Future Directions for Pharmacogenetics

1993 ◽  
Vol 6 (1) ◽  
pp. 44-46
Author(s):  
Michael W. Jann ◽  
Y.W. Francis Lam
Keyword(s):  
Molecular Mechanisms ◽  
Regulatory Control ◽  
Ethnic Variation ◽  
Metabolizing Enzymes ◽  
Future Directions ◽  
Clinical Investigations ◽  
Length Polymorphisms ◽  
Polymerase Chain

The discipline of pharmacogenetics will continue to expand as scientific and clinical investigations increase our understanding of genetic variabilities in drug metabolism and response. These research efforts will include determination of molecular mechanisms for the different polymorphisms and evaluation of their clinical significance. The availability of molecular methodologies such as restriction fragment length polymorphisms analysis, polymerase chain reaction, and expression of cDNAs in cell cultures will further the investigative work in detection of normal and mutant alleles, identification of new substrates for different polymorphic metabolizing enzymes, and evaluation of mechanisms of individual susceptibility to biological disorders. Other areas such as the role of pharmacogenetics in drug development and regulatory control, in evaluation of potential drug-drug interactions, ethnic variation in polymorphic metabolism, and response, also need to be evaluated.

scholarly journals MiR-145-5p Inhibits the Invasion of Prostate Cancer and Induces Apoptosis by Inhibiting WIP1

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jianming Sun ◽  
Linggang Deng ◽  
Ye Gong
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Luciferase Reporter Gene ◽  
Anticancer Effects ◽  
Polymerase Chain

Prostate cancer (PCa) is a common malignant tumor of the male genitourinary system that seriously affects the quality of life of patients. Studying the pathogenesis and therapeutic targets of PCa is important. In this study, we investigated the role of miR-145-5p in PCa and its potential molecular mechanisms. The expression levels of miR-145-5p in PCa tissues and adjacent control tissues were detected by real-time quantitative polymerase chain reaction. The effects of miR-145-5p overexpression on PCa were studied using cell proliferation, migration, and invasion experiments. Furthermore, WIP1 was the target gene of miR-145-5p through the bioinformatics website and dual-luciferase reporter gene experiment. Further studies found that WIP1 downregulation could inhibit the proliferation, invasion, and cloning of PCa cells. Overexpression of WIP1 reversed the anticancer effects of miR-145. The anticancer effect of miR-145 was achieved by inhibiting the PI3K/AKT signaling pathway and upregulating ChK2 and p-p38MAPK. Taken together, these results confirmed that miR-145-5p inhibited the growth and metastasis of PCa cells by inhibiting the expression of proto-oncogene WIP1, thereby playing a role in tumor suppression in PCa and may become a potential therapeutic target for the treatment of PCa.

Cerebrospinal fluid mitochondrial DNA levels in patients with multiple sclerosis

2018 ◽  
Vol 25 (11) ◽  
pp. 1535-1538 ◽  
Author(s):  
Nicolas Fissolo ◽  
Laura Cervera-Carles ◽  
Luisa María Villar Guimerans ◽  
Alberto Lleó ◽  
Jordi Clarimón ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Mitochondrial Dna ◽  
Clinically Isolated Syndrome ◽  
Chain Reaction ◽  
Pathological Conditions ◽  
Polymerase Chain ◽  
Digital Polymerase Chain Reaction

The role of cerebrospinal fluid (CSF) mitochondrial DNA (mtDNA) levels as biomarker in multiple sclerosis (MS) is unknown. We determined CSF mtDNA levels in a cohort of 237 individuals, including patients with MS and clinically isolated syndrome (CIS), inflammatory and non-inflammatory neurological controls, and cognitively healthy controls (HC). mtDNA concentration was measured by droplet digital polymerase chain reaction. CSF mtDNA levels were increased in all pathological conditions compared with HC, though no differences were observed between relapse-onset and progressive MS clinical forms, CIS patients and neurological controls. These findings do not support the determination of CSF mtDNA levels as a useful biomarker in MS clinical practice.

