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Molecules (Basel, Switzerland) Dec 2021Proliferating cancer cells have high energy demands, which is mainly obtained through glycolysis. The transmembrane trafficking of lactate, a major metabolite produced... (Meta-Analysis)
Meta-Analysis
Proliferating cancer cells have high energy demands, which is mainly obtained through glycolysis. The transmembrane trafficking of lactate, a major metabolite produced by glycolytic cancer cells, relies on monocarboxylate transporters (MCTs). MCT1 optimally imports lactate, although it can work bidirectionally, and its activity has been linked to cancer aggressiveness and poor outcomes. AZD3965, a specific MCT1 inhibitor, was tested both in vitro and in vivo, with encouraging results; a phase I clinical trial has already been undertaken. Thus, analysis of the experimental evidence using AZD3965 in different cancer types could give valuable information for its clinical use. This systematic review aimed to assess the in vivo anticancer activity of AZD3965 either alone (monotherapy) or with other interventions (combination therapy). Study search was performed in nine different databases using the keywords "AZD3965 in vivo" as search terms. The results show that AZD3965 successfully decreased tumor growth and promoted intracellular lactate accumulation, which confirmed its effectiveness, especially in combined therapy. These results support the setup of clinical trials, but other important findings, namely AZD3965 enhanced activity when given in combination with other therapies, or MCT4-induced treatment resistance, should be further considered in the clinical trial design to improve therapy response.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Disease Management; Disease Progression; Drug Evaluation, Preclinical; Energy Metabolism; Glycolysis; Humans; Lactic Acid; Monocarboxylic Acid Transporters; Neoplasms; Pyrimidinones; Signal Transduction; Symporters; Thiophenes; Tumor Microenvironment; Warburg Effect, Oncologic; Xenograft Model Antitumor Assays
PubMed: 35011413
DOI: 10.3390/molecules27010181 -
Renal Failure Dec 2021Inconsistent investigations of the risk factors for all-cause mortality in patients undergoing peritoneal dialysis (PD) were reported. The present meta-analysis aimed to... (Meta-Analysis)
Meta-Analysis
Inconsistent investigations of the risk factors for all-cause mortality in patients undergoing peritoneal dialysis (PD) were reported. The present meta-analysis aimed to assess the impact of some clinical characteristics on the risk of mortality in PD patients. PubMed and Embase were systematically searched for studies evaluating the risk factors for all-cause mortality in PD patients. Hazard ratio (HR) and 95% confidence interval (CI) were derived using a random-effect or fixed-effect model considering the heterogeneity across studies. A total of 26 studies were included in this meta-analysis in accordance with the inclusion and exclusion criteria. Age, primary cardiovascular diseases, diabetes mellitus, and high level of alkaline phosphatase showed significant positive associations with elevated risk of all-cause and cardiovascular mortality in PD patients, while hemoglobin acted as a benefit factor. Furthermore, early onset of peritonitis, high peritoneal transport status, elevated body mass index and high-sensitivity C-reactive protein could also considerably increase the risk of all-cause mortality. The absolute serum level of magnesium, potassium, and uric acid required to improve survival in PD patients should be verified further. Multiple factors could affect the risk of mortality in PD patients.
Topics: Alkaline Phosphatase; Cardiovascular Diseases; Cause of Death; Humans; Kidney Failure, Chronic; Mortality; Peritoneal Dialysis; Risk Assessment; Risk Factors
PubMed: 33913381
DOI: 10.1080/0886022X.2021.1918558 -
PloS One 2024An important cellular barrier to maintain the stability of the brain's internal and external environment is the blood-brain barrier (BBB). It also prevents harmful... (Meta-Analysis)
Meta-Analysis
Electroacupuncture stimulation enhances the permeability of the blood-brain barrier: A systematic review and meta-analysis of preclinical evidence and possible mechanisms.
