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Human Genetics Dec 2016Tooth agenesis and orofacial clefts represent the most common developmental anomalies and their co-occurrence is often reported in patients as well in animal models. The... (Review)
Review
Tooth agenesis and orofacial clefts represent the most common developmental anomalies and their co-occurrence is often reported in patients as well in animal models. The aim of the present systematic review is to thoroughly investigate the current literature (PubMed, EMBASE) to identify the genes and genomic loci contributing to syndromic or non-syndromic co-occurrence of tooth agenesis and orofacial clefts, to gain insight into the molecular mechanisms underlying their dual involvement in the development of teeth and facial primordia. Altogether, 84 articles including phenotype and genotype description provided 9 genomic loci and 26 gene candidates underlying the co-occurrence of the two congenital defects: MSX1, PAX9, IRF6, TP63, KMT2D, KDM6A, SATB2, TBX22, TGFα, TGFβ3, TGFβR1, TGFβR2, FGF8, FGFR1, KISS1R, WNT3, WNT5A, CDH1, CHD7, AXIN2, TWIST1, BCOR, OFD1, PTCH1, PITX2, and PVRL1. The molecular pathways, cellular functions, tissue-specific expression and disease association were investigated using publicly accessible databases (EntrezGene, UniProt, OMIM). The Gene Ontology terms of the biological processes mediated by the candidate genes were used to cluster them using the GOTermMapper (Lewis-Sigler Institute, Princeton University), speculating on six super-clusters: (a) anatomical development, (b) cell division, growth and motility, (c) cell metabolism and catabolism, (d) cell transport, (e) cell structure organization and (f) organ/system-specific processes. This review aims to increase the knowledge on the mechanisms underlying the co-occurrence of tooth agenesis and orofacial clefts, to pave the way for improving targeted (prenatal) molecular diagnosis and finally to reflect on therapeutic or ultimately preventive strategies for these disabling conditions in the future.
Topics: Anodontia; Brain; Cleft Lip; Cleft Palate; Gene Expression Regulation; Gene Ontology; Genetic Association Studies; Genotype; Humans; Organ Specificity; Phenotype; Protein Biosynthesis
PubMed: 27699475
DOI: 10.1007/s00439-016-1733-z -
Inflammation Research : Official... Mar 2016A systematic review of all literature was done to assess the ability of the progestin dienogest (DNG) to influence the inflammatory response of endometriotic cells. (Review)
Review
OBJECTIVE AND DESIGN
A systematic review of all literature was done to assess the ability of the progestin dienogest (DNG) to influence the inflammatory response of endometriotic cells.
MAIN OUTCOME MEASURES
In vitro and in vivo studies report an influence of DNG on the inflammatory response in eutopic or ectopic endometrial tissue (animal or human).
RESULTS
After strict inclusion criteria were satisfied, 15 studies were identified that reported a DNG influence on the inflammatory response in endometrial tissue. These studies identified a modulation of prostaglandin (PG) production and metabolism (PGE2, PGE2 synthase, cyclo-oxygenase-2 and microsomal PGE synthase-1), pro-inflammatory cytokine and chemokine production [interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, monocyte chemoattractant protein-1 and stromal cell-derived factor-1], growth factor biosynthesis (vascular endothelial growth factor and nerve growth factor) and signaling kinases, responsible for the control of inflammation. Evidence supports a progesterone receptor-mediated inhibition of the inflammatory response in PR-expressing epithelial cells. It also indicated that DNG inhibited the inflammatory response in stromal cells, however, whether this was via a PR-mediated mechanism is not clear.
CONCLUSIONS
DNG has a significant effect on the inflammatory microenvironment of endometriotic lesions that may contribute to its clinical efficacy. A better understanding of the specific anti-inflammatory activity of DNG and whether this contributes to its clinical efficacy can help develop treatments that focus on the inhibition of inflammation while minimizing hormonal modulation.