Application of GPIIIa Gene Taq I Polymorphism to Determination of Carrier Status in Glanzmann’s Thrombasthenia Families of Chinese Origin

1993 ◽  
Vol 69 (01) ◽  
pp. 064-069 ◽  
Author(s):  
Changgeng Ruan ◽  
Jianming Gu ◽  
Xiaodong Wang ◽  
Xiaohong Chu ◽  
Junliang Pan
Keyword(s):  
Carrier Status ◽  
Glanzmann’S Thrombasthenia ◽  
Chinese Origin ◽  
Length Polymorphisms ◽  
Glanzmann's Thrombasthenia ◽  
Pcr Method ◽  
Polymerase Chain ◽  
Asymptomatic Subjects ◽  
Autosomal Recessive Manner

SummaryGlanzmann’s thrombasthenia is a bleeding disorder caused by qualitative and/or quantitative defects of platelet membrane glycoprotein (GP) IIb/IIIa complex. The disease is inherited in an autosomal recessive manner. In this paper, cDNA probes were used to study restriction fragment length polymorphisms (RFLPs) in GPIIIa gene. A Taq I polymorphism was identified and this RFLP was composed of variant bands of 6.5 Kb/4.0 and 2.5 Kb with a frequency of 0.46/0.54 in Chinese population. The Taq I polymorphism was further localized by polymerase chain reaction (PCR) method to exon VIII of the GPIIIa gene. In two Glanzmann’s thrombasthenia families, the Taq I RFLP studied by both Southern blotting and PCR methods identified the defective GPIIIa gene inherited by patients, and determined the genotype of asymptomatic subjects. Analysis of this Taq I polymorphism by PCR method should be potentially useful in future for the carrier detection and prenatal diagnosis in Glanzmann’s thrombasthenia families.

Acquired cholesteatoma: summary of the cascade of molecular events

2013 ◽  
Vol 127 (6) ◽  
pp. 542-549 ◽  
Author(s):  
L Louw
Keyword(s):  
Molecular Mechanisms ◽  
Bone Erosion ◽  
Chronic Otitis Media ◽  
Future Directions ◽  
Molecular Events ◽  
Matrix Interactions ◽  
Proliferation And Apoptosis ◽  
Acquired Cholesteatoma ◽  
Role Players

AbstractBackground:Cholesteatoma is considered a benign, gradually expanding and destructive epithelial lesion of the temporal bone. The pathogenesis of different classifications of cholesteatoma is marked by similar underlying cellular and molecular processes. Stepwise explanations of the histopathogenesis have been described previously. The current paper focuses on expounding the molecular events of cholesteatoma.Method and results:Cholesteatoma pathogenesis encompasses a complex network of signalling pathways during: epidermal hyperplasia, perimatrix–matrix interactions and mucosal disease. This paper presents a review of the molecular events driven by inflammatory mediators and enzymes during: cholesteatoma growth (cell proliferation and apoptosis); maintenance and deterioration (angiogenesis and hypoxia, oxidative stress and toxicity); and complications (bone erosion and hearing loss). The cascade of molecular events applicable to atelectasis and cholesteatoma that coexist with chronic otitis media and bone erosion as sequelae is summarised.Conclusion:The role of lipids in this disease is relatively unexplored, but there is evidence in support of fatty acid role-players that needs confirmation. Future directions in lipid research to delineate molecular mechanisms are proposed.

scholarly journals Characterization of a transgenic mouse line over-expressing the human ornithine decarboxylase gene

1991 ◽  
Vol 278 (3) ◽  
pp. 895-898 ◽  
Author(s):  
M Halmekytö ◽  
L Alhonen ◽  
J Wahlfors ◽  
R Sinervirta ◽  
T Eloranta ◽  
...  
Keyword(s):  
Transgenic Mouse ◽  
Ornithine Decarboxylase ◽  
Transgenic Animals ◽  
Metabolizing Enzymes ◽  
Transgenic Mouse Line ◽  
Adenosylmethionine Decarboxylase ◽  
Transgenic Lines ◽  
Polymerase Chain

