keyword
https://read.qxmd.com/read/37866653/functional-implications-of-rs9373441-with-foxp3-treg-and-tr1-for-the-clinical-effectiveness-of-csdmards-in-rheumatoid-arthritis
#1
JOURNAL ARTICLE
Ting-Yu Hsieh, Jun-Fu Lin, Feng-Cheng Liu, Hsiang-Cheng Chen, Shan-Wen Lui, Yu-Tien Chang
Rheumatoid arthritis (RA) is characterized by a deficiency in regulatory T cells (Treg), which play a crucial role in immune regulation. While conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are widely used, there remains a challenge as efficacy varies among patients. In this genome-wide association study (GWAS) involving 410 RA patients, rs9373441 emerged as the most significantly linked single-nucleotide polymorphism (SNP) to csDMARDs response. This non-coding variant functions as a cis-acting regulatory element within the UTRN gene, which is associated with cortical erosion and osteoporosis...
October 20, 2023: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://read.qxmd.com/read/37524305/conserved-class-b-gpcr-activation-by-a-biased-intracellular-agonist
#2
JOURNAL ARTICLE
Li-Hua Zhao, Qian He, Qingning Yuan, Yimin Gu, Xinheng He, Hong Shan, Junrui Li, Kai Wang, Yang Li, Wen Hu, Kai Wu, Jianhua Shen, H Eric Xu
Class B G protein-coupled receptors (GPCRs), including glucagon-like receptor 1 (GLP-1R) and parathyroid hormone receptor 1 (PTH1R), are important drug targets1-5 . Injectable peptide drugs targeting these receptors have been developed but orally available small molecule drugs are hotly pursued 6,7 . Here we report the high-resolution structure of the human PTH1R in complex with the stimulatory G protein (Gs ) and a small molecule agonist, PCO371, which reveals an unexpected binding mode of PCO371 at the cytoplasmic interface of PTH1R with Gs ...
July 31, 2023: Nature
https://read.qxmd.com/read/37240884/parathyroid-hormone-pth-related-peptides-family-an-intriguing-role-in-the-central-nervous-system
#3
REVIEW
Cristina Dettori, Francesca Ronca, Marco Scalese, Federica Saponaro
Parathyroid Hormone (PTH) plays a crucial role in the maintenance of calcium homeostasis directly acting on bone and kidneys and indirectly on the intestine. However, a large family of PTH-related peptides exists that exerts other physiological effects on different tissues and organs, such as the Central Nervous System (CNS). In humans, PTH-related peptides are Parathyroid Hormone (PTH), PTH-like hormones (PTHrP and PTHLH), and tuberoinfundibular peptide of 39 (TIP39 or PTH2). With different affinities, these ligands can bind parathyroid receptor type 1 (PTH1R) and type 2 (PTH2R), which are part of the type II G-protein-coupled-receptors (GPCRs) family...
April 24, 2023: Journal of Personalized Medicine
https://read.qxmd.com/read/36856181/mum1l1-as-a-tumor-suppressor-and-potential-biomarker-in-ovarian-cancer-evidence-from-bioinformatics-analysis-and-basic-experiments
#4
JOURNAL ARTICLE
Lu Zhang, Xue Wu, Xue Fan, Hao Ai
Background Ovarian cancer (OC) is the most prevalent gynecologic malignancy, with high mortality rates. However, its pathogenesis remains unclear. The current study aimed to explore potential biomarkers and suppressor genes for diagnosing and treating OC. Methods Biochemical and bioinformatics approaches were used to detect differentially expressed genes (DEGs) in ovarian tissues via integration analysis. Kaplan-Meier plot analysis was performed to assess progression-free survival and overall survival according to DEGs...
March 1, 2023: Combinatorial Chemistry & High Throughput Screening
https://read.qxmd.com/read/36553445/genomic-analysis-of-gastrointestinal-parasite-resistance-in-akkaraman-sheep
#5
JOURNAL ARTICLE
Yunus Arzik, Mehmet Kizilaslan, Stephen N White, Lindsay M W Piel, Mehmet Ulaş Çınar
Genome-wide association studies (GWAS) have been used as an effective tool to understand the genetics of complex traits such as gastrointestinal parasite (GIP) resistance. The aim of this study was to understand the genetics of gastrointestinal parasite (nematodes, Moniezia spp. , Eimeria spp. ) resistance in Akkaraman sheep by performing genomic heritability estimations and conducting GWAS to uncover responsible genomic regions. This is one of the first studies to examine the genetic resistance of Akkaraman sheep to the tapeworm parasite...
