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Cardiovascular Diabetology Mar 2024Randomized controlled trials and real-world studies suggest that combination therapy with sodium-glucose transport protein 2 inhibitors (SGLT2is) and glucagon-like... (Meta-Analysis)
Meta-Analysis
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.
BACKGROUND
Randomized controlled trials and real-world studies suggest that combination therapy with sodium-glucose transport protein 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is associated with improvement in fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), systolic blood pressure (SBP), body mass index (BMI), and total cholesterol levels. However, a systematic review of available real-world evidence may facilitate clinical decision-making in the real-world scenario. This meta-analysis assessed the safety and effectiveness of combinations of SGLT2is + GLP-1RAs with a focus on their cardioprotective effects along with glucose-lowering ability in patients with type 2 diabetes mellitus (T2DM) in a real-world setting.
METHODS
Electronic searches were performed in the PubMed/MEDLINE, PROQuest, Scopus, CINAHL, and Google Scholar databases. Qualitative analyses and meta-analyses were performed using the Joanna Briggs Institute SUMARI software package and Review Manager v5.4, respectively.
RESULTS
The initial database search yielded 1445 articles; of these, 13 were included in this study. The analyses indicated that SGLT2is + GLP-1RAs combinations were associated with significantly lower all-cause mortality when compared with individual therapies (odds ratio [95% confidence interval [CI] 0.49 [0.41, 0.60]; p < 0.00001). Significant reductions in BMI (- 1.71 [- 2.74, - 0.67]; p = 0.001), SBP (- 6.35 [- 10.17, - 2.53]; p = 0.001), HbA1c levels (- 1.48 [- 1.75, - 1.21]; p < 0.00001), and FPG (- 2.27 [- 2.78, - 1.76]; p < 0.00001) were associated with the simultaneous administration of the combination. Changes in total cholesterol levels and differences between simultaneous and sequential combination therapies for this outcome were not significant.
CONCLUSION
This systematic review and meta-analysis based on real-world data suggests that the combination of SGLT2is + GLP-1RAs is associated with lower all-cause mortality and favorable improvements in cardiovascular, renal, and glycemic measurements. The findings drive a call-to-action to incorporate this combination early and simultaneously in managing T2DM patients and achieve potential cardiovascular benefits and renal protection.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Glucagon-Like Peptide-1 Receptor Agonists; Glycated Hemoglobin; Blood Glucose; Cholesterol; Glucagon-Like Peptide-1 Receptor
PubMed: 38500154
DOI: 10.1186/s12933-024-02192-4 -
Journal of Animal Science Jan 2024Improving the feeding efficiency of dairy cows is a key component to improve the utilization of land resources and meet the demand for high-quality protein. Advances in... (Meta-Analysis)
Meta-Analysis
Improving the feeding efficiency of dairy cows is a key component to improve the utilization of land resources and meet the demand for high-quality protein. Advances in genomic methods and omics techniques have made it possible to breed more efficient dairy cows through genomic selection. The aim of this review is to obtain a comprehensive understanding of the biological background of feed efficiency (FE) complex traits in purebred Holstein dairy cows including heritability estimate, and genetic markers, genes, and pathways participating in FE regulation mechanism. Through a literature search, we systematically reviewed the heritability estimation, molecular genetic markers, genes, biomarkers, and pathways of traits related to feeding efficiency in Holstein dairy cows. A meta-analysis based on a random-effects model was performed to combine reported heritability estimates of FE complex. The heritability of residual feed intake, dry matter intake, and energy balance was 0.20, 0.34, and 0.22, respectively, which proved that it was reasonable to include the related traits in the selection breeding program. For molecular genetic markers, a total of 13 single-nucleotide polymorphisms and copy number variance loci, associated genes, and functions were reported to be significant across populations. A total of 169 reported candidate genes were summarized on a large scale, using a higher threshold (adjusted P value < 0.05). Then, the subsequent pathway enrichment of these genes was performed. The important genes reported in the articles were included in a gene list and the gene list was enriched by gene ontology (GO):biological process (BP), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis. Three GO:BP terms and four KEGG terms were statistically significant, which mainly focused on adenosine triphosphate (ATP) synthesis, electron transport chain, and OXPHOS pathway. Among these pathways, involved genes such as ATP5MC2, NDUFA, COX7A2, UQCR, and MMP are particularly important as they were previously reported. Twenty-nine reported biological mechanisms along with involved genes were explained mainly by four biological pathways (insulin-like growth factor axis, lipid metabolism, oxidative phosphorylation pathways, tryptophan metabolism). The information from this study will be useful for future studies of genomic selection breeding and genetic structures influencing animal FE. A better understanding of the underlying biological mechanisms would be beneficial, particularly as it might address genetic antagonism.
