Deciphering the impact of microbial interactions on COPD exacerbation: An in-depth analysis of the lung microbiome.

In microbiome studies, the diversity and types of microbes have been extensively explored; however, the significance of microbial ecology is equally paramount. The comprehension of metabolic interactions among the wide array of microorganisms in the lung microbiota is indispensable for understanding chronic pulmonary disease and for the development of potent treatments. In this investigation, metabolic networks were simulated, and ecological theory was employed to assess the diagnosis of COPD, subsequently suggesting innovative treatment strategies for COPD exacerbation. Lung sputum 16S rRNA paired-end data from 112 COPD patients were utilized, and a supervised machine-learning algorithm was applied to identify taxa associated with sex and mortality. Subsequently, an OTU table with Greengenes 99 % dataset was generated. Finally, the interactions between bacterial species were analyzed using a simulated metabolic network. A total of 1781 OTUs and 1740 bacteria at the genus level were identified. We employed an additional dataset to validate our analyses. Notably, among the more abundant genera, Pseudomonas was detected in females, while Lactobacillus was detected in males. Additionally, a decrease in bacterial diversity was observed during COPD exacerbation, and mortality was associated with the high abundance of the Staphylococcus and Pseudomonas genera. Moreover, an increase in Proteobacteria abundance was observed during COPD exacerbations. In contrast, COPD patients exhibited decreased levels of Firmicutes and Bacteroidetes. Significant connections between microbial ecology and bacterial diversity in COPD patients were discovered, highlighting the critical role of microbial ecology in the understanding of COPD. Through the simulation of metabolic interactions among bacteria, the observed dysbiosis in COPD was elucidated. Furthermore, the prominence of anaerobic bacteria in COPD patients was revealed to be influenced by parasitic relationships. These findings have the potential to contribute to improved clinical management strategies for COPD patients.

A logic-based dynamic modeling approach to explicate the evolution of the central dogma of molecular biology.

It is nearly half a century past the age of the introduction of the Central Dogma (CD) of molecular biology. This biological axiom has been developed and currently appears to be all the more complex. In this study, we modified CD by adding further species to the CD information flow and mathematically expressed CD within a dynamic framework by using Boolean network based on its present-day and 1965 editions. We show that the enhancement of the Dogma not only now entails a higher level of complexity, but it also shows a higher level of robustness, thus far more consistent with the nature of biological systems. Using this mathematical modeling approach, we put forward a logic-based expression of our conceptual view of molecular biology. Finally, we show that such biological concepts can be converted into dynamic mathematical models using a logic-based approach and thus may be useful as a framework for improving static conceptual models in biology.

HOXB7 and Hsa-miR-222 as the Potential Therapeutic Candidates for Metastatic Colorectal Cancer.

BACKGROUND: Recent studies have shown that the high mortality of patients with colorectal cancer (CRC) is related to its ability to spread the surrounding tissues, thus there is a need for designing and developing new drugs. OBJECTIVE: Here, we proposed a combinational therapy strategy, an inhibitory peptide in combination with miRNA targeting, for modulating CRC metastasis. In this study, some of the recent patents were also reviewed. METHODS: After data analysis with GEO2R and gene annotation using DAVID server, regulatory interactions of differentially expressed genes (DEGs) were obtained from STRING, GeneMANIA, KEGG and TRED databases. In parallel, the corresponding validated microRNAs (miRNAs) were obtained from mirDIP web server and a miRNA-DEG regulatory network was also reconstructed. Clustering and topological analyses of the regulatory networks were performed using Cytoscape plug-ins. RESULTS: We found the HOXB family as the most important functional complex in DEG-derived regulatory network. Accordingly, an anti-HOXB7 peptide was designed based on the binding interface of its coactivator, PBX1. Topological analysis of miRNA-DEG network indicated that hsa-miR-222 is one of the most important oncomirs involved in regulation of DEGs activities. Thus, this miRNA, along with HOXB7, was also considered as the potential target for inhibiting CRC metastasis. Molecular docking studies exhibited that the designed peptide can bind to desired binding pocket of HOXB7 in a highaffinity manner. Further confirmations were also observed in Molecular dynamics (MD) simulations carried out by GROMACS v5.0.2 simulation package. CONCLUSION: In conclusion, our findings suggest that simultaneous targeting of key regulatory genes and miRNAs may be a useful strategy for prevention of CRC metastasis.

Expression of glutathione S-transferase variants in human airway wall after long-term response to sulfur mustard.

CONTEXT: Sulfur mustard (SM) is an alkylating agent identified as a potent chemical warfare agent. More recently, SM was used in the Iraq conflict against Iranian troops and civilians. At present, there are many people suffering from chronic obstructive pulmonary disease (COPD) due to mustard gas in Iran. SM increases the endogenous production of reactive oxygen species (ROS). The oxidant/antioxidant imbalance present in the lungs of these patients also results from the impaired capacity of the antioxidant/detoxification enzymes to detoxify the harmful reactive oxygen metabolites. OBJECTIVE: One of the major antioxidants in human airways is glutathione S-transferase. They facilitate the detoxification of various environmental of oxidative stress. In this study, we attempted to understand the significance different in expression of GSTs in airway wall of chemical patients and control. MATERIALS AND METHODS: Seven normal and 20 SM induced COPD individuals were studied. Bronchoscopy was performed in all subjects and two specimens were taken from the main bronchus for mRNA extraction, PCR analysis and immunohistochemistry. RESULTS: SM-induced COPD individuals showed expression of GSTA1 2.51 ± 0.83-, GSTM1 2.84 ± 1.71- and GSTP1 5.61 ± 2.59-folds higher than those of controls that revealed. GSTP1-immunoreactivity was strongly expressed in luminal border of normal samples. SM patient samples immunoreactivity for GSTP1 in the same area were negative. DISCUSSION AND CONCLUSION: According to these findings, we speculated that overexpression of GSTs mRNA in patients revealed that GSTs plays an important role in cellular protection against oxidative stress of MS in airway wall of patients.