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Autoimmunity Reviews Sep 2023Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The... (Review)
Review
BACKGROUND AND AIMS
Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The aim of this systematic review was to collect all published evidence regarding posttranslational modifications in PsA, and the main outcome was to evaluate an association between disease outcomes and specific posttranslational modifications in PsA.
METHODS
A systematic electronic search was performed in Medline, PubMed, Cochrane, Virtual Health Library, and Embase databases. A total of 587 articles were identified; 59 were evaluated after removing duplicates and scanning, of which 47 were included. A descriptive analysis was conducted, with results grouped according to the type of posttranslational modification evaluated. The protocol was registered at the PROSPERO database.
RESULTS
Seven posttranslational modifications were identified: citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress. Anti-citrullinated peptide and anti-carbamylated protein have been evaluated in rheumatoid arthritis. There is now information suggesting that these antibodies may be helpful in improving the diagnosis of PsA and that they may demonstrate a correlation with worse disease progression (erosions, polyarticular involvement, and poor treatment response). Glycosylation was associated with increased inflammation and phosphorylation products related to the expression of SIRT2 and pSTAT3 or the presence of Th17 and cytokine interleukin-22, suggesting a possible therapeutic target.
CONCLUSIONS
Posttranslational modifications often play a key role in modulating protein function in PsA and correlate with disease outcomes. Citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress were identified as associated with diagnosis and prognosis.
Topics: Humans; Arthritis, Psoriatic; Protein Processing, Post-Translational; Citrullination; Glycosylation; Arthritis, Rheumatoid
PubMed: 37487969
DOI: 10.1016/j.autrev.2023.103393 -
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 -
Frontiers in Oncology 2024Early-onset colorectal cancer (CRC), defined as diagnosis before age 50, has increased in recent decades. Although more often diagnosed at advanced stage, associations...
BACKGROUND
Early-onset colorectal cancer (CRC), defined as diagnosis before age 50, has increased in recent decades. Although more often diagnosed at advanced stage, associations with other histological and molecular markers that impact prognosis and treatment remain to be clarified. We conducted a systematic review and meta-analysis concerning the prevalence of prognostic and predictive tumor markers for early- vs. late-onset CRC, including oncogene mutations, microsatellite instability (MSI), and emerging markers including immune cells and the consensus molecular subtypes.
METHODS
We systematically searched PubMed for original research articles published between April 2013-January 2024. Included studies compared the prevalence of tumor markers in early- vs. late-onset CRC. A meta-analysis was completed and summary odds ratios (ORs) with 95% confidence intervals (CIs) were obtained from a random effects model via inverse variance weighting. A sensitivity analysis was completed to restrict the meta-analysis to studies that excluded individuals with Lynch syndrome, a hereditary condition that influences the distribution of tumor markers for early-onset CRC.
RESULTS
In total, 149 articles were identified. Tumors from early-onset CRC are less likely to include mutations in (OR, 95% CI: 0.91, 0.85-0.98), (0.63, 0.51-0.78), (0.70, 0.58-0.84), and (0.88, 0.78-1.00) but more likely to include mutations in (1.68, 1.04-2.73) and (1.34, 1.24-1.45). After limiting to studies that excluded Lynch syndrome, the associations between early-onset CRC and (0.77, 0.64-0.92) and mutation (0.81, 0.67-0.97) were attenuated, while an inverse association with mutation was also observed (0.88, 0.78-0.99). Early-onset tumors are less likely to develop along the CpG Island Methylator Phenotype pathway (0.24, 0.10-0.57), but more likely to possess adverse histological features including high tumor grade (1.20, 1.15-1.25), and mucinous (1.22, 1.16-1.27) or signet ring histology (2.32, 2.08-2.57). A positive association with MSI status (1.31, 1.11-1.56) was also identified. Associations with immune markers and the consensus molecular subtypes are inconsistent.
DISCUSSION
A lower prevalence of mutations in and is consistent with extended survival and superior response to targeted therapies for metastatic disease. Conversely, early-onset CRC is associated with aggressive histological subtypes and and mutations, which may serve as therapeutic targets.