An important cellular barrier to maintain the stability of the brain's internal and external environment is the blood-brain barrier (BBB). It also prevents harmful substances from entering brain tissue through blood circulation while providing protection for the central nervous system. It should be noted, however, that the intact BBB can be a barrier to the transport of most drugs into the brain via the conventional route of administration, which can prevent them from reaching effective concentrations for the treatment of disorders affecting the central nervous system. Electroacupuncture stimulation has been shown to be effective at opening the BBB in a series of experimental studies. This study systematically analyzes the possibility and mechanism by which electroacupuncture opens the BBB. In PubMed, Web of Science, VIP Database, Wanfang Database, and the Chinese National Knowledge Infrastructure, papers have been published for nearly 22 years aimed at opening the BBB and its associated structures. A comparison of EB content between electroacupuncture and control was selected as the primary outcome. There were also results on vascular endothelial growth factor (VEGF), nerve growth factor (NGF), P-Glycoprotein (P-gp), Matrix Metalloproteinase 9 (MMP-9), and glial fibrillary acidic protein (GFAP). We utilized Review Manager software analysis to analyze correlations between studies with a view to exploring the mechanisms of similarity. Evans Blue infiltration forest plot: pooled effect size of 2.04, 95% CI: 1.21 to 2.87, P < 0.01. These results indicate that electroacupuncture significantly increases EB penetration across the BBB. Most studies have reported that GFAP, MMP-9, and VEGF were upregulated after treatment. P-gp expression decreased as well. Electroacupuncture can open the BBB, and the sparse-dense wave is currently the most effective electroacupuncture frequency for opening the BBB. VEGF plays an important role in opening the BBB. It is also important to regulate the expression of MMP-9 and GFAP and inhibit the expression of P-gp.
Topics: Rats; Animals; Blood-Brain Barrier; Vascular Endothelial Growth Factor A; Matrix Metalloproteinase 9; Electroacupuncture; Rats, Sprague-Dawley; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily B; Permeability
PubMed: 38536776
DOI: 10.1371/journal.pone.0298533 -
Cardiovascular Diabetology Jun 2024
Correction to: Effectiveness and safety of the combination of sodium-glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies.
PubMed: 38824524
DOI: 10.1186/s12933-024-02283-2 -
Journal of Neuromuscular Diseases 2021Parkinson's disease (PD) is a disabling neurological condition characterized by the loss of dopaminergic neurons. Currently, the treatment for PD is symptomatic and...
Parkinson's disease (PD) is a disabling neurological condition characterized by the loss of dopaminergic neurons. Currently, the treatment for PD is symptomatic and compensates for the endogenous loss of dopamine production. In cases where the pharmacological therapy is only partly beneficial or results in major wearing-off complications, surgical interventions such as deep brain stimulation may be an alternative treatment. The disease cause often remains unknown, but in some patients, a monogenic cause can be identified. Mutations in at least six genes, LRRK2, SNCA, and VPS35 (dominant forms) or Parkin/PRKN, PINK1, and DJ1/PARK7 (recessive forms) have been unequivocally linked to PD pathogenesis. We here systematically screened 8,576 publications on these monogenic PD forms. We identified 2,226 mutation carriers from 456 papers. Levodopa was the most widely applied treatment; only 34 patients were indicated to be untreated at the time of reporting. Notably, detailed treatment data was rarely mentioned including response quantification (good, moderate, minimal) in 951 and/or dose in 293 patients only. Based on available data, levodopa showed an overall good outcome, especially in LRRK2, VPS35, Parkin, and PINK1 mutation carriers ("good" response in 94.6-100%). Side effects of levodopa therapy were reported in ∼15-40%of levodopa-treated patients across genes with dyskinesias as the most frequent one. Non-levodopa medication was indicated to be administered to <200 patients with mainly good outcome. Only a few reports were available on outcomes of brain surgery. Here, most mutation carriers showed a good response. Importantly, none of the available treatments is harmful to one genetic form but effective in another one. In the light of different medication schemes, the progressive nature of PD, and side effects, an improvement of therapeutic options for PD is warranted including a treatabolome database to guide clinicians in treatment decisions. Further, novel disease-cause-modifying drugs are needed.
Topics: Antiparkinson Agents; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Levodopa; Mutation; Parkinson Disease; Protein Deglycase DJ-1; Protein Kinases; Ubiquitin-Protein Ligases; Vesicular Transport Proteins; alpha-Synuclein
PubMed: 33459660
DOI: 10.3233/JND-200598 -
Medicina (Kaunas, Lithuania) May 2023: Colchicine has been proposed as a cytokine storm-blocking agent for COVID-19 due to its efficacy as an anti-inflammatory drug. The findings of the studies were... (Review)
Review
: Colchicine has been proposed as a cytokine storm-blocking agent for COVID-19 due to its efficacy as an anti-inflammatory drug. The findings of the studies were contentious on the role of colchicine in preventing deterioration in COVID-19 patients. We aimed to evaluate the efficacy of colchicine in COVID-19-hospitalized patients. : A retrospective observational cohort study was carried out at three major isolation hospitals in Alexandria (Egypt), covering multiple centers. In addition, a systematic review was conducted by searching six different databases for published studies on the utilization of colchicine in patients with COVID-19 until March 2023. The primary outcome measure was to determine whether colchicine could decrease the number of days that the patient needed supplemental oxygen. The secondary outcomes were to evaluate whether colchicine could reduce the number of hospitalization days and mortality rate in these patients. : Out of 515 hospitalized COVID-19 patients, 411 were included in the survival analysis. After adjusting for the patients' characteristics, patients not receiving colchicine had a shorter length of stay (median: 7.0 vs. 6.0 days) and fewer days of supplemental oxygen treatment (median: 6.0 vs. 5.0 days), < 0.05, but there was no significant difference in mortality rate. In a subgroup analysis based on oxygen equipment at admission, patients admitted on nasal cannula/face masks who did not receive colchicine had a shorter duration on oxygen supply than those who did [Hazard Ratio (HR) = 0.76 (CI 0.59-0.97)]. Using cox-regression analysis, clarithromycin compared to azithromycin in colchicine-treated patients was associated with a higher risk of longer duration on oxygen supply [HR = 1.77 (CI 1.04-2.99)]. Furthermore, we summarized 36 published colchicine studies, including 114,878 COVID-19 patients. COVID-19-hospitalized patients who were given colchicine had poorer outcomes in terms of the duration of supplemental oxygen use and the length of their hospital stay. Therefore, based on these findings, the use of colchicine is not recommended for COVID-19-hospitalized adults.
