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BMC Medical Genomics Sep 2017PD is a progressive neurodegenerative disorder commonly treated by levodopa. The findings from genetic studies on adverse effects (ADRs) and levodopa efficacy are mostly... (Meta-Analysis)
Meta-Analysis
BACKGROUND
PD is a progressive neurodegenerative disorder commonly treated by levodopa. The findings from genetic studies on adverse effects (ADRs) and levodopa efficacy are mostly inconclusive. Here, we aim to identify predictive genetic biomarkers for levodopa response (LR) and determine common molecular link with disease susceptibility. A systematic review for LR was conducted for ADR, and drug efficacy, independently. All included articles were assessed for methodological quality on 14 parameters. GWAS of PD were also reviewed. Protein-protein interaction (PPI) analysis using STRING and functional enrichment using WebGestalt was performed to explore the common link between LR and PD.
RESULTS
From 37 candidate studies on levodopa toxicity, 18 genes were found associated, of which, CA STR 13, 14 (DRD2) was most significantly associated with dyskinesia, followed by rs1801133 (MTHFR) with hyper-homocysteinemia, and rs474559 (HOMER1) with hallucination. Similarly, 8 studies on efficacy resulted in 4 genes in which rs28363170, rs3836790 (SLC6A3) and rs4680 (COMT), were significant. To establish the molecular connection between LR with PD, we identified 35 genes significantly associated with PD. With 19 proteins associated with LR and 35 with PD, two independent PPI networks were constructed. Among the 67 nodes (263 edges) in LR, and 62 nodes (190 edges) in PD pathophysiology, UBC, SNCA, FYN, SRC, CAMK2A, and SLC6A3 were identified as common potential candidates.
CONCLUSION
Our study revealed the genetically significant polymorphism concerning the ADRs and levodopa efficacy. The six common genes may be used as predictive markers for therapy optimization and as putative drug target candidates.
Topics: Genetic Predisposition to Disease; Humans; Levodopa; Parkinson Disease; Protein Interaction Maps
PubMed: 28927418
DOI: 10.1186/s12920-017-0291-0 -
Plant, Cell & Environment Apr 2023Phosphorus (P) is a macronutrient required for plant growth and reproduction. Orthophosphate (Pi), the preferred P form for plant uptake, is easily fixed in the soil,... (Review)
Review
Phosphorus (P) is a macronutrient required for plant growth and reproduction. Orthophosphate (Pi), the preferred P form for plant uptake, is easily fixed in the soil, making it unavailable to plants. Limited phosphate rock resources, low phosphate fertilizer use efficiency and high demands for green agriculture production make it important to clarify the molecular mechanisms underlying plant responses to P deficiency and to improve plant phosphate efficiency in crops. Over the past 20 years, tremendous progress has been made in understanding the regulatory mechanisms of the plant P starvation response. Here, we systematically review current research on the mechanisms of Pi acquisition, transport and distribution from the rhizosphere to the shoot; Pi redistribution and reuse during reproductive growth; and the molecular mechanisms of arbuscular mycorrhizal symbiosis in rice (Oryza sativa L.) under Pi deficiency. Furthermore, we discuss several strategies for boosting P utilization efficiency and yield in rice.
Topics: Oryza; Plant Proteins; Phosphates; Phosphorus; Crops, Agricultural; Plant Roots
PubMed: 36208118
DOI: 10.1111/pce.14457 -
Nutrients Sep 2020Matrix gla protein (MGP) is an important vitamin K-dependent inhibitor of vascular calcification. High levels of uncarboxylated, dephosphorylated MGP have been...
