CoCl2 Research Articles

FOS gene associated immune infiltration signature in perivascular adipose tissues of abdominal aortic aneurysm

Abdominal aortic aneurysms (AAA) are pathological dilations in local aortic wall. The inflammatory infiltrates of the perivascular adipose tissue (PAT) surrounding AAAs were associated with AAAs and have been shown to contribute vascular pathology. However, the mechanism by which PAT inflammation contributes to vascular pathology in AAA remains to be clarified. This study aimed to explore the association between immune cell infiltration and key gene expression profile in PAT of AAA. For that, a gene expression dataset of human dilated perivascular adipose tissue (dPAT), non-dilated perivascular adipose tissue (ndPAT), subcutaneous abdominal fat (SAF) and omental-visceral fat (OVF) samples, as well as another microarray dataset of the abdominal perivascular adipose tissue in peripheral artery disease patients were downloaded from GEO database for analysis in this study. The CIBERSORT algorithm, weighted gene co-expression network analysis (WGCNA) and LASSO algorithm were used for the identification of immune infiltration, immune-related genes and the development of diagnostic signature. Our data discovered a significant higher proportion of activated mast cells and follicular helper T (Tfh) cells in dPAT than ndPAT, OVT and SAF samples. Moreover, AP-1 family members (FOS, FOSB, ATF3, JUN and JUNB) were found to compose the hub genes of purple module in WGCNA. Among them, FOS gene acts as a higher efficient marker to discriminate dPAT from ndPAT, OVT and SAF in AAA. Meanwhile, the expression profiles of the AP-1 family members are all significantly positive correlated with activated mast cell, plasma cell and Tfh cell infiltration in dPAT of AAA. Therefore, in the PAT surrounding AAA, the signature of inflammatory infiltration might be represented by a FOS-dominated cell network consist of activated mast cell, plasma cell and Tfh cell. Given the complicated etiology of AAA, our results are likely to shed new light on the pathophysiologic mechanism of AAA influenced by the local dPAT.

P. aeruginosa type III and type VI secretion systems modulate early response gene expression in type II pneumocytes in vitro

BackgroundLung airway epithelial cells are part of innate immunity and the frontline of defense against bacterial infections. During infection, airway epithelial cells secrete proinflammatory mediators that participate in the recruitment of immune cells. Virulence factors expressed by bacterial pathogens can alter epithelial cell gene expression and modulate this response. Pseudomonas aeruginosa, a Gram-negative opportunistic pathogen, expresses numerous virulence factors to facilitate establishment of infection and evade the host immune response. This study focused on identifying the role of two major P. aeruginosa virulence factors, type III (T3SS) and type VI (T6SS) secretion systems, on the early transcriptome response of airway epithelial cells in vitro.ResultsWe performed RNA-seq analysis of the transcriptome response of type II pneumocytes during infection with P. aeruginosa in vitro. We observed that P. aeruginosa differentially upregulates immediate-early response genes and transcription factors that induce proinflammatory responses in type II pneumocytes. P. aeruginosa infection of type II pneumocytes was characterized by up-regulation of proinflammatory networks, including MAPK, TNF, and IL-17 signaling pathways. We also identified early response genes and proinflammatory signaling pathways whose expression change in response to infection with P. aeruginosa T3SS and T6SS mutants in type II pneumocytes. We determined that T3SS and T6SS modulate the expression of EGR1, FOS, and numerous genes that are involved in proinflammatory responses in epithelial cells during infection. T3SS and T6SS were associated with two distinct transcriptomic signatures related to the activation of transcription factors such as AP1, STAT1, and SP1, and the secretion of pro-inflammatory cytokines such as IL-6 and IL-8.ConclusionsTaken together, transcriptomic analysis of epithelial cells indicates that the expression of immediate-early response genes quickly changes upon infection with P. aeruginosa and this response varies depending on bacterial viability and injectosomes. These data shed light on how P. aeruginosa modulates host epithelial transcriptome response during infection using T3SS and T6SS.

