1-point increase in calf circumference (p = 0.002), and by 13.0% for each 1-point increase in albumin (p = 0.014). Conclusion: Our findings suggest that Comprehensive Geriatric Assessment parameters, such as cardiovascular disease, peptic ulcer disease, Mini Nutritional Assessment score, calf circumference, and albumin, were associated with depression. The Comprehensive Geriatric Assessment can assist in the early identification of depression in the elderly population.

The cGAS-STING pathway: more than fighting against viruses and cancer.

In the classic Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway, downstream signals can control the production of type I interferon and nuclear factor kappa-light-chain-enhancer of activated B cells to promote the activation of pro-inflammatory molecules, which are mainly induced during antiviral responses. However, with progress in this area of research, studies focused on autoimmune diseases and chronic inflammatory conditions that may be relevant to cGAS-STING pathways have been conducted. This review mainly highlights the functions of the cGAS-STING pathway in chronic inflammatory diseases. Importantly, the cGAS-STING pathway has a major impact on lipid metabolism. Different research groups have confirmed that the cGAS-STING pathway plays an important role in the chronic inflammatory status in various organs. However, this pathway has not been studied in depth in diabetes and diabetes-related complications. Current research on the cGAS-STING pathway has shown that the targeted therapy of diseases that may be caused by inflammation via the cGAS-STING pathway has promising outcomes.

The correlation between nutrition and frailty and the receiver operating characteristic curve of different nutritional indexes for frailty.

BACKGROUND: Frailty is a kind of geriatric syndrome, which is very common in the elderly. Patients with malnutrition are at higher risk of frailty. This study explored the correlation between nutrition and frailty and compared the receiver operating characteristic curve of different nutritional indexes for frailty. METHODS: This cross-sectional study included 179 inpatients aged ≥65 years old. Frailty was measured using Fried Frailty Phenotype, handgrip strength was measured using JAMAR@Plus and the 4.57 m usual gait speed was measured using a stopwatch. Comprehensive nutritional assessment refers to the application of Mini Nutritional Assessment (MNA) to assess the nutritional status of patients. RESULTS: Compared with the non-frailty group, the upper arm circumference, calf circumference, hemoglobin, albumin, prealbumin, cholesterol and low density lipoprotein in the frailty group were lower (P < 0.05). Comprehensive nutritional assessment, whether as a categorical variable or a continuous variable, was significantly correlated with frailty (P < 0.05). Model1 showed that the risk of frailty in malnourished patients was 3.381 times higher than that in well nourished patients (P = 0.036). Model2 showed that the risk of frailty decreased by 13.8% for every 1 point increase in MNA score (P = 0.009). The area under the curves of albumin, prealbumin and hemoglobin was larger (AUC > 0.65), AUC was 0.718, 0.693 and 0.743, respectively. CONCLUSIONS: Our results suggest that malnutrition is closely related to frailty. As for single nutritional indexes, albumin, prealbumin and hemoglobin were found to be associated with frailty. Further cohort studies are needed to verify their ability to screen for frailty.

Zinc as a countermeasure for cadmium toxicity.

Cadmium (Cd) is an important environmental pollutant and long-term Cd exposure is closely related to autoimmune diseases, cancer, cardiovascular diseases (CVD), and hepatic dysfunction. Zinc (Zn) is an essential metal that plays key roles in protein structure, catalysis, and regulation of their function. Numerous studies have shown that Zn can reduce Cd toxicity; however, the underlying mechanisms have not been extensively explored. Preclinical studies have revealed direct competition for sarcolemmal uptake between these two metals. Multiple sarcolemmal transporters participate in Cd uptake, including Zn transporters, calcium channels, and DMT1 (divalent metal transporter 1). Zn also induces several protective mechanisms, including MT (metallothionein) induction and favorable redox homeostasis. This review summarizes current knowledge related to the role of Zn and metal transporters in reducing Cd toxicity and discusses potential future directions of related research.

CD47 Enhances Cell Viability and Migration Ability but Inhibits Apoptosis in Endometrial Carcinoma Cells via the PI3K/Akt/mTOR Signaling Pathway.