Matrix gla protein (MGP) is an important vitamin K-dependent inhibitor of vascular calcification. High levels of uncarboxylated, dephosphorylated MGP have been associated with vascular calcification and are responsive to vitamin K treatment. In this systematic review, we summarize the available evidence examining whether vitamin K supplementation improves surrogate measures of cardiovascular disease including artery and valve calcification, atherosclerosis and artery stiffening. Data from controlled trials of adults were obtained by searching Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and the Web of Science Core Collection. We identified nine randomized controlled trials for review, including trials of vitamin K or vitamin K supplementation, that assessed a surrogate measure of cardiovascular disease including arterial calcification, atherosclerosis or arterial stiffening. For each trial, the risk of bias was assessed applying Cochrane Collaboration methodology. The findings indicate that vitamin K does not consistently prevent progression of calcification, atherosclerosis or arterial stiffness. There may be some benefit in people with calcification at study entry. Studies were heterogenous, with relatively short follow-up and outcome measures were varied. While vitamin K supplementation clearly improves the carboxylation of dephosphoylated MGP, its role in mitigating vascular calcification is uncertain, based on current evidence.
Topics: Animals; Arteries; Atherosclerosis; Calcium-Binding Proteins; Cardiovascular Diseases; Databases, Factual; Dietary Supplements; Disease Progression; Extracellular Matrix Proteins; Humans; Randomized Controlled Trials as Topic; Vascular Calcification; Vascular Stiffness; Vitamin K; Vitamin K 2; Matrix Gla Protein
PubMed: 32977548
DOI: 10.3390/nu12102909 -
Frontiers in Pediatrics 2022The links of sedentary behavior and physical activity with health outcomes in children and adolescents is well known. However, the molecular mechanisms involved are...
BACKGROUND
The links of sedentary behavior and physical activity with health outcomes in children and adolescents is well known. However, the molecular mechanisms involved are poorly understood. We aimed to synthesize the current knowledge of the association of sedentary behavior and physical activity (acute and chronic effects) with gene expression and epigenetic modifications in children and adolescents.
METHODS
PubMed, Web of Science, and Scopus databases were systematically searched until April 2022. A total of 15 articles were eligible for this review. The risk of bias assessment was performed using the Joanna Briggs Institute Critical Appraisal Tool for Systematic Reviews and/or a modified version of the Downs and Black checklist.
RESULTS
Thirteen studies used candidate gene approach, while only 2 studies performed high-throughput analyses. The candidate genes significantly linked to sedentary behavior or physical activity were: , , -α, , , , and . Non-coding Ribonucleic acids (RNAs) regulated by sedentary behavior or physical activity were: miRNA-222, miRNA-146, miRNA-16, miRNA-126, miR-320, and long non-coding RNA MALAT1. These molecules are involved in inflammation, immune function, angiogenic process, and cardiovascular disease. Transcriptomics analyses detected thousands of genes that were altered following an acute bout of physical activity and are linked to gene pathways related to immune function, apoptosis, and metabolic diseases.
CONCLUSION
The evidence found to date is rather limited. Multidisciplinary studies are essential to characterize the molecular mechanisms in response to sedentary behavior and physical activity in the pediatric population. Larger cohorts and randomized controlled trials, in combination with multi-omics analyses, may provide the necessary data to bring the field forward.
SYSTEMATIC REVIEW REGISTRATION
[www.ClinicalTrials.gov], identifier [CRD42021235431].
PubMed: 35813370
DOI: 10.3389/fped.2022.917152 -
Biochemical Society Transactions Jun 2021Hypoxia is a feature of most solid tumours and predicts for poor prognosis. In radiobiological hypoxia (<0.1% O2) cells become up to three times more resistant to...
Hypoxia is a feature of most solid tumours and predicts for poor prognosis. In radiobiological hypoxia (<0.1% O2) cells become up to three times more resistant to radiation. The biological response to radiobiological hypoxia is one of few physiologically relevant stresses that activates both the unfolded protein and DNA damage responses (UPR and DDR). Links between these pathways have been identified in studies carried out in normoxia. Based in part on these previous studies and recent work from our laboratory, we hypothesised that the biological response to hypoxia likely includes overlap between the DDR and UPR. While inhibition of the DDR is a recognised strategy for improving radiation response, the possibility of achieving this through targeting the UPR has not been realised. We carried out a systematic review to identify links between the DDR and UPR, in human cell lines exposed to <2% O2. Following PRISMA guidance, literature from January 2010 to October 2020 were retrieved via Ovid MEDLINE and evaluated. A total of 202 studies were included. LAMP3, ULK1, TRIB3, CHOP, NOXA, NORAD, SIAH1/2, DYRK2, HIPK2, CREB, NUPR1, JMJD2B, NRF2, GSK-3B, GADD45a, GADD45b, STAU1, C-SRC, HK2, CAV1, CypB, CLU, IGFBP-3 and SP1 were highlighted as potential links between the hypoxic DDR and UPR. Overall, we identified very few studies which demonstrate a molecular link between the DDR and UPR in hypoxia, however, it is clear that many of the molecules highlighted warrant further investigation under radiobiological hypoxia as these may include novel therapeutic targets to improve radiotherapy response.