Combinatorial Treatment with PARP-1 Inhibitors and Cisplatin Attenuates Cervical Cancer Growth through Fos-Driven Changes in Gene Expression.

Our observations, which link the gene regulatory effects of PARPi + cisplatin to the growth inhibitory effects of FOS expression in cervical cancer cells, strengthen the rationale for using PARPi with cisplatin as a therapy for cervical cancer.

Age-Dependent FOSB/ΔFOSB Response to Acute and Chronic Stress in the Extended Amygdala, Hypothalamic Paraventricular, Habenular, Centrally-Projecting Edinger-Westphal, and Dorsal Raphe Nuclei in Male Rats.

FOS proteins are early-responding gene products that contribute to the formation of activator protein-1. Several acute and chronic stimuli lead to Fos gene expression, accompanied by an increase of nuclear FOS, which appears to decline with aging. FOSB is another marker to detect acute cellular response, while ΔFOSB mirrors long-lasting changes in neuronal activity upon chronic stress. The notion that the occurrence of stress-related mood disorders shows some age dependence suggests that the brain’s stress sensitivity is also a function of age. To study age-dependent stress vulnerability at the immediate-early gene level, we aimed to describe how the course of aging affects the neural responses of FOSB/ΔFOSB in the acute restraint stress (ARS), and chronic variable mild stress (CVMS) in male rats. Fourteen brain areas [central, medial, basolateral (BLA) amygdala; dorsolateral- (BNSTdl), oval- (BNSTov), dorsomedial-, ventral- (BNSTv), and fusiform- (BNSTfu) divisions of the bed nucleus of the stria terminalis; medial and lateral habenula, hypothalamic paraventricular nucleus (PVN), centrally-projecting Edinger-Westphal nucleus, dorsal raphe nucleus, barrel field of somatosensory cortex (S1)] were examined in the course of aging. Eight age groups [1-month-old (M), 1.5 M, 2 M, 3 M, 6 M, 12 M, 18 M, and 24 M] of rats were exposed to a single ARS vs. controls. In addition, rats in six age groups (2, 3, 6, 12, 18, and 24 M) were subjected to CVMS. The FOSB/ΔFOSB immunoreactivity (IR) was a function of age in both controls, ARS- and CVMS-exposed rats. ARS increased the FOSB/ΔFOSB in all nuclei (except in BLA), but only BNSTfu, BNSTv, and PVN reacted throughout the examined lifespan. The CVMS did not increase the FOSB/ΔFOSB in BLA, BNSTov, BNSTdl, and S1. PVN showed a constantly maintained FOSB/ΔFOSB IR during the examined life period. The maximum stress-evoked FOSB/ΔFOSB signal was detected at 2–3 M periods in the ARS- and at 6 M, 18 M in CVMS- model. Corresponding to our previous observations on FOS, the FOSB/ΔFOSB response to stress decreased with age in most of the examined nuclei. Only the PVN exerted a sustained age-independent FOSB/ΔFOSB, which may reflect the long-lasting adaptation response and plasticity of neurons that maintain the hypothalamus-pituitary-adrenal axis response throughout the lifespan.

Bclaf1 promotes hematopoietic stem cell repopulating capacity and self-renewal

Abstract Hematopoietic stem cells (HSC) balance differentiation and self-renewal to promote maintenance of mature blood cell lineages. The mechanisms that regulate HSC expansion during fetal hematopoietic development and adult HSC maintenance remain significant knowledge gaps. BCLAF1 (Bcl2-associated factor 1), a transcriptional regulator, is highly expressed in hematopoietic cells. We recently defined its function as a modulator of ETS-family transcription factor activity in developing B cells. Our objective in this study is to determine the molecular mechanism of BCLAF1 in regulation of fetal and adult HSCs. We used mouse models with selective deletion of Bclaf1 in hematopoietic cells to test whether BCLAF1 regulates HSC development and function. We find that loss of Bclaf1 results in significantly reduced numbers of fetal HSCs. The reduced HSC numbers persist in adult mice; but there is no additional decline or development of bone marrow failure with aging. In competitive transplant experiments, Bclaf1-deficient fetal and adult HSCs have defective repopulation and self-renewal capacity resulting in reduced reconstitution of all hematopoietic populations. Bclaf1-deficient HSCs do not have abnormalities in emergence, proliferation, cell death, or homing activity. Using single cell RNA-sequencing of fetal HSCs, we find that loss of BCLAF1 results in reduction of a subpopulation of HSCs and upregulation of the early response genes Jun, Fos, and Egr1. Collectively, these findings suggest BCLAF1 restrains activity of immediate early genes to preserve HSC self-renewal capacity and promote HSC expansion during both fetal development and repopulation of hematopoiesis after HSC transplant. Supported by grants from Children's Discovery Institute, St. Louis Children's Hospital Foundation, Siteman Cancer Center, and NIH (T32 AI007163).