We have produced several transgenic mouse lines over-expressing the human ornithine decarboxylase (ODC) gene. We have now characterized one of the transgenic lines as regards the tissue accumulation of the polyamines and the activities of their metabolizing enzymes. Among the tissues analysed, the polyamine pattern was most strikingly changed in testis and brain of the transgenic animals. ODC activity was greatly enhanced in all tissues, except kidney, of the transgenic animals. The most dramatic increase, 80-fold, was found in brain of the transgenic mice. The activities of S-adenosylmethionine decarboxylase and spermidine and spermine syntheses were likewise significantly increased in testis of the transgenic animals. The activities of the enzymes involved in the back-conversion of the polyamines, namely spermidine/spermine acetyltransferase and polyamine oxidase, were similar in the transgenic and non-transgenic animals. As analysed by reverse transcriptase/polymerase chain reaction, all the six tissues of the transgenic animals expressed human-specific ODC mRNA. Determination of the half-life of testicular ODC revealed a stabilization of the enzyme in the transgenic males.

scholarly journals New Insights Into the Role of Aberrant Hippocampal Neurogenesis in Epilepsy

2021 ◽  
Vol 12 ◽  
Author(s):  
Peng Chen ◽  
Fuchao Chen ◽  
Yue Wu ◽  
Benhong Zhou
Keyword(s):  
Molecular Mechanisms ◽  
Wide Spectrum ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Future Directions ◽  
The Past ◽  
The Central Nervous System ◽  
Spontaneous Recurrent Seizures ◽  
Patients With Epilepsy

Data accumulated over the past four decades have confirmed that adult hippocampal neurogenesis (HN) plays a key role in the wide spectrum of hippocampal pathology. Epilepsy is a disorder of the central nervous system characterized by spontaneous recurrent seizures. Although neurogenesis in persistent germinative zones is altered in the adult rodent models of epilepsy, the effects of seizure-induced neurogenesis in the epileptic brain, in terms of either a pathological or reparative role, are only beginning to be explored. In this review, we described the most recent advances in neurogenesis in epilepsy and outlooked future directions for neural stem cells (NSCs) and epilepsy-in-a-dish models. We proposed that it may help in refining the underlying molecular mechanisms of epilepsy and improving the therapies and precision medicine for patients with epilepsy.

scholarly journals Norovirus Attachment and Entry

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 495 ◽  
Author(s):  
Vincent R. Graziano ◽  
Jin Wei ◽  
Craig B. Wilen
Keyword(s):  
Viral Entry ◽  
Molecular Mechanisms ◽  
Viral Gastroenteritis ◽  
Blood Group Antigens ◽  
Cell Tropism ◽  
Murine Norovirus ◽  
Human Norovirus ◽  
Future Directions ◽  
Minor Capsid Protein

Human norovirus is a major human pathogen causing the majority of cases of viral gastroenteritis globally. Viral entry is the first step of the viral life cycle and is a significant determinant of cell tropism, host range, immune interactions, and pathogenesis. Bile salts and histo-blood group antigens are key mediators of norovirus entry; however, the molecular mechanisms by which these molecules promote infection and the identity of a potential human norovirus receptor remain unknown. Recently, there have been several important advances in norovirus entry biology including the identification of CD300lf as the receptor for murine norovirus and of the role of the minor capsid protein VP2 in viral genome release. Here, we will review the current understanding about norovirus attachment and entry and highlight important future directions.

scholarly journals Metabolic signaling functions of ER–mitochondria contact sites: role in metabolic diseases

2017 ◽  
Vol 58 (2) ◽  
pp. R87-R106 ◽  
Author(s):  
Emily Tubbs ◽  
Jennifer Rieusset
Keyword(s):  
Cell Fate ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Treatment Strategies ◽  
Contact Sites ◽  
Novel Treatment ◽  
Functional Features ◽  
Novel Treatment Strategies

