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Frontiers in Endocrinology 2024Acetaldehyde dehydrogenase 2 (ALDH2) had reported as a prominent role in the development of cardiometabolic diseases among Asians. Our study aims to investigate the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Acetaldehyde dehydrogenase 2 (ALDH2) had reported as a prominent role in the development of cardiometabolic diseases among Asians. Our study aims to investigate the relationship between ALDH2 polymorphism and cardiometabolic risk factors in East Asian population.
METHOD
We searched databases of PubMed, Web of Science, and Embase updated to Oct 30, 2023. We extracted data of BMI, Hypertension, SBP, DBP, T2DM, FBG, PPG, HbA1c, TG, TC, LDL-C and HDL-C.
RESULT
In total, 46 studies were finally included in our meta-analysis, containing, 54068 GG and, 36820 GA/AA participants. All outcomes related to blood pressure revealed significant results (hypertension OR=0.83 [0.80, 0.86]; SBP MD=-1.48 [-1.82, -1.14]; DBP MD=-1.09 [-1.58, -0.61]). FBG showed a significant difference (MD=-0.10 [-0.13, -0.07]), and the lipid resulted significantly in some outcomes (TG MD=-0.07 [-0.09, -0.04]; LDL-C MD=-0.04 [-0.05, -0.02]). As for subgroups analysis, we found that in populations without severe cardiac-cerebral vascular diseases (CCVDs), GG demonstrated a significantly higher incidence of T2DM (T2DM OR=0.88 [0.79, 0.97]), while the trend was totally opposite in population with severe CCVDs (T2DM OR=1.29 [1.00, 1.66]) with significant subgroup differences.
CONCLUSION
Our updated meta-analysis demonstrated that ALDH2 rs671 GG populations had significantly higher levels of BMI, blood pressure, FBG, TG, LDL-C and higher risk of hypertension than GA/AA populations. Besides, to the best of our knowledge, we first report GG had a higher risk of T2DM in population without severe CCVDs, and GA/AA had a higher risk of T2DM in population with severe CCVDs. https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023389242.
Topics: Humans; Aldehyde Dehydrogenase, Mitochondrial; Asian People; Cardiometabolic Risk Factors; Cholesterol, LDL; Diabetes Mellitus, Type 2; East Asian People; Hypertension
PubMed: 38567307
DOI: 10.3389/fendo.2024.1333595 -
Disease Markers 2024The present article aims to comprehensively review the existing literature on superoxide dismutase (SOD) levels, an antioxidant enzyme, in oral cancer. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The present article aims to comprehensively review the existing literature on superoxide dismutase (SOD) levels, an antioxidant enzyme, in oral cancer.
METHOD
An extensive literature search was conducted across various databases, including PubMed, Wiley Online Library, Science Direct, and Cross Reference, spanning 1998-2023. At the outset, 1,177 articles were initially identified, and 907 studies were excluded due to irrelevance or duplication of the research question. Subsequently, 270 articles underwent screening evaluation, resulting in the selection of 85 articles meeting the inclusion criteria. Following this, 68 articles underwent a full-text comprehensive assessment, and ultimately, 39 were chosen for data extraction. The risk of bias in the designated articles was assessed using the Newcastle-Ottawa Scale. Finally, 13 studies were meticulously selected, offering consistent data for the ensuing meta-analysis. Meta-analysis was executed using comprehensive meta-analysis (CMA) version 3 software (Bio Stat Inc., Englewood, NJ, USA). The meta-analysis findings revealed a statistically significant decrease in SOD levels in both erythrocyte samples ( < 0.001) and tissue samples ( < 0.05) among individuals with oral cancer (OSCC) compared to the normal control group. Conversely, the analysis of three studies on salivary samples demonstrated a significant increase ( < 0.05) in SOD levels in the oral cancer group compared to the healthy controls.
CONCLUSION
This systematic review underscores a statistically significant decline in SOD levels observed across diverse bio-samples in individuals with oral cancer, indicating an excess of oxidative stress (OS). Additional research is needed to delve into the relationship between SOD levels and clinic-pathological prognostic markers within the oral cancer cohort. Such investigations have the potential to significantly contribute to the development of prognostic tools grounded in OS, thereby guiding strategies for treatment planning.