Solid supported synthesis of unsymmetrical bi-functionalized ferrocenyl-rhodaminyl molecular system to explore phosgene, heavy metal ion sensing, and cell imaging properties

A series of 1,1′-unsymmetrical bi-functionalized ferrocenyl hydrazone – enone molecular compounds (3–7) have been synthesized using a facile redmud supported solid state synthetic method. These unsymmetrical bi-functionalized derivatives involving fluorescent active group have been explored for their fluorescence based signaling and sensing behavior of metal cations in the subcellular level. The study showed significant intracellular metal recognition and imaging characteristics for their potential in applications related to bioimaging of heavy metal ions. Sensing behavior has also been studied to understand their scope in the detection of toxic phosgene gas using multi-probe spectroscopic and electrochemical methods.

Recent advances in the green synthesis of Betti bases and their applications: a review.

Well-known Betti bases are the products obtained by the one-pot multicomponent reaction of 1-naphthol/2-naphthol, aliphatic/aromatic aldehydes, and secondary amines, and this reaction is known as the Betti reaction. During recent years, due to the unveiling of the pharmacological and synthetic potential of Betti bases, a tremendous increase in the studies reporting novel synthetic methods for the efficient synthesis of Betti bases was observed. This review presents the recent key developments in the green synthesis of the Betti bases and accounts for the significant number of the literature reported during 2019-2022. Both catalyst free as well as the catalyst promoted synthesis (nanocatalyst, biocatalyst, transition metal catalyst, etc.) along with the synthetic applications (catalyst, ligands/chiral auxiliaries, and valuable synthons), optoelectronic applications (fluorescence sensors for phosgene gas, Hg2+, and Cr3+ detection, quasi-reversible redox potential) and biological properties (anticancer agents, antioxidant, anti-inflammatory agents, antitubercular agents, pesticidal agents, anti-Alzheimer agents, Topoisomerase I inhibitors, YAP-TEAD interaction inhibitors, and DNA binding and cleavage activity) are discussed. There is a surge of interest for the development of the green and efficient Betti reaction for the construction of C-C and C-N bond in a single-step reaction accessing Betti bases as products. Along with key methodological developments for the green synthesis of Betti bases, their applications in synthetic organic chemistry, optoelectronic sensors, advanced materials synthesis, agrochemicals and pharmaceutically active scaffolds, during the period of 2019-2022, have been considered.

Titanium doping effect on the sensing performance of ZnO nanosheets toward phosgene gas

The density functional B3LYP was utilized for scrutinizing the effect of Ti-doping on the sensing performance of a ZnO nano-sheet (ZnONS) in detecting phosgene. Pure ZnONS had a weak interaction with phosgene, and the sensing response (SR) was approximately 9.4. There was an increase in the energy of adsorption (Ead) for phosgene from −5.5 to −22.8 kcal mol−1 after the doping of a Ti atom onto the surface of ZnONS. Following the doping of Ti, there was also a dramatic increase in the SR to 84.2. The recovery time (RT) for the desorption of phosgene from the ZnONS that was doped with Ti was 16.4 s. This suggested that Ti-doped ZnONS might be used as a phosgene sensor with a high sensitivity and a shorter RT.

Expression of CCL2, FOS, and JUN May Help to Distinguish Patients With IgA Nephropathy From Healthy Controls.

