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International Journal of Molecular... Apr 2023The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global health concern. Three years... (Review)
Review
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global health concern. Three years since its origin, despite the approval of vaccines and specific treatments against this new coronavirus, there are still high rates of infection, hospitalization, and mortality in some countries. COVID-19 is characterised by a high inflammatory state and coagulation disturbances that may be linked to purinergic signalling molecules such as adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine (ADO), and purinergic receptors (P1 and P2). These nucleotides/nucleosides play important roles in cellular processes, such as immunomodulation, blood clot formation, and vasodilation, which are affected during SARS-CoV-2 infection. Therefore, drugs targeting this purinergic pathway, currently used for other pathologies, are being evaluated in preclinical and clinical trials for COVID-19. In this review, we focus on the potential of these drugs to control the release, degradation, and reuptake of these extracellular nucleotides and nucleosides to treat COVID-19. Drugs targeting the P1 receptors could have therapeutic efficacy due to their capacity to modulate the cytokine storm and the immune response. Those acting in P2X7, which is linked to NLRP3 inflammasome activation, are also valuable candidates as they can reduce the release of pro-inflammatory cytokines. However, according to the available preclinical and clinical data, the most promising medications to be used for COVID-19 treatment are those that modulate platelets behaviour and blood coagulation factors, mainly through the P2Y12 receptor.
Topics: Humans; Nucleosides; COVID-19 Drug Treatment; COVID-19; SARS-CoV-2; Adenosine Triphosphate; Adenosine Diphosphate; Receptors, Purinergic
PubMed: 37175571
DOI: 10.3390/ijms24097865 -
Metabolism: Clinical and Experimental Jul 2023Thiamine (vitamin B1) is an essential cofactor in glucose metabolism, but it remains unclear whether thiamine status is lower in individuals with diabetes compared to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thiamine (vitamin B1) is an essential cofactor in glucose metabolism, but it remains unclear whether thiamine status is lower in individuals with diabetes compared to individuals with normal glucose metabolism.
AIMS
We conducted a systematic review and meta-analysis to study whether the circulating concentrations of various thiamine analytes differ between people with and those without diabetes.
METHODS
PubMed and the Cochrane Central Register of Controlled Trials were searched according to the study protocol. The standardized mean difference (SMD) and 95 % confidence intervals (CI) of thiamine markers between individuals with and without diabetes were used as effect size (random effects model). Subgroup analysis considered albuminuria as an additional variable.
RESULTS
Out of the 459 articles identified, 24 full-texts were eligible for the study, 20 of which qualified for the data analysis and four were evaluated for coherence. Compared to controls, individuals with diabetes showed lower concentrations of thiamine (pooled estimate SMD [95 % CI]: -0.97 [-1.89, -0.06]), thiamine monophosphate (-1.16 [-1.82, -0.50]), and total thiamine compounds (-1.01 [-1.48, -0.54]). Thiamine diphosphate (-0.72 [-1.54, 0.11] and erythrocyte transketolase activity (-0.42 [-0.90, 0.05]) tended to be lower in persons with diabetes than in controls without reaching statistical significance. Subgroup analysis showed that individuals with diabetes and albuminuria had lower thiamine levels than the controls (-2.68 [-5.34, -0.02]).
CONCLUSIONS
Diabetes is associated with lower levels of various thiamine markers, suggesting that individuals with diabetes may have higher thiamine requirements than those without diabetes, but well-designed studies are required to confirm these findings.
Topics: Humans; Thiamine; Albuminuria; Diabetes Mellitus; Thiamine Pyrophosphate; Glucose
PubMed: 37094704
DOI: 10.1016/j.metabol.2023.155565 -
Biotechnology Advances 2023Polyphenolic compounds (such as quercetin and resveratrol) possess potential medicinal values due to their various bioactivities, but poor water solubility hinders their... (Review)
Review
Polyphenolic compounds (such as quercetin and resveratrol) possess potential medicinal values due to their various bioactivities, but poor water solubility hinders their health benefits to humankind. Glycosylation is a well-known post-modification method to biosynthesize natural product glycosides with improved hydrophilicity. Glycosylation has profound effects on decreasing toxicity, increasing bioavailability and stability, together with changing bioactivity of polyphenolic compounds. Therefore, polyphenolic glycosides can be used as food additives, therapeutics, and nutraceuticals. Engineered biosynthesis provides an environmentally friendly and cost-effective approach to generate polyphenolic glycosides through the use of various glycosyltransferases (GTs) and sugar biosynthetic enzymes. GTs transfer the sugar moieties from nucleotide-activated diphosphate sugar (NDP-sugar) donors to sugar acceptors such as polyphenolic compounds. In this review, we systematically review and summarize the representative polyphenolic O-glycosides with various bioactivities and their engineered biosynthesis in microbes with different biotechnological strategies. We also review the major routes towards NDP-sugar formation in microbes, which is significant for producing unusual or novel glycosides. Finally, we discuss the trends in NDP-sugar based glycosylation research to promote the development of prodrugs that positively impact human health and wellness.
