Adrenoceptor Beta Research Articles

Effect of isoproterenol, a β-adrenergic agonist, on the differentiation of insulin-producing pancreatic β cells derived from human pluripotent stem cells

Research on islet replacement through the differentiation of functionally matured insulin-producing β-like cells for the treatment of diabetes presents a significant challenge. Neural signals in β cell differentiation significantly impact the pancreatic microenvironment in glucose metabolism, but they are not fully understood. In this study, isoproterenol, a β adrenoreceptor agonist, was introduced into pancreatic progenitor cells, derived from human pluripotent stem cells in vitro, undergoing endocrine differentiation, using 2-dimensional (2D) and 3-dimensional (3D) differentiation protocols. This resulted in increased insulin and C-peptide secretion, along with elevated expression of key pancreatic beta cell transcription factors, including PDX-1, NKX6.1, and MAFA, and improved function, demonstrated by increased responsiveness to glucose determined via a glucose-stimulated insulin secretion test. Moreover, RNA transcriptome analysis of isoproterenol-treated endocrine progenitors facilitated the identification of biological pathways and genes that contribute to mature beta cell differentiation efficiency correlated with neural signals, such as adrenoceptor beta 1, calcium/calmodulin dependent protein kinase II alpha, phospholipase C delta 4, and neurotrophic receptor tyrosine kinase 1. Among those genes, calcium/calmodulin dependent protein kinase II alpha was suggested as the most notable gene involved in the isoproterenol mechanism through inhibitor assays. This study illustrates that isoproterenol significantly enhances endocrine differentiation and underscores its effects on stem cell-derived beta cell maturation, emphasizing its therapeutic potential for the treatment of diabetes.

Intrinsic ADRB2 inhibition improves CAR-T cell therapy efficacy against prostate cancer

Chimeric antigen receptor (CAR)-T cell therapy has shown limited success in patients with solid tumors. Recent invitro and invivo data have shown that adrenoceptor beta-2 (ADRB2) is a novel checkpoint receptor that inhibits Tcell-mediated anti-tumor responses. To inhibit ADRB2-mediated inhibitory signaling, we downregulated ADRB2 in CAR-T (shβ2-CAR-T) cells via RNA interference, assessed different parameters, and compared them with conventional second-generation CAR-T cells. ADRB2 knockdown CAR-T cells exhibited enhanced cytotoxicity against prostate cancer cell lines invitro, by increasing CD69, CD107a, GzmB, IFN-γ, T-bet, and GLUT-1. In addition, ADRB2 deficiency led to improved proliferation, increased CD8/CD4 Tcell ratio, and decreased apoptosis in CAR-T cells. shβ2-CAR-T cells expressed more Bcl-2 and led to the generation of more significant proportions of T central memory cells. Finally, the ZAP-70/NF-κB signaling axis was shown to be responsible for the improved functions of novel CAR-T cells. In tumor-bearing mice, shβ2-CAR-T cells performed better than conventional CAR-T cells in eradicating prostate tumors. The study provides the basis for future clinical and translational CAR-T cell research to focus on adrenergic stress-mediated challenges in the tumor microenvironment of stressed tumors.

Differential expression of ADRB1 causes different responses to norepinephrine in adipocytes of Duroc-Landrace-Yorkshire pigs and min pigs

