Association between single-nucleotide polymorphism of cytokines genes and chronic obstructive pulmonary disease: A systematic review and meta-analysis.

Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease with high morbidity and mortality rates worldwide. Cytokines, which are the main regulators of immune responses, play crucial roles in inflammatory diseases such as COPD. Moreover, certain genetic variations can alter cytokine expression, and changes in cytokine level or function can affect disease susceptibility. Therefore, investigating the association between genetic variations and disease progression can be useful for prevention and treatment. Several studies have explored the association between common genetic variations in cytokine genes and COPD susceptibility. In this study, we summarized the reported studies and, where possible, conducted a systematic review and meta-analysis to evaluate the genetic association between various cytokines and COPD pathogenesis. We extracted relevant articles from PubMed and Google Scholar databases using a standard systematic search strategy. We included a total of 183 studies from 78 separate articles that evaluated 50 polymorphisms in 12 cytokine genes in this study. Our analysis showed that among all reported cytokine polymorphisms (including TNF-α, TGF-ß, IL1, IL1RN, IL4, IL4R, IL6, IL10, IL12, IL13, IL17, IL18, IL27, and IL33), only four variants, including TNF-α-rs1800629, TGF-ß1-rs6957, IL13-rs1800925, and IL6-rs1800796, were associated with the risk of COPD development. This updated meta-analysis strongly supports the association of TNF-α-rs1800629, TGF-ß1-rs6957, IL13-rs1800925, and IL6-rs1800796 variants with a high risk of COPD.

cAMP-PDE signaling in COPD: Review of cellular, molecular and clinical features.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death among non-contagious diseases in the world. PDE inhibitors are among current medicines prescribed for COPD treatment of which, PDE-4 family is the predominant PDE isoform involved in hydrolyzing cyclic adenosine monophosphate (cAMP) that regulates the inflammatory responses in neutrophils, lymphocytes, macrophages and epithelial cells The aim of this study is to investigate the cellular and molecular mechanisms of cAMP-PDE signaling, as an important pathway in the treatment management of patients with COPD. In this review, a comprehensive literature review was performed about the effect of PDEs in COPD. Generally, PDEs are overexpressed in COPD patients, resulting in cAMP inactivation and decreased cAMP hydrolysis from AMP. At normal amounts, cAMP is one of the essential agents in regulating metabolism and suppressing inflammatory responses. Low amount of cAMP lead to activation of downstream inflammatory signaling pathways. PDE4 and PDE7 mRNA transcript levels were not altered in polymorphonuclear leukocytes and CD8 lymphocytes originating from the peripheral venous blood of stable COPD subjects compared to healthy controls. Therefore, cAMP-PDE signaling pathway is one of the most important signaling pathways involved in COPD. By examining the effects of different drugs in this signaling pathway critical steps can be taken in the treatment of this disease.

Causal Path of COPD Progression-Associated Genes in Different Biological Samples.

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease with pulmonary and extra-pulmonary complications. Due to the disease's systemic nature, many investigations investigated the genetic alterations in various biological samples. We aimed to infer causal genes in COPD's pathogenesis in different biological samples using elastic-net logistic regression and the Structural Equation Model. Samples of small airway epithelial cells, bronchoalveolar lavage macrophages, lung tissue biopsy, sputum, and blood samples were selected (135, 70, 235, 143, and 226 samples, respectively). Elastic-net Logistic Regression analysis was implemented to identify the most important genes involved in COPD progression. Thirty-three candidate genes were identified as essential factors in the pathogenesis of COPD and regulation of lung function. Recognized candidate genes in small airway epithelial (SAE) cells have the highest area under the ROC curve (AUC = 97%, SD = 3.9%). Our analysis indicates that macrophages and epithelial cells are more influential in COPD progression at the transcriptome level.

Antiviral Activity of Medicinal Plants against Human Coronavirus: a systematic scoping review of and experimentations.