BackgroundIgA nephropathy (IgAN), the most common type of glomerulonephritis worldwide, can only be diagnosed mainly by renal biopsy owing to lack of effective biomarkers. It is urgent to explore and identify the potential diagnostic biomarkers through assessing the gene expression profiles of patients with IgAN.MethodsTwo datasets were obtained from the Gene Expression Omnibus (GEO) database, including GSE115857 (55 IgAN, 7 living healthy donors) and GSE35487 (25 IgAN, 6 living healthy donors), then underwent differentially expressed genes (DEGs) and function enrichment analyses utilizing R packages. The common gene list was screened out between DEGs and immune-associated genes by Venn diagram, then performed gene-gene interaction, protein-protein interaction (PPI) and function enrichment analyses. Top three immune-associated hub genes were selected by Maximal Clique Centrality (MCC) method, then the expression and diagnostic value of these hub genes were determined. Consensus clustering algorithm was applied to conduct the unsupervised cluster analysis of the immune-associated hub gene list in IgAN. Finally, the Nephroseq V5 tool was applied to identify the expression level of CCL2, FOS, JUN in kidney diseases, as well as the correlation between CCL2, FOS, JUN expression and renal function in the patients with IgAN.ResultsA total of 129 DEGs were obtained through comparing IgAN with healthy controls via the GSE115857 and GSE35487 datasets. Then, we screened out 24 immune-associated IgAN DEGs. CCL2, JUN, and FOS were identified as the top three hub genes, and they were all remarkably downregulated in IgAN. More importantly, CCL2, JUN, and FOS had a high accuracy [area under the curve (AUC) reached almost 1] in predicting IgAN, which could easily distinguish between IgAN patients and healthy individuals. Three distinct subgroups of IgAN were determined based on 24 immune-associated DEGs, with significant differences in the expression of CCL2, JUN, and FOS genes. Finally, CCL2, FOS, JUN were manifested a meaningful association with proteinuria, glomerular filtration rate (GFR), and serum creatinine level.ConclusionIn summary, our study comprehensively uncovers that CCL2, JUN, and FOS may function as promising biomarkers for diagnosis of IgAN.

Skin transcriptome analysis identifies the key genes underlying fur development in Chinese Tan sheep in the birth and Er-mao periods.

Hair follicle development in Tan sheep differs significantly between the birth and Er-mao periods, but the underlying molecular mechanism is still unclear. We profiled the skin transcriptomes of Tan sheep in the birth and Er-mao periods via RNA-seq technology. The Tan sheep examined consisted of three sheep in the birth period and three sheep in the Er-mao period. A total of 364 differentially expressed genes (DEGs) in the skin of Tan sheep between the birth period and the Er-mao period were identified, among which 168 were upregulated and 196 were downregulated. Interestingly, the FOS proto-oncogene (FOS) (fold change=22.67, P value=2.15*10^-44) was the most significantly differentially expressed gene. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the FOS gene was significantly enriched in the signaling pathway related to hair follicle development. Immunohistochemical analysis showed that the FOS gene was expressed in the skin of Chinese Tan sheep at the birth and Er-mao periods, with significantly higher expression in the Er-mao period. Our findings suggest that the FOS gene promotes hair follicle development in Tan sheep.

NEDD4 attenuates phosgene-induced acute lung injury through the inhibition of Notch1 activation.