Research has shown that pigs from different regions exhibit varying responses to cold stimuli. Typically, cold stimuli induce browning of white adipose tissue mediated by adrenaline, promoting non-shivering thermogenesis. However, the molecular mechanisms underlying differential response of pig breeds to norepinephrine are unclear.The aim of this study was to investigate the differences and molecular mechanisms of the effects of norepinephrine (NE) treatment on adipocytes of Min pigs (a cold-resistant pig breed) and Duroc-Landrace-Yorkshire (DLY) pigs. Real time-qPCR, western blot, and immunofluorescence were performed following NE treatment on cell cultures of adipocytes originating from Min pigs (n = 3) and DLY pigs (n = 3) to assess the expressions of adipogenesis markers, beige fat markers, and mitochondrial biogenesis markers. The results showed that NE did not affect browning of adipocytes in DLY pigs, whereas promoted browning of adipocytes in Min pigs. Further, the expression of ADRB1 (Adrenoceptor Beta 1, ADRB1) was higher in subcutaneous adipose tissue and adipocytes of Min pigs than those of DLY pigs. Overexpression of ADRB1 in DLY pig adipocytes enhanced sensitivity to NE, exhibiting decreased adipogenesis markers, upregulated beige fat markers, and increased mitochondrial biogenesis. Conversely, adipocytes treated with ADRB1 antagonist in Min pigs resulted in decreased cellular sensitivity to NE. Further studies revealed differential CpG island methylation in ADRB1 promoter region, with lower methylation levels in Min pigs compared to DLY pigs. In conclusion, differential methylation of the ADRB1 promoter region leads to different ADRB1 expression, resulting in varying responsiveness to NE in adipocytes of two pig breeds. Our results provide new insights for further analysis of the differential cold responsiveness in pig breeds from different regions.

Chronic stress promotes gastric cancer progression via the adrenoceptor beta 2/PlexinA1 pathway.

Chronic stress is a common emotional disorder in cancer patients. Chronic stress promotes progression of gastric cancer (GC) and leads to poor outcomes. However, the underlying mechanisms remain not clear. Herein, we explored the possible mechanisms of chronic stress in GC progression. The Cancer Genome Atlas (TCGA) datasets were analyzed for differentially expressed genes. Clinical data of GC were evaluated for their association with PlexinA1 using TCGAand Kaplan-Meier-plotter databases. Chronic stress of GC patients was evaluated using the Self-Rating Anxiety Scale and Self-Rating Depression Scale. Chronic unpredictable mild stress (CUMS) was used to induce chronic stress in mice. Gastric xenograft tumor was constructed using the sewing method. Chronic stress-like behaviors were assessed using light/dark box and tail suspension tests. Protein expression was detected using immunohistochemistry and Western blot analysis. Analyses of TCGA and the Kaplan-Meier-plotter databases showed that patients with high levels of PlexinA1 in GC had worse overall survival than those with low levels of PlexinA1. A total of 36 GC patients were enrolled in the study, and about 33% of the patients had chronic stress. Compared with patients without chronic stress, higher expression levels of adrenoceptor beta 2 and PlexinA1 were observed in patients with chronic stress. The tumor size in mice under CUMS was significantly increased compared with the control mice. Adrenoceptor beta 2, PlexinA1, N-cadherin, and alpha-smooth muscle actin, as well as Ki67 were highly expressed in the tumors of CUMS group. However, E-cadherin was lowly expressed in the tumors of CUMS group. Importantly, chemical sympathectomy with 6-hydroxydopamineor treatment with a selective β2 adrenergic receptor antagonist (ICI118,551) could reverse these effects. Our findings suggest that chronic stress plays an important role in GC progression and there is a potential for blocking the epinephrine-β2AR/PlexinA1 pathway in the treatment of GC.

Влияние генов ADRB2 и PPARGC1A на развитие физического качества «выносливость» у единоборцев города Перми