Topics: Humans; Superoxide Dismutase; Antioxidants; Mouth Neoplasms; Oxidative Stress
PubMed: 38525070
DOI: 10.1155/2024/2264251 -
Clinical and Translational Science Mar 2024Aminobenzotriazole (ABT) is commonly used as a non-selective inhibitor of cytochrome P450 (CYP) enzymes to assign contributions of CYP versus non-CYP pathways to the...
Aminobenzotriazole (ABT) is commonly used as a non-selective inhibitor of cytochrome P450 (CYP) enzymes to assign contributions of CYP versus non-CYP pathways to the metabolism of new chemical entities. Despite widespread use, a systematic review of the drug-drug interaction (DDI) potential for ABT has not been published nor have the implications for using it in plated hepatocyte models for low clearance reaction phenotyping. The goal being to investigate the utility of ABT as a pan-CYP inhibitor for reaction phenotyping of low clearance compounds by evaluating stability over the incubation period, inhibition potential against UGT and sulfotransferase enzymes, and interaction with nuclear receptors involved in the regulation of drug metabolizing enzymes and transporters. Induction potential for additional inhibitors used to ascribe fraction metabolism (f ), pathway including erythromycin, ketoconazole, azamulin, atipamezole, ZY12201, and quinidine was also investigated. ABT significantly inhibited the clearance of a non-selective UGT substrate 4-methylumbelliferone, with several UGTs shown to be inhibited using selective probe substrates in human hepatocytes and rUGTs. The inhibitors screened in the induction assay were shown to induce enzymes regulated through Aryl Hydrocarbon Receptor, Constitutive Androstane Receptor, and Pregnane X Receptor. Lastly, a case study identifying the mechanisms of a clinical DDI between Palbociclib and ARV-471 is provided as an example of the potential consequences of using ABT to derive f . This work demonstrates that ABT is not an ideal pan-CYP inhibitor for reaction phenotyping of low clearance compounds and establishes a workflow that can be used to enable robust characterization of other prospective inhibitors.
Topics: Humans; Cytochrome P-450 Enzyme System; Hepatocytes; Receptors, Cytoplasmic and Nuclear
PubMed: 38501263
DOI: 10.1111/cts.13746 -
BMC Infectious Diseases Mar 2024Coronavirus disease 2019 (COVID-19) is frequntly accompanied by venous thromboembolism (VTE), and its mechanism may be related to the abnormal inflammation and immune... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Coronavirus disease 2019 (COVID-19) is frequntly accompanied by venous thromboembolism (VTE), and its mechanism may be related to the abnormal inflammation and immune status of COVID-19 patients. It has been proved that interleukin-6 (IL-6), ferritin and lactate dehydrogenase (LDH) may play an important role in the occurrence of VTE in COVID-19 infection. But whether they can server as predictors for VTE in COVID-19 is still unclear. In this study, we performed a systematic review and meta-analysis to compare IL-6, ferritin and LDH in VTE and non-VTE COVID-19 patients in order to shed light on the prevention and treatment of VTE.
METHODS
Related literatures were searched in PubMed, Embase, Web of Science, Google Scholar, China National Knowledge Infrastructure (CNKI), WANGFANG. COVID-19 patients were divided into VTE group and non-VTE group. Meta-analysis was then conducted to compare levels of IL-6, ferritin and LDH between the two groups.
RESULTS
We finally included and analyzed 17 literatures from January 2019 to October 2022. There was a total of 7,035 COVID-19 patients, with a weighted mean age of 60.01 years. Males accounted for 62.64% and 61.34% patients were in intensive care unit (ICU). Weighted mean difference (WMD) of IL-6, ferritin and LDH was 31.15 (95% CI: 9.82, 52.49), 257.02 (95% CI: 51.70, 462.33) and 41.79 (95% CI: -19.38, 102.96), respectively. The above results indicated that than compared with non-VTE group, VTE group had significantly higher levels of IL-6 and ferritin but similar LDH.
CONCLUSION
This systematic review and meta-analysis pointed out that elevated levels of IL-6 and ferritin were significantly possitive associated with VTE, thus could be used as biological predictive indicators of VTE among COVID-19 patients. However, no association was found between level of LDH and VTE. Therefore, close monitoring of changes in IL-6 and ferritin concentrations is of great value in assisting clinicans to rapidly identify thrombotic complications among COVID-19 patients, hence facilitating the timely effective managment. Further studies are required in terms of the clinical role of cytokines in the occurrence of VTE among COVID-19 infection, with more reliable systematic controls and interventional trials.
