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Trends in Molecular Medicine Sep 2020
Topics: Humans; Molecular Medicine
PubMed: 32857967
DOI: 10.1016/j.molmed.2020.07.003 -
Med (New York, N.Y.) Feb 2021Studies of the major hemoglobin disorders, β-thalassemia and sickle cell disease (SCD), have laid a foundation for molecular medicine. While enormous progress has been... (Review)
Review
Studies of the major hemoglobin disorders, β-thalassemia and sickle cell disease (SCD), have laid a foundation for molecular medicine. While enormous progress has been made in understanding gene structure and regulation, translating molecular insights to therapy for the many individuals affected with these disorders has been challenging. Advances in three activities have recently converged to bring novel genetic and potentially curative treatments to clinical trials. First, improved lentiviral vectors for gene transfer into hematopoietic stem cells have revived somatic gene therapy for blood disorders. Second, elucidation of regulatory factors and mechanisms that control the normal developmental switch from fetal to adult hemoglobin has provided a route to reactivation of the fetal form for therapy. Third, revolutionary methods of gene engineering permit molecular insights to be leveraged for patients. Here I review how the promise of molecular medicine to bring transformative treatments to the clinical arena is finally being realized.
Topics: Adult; Genetic Therapy; Hemoglobinopathies; Hemoglobins; Humans; Molecular Medicine; beta-Thalassemia
PubMed: 33688634
DOI: 10.1016/j.medj.2020.12.011 -
The American Journal of Pathology Jul 2019The past decade has witnessed exponential growth in the generation of high-throughput human data across almost all known dimensions of biological systems. The discipline... (Review)
Review
The past decade has witnessed exponential growth in the generation of high-throughput human data across almost all known dimensions of biological systems. The discipline of network medicine has rapidly evolved in parallel, providing an unbiased, comprehensive biological framework through which to interrogate and integrate systematically these large-scale, multi-omic data to enhance our understanding of disease mechanisms and to design drugs that reflect a deep knowledge of molecular pathobiology. In this review, we discuss the key principles of network medicine and the human disease network and explore the latest applications of network medicine in this multi-omic era. We also highlight the current conceptual and technological challenges, which serve as exciting opportunities by which to improve and expand the network-based applications beyond the artificial boundaries of the current state of human pathobiology.
Topics: Humans; Pathology, Clinical; Pathology, Molecular
PubMed: 31014954
DOI: 10.1016/j.ajpath.2019.03.009 -
Zhonghua Bing Li Xue Za Zhi = Chinese... Jan 2022With the technological progresses and applications of human genome sequencing, bioinformatics analysis and data mining, and molecular pathology and artificial...
With the technological progresses and applications of human genome sequencing, bioinformatics analysis and data mining, and molecular pathology and artificial intelligence-assisted pathological diagnosis, the development of clinical medicine is moving towards the era of precision diagnosis and treatment. In the context of this era, the traditional diagnostic pathology is facing unprecedented opportunities and challenges in our history and is striving towards the "next-generation diagnostic pathology" (NGDP). NGDP is based on histomorphology and clinical data, and characterized by the combination of molecular detection and bioinformatics analysis, intelligent sampling and process quality control, intelligent diagnosis and remote consultation, lesion visualization and "non-invasive" pathology as well as other innovative cutting edge interdisciplinary technologies. The NGDP reports will include the results from multi-omics and cross-scale integrated diagnosis for final diagnosis. NGDP will also be applied for predicting disease progression and outcomes, and determining optional therapeutics as well as assessing treatment responses, so that a novel "golden standard" of disease diagnosis can be established. In the near fature, it is necessary to stimulate the innovative vitality of pathology disciplines, accelerate the maturity and application for NGDP, update the theory and technical system of pathology, and perform its important applicable role in the prevention, diagnosis, treatment of diseases so that the futher development of clinical medicine will be promoted and the strategy for maintenance of being healthy in China will be served.
Topics: Artificial Intelligence; China; Computational Biology; Humans; Pathology, Molecular
PubMed: 34979745
DOI: 10.3760/cma.j.cn112151-20211005-00726 -
American Journal of Respiratory and... Jun 2022Pulmonary arterial hypertension (PAH) is characterized by structural remodeling of pulmonary arteries and arterioles. Underlying biological processes are likely...
