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Does a high-fat diet affect the circadian clock, or is it the other way around? A systematic review.Nutrition Research (New York, N.Y.) Dec 2020This paper reviews studies that addressed the influence of diet on circadian rhythmicity in mice and, in turn, circadian clock chronodisruption and its role in the...
This paper reviews studies that addressed the influence of diet on circadian rhythmicity in mice and, in turn, circadian clock chronodisruption and its role in the development of metabolic disorders. Studies from the past 14 years were selected via a systematic search conducted using the PubMed electronic database. After applying the inclusion and exclusion criteria, 291 studies were selected, of which 13 were chosen using the following inclusion criteria: use of a high-fat diet for mice, evaluation of clock gene expression, and the association between chronodisruption and lipid metabolism disorders. These studies reported changes in animals' biological clock when they developed metabolic disorders by consuming a high-fat diet. It was also evident that some clock gene mutations or deletions triggered metabolic changes. Disturbances of clock gene machinery may play important roles in lipid metabolism and the development of atherosclerotic processes. However, many metabolic processes also affect the function of clock genes and circadian systems. In summary, this review's results may provide new insights into the reciprocal regulation of energy homeostasis and the biological clock.
Topics: Animals; CLOCK Proteins; Circadian Clocks; Circadian Rhythm; Diet, High-Fat; Dietary Fats; Female; Gene Expression; Lipid Metabolism; Lipid Metabolism Disorders; Male; Mice
PubMed: 33213889
DOI: 10.1016/j.nutres.2020.10.003 -
The British Journal of Nutrition Oct 2022Elevated levels of liver enzymes are the main markers of liver dysfunction. Liver enzymes are the important indicators of non-alcoholic fatty liver disease (NAFLD) in... (Meta-Analysis)
Meta-Analysis
Elevated levels of liver enzymes are the main markers of liver dysfunction. Liver enzymes are the important indicators of non-alcoholic fatty liver disease (NAFLD) in the general population. Previous randomised clinical trials (RCT) investigated the effects of Mediterranean diet (MedDiet) as a plant-based diet on features of NAFLD like liver enzymes, but their results are contradictory. This study aimed to systematically review and meta-analyse RCT investigating the effect of MedDiet on liver enzymes. PubMed, Web of Science, Scopus and Google Scholar were searched until December 2020. A total of ten RCT ( 705 participants) evaluating the effect of MedDiet on liver enzymes including aspartate aminotransferase (AST), alanine transaminase (ALT) and -glutamyltransferase (GGT) were included. A random effects model was used to estimate the pooled effect size. To evaluate the heterogeneity among the included studies, the Cochran's -test and I-squared test were used. The MedDiet significantly reduced AST (weighted mean difference (WMD) = -0·38 IU/l; 95 % CI - 0·73, -0·03 IU/l; = 0·03) and GGT (WMD = -0·16 IU/l; 95 % CI - 0·32, -0·006 IU/l; = 0·04) but had no significant effect on ALT (WMD = -0·55 IU/l; 95 % CI - 1·25, 0·13 IU/l; = 0·11). However, sensitivity analysis revealed that the overall effects of MedDiet on AST, GGT and ALT were significantly influenced by removing some studies. There was no publication bias based on Begg's and Egger's tests. Generally, MedDiet can improve liver enzymes. To better conclusion, further RCT investigating the effect of MedDiet on liver enzymes, especially in patients with NAFLD, are still required.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Liver; Diet, Mediterranean; gamma-Glutamyltransferase; Alanine Transaminase; Aspartate Aminotransferases; Randomized Controlled Trials as Topic
PubMed: 34165054
DOI: 10.1017/S0007114521002270 -
Brain : a Journal of Neurology Jun 2024Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism and hair...
Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism and hair anomalies. PNPLA6 encodes neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear. We present a systematic evidence-based review of a novel cohort of 23 new patients along with 95 reported individuals with PNPLA6 variants that implicate missense variants as a driver of disease pathogenesis. Measuring esterase activity of 46 disease-associated and 20 common variants observed across PNPLA6-associated clinical diagnoses unambiguously reclassified 36 variants as pathogenic and 10 variants as likely pathogenic, establishing a robust functional assay for classifying PNPLA6 variants of unknown significance. Estimating the overall NTE activity of affected individuals revealed a striking inverse relationship between NTE activity and the presence of retinopathy and endocrinopathy. This phenomenon was recaptured in vivo in an allelic mouse series, where a similar NTE threshold for retinopathy exists. Thus, PNPLA6 disorders, previously considered allelic, are a continuous spectrum of pleiotropic phenotypes defined by an NTE genotype:activity:phenotype relationship. This relationship, and the generation of a preclinical animal model, pave the way for therapeutic trials, using NTE as a biomarker.
Topics: Animals; Female; Humans; Male; Mice; Acyltransferases; Carboxylic Ester Hydrolases; Mutation, Missense; Phenotype; Phospholipases; Retinal Diseases
PubMed: 38735647
DOI: 10.1093/brain/awae055 -
Pediatric Surgery International Jun 2024Biliary atresia (BA), a progressive condition affecting canalicular-bile duct function/anatomy, requires prompt surgical intervention for favorable outcomes. Therefore,... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
Biliary atresia (BA), a progressive condition affecting canalicular-bile duct function/anatomy, requires prompt surgical intervention for favorable outcomes. Therefore, we conducted a network meta-analysis of common diagnostic methods to assess their performance and provide evidence-based support for clinical decision-making.
METHODS
We reviewed literature in PubMed, EMBASE, and Cochrane for BA diagnostics. The search included gamma-glutamyl transferase (GGT), direct/combined bilirubin, matrix metalloproteinase 7 (MMP-7), ultrasonic triangular cord sign (TCS), hepatic scintigraphy (HS), and percutaneous cholangiocholangiography/percutaneous transhepatic cholecysto-cholangiography (PCC/PTCC). QUADAS-2 assessed study quality. Heterogeneity and threshold effect were evaluated using I2 and Spearman's correlation. We combined effect estimates, constructed SROC models, and conducted a network meta-analysis based on the ANOVA model, along with meta-regression and subgroup analysis, to obtain precise diagnostic performance assessments for BA.
RESULTS
A total of 40 studies were included in our analysis. GGT demonstrated high diagnostic accuracy for BA with a sensitivity of 81.5% (95% CI 0.792-0.836) and specificity of 72.1% (95% CI 0.693-0.748). Direct bilirubin/conjugated bilirubin showed a sensitivity of 87.6% (95% CI 0.833-0.911) but lower specificity of 59.4% (95% CI 0.549-0.638). MMP-7 exhibited a total sensitivity of 91.5% (95% CI 0.893-0.934) and a specificity of 84.3% (95% CI 0.820-0.863). TCS exhibited a sensitivity of 58.1% (95% CI 0.549-0.613) and high specificity of 92.9% (95% CI 0.911-0.944). HS had a high sensitivity of 98.4% (95% CI 0.968-0.994) and moderate specificity of 79.0% (95% CI 0.762-0.816). PCC/PTCC exhibited excellent diagnostic performance with a sensitivity of 100% (95% CI 0.900-1.000) and specificity of 87.0% (95% CI 0.767-0.939). Based on the ANOVA model, the network meta-analysis revealed that MMP-7 ranked second overall, with PCC/PTCC ranking first, both exhibiting superior diagnostic accuracy compared to other techniques. Our analysis showed no significant bias in most methodologies, but MMP-7 and hepatobiliary scintigraphy exhibited biases, with p values of 0.023 and 0.002, respectively.
CONCLUSION
MMP-7 and ultrasound-guided PCC/PTCC show diagnostic potential in the early diagnosis of BA, but their clinical application is restricted due to practical limitations. Currently, the cutoff value of MMP-7 is unclear, and further evidence-based medical research is needed to firmly establish its diagnostic value. Until more evidence is available, MMP-7 is not suitable for widespread diagnostic use. Therefore, considering cost and operational simplicity, liver function tests combined with ultrasound remain the most clinically valuable non-invasive diagnostic methods for BA.