PubMed: 38737895
DOI: 10.3389/fonc.2024.1349572 -
Experimental Gerontology Jun 2023Consistent with the inflammaging concept, cross-sectional associations have been established between inflammatory biomarkers, frailty and sarcopenia. Less certain is the... (Meta-Analysis)
Meta-Analysis Review
Consistent with the inflammaging concept, cross-sectional associations have been established between inflammatory biomarkers, frailty and sarcopenia. Less certain is the value of inflammatory markers in monitoring potential anti-inflammatory effects of therapeutic interventions targeted at frailty and sarcopenia. The aims of this systematic review and meta-analysis are to determine if there is a measurable change in inflammatory or immune biomarkers in interventions that improve frailty or sarcopenia and 2. To determine if there are specific inflammatory biomarkers with greater sensitivity to change. In total, 3051 articles were scanned with 16, primarily exercise and nutrition interventions, included in the systematic review and 11 in the meta-analysis. At least one of C reactive protein (CRP), interleukin-6 (IL-6) or tumour necrosis factor alpha (TNF-α) was reduced in 10 of the 16 review studies but only 3/13 studies reported reductions in multiple markers. CRP, IL-6 and TNF-α were individually sensitive to change in 5/11, 3/12 and 5/12 studies respectively. In meta-analyses, there was a positive effect favouring intervention conditions for CRP (SMD = -0.28, p = 0.05) and IL-6 (SMD = -0.28, p = 0.05) but not TNF- α (SMD = -0.12, p = 0.48). There were specific issues with the quality of these studies which were not designed with an inflammatory marker as the primary outcome. In conclusion, interventions that improve frailty and sarcopenia can also reduce CRP, IL-6 and TNF-α but the literature lacks consistency. We are unable to conclude any one marker as being superior to others.
Topics: Humans; Aged; Sarcopenia; Interleukin-6; Frailty; Tumor Necrosis Factor-alpha; Frail Elderly; Cross-Sectional Studies; Inflammation; Biomarkers; C-Reactive Protein
PubMed: 37156445
DOI: 10.1016/j.exger.2023.112199 -
Cancers Jun 2019pancreatic cancer (PC) has increasing incidence and mortality in developing countries, and drug resistance is a significant hindrance to the efficacy of successful... (Review)
Review
BACKGROUND
pancreatic cancer (PC) has increasing incidence and mortality in developing countries, and drug resistance is a significant hindrance to the efficacy of successful treatment. The objective of this systematic review and meta-analysis was to evaluate the association between miRNAs and response to chemotherapy in pancreatic cancer patients.
METHODS
the systematic review and meta-analysis was based on articles collected from a thorough search of PubMed and Science Direct databases for publications spanning from January 2008 to December 2018. The articles were screened via a set of inclusion and exclusion criteria based on the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Data was extracted, collated and tabulated in MS Excel for further synthesis. Hazard ratio (HR) was selected as the effect size metric to be pooled across studies for the meta-analysis, with the random effects model being applied. Subgroup analysis was also conducted, and the presence of publication bias in the selected studies was assessed. Publication bias of the included studies was quantified.
FINDINGS
of the 169 articles screened, 43 studies were included in our systematic review and 13 articles were included in the meta-analysis. Gemcitabine was observed to be the principal drug used in a majority of the studies. A total of 48 miRNAs have been studied, and 18 were observed to have possible contributions to chemoresistance, while 15 were observed to have possible contributions to chemosensitivity. 41 drug-related genetic pathways have been identified, through which the highlighted miRNA may be affecting chemosensitivity/resistance. The pooled HR value for overall survival was 1.603; (95% Confidence Interval (CI) 1.2-2.143; -value: 0.01), with the subgroup analysis for miR-21 showing HR for resistance of 2.061; 95% CI 1.195-3.556; -value: 0.09.
INTERPRETATION
our results highlight multiple miRNAs that have possible associations with modulation of chemotherapy response in pancreatic cancer patients. Further studies are needed to discover the molecular mechanisms underlying these associations before they can be suggested for use as biomarkers of response to chemotherapeutic interventions in pancreatic cancer.
PubMed: 31252688
DOI: 10.3390/cancers11070900 -
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 -
The Journal of Headache and Pain May 2023Neuroimaging studies have made an important contribution to our understanding of headache pathophysiology. This systematic review aims to provide a comprehensive... (Review)
Review
BACKGROUND
Neuroimaging studies have made an important contribution to our understanding of headache pathophysiology. This systematic review aims to provide a comprehensive overview and critical appraisal of mechanisms of actions of headache treatments and potential biomarkers of treatment response disclosed by imaging studies.