Beyond the maintenance of cellular homeostasis and the determination of cell fate, ER–mitochondria contact sites, defined as mitochondria-associated membranes (MAM), start to emerge as an important signaling hub that integrates nutrient and hormonal stimuli and adapts cellular metabolism. Here, we summarize the established structural and functional features of MAM and mainly focus on the latest breakthroughs highlighting a crucial role of organelle crosstalk in the control of metabolic homeostasis. Lastly, we discuss recent studies that have revealed the importance of MAM in not only metabolic diseases but also in other pathologies with disrupted metabolism, shedding light on potential common molecular mechanisms and leading hopefully to novel treatment strategies.

scholarly journals Emerging Role of Purine Metabolizing Enzymes in Brain Function and Tumors

2018 ◽  
Vol 19 (11) ◽  
pp. 3598 ◽  
Author(s):  
Mercedes Garcia-Gil ◽  
Marcella Camici ◽  
Simone Allegrini ◽  
Rossana Pesi ◽  
Edoardo Petrotto ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Brain Function ◽  
Molecular Mechanisms ◽  
Purinergic Signaling ◽  
Adenosine Kinase ◽  
Synthesis Rate ◽  
Metabolizing Enzymes ◽  
And Function ◽  
Hypoxanthine Guanine Phosphoribosyl Transferase

The growing evidence of the involvement of purine compounds in signaling, of nucleotide imbalance in tumorigenesis, the discovery of purinosome and its regulation, cast new light on purine metabolism, indicating that well known biochemical pathways may still surprise. Adenosine deaminase is important not only to preserve functionality of immune system but also to ensure a correct development and function of central nervous system, probably because its activity regulates the extracellular concentration of adenosine and therefore its function in brain. A lot of work has been done on extracellular 5′-nucleotidase and its involvement in the purinergic signaling, but also intracellular nucleotidases, which regulate the purine nucleotide homeostasis, play unexpected roles, not only in tumorigenesis but also in brain function. Hypoxanthine guanine phosphoribosyl transferase (HPRT) appears to have a role in the purinosome formation and, therefore, in the regulation of purine synthesis rate during cell cycle with implications in brain development and tumors. The final product of purine catabolism, uric acid, also plays a recently highlighted novel role. In this review, we discuss the molecular mechanisms underlying the pathological manifestations of purine dysmetabolisms, focusing on the newly described/hypothesized roles of cytosolic 5′-nucleotidase II, adenosine kinase, adenosine deaminase, HPRT, and xanthine oxidase.

scholarly journals Circular RNAs as Competing Endogenous RNAs in Cardiovascular and Cerebrovascular Diseases: Molecular Mechanisms and Clinical Implications

2021 ◽  
Vol 8 ◽  
Author(s):  
Xue Min ◽  
Dong-liang Liu ◽  
Xing-dong Xiong
Keyword(s):  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Suppressive Effect ◽  
Cerebrovascular Diseases ◽  
Circular Rnas ◽  
Clinical Implications ◽  
Future Directions ◽  
Rna Molecules ◽  
Competing Endogenous Rnas

Circular RNAs (circRNAs) represent a novel class of widespread and diverse endogenous RNA molecules. This unusual class of RNA species is generated by a back-splicing event of exons or introns, resulting in a covalently closed circRNA molecule. Accumulating evidence indicates that circRNA plays an important role in the biological functions of a network of competing endogenous RNA (ceRNA). CircRNAs can competitively bind to miRNAs and abolish the suppressive effect of miRNAs on target RNAs, thus regulating gene expression at the posttranscriptional level. The role of circRNAs as ceRNAs in the pathogenesis of cardiovascular and cerebrovascular diseases (CVDs) has been recently reported and highlighted. Understanding the underlying molecular mechanism could aid the discovery of therapeutic targets or strategies against CVDs. Here, we review the progress in studying the role of circRNAs as ceRNAs in CVDs, with emphasis on the molecular mechanism, and discuss future directions and possible clinical implications.

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