Knowledge of genetic predisposition to certain types of sport activities will help improve the development of important physical qualities, and will also allow of scientifically based selection of the most promising athletes and adjustment of their training process. The purpose of this study is to identify the relationship between polymorphic variants of the ADRB2 (Adrenoceptor Beta 2) and PPARGC1A (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha) genes associated with endurance in athletes involved in jiu-jitsu and freestyle wrestling and schoolchildren not involved in sports. The sample for the investigation included 100 people, divided into Group I, which included martial artists, and a comparison group (Group II), which consisted of schoolchildren who did not participate sports. Studies were conducted using real-time polymerase chain reaction (RT-PCR) in subjects aged 10 to 16 years, and polymorphisms G/A of the PPARGC1A gene (rs8192678) and A/G of the ADRB2 gene (rs1042713) were identified. An analysis of the relationship between allelic variants of genes in martial artists and the comparison group was carried out. Significant differences were established between Group I and Group II for genotype G/G (Fop 3.13>1.96 at p=0.05) and genotype G/A (Fop 2.76>1.96 at p=0.05) of the PPARGC1A gene. For athletes involved in jiu-jitsu and freestyle wrestling, it has been shown that genotypes G/G and G/A of the PPARGC1A gene can be used as markers to predict the formation of the physical quality endurance. The frequency of the total genetic score (TGS) calculated for the physical quality endurance based on the polymorphism of the ADRB2 and PPARGC1A genes in 100 subjects, varied from 0 to 100. Genetic analysis data is necessary in the process of training martial artists in sports schools: based on this data, it is possible to create individual training programs taking into account the genotype and physical fitness characteristics of a particular athlete.

P54-2 Salmonella inhibition tumor metastasis by down-regulation of adrenoceptor beta 3

P54-2 Salmonella inhibition tumor metastasis by down-regulation of adrenoceptor beta 3

Comprehensive analysis of transcriptomic and metabolomic profiles uncovered the age-induced dynamic development pattern of subcutaneous fat in Ningxiang pig

Enhancing meat production and quality is the eternal theme for pig breeding industries. Fat deposition has always been the focus of research in practical production because it is closely linked to pig production efficiency and pork quality. In the current study, multi-omics techniques were performed to explore the modulatory mechanisms of backfat (BF) accumulation at three core developmental stages for Ningxiang pigs. Our results identified that 15 differentially expressed genes (DEGs) and 9 significantly changed metabolites (SCMs) contributed to the BF development via the cAMP signaling pathway, regulation of lipolysis in adipocytes, and biosynthesis of unsaturated fatty acids. Herein, we found a series of candidate genes such as adrenoceptor beta 1 (ADRB1), adenylate cyclase 5 (ADCY5), ATPase Na+/K+ transporting subunit beta 1 (ATP1B1), ATPase plasma membrane Ca2+ transporting 3 (ATP2B3), ATPase Na+/K+ transporting subunit alpha 2 (ATP1A2), perilipin 1 (PLIN1), patatin like phospholipase domain containing 3 (PNPLA3), ELOVL fatty acid elongase 5 (ELOVL5) and metabolites like epinephrine, cAMP, arachidonic acid, oleic acid, linoleic acid, and docosahexaenoic acid existed age-specificeffects and played important roles in lipolysis, fat accumulation, and fatty acid composition. Our findings provide a reference for molecular mechanisms in BF tissue development and the optimization of carcass quality.

A Review of Genes Associated with Obesity Susceptibility: Findings from Association Studies

Obesity is described as the accumulation of excess body fat. Several health issues are caused by excess fat, including cancer, type 2 diabetes, and cardiovascular disease. Additionally, obesity rates among schoolchildren and young adults are rising globally, putting young people at risk of chronic diseases. Genetics, epigenetic modification, epigenomics, and environmental factors influence inheritance patterns significantly. This systematic study aimed to classify and investigate the polymorphisms of novel candidate obesity genes. Several genes have been suggested, includingat mass and obesity-associated gene (FTO), leptin gene (LEP), leptin receptor gene (LEPR), peroxisome proliferatoractivated receptor gamma gene (PPARG), melanocortin 4 receptor (MC4R), insulin-induced gene 2 (INSIG2), proprotein convertase subtilisin/kexin type 1 (PCSK1), adrenoceptor beta 2 (ADRB2), and uncoupling protein 2 (UCP2). The study’s literature review identified genes in scientific papers published in databases such as Web of Science, PubMed, Google Scholar, Embase, and others over the past three decades. There is evidence that genetic variations contribute to childhood obesity, adolescent obesity, and young adult obesity. Identifying functional differences and further defining the implicated molecularly and physiologically involved genes andpathways in efficient therapeutic approaches in fighting. Technological advances have recently demonstrated that genetic changes and mutations can be used as biological markers, risk indicators, and therapeutic targets.