November 22, 2022: Genes
https://read.qxmd.com/read/36260369/quantification-of-changes-in-human-islet-g-protein-coupled-receptor-mrna-expression-in-obesity
#6
JOURNAL ARTICLE
Zekun Lyu, Min Zhao, Patricio Atanes, Shanta Jean Persaud
BACKGROUND: G protein-coupled receptors (GPCRs) play crucial roles in regulating islet function, with Gαs- and Gαq-coupled receptors being linked to stimulation of insulin secretion. We have quantified mRNA expression of 384 non-olfactory GPCRs in islets isolated from lean and obese organ donors to determine alterations in islet GPCR mRNA expression in obesity. METHODS: RT-qPCR was used to quantify GPCR mRNAs relative to five reference genes (ACTB, GAPDH, PPIA, TBP, and TFRC) in human islets isolated from lean (BMI=22...
October 19, 2022: Diabetic Medicine: a Journal of the British Diabetic Association
https://read.qxmd.com/read/35499975/behavioural-actions-of-tuberoinfundibular-peptide-39-parathyroid-hormone-2
#7
REVIEW
Dávid Keller, Mumeko C Tsuda, Ted B Usdin, Arpád Dobolyi
Tuberoinfundibular peptide of 39 residues (TIP39) acts via its endogenous class B G-protein coupled receptorthe parathyroid hormone 2 receptor (PTH2R). Hence, it is also known as parathyroid hormone 2. The peptide is expressed in the brain by a small number of neurons with a highly restricted distribution, which in turn project to a large number of brain regions that contain PTH2R. This peptide neuromodulator system has been extensively investigated over the past 20 years including its behavioural actions, such as its role in the control of nociception, fear and fear incubation, anxiety and depression-like behaviours, and maternal and social behaviours...
March 28, 2022: Journal of Neuroendocrinology
https://read.qxmd.com/read/35410353/pth2r-is-related-to-cell-proliferation-and-migration-in-ovarian-cancer-a-multi-omics-analysis-of-bioinformatics-and-experiments
#8
JOURNAL ARTICLE
Wang Xiaowei, Lu Tong, Qu Yanjun, Fan Lili
BACKGROUND: Ovarian cancer is a common gynecological disease and seriously endangers women's health. Currently, there is still a lack of effective molecular markers for the diagnosis and treatment of ovarian cancer. The present study aimed to investigate the molecular markers associated with ovarian cancer. METHODS: The molecular and gene related to ovarian cancer were extracted from GEO database and TCGA database by bioinformatics, and the related genes and functions were further analyzed...
April 11, 2022: Cancer Cell International
https://read.qxmd.com/read/34353904/molecular-insights-into-differentiated-ligand-recognition-of-the-human-parathyroid-hormone-receptor-2
#9
JOURNAL ARTICLE
Xi Wang, Xi Cheng, Lihua Zhao, Yuzhe Wang, Chenyu Ye, Xinyu Zou, Antao Dai, Zhaotong Cong, Jian Chen, Qingtong Zhou, Tian Xia, Hualiang Jiang, H Eric Xu, Dehua Yang, Ming-Wei Wang
The parathyroid hormone receptor 2 (PTH2R) is a class B1 G protein-coupled receptor (GPCR) involved in the regulation of calcium transport, nociception mediation, and wound healing. Naturally occurring mutations in PTH2R were reported to cause hereditary diseases, including syndromic short stature. Here, we report the cryogenic electron microscopy structure of PTH2R bound to its endogenous ligand, tuberoinfundibular peptide (TIP39), and a heterotrimeric Gs protein at a global resolution of 2.8 Å. The structure reveals that TIP39 adopts a unique loop conformation at the N terminus and deeply inserts into the orthosteric ligand-binding pocket in the transmembrane domain...
August 10, 2021: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/33550301/asbestos-induced-lung-cancer-associated-snp-rs13383928-regulates-pth2r-expression-in-lung-tissue
#10
Yuan-Qing Meng, Qiang Shi, Si-Jing Zhu, Guang-Huan He, Shi-Jiao Zhang, Chang Sun
BACKGROUND: Lung cancer is one of the most common malignant tumors, and asbestos exposure was suggested to contribute to a proportion of lung cancer cases. Previous genome-wide gene-environment interaction analysis reported that rs13383928 was associated with asbestos-related lung cancer. However, the mechanism of this association was still unclear. METHODS: In the present study, we retrieved the genotype data from the 1,000 Genomes Project on single-nucleotide polymorphisms (SNPs) surrounding rs13383928 and analyzed the linkage disequilibrium (LD) pattern of this region...
