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Critical Reviews in Oncology/hematology Aug 2023Folate metabolism is a target for various chemotherapeutic drugs. Folate and its synthetic variant folic acid are B-vitamins. To what extent these vitamins impact... (Review)
Review
Folate metabolism is a target for various chemotherapeutic drugs. Folate and its synthetic variant folic acid are B-vitamins. To what extent these vitamins impact treatment tolerance in patients with cancer remains unclear. A systematic literature review was conducted on intake and status of folate and folic acid in relation to chemotherapy-induced toxicities in children and adults with cancer. A total of 6231 publications were identified, of which 40 publications met the inclusion criteria. In 12 out of 22 studies focusing on antifolates, a deficient folate status and lower folate and folic acid intake were associated with a higher risk of toxicities. In 8 out of 14 studies focusing on fluoropyrimidine treatments, a higher folate status and intake were associated with a higher risk of toxicities. These findings might explain interindividual differences in treatment tolerance and highlight the importance of evaluating nutritional status in oncology care.
Topics: Adult; Child; Humans; Folic Acid; Vitamin B Complex; Nutritional Status; Neoplasms; Antineoplastic Agents; Dietary Supplements
PubMed: 37353179
DOI: 10.1016/j.critrevonc.2023.104061 -
Metabolomics : Official Journal of the... Aug 2023Head and neck cancer (HNC) is the fifth most common cancer globally. Diagnosis at early stages are critical to reduce mortality and improve functional and esthetic... (Review)
Review
INTRODUCTION
Head and neck cancer (HNC) is the fifth most common cancer globally. Diagnosis at early stages are critical to reduce mortality and improve functional and esthetic outcomes associated with HNC. Metabolomics is a promising approach for discovery of biomarkers and metabolic pathways for risk assessment and early detection of HNC.
OBJECTIVES
To summarize and consolidate the available evidence on metabolomics and HNC in plasma/serum, saliva, and urine.
METHODS
A systematic search of experimental research was executed using PubMed and Web of Science. Available data on areas under the curve was extracted. Metabolic pathway enrichment analysis were performed to identify metabolic pathways altered in HNC. Fifty-four studies were eligible for data extraction (33 performed in plasma/serum, 15 in saliva and 6 in urine).
RESULTS
Metabolites with high discriminatory performance for detection of HNC included single metabolites and combination panels of several lysoPCs, pyroglutamate, glutamic acid, glucose, tartronic acid, arachidonic acid, norvaline, linoleic acid, propionate, acetone, acetate, choline, glutamate and others. The glucose-alanine cycle and the urea cycle were the most altered pathways in HNC, among other pathways (i.e. gluconeogenesis, glycine and serine metabolism, alanine metabolism, etc.). Specific metabolites that can potentially serve as complementary less- or non-invasive biomarkers, as well as metabolic pathways integrating the data from the available studies, are presented.
CONCLUSION
The present work highlights utility of metabolite-based biomarkers for risk assessment, early detection, and prognostication of HNC, as well as facilitates incorporation of available metabolomics studies into multi-omics data integration and big data analytics for personalized health.
Topics: Humans; Alanine; Body Fluids; Glucose; Head and Neck Neoplasms; Metabolomics
PubMed: 37644353
DOI: 10.1007/s11306-023-02038-2 -
PeerJ 2023To explore the comparative effectiveness of nutritional supplements in improving glycolipid metabolism and endocrine function in patients with polycystic ovary syndrome... (Meta-Analysis)
Meta-Analysis
Comparison of nutritional supplements in improving glycolipid metabolism and endocrine function in polycystic ovary syndrome: a systematic review and network meta-analysis.
OBJECTIVE
To explore the comparative effectiveness of nutritional supplements in improving glycolipid metabolism and endocrine function in patients with polycystic ovary syndrome (PCOS).
METHOD
Randomized controlled clinical trials on the effects of nutritional supplements in PCOS patients were searched in PubMed, Embase, Cochrane Library, and Web of Science from their establishments to March 15, 2023. Then, literature screening, data extraction, and network meta-analysis were performed. This study was registered at PROSPERO (registration number CRD 42023441257).
RESULT
Forty-one articles involving 2,362 patients were included in this study. The network meta-analysis showed that carnitine, inositol, and probiotics reduced body weight and body mass index (BMI) compared to placebo, and carnitine outperformed the other supplements (SUCRAs: 96.04%, 97.73%, respectively). Omega-3 lowered fasting blood glucose (FBG) (SUCRAs: 93.53%), and chromium reduced fasting insulin (FINS) (SUCRAs: 72.90%); both were superior to placebo in improving insulin resistance index (HOMA-IR), and chromium was more effective than Omega-3 (SUCRAs: 79.99%). Selenium was potent in raising the quantitative insulin sensitivity index (QUICKI) (SUCRAs: 87.92%). Coenzyme Q10 was the most effective in reducing triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels (SUCRAs: 87.71%, 98.78%, and 98.70%, respectively). Chromium and probiotics decreased TG levels, while chromium and vitamin D decreased TC levels. No significant differences were observed in high-density lipoprotein cholesterol (HDL-C), total testosterone (TT), sex-hormone binding globulin (SHBG), and C-reactive protein (CRP) between nutritional supplements and placebo.