Topics: Adult; Humans; COVID-19; Colchicine; Retrospective Studies; SARS-CoV-2; Oxygen Saturation; Oxygen; Observational Studies as Topic
PubMed: 37241167
DOI: 10.3390/medicina59050934 -
International Journal of Molecular... Oct 2021The Epithelial Sodium Channel/Degenerin (ENaC/DEG) family is a superfamily of sodium-selective channels that play diverse and important physiological roles in a wide...
The Epithelial Sodium Channel/Degenerin (ENaC/DEG) family is a superfamily of sodium-selective channels that play diverse and important physiological roles in a wide variety of animal species. Despite their differences, they share a high homology in the pore region in which the ion discrimination takes place. Although ion selectivity has been studied for decades, the mechanisms underlying this selectivity for trimeric channels, and particularly for the ENaC/DEG family, are still poorly understood. This systematic review follows PRISMA guidelines and aims to determine the main components that govern ion selectivity in the ENaC/DEG family. In total, 27 papers from three online databases were included according to specific exclusion and inclusion criteria. It was found that the G/SxS selectivity filter (glycine/serine, non-conserved residue, serine) and other well conserved residues play a crucial role in ion selectivity. Depending on the ion type, residues with different properties are involved in ion permeability. For lithium against sodium, aromatic residues upstream of the selectivity filter seem to be important, whereas for sodium against potassium, negatively charged residues downstream of the selectivity filter seem to be important. This review provides new perspectives for further studies to unravel the mechanisms of ion selectivity.
Topics: Amiloride; Animals; Epithelial Sodium Channels; Humans; Ion Transport; Lithium; Molecular Dynamics Simulation; Mutagenesis, Site-Directed; Protein Structure, Quaternary; Sodium
PubMed: 34681656
DOI: 10.3390/ijms222010998 -
BMC Cardiovascular Disorders Mar 2020Depression has been recognized as an independent risk factor of coronary heart disease (CHD). Moreover, there is interrelationship of both depression and CHD. However,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Depression has been recognized as an independent risk factor of coronary heart disease (CHD). Moreover, there is interrelationship of both depression and CHD. However, the potential pathophysiological mechanisms remain unknown. It might be influenced by genetic and environmental factors. According to recent researches, there is potential association between serotonin transporter gene-linked polymorphic region (5-HTTLPR) polymorphism and risk of depression in CHD patients, but the results are still inconclusive. Therefore, we performed this meta-analysis based on unadjusted and adjusted data to ascertain a more precise conclusion.
METHODS
We searched relevant articles through PubMed, Embase, Web of Science, Chinese BioMedical Literature (CBM) and Chinese National Knowledge Infrastructure (CNKI) databases up to August 26, 2019. Study selection and data extraction were accomplished by two authors independently. The strength of the correlation was assessed via odds ratios (ORs) with their 95% confidence intervals (95%CIs).
RESULTS
This meta-analysis enrolled six observational studies. Based on unadjusted data, there was significant relationship between 5-HTTLPR polymorphism and depression risk in CHD patients under all genetic models (S vs. L: OR = 1.31, 95%CI = 1.07-1.60; SS vs. LL: OR = 1.73, 95%CI = 1.12-2.67; LS vs. LL: OR = 1.47, 95%CI = 1.13-1.92; LS + SS vs. LL: OR = 1.62, 95%CI = 1.25-2.09; SS vs. LL + LS: OR = 1.33, 95%CI = 1.02-1.74). The results of adjusted data further strengthened this relationship (SS vs. LL: OR = 1.89, 95%CI = 1.28-2.80; LS vs. LL: OR = 1.69, 95%CI = 1.14-2.51; LS + SS vs. LL: OR = 1.80, 95%CI = 1.25-2.59). Subgroup analyses based on ethnicity and major depressive disorder revealed similar results to that of the overall analysis. No evidence of publication bias was observed.