Topics: Humans; Glycosides; Carbohydrates; Glycosylation; Glycosyltransferases; Sugars; Nucleotides
PubMed: 37028465
DOI: 10.1016/j.biotechadv.2023.108146 -
BMC Cancer Jan 2023To analyze the incidence and risk of hypertension associated with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors in cancer patients and provide... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To analyze the incidence and risk of hypertension associated with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors in cancer patients and provide reference for clinicians.
METHODS
We used R software to conduct a meta-analysis of phase II/III randomized controlled trials (RCT) on PARP inhibitors for cancer treatment published in PubMed, Embase, Clinical Trials, Cochrane Library and Web of Science from inception to July 29th, 2022.
RESULTS
We included 32 RCTs with 10,654 participants for this meta-analysis. For total PARP inhibitors, the incidence and risk ratio of all-grade hypertension were 12% and 1.22 (95% CI: 0.91-1.65, P = 0.19, I = 81%), and the incidence and risk ratio of grade 3-4 hypertension were 4% and 1.24 (95% CI: 0.74-2.08, P = 0.42, I = 68%). Compared with the control group, the niraparib group, olaparib 800 mg/day group, and olaparib plus cediranib group increased the risk of any grade and grade 3-4 hypertension, while the veliparib group and rucaparib group did not increase the risk of any grade and grade 3-4 hypertension, and olaparib 200 mg-600 mg/day group (exclude olaparib plus cediranib regime) reduced the risk of any grade and grade 3-4 hypertension.
CONCLUSION
Olaparib 200-600 mg/day (excluding olaparib plus cediranib regimen) may be the most suitable PARP inhibitor for cancer patients with high risk of hypertension, followed by veliparib and rucaparib. Niraparib, olaparib 800 mg/day and olaparib combined with cediranib may increase the risk of developing hypertension in cancer patients, clinicians should strengthen the monitoring of blood pressure in cancer patients and give medication in severe cases.
Topics: Humans; Antineoplastic Agents; Hypertension; Incidence; Phthalazines; Poly(ADP-ribose) Polymerase Inhibitors; Neoplasms
PubMed: 36717798
DOI: 10.1186/s12885-023-10571-5 -
Nutrients Jan 2023Cognitive impairment is a staggering personal and societal burden; accordingly, there is a strong interest in potential strategies for its prevention and treatment.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cognitive impairment is a staggering personal and societal burden; accordingly, there is a strong interest in potential strategies for its prevention and treatment. Nutritional supplements have been extensively investigated, and citicoline seems to be a promising agent; its role in clinical practice, however, has not been established. We systematically reviewed studies on the effect of citicoline on cognitive performance.
METHODS
We searched the PubMed and Cochrane Library databases for articles published between 2010 and 2022. Relevant information was extracted and presented following the PRISMA recommendations. Data were pooled using the inverse-variance method with random effects models.
RESULTS
We selected seven studies including patients with mild cognitive impairment, Alzheimer's disease or post-stroke dementia. All the studies showed a positive effect of citicoline on cognitive functions. Six studies could be included in the meta-analysis. Overall, citicoline improved cognitive status, with pooled standardized mean differences ranging from 0.56 (95% CI: 0.37-0.75) to 1.57 (95% CI: 0.77-2.37) in different sensitivity analyses. The overall quality of the studies was poor.
DISCUSSION
Available data indicate that citicoline has positive effects on cognitive function. The general quality of the studies, however, is poor with significant risk of bias in favor of the intervention. Other: PubMed and the Cochrane Library.