OBJECTIVE: To investigate the and studies of natural compounds and medicinal plants with anti-coronavirus activity. METHODS: A systematic review was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Animal Research: Reporting of experiments guidelines to find data for medicinal plants and natural products effective against human coronaviruses in or studies. Studies published up to September 6, 2020 were included. Studies ( or ) reporting the effect of medicinal plants and natural products or their derivatives on human coronavirus were included RESULTS: Promising anti-coronavirus effects are seen with different herbal compounds like some diterpenoids, sesquiterpenoids, and three compounds in tea with 3CLpro inhibiting effect of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV); Hirsutenone, Six cinnamic amides and bavachinin are PLpro inhibitors and Tanshinones are active on both 3CLpro and PLpro. Some flavonoid compounds of Citrus fruits act on Immun-oregulation and target angiotensin-converting enzyme 2 which is used by SARS-COV for entry. Virus helicase is possibly inhibited by two compounds myricetin and scutellarein. CONCLUSION: This review shows that complementary medicine have the potential for new drug discovery against coronavirus. Further research is needed before definitive conclusions can be made concerning the safety and efficacy of the use of these medicinal plants.

Atopic dermatitis: molecular, cellular, and clinical aspects.

Atopic dermatitis (AD) is a complicated, inflammatory skin disease, which numerous genetic and environmental factors play roles in its development. AD is categorized into different phenotypes and stages, although they are mostly similar in their pathophysiological aspects. Immune response alterations and structural distortions of the skin-barrier layer are evident in AD patients. Genetic makeup, lifestyle, and environment are also significantly involved in contextual factors. Genes involved in AD-susceptibility, including filaggrin and natural moisturizing, cause considerable structural modifications in the skin's lipid bilayer and cornified envelope. Additionally, the skin's decreased integrity and altered structure are accompanied by biochemical changes in the normal skin microflora's dysbiosis. The dynamic immunological responses, genetic susceptibilities, and structural modifications associated with AD's pathophysiology will be extensively discussed in this review, each according to the latest achievements and findings.

Re-wiring and gene expression changes of AC025034.1 and ATP2B1 play complex roles in early-to-late breast cancer progression.

BACKGROUND: Elucidating the dynamic topological changes across different stages of breast cancer, called stage re-wiring, could lead to identifying key latent regulatory signatures involved in cancer progression. Such dynamic regulators and their functions are mostly unknown. Here, we reconstructed differential co-expression networks for four stages of breast cancer to assess the dynamic patterns of cancer progression. A new computational approach was applied to identify stage-specific subnetworks for each stage. Next, prognostic traits of genes and the efficiency of stage-related groups were evaluated and validated, using the Log-Rank test, SVM classifier, and sample clustering. Furthermore, by conducting the stepwise VIF-feature selection method, a Cox-PH model was developed to predict patients' risk. Finally, the re-wiring network for prognostic signatures was reconstructed and assessed across stages to detect gain/loss, positive/negative interactions as well as rewired-hub nodes contributing to dynamic cancer progression. RESULTS: After having implemented our new approach, we could identify four stage-specific core biological pathways. We could also detect an essential non-coding RNA, AC025034.1, which is not the only antisense to ATP2B1 (cell proliferation regulator), but also revealed a statistically significant stage-descending pattern; Moreover, AC025034.1 revealed both a dynamic topological pattern across stages and prognostic trait. We also identified a high-performance Overall-Survival-Risk model, including 12 re-wired genes to predict patients' risk (c-index = 0.89). Finally, breast cancer-specific prognostic biomarkers of LINC01612, AC092142.1, and AC008969.1 were identified. CONCLUSIONS: In summary new scoring method highlighted stage-specific core pathways for early-to-late progressions. Moreover, detecting the significant re-wired hub nodes indicated stage-associated traits, which reflects the importance of such regulators from different perspectives.

Laboratory methods to decipher epigenetic signatures: a comparative review.