Topics: Animals; Cytokines; Endometriosis; Epithelial Cells; Female; Hormone Antagonists; Humans; Immunologic Factors; Intercellular Signaling Peptides and Proteins; Nandrolone; Prostaglandins; Stromal Cells
PubMed: 26650031
DOI: 10.1007/s00011-015-0909-7 -
Oncotarget Mar 2017Glucose transporter 1 (GLUT1), the uniporter protein encoded by the SLC2A1 gene, is a key rate-limiting factor in the transport of glucose in cancer cells, and... (Meta-Analysis)
Meta-Analysis Review
Glucose transporter 1 (GLUT1), the uniporter protein encoded by the SLC2A1 gene, is a key rate-limiting factor in the transport of glucose in cancer cells, and frequently expressed in a significant proportion of human cancers. Numerous studies have reported paradoxical evidence of the relationship between GLUT1 expression and prognosis in solid human tumors. To address this discrepancy, we conducted a thorough search of Pubmed and Web of Science for studies evaluating the expression of GLUT1 and overall survival (OS) and disease-free survival (DFS) in patients with solid cancer from 1993 to April 2016. Data from published researches were extracted and computed into odds ratio (OR). A total of 26 studies including 2948 patients met our search criteria and were evaluated. Overexpression of GLUT1 was found to significantly correlate with poor 3-year OS (OR: 2.86; 95% CI, 1.90-4.32, P < 0.00001) and 5-year OS (OR: 2.52; 95% CI, 1.75-3.61, P < 0.00001) of solid tumors. Similar results were observed when analysis of DFS was performed. Subgroup analysis revealed that elevated GLUT1 expression was associated with worse prognosis of oral squamous cell carcinoma and breast cancer. Taken together, overexpression of GLUT1 is correlated with poor survival in most solid tumors, suggesting that the expression status of GLUT1 is a vital prognostic indicator and promising therapeutic target in solid tumors.
Topics: Biomarkers, Tumor; Disease-Free Survival; Glucose Transporter Type 1; Humans; Neoplasms; Prognosis
PubMed: 28187435
DOI: 10.18632/oncotarget.15171 -
Indian Heart Journal 2017The various studies have examined the relationship between FTO gene expression and macronutrients levels. In order to obtain better viewpoint from this interactions, all... (Review)
Review
The various studies have examined the relationship between FTO gene expression and macronutrients levels. In order to obtain better viewpoint from this interactions, all of existing studies were reviewed systematically. All published papers have been obtained and reviewed using standard and sensitive keywords from databases such as CINAHL, Embase, PubMed, PsycInfo, and the Cochrane, from 1990 to 2016. The results indicated that all of 6 studies that met the inclusion criteria (from a total of 428 published article) found FTO gene expression changes at short-term follow-ups. Four of six studies found an increased FTO gene expression after calorie restriction, while two of them indicated decreased FTO gene expression. The effect of protein, carbohydrate and fat were separately assessed and suggested by all of six studies. In Conclusion, The level of FTO gene expression in hypothalamus is related to macronutrients levels. Future research should evaluate the long-term impact of dietary interventions.
Topics: Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Cardiovascular Diseases; Food; Gene Expression Regulation; Genetic Predisposition to Disease; Humans; Hypothalamus; Obesity; Risk Factors
PubMed: 28460778
DOI: 10.1016/j.ihj.2017.01.014 -
Bone Research Aug 2022Approximately 40% of treatments of chronic and recurrent osteomyelitis fail in part due to bacterial persistence. Staphylococcus aureus, the predominant pathogen in... (Review)
Review
Approximately 40% of treatments of chronic and recurrent osteomyelitis fail in part due to bacterial persistence. Staphylococcus aureus, the predominant pathogen in human osteomyelitis, is known to persist by phenotypic adaptation as small-colony variants (SCVs) and by formation of intracellular reservoirs, including those in major bone cell types, reducing susceptibility to antibiotics. Intracellular infections with S. aureus are difficult to treat; however, there are no evidence-based clinical guidelines addressing these infections in osteomyelitis. We conducted a systematic review of the literature to determine the demonstrated efficacy of all antibiotics against intracellular S. aureus relevant to osteomyelitis, including protein biosynthesis inhibitors (lincosamides, streptogramins, macrolides, oxazolidines, tetracyclines, fusidic acid, and aminoglycosides), enzyme inhibitors (fluoroquinolones and ansamycines), and cell wall inhibitors (beta-lactam inhibitors, glycopeptides, fosfomycin, and lipopeptides). The PubMed and Embase databases were screened for articles related to intracellular S. aureus infections that compared the effectiveness of multiple antibiotics or a single antibiotic together with another treatment, which resulted in 34 full-text articles fitting the inclusion criteria. The combined findings of these studies were largely inconclusive, most likely due to the plethora of methodologies utilized. Therefore, the reported findings in the context of the models employed and possible solutions for improved understanding are explored here. While rifampicin, oritavancin, linezolid, moxifloxacin and oxacillin were identified as the most effective potential intracellular treatments, the scientific evidence for these is still relatively weak. We advocate for more standardized research on determining the intracellular effectiveness of antibiotics in S. aureus osteomyelitis to improve treatments and patient outcomes.
