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BMC Geriatrics Aug 2022Healthy aging relies on mitochondrial functioning because this organelle provides energy and diminishes oxidative stress. Single nucleotide polymorphisms (SNPs) in...
INTRODUCTION
Healthy aging relies on mitochondrial functioning because this organelle provides energy and diminishes oxidative stress. Single nucleotide polymorphisms (SNPs) in TOMM40, a critical gene that produces the outer membrane protein TOM40 of mitochondria, have been associated with mitochondrial dysfunction and neurodegenerative processes. Yet it is not clear whether or how the mitochondria may impact human longevity. We conducted this review to ascertain which SNPs have been associated with markers of healthy aging.
METHODS
Using the PRISMA methodology, we conducted a systematic review on PubMed and Embase databases to identify associations between TOMM40 SNPs and measures of longevity and healthy aging.
RESULTS
Twenty-four articles were selected. The TOMM40 SNPs rs2075650 and rs10524523 were the two most commonly identified and studied SNPs associated with longevity. The outcomes associated with the TOMM40 SNPs were changes in BMI, brain integrity, cognitive functions, altered inflammatory network, vulnerability to vascular risk factors, and longevity.
DISCUSSIONS
Our systematic review identified multiple TOMM40 SNPs potentially associated with healthy aging. Additional research can help to understand mechanisms in aging, including resilience, prevention of disease, and adaptation to the environment.
Topics: Aging; Healthy Aging; Humans; Longevity; Membrane Transport Proteins; Mitochondrial Precursor Protein Import Complex Proteins; Polymorphism, Single Nucleotide
PubMed: 35964003
DOI: 10.1186/s12877-022-03337-4 -
Oncotarget Mar 2017Glucose transporter 1 (GLUT1), the uniporter protein encoded by the SLC2A1 gene, is a key rate-limiting factor in the transport of glucose in cancer cells, and... (Meta-Analysis)
Meta-Analysis Review
Glucose transporter 1 (GLUT1), the uniporter protein encoded by the SLC2A1 gene, is a key rate-limiting factor in the transport of glucose in cancer cells, and frequently expressed in a significant proportion of human cancers. Numerous studies have reported paradoxical evidence of the relationship between GLUT1 expression and prognosis in solid human tumors. To address this discrepancy, we conducted a thorough search of Pubmed and Web of Science for studies evaluating the expression of GLUT1 and overall survival (OS) and disease-free survival (DFS) in patients with solid cancer from 1993 to April 2016. Data from published researches were extracted and computed into odds ratio (OR). A total of 26 studies including 2948 patients met our search criteria and were evaluated. Overexpression of GLUT1 was found to significantly correlate with poor 3-year OS (OR: 2.86; 95% CI, 1.90-4.32, P < 0.00001) and 5-year OS (OR: 2.52; 95% CI, 1.75-3.61, P < 0.00001) of solid tumors. Similar results were observed when analysis of DFS was performed. Subgroup analysis revealed that elevated GLUT1 expression was associated with worse prognosis of oral squamous cell carcinoma and breast cancer. Taken together, overexpression of GLUT1 is correlated with poor survival in most solid tumors, suggesting that the expression status of GLUT1 is a vital prognostic indicator and promising therapeutic target in solid tumors.
Topics: Biomarkers, Tumor; Disease-Free Survival; Glucose Transporter Type 1; Humans; Neoplasms; Prognosis
PubMed: 28187435
DOI: 10.18632/oncotarget.15171 -
Medicine May 2017We aimed to assess the safety and efficiency of the novel sodium glucose co-transporter 2 (SGLT2) inhibitor in combinations with insulin for type 1 and type 2 diabetes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We aimed to assess the safety and efficiency of the novel sodium glucose co-transporter 2 (SGLT2) inhibitor in combinations with insulin for type 1 and type 2 diabetes mellitus (T1DM and T2DM).
METHODS
We searched Medline, Pubmed, Embase, and the Cochrane Collaboration Library from January 2010 to December 2016 without restriction of language. FDA data and Clinical Trials (http://www.clinicaltrials.gov) were also searched. Study selection, data extraction, and evaluation of risk of bias were performed by 2 persons independently. The risk of bias was assessed by Cochrance System Evaluate Method and Q test was used to evaluate the heterogeneity between studies. We used random effect model to analyze the results by Revman 5.3. This meta-analysis has been registered at online public registry PROSPERO (registration number is: CRD42017054718).