February 5, 2021: Human Heredity
https://read.qxmd.com/read/33401985/identification-of-vascular-dementia-and-alzheimer-s-disease-hub-genes-expressed-in-the-frontal-lobe-and-temporal-cortex-by-weighted-co-expression-network-analysis-and-construction-of-a-protein-protein-interaction
#11
JOURNAL ARTICLE
Xiaodou Tian, Yao Qin, Yuling Tian, Xiaoyan Ge, Jing Cui, Hongjuan Han, Long Liu, Hongmei Yu
Background: It is difficult to distinguish cognitive decline due to AD from that sustained by cerebrovascular disease in view of the great overlap. It is uncertain in the molecular biological pathway behind AD and VaD. Objective: Our study aimed to explore the hub molecules and their associations with each other to identify potential biomarkers and therapeutic targets for the AD and VaD.Methods: We screened the differentially expressed genes of AD and VaD, used weighted gene co-expression network analysis and then constructed a VaD-AD-specific protein-protein interaction network with functional annotation to their related metabolic pathways...
October 2022: International Journal of Neuroscience
https://read.qxmd.com/read/33249322/development-and-characterization-of-a-novel-human-3d-model-of-bone-metastasis-from-breast-carcinoma-in-vitro-cultured
#12
JOURNAL ARTICLE
Francesca Salamanna, Veronica Borsari, Stefania Pagani, Giovanni Barbanti Brodano, Alessandro Gasbarrini, Milena Fini
Breast cancer frequently metastasizes to the skeleton causing significant morbidity. None of the therapeutic strategies used to manage breast cancer bone metastases are really curative. Here, we set-up a novel and advanced model by using fresh tissue from human vertebral bone metastasis from breast carcinoma patients able to retain the tumor microenvironment. The tissue model is based on an ex-vivo culture for up to 40 days and on a constant monitoring of tissue viability, gene expression profile (IL10, IL1b, MMP1, MMP7, PTH1R, PTH2R, TNF, ACP5, SPI1, VEGFA, CTSK, TGF-β) and histological and immunohistochemical analyses (CDH1/E-cadherin, CDH2/N-cadherin, KRT8/Cytokeratin 8, KRT18/Cytokeratin 18, Ki67, CASP3/Caspase 3, ESR1/Estrogen Receptor Alpha, CD68 and CD8)...
February 2021: Bone
https://read.qxmd.com/read/31423747/mental-effects-of-excess-parathyroid-hormone-in-hemodialysis-patients-a-possible-role-for-parathyroid-2-hormone-receptor
#13
JOURNAL ARTICLE
James Diskin, Charles J Diskin
Depression as measured by the kidney disease quality of life (KDQOL) form is known to be an independent risk factor for mortality dialysis patients. Excess parathyroid hormone (PTH) has long been associated with neuropsychiatric disturbances. Those psychiatric complications are currently attributed to hypercalcemia with very little evidence; however, with the discovery of the parathyroid hormone 2 receptor (PTH2R) in the brain which can be activated by PTH, PTH2R might indicate a direct effect of PTH. As secondary and tertiary hyperparathyroidism is common in dialysis patients where the serum calcium is low or normal, we chose to investigate a possible relationship between PTH levels and depression in dialysis patients...
August 18, 2019: Therapeutic Apheresis and Dialysis
https://read.qxmd.com/read/30661062/development-of-a-prognostic-index-based-on-an-immunogenomic-landscape-analysis-of-papillary-thyroid-cancer
#14
JOURNAL ARTICLE
Peng Lin, Yi-Nan Guo, Lin Shi, Xiao-Jiao Li, Hong Yang, Yun He, Qing Li, Yi-Wu Dang, Kang-Lai Wei, Gang Chen
BACKGROUND: Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer, and inflammation relates significantly to its initiation and prognosis. Systematic exploration of the immunogenomic landscape therein to assist in PTC prognosis is therefore urgent. The Cancer Genome Atlas (TCGA) project provides a large number of genetic PTC samples that enable a comprehensive and reliable immunogenomic study. METHODS: We integrated the expression profiles of immune-related genes (IRGs) and progression-free intervals (PFIs) in survival in 493 PTC patients based on the TCGA dataset...
January 20, 2019: Aging
https://read.qxmd.com/read/30486541/-study-on-mechanism-of-drynariae-rhizoma-in-treating-osteoporosis-with-integrative-pharmacology-perspective
#15
JOURNAL ARTICLE
Yi-Li Zhang, Bin Tang, Jun-Jie Jiang, Hao Shen, Yan-Ming Xie, Xu Wei
Drynariae Rhizoma has great significance in the clinical practice of osteoporosis treatment. Based on the perspective of integrative pharmacology, the study explored the mechanism of action of Drynariae Rhizoma in the treatment of osteoporosis. Six active components in Drynariae Rhizoma were obtained, mainly including glycosides and sterols. Taking the median of 2 times of "node connectivity" as the card value, the core node of the Chinese medicine target disease gene interaction network was selected. Based on this, three topological structural eigenvalues, such as "node connectivity" "node tightness" and "node connectivity" were calculated, thereby screening out four core targets of Drynariae Rhizoma treatment for osteoporosis, including thyroid parathyroid hormone 1 receptor (PTH1R), parathyroid hormone 2 receptor (PTH2R), calcitonin receptor gene (CALCR), and SPTBN1 gene (SPTBN1)...
