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Frontiers in Physiology 2020Endogenous circadian rhythms are biological processes generated by an internal body clock. They are self-sustaining, and they govern biochemical and physiological...
Endogenous circadian rhythms are biological processes generated by an internal body clock. They are self-sustaining, and they govern biochemical and physiological processes. However, circadian rhythms are influenced by many external stimuli to reprogram the phase in response to environmental change. Through their adaptability to environmental changes, they synchronize physiological responses to environmental challenges that occur within a sidereal day. The precision of this circadian system is assured by many post-translational modifications (PTMs) that occur on the protein components of the circadian clock mechanism. The most ancient example of circadian rhythmicity driven by phosphorylation of clock proteins was observed in cyanobacteria. The influence of phosphorylation on the circadian system is observed through different kingdoms, from plants to humans. Here, we discuss how phosphorylation modulates the mammalian circadian clock, and we give a detailed overview of the most critical discoveries in the field.
PubMed: 33324245
DOI: 10.3389/fphys.2020.612510 -
Translational Psychiatry Mar 2016The D2 dopamine receptor mediates neuropsychiatric symptoms and is a target of pharmacotherapy. Inter-individual variation of D2 receptor density is thought to influence... (Meta-Analysis)
Meta-Analysis Review
The D2 dopamine receptor mediates neuropsychiatric symptoms and is a target of pharmacotherapy. Inter-individual variation of D2 receptor density is thought to influence disease risk and pharmacological response. Numerous molecular imaging studies have tested whether common genetic variants influence D2 receptor binding potential (BP) in humans, but demonstration of robust effects has been limited by small sample sizes. We performed a systematic search of published human in vivo molecular imaging studies to estimate effect sizes of common genetic variants on striatal D2 receptor BP. We identified 21 studies examining 19 variants in 11 genes. The most commonly studied variant was a single-nucleotide polymorphism in ANKK1 (rs1800497, Glu713Lys, also called 'Taq1A'). Fixed- and random-effects meta-analyses of this variant (5 studies, 194 subjects total) revealed that striatal BP was significantly and robustly lower among carriers of the minor allele (Lys713) relative to major allele homozygotes. The weighted standardized mean difference was -0.57 under the fixed-effect model (95% confidence interval=(-0.87, -0.27), P=0.0002). The normal relationship between rs1800497 and BP was not apparent among subjects with neuropsychiatric diseases. Significant associations with baseline striatal D2 receptor BP have been reported for four DRD2 variants (rs1079597, rs1076560, rs6277 and rs1799732) and a PER2 repeat polymorphism, but none have yet been tested in more than two independent samples. Our findings resolve apparent discrepancies in the literature and establish that rs1800497 robustly influences striatal D2 receptor availability. This genetic variant is likely to contribute to important individual differences in human striatal function, neuropsychiatric disease risk and pharmacological response.
Topics: Brain; Genetic Variation; Humans; Molecular Imaging; Positron-Emission Tomography; Receptors, Dopamine D2; Tomography, Emission-Computed, Single-Photon
PubMed: 26926883
DOI: 10.1038/tp.2016.22 -
European Urology Open Science Oct 2022Urine culture has low sensitivity in the diagnosis of urinary tract infection (UTI). Next-generation sequencing (NGS) and polymerase chain reaction (PCR) are... (Review)
Review
CONTEXT
Urine culture has low sensitivity in the diagnosis of urinary tract infection (UTI). Next-generation sequencing (NGS) and polymerase chain reaction (PCR) are culture-independent molecular methods available for commercial use to diagnose UTI.
OBJECTIVE
To systematically evaluate the evidence comparing the diagnostic and therapeutic values of molecular diagnostic methods to urine culture in the management of UTI in adults.
EVIDENCE ACQUISITION
We performed a critical review of Embase, Ovid, and PubMed in February 2022 according to the Preferred Reporting Items for Systematic Review and Meta-analyses statement. Studies involving pregnant women, ureteral stones, ureteral stents, and percutaneous nephrostomy tubes were excluded. Risk of bias and methodological quality were assessed using the Cochrane risk of bias tool and Newcastle Ottawa Scale. Fifteen publications were selected for inclusion.
EVIDENCE SYNTHESIS
Included reports compared NGS (nine studies) and PCR (six studies) to urine culture. A meta-analysis of seven similar studies utilizing NGS demonstrates that NGS is more sensitive in the identification of urinary bacteria and detects greater species diversity per urine sample than culture. PCR protocols designed to detect a diverse range of microbes had increased sensitivity and species diversity compared with culture. Phenotypic and genotypic resistomes are concordant in approximately 85% of cases. There is insufficient evidence to compare patient symptomatic responses to antibiotic therapy guided by molecular testing versus standard susceptibility testing.