RESULTS
Nine trials including 3069 patients were analyzed. Compared with control group, SGLT2 inhibitor produced absolute reduction in glycosylated hemoglobin A1c (HbA1c) (MD -1.35%, 95% confidence interval [CI] [-2.36 to -0.34], P = .009), fasting plasma glucose (FPG) (MD -1.01 mmol/L, 95%CI [-1.98 to 0.04], P = .04), insulin dosage (MD -4.85 U/24 hours, 95%CI [-7.42 to -2.29], P = .002), and body weight (MD -2.30 kg, 95%CI [-3.09 to -1.50], P < .00001). But the risk of hypoglycemia (OR 1.18, 95%CI [0.86, 1.61], P = . 30) and urinary tract infection (UTI) (OR 1.34, 95%CI [0.79, 2.27], P = .28) were proved as no difference and genital tract infection (GTI) with SGLT2 inhibitors was higher than control group (OR 2.96, 95%CI [1.05, 8.37], P = .04), in which cases were mild and responded to the therapy. According to the subgroup analysis, SGLT2 inhibitors had a similar effect in effective factors of both T1DM and T2DM, but the risk of GTI mainly increased in T2DM versus T1DM (T1DM OR 0.27 [0.01, 7.19], P = .43 vs T2DM OR 4.28 [2.00, 9.16], P = .0002).
CONCLUSION
SGLT2 inhibitors have improved the HbA1c, FPG, and body weight when combined with insulin and decreased the dose of insulin without increasing the risk of hypoglycemia. However, SGLT2 inhibitor was proved to be related to the events of GTI, despite SGLT2 inhibitors appeared to be well tolerated. We suggest that more monitoring should be done to prevent the events of GTI, and more randomized controlled trials should be planned next step.
Topics: Diabetes Mellitus; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 28538386
DOI: 10.1097/MD.0000000000006944 -
Journal of Cystic Fibrosis : Official... May 2023The combination of CFTR modulators ivacaftor, tezacaftor and elexacaftor (Trikafta®, Kaftrio®) significantly improve outcomes, including survival in a broad range of... (Review)
Review
The combination of CFTR modulators ivacaftor, tezacaftor and elexacaftor (Trikafta®, Kaftrio®) significantly improve outcomes, including survival in a broad range of cystic fibrosis patients. These drugs have complicated metabolic profiles that make the potential for drug interactions an important consideration for prescribers, care providers and patients. Prolonged survival also increases risk of age-related disease and their associated pharmacotherapy, further increasing the risk of drug interactions and the need for increased vigilance amongst care providers. We systematically searched the literature for studies identifying and evaluating pharmacokinetic and pharmacodynamic drug interactions involving the components of Trikafta®/Kaftrio®. We also searched electronic databases of drugs for possible drug interactions based on metabolic profiles. We identified 86 potential drug interactions of which 13 were supported by 14 studies. There is a significant need for research to describe the likelihood, magnitude and clinical impact of the drug interactions proposed here.
Topics: Humans; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Mutation; Aminophenols; Benzodioxoles; Drug Combinations; Drug Interactions
PubMed: 36653239
DOI: 10.1016/j.jcf.2023.01.005 -
Annals of the New York Academy of... Sep 2022Electrical conductivity is of great significance to cardiac tissue engineering and permits the use of electrical stimulation in mimicking cardiac pacing. The development... (Review)
Review
Electrical conductivity is of great significance to cardiac tissue engineering and permits the use of electrical stimulation in mimicking cardiac pacing. The development of biomaterials for tissue engineering can incorporate physical properties that are uncommon to standard cell culture and can facilitate improved cardiomyocyte function. In this review, the PICOT question asks, "How has the application of external electrical stimulation in conductive scaffolds for tissue engineering affected cardiomyocyte behavior in in vitro cell culture?" The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, with predetermined inclusion and quality appraisal criteria, were used to assess publications from PubMed, Web of Science, and Scopus. Results revealed carbon nanotubes to be the most common conductive agent in biomaterials and rodent-sourced cell types as the most common cardiomyocytes used. To assess cardiomyocytes, immunofluorescence was used most often, utilizing proteins, such as connexin 43, cardiac α-actinin, and cardiac troponins. It was determined that the modal average stimulation protocol comprised 1-3 V square biphasic 50-ms pulses at 1 Hz, applied toward the end of cell culture. The addition of electrical stimulation to in vitro culture has exemplified it as a powerful tool for cardiac tissue engineering and brings researchers closer to creating optimal artificial cardiac tissue constructs.