Topics: Humans; Cytidine Diphosphate Choline; Alzheimer Disease; Cognitive Dysfunction; Cognition Disorders; Cognition
PubMed: 36678257
DOI: 10.3390/nu15020386 -
AIDS and Behavior Jul 2023Optimal adherence to pre-exposure prophylaxis (PrEP) is critical, but challenging. Men who have sex with men and transgender women have high rates of HIV incidence and... (Review)
Review
Optimal adherence to pre-exposure prophylaxis (PrEP) is critical, but challenging. Men who have sex with men and transgender women have high rates of HIV incidence and substance use. Substance use is associated with reduced adherence to other medications, but associations between substance use and adherence to PrEP are less clear. Thus, the current review 1) systematically evaluates the measurement of substance use and PrEP adherence in studies examining both and 2) summarizes reported findings. Peer-reviewed articles published between 2010 - April 2021 examining associations between substance use and PrEP adherence were reviewed. Fifty studies met inclusion criteria. Assessment of substance use (i.e., mostly via self-reports at baseline) and PrEP adherence (i.e., often via tenofovir diphosphate [TFV-DP] concentration levels at follow-up) varied considerably across studies. Many studies used categorical variables (e.g., substance use: yes/no). Studies using TFV-DP levels defined adherence consistently (i.e., TFV-DP ≥ 700 fmol/punch), with slight variations. Qualitative studies (n = 10) indicated that substance use (mainly alcohol) is related to poorer PrEP adherence. While quantitative findings to date are equivocal for alcohol, there is a pattern of findings linking stimulant use with poorer PrEP adherence. This review reveals four methodological gaps, which can be addressed in future research by: 1) use of uniform benchmarks for substance use measures, 2) prospective assessment for substance use, 3) use of continuous outcome variables wherever possible, and 4) more extensive consideration of potential confounders. Addressing these methodological gaps may help us reach more definitive conclusions regarding associations between substance use and PrEP adherence.
Topics: Male; Humans; Female; HIV Infections; Homosexuality, Male; Tenofovir; Pre-Exposure Prophylaxis; Transgender Persons; Sexual and Gender Minorities; Prospective Studies; Medication Adherence; Substance-Related Disorders; Anti-HIV Agents
PubMed: 36538138
DOI: 10.1007/s10461-022-03948-3 -
Journal of Cardiovascular Medicine... Sep 2022Ticagrelor and clopidogrel are antiplatelet drugs that act by binding to the adenosine diphosphate P2Y12 receptor. Previous studies have compared between them regarding...
BACKGROUND
Ticagrelor and clopidogrel are antiplatelet drugs that act by binding to the adenosine diphosphate P2Y12 receptor. Previous studies have compared between them regarding the endothelial function effect.
OBJECTIVES
This systematic review aims to summarize the evidence comparing the efficacy of ticagrelor vs. clopidogrel in improving endothelial function in patients with coronary artery disease (CAD).
METHODS
In August 2021, the Scopus, PubMed, Web of Science, and Cochrane library were searched systematically for eligible trials. We included randomized controlled trials that compared the efficacy of ticagrelor vs. clopidogrel in improving endothelial function in patients with CAD.
RESULTS
Seven trials (n = 511) were included in our systematic review. Ticagrelor resulted in a greater elevation of the level of progenitor cells CD34+ KDR+ and CD34+ 133+ (P = 0.036 and P = 0.019, respectively), with a lower rate of endothelial cell apoptosis rate (P < 0.001). Moreover, ticagrelor showed superiority regarding nitric oxide, radical oxygen species, and soluble P-selectin levels (P = 0.03, P = 0.02, and P = 0.019, respectively). Flow-mediated dilation findings differed between the studies (P = 0.004 vs. P = 0.39).
CONCLUSION
Ticagrelor appears to exert an additional improvement in endothelial function compared with clopidogrel in patients with coronary heart disease.
Topics: Acute Coronary Syndrome; Clopidogrel; Coronary Artery Disease; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome
PubMed: 35994706
DOI: 10.2459/JCM.0000000000001345 -
Journal of Clinical Oncology : Official... Sep 2022To update the ASCO Biomarkers to Guide Systemic Therapy for Metastatic Breast Cancer (MBC) guideline.
PURPOSE
To update the ASCO Biomarkers to Guide Systemic Therapy for Metastatic Breast Cancer (MBC) guideline.
METHODS
An Expert Panel conducted a systematic review to identify randomized clinical trials and prospective-retrospective studies from January 2015 to January 2022.
RESULTS
The search identified 19 studies informing the evidence base.