Topics: Female; Cattle; Animals; Lactation; Genetic Markers; Phenotype; Genome; Eating; Animal Feed; Milk
PubMed: 38354297
DOI: 10.1093/jas/skae040 -
Biomedical and Environmental Sciences :... Jan 2024This study explored the potentially modifiable factors for depression and major depressive disorder (MDD) from the MR-Base database and further evaluated the...
OBJECTIVE
This study explored the potentially modifiable factors for depression and major depressive disorder (MDD) from the MR-Base database and further evaluated the associations between drug targets with MDD.
METHODS
We analyzed two-sample of Mendelian randomization (2SMR) using genetic variant depression ( = 113,154) and MDD ( = 208,811) from Genome-Wide Association Studies (GWAS). Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes. The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD. Inverse variance weighted (IVW), fixed-effect inverse variance weighted (FE-IVW), MR-Egger, weighted median, and weighted mode were used for complementary calculation.
RESULTS
The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD. Also, the associations between drug targets and MDD showed that , , , , and expression are associated with an increased risk of depression. In contrast, , , , , and genes are candidate protective factors against depression.
CONCLUSION
This study identified the risk factors causally associated with depression and MDD, and estimated 10 drug targets with significant impact on MDD, providing essential information for formulating strategies to prevent and treat depression.
Topics: Humans; Depressive Disorder, Major; Depression; Genome-Wide Association Study; Mendelian Randomization Analysis; Risk Factors; Serotonin Plasma Membrane Transport Proteins
PubMed: 38326723
DOI: 10.3967/bes2024.007 -
International Immunopharmacology Mar 2024Immune checkpoint inhibitors (ICIs) have effectively improved the clinical outcome of advanced non-small cell lung cancer (NSCLC). Opioids are commonly used for pain... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Immune checkpoint inhibitors (ICIs) have effectively improved the clinical outcome of advanced non-small cell lung cancer (NSCLC). Opioids are commonly used for pain relief in cancer patients. This study aims to clarify the prognostic impact of opioid use in advanced NSCLC patients receiving ICI therapy.
METHODS
A systematic literature review was carried out using online databases before July 2023. The meta-analysis was used to clarify the correlation of opioid use with the overall survival (OS) or progression-free survival (PFS) of ICI-treated NSCLC patients, both of which were determined using hazard ratios (HRs) coupled with 95 % confidence intervals (CIs). Then, an independent cohort enrolling 181 NSCLC patients was utilized for validation. Finally, a comprehensive bioinformatics analysis based on TCGA cohort was performed to investigate the prognostic significance of opioid target genes (OTGs) and their correlation with immune infiltration in NSCLC patients.
RESULTS
A total of 8 studies enrolling 1174 patients were included in the meta-analysis. Opioid use was negatively associated with worse PFS (HR = 2.16, 95 %CI: 1.26-3.71) and OS (HR = 2.02, 95 %CI: 1.54-2.63) in ICI-treated NSCLC patients. The retrospective validation confirmed the above result and identified opioid use as an independent unfavorable predictor for PFS and OS in both the entire cohort and ICI subgroup. The bioinformatic analysis identified 14 prognostic OTGs (CYP17A1, PDYN, PYCARD, FGA, NTSR1, FABP1, HPCA, PENK, PDGFB, LIN7A, FKBP5, TYMS, CACNA1H and LDHA), most of which were correlated with immune infiltration in NSCLC. A risk model was constructed based on 14 OTGs and found to effectively stratify the clinical outcome in both the training and validation set, independent of age, gender and TNM staging system. The model was also significantly correlated with infiltration of activated dendritic cells, neutrophils and tumor infiltrating lymphocytes. Finally, a nomogram was constructed based on the model, age, gender and TNM stage, which could predict well the 1-, 3- and 5-year survival of NSCLC patients.