MAIN BODY
We performed a systematic literature search on PubMed and Embase databases for imaging studies investigating central and vascular effects of pharmacological and non-pharmacological treatments used to abort and prevent headache attacks. Sixty-three studies were included in the final qualitative analysis. Of these, 54 investigated migraine patients, 4 cluster headache patients and 5 patients with medication overuse headache. Most studies used functional magnetic resonance imaging (MRI) (n = 33) or molecular imaging (n = 14). Eleven studies employed structural MRI and a few used arterial spin labeling (n = 3), magnetic resonance spectroscopy (n = 3) or magnetic resonance angiography (n = 2). Different imaging modalities were combined in eight studies. Despite of the variety of imaging approaches and results, some findings were consistent. This systematic review suggests that triptans may cross the blood-brain barrier to some extent, though perhaps not sufficiently to alter the intracranial cerebral blood flow. Acupuncture in migraine, neuromodulation in migraine and cluster headache patients, and medication withdrawal in patients with medication overuse headache could promote headache improvement by reverting headache-affected pain processing brain areas. Yet, there is currently no clear evidence for where each treatment acts, and no firm imaging predictors of efficacy. This is mainly due to a scarcity of studies and heterogeneous treatment schemes, study designs, subjects, and imaging techniques. In addition, most studies used small sample sizes and inadequate statistical approaches, which precludes generalizable conclusions.
CONCLUSION
Several aspects of headache treatments remain to be elucidated using imaging approaches, such as how pharmacological preventive therapies work, whether treatment-related brain changes may influence therapy effectiveness, and imaging biomarkers of clinical response. In the future, well-designed studies with homogeneous study populations, adequate sample sizes and statistical approaches are needed.
Topics: Humans; Cluster Headache; Headache; Brain; Migraine Disorders; Headache Disorders, Secondary
PubMed: 37221469
DOI: 10.1186/s10194-023-01590-5 -
Biomedicine & Pharmacotherapy =... Oct 2021β-blockers are commonly prescribed to treat multiple cardiovascular (CV) diseases, but, frequently, adverse drug reactions and intolerance limit their use in clinical... (Meta-Analysis)
Meta-Analysis
β-blockers are commonly prescribed to treat multiple cardiovascular (CV) diseases, but, frequently, adverse drug reactions and intolerance limit their use in clinical practice. Interindividual variability in response to β-blockers may be explained by genetic differences. In fact, pharmacogenetic interactions for some of these drugs have been widely studied, such as metoprolol. But studies that explore genetic variants affecting bisoprolol response are inconclusive, limited or confusing because of mixed results with other β-Blockers, different genetic polymorphisms observed, endpoint studied etc. Because of this, we performed a systematic review in order to find relevant genetic variants affecting bisoprolol response. We have found genetic polymorphism in several genes, but most of the studies focused in ADRB variants. The ADRB1 Arg389Gly (rs1801253) was the most studied genetic polymorphism and it seems to influence the response to bisoprolol, although studies are inconclusive. Even, we performed a meta-analysis about its influence on systolic/diastolic blood pressure in patients treated with bisoprolol, but this did not show statistically significant results. In conclusion, many genetic polymorphisms have been assessed about their influence on patients´ response to bisoprolol and the ADRB1 Arg389Gly (rs1801253) seems the most relevant genetic polymorphism in this regard but results have not been confirmed with a meta-analysis. Our results support the need of further studies about the impact of genetic variants on bisoprolol response, considering different genetic polymorphisms and conducting single and multiple SNPs analysis, including other clinical parameters related to bisoprolol response in a multivariate study.
Topics: Adrenergic beta-1 Receptor Antagonists; Bisoprolol; Blood Pressure; Cardiovascular Diseases; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide; Receptors, Adrenergic, beta-1; Treatment Outcome
PubMed: 34470728
DOI: 10.1016/j.biopha.2021.112069 -
The Lancet Regional Health. Western... Sep 2023The treatment of esophageal cancer has entered a new phase with the development of immunotherapy. The current investigation purpose is to investigate and contrast the...
Efficacy and safety of immunochemotherapy, immunotherapy, chemotherapy, and targeted therapy as first-line treatment for advanced and metastatic esophageal cancer: a systematic review and network meta-analysis.
BACKGROUND
The treatment of esophageal cancer has entered a new phase with the development of immunotherapy. The current investigation purpose is to investigate and contrast the efficacy and safety of immunotherapy, immunochemotherapy, chemotherapy, and targeted therapy as first-line treatment for individuals suffering from advanced and metastatic esophageal cancer.