CONCLUSIONS
Moderately strong evidence exists that molecular diagnostics demonstrate increased sensitivity in detecting urinary bacteria at the expense of poor specificity in controls. Additional data comparing patient symptoms and cure rates following antibiotic selection directed by molecular methods compared with culture are needed to elucidate their place in UTI care.
PATIENT SUMMARY
We compare culture-independent molecular methods with urine culture in the management of urinary tract infection. We found good evidence that molecular methods detect more bacteria than culture; however, the clinical implications to support their routine use are unclear.
PubMed: 36093322
DOI: 10.1016/j.euros.2022.08.009 -
Lasers in Medical Science Oct 2022Low-level laser therapy (LLLT)-induced photobiomodulation (PBM) stimulates bone tissue regeneration by inducing osteoblast differentiation and mitochondrial activation.... (Review)
Review
Low-level laser therapy (LLLT)-induced photobiomodulation (PBM) stimulates bone tissue regeneration by inducing osteoblast differentiation and mitochondrial activation. However, the role of reactive oxygen species (ROS) in this process remains controversial. The aim of this systematic review was to collect and analyze the available literature on the cellular and molecular effects of LLLT on osteoblasts and the role of ROS in this process. A search was conducted in PubMed, ScienceDirect, Scopus, and Web of Science. Studies published in English over the past 15 years were selected. Fourteen articles were included with moderate (n = 9) and low risk of bias (n = 5). Thirteen studies reported the use of diode lasers with wavelengths (λ) between 635 and 980 nm. One study used an Nd:YAG laser (λ1064 nm). The most commonly used λ values were 808 and 635 nm. The energy densities ranged from 0.378 to 78.75 J/cm, and irradiation times from 1.5 to 300 s. Most studies found increases in proliferation, ATP synthesis, mitochondrial activity, and osteoblastic differentiation related to moderate and dose-dependent increases in intracellular ROS levels. Only two studies reported no significant changes. The data presented heterogeneity owing to the variety of LLLT protocols. Although several studies have shown a positive role of ROS in the induction of proliferation, migration, and differentiation of different cell types, further research is required to determine the specific role of ROS in the osteoblastic cell response and the molecular mechanisms involved in triggering previously reported cellular events.
Topics: Adenosine Triphosphate; Cell Proliferation; Lasers, Semiconductor; Low-Level Light Therapy; Osteoblasts; Reactive Oxygen Species
PubMed: 35751706
DOI: 10.1007/s10103-022-03587-z -
Clinical Colorectal Cancer Dec 2016Surgery remains the standard of care for patients with colorectal liver metastases (CLMs), with a 5-year survival rate approaching 35%. Perioperative chemotherapy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Surgery remains the standard of care for patients with colorectal liver metastases (CLMs), with a 5-year survival rate approaching 35%. Perioperative chemotherapy confers a survival benefit in selected patients with CLMs. The use of molecular targeted therapy combined with neoadjuvant chemotherapy for CLMs, however, remains controversial. We reviewed the published data on combination neoadjuvant chemotherapy and molecular targeted therapy for resectable and initially unresectable CLMs.
MATERIALS AND METHODS
A literature search of the Medline and PubMed databases was conducted to identify studies of neoadjuvant chemotherapy plus molecular targeted therapy in the management of resectable or initially unresectable CLMs. We calculated the pooled proportion and 95% confidence intervals using a random effects model for the relationship of the combination neoadjuvant treatment on the overall response rate and performed a systematic review of all identified studies. The analysis was stratified according to the study design.
RESULTS
The data from 11 studies of 908 patients who had undergone systemic chemotherapy plus targeted therapy for CLM were analyzed. The use of combination neoadjuvant therapy was associated with an overall response rate of 68% (95% confidence interval, 63%-73%), with significant heterogeneity observed in the studies (I = 89.35; P < .001). Of the 11 studies, 4 used a combination that included oxaliplatin, 2 included irinotecan, and 5 included a combination of both. Also, 7 studies used cetuximab and 4 bevacizumab. The overall progression-free survival was estimated at 14.4 months.
CONCLUSION
Current evidence suggests that neoadjuvant chemotherapy plus molecular targeted agents for CLM confers high overall response rates. Combination treatment might also increase the resectability rates in initially unresectable CLM. Further studies are needed to examine the survival outcomes, with a focus on the differential role of molecular targeted therapy in the neoadjuvant versus adjuvant setting.