CONCLUSION
Opioid use is correlated with the poor clinical outcome in ICI-treated NSCLC patients. Precise pain management is highly advocated and opioids are recommended to be cautiously used in these patients. OTGs have the potential to be prognostic biomarkers for NSCLC patients and their role in tumor immunity needs to be further investigated.
Topics: Humans; Analgesics, Opioid; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Membrane Proteins; Opioid-Related Disorders; Retrospective Studies; Vesicular Transport Proteins
PubMed: 38325047
DOI: 10.1016/j.intimp.2024.111611 -
Acta Cytologica 2024The diagnosis of salivary gland secretory carcinoma (SC) in fine-needle aspiration specimens is challenging because its low-grade nature makes it difficult to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The diagnosis of salivary gland secretory carcinoma (SC) in fine-needle aspiration specimens is challenging because its low-grade nature makes it difficult to differentiate it from various benign or malignant salivary gland neoplasms. Currently, the gold standard is demonstration of ETV6-NTRK3 fusion gene. However, the decision for ordering this costly molecular testing can be facilitated by the correct recognition of its cytomorphological features. The aim of the review was to determine the accuracy of fine-needle aspiration cytology (FNAC) in diagnosis of salivary gland SC. The secondary objective was to recognize varied cytomorphological patterns, characteristic features of SC and differentiate it from other neoplasms.
METHODS
PubMed/MEDLINE, Science Direct, Embase, Cochrane review, and PROSPERO databases were searched for studies having the following key search terms: ("secretory carcinoma of salivary gland" OR "mammary analogue secretory carcinoma of salivary gland") AND ("Cytology" OR "Cytological features" OR "aspirate" OR "cytodiagnosis") published in the time frame of 2010 to June 2023. Studies reporting cytological features of the salivary gland tumors which were confirmed/diagnosed as SC on molecular investigation, were included in the systematic review. Finally, seventeen studies reporting a total of 45 cases were included in the metanalysis.
RESULTS
The sensitivity of the FNAC in diagnosing SC in salivary gland is 27.7% (95% CI: 16.6-42.5%). The LR+ (positive likelihood ratio) was 0.654 (0.344-1.245), LR- (negative likelihood ratio) was 1.023 (0.538-1.946), and diagnostic odds ratio was 0.421 (0.129-1.374). The molecular testing and/or immunohistochemistry performed on cell block increased the diagnostic accuracy.
CONCLUSION
Recognition of subtle cytomorphological patterns, i.e., papillary formation, clusters, and singly dispersed cells along with presence of fine intracytoplasmic vacuolations were the characteristic findings in majority of cases, confirmed with diagnostic molecular profiling. This may be helpful in identification of this rare entity with limited published literature and help in increasing diagnostic accuracy.
Topics: Humans; Biopsy, Fine-Needle; Salivary Gland Neoplasms; Female; Predictive Value of Tests; Salivary Glands; Adult; Male; Reproducibility of Results; Biomarkers, Tumor; Middle Aged; Carcinoma; Mammary Analogue Secretory Carcinoma; Oncogene Proteins, Fusion; Young Adult; Adolescent; Cytodiagnosis; Aged; Diagnosis, Differential; Child; Cytology; ETS Translocation Variant 6 Protein; Receptor, trkC
PubMed: 38228123
DOI: 10.1159/000536249 -
Current Issues in Molecular Biology Dec 2023Lipids are important modifiers of protein function, particularly as parts of lipoproteins, which transport lipophilic substances and mediate cellular uptake of... (Review)
Review
Lipids are important modifiers of protein function, particularly as parts of lipoproteins, which transport lipophilic substances and mediate cellular uptake of circulating lipids. As such, lipids are of particular interest as blood biological markers for cardiovascular disease (CVD) as well as for conditions linked to CVD such as atherosclerosis, diabetes mellitus, obesity and dietary states. Notably, lipid research is particularly well developed in the context of CVD because of the relevance and multiple causes and risk factors of CVD. The advent of methods for high-throughput screening of biological molecules has recently resulted in the generation of lipidomic profiles that allow monitoring of lipid compositions in biological samples in an untargeted manner. These and other earlier advances in biomedical research have shaped the knowledge we have about lipids in CVD. To evaluate the knowledge acquired on the multiple biological functions of lipids in CVD and the trends in their research, we collected a dataset of references from the PubMed database of biomedical literature focused on plasma lipids and CVD in human and mouse. Using annotations from these records, we were able to categorize significant associations between lipids and particular types of research approaches, distinguish non-biological lipids used as markers, identify differential research between human and mouse models, and detect the increasingly mechanistic nature of the results in this field. Using known associations between lipids and proteins that metabolize or transport them, we constructed a comprehensive lipid-protein network, which we used to highlight proteins strongly connected to lipids found in the CVD-lipid literature. Our approach points to a series of proteins for which lipid-focused research would bring insights into CVD, including Prostaglandin G/H synthase 2 (PTGS2, a.k.a. COX2) and Acylglycerol kinase (AGK). In this review, we summarize our findings, putting them in a historical perspective of the evolution of lipid research in CVD.