Topics: Biliary Atresia; Humans; Network Meta-Analysis; Early Diagnosis; gamma-Glutamyltransferase; Sensitivity and Specificity
PubMed: 38822892
DOI: 10.1007/s00383-024-05730-z -
Expert Review of Gastroenterology &... Mar 2020: This article provides a comprehensive overview of the development and application of serological tests used routinely in clinical practice for the diagnosis and...
: This article provides a comprehensive overview of the development and application of serological tests used routinely in clinical practice for the diagnosis and management of adult celiac disease.: We summarize existing scientific literature related to anti-endomyseal, anti-tissue transglutaminase, and anti-deamidated gliadin peptide antibodies and detail the current and potential future applications of these tests in celiac disease.: Current serological tests in celiac disease have some of the best performance characteristics among disease-specific tests. However, in adult celiac disease, current diagnostic algorithms still rely on duodenal biopsies to confirm the diagnosis. A 'biopsy avoidance strategy' has been implemented in pediatric celiac disease. Future high-quality studies will help inform on whether this approach can be implemented into adult gastroenterology services. It is envisaged that the next 5 years will see an increasing reliance on serology in the diagnosis of adult celiac disease.
Topics: Adult; Autoantibodies; Biopsy; Celiac Disease; Continuity of Patient Care; Diet, Gluten-Free; Duodenum; Gliadin; Humans; Immunoglobulin Isotypes; Serologic Tests; Transglutaminases
PubMed: 32011187
DOI: 10.1080/17474124.2020.1725472 -
Orphanet Journal of Rare Diseases Nov 2019Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies are rare fatty acid β-oxidation disorders. Without dietary...
Evaluation of earlier versus later dietary management in long-chain 3-hydroxyacyl-CoA dehydrogenase or mitochondrial trifunctional protein deficiency: a systematic review.
BACKGROUND
Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies are rare fatty acid β-oxidation disorders. Without dietary management the conditions are life-threatening. We conducted a systematic review to investigate whether pre-symptomatic dietary management following newborn screening provides better outcomes than treatment following symptomatic detection.
METHODS
We searched Web of Science, Medline, Pre-Medline, Embase and the Cochrane Library up to 23rd April 2018. Two reviewers independently screened titles, abstracts and full texts for eligibility and quality appraised the studies. Data extraction was performed by one reviewer and checked by another.
RESULTS
We included 13 articles out of 7483 unique records. The 13 articles reported on 11 patient groups, including 174 people with LCHAD deficiency, 18 people with MTP deficiency and 12 people with undifferentiated LCHAD/MTP deficiency. Study quality was moderate to weak in all studies. Included studies suggested fewer heart and liver problems in screen-detected patients, but inconsistent results for mortality. Follow up analyses compared long-term outcomes of (1) pre-symptomatically versus symptomatically treated patients, (2) screened versus unscreened patients, and (3) asymptomatic screen-detected, symptomatic screen-detected, and clinically diagnosed patients in each study. For follow up analyses 1 and 2, we found few statistically significant differences in the long-term outcomes. For follow up analysis 3 we found a significant difference for only one comparison, in the incidence of cardiomyopathy between the three groups.
CONCLUSIONS
There is some evidence that dietary management following screen-detection might be associated with a lower incidence of some LCHAD and MTP deficiency-related complications. However, the evidence base is limited by small study sizes, quality issues and risk of confounding. An internationally collaborative research effort is needed to fully examine the risks and the benefits to pre-emptive dietary management with particular attention paid to disease severity and treatment group.
Topics: Cardiomyopathies; Female; Humans; Lipid Metabolism, Inborn Errors; Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; Male; Mitochondrial Myopathies; Mitochondrial Trifunctional Protein; Nervous System Diseases; Rhabdomyolysis
PubMed: 31730477
DOI: 10.1186/s13023-019-1226-y -
Medicine Nov 2020Amplified in breast cancer 1 (AIB1) expression is known to be involved in the initiation and progression of malignant breast cancer (BC), but its prognostic role remains... (Meta-Analysis)
Meta-Analysis
PURPOSE
Amplified in breast cancer 1 (AIB1) expression is known to be involved in the initiation and progression of malignant breast cancer (BC), but its prognostic role remains uncertain. This meta-analysis assessed reported studies to evaluate this relationship.