Purposes: To measure expression levels of CD47 during endometrial carcinoma development, and to determine specific modulatory effects. Methods: CD47 expression levels in endometrial carcinoma tissues and adjacent tissues were analyzed using qRT-PCR. CD47-overexpressed or downregulated cell models were established using CD47 plasmid or CD47 shRNA. The effects of CD47 on HEC-1A and Ishikawa cell growth were evaluated using CCK-8 assays. Migration ability of transfected HEC-1A and Ishikawa cells were examined using wound healing assays. Flow cytometry was used to measure the effects of CD47 on apoptosis and the cell cycle in HEC-1A and Ishikawa cells. Western blot was used to analyze the correlation between CD47 expression level and PI3K/Akt/mTOR signaling pathway. Results: Highly expressed CD47 was observed in endometrial carcinoma tissues, with higher levels in more advanced tissues than in early tissues. Upregulation of CD47 enhanced cell viability and migration ability in HEC-1A and Ishikawa cells, while silencing CD47 caused the opposite results. CD47 overexpression suppressed apoptosis and inhibited cell cycle arrest in HEC-1A and Ishikawa cells. CD47 upregulation contributes to the activation of PI3K/Akt/mTOR signaling pathway in endometrial carcinoma cells. Conclusion: CD47 exerts oncogenic functions in endometrial carcinoma by activating PI3K/Akt/mTOR signaling, suggesting it may be a novel immunotherapeutic target for therapeutic interventions.

Rg1 protects H9C2 cells from high glucose-/palmitate-induced injury via activation of AKT/GSK-3ß/Nrf2 pathway.

Our previous studies have assessed ginsenoside Rg1 (Rg1)-mediated protection in a type 1 diabetes rat model. To uncover the mechanism through which Rg1 protects against cardiac injury induced by diabetes, we mimicked diabetic conditions by culturing H9C2 cells in high glucose/palmitate. Rg1 had no toxic effect, and it alleviated the high glucose/palmitate damage in a dose-dependent manner, as indicated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and lactate dehydrogenase release to the culture medium. Rg1 prevented high glucose/palmitate-induced cell apoptosis, assessed using cleaved caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labelling staining. Rg1 also reduced high glucose-/palmitate-induced reactive oxygen species formation and increased intracellular antioxidant enzyme activity. We found that Rg1 activates protein kinase B (AKT)/glycogen synthase kinase-3 (GSK-3ß) pathway and antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, indicated by increased phosphorylation of AKT and GSK-3ß, and nuclear translocation of Nrf2. We used phosphatidylinositol-3-kinase inhibitor Ly294002 to block the activation of the AKT/GSK-3ß pathway and found that it partially reversed the protection by Rg1 and decreased Nrf2 pathway activation. The results suggest that Rg1 exerts a protective effect against high glucose and palmitate damage that is partially AKT/GSK-3ß/Nrf2-mediated. Further studies are required to validate these findings using primary cardiomyocytes and animal models of diabetes.

Glatiramer acetate protects against oxygen-glucose deprivation/reperfusion-induced injury by inhibiting Egr-1 in H9c2 cells.

Myocardial infarction (MI) or heart attack is a deadly event with high prevalence. In the present study, we investigated the effects of the polypeptide copolymer glatiramer acetate (GA) in H9c2 rat cardiomyocytes exposed to oxygen-glucose deprivation/reperfusion injury. Immediately following MI, an acute inflammatory response is triggered that causes activation of various proinflammatory cytokines, infiltration of immune cells, and neovascularization. This response is largely mediated by some genes such as TNF-α, IL-6, ICAM-1, and VEGF. Additionally, the rapid influx of oxidants, such as reactive oxygen species (ROS), leads to a harmful state of oxidative stress. Here, we found that GA could reduce OGD/R-induced inflammation and oxidative stress by inhibiting the expression of TNF-α, IL-6, ICAM-1, and VEGF, and suppressing the production of ROS via reduced NADPH oxidase 1 (NOX1) expression. To elucidate the pathways involved in these promising results, we took a close look at the impact of the endothelial growth response-1 (Egr-1), a transcriptional factor recognized as a mediator of MI-related inflammation and cellular injury. Using siRNA for Egr-1, we found that GA could reduce the expression of ICAM-1 and VEGF by inhibiting Egr-1 expression. Together, our findings indicate a novel therapeutic potential of GA in the treatment of MI.

Zinc protects against cadmium-induced toxicity in neonatal murine engineered cardiac tissues via metallothionein-dependent and independent mechanisms.