Transcriptomic analysis of the effects of the HPV18 E6E7 gene on the cell death mode in esophageal squamous cell carcinoma.

Human papillomavirus (HPV) infection is one of the main causes of esophageal carcinoma (ESCA), and its carcinogenic mechanisms in ESCA require further investigation. E6 and E7 are HPV oncogenes, and their genomic integration is a crucial reason for the transformation of host cells into cancer cells. In order to reveal the role of oncogenes E6 and E7 in ESCA cells, the RNA-Seq raw data for HPV18-positive and -negative esophageal squamous cell carcinoma (ESCC) samples derived from the NCBI BioProject database were analyzed, and the differentially expressed genes were identified. Moreover, differentially expressed genes were enriched significantly in multiple cell death pathways, including apoptosis (cyclin-dependent kinase inhibitor 2A, plakophilin 1 and desmoglein 3), pyroptosis (gasdermin A, gasdermin C, NLR family pyrin domain containing 3, absent in melanoma 2, NLR family pyrin domain containing 1 and Toll like receptor 1) and autophagy (Unc-51 like autophagy activating kinase 1, adrenoceptor beta 2). Consequently, the effects of cisplatin-induced apoptosis and Hank's balanced salt solution-induced autophagy, and α-ketoglutarate-induced pyroptosis in the ESCC-expressing E6 and E7 cells were verified. Therefore, the expression of E6E7 may culminate in the inhibition of multiple cell death modes, which may also be one of the mechanisms of oncogene-induced carcinogenesis.

Preliminary Study of the Distinctive Mechanism of Shenqi Compound in Treating Rats with Type 2 Diabetes Mellitus by Comparing with Metformin.

In China, traditional Chinese medicine (TCM) has been used to treat type 2 diabetes mellitus (T2DM) for centuries. To investigate how the TCM ShenQi (SQC) formulation differs from metformin, four rat groups, including control, model, T2DM rats treated using SQC (SQC group), and T2DM rats treated using metformin (Met group), were constructed. The differentially expressed genes (DEGs) between SQC and metformin groups were screened, and the co-expression modules of the DEGs were constructed based on the weighted correlation network analysis (WGCNA) method. The correlation between modules and metabolic pathways was also calculated. The potential gene targets of SQC were obtained via the TCM systems pharmacology analysis. A total of 962 DEGs between SQC and Met groups were screened, and these DEGs were significantly enriched in various functions, such as sensory perception of the chemical stimulus, NADH dehydrogenase (ubiquinone) activity, and positive regulation of the fatty acid metabolic process. In addition, seven co-expression modules were constructed after the redundancy-reduced process. Four of these modules involved specific activated or inhibited metabolic pathways. Moreover, 334 effective ingredients of SQC herbs were collected, and four genes (RNASE1 (ribonuclease A family member 1, pancreatic), ADRB1 (adrenoceptor beta 1), PPIF (peptidylprolyl isomerase F), and ALDH1B1 (aldehyde dehydrogenase 1 family member B1)) were identified as potential targets of SQC. Comparing SQC with metformin to treat T2DM rats revealed several potential gene targets. These genes provide clues for elucidating the therapeutic mechanisms of SQC.