PubMed: 38132464
DOI: 10.3390/cimb45120618 -
Pharmacological Research Jan 2024Zinc is a crucial trace element in the human body, playing a role in various physiological processes such as oxidative stress, neurotransmission, protein synthesis, and...
Zinc is a crucial trace element in the human body, playing a role in various physiological processes such as oxidative stress, neurotransmission, protein synthesis, and DNA repair. The zinc transporters (ZnTs) family members are responsible for exporting intracellular zinc, while Zrt- and Irt-like proteins (ZIPs) are involved in importing extracellular zinc. These processes are essential for maintaining cellular zinc homeostasis. Imbalances in zinc metabolism have been linked to the development of neurodegenerative diseases. Disruptions in zinc levels can impact the survival and activity of neurons, thereby contributing to the progression of neurodegenerative diseases through mechanisms like cell apoptosis regulation, protein phase separation, ferroptosis, oxidative stress, and neuroinflammation. Therefore, conducting a systematic review of the regulatory network of zinc and investigating the relationship between zinc dysmetabolism and neurodegenerative diseases can enhance our understanding of the pathogenesis of these diseases. Additionally, it may offer new insights and approaches for the treatment of neurodegenerative diseases.
Topics: Humans; Cation Transport Proteins; Disease Progression; Homeostasis; Neurodegenerative Diseases; Zinc
PubMed: 38123108
DOI: 10.1016/j.phrs.2023.107039 -
Journal of Oncology Pharmacy Practice :... Apr 2024The plasma cell malignancy, multiple myeloma (MM), remains incurable despite advanced treatment protocols. Overexpression of Bcl-2 (an anti-apoptotic protein), in MM...
BACKGROUND
The plasma cell malignancy, multiple myeloma (MM), remains incurable despite advanced treatment protocols. Overexpression of Bcl-2 (an anti-apoptotic protein), in MM harboring the translocation (11;14), contributes to resistance to prior therapy. Venetoclax, a selective oral inhibitor of BCL-2 is a novel agent that shows promise as a therapeutic agent.
AIMS
The objective of this systematic review is to address how the use of venetoclax, alone or as a combination regimen, contributed to the treatment of patients with t(11:14) positive relapsed/refractory multiple myeloma (RRMM).
DATA SOURCES
This systematic review was conducted in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was done on 5th June 2022. A literature search was conducted on PubMed and Scopus, 145 articles were screened and 10 studies were included. Risk of bias assessment was performed using the Methodological Index for Non-Randomized Studies (MINORS) criteria.
DATA SUMMARY
Across the studies reviewed, a total of 311 patients were identified with t(11;14) positive RRMM. The overall response rate achieved ranged between 33% and 95.5%. Furthermore, the use of venetoclax has exhibited a favorable adverse effect profile. Side effects included hematological side effects, nausea, vomiting, and diarrhea.
CONCLUSION
Venetoclax demonstrates promising results. When given with drugs like dexamethasone, daratumumab and carfilzomib, a synergistic effect is seen in treating translocation (11:14) positive relapsed/refractory MM. The use of venetoclax in clinical practice can potentially improve outcomes and quality of life in RRMM patients, and future research should continue to explore this promising treatment option.