Topics: Male; Humans; Middle Aged; COVID-19; Interleukin-6; Venous Thromboembolism; Ferritins; L-Lactate Dehydrogenase
PubMed: 38493138
DOI: 10.1186/s12879-024-09205-3 -
Frontiers in Endocrinology 2024Thyroglobulin antibody (TgAb) has been found to be associated with the occurrence and development of differentiated thyroid cancer (DTC) for several years, but there is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thyroglobulin antibody (TgAb) has been found to be associated with the occurrence and development of differentiated thyroid cancer (DTC) for several years, but there is still controversy over whether thyroid peroxidase antibody (TPOAb) is related to differentiated thyroid cancer.
METHODS
We scrutinized relevant studies published up to July 2023 across four major databases including PubMed, Embase, Cochrane Library, and Web of Science, to examine the association between TPOAb and DTC. Clinical outcome measures include the incidence of DTC, tumor size, extrathyroidal invasion, lymph node metastasis, multifocality, recurrence and bilaterality.
RESULTS
12 original studies were included, involving a total of 20,330 subjects. Our analysis of the included studies revealed that TPOAb+ individuals exhibited a higher risk of developing DTC (OR=1.57 [95% CI: 1.00-2.45], p=0.049) than TPOAb- individuals. Furthermore, TPOAb+ DTC patients were more prone to present with bilateral (OR=1.40 [95% CI: 1.21-1.62], p<0.00001) and multifocal (OR=1.40 [95% CI: 1.23-1.60], p<0.00001) tumors than TPOAb- patients. Sensitivity analysis indicated a high sensitivity for these three findings. No significant differences in the risk of extrathyroidal extension and lymph node metastasis, recurrence rate, tumor size, were observed between TPOAb+ and TPOAb- DTC patients.
CONCLUSION
The presence of TPOAb is correlated with an increase prevalence of DTC. However, its effectiveness as a prognostic marker for DTC patients warrants further investigation.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023448824.
Topics: Humans; Lymphatic Metastasis; Thyroid Neoplasms; Adenocarcinoma; Databases, Factual; Iodide Peroxidase
PubMed: 38476675
DOI: 10.3389/fendo.2024.1349041 -
Diagnostic Pathology Mar 2024Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Due to the limited knowledge about potential biomarkers that help in early diagnosis... (Review)
Review
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Due to the limited knowledge about potential biomarkers that help in early diagnosis and monitoring disease progression, today's diagnoses are based on ruling out other diseases, neurography, and electromyography examination, which takes a time-consuming procedure.
METHODS
PubMed, ScienceDirect, and Web of Science were explored to extract articles published from January 2015 to June 2023. In the searching strategy following keywords were included; amyotrophic lateral sclerosis, biomarkers, cerebrospinal fluid, serum, and plama.
RESULTS
A total number of 6 studies describing fluid-based exosomal biomarkers were included in this study. Aggregated proteins including SOD1, TDP-43, pTDP-43, and FUS could be detected in the microvesicles (MVs). Moreover, TDP-43 and NFL extracted from plasma exosomes could be used as prognostic biomarkers. Also, downregulated miR-27a-3p detected through exoEasy Maxi and exoQuick Kit in the plasma could be measured as a diagnostic biomarker. Eventually, the upregulated level of CORO1A could be used to monitor disease progression.
CONCLUSION
Based on the results, each biomarker alone is insufficient to evaluate ALS. CNS-derived exosomes contain multiple ALS-related biomarkers (SOD1, TDP-43, pTDP-43, FUS, and miRNAs) that are detectable in cerebrospinal fluid and blood is a proper alternation. Exosome detecting kits listed as exoEasy, ExoQuick, Exo-spin, ME kit, ExoQuick Plus, and Exo-Flow, are helpful to reach this purpose.
Topics: Humans; Exosomes; Amyotrophic Lateral Sclerosis; Superoxide Dismutase-1; Biomarkers; DNA-Binding Proteins; Disease Progression
PubMed: 38429818
DOI: 10.1186/s13000-024-01473-6 -
Orphanet Journal of Rare Diseases Feb 2024Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common lipid storage myopathy. There are sex differences in fat metabolism and it is not known... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common lipid storage myopathy. There are sex differences in fat metabolism and it is not known whether late-onset MADD affects men and women equally.