Topics: Antineoplastic Agents; Chemotherapy, Adjuvant; Colorectal Neoplasms; Female; Humans; Liver Neoplasms; Male; Molecular Targeted Therapy; Neoadjuvant Therapy
PubMed: 27174607
DOI: 10.1016/j.clcc.2016.03.007 -
International Journal of Molecular... Aug 2021Maintaining appropriate levels of physical exercise is an optimal way for keeping a good state of health. At the same time, optimal exercise performance necessitates an... (Review)
Review
Maintaining appropriate levels of physical exercise is an optimal way for keeping a good state of health. At the same time, optimal exercise performance necessitates an integrated organ system response. In this respect, physical exercise has numerous repercussions on metabolism and function of different organs and tissues by enhancing whole-body metabolic homeostasis in response to different exercise-related adaptations. Specifically, both prolonged and intensive physical exercise produce vast changes in multiple and different lipid-related metabolites. Lipidomic technologies allow these changes and adaptations to be clarified, by using a biological system approach they provide scientific understanding of the effect of physical exercise on lipid trajectories. Therefore, this systematic review aims to indicate and clarify the identifying biology of the individual response to different exercise workloads, as well as provide direction for future studies focused on the body's metabolome exercise-related adaptations. It was performed using five databases (Medline (PubMed), Google Scholar, Embase, Web of Science, and Cochrane Library). Two author teams reviewed 105 abstracts for inclusion and at the end of the screening process 50 full texts were analyzed. Lastly, 14 research articles specifically focusing on metabolic responses to exercise in healthy subjects were included. The Oxford quality scoring system scale was used as a quality measure of the reviews. Information was extracted using the participants, intervention, comparison, outcomes (PICOS) format. Despite that fact that it is well-known that lipids are involved in different sport-related changes, it is unclear what types of lipids are involved. Therefore, we analyzed the characteristic lipid species in blood and skeletal muscle, as well as their alterations in response to chronic and acute exercise. Lipidomics analyses of the studies examined revealed medium- and long-chain fatty acids, fatty acid oxidation products, and phospholipids qualitative changes. The main cumulative evidence indicates that both chronic and acute bouts of exercise determine significant changes in lipidomic profiles, but they manifested in very different ways depending on the type of tissue examined. Therefore, this systematic review may offer the possibility to fully understand the individual lipidomics exercise-related response and could be especially important to improve athletic performance and human health.
Topics: Blood Chemical Analysis; Exercise; Female; Humans; Lipidomics; Male; Muscle, Skeletal; Organ Specificity
PubMed: 34445440
DOI: 10.3390/ijms22168734 -
Genes Feb 2023Adaptive evolution is a process in which variation that confers an evolutionary advantage in a specific environmental context arises and is propagated through a... (Review)
Review
Adaptive evolution is a process in which variation that confers an evolutionary advantage in a specific environmental context arises and is propagated through a population. When investigating this process, researchers have mainly focused on describing advantageous phenotypes or putative advantageous genotypes. A recent increase in molecular data accessibility and technological advances has allowed researchers to go beyond description and to make inferences about the mechanisms underlying adaptive evolution. In this systematic review, we discuss articles from 2016 to 2022 that investigated or reviewed the molecular mechanisms underlying adaptive evolution in vertebrates in response to environmental variation. Regulatory elements within the genome and regulatory proteins involved in either gene expression or cellular pathways have been shown to play key roles in adaptive evolution in response to most of the discussed environmental factors. Gene losses were suggested to be associated with an adaptive response in some contexts. Future adaptive evolution research could benefit from more investigations focused on noncoding regions of the genome, gene regulation mechanisms, and gene losses potentially yielding advantageous phenotypes. Investigating how novel advantageous genotypes are conserved could also contribute to our knowledge of adaptive evolution.
Topics: Animals; Evolution, Molecular; Vertebrates; Phylogeny; Genome; Gene Expression Regulation
PubMed: 36833343
DOI: 10.3390/genes14020416 -
JCO Precision Oncology Aug 2022Non-V600 mutations comprise approximately 35% of all BRAF mutations in cancer. Many of these mutations have been identified as oncogenic drivers and can be classified... (Meta-Analysis)
Meta-Analysis
PURPOSE
Non-V600 mutations comprise approximately 35% of all BRAF mutations in cancer. Many of these mutations have been identified as oncogenic drivers and can be classified into three classes according to molecular characteristics. Consensus treatment strategies for class 2 and 3 BRAF mutations have not yet been established.
METHODS
We performed a systematic review and meta-analysis with published reports of individual patients with cancer harboring class 2 or 3 BRAF mutations from 2010 to 2021, to assess treatment outcomes with US Food and Drug Administration-approved mitogen-activated protein kinase (MAPK) pathway targeted therapy (MAPK TT) according to BRAF class, cancer type, and MAPK TT type. Coprimary outcomes were response rate and progression-free survival.