Topics: Actinin; Biocompatible Materials; Connexin 43; Electric Conductivity; Electric Stimulation; Myocytes, Cardiac; Nanotubes, Carbon; Tissue Engineering; Tissue Scaffolds; Troponin
PubMed: 35676231
DOI: 10.1111/nyas.14812 -
Epilepsy Research Sep 2021Accumulating evidence indicates that genetic polymorphisms in ATP-binding cassette superfamily members, such asABCC2 and ABCG2, alter responses to antiepileptic drugs... (Meta-Analysis)
Meta-Analysis
PURPOSE
Accumulating evidence indicates that genetic polymorphisms in ATP-binding cassette superfamily members, such asABCC2 and ABCG2, alter responses to antiepileptic drugs (AEDs); however, this evidence is controversial and inconclusive. To provide strong evidence of the association between common polymorphisms in ABCC2 and ABCG2 and AED responses in patients with epilepsy, we performed a systematic review and meta-analysis.
METHODS
A literature search of electronic databases (PubMed, EBSCO, Ovid and the China National Knowledge Infrastructure) was performed. To evaluate the association of genetic polymorphisms inABCC2 and ABCG2 and risk of AED treatment, we calculated pooled odds ratios (ORs) and 95 % confidence intervals (CIs) using a fixed- or random-effect model.
RESULTS
A significant association of theABCC2 rs717620 polymorphism with resistance to AEDs was found in the overall pooled populations (homozygous comparison: OR = 1.77, 95 % CI, 1.27-2.48; dominant model: OR = 1.23, 95 % CI, 1.06-1.43; recessive model: OR = 1.75, 95 % CI, 1.28-2.40) and Asians (dominant model: OR = 1.21, 95 % CI, 1.03-1.42; recessive model: OR = 1.80, 95 % CI, 1.30-2.50). Using a recessive model, a similarly significant association of ABCC2 rs3740066 with AED resistance was observed in the overall pooled populations (OR = 2.29, 95 % CI, 1.44-3.64) and Asians (OR = 2.53, 95 % CI, 1.56-4.08). However, ABCC2 rs2273697, ABCG2 rs2231137 and rs2231142 were not found to be associated with AED responsiveness.
CONCLUSION
This meta-analysis suggests thatABCC2 rs717620 and rs3740066 are risk factors that predict responses to AEDs in epileptic patients.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 2; Anticonvulsants; Asian People; Epilepsy; Humans; Multidrug Resistance-Associated Protein 2; Neoplasm Proteins; Polymorphism, Single Nucleotide
PubMed: 34087576
DOI: 10.1016/j.eplepsyres.2021.106678 -
European Journal of Neurology Oct 2023Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin-4-IgG. While... (Review)
Review
BACKGROUND
Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin-4-IgG. While multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein-IgG associated disease (MOGAD) represent major and well-defined differential diagnoses, non-demyelinating NMOSD mimics remain poorly characterized.
METHODS
We conducted a systematic review on PubMed/MEDLINE to identify reports of patients with non-demyelinating disorders that mimicked or were misdiagnosed as NMOSD. Three novel cases seen at the authors' institutions were also included. The characteristics of NMOSD mimics were analyzed and red flags associated with misdiagnosis identified.
RESULTS
A total of 68 patients were included; 35 (52%) were female. Median age at symptoms onset was 44 (range, 1-78) years. Fifty-six (82%) patients did not fulfil the 2015 NMOSD diagnostic criteria. The clinical syndromes misinterpreted for NMOSD were myelopathy (41%), myelopathy + optic neuropathy (41%), optic neuropathy (6%), or other (12%). Alternative etiologies included genetic/metabolic disorders, neoplasms, infections, vascular disorders, spondylosis, and other immune-mediated disorders. Common red flags associated with misdiagnosis were lack of cerebrospinal fluid (CSF) pleocytosis (57%), lack of response to immunotherapy (55%), progressive disease course (54%), and lack of magnetic resonance imaging gadolinium enhancement (31%). Aquaporin-4-IgG positivity was detected in five patients by enzyme-linked immunosorbent assay (n = 2), cell-based assay (n = 2: serum, 1; CSF, 1), and non-specified assay (n = 1).