Integrated network pharmacology and molecular docking analyses of the mechanisms underlying the antihypertensive effects of lotusine

Hypertension is a modifiable cardiovascular risk factor and cause of death worldwide. Lotusine, an alkaloid extracted from a plant used in traditional Chinese Medicine, has shown anti-hypertensive effects. However, its therapeutic efficacy requires further investigation. We adopted integrated network pharmacology and molecular docking approaches with the aim of investigating lotusine's antihypertensive effects and mechanisms of action in rat models. After identifying the optimal intravenous dosage, we observed the effects of lotusine administration on two-kidney, one-clip (2K1C) rats and spontaneously hypertensive rats (SHRs). Based on network pharmacology and molecular docking analyses, we measured renal sympathetic nerve activity (RSNA) to evaluate lotusine's effect. Finally, an abdominal aortic coarctation (AAC) model was established to evaluate lotusine's long-term effects. The network pharmacology analysis identified 21 intersection targets; of these, 17 were also implicated by the neuroactive live receiver interaction. Further integrated analysis showed high lotusine affinity for the cholinergic receptor nicotinic alpha 2 subunit, adrenoceptor beta 2, and adrenoceptor alpha 1B. Blood pressure of the 2K1C rats and SHRs decreased after treatment with 2.0 and 4.0 mg/kg of lotusine (P < 0.001 versus saline control). We also observed RSNA decreases consistent with the network pharmacology and molecular docking analysis results. Results from the AAC rat model indicated that myocardial hypertrophy was decreased with lotusine administration, demonstrated by echocardiography and hematoxylin and eosin and Masson staining. This study provides insights into the antihypertensive effects and underlying mechanisms of lotusine; lotusine may exert long-term protective effects against myocardial hypertrophy caused by elevated blood pressure.

ADRB2 Regulates the Proliferation and Metastasis of Gastrointestinal Stromal Tumor Cells by Enhancing the ETV1-c-KIT Signaling.

Gastrointestinal stromal tumor (GIST) originates from a pacemaker cell, the Cajal cell. However, little is known about the cancer neuroscience in GIST. In this study, we aimed to elucidate the clinical and biological roles of adrenoceptor beta 2 (ADRB2) in GIST. Immunohistochemistry was used to evaluate the expression of ADRB2 in GIST tissues. The biological effects of ADRB2 on GIST cell proliferation, migration, invasion, and apoptosis were explored using Cell Counting Kit -8, plate colony formation assay, transwell invasion assay, and flow cytometry. We also explored the growth and metastasis of xenograft tumors in nude mice. Western blotting was used to quantify protein expression and phosphorylation. ADRB2 is generally highly expressed in GIST. High ADRB2 expression was significantly associated with risk level, tumor size, mitotic count, and metastasis. Overexpression of ADRB2 promoted GIST cell proliferation, migration, invasion, and apoptosis, while silencing ADRB2 expression showed the opposite effects. Furthermore, we found that silencing endogenous ADRB2 inhibited GIST progression and metastasis in nude mice. ADRB2-induced ETV1 upregulation enhanced the activation of c-KIT. ADRB2 plays an important role in the proliferation and metastasis of GIST and is expected to be a potential target for the treatment of GIST.

Pharmacogenetics in treatment of anthracycline-induced cardiotoxicity in women without prior cardiovascular diseases

Aim. To evaluate the role of polymorphisms in adrenoceptor beta 1 (ADRB1) (Arg389Gly, rs1801253) and angiotensin-converting enzyme (ACE) (I/D, rs4343) genes in assessing the effectiveness of β-blocker (carvedilol) and ACE inhibitor (enalapril) therapy in women with anthracycline-induced cardiotoxicity (AIC) without prior cardiovascular diseases (CVD) during 12-month follow-up.Materials and methods. A total of 82 women (average age 45.0 (42.0; 50.0) years) with AIC and without prior CVD were included in the study. Echocardiography was performed and serum levels of NT-proBNP were determined at baseline and at 12 months after the enrollment. Gene polymorphisms in ADRB1 and ACE genes were evaluated by polymerase chain reaction at baseline.Results. Carriers of the G/G genotype in the ADRB1 gene and G/G genotype in the ACE (I/D, rs4343) gene showed a significant increase in left ventricular ejection fraction (LVEF), a decrease in the size of the left ventricle (LV) and left atrium (LA), and a fall in the NT-proBNP level. Carriers of other genotypes had further progression of AIC which was manifested through a decrease in LVEF and an increase in the size of LV and LA.Conclusion. Evaluation of gene polymorphisms in ADRB1 (Arg389Gly, rs1801253) and ACE (I/D, rs4343) genes may be recommended before treatment initiation for AIC in women without prior CVD to determine who will benefit from carvedilol and enalapril therapy, as well as to identify a priority group of patients for personalized intensification and optimization of treatment for decreasing development of adverse cardiovascular events.