Phosgene gas leakage can cause life‐threatening acute lung injury (ALI), which is characterized by inflammation, increased vascular permeability, pulmonary oedema and oxidative stress. Although the downregulation of neuronal precursor cell‐expressed developmentally downregulated 4 (NEDD4) is known to be associated with inflammation and oxidative damage, its functions in phosgene‐induced ALI remain unclear. In this study, rats with phosgene‐induced ALI were intravenously injected with NEDD4‐overexpressing lentiviruses to determine the functions of NEDD4 in this inflammatory condition. NEDD4 expression was decreased in the lung parenchyma of phosgene‐exposed control rats, whereas its expression level was high in the NEDD4‐overexpressing rats. Phosgene exposure increased the wet‐to‐dry lung weight ratio, but NEDD4 abrogated this effect. NEDD4 overexpression attenuated phosgene‐induced lung inflammation, lowering the high lung injury score (based on total protein, inflammatory cells and inflammatory factors in bronchoalveolar lavage fluid) and also reduced phosgene‐induced oxidative stress and cell apoptosis. Finally, NEDD4 was found to interact with Notch1, enhancing its ubiquitination and thereby its degradation, thus attenuating the inflammatory responses to ALI. Therefore, we demonstrated that NEDD4 plays a protective role in alleviating phosgene‐induced ALI, suggesting that enhancing the effect of NEDD4 may be a new approach for treating phosgene‐induced ALI.

Identification and Verification of Potential Hub Genes in Amphetamine-Type Stimulant (ATS) and Opioid Dependence by Bioinformatic Analysis.

Objective: Amphetamine-type stimulant (ATS) and opioid dependencies are chronic inflammatory diseases with similar symptoms and common genomics. However, their coexpressive genes have not been thoroughly investigated. We aimed to identify and verify the coexpressive hub genes and pathway involved in the pathogenesis of ATS and opioid dependencies. Methods: The microarray of ATS- and opioid-treatment mouse models was obtained from the Gene Expression Omnibus database. GEO2R and Venn diagram were performed to identify differentially expressed genes (DEGs) and coexpressive DEGs (CDEGs). Functional annotation and protein–protein interaction network detected the potential functions. The hub genes were screened using the CytoHubba and MCODE plugin with different algorithms, and further validated by receiver operating characteristic analysis in the GSE15774 database. We also validated the hub genes mRNA levels in BV2 cells using qPCR. Result: Forty-four CDEGs were identified between ATS and opioid databases, which were prominently enriched in the PI3K/Akt signaling pathway. The top 10 hub genes were mainly enriched in apoptotic process (CD44, Dusp1, Sgk1, and Hspa1b), neuron differentiation, migration, and proliferation (Nr4a2 and Ddit4), response to external stimulation (Fos and Cdkn1a), and transcriptional regulation (Nr4a2 and Npas4). Receiver operating characteristic (ROC) analysis found that six hub genes (Fos, Dusp1, Sgk1, Ddit4, Cdkn1a, and Nr4a2) have an area under the curve (AUC) of more than 0.70 in GSE15774. The mRNA levels of Fos, Dusp1, Sgk1, Ddit4, Cdkn1a, PI3K, and Akt in BV2 cells and GSE15774 with METH and heroin treatments were higher than those of controls. However, the Nr4a2 mRNA levels increased in BV2 cells and decreased in the bioinformatic analysis. Conclusions: The identification of hub genes was associated with ATS and opioid dependencies, which were involved in apoptosis, neuron differentiation, migration, and proliferation. The PI3K/Akt signaling pathway might play a critical role in the pathogenesis of substance dependence.

Deciphering Key Foreign Body Reaction-Related Transcription Factors and Genes Through Transcriptome Analysis.