Pulmonary arterial hypertension (PAH) is characterized by structural remodeling of pulmonary arteries and arterioles. Underlying biological processes are likely reflected in a perturbation of circulating proteins. To quantify and analyze the plasma proteome of patients with PAH using inherited genetic variation to inform on underlying molecular drivers. An aptamer-based assay was used to measure plasma proteins in 357 patients with idiopathic or heritable PAH, 103 healthy volunteers, and 23 relatives of patients with PAH. In discovery and replication subgroups, the plasma proteomes of PAH and healthy individuals were compared, and the relationship to transplantation-free survival in PAH was determined. To examine causal relationships to PAH, protein quantitative trait loci (pQTL) that influenced protein levels in the patient population were used as instruments for Mendelian randomization (MR) analysis. From 4,152 annotated plasma proteins, levels of 208 differed between patients with PAH and healthy subjects, and 49 predicted long-term survival. MR based on -pQTL located in proximity to the encoding gene for proteins that were prognostic and distinguished PAH from health estimated an adverse effect for higher levels of netrin-4 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.16-2.08) and a protective effect for higher levels of thrombospondin-2 (OR, 0.83; 95% CI, 0.74-0.94) on PAH. Both proteins tracked the development of PAH in previously healthy relatives and changes in thrombospondin-2 associated with pulmonary arterial pressure at disease onset. Integrated analysis of the plasma proteome and genome implicates two secreted matrix-binding proteins, netrin-4 and thrombospondin-2, in the pathobiology of PAH.
Topics: Blood Proteins; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Netrins; Pathology, Molecular; Proteome; Pulmonary Arterial Hypertension; Thrombospondins
PubMed: 35394406
DOI: 10.1164/rccm.202109-2106OC -
Trends in Molecular Medicine Apr 2021
Topics: Biographies as Topic; Humans; Molecular Medicine
PubMed: 33685849
DOI: 10.1016/j.molmed.2021.02.002 -
Surgical Pathology Clinics Sep 2021Urothelial carcinoma is characterized by the presence of a wide spectrum of histopathologic features and molecular alterations that contribute to its morphologic and... (Review)
Review
Urothelial carcinoma is characterized by the presence of a wide spectrum of histopathologic features and molecular alterations that contribute to its morphologic and genomic heterogeneity. It typically harbors high rates of somatic mutations with considerable genomic and transcriptional complexity and heterogeneity that is reflective of its varied histomorphologic and clinical features. This review provides an update on the recent advances in the molecular characterization and novel molecular taxonomy of urothelial carcinoma and variant histologies.
Topics: Carcinoma, Transitional Cell; Genomics; Humans; Pathology, Molecular; Urinary Bladder Neoplasms
PubMed: 34373092
DOI: 10.1016/j.path.2021.05.005 -
Surgical Pathology Clinics Sep 2021Molecular profiling studies have shed new light on the complex biology of prostate cancer. Genomic studies have highlighted that structural rearrangements are among the... (Review)
Review
Molecular profiling studies have shed new light on the complex biology of prostate cancer. Genomic studies have highlighted that structural rearrangements are among the most common recurrent alterations. In addition, both germline and somatic mutations in DNA repair genes are enriched in patients with advanced disease. Primary prostate cancer has long been known to be multifocal, but recent studies demonstrate that a large fraction of prostate cancer shows evidence of multiclonality, suggesting that genetically distinct, independently arising tumor clones coexist. Metastatic prostate cancer shows a high level of morphologic and molecular diversity, which is associated with resistance to systemic therapies. The resulting high level of intratumoral heterogeneity has important implications for diagnosis and poses major challenges for the implementation of molecular studies. Here we provide a concise review of the molecular pathology of prostate cancer, highlight clinically relevant alterations, and discuss opportunities for molecular testing.
Topics: Genomics; Humans; Male; Pathology, Molecular; Prostatic Neoplasms
PubMed: 34373091
DOI: 10.1016/j.path.2021.05.004 -
Clinics in Laboratory Medicine Dec 2022
Topics: Humans; Precision Medicine; Pathology, Molecular; Neoplasms
PubMed: 36368791
DOI: 10.1016/j.cll.2022.09.019 -
Clinics in Laboratory Medicine Jun 2022The COVID-19 pandemic remains a significant problem involving health systems worldwide. Several diagnostic methods are reported for detecting the coronavirus in... (Review)
Review
The COVID-19 pandemic remains a significant problem involving health systems worldwide. Several diagnostic methods are reported for detecting the coronavirus in clinical, research, and public health laboratories. rRT-PCR is considered the gold standard; however, as it required skilled personnel and special equipment, rapid antigen tests have been developed and used as first-line screening. The serologic testing of antibodies can also be used to enhance the detection sensitivity and accuracy, which are used to assess the overall infection rate. This review summarizes the molecular techniques and serologic assays widely used in China and discusses the advantages and disadvantages of these techniques.
Topics: COVID-19; China; Humans; Pandemics; Pathology, Molecular; SARS-CoV-2; Sensitivity and Specificity
PubMed: 35636821
DOI: 10.1016/j.cll.2022.03.003