CONCLUSIONS
The spectrum of NMOSD mimics is broad. Misdiagnosis frequently results from incorrect application of diagnostic criteria, in patients with multiple identifiable red flags. False aquaporin-4-IgG positivity, generally from nonspecific testing assays, may rarely contribute to misdiagnosis.
Topics: Humans; Female; Male; Neuromyelitis Optica; Contrast Media; Myelin-Oligodendrocyte Glycoprotein; Autoantibodies; Gadolinium; Aquaporin 4; Spinal Cord Diseases; Immunoglobulin G
PubMed: 37433584
DOI: 10.1111/ene.15983 -
Drug and Alcohol Dependence Oct 2022Nicotine produces its effects by binding to nicotinic acetylcholine receptors (nAChRs). Variants of genes encoding properties of nAChRs are candidates for affecting... (Review)
Review
BACKGROUND
Nicotine produces its effects by binding to nicotinic acetylcholine receptors (nAChRs). Variants of genes encoding properties of nAChRs are candidates for affecting likelihood of smoking cessation.
METHODS
A systematic review was conducted summarizing evidence of associations between single nucleotide polymorphisms (SNPs) of nAChR genes and smoking cessation. From 24 articles meeting inclusion criteria, summary odds ratios (ORs) for associations between nine SNPs and smoking cessation were calculated from 26 studies (N = 233-29,072) stratified by gene, ancestry, study design, and pharmacotherapy; SNPs in linkage disequilibrium were pooled. Results for a tenth SNP from two GWAS were summarized.
RESULTS
People of European ancestry with minor alleles of CHRNA5 rs16969968 and CHRNA3 rs1051730 had longer time to cessation [HR = 0.90, 95 % CI 0.88 - 0.92 (n = 2 studies)] and lower odds of cessation [OR = 0.88, 95 % CI 0.80 - 0.97 (n = 5 cohort studies), OR = 0.64, 95 % CI 0.45 - 0.90 (n = 4 placebo arms)]. Risk of persistent smoking associated with these alleles was attenuated in smokers receiving nicotine replacement therapy (NRT). Recipients of bupropion alone or with NRT with these alleles had higher, though not statistically significant, odds of cessation. Results for CHRNA5 rs588765 and rs680244 were similar to rs16969968/rs1051730 findings. Evidence was limited for other SNPs.
CONCLUSION
Evidence consistently indicates the minor alleles of four SNPs within CHRNA3 or CHRNA5 are risk alleles for cessation failure. Analysis by pharmacotherapy revealed bupropion may be the most efficacious intervention for people with these alleles.
Topics: Bupropion; Genetic Variation; Humans; Nicotine; Polymorphism, Single Nucleotide; Receptors, Nicotinic; Smoking Cessation; Tobacco Products; Tobacco Use Cessation Devices
PubMed: 35981468
DOI: 10.1016/j.drugalcdep.2022.109596 -
Disease Markers 2020As an important component of miRNA processing genes, RAN gene encodes the ras-related nuclear protein, which is a unique member of the Ras superfamily of GTPases. The... (Meta-Analysis)
Meta-Analysis
As an important component of miRNA processing genes, RAN gene encodes the ras-related nuclear protein, which is a unique member of the Ras superfamily of GTPases. The mutations in RAN gene are very likely to play a critical role in pathology-related changes to miRNA transport and expression and thus participate in tumor genesis and development. Currently, accumulating studies have explored the association between RAN SNPs and cancer risk. However, the results are conflicting. In the present study, we performed a systematic review for the association of RAN SNPs with overall cancer risk. Meanwhile, a meta-analysis was conducted based on available data, aiming at clarifying the association between RAN SNPs and cancer susceptibility. After literature search and data extraction, 17 studies containing four RAN SNPs were involved in the systematic review. And 12 studies with two highly studied SNPs (RAN rs14035 C>T and rs3803012 A>G) were included in the final meta-analysis, consisting of 7662 cases and 9807 controls. The results showed that the rs14035 polymorphism was linked to a decreased cancer risk in overall subjects and hospital-based (HB) subgroup, while the rs3803012 polymorphism conferred to an increased cancer risk in overall subjects and population-based (PB) subgroup. Our findings suggested that the two SNPs had the potential to be predictive biomarkers for cancer risk. The study would provide novel clues for the identification of miRNA-related genetic biomarkers applied to predicting cancer susceptibility.
Topics: Humans; Neoplasms; Polymorphism, Single Nucleotide; ran GTP-Binding Protein
PubMed: 32015773
DOI: 10.1155/2020/9026707 -
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