METHODS
Electronic databases were systematically reviewed to collect eligible studies using pre-established criteria. Hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were pooled to estimate the impact of AIB1 protein expression on overall survival (OS) and clinicopathologic properties of BC cases.
RESULTS
Nine eligible studies, including 6774 patients, were finally assessed by the current clinical meta-analysis. AIB1 positivity correlated with reduced OS (pooled HR = 1.409, 95% CI 1.159-1.714, P = .001). AIB1 overexpression also impacted prognosis as shown by univariate (pooled HR = 1.420, 95% CI 1.154-1.747, P = .001) and multivariate (pooled HR = 1.446, 95% CI 1.099-1.956; P = .009) analyses. Notably, subgroup analyses also revealed that AIB1 overexpression was associated with poor OS in some subgroups, such as ER-positive group (pooled HR = 1.511, 95% CI 1.138-2.006, P = .004), ER-positive without tamoxifen administration group (pooled HR = 2.338, 95% CI 1.489-3.627, P < .001), and premenopausal women group (pooled HR = 1.715, 95% CI 1.231-2.390, P = .001). Additionally, high AIB1 protein levels were associated with HER2 positivity (pooled OR = 0.331, 95% CI 0.245-0.448; P < .001), poorly differentiated histological grade (pooled OR = 0.377, 95% CI 0.317-0.448; P < .001), high Ki67 (pooled OR = 0.501, 95% CI 0.410-0.612; P < .001), presence of lymph node metastases (pooled OR = 0.866, 95% CI 0.752-0.997; P = .045), and absence of progesterone receptor (pooled OR = 1.447, 95% CI 1.190-1.759; P < .001).
CONCLUSIONS
This analysis demonstrated that AIB1 overexpression is related to aggressive phenotypes and unfavorable clinical outcomes in BC, and might involve in tamoxifen resistance. AIB1 may be a new prognostic biomarker and therapeutic target in BC.
Topics: Adult; Biomarkers, Tumor; Breast Neoplasms; Early Detection of Cancer; Female; Gene Expression Regulation, Neoplastic; Humans; Nuclear Receptor Coactivator 3; Predictive Value of Tests; Prognosis
PubMed: 33181714
DOI: 10.1097/MD.0000000000023248 -
Archives of Medical Research Jan 2020Possible Hepato-protective effects of L-carnitine have been reported in previous studies. Present study was conducted to systematically review the efficacy of... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Possible Hepato-protective effects of L-carnitine have been reported in previous studies. Present study was conducted to systematically review the efficacy of L-carnitine supplementation on liver enzymes.
METHODS
The following databases were searched up to December 2018: PubMed, Scopus, ISI Web of Science, and the Cochrane library. Only randomized controlled trials (RCTs) evaluating the effects of L-carnitine supplementation on liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) were included. Pooled effect size measured using random effect model (Dersimonian-Liard).
RESULTS
A total of 16 studies (including 1025 participants) were included in the present meta-analysis. Pooled analysis indicated that L-carnitine supplementation significantly decreased ALT (weighted mean difference (WMD): -10.729 IU/L, 95% CI: -13.787, -7.672, p <0.001; I = 95.9%), AST (WMD: -7.149 IU/L, 95% CI: -9.202, -5.096, p <0.001; I = 93.5%) and GGT (WMD: -7.395: IU/L, 95% CI: -9.171, -5.619, p <0.001; I = 80.1%). Subgroup analysis revealed that effect of L-carnitine supplementation on liver enzymes was not significant in normal weight and healthy subjects. Baseline BMI and health status were the potential source of heterogeneity.
CONCLUSION
L-carnitine supplementation showed beneficial hepato-protective effects on circulating liver enzymes.