METHODS
In this systematic review and meta-analysis, the PubMed, Embase, Web of Science, CNKI, CBM, and Wanfang databases were searched until 01/08/2023. Studies reporting sex distribution in patients with late-onset MADD were included. Two authors independently screened studies for eligibility, extracted data, and assessed risk of bias. Pre-specified outcomes of interest were the male-to-female ratio (MFR) of patients with late-onset MADD, the differences of clinical characteristics between the sexes, and factors influencing the MFR.
RESULTS
Of 3379 identified studies, 34 met inclusion criteria, yielding a total of 609 late-onset MADD patients. The overall pooled percentage of males was 58% (95% CI, 54-63%) with low heterogeneity across studies (I = 2.99%; P = 0.42). The mean onset ages, diagnostic delay, serum creatine kinase (CK), and allelic frequencies of 3 hotspot variants in ETFDH gene were similar between male and female patients (P > 0.05). Meta-regressions revealed that ethnic group was associated with the MFR in late-onset MADD, and subgroup meta-analyses demonstrated that East-Asian patients had a higher percentage of male, lower CK, and higher proportion of hotspot variants in ETFDH gene than non-East-Asian patients (P < 0.05).
CONCLUSIONS
Male patients with late-onset MADD were more common than female patients. Ethnicity was proved to be a factor influencing the MFR in late-onset MADD. These findings suggest that male sex may be a risk factor for the disease.
Topics: Humans; Male; Female; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Mutation; Delayed Diagnosis; Electron-Transferring Flavoproteins; Iron-Sulfur Proteins; Oxidoreductases Acting on CH-NH Group Donors; Acyl-CoA Dehydrogenase
PubMed: 38365830
DOI: 10.1186/s13023-024-03072-6 -
Medicine Feb 2024Deep learning techniques explain the enormous potential of medical image analysis, particularly in digital pathology. Concurrently, molecular markers have gained...
BACKGROUND
Deep learning techniques explain the enormous potential of medical image analysis, particularly in digital pathology. Concurrently, molecular markers have gained increasing significance over the past decade in the context of glioma patients, providing novel insights into diagnosis and more personalized treatment options. Deep learning combined with imaging and molecular analysis enables more accurate prognostication of patients, more accurate treatment plan proposals, and accurate biomarker (IDH) prediction for gliomas. This systematic study examines the development of deep learning techniques for IDH prediction using histopathology images, spanning the period from 2019 to 2023.
METHOD
The study adhered to the PRISMA reporting requirements, and databases including PubMed, Google Scholar, Google Search, and preprint repositories (such as arXiv) were systematically queried for pertinent literature spanning the period from 2019 to the 30th of 2023. Search phrases related to deep learning, digital pathology, glioma, and IDH were collaboratively utilized.
RESULTS
Fifteen papers meeting the inclusion criteria were included in the analysis. These criteria specifically encompassed studies utilizing deep learning for the analysis of hematoxylin and eosin images to determine the IDH status in patients with gliomas.
CONCLUSIONS
When predicting the status of IDH, the classifier built on digital pathological images demonstrates exceptional performance. The study's predictive effectiveness is enhanced with the utilization of the appropriate deep learning model. However, external verification is necessary to showcase their resilience and universality. Larger sample sizes and multicenter samples are necessary for more comprehensive research to evaluate performance and confirm clinical advantages.
Topics: Humans; Brain Neoplasms; Deep Learning; Glioma; Biomarkers; Isocitrate Dehydrogenase; Mutation; Magnetic Resonance Imaging; Multicenter Studies as Topic
PubMed: 38363910
DOI: 10.1097/MD.0000000000037150 -
Renal Failure Dec 2024This systematic review and meta-analysis were conducted to evaluate the cardiac and kidney-related adverse effects of roxadustat for the treatment of anemia in CKD... (Meta-Analysis)
Meta-Analysis Review
Cardiovascular and renal safety outcomes of hypoxia-inducible factor prolyl-hydroxylase inhibitor roxadustat for anemia patients with chronic kidney disease: a systematic review and meta-analysis.