Hemangioma-related gene polymorphisms in the pathogenesis of intraventricular hemorrhage in preterm infants

PurposeThe aim of this study was to evaluate the possible relationship between four single nucleotide polymorphisms of hemangioma-linked genes encoding for anthrax toxin receptor 1 (ANTXR1 G976A), R kinase insert domain receptor (KDR T1444C), adrenoceptor beta 2 (ADRB C79CG), and insulin-like growth factor 1 receptor (IGF-1R G3174A) and the occurrence of IVH in a population of preterm infants.MethodsThe study includes a population of 105 infants born from 24 + 0 to 32 + 0 weeks of gestation and hospitalized at the Department of Neonatology (III level hospital) of Poznan University of Medical Science. Intraventricular hemorrhage was diagnosed with the use of cranial ultrasound. The classification of intraventricular bleeding was based on the Papile IVH classification.ResultsThe incidence of IVH was higher in infants with lower birth weight, lower APGAR scores, and low birth weight. The study revealed that IVH was approximately two times less likely to occur in infants with the allele G of IGF-1R 3174G > A.ConclusionIdentifying susceptible premature infants through genetic analysis could be a potential way to alleviate severe IVH and its subsequent consequences. Further research examining a wider range of relevant gene polymorphisms could help highlight any genetic patterns in this deleterious bleeding complication.

Big Data analytics for improved prediction of ligand binding and conformational selection.

This research introduces new machine learning and deep learning approaches, collectively referred to as Big Data analytics techniques that are unique to address the protein conformational selection mechanism for protein:ligands complexes. The novel Big Data analytics techniques presented in this work enables efficient data processing of a large number of protein:ligand complexes, and provides better identification of specific protein properties that are responsible for a high probability of correct prediction of protein:ligand binding. The GPCR proteins ADORA2A (Adenosine A2a Receptor), ADRB2 (Adrenoceptor Beta 2), OPRD1 (Opioid receptor Delta 1) and OPRK1 (Opioid Receptor Kappa 1) are examined in this study using Big Data analytics techniques, which can efficiently process a huge ensemble of protein conformations, and significantly enhance the prediction of binding protein conformation (i.e., the protein conformations that will be selected by the ligands for binding) about 10-38 times better than its random selection counterpart for protein conformation selection. In addition to providing a Big Data approach to the conformational selection mechanism, this also opens the door to the systematic identification of such "binding conformations" for proteins. The physico-chemical features that are useful in predicting the "binding conformations" are largely, but not entirely, shared among the test proteins, indicating that the biophysical properties that drive the conformation selection mechanism may, to an extent, be protein-specific for the protein properties used in this work.

10-Gingerol Enhances the Effect of Taxol in Triple-Negative Breast Cancer via Targeting ADRB2 Signaling