METHODS
Within the framework of this systematic review and network meta-analysis, clinical trials published or reported in English up until 01 May, 2022, were retrieved from Embase, PubMed, Cochrane Central Register of Controlled Trials, the ClinicalTrials.gov databases, ESMO, and ASCO. The analysis incorporated randomized controlled trials (RCTs) from phase 2 to 3 that evaluated a minimum of two first-line therapeutic regimens for metastatic esophageal cancer were included in the analysis. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary clinical outcomes included the incidence of objective response rate (ORR), and adverse events (AEs) of any grade and ≥3 grade. Relative summary data were extracted from included studies by GZ, HS, WS, and TD. For clear statistical analysis, chemotherapy was divided into two categories of fluorouracil-based chemotherapy (FbCT) and fluorouracil-free chemotherapy (FfCT). Bayesian frequentist approach was employed to conduct the network meta-analysis. The indirect intercomparison between regimens was presented with league tables (HRs and 95% CI for OS and PFS, ORs and 95% CI for ORR and AEs). A greater surface value under the cumulative ranking (SUCRA) indicates a higher potential ranking for the corresponding treatment. A further calculation of relative results about esophageal squamous cell cancer was performed in the subgroup analysis. The current protocol for the systematic review has been properly registered on PROSPERO (registration number: CRD42021241145).
FINDINGS
The final analysis comprised 17 trials that involved 9128 patients and 19 distinct treatment regimens. Within the scope of investigated immunotherapy (IO) combinations, toripalimab + FfCT (tori + FfCT) demonstrated the best OS advantages (tori + FfCT vs. FbCT, HR 0.57, 95% CI 0.38-0.85; tori + FfCT vs. FfCT, HR 0.58, 95% CI 0.43-0.78). In terms of PFS, camrelizumab + FfCT (cam + FfCT) demonstrated the best PFS advantages (FbCT vs. cam + FfCT, HR 1.79, 95% CI 1.22-2.63; FfCT vs. cam + FfCT, HR 1.79, 95% CI 1.47-2.17). Nivolumab + FbCT (nivo + FbCT vs. FfCT, OR 3.29, 95% CI 1.43-7.56) showed the best objective responses. Compared to the conventional chemotherapy regimen, the toxicity was observed to be the slightest for the tori + FfCT (FbCT vs. tori + FfCT, OR 3.07, 95% CI 1.22-7.7) and sintilimab + FfCT (FbCT vs. sin + FfCT, OR 2.93, 95% CI 1.16-7.37). The results in this study were evaluated as having a low heterogeneity since the I value was ≤25% in all analyses.
INTERPRETATION
Compared to foreign IO combinations, sin + FfCT, tori + FfCT, cam + FfCT, and tisle + FbCT are superior first-line treatment options for patients with advanced and metastatic esophageal cancer. Although foreign IO combinations, such as pembro + FbCT and nivo + FbCT obtained better objective response rates than other IO combinations, the addition of chemotherapy to IO worsens the safety profiles. Our findings could provide complementary evidence for current guideline recommendations.
FUNDING
This work was supported by a grant from the Science and Technology Program of Guangzhou, China (202206010103); and Natural Science Foundation of Guangdong Province (2022A1515012469).
PubMed: 37457900
DOI: 10.1016/j.lanwpc.2023.100841 -
Biotechnology Advances Oct 2023Temperature affects cellular processes at different spatiotemporal scales, and identifying the genetic and molecular mechanisms underlying temperature responses paves... (Review)
Review
Temperature affects cellular processes at different spatiotemporal scales, and identifying the genetic and molecular mechanisms underlying temperature responses paves the way to develop approaches for mitigating the effects of future climate scenarios. A systems view of the effects of temperature on cellular physiology can be obtained by focusing on metabolism since: (i) its functions depend on transcription and translation and (ii) its outcomes support organisms' development, growth, and reproduction. Here we provide a systematic review of modelling efforts directed at investigating temperature effects on properties of single biochemical reactions, system-level traits, metabolic subsystems, and whole-cell metabolism across different prokaryotes and eukaryotes. We compare and contrast computational approaches and theories that facilitate modelling of temperature effects on key properties of enzymes and their consideration in constraint-based as well as kinetic models of metabolism. In addition, we provide a summary of insights from computational approaches, facilitating integration of omics data from temperature-modulated experiments with models of metabolic networks, and review the resulting biotechnological applications. Lastly, we provide a perspective on how different types of metabolic modelling can profit from developments in machine learning and models of different cellular layers to improve model-driven insights into the effects of temperature relevant for biotechnological applications.
Topics: Temperature; Metabolic Networks and Pathways; Phenotype; Models, Biological
PubMed: 37348662
DOI: 10.1016/j.biotechadv.2023.108203