CONCLUSION
Carnitine was relatively effective in reducing body mass, while chromium, Omega-3, and selenium were beneficial for improving glucose metabolism. Meanwhile, coenzyme Q10 was more efficacious for improving lipid metabolism. However, publication bias may exist, and more high-quality clinical randomized controlled trials are needed.
Topics: Female; Humans; Polycystic Ovary Syndrome; Network Meta-Analysis; Selenium; Carnitine; Cholesterol, HDL; Lipid Metabolism; Chromium; Glycolipids; Randomized Controlled Trials as Topic
PubMed: 38025704
DOI: 10.7717/peerj.16410 -
Osteoporosis International : a Journal... Sep 2023Poor adherence reduces the effectiveness of osteoporosis treatment, resulting in lower bone mineral density and subsequently higher fracture rates. Reliable and... (Review)
Review
Poor adherence reduces the effectiveness of osteoporosis treatment, resulting in lower bone mineral density and subsequently higher fracture rates. Reliable and practical tools are needed to measure medication adherence. The aim of this systematic review was to find osteoporosis medication adherence measurement tools and assess their applicability. Osteoporosis adherence measurement tools and all their related keywords in PubMed, Embase, Web of Science, and Scopus databases were searched on 4 December, 2022. After excluding duplicates in the Endnote software, two researchers independently investigated the remaining articles and included all those that used a method for measuring adherence to osteoporosis pharmacotherapy. Articles that did not specify the medications evaluated or if the primary focus was not adherence excluded. Two common measures of adherence, i.e., compliance and persistence were included. Four separate tables were designed, one for direct methods, one for formulas, one for questionnaires, and one for electronic methods of measuring adherence to treatment. Quality assessment was performed for selected articles by the Newcastle-Ottawa Quality Assessment Scale (NOS). A total of 3821 articles were found, of which 178 articles met the inclusion and exclusion criteria. In general, five types of methods were observed to measure medication adherence of osteoporosis, including direct methods (n = 4), pharmacy records (n = 17), questionnaires (n = 13), electronic methods (n = 1), and tablet counting (n = 1). The most commonly used adherence measurement tool, based on pharmacy records, was medication possession ratio (MPR). Among questionnaires, Morisky Medication Adherence Scale was mostly used. Our findings show what tools have been used to measure medication adherence in osteoporosis patients. Among these tools, direct methods and electronic methods are the most accurate methods. However, due to their high cost, they are practically not used in measuring osteoporosis medication adherence. Questionnaires are the most popular among them and are mostly used in osteoporosis.
Topics: Humans; Bone Density Conservation Agents; Osteoporosis; Medication Adherence; Fractures, Bone; Bone Density
PubMed: 37286664
DOI: 10.1007/s00198-023-06789-5 -
European Journal of Medicinal Chemistry Dec 2023Proteolysis-targeting chimeras (PROTACs) have been an area of intensive research with the potential to extend drug space not target to traditional molecules. In the last... (Review)
Review
Proteolysis-targeting chimeras (PROTACs) have been an area of intensive research with the potential to extend drug space not target to traditional molecules. In the last half decade, we have witnessed several PROTACs initiated phase I/II/III clinical trials, which inspired us a lot. However, the structure of PROTACs beyond "rule of 5" resulted in developing PROTACs with acceptable oral pharmacokinetic (PK) properties remain one of the biggest bottleneck tasks. Many reports have demonstrated that it is possible to access orally bioavailable PROTACs through rational ligand and linker modifications. In this review, we systematically reviewed and highlighted the most recent advances in orally bioavailable PROTACs development, especially focused on the medicinal chemistry campaign of discovery process and in vivo oral PK properties. Moreover, the constructive strategies for developing oral PROTACs were proposed comprehensively. Collectively, we believe that the strategies summarized here may provide references for further development of oral PROTACs.
Topics: Proteolysis Targeting Chimera; Chemistry, Pharmaceutical; Proteolysis; Ubiquitin-Protein Ligases
PubMed: 37708797
DOI: 10.1016/j.ejmech.2023.115793 -
Phytomedicine : International Journal... Sep 2023Liver diseases have a negative impact on global health and are a leading cause of death worldwide. Chlorogenic acids (CGAs), a family of esters formed between certain... (Review)
Review
BACKGROUND
Liver diseases have a negative impact on global health and are a leading cause of death worldwide. Chlorogenic acids (CGAs), a family of esters formed between certain trans-cinnamic acids and quinic acid, are natural polyphenols abundant in coffee, tea, and a variety of traditional Chinese medicines (TCMs). They are reported to have good hepatoprotective effects against various liver diseases.