This systematic review and meta-analysis were conducted to evaluate the cardiac and kidney-related adverse effects of roxadustat for the treatment of anemia in CKD patients. 18 trials with a total of 8806 participants were identified for analysis. We employed a fixed-effects model for analysis. The pooled result revealed no significant difference in the risk of occurrence of cardiac disorders when comparing CKD patients receiving roxadustat with the placebo (RR = 1.049; CI [0.918 to 1.200]) or ESA (RR = 1.066; CI [0.919 to 1.235]), in both dialysis-dependent (DD) (RR = 1.094; CI [0.925 to 1.293]) or non-dialysis-dependent (NDD) (RR = 1.036; CI [0.916 to 1.171]) CKD patients. No significant difference was observed in the risk of kidney-related adverse events when comparing roxadustat with the placebo (RR = 1.088; CI [0.980 to 1.209]) or ESA (RR = 0.968; CI [0.831 to 1.152]), in DD (RR = 2.649; CI [0.201 to 34.981]) or NDD (RR = 1.053; CI [0.965 to 1.149]) CKD patients. A high risk of hyperkalemia was observed in the roxadustat group in DD (RR = 0.939; CI [0.898 to 0.981]). Incidence of hypertension was higher in the roxadustat for NDD patients (RR = 1.198; CI [1.042 to 1.377]), or compared to the placebo (RR = 1.374; CI [1.153 to 1.638]). In summary, the risk of cardiac or kidney-related events observed in the roxadustat was not significantly increase whether in DD or NDD patients. However, attention must be paid to the occurrence of hyperkalemia for DD patients and hypertension in NDD patients using roxadustat.
Topics: Humans; Prolyl-Hydroxylase Inhibitors; Prolyl Hydroxylases; Hyperkalemia; Anemia; Renal Insufficiency, Chronic; Hypertension; Kidney; Hypoxia
PubMed: 38345037
DOI: 10.1080/0886022X.2024.2313864 -
BMC Nephrology Feb 2024This study aimed to investigate the association between cytochrome P450 (CYP) 3A4*22 and cytochrome P450 oxidoreductase (POR)*28 variations and the pharmacokinetics of... (Meta-Analysis)
Meta-Analysis
PURPOSE
This study aimed to investigate the association between cytochrome P450 (CYP) 3A4*22 and cytochrome P450 oxidoreductase (POR)*28 variations and the pharmacokinetics of tacrolimus.
METHODS
Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (SCI), MEDLINE, and Embase were systematically searched from inception to August 2022. The outcomes were weight-adjusted daily dose and dose-adjusted trough concentration (C/Dose).
RESULTS
The study included 2931 renal transplant recipients from 18 publications. Weight-adjusted daily dose of CYP3A4*1/*1 carriers was 0.04 (WMD = 0.04, 95% CI: 0.02 to 0.06), 0.03 (WMD = 0.03, 95% CI: 0.02 to 0.05), 0.02 (WMD = 0.02, 95% CI: 0.01 to 0.03), or 0.02 mg/kg/day (WMD = 0.02, 95% CI: 0.00 to 0.04) higher than CYP3A4*22 carriers in Caucasians at 1 month, 3 months, 6 months, or 12 months post-transplantation. Conversely, C0/Dose was lower for CYP3A4*1/*1 carriers at 3 days (SMD = -0.35, 95% CI: -0.65 to -0.06), 1 month (SMD = -0.67, 95% CI: -1.16 to -0.18), 3 months (SMD = -0.60, 95% CI: -0.89 to -0.31), 6 months (SMD = -0.76, 95% CI: -1.49 to -0.04), or 12 months post-transplantation (SMD = -0.69, 95% CI: -1.37 to 0.00). Furthermore, C/Dose of POR*1/*1 carriers was 22.64 (WMD = 22.64, 95% CI: 2.54 to 42.74) or 19.41 (ng/ml)/(mg/kg/day) (WMD = 19.41, 95% CI: 9.58 to 29.24) higher than POR*28 carriers in CYP3A5 expressers at 3 days or 7 days post-transplantation, and higher in Asians at 6 months post-transplantation (SMD = 0.96, 95% CI: 0.50 to 1.43).
CONCLUSIONS
CYP3A4*22 variant in Caucasians restrains the metabolism of tacrolimus, while POR*28 variant in CYP3A5 expressers enhances the metabolism of tacrolimus for renal transplant recipients. However, further well-designed prospective studies are necessary to substantiate these conclusions given some limitations.
Topics: Humans; Tacrolimus; Cytochrome P-450 CYP3A; Immunosuppressive Agents; Kidney Transplantation; Prospective Studies; Polymorphism, Single Nucleotide; Transplant Recipients; Genotype
PubMed: 38321419
DOI: 10.1186/s12882-024-03467-4