Cadmium (Cd) is a nonessential heavy metal and a prevalent environmental toxin that has been shown to induce significant cardiomyocyte apoptosis in neonatal murine engineered cardiac tissues (ECTs). In contrast, zinc (Zn) is a potent metallothionein (MT) inducer, which plays an important role in protection against Cd toxicity. In this study, we investigated the protective effects of Zn against Cd toxicity in ECTs and explore the underlying mechanisms. ECTs were constructed from neonatal ventricular cells of wild-type (WT) mice and mice with global MT gene deletion (MT-KO). In WT-ECTs, Cd (5-20 µM) caused a dose-dependent toxicity that was detected within 8 h evidenced by suppressed beating, apoptosis, and LDH release; Zn (50-200 µM) dose-dependently induced MT expression in ECTs without causing ECT toxicity; co-treatment of ECT with Zn (50 µM) prevented Cd-induced toxicity. In MT-KO ECTs, Cd toxicity was enhanced; but unexpectedly, cotreatment with Zn provided partial protection against Cd toxicity. Furthermore, Cd, but not Zn, significantly activated Nrf2 and its downstream targets, including HO-1; inhibition of HO-1 by a specific HO-1 inhibitor, ZnPP (10 µM), significantly increased Cd-induced toxicity, but did not inhibit Zn protection against Cd injury, suggesting that Nrf2-mediated HO-1 activation was not required for Zn protective effect. Finally, the ability of Zn to reduce Cd uptake provided an additional MT-independent mechanism for reducing Cd toxicity. Thus, Zn exerts protective effects against Cd toxicity for murine ECTs that are partially MT-mediated. Further studies are required to translate these findings towards clinical trials.

Neonatal murine engineered cardiac tissue toxicology model: Impact of dexrazoxane on doxorubicin induced injury.

Doxorubicin (DOX) induced cardiotoxicity is a life-threatening side effect of chemotherapy and decreased cardiac function can present years after treatment. Despite the investigation of a broad range of pharmacologic interventions, to date the only drug shown to reduce DOX-related cardiotoxicity in preclinical studies and limited clinical trials is the iron chelating agent, dexrazoxane (DRZ), although the mechanisms responsible for DRZ mediated protection from DOX related cardiotoxicity remain unclear. Engineered cardiac tissues (ECTs) can be used for tissue repair strategies and as in vitro surrogate models to test cardiac toxicities and preventative countermeasures. Neonatal murine ECTs display cardiotoxicity in response to the environmental toxin, cadmium, and reduced cadmium toxicity with Zinc co-treatment, in part via the induction of the anti-oxidant Metallothionein (MT). We adapted our in vitro ECT model to determine the feasibility of using the ECT approach to investigate DOX-related cardiac injury and DRZ prevention. We found: (1) DOX induced dose and time dependent cell death in ECTs; (2) Zinc did not show protection from DOX cardiotoxicity; (3) MT overexpression induced by Zinc, low dose Cd pretreatment, or MT-overexpression (MT-TG) did not reduce ECT DOX cardiotoxicity; (4) DRZ reduced ECT DOX induced cell death; and (5) The mechanism of DRZ ECT protection from DOX cardiotoxicity was topoisomerase 2B (TOP2B) inhibition rather than reduced reactive oxygen species. Our data support the feasibility of ECTs as an in vitro platform technology for the investigation of drug induced cardiotoxicities including the role of TOP2B in DOX toxicity and DRZ mediated DOX toxicity prevention.

AMPK: a balancer of the renin-angiotensin system.

The renin-angiotensin system (RAS) is undisputedly well-studied as one of the oldest and most critical regulators for arterial blood pressure, fluid volume, as well as renal function. In recent studies, RAS has also been implicated in the development of obesity, diabetes, hyperlipidemia, and other diseases, and also involved in the regulation of several signaling pathways such as proliferation, apoptosis and autophagy, and insulin resistance. AMP-activated protein kinase (AMPK), an essential cellular energy sensor, has also been discovered to be involved in these diseases and cellular pathways. This would imply a connection between the RAS and AMPK. Therefore, this review serves to draw attention to the cross-talk between RAS and AMPK, then summering the most recent literature which highlights AMPK as a point of balance between physiological and pathological functions of the RAS.

RETRACTED: Astragaloside IV protects cardiomyocytes from hypoxia-induced injury by down-regulation of lncRNA GAS5.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Concerns were raised about the background pattern of the Western Blots from Figures 1B and 1E. Given the comments of Dr Elisabeth Bik regarding this article "This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels", the journal requested the authors to provide the raw data. However, the authors were not able to provide raw data of sufficient quality and detail for the journal to independently audit the provenance and validity of the data, and therefore the Editor-in-Chief decided to retract the article.