PubMed: 35961964
DOI: 10.1038/s41413-022-00227-8 -
Cancer Metastasis Reviews Mar 2017Human epidermal growth factor receptor 2 (HER2) overexpression and amplification have been reported as predictive markers for HER2-targeted therapy in breast and gastric... (Meta-Analysis)
Meta-Analysis Review
Human epidermal growth factor receptor 2 (HER2) overexpression and amplification have been reported as predictive markers for HER2-targeted therapy in breast and gastric cancer, whereas human epidermal growth factor receptor 3 (HER3) is emerging as a potential resistance factor. The aim of this study was to perform a systematic review and meta-analysis of the HER2 and HER3 overexpression and amplification in biliary tract cancers (BTCs). An electronic search of MEDLINE, American Society of Clinical Oncology (ASCO), European Society of Medical Oncology Congress (ESMO), and American Association for Cancer Research (AACR) was performed to identify studies reporting HER2 and/or HER3 membrane protein expression by immunohistochemistry (IHC) and/or gene amplification by in situ hybridization (ISH) in BTCs. Studies were classified as "high quality" (HQ) if IHC overexpression was defined as presence of moderate/strong staining or "low quality" (LQ) where "any" expression was considered positive. Of 440 studies screened, 40 met the inclusion criteria. Globally, HER2 expression rate was 26.5 % (95 % CI 18.9-34.1 %). When HQ studies were analyzed (n = 27 studies), extrahepatic BTCs showed a higher HER2 overexpression rate compared to intrahepatic cholangiocarcinoma: 19.9 % (95 % CI 12.8-27.1 %) vs. 4.8 % (95 % CI 0-14.5 %), respectively, p value 0.0049. HER2 amplification rate was higher in patients selected by HER2 overexpression compared to "unselected" patients: 57.6 % (95 % CI 16.2-99 %) vs. 17.9 % (95 % CI 0.1-35.4 %), respectively, p value 0.0072. HER3 overexpression (4/4 HQ studies) and amplification rates were 27.9 % (95 % CI 9.7-46.1 %) and 26.5 % (one study), respectively. Up to 20 % of extrahepatic BTCs appear to be HER2 overexpressed; of these, close to 60 % appear to be HER2 amplified, while HER3 is overexpressed or amplified in about 25 % of patients. Clinical relevance for targeted therapy should be tested in prospective clinical trials.
Topics: Biliary Tract Neoplasms; Humans; Metabolic Networks and Pathways; Receptor, ErbB-2; Receptor, ErbB-3
PubMed: 27981460
DOI: 10.1007/s10555-016-9645-x -
PloS One 2015Emerging data suggest that Electro-Convulsive Treatment (ECT) may reduce depressive symptoms by increasing the expression of Brain-Derived Neurotrophic Factor (BDNF).... (Meta-Analysis)
Meta-Analysis Review
Emerging data suggest that Electro-Convulsive Treatment (ECT) may reduce depressive symptoms by increasing the expression of Brain-Derived Neurotrophic Factor (BDNF). Yet, conflicting findings have been reported. For this reason we performed a systematic review and meta-analysis of the preclinical and clinical literature on the association between ECT treatment (ECS in animals) and changes in BDNF concentrations and their effect on behavior. In addition, regional brain expression of BDNF in mouse and human brains were compared using Allen Brain Atlas. ECS, over sham, increased BDNF mRNA and protein in animal brain (effect size [Hedge's g]: 0.38-0.54; 258 effect-size estimates, N = 4,284) but not in serum (g = 0.06, 95% CI = -0.05-0.17). In humans, plasma but not serum BDNF increased following ECT (g = 0.72 vs. g = 0.14; 23 effect sizes, n = 281). The gradient of the BDNF increment in animal brains corresponded to the gradient of the BDNF gene expression according to the Allen brain atlas. Effect-size estimates were larger following more ECT sessions in animals (r = 0.37, P < .0001) and in humans (r = 0.55; P = 0.05). There were some indications that the increase in BDNF expression was associated with behavioral changes in rodents, but not in humans. We conclude that ECS in rodents and ECT in humans increase BDNF concentrations but this is not consistently associated with changes in behavior.
Topics: Animals; Behavior, Animal; Brain-Derived Neurotrophic Factor; Depression; Electric Stimulation Therapy; Gene Expression Regulation; Humans; Mice; RNA, Messenger
PubMed: 26529101
DOI: 10.1371/journal.pone.0141564 -
International Journal of Molecular... May 2021Bicistronic reporter assays have been instrumental for transgene expression, understanding of internal ribosomal entry site (IRES) translation, and identification of...