Background: Silicone implants are widely used in the field of plastic surgery for wound repair and cosmetic augmentation. However, molecular mechanisms and signaling pathways underlying the foreign body reaction (FBR) of a host tissue to the silicone require further elucidation. The purpose of this study was to identify key FBR-related transcription factors (TFs) and genes through transcriptome analysis. Methods: We used a rat model with a subcutaneous silicone implant in the scalp and performed high throughput sequencing to determine the transcriptional profiles involved in the FBR. The function was analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-enrichment analysis. A protein-protein interaction (PPI) network of differentially expressed mRNAs (DEmRNAs) was constructed to identify the hub genes and key modules and to determine the regulatory TF-mRNA relationships. In addition, the hub gene and transcript expression levels were determined by Quantitative Reverse Transcription polymerase Chain Reaction (qRT-PCR). Myofibroblasts differentiation and macrophage recruitment were identified by immunofluorescence. The protein expression of MMP9 was detected by immunohistochemistry and Western blot. Results: We identified ten hub genes (Fos, Spp1, Fn1, Ctgf, Tlr2, Itgb2, Itgax, Ccl2, Mmp9, and Serpine1) and 3 TFs (FOS, IRF4, and SPI1) that may be crucial (particularly FOS) for the FBR. Furthermore, we identified multiple differentially expressed genes involved in several important biological processes, including leukocyte migration, cytokine‒ cytokine receptor interaction, phagocytosis, extracellular matrix (ECM) organization, and angiogenesis. We also identified potentially significant signaling pathways, including cytokine‒cytokine receptor interaction, phagosome, ECM‒receptor interaction, complement and coagulation cascades, the IL-17 signaling pathway, and the PI3K‒Akt signaling pathway. In addition, qRT-PCR confirmed the expression patterns of the TFs and hub genes, Western blot and immunohistochemistry validated the expression patterns of MMP9. Conclusion: We generated a comprehensive overview of the gene networks underlying the FBR evoked by silicone implants. Moreover, we identified specific molecular and signaling pathways that may perform key functions in the silicone implant-induced FBR. Our results provide significant insights into the molecular mechanisms underlying silicone-induced FBR and determine novel therapeutic targets to reduce complications related to silicone implantation.

Investigation of pristine and B/N/Pt/Au/Pd doped single-walled carbon nanotube as phosgene gas sensor: A first-principles analysis

The present work investigates a novel CNT based sensor for detection of highly toxic phosgene gas, which is widely used as a chemical agent. The investigation is performed via first-principle means in the vicinity of Density Functional Theory (DFT) and Non-Equilibrium Green’s Function (NEGF) formalisms. Though the pristine CNT is less reactive towards the phosgene gas, the near valence (B and N) and transition metal (Pt/Au/Pd) doped CNTs show very good reactivity, and the sensing mechanism is guided by Van der Waals interaction based physisorption phenomenon. The sensing mechanism is assessed with the help of various properties/parameters which include adsorption energies, electronic nature, density of states, charge transfer, electrical transport (I-V), recovery time and sensitivity. Unlike the pristine CNT, the doped CNTs exhibited significant sensing behaviour towards the phosgene, especially the transition metal dopants as witnessed from the I-V characteristics. Au-doped CNT offers tremendous reduction in the drive current on adsorption of phosgene gas, which can be used as an electronic fingerprint of detection. In particular, the Pd-doped CNT exhibits superior sensing behaviour in comparison to the other considered dopants, owing to its significant variation in the I-V, a Mulliken charge transfer of 0.24e, excellent sensitivity of 134.75 %, and very less recovery time of 8.9 ns. Thus, the transition metals (in particular Pd) doped CNTs could prove useful for the design of CNT based physical sensors to detect phosgene gas in various industries such as defence sector where phosgene is used as a chemical warfare agent, and in chemical sector where it is used as a precursor to synthesize several chemicals.

Ti, Ni, and Cu decorated borospherene as potential molecular sensor for phosgene

The interaction of phosgene molecule on pristine borospherene (B40) and decorated B40 with Ti, Ni, and Cu atoms was studied using density functional theory (DFT). In this study, the adsorption energy, dipole moment, charges from natural bond orbitals (NBO), frontier molecular orbitals (FMOs), electron localization function (ELF), density of states (DOS), projected density of states (PDOS) and thermodynamic parameters were analyzed. Our results reveal that the adsorption energy and electric conductivity of phosgene on decorated B40 increase, so the sensitivity of decorated B40 may be improved towards phosgene. Therefore, Ti decorated B40 is a good sensor to improve their sensitivity towards phosgene gas.