PURPOSE
This review aims to analyze the available literature on the hepatoprotective effect of CGAs, with particular emphasis on their mechanisms.
METHODS
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed and Web of Science databases were adopted to retrieve all relevant literature on CGAs for liver disease from 2013 to March 2023.
RESULTS
Research has indicated that CGAs play a crucial role in improving different types of liver diseases, including drug-induced liver injury (DILI), alcoholic liver disease (ALD), metabolic (dysfunction)-associated fatty liver disease (MAFLD), cholestatic liver disease (CLD), liver fibrosis, and liver cancer. CGAs display remarkable antioxidant and anti-inflammatory effects by activating erythroid 2-related factor 2 (Nrf2) and inhibiting toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathways. Some important molecules such as AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), and other key physiological processes like intestinal barrier and gut microbiota have also been discovered to participate in CGAs-provided amelioration on various liver diseases.
CONCLUSION
In this review, different studies indicate that CGAs have an excellent protective effect against various liver diseases associated with various signaling pathways.
Topics: Humans; Chlorogenic Acid; Polyphenols; Antioxidants; Liver Diseases, Alcoholic; Nucleotidyltransferases; Liver
PubMed: 37453191
DOI: 10.1016/j.phymed.2023.154961 -
Journal of Nanobiotechnology Jan 2024Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins,... (Review)
Review
Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins, lipids, and nucleic acids. Engineered exosomes generated through genetic modification of parent cells show promise as drug delivery vehicles, and they have been demonstrated to have great therapeutic potential for treating cancer, cardiovascular, neurological, and immune diseases, but systematic knowledge is lacking regarding optimization of drug loading and assessment of delivery efficacy. This review summarizes current approaches for engineering exosomes and evaluating their drug delivery effects, and current techniques for assessing exosome drug loading and release kinetics, cell targeting, biodistribution, pharmacokinetics, and therapeutic outcomes are critically examined. Additionally, this review synthesizes the latest applications of exosome engineering and drug delivery in clinical translation. The knowledge compiled in this review provides a framework for the rational design and rigorous assessment of exosomes as therapeutics. Continued advancement of robust characterization methods and reporting standards will accelerate the development of exosome engineering technologies and pave the way for clinical studies.
Topics: Humans; Exosomes; Tissue Distribution; Drug Delivery Systems; Extracellular Vesicles; Neoplasms; Pharmaceutical Preparations
PubMed: 38172932
DOI: 10.1186/s12951-023-02259-6 -
Osteoporosis International : a Journal... Dec 2023This meta-analysis aims to evaluate the impact of Sodium Glucose Transporter 2 (SGLT2) inhibitors on fractures, bone mineral density (BMD), and bone metabolism markers... (Meta-Analysis)
Meta-Analysis Review
This meta-analysis aims to evaluate the impact of Sodium Glucose Transporter 2 (SGLT2) inhibitors on fractures, bone mineral density (BMD), and bone metabolism markers in type 2 diabetes mellitus (T2DM) patients. Pooled relative risk (RR) with 95% confidence interval (CI) assessed the relationship between SGLT2 inhibitors and fracture risk. Weighted mean difference (WMD) with 95% CI explored the correlation between SGLT2 inhibitors and BMD, as well as bone metabolism markers. A total of 20 randomised controlled trials (RCTs) involving 12,764 patients were analysed. No significant association emerged between SGLT2 inhibitor use and elevated fracture risk (pooled RR = 1.21, 95% CI [0.95, 1.54], I = 22%). Furthermore, SGLT2 inhibitors exhibited no substantial effects on BMD changes at the lumbar spine (WMD = -0.02, 95% CI [-0.38, 0.34]), femoral neck (WMD = 0.11, 95% CI [-0.28, 0.50]), total hip (WMD = -0.20, 95% CI [-0.41, 0.01]), and distal forearm (WMD = -0.20, 95% CI [-0.62, 0.22]). Similarly, no notable impact of SGLT2 inhibitors on bone metabolism markers, including CTX (WMD = 0.04, 95% CI [-0.02, 0.09]), P1NP (WMD = 1.06, 95% CI [-0.44, 2.57]), PTH (WMD = 0.34, 95% CI [-0.07, 0.75]), calcium (WMD = 0.01, 95% CI [-0.02, 0.04]), and phosphate (WMD = 2.37, 95% CI [-0.76, 5.49]). The findings suggest that the utilization of SGLT2 inhibitors is not significantly linked to an elevated risk of fractures in individuals with T2DM. However, further clinical investigations and extended follow-up periods are warranted to establish more conclusive determinations.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Bone Density; Fractures, Bone; Diabetes Mellitus, Type 2; Risk; Randomized Controlled Trials as Topic
PubMed: 37695339
DOI: 10.1007/s00198-023-06908-2 -
Nephrology, Dialysis, Transplantation :... Oct 2023Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis),... (Meta-Analysis)
Meta-Analysis
The association between dual RAAS inhibition and risk of acute kidney injury and hyperkalemia in patients with diabetic kidney disease: a systematic review and meta-analysis.