CONCLUSIONS
Our results suggest that 5-HTTLPR polymorphism may have an important effect on the risk of depression among patients with CHD, and carriers of the S allele of 5-HTTLPR are more vulnerable to depression.
Topics: Affect; Coronary Disease; Depression; Genetic Predisposition to Disease; Humans; Phenotype; Polymorphism, Genetic; Risk Factors; Serotonin Plasma Membrane Transport Proteins
PubMed: 32188408
DOI: 10.1186/s12872-020-01424-1 -
The Journal of International Advanced... Dec 2020To establish outcomes following cochlear implantation (CI) in patients with postsynaptic auditory neuropathy (AN). Systematic review and narrative synthesis. Databases...
To establish outcomes following cochlear implantation (CI) in patients with postsynaptic auditory neuropathy (AN). Systematic review and narrative synthesis. Databases searched: MEDLINE, PubMed, EMBASE, Web of Science, Cochrane Collection and ClinicalTrials.gov. No limits placed on language or year of publication. Review conducted in accordance with the PRISMA statement. Searches identified 98 studies in total, of which 14 met the inclusion criteria reporting outcomes in 25 patients with at least 28 CIs. Of these, 4 studies focused on Charcot-Marie-Tooth disease (CMT), 3 on Brown-Vialetto-Van-Laere syndrome (BVVL), 2 on Friedreich Ataxia (FRDA), 2 on Syndromic dominant optic atrophy (DOA+), 2 on Cerebellar ataxia - areflexia - pes cavus - optic atrophy - sensorineural hearing loss (CAPOS) syndrome, and 1 on Deafness-dystonia-optic neuronopathy (DDON) syndrome. All studies were Oxford Centre for Evidence Based Medicine (OCEBM) grade IV. Overall trend was towards good post-CI outcomes with 22 of the total 25 patients displaying modest to significant benefit. Hearing outcomes following CI in postsynaptic ANs are variable but generally good with patients showing improvements in hearing thresholds and speech perception. In the future, development of a clearer stratification system into pre, post, and central AN would have clinical and academic benefits. Further research is required to understand AN pathophysiology and develop better diagnostic tools for more accurate identification of lesion sites. Multicenter longitudinal studies with standardized comprehensive outcome measures including health-related quality of life data will be key in establishing a better understanding of short and long-term post-CI outcomes.
Topics: Adolescent; Adult; Child; Child, Preschool; Cochlear Implantation; Cochlear Implants; Female; Hearing Loss, Central; Hearing Loss, Sensorineural; Humans; Male; Membrane Transport Proteins; Multicenter Studies as Topic; Quality of Life; Retrospective Studies; Sodium-Potassium-Exchanging ATPase; Speech Perception
PubMed: 33136025
DOI: 10.5152/iao.2020.9035 -
International Journal of Molecular... Oct 2019Missing heritability is a common problem in psychiatry that impedes precision medicine approaches to autism and other heritable complex disorders. This proof-of-concept... (Meta-Analysis)
Meta-Analysis
Missing heritability is a common problem in psychiatry that impedes precision medicine approaches to autism and other heritable complex disorders. This proof-of-concept study uses a systematic review and meta-analysis of the association between variants of the serotonin transporter promoter (5-HTTLPR) and autism to explore the hypothesis that some missing heritability can be explained using an optimum curve. A systematic literature search was performed to identify transmission disequilibrium tests on the short/long (S/L) 5-HTTLPR polymorphism in relation to autism. We analysed five American, seven European, four Asian and two American/European samples. We found no transmission preference in the joint samples and in Europe, preferential transmission of S in America and preferential transmission of L in Asia. Heritability will be underestimated or missed in genetic association studies if two alternative genetic variants are associated with the same disorder in different subsets of a sample. An optimum curve, relating a multifactorial biological variable that incorporates genes and environment to a score for a human trait, such as social competence, can explain this. We suggest that variants of functionally related genes will sometimes appear in fixed combinations at both sides of an optimum curve and propose that future association studies should account for such combinations.
Topics: Autism Spectrum Disorder; Genetic Predisposition to Disease; Humans; Odds Ratio; Polymorphism, Single Nucleotide; Risk Assessment; Serotonin Plasma Membrane Transport Proteins
PubMed: 31618836
DOI: 10.3390/ijms20205104