Topics: Animals; Apoptosis; Cell Line, Tumor; DNA Damage; Humans; Hypoxia; Neoplasms; Protein Serine-Threonine Kinases; Signal Transduction; Unfolded Protein Response
PubMed: 34003246
DOI: 10.1042/BST20200861 -
European Journal of Cancer (Oxford,... Jan 2023We sought to characterise oncology basket and umbrella trials that have been implemented, determine how many have been completed, and calculate the response rate, by...
INTRODUCTION
We sought to characterise oncology basket and umbrella trials that have been implemented, determine how many have been completed, and calculate the response rate, by tumour type and drug target.
METHODS
We conducted a retrospective, cross-sectional review of PubMed, Embase, and clinicaltrials.gov for all oncology basket and umbrella trials. We included all trials and publications reporting on the results of these trials, and we calculated overall response rates, stratified by tumour type and drug target.
RESULTS
Most basket and umbrella trials are phase II and non-randomised in design. Of the 180 basket trials, 99 (55.0%) had published results and 81 (45.0%) did not. Of the 73 umbrella trials, 28 (38.4%) had published results and 45 (61.6%) did not. The median response rate was 14.0 (IQR: 4.2, 31.2) for basket trials and 17.8 (IQR: 3.8, 40.4) for umbrella trials. These responses varied, depending on tumour type and drug target.
CONCLUSIONS
Understanding what is known about these trials, especially given the limited but heterogenous response reported in these trials, provides context about the strengths and limitations of drugs, especially since several drugs have been approved in recent years for tumour-agnostic indications, based on the results of these types of trials.
Topics: Humans; Cross-Sectional Studies; Retrospective Studies; Medical Oncology; Neoplasms
PubMed: 36493558
DOI: 10.1016/j.ejca.2022.10.027 -
Antioxidants (Basel, Switzerland) Aug 2022The coronavirus disease (COVID-19) pandemic is a leading global health and economic challenge. What defines the disease's progression is not entirely understood, but... (Review)
Review
The coronavirus disease (COVID-19) pandemic is a leading global health and economic challenge. What defines the disease's progression is not entirely understood, but there are strong indications that oxidative stress and the defense against reactive oxygen species are crucial players. A big influx of immune cells to the site of infection is marked by the increase in reactive oxygen and nitrogen species. Our article aims to highlight the critical role of oxidative stress in the emergence and severity of COVID-19 and, more importantly, to shed light on the underlying molecular and genetic mechanisms. We have reviewed the available literature and clinical trials to extract the relevant genetic variants within the oxidative stress pathway associated with COVID-19 and the anti-oxidative therapies currently evaluated in the clinical trials for COVID-19 treatment, in particular clinical trials on glutathione and N-acetylcysteine.
PubMed: 36009328
DOI: 10.3390/antiox11081609 -
Annual Review of Microbiology Oct 2021Most bacteria are protected from environmental offenses by a cell wall consisting of strong yet elastic peptidoglycan. The cell wall is essential for preserving... (Review)
Review
Most bacteria are protected from environmental offenses by a cell wall consisting of strong yet elastic peptidoglycan. The cell wall is essential for preserving bacterial morphology and viability, and thus the enzymes involved in the production and turnover of peptidoglycan have become preferred targets for many of our most successful antibiotics. In the past decades, , the gram-negative pathogen causing the diarrheal disease cholera, has become a major model for understanding cell wall genetics, biochemistry, and physiology. More than 100 articles have shed light on novel cell wall genetic determinants, regulatory links, and adaptive mechanisms. Here we provide the first comprehensive review of 's cell wall biology and genetics. Special emphasis is placed on the similarities and differences with , the paradigm for understanding cell wall metabolism and chemical structure in gram-negative bacteria.