Although paclitaxel is widely used in cancer treatment, severe side effects and drug resistance limit its clinical use. 10-gingerol (10-G) is a natural compound isolated from ginger, which displays anti-inflammatory, antioxidant, and antiproliferative properties. However, the chemotherapy-sensitization effect of 10-G on triple-negative breast cancer (TNBC) has not been fully clarified. This study is aimed at investigating the effect of 10-G on the paclitaxel sensitivity in TNBC, and its underlying mechanism. The study was determined through in vitro and in vivo experiments. Cell viability and proliferation were detected by cell counting kit 8 (CCK-8) and colony formation. To detect cell apoptosis, flow cytometry and TUNEL were used. The expression of proteins was detected by Western blotting and immunohistochemistry. The molecular docking and gene knockout were corroborated by interactions between 10-G and adrenoceptor Beta 2 (ADRB2). The body weight of mice, histopathology and organs (kidney and spleen) coefficients were used to monitor the drug toxicities. In vitro, 10-G increased the sensitivity of TNBC cells to paclitaxel, and could synergistically promote the apoptosis of TNBC cells induced by paclitaxel. In combination with molecular docking and lentivirus knockdown studies, ADRB2 was identified as a 10-G binding protein. 10-G inhibited ADRB2 by binding to the active site of ADRB2. Knockdown of ADRB2 reduces the proliferation activity of TNBC cells but also attenuates the sensitizing effects of 10-G to paclitaxel. Western blotting and immunohistochemistry showed that 10-G played an anti-proliferation and chemotherapy-sensitizing role by inhibiting the ADRB2/ERK signal. Toxicity evaluation showed that 10-G would not increase hepatorenal toxicity with paclitaxel. This data suggests that 10-G may be used as a new chemotherapeutic synergist in combination with paclitaxel to enhance anticancer activity. The potential value of ADRB2 as a target for improving chemotherapy sensitivity was also emphasized.

Молекулярно-генетический анализ генов ADRB2, NOS3 и PPARGC1A у единоборцев города Перми

The study of genetic predisposition to certain types of sports activities will make it possible to sci-entifically select the most promising athletes and adjust their training process, since these data influence the formation of the physical qualities of athletes. The purpose of this study is to identify the relationship between pol-ymorphic variants of the ADRB2 (Adrenoceptor Beta 2), NOS3 (Nitric Oxide Synthase 3) и PPARGC1A (Peroxi-some Proliferator-Activated Receptor Gamma Coactivator 1-Alpha) genes associated with endurance in judo and freestyle wrestling athletes with different sports qualifications. The sample for the study included 50 ath-letes, of which 27 were athletes involved in judo at the «Vityaz» sports school, and 23 athletes involved in free-style wrestling at the «Planeta» sports and health club in the city of Perm. Depending on their sporting success, the combatants were distributed into Group I with high qualifications and into Group II with low qualifications. In 50 martial artists aged 10 to 16 years, laboratory research was carried out using real-time polymerase chain reaction (PCR-RT) and polymorphisms of three genes were identified: G/T polymorphism of the NOS3 gene (rs1799983), G/A polymorphism of the PPARGC1A gene (rs8192678) and A/G polymorphism of the ADRB2 gene (rs1042713). An analysis of the relationship between allelic variants of genes in martial artists and their sports qualifications was carried out. An analysis of the relationship between allelic variants of genes in martial artists and their sports qualifications was carried out; significant differences were established between Group I and Group II for genotype A/A (Fexp 2.98&gt;1.96 at p=0.05) and genotype G/G (Fexp 2.60&gt;1.96 at p=0.05) of the ADRB2 gene, and also for the G/A genotype of the PPARGC1A gene (Fexp 2.43&gt;1.96 at p=0.05). The frequency of occurrence of TGS, calculated for the physical quality “endurance”, based on the polymorphism of the ADRB2, NOS3 and PPARGC1A genes in 50 martial artists, ranged from 33 to 100. Combatants with the greatest TGS are highly qualified. The relationship between the two samples (Group I with high qualifications and Group II with low qualifications) and TGS, established based on the analysis of polymorphic positions of three genes (ADRB2, NOS3 and PPARGC1A) is statistically insignificant.

ADRB2 expression predicts the clinical outcomes and is associated with immune cells infiltration in lung adenocarcinoma.