Topics: Alanine Transaminase; Aspartate Aminotransferases; Carnitine; Cytoprotection; Dietary Supplements; Humans; Liver; Protective Agents; Randomized Controlled Trials as Topic; gamma-Glutamyltransferase
PubMed: 32113058
DOI: 10.1016/j.arcmed.2019.12.005 -
European Journal of Pharmacology Aug 2021Melatonin has shown promising effects in controlling the progress of non-alcoholic fatty liver disease (NAFLD), introducing it as a possible candidate for NAFLD... (Meta-Analysis)
Meta-Analysis
Melatonin has shown promising effects in controlling the progress of non-alcoholic fatty liver disease (NAFLD), introducing it as a possible candidate for NAFLD treatment. In this context, the current study is aimed to evaluate melatonin's effect on the plasma levels of Gamma-glutamyl transpeptidase, cholesterol, triglyceride, and liver aminotransferases in NAFLD patients. NAFLD and melatonin, as well as their related terms, were searched in electronic databases, until May 1st, 2020. The initial search identified 1152 studies. Considering inclusion and exclusion criteria, the final seven articles were included in the study. The methodology of the articles was assessed by the Newcastle-Ottawa Scale. Alanine transaminase levels were significantly lowered with melatonin treatment but not earlier than the 4th week (P = 0.010 and 0.519, respectively). Aspartate aminotransferase levels didn't show significant alteration before 4 weeks, although exhibiting substantial decline in total (P = 0.697 and 0.008, respectively). Alkaline phosphatase changes under 4 weeks of follow-up were not significant (P = 0.3), however, it decreased significantly in total (P = 0.006). A significant decline was detected in triglyceride levels after melatonin treatment (P = 0.015). There was a significant reduction in cholesterol levels (P = 0.005). Gamma-glutamyl transpeptidase levels were also significantly different after the administration of melatonin (P < 0.001). Melatonin could reduce the progress of NAFLD. It might also decrement hepatic function parameters. Thus, it could be used for managing NAFLD and possibly as part of the treatment plan for patients with NAFLD.
Topics: Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Humans; Lipids; Liver; Melatonin; Non-alcoholic Fatty Liver Disease; gamma-Glutamyltransferase
PubMed: 34058202
DOI: 10.1016/j.ejphar.2021.174154 -
Pharmacological Research Jan 2021Previous studies have suggested that sodium-glucose co-transporter-2 (SGLT2) inhibitors may improve hepatic function; however, the evidence is scarce. Hence, we... (Meta-Analysis)
Meta-Analysis
Previous studies have suggested that sodium-glucose co-transporter-2 (SGLT2) inhibitors may improve hepatic function; however, the evidence is scarce. Hence, we performed a meta-analysis of randomized controlled trials to evaluate the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on hepatic parameters. PubMed, Web of Science, Scopus, and Google Scholar databases were searched to identify randomized controlled trials examining the effect of SGLT2 inhibitors on hepatic parameters. Meta-analysis was performed using a random-effects model and sensitivity analysis. Meta-analysis revealed that SGLT2 inhibitors therapy significantly lowered alanine aminotransferase (ALT) (WMD: -4.79 U/L, 95 % CI: -6.10, -3.47, I = 62 %, p < 0.00001), aspartate aminotransferase (AST) (WMD: -2.49 U/L, 95 % CI: -3.30, -1.68, I = 54 %, p < 0.00001), alkaline phosphatase (AP) (WMD: -1.13 U/L, 95 % CI: -2.03, -0.22, I = 23 %, p = 0.02), and gamma-glutamyl transferase (GGT) (WMD: -7.77 U/L, 95 % CI: -9.33, -6.21, I = 5 %, p < 0.00001). Additionally, SGLT2 inhibitors showed a significant increase in bilirubin levels (WMD: 0.64 U/L, 95 % CI: 0.27, 1.00, I = 53 %, p < 0.0006. Finally, no significant changes were found on albumin levels (WMD: 0.13 U/L, 95 % CI: -0.06, 0.32, I = 53 %, p < 0.0006) after SGLT2 inhibitors treatment. In conclusion, our results suggest that treatment with SGLT2 inhibitors exerts a beneficial effect on liver function tests through decreased ALT, AST, AP, and GGT concentrations.
Topics: Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Diabetes Mellitus, Type 2; Humans; Liver; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors; gamma-Glutamyltransferase
PubMed: 33246172
DOI: 10.1016/j.phrs.2020.105319