Epigenetics refers to nucleotide sequence-independent events, and heritable changes, including DNA methylation and histone modification (as the two main processes), contributing to the phenotypic features of the cell. Both genetics and epigenetics contribute to determining the outcome of regulatory gene expression systems. Indeed, the flexibility of epigenetic effects and stability of genetic coding lead to gene regulation complexity in response signals. Since some epigenetic changes are significant in abnormalities such as cancers and neurodegenerative diseases, the initial changes, dynamic and reversible properties, and diagnostic potential of epigenomic phenomena are subject to epigenome-wide association studies (EWAS) for therapeutic aims. Based on recent studies, methodological developments are necessary to improve epigenetic research. As a result, several methods have been developed to explore epigenetic alterations at low, medium, and high scales, focusing on DNA methylation and histone modification detection. In this research field, bisulfite-, enzyme sensitivity- and antibody specificity-based techniques are used for DNA methylation, whereas histone modifications are gained based on antibody recognition. This review provides a mechanism-based understanding and comparative overview of the most common techniques for detecting the status of epigenetic effects, including DNA methylation and histone modifications, for applicable approaches from low- to high-throughput scales.

The composition of lung microbiome in lung cancer: a systematic review and meta-analysis.

BACKGROUND: Although recent studies have indicated that imbalance in the respiratory microbiome composition is linked to several chronic respiratory diseases, the association between the lung microbiome and lung cancer has not been extensively studied. Conflicting reports of individual studies on respiratory microbiome alterations in lung cancer complicate the matter for specifying how the lung microbiome is linked to lung cancer. Consequently, as the first meta-analysis on this topic, we integrate publicly available 16S rRNA gene sequence data on lung tissue samples of lung cancer patients to identify bacterial taxa which differ consistently between case and control groups. RESULTS: The findings of the current study suggest that the relative abundance of several bacterial taxa including Actinobacteria phylum, Corynebacteriaceae and Halomonadaceae families, and Corynebacterium, Lachnoanaerobaculum, and Halomonas genera is significantly decreased (p < 0.05) in lung tumor tissues of lung cancer patients in comparison with tumor-adjacent normal tissues. CONCLUSIONS: Despite the underlying need for scrutinizing the findings further, the present study lays the groundwork for future research and adds to our limited understanding of the key role of the lung microbiome and its complex interaction with lung cancer. More data on demographic factors and tumor tissue types would help establish a greater degree of accuracy in characterizing the lung microbial community which accords with subtypes and stages of the disease and fully capturing the changes of the lung microbiome in lung cancer.

Involvement of immune system and Epithelial-Mesenchymal-Transition in increased invasiveness of clustered circulatory tumor cells in breast cancer.

BACKGROUND: Circulating tumor cells (CTCs) are the critical initiators of distant metastasis formation. In which, the reciprocal interplay among different metastatic pathways and their metastasis driver genes which promote survival of CTCs is not well introduced using network approaches. METHODS: Here, to investigate the unknown pathways of single/cluster CTCs, the co-expression network was reconstructed, using WGCNA (Weighted Correlation Network Analysis) method. Having used the hierarchical clustering, we detected the Immune-response and EMT subnetworks. The metastatic potential of genes was assessed and validated through the support vector machine (SVM), neural network, and decision tree methods on two external datasets. To identify the active signaling pathways in CTCs, we reconstructed a casual network. The Log-Rank test and Kaplan-Meier curve were applied to detect prognostic gene signatures for distant metastasis-free survival (DMFS). Finally, a predictive model was developed for metastasis risk of patients using VIF-stepwise feature selection. RESULTS: Our results showed the crosstalk among EMT, the immune system, menstrual cycles, and the stemness pathway in CTCs. In which, fluctuation of menstrual cycles is a new detected pathway in breast cancer CTCs. The reciprocal association between immune responses and EMT was identified in CTCs. The SVM model indicated a high metastatic potential of EMT subnetwork (accuracy, sensitivity, and specificity scores were 87%). The DMFS model was identified to predict patients' metastasis risks. (c-index = 0.7). Finally, novel metastatic biomarkers of KRT18 and KRT19 were detected in breast cancer CTCs. CONCLUSIONS: In conclusion, the reciprocal interplay among critical unknown pathways in CTCs manifests both their survival in blood and metastatic potentials. Such findings may help to develop more precise predictive metastatic-risk models or detect pivotal metastatic biomarkers.