Topics: Biology; Cell Wall; Escherichia coli; Peptidoglycan; Vibrio cholerae
PubMed: 34623898
DOI: 10.1146/annurev-micro-040621-122027 -
Annals of Surgical Oncology Apr 2012Selected patients with unresectable colorectal liver metastases (CLM) may be rendered resectable after systemic chemotherapy. We reviewed the evidence of downsizing... (Review)
Review
A systematic review of clinical response and survival outcomes of downsizing systemic chemotherapy and rescue liver surgery in patients with initially unresectable colorectal liver metastases.
BACKGROUND
Selected patients with unresectable colorectal liver metastases (CLM) may be rendered resectable after systemic chemotherapy. We reviewed the evidence of downsizing systemic chemotherapy followed by rescue liver surgery in patients with initially unresectable CLM.
METHODS
Literature search of databases (Medline and PubMed) to identify published studies of neoadjuvant chemotherapy followed by liver resection in patients with initially unresectable CLM was undertaken and focused on response rate of chemotherapy and survival outcomes.
RESULTS
Ten observational studies were reviewed. A total of 1,886 patients with initially unresectable CLM underwent systemic chemotherapy. An objective response was observed in 64% (range, 43-79%) of patients after systemic chemotherapy. Of these, 22.5% underwent macroscopically curative liver resection. Median overall survival was 45 (range, 36-60) months with 19% of patients alive and recurrence-free.
CONCLUSIONS
Current evidence suggests that downsizing systematic chemotherapy followed by rescue liver resection is safe and effective for selected patients with initially unresectable CLM. Further studies are required to examine response rates and secondary resectability using new targeted molecular therapy-based regimens.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colorectal Neoplasms; Disease-Free Survival; Fluorouracil; Follow-Up Studies; Hepatectomy; Humans; Leucovorin; Liver Neoplasms; Metastasectomy; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Premedication; Survival Rate; Treatment Outcome
PubMed: 21922338
DOI: 10.1245/s10434-011-2061-0 -
Parkinsonism & Related Disorders Aug 2019To estimate the magnitude of the nocebo response in Parkinson's disease and explore possible associations with study characteristics. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate the magnitude of the nocebo response in Parkinson's disease and explore possible associations with study characteristics.
METHODS
Databases were searched up to February 2017. Placebo-controlled, parallel-group randomized controlled trials investigating pharmacological interventions in people with Parkinson's disease were included. Data were derived from the last measured within-group response in the placebo and intervention arms of randomized controlled trials, after independent extraction. A random-effects model was used to pool study data. The main outcome was the nocebo response, measured as the proportion of placebo-treated participants experiencing any adverse events (AEs). We also measured the proportion of patients with serious AEs (SAEs), and the rates of study dropouts (including due to AEs) and death. PROSPERO registration number is CRD42017070471.
RESULTS
We included 236 randomized controlled trials, with a combined population of 17,381 participants allocated to placebo. The nocebo response was 56.0% (95% CI, 51.7%-60.4%; 148 trials; I = 98%). SAEs were reported in 4.0% (95% CI, 3.4%-4.6%, 157 trials; I = 73%) of placebo-treated patients, dropouts in 14.0% (95% CI, 12.5%-15.5%, 225 trials; I = 91%), dropouts due to AEs in 5.7% (95% CI, 5.1%-6.4%, 219 trials; I = 73%). Deaths occurred in 0.6% (95% CI, 0.5%-0.7%, 227 trials; I = 0%). Similar proportions were identified in patients in intervention arms.
CONCLUSIONS
The magnitude of the nocebo response in parallel-designed randomized controlled trials in Parkinson's disease is substantial and should be considered in the interpretation of safety results and in the design and interpretation of future clinical trials.
Topics: Humans; Nocebo Effect; Parkinson Disease; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31103487
DOI: 10.1016/j.parkreldis.2019.04.015