The gene encoding beta2-adrenergic receptor (β2-AR), adrenoceptor beta 2 (ADRB2), has been reported to closely associated with various cancers. However, its role in lung adenocarcinoma (LUAD) remains controversial. This research shed light on the prognostic value of ADRB2 in LUAD and further explored its association with immune cell infiltration. ADRB2 was significantly decreased in LUAD. ADRB2 expression in LUAD was significantly correlated with gender, smoking status, T classification, and pathologic stage. Patients in the low ADRB2 expression group presented with significantly poorer overall survival (OS) and disease-specific survival (DSS). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) results showed that ADRB2 participates in immune response. The expression of ADRB2 was positively correlated with the infiltration level of most immune cells. Notably, ADRB2 is involved in LUAD progression partly by regulating the immune microenvironment, which may potentially serve as a significant prognostic biomarker as well as a potential drug target.

Cervical Cancer Imaging Features Associated With ADRB1 as a Risk Factor for Cerebral Neurovascular Metastases.

Bioinformatics tools are used to create a clinical prediction model for cervical cancer metastasis and to investigate the neurovascular-related genes that are involved in brain metastasis of cervical cancer. One hundred eighteen patients with cervical cancer were divided into two groups based on the presence or absence of metastases, and the clinical data and imaging findings of the two groups were compared retrospectively. The nomogram-based model was successfully constructed by taking into account four clinical characteristics (age, stage, N, and T) as well as one imaging characteristic (original_glszm_GrayLevelVariance Rad-score). In patients with cervical cancer, headaches and vomiting were more often reported in the brain metastasis group than in the other metastasis groups. According to the TCGA data, mRNA differential gene expression analysis of patients with cervical cancer revealed an increase in the expression of neurovascular-related gene Adrenoceptor Beta 1 (ADRB1) in the brain metastasis group. An analysis of the correlation between imaging features and ADRB1 expression revealed that ADRB1 expression was significantly higher in the low Rad-score group compared with the high Rad-score group (P = 0.025). Therefore, ADRB1 expression in cervical cancer was correlated with imaging features and was associated as a risk factor for cerebral neurovascular metastases. This study developed a nomogram prediction model for cervical cancer metastasis using age, stage, N, T and original_glszm_GrayLevelVariance. As a risk factor associated with the development of cerebral neurovascular metastases of cervical cancer, ADRB1 expression was significantly higher in brain metastases from cervical cancer.

Abstract 3349: In-silico analysis identifies the unique role of the ADRB2-USP20 axis in T cell lymphoma

Abstract T cell lymphoma represents an aggressive subgroup of lymphoma having a poor prognosis. Many factors, including psychological stress, define the onset/progression of the disease. Although psychological stress can cause several health problems, preclinical and clinical reports regarding its role in cancer have been mixed. Therefore, in this study, we sought to determine the role of psychological stress hormone in the progression of T cell lymphoma and provide a mechanistic framework of activity. Initially, we used the cBioportal and performed expression analysis of genes involved in stress pathways with large-scale cancer genomics TCGA datasets having nearly 10071 patient samples. Through a series of in-silico investigations, we identified Adrenoceptor Beta 2 (ADRB2), a key mediator of stress, highly expressed in T cell lymphoma compared to other tumors.Furthermore, the expression of ADRB2 was not gender-specific and equally represented in both males and females. String analysis further identified the interaction of ADRB2 with Ubiquitin carboxyl-terminal hydrolase 20 (USP20), which directly regulates Hypoxia-inducible factor 1-alpha (HIF1-A) and ADRB2. This regulation could lead to enhanced glucose metabolism to support T cell lymphoma growth and progression. Collectively, our in-silico findings suggest that psychological stress releases hormones that could modulate T cell lymphoma proliferation through the ADRB2-USP20 axis. Ongoing preclinical studies with stress hormones will be presented to provide undescribed mechanisms of their protumorigenic activity through the ADRB2-USP20 axis and their role in regulating cancer-specific metabolism. We sought to determine the role of psychological stress hormone These studies will provide an opportunity to learn the involvement of stress hormones in cancer progression and provide a framework for developing a novel approach for stress management during cancer. Citation Format: Rajan Kumar Tiwari, Ajay Kumar. In-silico analysis identifies the unique role of the ADRB2-USP20 axis in T cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3349.