Derivation of thresholds for inhaled chemically reactive irritants: Searching for substance-specific common denominators for read-across prediction

Emergency response planning guideline values are used to protect the public when there has been a short-term chemical release. These values serve the purpose of identifying areas where a hazard exists if the concentration of hazardous chemicals is exceeded for the specified exposure duration. This paper focuses on carbonyl chlorides, a class of highly irritant/corrosive chemical intermediates characterized by the reactive moiety R–COCl. Despite their unifying property of reacting with nucleophilic biopolymers/peptides lining the airways of the respiratory tract, their adverse outcome pathway (AOP), in addition to surface area dose, appears to be dominated by their site(s) of major deposition (liquid) or retention (gas) within the respiratory tract. Thus, the physicochemical properties “phase” and “lipophilicity” become more decisive for the AOP than the chemical structure. This complicates the grouping of portal-of-entry irritant chemicals for the read-across prediction of chemicals, especially those with semivolatile properties. Phosgene (COCl2) served as a template to predict emergency response planning levels 2 (non-incapacitating, reversible injury) and 3 (nonlethal) for related chemicals such as SOCl2, formates, and acid chlorides. A rationale and guide to the systematic characterization of uncertainties associated with the lung region, water solubility of the vapor phase, and chemical specificity is given. The approach described in this paper highlights the regional differences and outcomes that are phenotypically described as irritation of the respiratory tract. Especially for such a data-lean group of chemicals, reliable read-across predictions could reduce the uncertainty associated with the derivation of values used for emergency-related risk assessment and management. Likewise, the approach suggested could improve the grouping and categorization of such chemicals, providing a means to reduce animal testing with potentially corrosive chemicals. Overall, the course taken for read-across predictions provided valid estimates as long as emphasis was directed to the physicochemical properties determining the most critical regional injury within the respiratory tract.

Luteolin Potentially Treating Prostate Cancer and COVID-19 Analyzed by the Bioinformatics Approach: Clinical Findings and Drug Targets.

Coronavirus disease 2019 (COVID-19) is a serious epidemic, characterized by potential mutation and can bring about poor vaccine efficiency. It is evidenced that patients with malignancies, including prostate cancer (PC), may be highly vulnerable to the SARS-CoV-2 infection. Currently, there are no existing drugs that can cure PC and COVID-19. Luteolin can potentially be employed for COVID-19 treatment and serve as a potent anticancer agent. Our present study was conducted to discover the possible drug target and curative mechanism of luteolin to serve as treatment for PC and COVID-19. The differential gene expression of PC cases was determined via RNA sequencing. The application of network pharmacology and molecular docking aimed to exhibit the drug targets and pharmacological mechanisms of luteolin. In this study, we found the top 20 up- and downregulated gene expressions in PC patients. Enrichment data demonstrated anti-inflammatory effects, where improvement of metabolism and enhancement of immunity were the main functions and mechanism of luteolin in treating PC and COVID-19, characterized by associated signaling pathways. Additional core drug targets, including MPO and FOS genes, were computationally identified accordingly. In conclusion, luteolin may be a promising treatment for PC and COVID-19 based on bioinformatics findings, prior to future clinical validation and application.

Identifying of miRNA-mRNA Regulatory Networks Associated with Acute Kidney Injury by Weighted Gene Co-Expression Network Analysis.

BackgroundAcute kidney injury (AKI) is a clinical emergency characterized by a dramatic decline in renal function and the accumulation of metabolic waste products in the body, with a high morbidity and mortality rate. The pathogenesis of AKI remains unclear and there are no effective treatment options.MethodsWe aimed to identify critical genes involved in the pathogenesis of AKI and construct a miRNA–mRNA regulatory network using gene expression data downloaded from Gene Expression Omnibus (GSE85957) for 38 kidneys of AKI and 19 control rats and cisplatin treated kidneys of 3 AKI and 3 control rats. Data in GSE85957 were processed using weighted gene co-expression network analysis (WGCNA), and biological function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to analyze the functions associated with critical genes.ResultsTwenty-eight modules in the GSE85957 dataset were identified by WGCNA, of which 103 genes in the orange module and 30 genes in the black module were closely associated with AKI and dose. Biological function analysis of genes in the orange and black modules revealed that skeletal muscle cell differentiation, tissue development and organ development were involved in the pathological changes of AKI. Combining with our experimentally processed AKI rat kidney data, eight genes (Atf3, Egr1, Egr2, Fos, Fosb, Gdf15, Serpine1 and Nr1d1) were identified as potential biomarkers of AKI, and miRNA–mRNA regulatory networks were constructed based on the above eight critical genes. Further tissue validation revealed that Egr1 and Fos were highly expressed in AKI.ConclusionOur study identified potential biomarkers of AKI and constructed an associated miRNA–mRNA regulatory network, which may provide new insights into the molecular pathogenesis of AKI.