RESULTS
A total of 18,167 studies were screened, identifying 80 studies with 238 patients who met inclusion criteria. This included 167 patients with class 2 and 71 patients with class 3 BRAF mutations. Overall, 77 patients achieved a treatment response. In both univariate and multivariable analyses, response rate and progression-free survival were higher among patients with class 2 compared with class 3 mutations, findings that remain when analyses are restricted to patients with melanoma or lung primary cancers. MEK ± BRAF inhibitors demonstrated greater clinical activity in class 2 compared with class 3 BRAF-mutant tumors than BRAF or EGFR inhibitors.
CONCLUSION
This meta-analysis suggests that MAPK TTs have clinical activity in some class 2 and 3 BRAF-mutant cancers. BRAF class may dictate responsiveness to current and emerging treatment strategies, particularly in melanoma and lung cancers. Together, this analysis provides clinical validation of predictions made on the basis of a mutation classification system established in the preclinical literature. Further evaluation with prospective clinical trials is needed for this population.
Topics: Humans; Lung Neoplasms; Melanoma; Mitogen-Activated Protein Kinases; Prospective Studies; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; United States
PubMed: 35977349
DOI: 10.1200/PO.22.00107 -
European Journal of Nuclear Medicine... Feb 2021To investigate the ability of F-FDG PET/CT to assess the response of patients with metastatic melanoma to immunotherapy. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To investigate the ability of F-FDG PET/CT to assess the response of patients with metastatic melanoma to immunotherapy.
METHODS
A comprehensive search of the literature for studies examining the prognostic value of F-FDG PET/CT in monitoring the response of patients with metastatic melanoma to immunotherapy was performed. We also screened the references of the selected articles to identify any other relevant studies. Detailed data were extracted and categorized. Comprehensive meta-analysis software was used for analysis.
RESULTS
Twenty four eligible articles were included in the systematic review. Based on the baseline F-FDG PET/CT imaging, the pooled hazard ratios of MTV, SLR, SUV/SULmax, SUV/SULpeak, and TLG for overall survival (OS) were 1.777 (95%CI: 1.389-2.275, p < 0.001), 3.425 (95%CI: 1.707-6.869, p = 0.001), 0.941 (95%CI: 0.599-1.477, p = 0.791), 1.704 (95%CI: 1.253-2.316, p = 0.016), and 1.755 (95%CI: 1.315-2.342, p < 0.001), respectively. The conventional and modified response assessment criteria exhibited a pooled sensitivity of 64% (95%CI: 46-79%) and 94% (95%CI: 81-99%) and a pooled specificity of 80% (95%CI: 59-93%) and 84% (95%CI: 64-95%), respectively, for the early F-FDG PET/CT scan. On the other hand, based on the late F-FDG PET/CT scan, the pooled sensitivity of 67% (95%CI: 35-90%) and 92% (95%CI: 73-99%) and pooled specificity of 77% (95%CI: 56-91%) and 76% (95%CI: 50-93%) were observed for the conventional and modified criteria, respectively. PET-detectable immune-related adverse events (irAEs) were associated with the response to therapy.
CONCLUSIONS
The baseline SUVpeak, MTV, and TLG parameters represent promising predictors of the final response of metastatic melanoma patients to immunotherapy. Modified response assessment criteria are potentially an appropriate method for monitoring immunotherapy. irAEs are also valuable for predicting eventual clinical benefit of treatment.
Topics: Fluorodeoxyglucose F18; Humans; Immunotherapy; Melanoma; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prognosis
PubMed: 32728798
DOI: 10.1007/s00259-020-04967-9 -
Chinese Medicine 2018Rhizoma coptidis has been used in China for thousands of years with the functions of heating dampness and purging fire detoxification. But the underlying molecular... (Review)
Review
Rhizoma coptidis has been used in China for thousands of years with the functions of heating dampness and purging fire detoxification. But the underlying molecular mechanisms of Rhizoma coptidis are still far from being fully elucidated. Alkaloids, especially berberine, coptisine and palmatine, are responsible for multiple pharmacological effects of Rhizoma coptidis. In this review, we studied on the effects and molecular mechanisms of Rhizoma coptidis on NF-κB/MAPK/PI3K-Akt/AMPK/ERS and oxidative stress pathways. Then we summarized the mechanisms of these alkaloid components of Rhizoma coptidis on cardiovascular and cerebrovascular diseases, diabetes and diabetic complications. Evidence presented in this review implicated that Rhizoma coptidis exerted beneficial effects on various diseases by regulation of NF-κB/MAPK/PI3K-Akt/AMPK/ERS and oxidative stress pathways, which support the clinical application of Rhizoma coptidis and offer references for future researches.
PubMed: 29930696
DOI: 10.1186/s13020-018-0184-y