Bicistronic reporter assays have been instrumental for transgene expression, understanding of internal ribosomal entry site (IRES) translation, and identification of novel cap-independent translational elements (CITE). We observed a large methodological variability in the use of bicistronic reporter assays and data presentation or normalization procedures. Therefore, we systematically searched the literature for bicistronic IRES reporter studies and analyzed methodological details, data visualization, and normalization procedures. Two hundred fifty-seven publications were identified using our search strategy (published 1994-2020). Experimental studies on eukaryotic adherent cell systems and the cell-free translation assay were included for further analysis. We evaluated the following methodological details for 176 full text articles: the bicistronic reporter design, the cell line or type, transfection methods, and time point of analyses post-transfection. For the cell-free translation assay, we focused on methods of in vitro transcription, type of translation lysate, and incubation times and assay temperature. Data can be presented in multiple ways: raw data from individual cistrons, a ratio of the two, or fold changes thereof. In addition, many different control experiments have been suggested when studying IRES-mediated translation. In addition, many different normalization and control experiments have been suggested when studying IRES-mediated translation. Therefore, we also categorized and summarized their use. Our unbiased analyses provide a representative overview of bicistronic IRES reporter use. We identified parameters that were reported inconsistently or incompletely, which could hamper data reproduction and interpretation. On the basis of our analyses, we encourage adhering to a number of practices that should improve transparency of bicistronic reporter data presentation and improve methodological descriptions to facilitate data replication.
Topics: Animals; Genes, Reporter; Humans; Internal Ribosome Entry Sites; Protein Biosynthesis; Regulatory Sequences, Nucleic Acid; Ribosomes
PubMed: 34068921
DOI: 10.3390/ijms22105193 -
Pharmacogenomics 2015Drug addiction is a serious disease with damaging effects on the brain and physical health. Despite the increase in the number of affected individuals, there are few... (Meta-Analysis)
Meta-Analysis Review
Drug addiction is a serious disease with damaging effects on the brain and physical health. Despite the increase in the number of affected individuals, there are few effective pharmacological treatment options for substance use disorders. The study of the influence of an individual's genetic features on the treatment response may help to identify more efficacious treatment options. This systematic review focuses on the serotonergic system because of its relevant role in mood and impulse control disorders, and its contribution to the development and maintenance of drug use disorders. In particular, we examine the role of serotonergic genes in the response to pharmacotherapy for alcohol, cocaine and nicotine addiction. Current evidence suggests that genetic variability of the serotonergic biosynthesis enzyme tryptophan hydroxylase 2 (TPH2) and the serotonin transporter (SLC6A4) genes mediates the efficacy of several addiction treatments, such as ondansetron and disulfiram, and the antidepressants bupropion, nortriptyline and sertraline.
Topics: Genetic Variation; Humans; Serotonin; Serotonin Agents; Serotonin Plasma Membrane Transport Proteins; Substance-Related Disorders; Tryptophan Hydroxylase
PubMed: 26265436
DOI: 10.2217/pgs.15.72 -
Signal Transduction and Targeted Therapy Oct 2020Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that is highly pathogenic and has caused the recent worldwide pandemic officially named...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that is highly pathogenic and has caused the recent worldwide pandemic officially named coronavirus disease (COVID-19). Currently, considerable efforts have been put into developing effective and safe drugs and vaccines against SARS-CoV-2. Vaccines, such as inactivated vaccines, nucleic acid-based vaccines, and vector vaccines, have already entered clinical trials. In this review, we provide an overview of the experimental and clinical data obtained from recent SARS-CoV-2 vaccines trials, and highlight certain potential safety issues that require consideration when developing vaccines. Furthermore, we summarize several strategies utilized in the development of vaccines against other infectious viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), with the aim of aiding in the design of effective therapeutic approaches against SARS-CoV-2.
Topics: Angiotensin-Converting Enzyme 2; Antibodies, Viral; Betacoronavirus; COVID-19; COVID-19 Vaccines; Clinical Trials as Topic; Coronavirus Infections; Gene Expression Regulation; Humans; Immunity, Innate; Immunization Schedule; Immunogenicity, Vaccine; Middle East Respiratory Syndrome Coronavirus; Pandemics; Patient Safety; Peptidyl-Dipeptidase A; Pneumonia, Viral; Protein Binding; Receptors, Virus; Severe acute respiratory syndrome-related coronavirus; SARS-CoV-2; Severe Acute Respiratory Syndrome; Spike Glycoprotein, Coronavirus; Vaccines, Attenuated; Vaccines, DNA; Vaccines, Subunit; Vaccines, Virus-Like Particle; Viral Vaccines
PubMed: 33051445
DOI: 10.1038/s41392-020-00352-y