PI3K signalling in chronic obstructive pulmonary disease and opportunities for therapy.

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterised by airway inflammation and progressive obstruction of the lung airflow. Current pharmacological treatments include bronchodilators, alone or in combination with steroids, or other anti-inflammatory agents, which have only partially contributed to the inhibition of disease progression and mortality. Therefore, further research unravelling the underlying mechanisms is necessary to develop new anti-COPD drugs with both lower toxicity and higher efficacy. Extrinsic signalling pathways play crucial roles in COPD development and exacerbations. In particular, phosphoinositide 3-kinase (PI3K) signalling has recently been shown to be a major driver of the COPD phenotype. Therefore, several small-molecule inhibitors have been identified to block the hyperactivation of this signalling pathway in COPD patients, many of them showing promising outcomes in both preclinical animal models of COPD and human clinical trials. In this review, we discuss the critically important roles played by hyperactivated PI3K signalling in the pathogenesis of COPD. We also critically review current therapeutics based on PI3K inhibition, and provide suggestions focusing on PI3K signalling for the further improvement of the COPD phenotype. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A multimodal deep learning-based drug repurposing approach for treatment of COVID-19.

Recently, various computational methods have been proposed to find new therapeutic applications of the existing drugs. The Multimodal Restricted Boltzmann Machine approach (MM-RBM), which has the capability to connect the information about the multiple modalities, can be applied to the problem of drug repurposing. The present study utilized MM-RBM to combine two types of data, including the chemical structures data of small molecules and differentially expressed genes as well as small molecules perturbations. In the proposed method, two separate RBMs were applied to find out the features and the specific probability distribution of each datum (modality). Besides, RBM was used to integrate the discovered features, resulting in the identification of the probability distribution of the combined data. The results demonstrated the significance of the clusters acquired by our model. These clusters were used to discover the medicines which were remarkably similar to the proposed medications to treat COVID-19. Moreover, the chemical structures of some small molecules as well as dysregulated genes' effect led us to suggest using these molecules to treat COVID-19. The results also showed that the proposed method might prove useful in detecting the highly promising remedies for COVID-19 with minimum side effects. All the source codes are accessible using https://github.com/LBBSoft/Multimodal-Drug-Repurposing.git.

Isolation of Novel Probiotic Lactobacillus and Enterococcus Strains From Human Salivary and Fecal Sources.

Probiotics are non-pathogenic microorganisms that can interact with the gastrointestinal microbiota. They have numerous beneficial health effects that include enhancement of the host immune response, antiallergic, antimicrobial, anti-cancer, and anti-inflammatory properties. Probiotics are capable of restoring the impaired microbiome of a dysbiotic gut. They can be isolated from different environments. However, it is frequently suggested that probiotics for human use should come from human sources. The objective of this study was to isolate and characterize novel probiotic strains from the saliva and feces of healthy human individuals. To meet the criteria for probiotic attributes, the isolates were subjected to numerous standard morphological and biochemical tests. These tests included Gram staining, catalase tests, antibiotic susceptibility testing, hemolytic and antagonistic evaluation, tolerance tests involving temperature, NaCl levels, pH and bile salts, adherence ability assays, and genotypic characterization involving 16S rRNA gene sequencing. From 26 saliva and 11 stool samples, 185 microbial strains were isolated. Based on morphological and biochemical characteristics, 14 potential probiotic candidates were selected and identified genotypically. The new strains belonged to Lactobacillus fermentum, Enterococcus faecium, and Enterococcus hire. The selected strains were non-hemolytic, showed high tolerance to low pH and bile salts, and strong adherence abilities. Furthermore, the strains displayed a wide range of antimicrobial activities, particularly against antibiotic-resistant pathogens such as methicillin resistant Staphylococcus aureus (MRSA). Moreover, five of the selected isolates demonstrated antiproliferative features against human colon cancer cell line (Caco-2). The results of this investigation confirm the diversity of microbial populations in the human gut and saliva, and since these strains are of human origin, they will highly likely display maximal activities in food and drugs set for human use. Hence, the new strains of this study require additional in vivo experiments to assess their health-promoting effects.