October 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://read.qxmd.com/read/30214614/integrated-bioinformatic-analysis-of-microarray-data-reveals-shared-gene-signature-between-mds-and-aml
#16
JOURNAL ARTICLE
Zhen Zhang, Lin Zhao, Xijin Wei, Qiang Guo, Xiaoxiao Zhu, Ran Wei, Xunqiang Yin, Yunhong Zhang, Bin Wang, Xia Li
Myeloid disorders, especially myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), cause significant mobility and high mortality worldwide. Despite numerous attempts, the common molecular events underlying the development of MDS and AML remain to be established. In the present study, 18 microarray datasets were selected, and a meta-analysis was conducted to identify shared gene signatures and biological processes between MDS and AML. Using NetworkAnalyst, 191 upregulated and 139 downregulated genes were identified in MDS and AML, among which, PTH2R, TEC , and GPX1 were the most upregulated genes, while MME, RAG1 , and CD79B were mostly downregulated...
October 2018: Oncology Letters
https://read.qxmd.com/read/28735615/new-mechanisms-of-ecm-production-during-wound-healing-a-role-for-parathyroid-hormone-2-receptor-signaling
#17
REVIEW
Traci A Wilgus
Extracellular matrix deposition is required for wound healing. Studies by Sato et al. reveal a role for parathyroid hormone 2 receptor (PTH2R) in extracellular matrix production in wounds. Deficiencies in PTH2R or its ligand tuberoinfundibular peptide of 39 residues (TIP39) delayed repair, and TIP39 treatment accelerated healing. TIP39-PTH2R signaling induced decorin expression, which may explain the beneficial effects of PTH2R signaling on healing. These studies identify a novel role for PTH2R signaling in extracellular matrix production...
August 2017: Journal of Investigative Dermatology
https://read.qxmd.com/read/28454729/activation-of-parathyroid-hormone-2-receptor-induces-decorin-expression-and-promotes-wound-repair
#18
JOURNAL ARTICLE
Emi Sato, Ling-Juan Zhang, Robert A Dorschner, Christopher A Adase, Biswa P Choudhury, Richard L Gallo
In this study, we report that TIP39, a parathyroid hormone ligand family member that was recently identified to be expressed in the skin, can induce decorin expression and enhance wound repair. Topical treatment of mice with TIP39 accelerated wound repair, whereas TIP39-deficient mice had delayed repair that was associated with formation of abnormal collagen bundles. To study the potential mechanism responsible for the action of TIP39 in the dermis, fibroblasts were cultured in three-dimensional collagen gels, a process that results in enhanced decorin expression unless activated to differentiate to adipocytes, whereupon these cells reduce expression of several proteoglycans, including decorin...
August 2017: Journal of Investigative Dermatology
https://read.qxmd.com/read/27000502/the-parathyroid-hormone-second-receptor-pth2r-and-its-ligand-tuberoinfundibular-peptide-of-39-residues-tip39-regulate-intracellular-calcium-and-influence-keratinocyte-differentiation
#19
JOURNAL ARTICLE
Emi Sato, Jun Muto, Ling-Juan Zhang, Christopher A Adase, James A Sanford, Toshiya Takahashi, Teruaki Nakatsuji, Ted B Usdin, Richard L Gallo
Genes related to the parathyroid hormone (PTH) influence cutaneous immune defense and development, but the full functions of the PTH family in cutaneous biology remain incompletely understood. In this study, we examined the expression and potential functions of the PTH second receptor (PTH2R) and its ligand, the tuberoinfundibular peptide of 39 residues (TIP39), in the skin. TIP39 and PTH2R mRNA and protein were detectable in both human and mouse skin, and in cultured keratinocytes and adipocytes. TIP39 was observed in the basal layer of human skin, whereas PTH2R was detected in the spinous to granular layer...
July 2016: Journal of Investigative Dermatology
https://read.qxmd.com/read/26374166/a-genome-wide-association-study-reveals-a-quantitative-trait-locus-for-days-open-on-chromosome-2-in-japanese-black-cattle
#20
JOURNAL ARTICLE
Shinji Sasaki, Takayuki Ibi, Takatoshi Kojima, Yoshikazu Sugimoto
Days open (DO), which is the interval from calving to conception, is an important trait related to reproductive performance in cattle. To identify quantitative trait loci for DO in Japanese Black cattle, we conducted a genome-wide association study with 33,303 single nucleotide polymorphisms (SNPs) using 459 animals with extreme DO values selected from a larger group of 15,488 animals. We identified a SNP on bovine chromosome 2 (BTA2) that was associated with DO. After imputation using phased haplotype data inferred from 586 812 SNPs of 1041 Japanese Black cattle, six SNPs associated with DO were located in an 8...
February 2016: Animal Genetics
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