Silence of LncRNA GAS5 Protects Cardiomyocytes H9c2 against Hypoxic Injury via Sponging miR-142-5p.

The regulatory role of long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) in both cancerous and noncancerous cells have been widely reported. This study aimed to evaluate the role of lncRNA GAS5 in heart failure caused by myocardial infarction. We reported that silence of lncRNA GAS5 attenuated hypoxia-triggered cell death, as cell viability was increased and apoptosis rate was decreased. This phenomenon was coupled with the down-regulated expression of p53, Bax and cleaved caspase-3, as well as the up-regulated expression of CyclinD1, CDK4 and Bcl-2. At the meantime, the expression of four heart failure-related miRNAs was altered when lncRNA GAS5 was silenced (miR-21 and miR-142-5p were up-regulated; miR-30b and miR-93 were down-regulated). RNA immunoprecipitation assay results showed that lncRNA GAS5 worked as a molecular sponge for miR-142-5p. More interestingly, the protective actions of lncRNA GAS5 silence on hypoxia-stimulated cells were attenuated by miR-142-5p suppression. Besides, TP53INP1 was a target gene for miR-142-5p. Silence of lncRNA GAS5 promoted the activation of PI3K/AKT and MEK/ERK signaling pathways in a miR-142-5p-dependent manner. Collectively, this study demonstrated that silence of lncRNA GAS5 protected H9c2 cells against hypoxia-induced injury possibly via sponging miR-142-5p, functionally releasing TP53INP1 mRNA transcripts that are normally targeted by miR-142-5p.

Functional analysis of gene expression profiling-based prediction in bladder cancer.

The present study aimed to analyze the modification of gene expression in bladder cancer (BC) by identifying significant differentially expressed genes (DEGs) and functionally assess them using bioinformatics analysis. To achieve this, two microarray datasets, GSE24152 (which included 10 fresh tumor tissue samples from urothelial bladder carcinoma patients and 7 benign mucosa samples from the bladder), and GSE42089 (which included 10 tissues samples from urothelial cell carcinoma patients and 8 tissues samples from the normal bladder), were downloaded from the Gene Expression Omnibus database for further analysis. Differentially expressed genes (DEGs) were screened between benign the mucosa and control groups in GSE24152 and GSE42089 datasets. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis were performed on overlapping DEGs identified in GSE24152 and GSE42089. Protein-protein interaction (PPI) networks and sub-networks were then constructed to identify key genes and main pathways. GO terms analysis was also performed for the selected clusters. In total, 1,325 DEGs in GSE24152 and 647 DEGs in GSE42089 were screened, in which 619 common DEGs were identified. The DEGs were mainly enriched in pathways and GO terms associated with mitotic and chromosome assembly, including nucleosome assembly, spindle checkpoint and DNA replication. In the interaction network, progesterone receptor (PGR), MAF bZIP transcription factor G (MAFG), cell division cycle 6 (CDC6) and members of the minichromosome maintenance family (MCMs) were identified as key genes. Histones were also considered to be significant factors in BC. Nucleosome assembly and sequence-specific DNA binding were the most significant clustered GO terms. In conclusion, the DEGs, including PGR, MAFG, CDC6 and MCMs, and those encoding the core histone family were closely associated with the development of BC via pathways associated with mitotic and chromosome assembly.

A review of DNA methylation in depression.

As one of the most common psychiatric disorders, depression has been a major public health problem. Growing evidence suggests that epigenetic modification is essential in biological processes of depression. Recently, DNA methylation has been regarded as a potential link between environment and depression. In this review, we reviewed current studies of the association between DNA methylation and depression. The association between DNA methylation of seven genes, including BDNF, SLC6A4, NR3C1, 5-HTR (1A, 2A, and 3A), FKBP5, MAO-A and OXTR, and depression were reviewed in this study. Most studies showed BDNF and NR3C1 gene methylation levels were correlated with depression while the connection of SLC6A4 and depression was conflicting. Although evidence provided insights to epigenetic processes in depression, the findings were inconsistent. Therefore, longitudinal studies in animal models and in patients with depression are needed to further investigate the diagnostic predictive value of DNA methylation reliably.