Topics: Humans; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 14; Drug Resistance, Neoplasm; Multiple Myeloma; Neoplasm Recurrence, Local; Sulfonamides; Translocation, Genetic
PubMed: 38113108
DOI: 10.1177/10781552231218999 -
The Cochrane Database of Systematic... Nov 2023Cystic fibrosis (CF) is a common life-shortening genetic condition caused by a variant in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A class... (Review)
Review
BACKGROUND
Cystic fibrosis (CF) is a common life-shortening genetic condition caused by a variant in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A class II CFTR variant F508del is the commonest CF-causing variant (found in up to 90% of people with CF (pwCF)). The F508del variant lacks meaningful CFTR function - faulty protein is degraded before reaching the cell membrane, where it needs to be to effect transepithelial salt transport. Corrective therapy could benefit many pwCF. This review evaluates single correctors (monotherapy) and any combination of correctors (most commonly lumacaftor, tezacaftor, elexacaftor, VX-659, VX-440 or VX-152) and a potentiator (e.g. ivacaftor) (dual and triple therapies).
OBJECTIVES
To evaluate the effects of CFTR correctors (with or without potentiators) on clinically important benefits and harms in pwCF of any age with class II CFTR mutations (most commonly F508del).
SEARCH METHODS
We searched the Cochrane CF Trials Register (28 November 2022), reference lists of relevant articles and online trials registries (3 December 2022).
SELECTION CRITERIA
Randomised controlled trials (RCTs) (parallel design) comparing CFTR correctors to control in pwCF with class II mutations.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data, assessed risk of bias and judged evidence certainty (GRADE); we contacted investigators for additional data.
MAIN RESULTS
We included 34 RCTs (4781 participants), lasting between 1 day and 48 weeks; an extension of two lumacaftor-ivacaftor studies provided additional 96-week safety data (1029 participants). We assessed eight monotherapy RCTs (344 participants) (4PBA, CPX, lumacaftor, cavosonstat and FDL169), 16 dual-therapy RCTs (2627 participants) (lumacaftor-ivacaftor or tezacaftor-ivacaftor) and 11 triple-therapy RCTs (1804 participants) (elexacaftor-tezacaftor-ivacaftor/deutivacaftor; VX-659-tezacaftor-ivacaftor/deutivacaftor; VX-440-tezacaftor-ivacaftor; VX-152-tezacaftor-ivacaftor). Participants in 21 RCTs had the genotype F508del/F508del, in seven RCTs they had F508del/minimal function (MF), in one RCT F508del/gating genotypes, in one RCT either F508del/F508del genotypes or F508del/residual function genotypes, in one RCT either F508del/gating or F508del/residual function genotypes, and in three RCTs either F508del/F508del genotypes or F508del/MF genotypes. Risk of bias judgements varied across different comparisons. Results from 16 RCTs may not be applicable to all pwCF due to age limits (e.g. adults only) or non-standard designs (converting from monotherapy to combination therapy). Monotherapy Investigators reported no deaths or clinically relevant improvements in quality of life (QoL). There was insufficient evidence to determine effects on lung function. No placebo-controlled monotherapy RCT demonstrated differences in mild, moderate or severe adverse effects (AEs); the clinical relevance of these events is difficult to assess due to their variety and few participants (all F508del/F508del). Dual therapy In a tezacaftor-ivacaftor group there was one death (deemed unrelated to the study drug). QoL scores (respiratory domain) favoured both lumacaftor-ivacaftor and tezacaftor-ivacaftor therapy compared to placebo at all time points (moderate-certainty evidence). At six months, relative change in forced expiratory volume in one second (FEV) % predicted improved with all dual combination therapies compared to placebo (high- to moderate-certainty evidence). More pwCF reported early transient breathlessness with lumacaftor-ivacaftor (odds ratio (OR) 2.05, 99% confidence interval (CI) 1.10 to 3.83; I = 0%; 2 studies, 739 participants; high-certainty evidence). Over 120 weeks (initial study period and follow-up), systolic blood pressure rose by 5.1 mmHg and diastolic blood pressure by 4.1 mmHg with twice-daily 400 mg lumacaftor-ivacaftor (80 participants). The tezacaftor-ivacaftor RCTs did not report these adverse effects. Pulmonary exacerbation rates decreased in pwCF receiving additional therapies to ivacaftor compared to placebo (all moderate-certainty evidence): lumacaftor 600 mg (hazard ratio (HR) 0.70, 95% CI 0.57 to 0.87; I = 0%; 2 studies, 739 participants); lumacaftor 400 mg (HR 0.61, 95% CI 0.49 to 0.76; I = 0%; 2 studies, 740 participants); and tezacaftor (HR 0.64, 95% CI 0.46 to 0.89; 1 study, 506 participants). Triple therapy No study reported any deaths (high-certainty evidence). All other evidence was low- to moderate-certainty. QoL respiratory domain scores probably improved with triple therapy compared to control at six months (six studies). There was probably a greater relative and absolute change in FEV % predicted with triple therapy (four studies each across all combinations). The absolute change in FEV % predicted was probably greater for F508del/MF participants taking elexacaftor-tezacaftor-ivacaftor compared to placebo (mean difference 14.30, 95% CI 12.76 to 15.84; 1 study, 403 participants; moderate-certainty evidence), with similar results for other drug combinations and genotypes. There was little or no difference in adverse events between triple therapy and control (10 studies). No study reported time to next pulmonary exacerbation, but fewer F508del/F508del participants experienced a pulmonary exacerbation with elexacaftor-tezacaftor-ivacaftor at four weeks (OR 0.17, 99% CI 0.06 to 0.45; 1 study, 175 participants) and 24 weeks (OR 0.29, 95% CI 0.14 to 0.60; 1 study, 405 participants); similar results were seen across other triple therapy and genotype combinations.