BACKGROUND AND OBJECTIVES
Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis), angiotensin-receptor blockers (ARBs), direct renin inhibitors (DRIs), or mineralocorticoid receptor antagonists (MRAs). It is hypothesized that dual RAAS blockade would result in a more complete inhibition of the RAAS cascade. However, large clinical trials on dual RAAS inhibition have shown increased risk of acute kidney injury (AKI) and hyperkalemia without additional benefit on mortality, cardiovascular events, or chronic kidney disease (CKD) progression compared to RAAS inhibitor monotherapy in patients with diabetic kidney disease (DKD). The development of newer, more selective non-steroidal MRAs as cardiorenal protective therapies has created a new opportunity for dual RAAS inhibition. We conducted a systematic review and meta-analysis of the risks of AKI and hyperkalemia with dual RAAS blockade in patients with DKD.
DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS
This is a systematic review and meta-analysis of the randomized controlled trials (RCT) published from 1 January 2006 to 30 May 2022. The study population included adult patients with DKD receiving dual RAAS blockade. A total of 31 RCTs and 33 048 patients were included in the systematic review. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random effects.
RESULTS
There were 208 AKI events in 2690 patients on ACEi + ARB versus 170 in 4264 patients with ACEi or ARB monotherapy (pooled RR 1.48, 95% CI: 1.23-1.39). There were 304 hyperkalemia events in 2818 patients on ACEi + ARB versus 208 in 4396 patients with ACEi or ARB monotherapy (pooled RR 1.97, 95% CI: 1.32-2.94). A non-steroidal MRA + ACEi or ARB showed no increase in the risk of AKI (pooled RR 0.97, 95% CI: 0.81-1.16) compared to ACEi or ARB monotherapy but had a 2-fold higher risk of hyperkalemia with 953 events in 7837 patients in dual therapy versus 454 events in 6895 patients in monotherapy (pooled RR 2.05, 95% CI: 1.84-2.28). A steroidal MRA + ACEi or ARB had a 5-fold higher risk of hyperkalemia with 28 events in 245 at risk in dual therapy versus five events in 248 at risk in monotherapy (pooled RR 5.42 95% CI: 2.15-13.67).
CONCLUSION
Dual therapy with RAASi is associated with an increased risk of AKI and hyperkalemia compared to RAASi monotherapy. Conversely, dual therapy with RAAS inhibitors and non-steroidal MRAs have no additional risk of AKI but a similar risk of hyperkalemia, which is lower than dual therapy with RAAS inhibitors and steroidal MRAs.
Topics: Adult; Humans; Renin-Angiotensin System; Diabetic Nephropathies; Hyperkalemia; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Acute Kidney Injury; Diabetes Mellitus
PubMed: 37309038
DOI: 10.1093/ndt/gfad101 -
Clinical Nutrition (Edinburgh, Scotland) Dec 2023Diabetes mellitus is a risk factor for muscle loss and sarcopenia. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) or "gliflozins" are one of the newest... (Review)
Review
Diabetes mellitus is a risk factor for muscle loss and sarcopenia. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) or "gliflozins" are one of the newest anti-hyperglycemic drugs. They reduce blood glucose levels by inhibiting renal glucose reabsorption in the early proximal convoluted tubule. Various randomized trials showed that SGLT2i have cardio-protective and reno-protective action. SGLT2i also affect body composition. They usually decrease body fat percentage, visceral and subcutaneous adipose tissue. However, regarding the muscle mass, there are conflicting findings some studies showing detrimental effects and others showed neutral or beneficial effects. This issue is extremely important not only because of the wide use of SGLT2i around globe; but also skeletal muscle mass consumes large amounts of calories during exercise and is an important determinant of resting metabolic rate and skeletal muscle loss hinders energy consumption leading to obesity. In this systematic review, we extensively reviewed the experimental and clinical studies regarding the impact of SGLT2i on muscle mass and related metabolic alterations. Importantly, studies are heterogeneous and there is unmet need to highlight the alterations in muscle during SGLT2i use.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Sarcopenia; Glucose; Sodium; Symporters
PubMed: 37862820
DOI: 10.1016/j.clnu.2023.10.004