MiR-486-5p enhances cisplatin sensitivity of human muscle-invasive bladder cancer cells by induction of apoptosis and down-regulation of metastatic genes.

OBJECTIVES: Cisplatin is one of the common chemotherapy drugs for bladder cancer, and resistance to this drug is one of the major obstacles to effective chemotherapy. MicroRNAs (miRNAs) are a category of small noncoding RNAs that can regulate the expression of numerous genes. Recent studies showed that miRNAs can act as a powerful regulator of chemo-sensitivity in cancer cells. Hence, this study aimed to investigate the effects of miRNA-486-5p on cisplatin-sensitivity of different bladder cancer cells. MATERIAL AND METHODS: The 5637 and EJ138 cancer cells were treated with miRNA-486-5p and cisplatin, individually or in combination. RESULTS: Afterward, the cytotoxicity effects of these treatments were determined by MTT assay and the increased cisplatin-sensitivity observed in both cell lines, especially, 5637 cells. Moreover, subG1 phase cell cycle arrest, changes in the expression of caspase-9, caspase-3, P53, SIRT1, OLFM4, SMAD2, and Bcl-2 genes and nuclear fragmentation also revealed the induction of apoptosis in all treatments, which increased in combination groups. Also, the combination of miRNA-486-5p with cisplatin significantly down-regulated the expression of migration associated genes including ROCK, CD44, and MMP-9 as compared with cisplatin alone. CONCLUSION: Altogether, these results indicated that the miRNA-486-5p could induce apoptosis and inhibit cell migration ability of the cells. It seems that pre-electroporation of cells with miRNA-486-5p has useful results in the enhancement of cisplatin sensitivity of 5637 and EJ138 cancer cells and this combination may be a promising treatment strategy for bladder cancer therapy.

An efficient hybrid feature selection method to identify potential biomarkers in common chronic lung inflammatory diseases.

Asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) are three serious lung inflammatory diseases. The understanding of the pathogenesis mechanism and the identification of potential prognostic biomarkers of these diseases can provide the patients with more efficient treatments. In this study, an efficient hybrid feature selection method was introduced in order to extract informative genes. We implemented an ontology-based ranking approach on differentially expressed genes following a wrapper method. The examination of the different gene ontologies and their combinations motivated us to propose a biological functional-based method to improve the performance of further wrapper methods. The results identified: TOM1L1, SRSF1, and GIT2 in asthma; CHCHD4, PAIP2, CRLF3, UBQLN4, TRAK1, PRELID1, VAMP4, CCM2, and APBB1IP in COPD; and TUFT1, GAB2, B4GALNT1, TNFRSF17, PRDM8, and SETDB2 in IPF as the potential biomarkers. The proposed method can be used to identify hub genes in other high-throughput datasets.

Small regulatory noncoding RNAs in Drosophila melanogaster: biogenesis and biological functions.

RNA interference (RNAi) is an important phenomenon that has diverse genetic regulatory functions at the pre- and posttranscriptional levels. The major trigger for the RNAi pathway is double-stranded RNA (dsRNA). dsRNA is processed to generate various types of major small noncoding RNAs (ncRNAs) that include microRNAs (miRNAs), small interfering RNAs (siRNAs) and PIWI-interacting RNAs (piRNAs) in Drosophila melanogaster (D. melanogaster). Functionally, these small ncRNAs play critical roles in virtually all biological systems and developmental pathways. Identification and processing of dsRNAs and activation of RNAi machinery are the three major academic interests that surround RNAi research. Mechanistically, some of the important biological functions of RNAi are achieved through: (i) supporting genomic stability via degradation of foreign viral genomes; (ii) suppressing the movement of transposable elements and, most importantly, (iii) post-transcriptional regulation of gene expression by miRNAs that contribute to regulation of epigenetic modifications such as heterochromatin formation and genome imprinting. Here, we review various routes of small ncRNA biogenesis, as well as different RNAi-mediated pathways in D. melanogaster with a particular focus on signaling pathways. In addition, a critical discussion of the most relevant and latest findings that concern the significant contribution of small ncRNAs to the regulation of D. melanogaster physiology and pathophysiology is presented.