AUTHORS' CONCLUSIONS
There is insufficient evidence of clinically important effects from corrector monotherapy in pwCF with F508del/F508del. Additional data in this review reduced the evidence for efficacy of dual therapy; these agents can no longer be considered as standard therapy. Their use may be appropriate in exceptional circumstances (e.g. if triple therapy is not tolerated or due to age). Both dual therapies (lumacaftor-ivacaftor, tezacaftor-ivacaftor) result in similar small improvements in QoL and respiratory function with lower pulmonary exacerbation rates. While the effect sizes for QoL and FEV still favour treatment, they have reduced compared to our previous findings. Lumacaftor-ivacaftor was associated with an increase in early transient shortness of breath and longer-term increases in blood pressure (not observed for tezacaftor-ivacaftor). Tezacaftor-ivacaftor has a better safety profile, although data are lacking in children under 12 years. In this population, lumacaftor-ivacaftor had an important impact on respiratory function with no apparent immediate safety concerns, but this should be balanced against the blood pressure increase and shortness of breath seen in longer-term adult data when considering lumacaftor-ivacaftor. Data from triple therapy trials demonstrate improvements in several key outcomes, including FEV and QoL. There is probably little or no difference in adverse events for triple therapy (elexacaftor-tezacaftor-ivacaftor/deutivacaftor; VX-659-tezacaftor-ivacaftor/deutivacaftor; VX-440-tezacaftor-ivacaftor; VX-152-tezacaftor-ivacaftor) in pwCF with one or two F508del variants aged 12 years or older (moderate-certainty evidence). Further RCTs are required in children under 12 years and those with more severe lung disease.
Topics: Adult; Child; Humans; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Aminophenols; Dyspnea; Mutation
PubMed: 37983082
DOI: 10.1002/14651858.CD010966.pub4 -
International Journal of Medical... 2023The members of the transmembrane emp24 domain-containing protein (TMED) family are summarized in human as four subfamilies, α (TMED 4, 9), β (TMED 2), γ (TMED1, 3, 5,... (Review)
Review
The members of the transmembrane emp24 domain-containing protein (TMED) family are summarized in human as four subfamilies, α (TMED 4, 9), β (TMED 2), γ (TMED1, 3, 5, 6, 7) and δ (TMED 10), with a total of nine members, which are important regulators of intracellular protein transport and are involved in normal embryonic development, as well as in the pathogenic processes of many human diseases. Here we systematically review the composition, structure and function of TMED family members, and describe the progress of TMED family in human diseases, including malignancies (head and neck tumors, lung cancer, breast cancer, ovarian cancer, endometrial cancer, gastrointestinal tumors, urological tumors, osteosarcomas, etc.), immune responses, diabetes, neurodegenerative diseases, and nonalcoholic fatty liver disease, dilated cardiomyopathy, mucin 1 nephropathy (MKD), and desiccation syndrome (SS). Finally, we discuss and prospect the potential of TMED for disease prognosis prediction and therapeutic targeting, with a view to laying the foundation for therapeutic research based on TMED family causative genes.
Topics: Pregnancy; Female; Humans; Membrane Proteins; Protein Transport; Non-alcoholic Fatty Liver Disease; Vesicular Transport Proteins
PubMed: 37928880
DOI: 10.7150/ijms.87272