The initial expression alterations occurring to transcription factors during the formation of breast cancer: Evidence from bioinformatics.

BackgroundBreast cancer (BC) is the leading malignancy among women worldwide.AimThis work aimed to present a comprehensively bioinformatic analysis of gene expression profiles and to identify the hub genes during BC tumorigenesis, providing potential biomarkers and targets for the diagnosis and therapy of BC.Materials & MethodsIn this study, multiple public databases, bioinformatics approaches, and online analytical tools were employed and the real‐time reverse transcription polymerase chain reaction was implemented.ResultsFirst, we identified 10, 107, and 3869 differentially expressed genes (DEGs) from three gene expression datasets (GSE9574, GSE15852, and GSE42568, covering normal, para‐cancerous, and BC samples, respectively), and investigated different biological functions and pathways involved. Then, we screened out 8, 16, and 29 module genes from these DEGs, respectively. Next, 10 candidate genes were determined through expression and survival analyses. We noted that seven candidate genes JUN, FOS, FOSB, EGR1, ZFP36, CFD, and PPARG were downregulated in BC compared to normal tissues and lower expressed in aggressive types of BC (basal, HER2+, and luminal B), TP53 mutation group, younger patients, higher stage BC, and lymph node metastasis BC, while CD27, PSMB9, and SELL were upregulated. The present study discovered that the expression levels of these candidate genes were correlated with the infiltration of immune cells (CD8+ T cell, macrophage, natural killer [NK] cell, and cancer‐associated fibroblast) in BC, as well as biomarkers of immune cells and immune checkpoints. We also revealed that promoter methylation, amplification, and deep deletion might contribute to the abnormal expressions of candidate genes. Moreover, we illustrated downstream‐targeted genes of JUN, FOS, FOSB, EGR1, and ZFP36 and demonstrated that these targeted genes were involved in “positive regulation of cell death”, “pathways in cancer”, “PI3K‐Akt signaling pathway”, and so on.Discussion & ConclusionWe presented differential gene expression profiles among normal, para‐cancerous, and BC tissues and further identified candidate genes that might contribute to tumorigenesis and progression of BC, as potential diagnostic and prognostic targets for BC patients.

Analysis and Validation of Hub Genes in Blood Monocytes of Postmenopausal Osteoporosis Patients.

Osteoporosis is a common systemic bone disease caused by the imbalance between osteogenic activity and osteoclastic activity. Aged women are at higher risk of osteoporosis, partly because of estrogen deficiency. However, the underlying mechanism of how estrogen deficiency affects osteoclast activity has not yet been well elucidated. In this study, GSE2208 and GSE56815 datasets were downloaded from GEO database with 25 PreH BMD women and 25 PostL BMD women in total. The RRA algorithm determined 38 downregulated DEGs and 30 upregulated DEGs. Through GO analysis, we found that downregulated DEGs were mainly enriched in myeloid cell differentiation, cytokine-related functions while upregulated DEGs enriched in immune-related biological processes; pathways like Notch signaling and MAPK activation were found in KEGG/Rectome pathway database; a PPI network which contains 66 nodes and 91 edges was constructed and three Modules were obtained by Mcode; Correlation analysis helped us to find highly correlated genes in each module. Moreover, three hub genes FOS, PTPN6, and CTSD were captured by Cytohubba. Finally, the hub genes were further confirmed in blood monocytes of ovariectomy (OVX) rats by real-time PCR assay. In conclusion, the integrative bioinformatics analysis and real-time PCR analysis were utilized to offer fresh light into the role of monocytes in premenopausal osteoporosis and identified FOS, PTPN6, and CTSD as potential biomarkers for postmenopausal osteoporosis.