Identification of biomarkers in common chronic lung diseases by co-expression networks and drug-target interactions analysis.

BACKGROUND: asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) are three serious pulmonary diseases that contain common and unique characteristics. Therefore, the identification of biomarkers that differentiate these diseases is of importance for preventing misdiagnosis. In this regard, the present study aimed to identify the disorders at the early stages, based on lung transcriptomics data and drug-target interactions. METHODS: To this end, the differentially expressed genes were found in each disease. Then, WGCNA was utilized to find specific and consensus gene modules among the three diseases. Finally, the disease-disease similarity was analyzed, followed by determining candidate drug-target interactions. RESULTS: The results confirmed that the asthma lung transcriptome was more similar to COPD than IPF. In addition, the biomarkers were found in each disease and thus were proposed for further clinical validations. These genes included RBM42, STX5, and TRIM41 in asthma, CYP27A1, GM2A, LGALS9, SPI1, and NLRC4 in COPD, ATF3, PPP1R15A, ZFP36, SOCS3, NAMPT, and GADD45B in IPF, LRRC48 and CETN2 in asthma-COPD, COL15A1, GIMAP6, and JAM2 in asthma-IPF and LMO7, TSPAN13, LAMA3, and ANXA3 in COPD-IPF. Finally, analyzing drug-target networks suggested anti-inflammatory candidate drugs for treating the above mentioned diseases. CONCLUSION: In general, the results revealed the unique and common biomarkers among three chronic lung diseases. Eventually, some drugs were suggested for treatment purposes.

Bacterial infections in acute exacerbation of chronic obstructive pulmonary disease: a systematic review and meta-analysis.

OBJECTIVE: Due to the importance of Chronic obstructive pulmonary disease (COPD) as the fourth cause of mortality worldwide and the lack of studies evaluating the prevalence of bacterial infections in disease exacerbation, this systematic review and meta-analysis was performed to determine the prevalence rate of bacterial infections in COPD patients. METHODS: PubMed, ISI Web of Science, and Scopus databases were systematically searched for population-based prevalence studies (1980-2018). MeSH terms for "Bacterial infections" and "AECOPD" were used as search keywords. The selected studies were filtered according to the inclusion and exclusion criteria. Fixed and random-effects models were used for estimation of summary effect sizes. Between-study heterogeneity, as well as publication bias, were calculated. RESULTS: Finally, 118 out of 31,440 studies were selected. The overall estimation of the prevalence of bacterial infection was 49.59% [95% confidence interval (CI) 0.4418-0.55]. The heterogeneity in estimating the pooled prevalence of bacterial infections was shown in the studies (Cochran Q test: 6615, P < 0.0001, I2 = 98.23%). In addition, S. pneumoniae, H. influenzae, M. catarrhalis, A. baumannii, P. aeruginosa, and S. aureus were the most prevalent reported bacteria. CONCLUSIONS: Our results as the first meta-analysis for the issue demonstrated that bacterial infections are an important risk factor for AECOPD. Further studies must be performed for understanding the exact role of bacterial agents in AECOPD and help physicians for more applicable preventive and therapeutic measurements.