RECOMMENDATIONS
Candidates for a regimen with a phosphatidylinositol 3-kinase inhibitor and hormonal therapy should undergo testing for mutations using next-generation sequencing of tumor tissue or circulating tumor DNA (ctDNA) in plasma to determine eligibility for alpelisib plus fulvestrant. If no mutation is found in ctDNA, testing in tumor tissue, if available, should be used. Patients who are candidates for poly (ADP-ribose) polymerase (PARP) inhibitor therapy should undergo testing for germline and pathogenic or likely pathogenic mutations to determine eligibility for a PARP inhibitor. There is insufficient evidence for or against testing for a germline pathogenic variant to determine eligibility for PARP inhibitor therapy in the metastatic setting. Candidates for immune checkpoint inhibitor therapy should undergo testing for expression of programmed cell death ligand-1 in the tumor and immune cells to determine eligibility for treatment with pembrolizumab plus chemotherapy. Candidates for an immune checkpoint inhibitor should also undergo testing for deficient mismatch repair/microsatellite instability-high to determine eligibility for dostarlimab-gxly or pembrolizumab, as well as testing for tumor mutational burden. Clinicians may test for fusions to determine eligibility for TRK inhibitors. There are insufficient data to recommend routine testing of tumors for mutations, for homologous recombination deficiency, or for TROP2 expression to guide MBC therapy selection. There are insufficient data to recommend routine use of ctDNA or circulating tumor cells to monitor response to therapy among patients with MBC.Additional information can be found at www.asco.org/breast-cancer-guidelines.
Topics: Adenosine Diphosphate; Antibodies, Monoclonal, Humanized; Biomarkers, Tumor; Breast Neoplasms; Circulating Tumor DNA; Class I Phosphatidylinositol 3-Kinases; Female; Fulvestrant; Humans; Immune Checkpoint Inhibitors; Ligands; Phosphatidylinositol 3-Kinases; Poly(ADP-ribose) Polymerase Inhibitors; Prospective Studies; Retrospective Studies; Ribose
PubMed: 35759724
DOI: 10.1200/JCO.22.01063 -
Journal of Gynecology Obstetrics and... Sep 2022
Corrigendum to "correlation of poly (adenosine diphosphate [ADP]-ribose) polymerase expression and prognosis in ovarian cancer: A systematic review and meta-analysis" [J Gynecol Obstet Hum Reprod 2022;51(4): 102344. Doi: 10.1016/j.jogoh.2022.102344].
PubMed: 35717833
DOI: 10.1016/j.jogoh.2022.102427 -
Journal of Cancer Research and... Dec 2021To evaluate the efficacy, safety, and potential advantages of Poly (ADP-ribose) polymerase inhibitors (PARPi) in treating BRCA-mutated breast cancer, we performed a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluate the efficacy, safety, and potential advantages of Poly (ADP-ribose) polymerase inhibitors (PARPi) in treating BRCA-mutated breast cancer, we performed a meta-analysis of published studies.
MATERIALS AND METHODS
Four randomized controlled trials (RCTs) were included in the meta-analysis. Data analysis was conducted in Review Manager 5.4.
RESULTS
The progression-free survival (PFS) of the patients with triple-negative (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.74-0.88; P < 0.00001) or hormone receptor-positive (HR 0.83; 95% CI 0.77-0.91; P < 0.0001) BRCA-mutated breast cancer was significantly extended in the containing PARPi therapy arm versus the chemotherapy arm. PFS of the patients who did not receive platinum-based therapy (HR 0.78; 95% CI 0.70-0.86; P < 0.0001) was significantly extended in the PARPi monotherapy arm versus the chemotherapy arm. The objective response rate of patients treated by PARPi monotherapy (risk ratio [RR] 2.51; 95% CI 1.81-3.47; P < 0.00001) was significantly higher than that of patients treated by chemotherapy. The incidence of thrombocytopenia in patients received PARPi combined therapy was obviously increased compared with chemotherapy group (RR 1.36; 95% CI 1.07-1.72; P = 0.01). PARPi monotherapy markedly increased the incidence of anemia (RR 5.83; 95% CI 2.64-12.88; P < 0.0001) versus chemotherapy. However, the risk of neutropenia (RR 0.48; 95% CI 0.29-0.81; P = 0.006) was reduced in the PARPi monotherapy arm. There were no statistical differences in other adverse events among these three groups.
CONCLUSIONS
PARPi combined therapy and monotherapy improved PFS of patients with BRCA-mutated breast cancer compared with standard chemotherapy, which was unrelated to type of BRCA mutation and status of hormone receptor. PARPi therapy has slightly higher hematological toxicity and better overall safety and tolerance.
PROSPERO REGISTRATION NUMBER
CRD42020204385.
Topics: Adenosine Diphosphate; Breast Neoplasms; Female; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Progression-Free Survival; Ribose
PubMed: 35381738
DOI: 10.4103/jcrt.jcrt_2085_21