TNF-α -308 G/A variant and susceptibility to chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: TNF-α -308 G/A variant is recognized to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Although many studies have investigated the association of TNF-α-308 and COPD risk, a deep understanding of this association is lacking due to small subjects sizes and insufficiently study designs among different investigations. In this study, a systematic review and meta-analysis was performed based on published reports on the association of TNF-α and COPD. METHOD: The published studies concerned the association between TNF-α and COPD were identified using a systematic research in Scopus, Google Scholar, and PubMed up to April 2018. A total of 46 different papers studying the rs1800629 variant in TNF-α gene were included. Then, human studies were selected to further analysis regardless of papers language. RESULTS: Based on the results, the major outcome of this meta-analysis can be represented as follows: individuals with GG and GA genotypes possess less risk of developing COPD (OR = 0.58, 95%CI: (0.44-0.79), P < 0.00) compared to AA genotype carriers. In contrast, the AA genotype carriers of the TNF-α rs1800629 has a significantly higher risk of developing COPD (OR = 1.83, 95%CI: (1.34-2.51), P < 0.00) compared to GG carrier. Despite the previous meta-analysis results which reported significantly decreasing of heterogeneity with ethnicity, we found that the source of controls has a significant contribution to observed heterogeneity. CONCLUSIONS: Thanks to the global burden of COPD studies, proving TNF-α 308 gene variant as an independent factor in its pathogenesis opens new insights to diagnosis and management of COPD.

Detection of novel biomarkers for early detection of Non-Muscle-Invasive Bladder Cancer using Competing Endogenous RNA network analysis.

Bladder Cancer (BC) is one of the most common cancers in the world. Recent studies show that non-coding RNAs such as lncRNAs and circRNAs play critical roles in the progression of this cancer, but their regulatory relationships and functions are still largely unknown. As a new regulatory process within the cell, the coding and non-coding RNAs compete with each other to sponge their target miRNAs. This mechanism is described as "the competing endogenous RNA (ceRNA) hypothesis" which provides a new perspective to understand the regulation of gene expression in health and diseases such as cancer. In this study, to investigate the role of non-coding RNAs in BC, a new approach was used to reconstruct the ceRNA network for Non-Muscle Invasive Bladder Cancer (NMIBC) based on the expression data of coding and non-coding genes. Analysis of ceRNA networks in the early stage of BC led to the detection of an important module containing the lncRNA MEG3 as the central gene. The results show that the lncRNAs CARMN, FENDRR and ADAMTS9-AS2 may regulate MEG3 in NMIBC through sponging some important miRNAs such as miR-143-3p, miR-106a-5p and miR-34a-3p. Also, the lncRNA AC007608.2 is shown to be a potential BC related lncRNA for the first time based on ceRNA stage-specific network analysis. Furthermore, hub and altered genes in stage-specific and between stage networks led to the detection of hsa_circ_0017586 and hsa_circ_0001741 as novel potential circRNAs related to NMIBC. Finally, the hub genes in the networks were shown to be valuable candidates as biomarkers for the early stage diagnosis of BC.

Association between chronic obstructive pulmonary disease and interleukins gene variants: A systematic review and meta-analysis.

Interleukins are cytokines involved in systemic inflammation and immune system regulation. Many studies have investigated the association between common genetic variations in interleukin-coding genes and COPD susceptibility. In this study, a systematic review and meta-analysis was performed to evaluate the association between interleukin gene variations and COPD pathogenesis. Association studies were retrieved from PubMed and Google Scholar databases using the standard systematic search strategy. A total of 26 different studies evaluating eight polymorphisms in four interleukin genes were included in this study. In overall comparisons, IL1ß-rs16944, -rs1143627, -rs1143634, IL13-rs20541 polymorphisms were found not to be associated with the increased risk for developing COPD. However, IL1RN-rs2234663 and IL13-rs1800925 showed a strong association with COPD. We showed that the CC genotype carriers of the IL6-rs1800795 are at significantly higher risk of developing COPD (OR = 1.31, 95% CI: 1.04-1.64, P = 0.01) compared to GG carriers. In case of IL6-rs1800796, individuals with CC and CG genotypes showed a lower risk to develop COPD (OR = 0.46, 95%CI: 0.32-0.66, P > 0.00). This updated meta-analysis strongly supports the association of IL1RN-rs2234663, IL6-rs1800795, -rs1800795 and IL13-rs1800925 variants with COPD.