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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 -
The Japanese Dental Science Review Dec 2023The mechanisms modulated by periodontal pathogens in atherosclerosis are not fully understood. Aim: to perform an integrative analysis of gene and protein expression... (Review)
Review
UNLABELLED
The mechanisms modulated by periodontal pathogens in atherosclerosis are not fully understood. Aim: to perform an integrative analysis of gene and protein expression modulated by periodontal pathogens in cells and animal models for atherosclerosis.
METHODS
Cochrane, PRISMA and AMSTAR2 guidelines for systematic reviews were followed. Data search was conducted in Pub-med, LILACS and Science Direct databases. Gene and protein expression data were collected from the included papers to perform an overrepresentation analysis using the Reactome Pathway Analysis tool and the KEGG database.
RESULTS
Thirty-two papers were included in the review, they analyzed the effect of , , , , , and or/and their virulent factors on gene and protein expression in human cells and animal models of atherosclerosis. Some of the modulated pathways include the immune system, programmed cell death, cellular responses to external stimuli, transport of small molecules, and signal transduction (p < 0.05). Those pathways are known to be involved in different stages of atherosclerosis progression.
CONCLUSION
Based on the performed analysis, it is possible to state that periodontal pathogens have the potential to be a contributing factor for atherosclerosis even in absence of a high-fat diet or high shear stress.
PubMed: 36654677
DOI: 10.1016/j.jdsr.2022.12.001 -
Reviews in Medical Virology Sep 2023Genome-wide association studies (GWASs) have identified single nucleotide polymorphisms (SNPs) associated with susceptibility and severity of coronavirus disease 2019... (Meta-Analysis)
Meta-Analysis Review
Genome-wide association studies (GWASs) have identified single nucleotide polymorphisms (SNPs) associated with susceptibility and severity of coronavirus disease 2019 (COVID-19). However, identified SNPs are inconsistent across studies, and there is no compelling consensus that COVID-19 status is determined by genetic factors. Here, we conducted a systematic review and meta-analysis to determine the effect of genetic factors on COVID-19. A random-effect meta-analysis was performed to estimate pooled odds ratios (ORs) of SNP effects, and SNP-based heritability (SNP-h ) of COVID-19. The analyses were performed using meta-R package, and Stata version 17. The meta-analysis included a total of 96,817 COVID-19 cases and 6,414,916 negative controls. The meta-analysis showed that a cluster of highly correlated 9 SNPs (R > 0.9) at 3p21.31 gene locus covering LZTFL1 and SLC6A20 genes was significantly associated with COVID-19 severity, with a pooled OR of 1.8 [1.5-2.0]. Meanwhile, another 3 SNPs (rs2531743-G, rs2271616-T, and rs73062389-A) within the locus was associated with COVID-19 susceptibility, with pooled estimates of 0.95 [0.93-0.96], 1.23 [1.19-1.27] and 1.15 [1.13-1.17], respectively. Interestingly, SNPs associated with susceptibility and SNPs associated with severity in this locus are in linkage equilibrium (R < 0.026). The SNP-h on the liability scale for severity and susceptibility was estimated at 7.6% (Se = 3.2%) and 4.6% (Se = 1.5%), respectively. Genetic factors contribute to COVID-19 susceptibility and severity. In the 3p21.31 locus, SNPs that are associated with susceptibility are not in linkage disequilibrium (LD) with SNPs that are associated with severity, indicating within-locus heterogeneity.
Topics: Humans; Genetic Predisposition to Disease; Genome-Wide Association Study; COVID-19; Linkage Disequilibrium; Polymorphism, Single Nucleotide; Membrane Transport Proteins
PubMed: 37303119
DOI: 10.1002/rmv.2466 -
Neuroscience and Biobehavioral Reviews Sep 2023Recent lifestyle changes have resulted in tremendous peer pressure and mental stress, and increased the incidences of chronic psychological disorders; like addiction,... (Review)
Review
Recent lifestyle changes have resulted in tremendous peer pressure and mental stress, and increased the incidences of chronic psychological disorders; like addiction, depression and anxiety (ADA). In this context, the stress-tolerance levels vary amongst individuals and genetic factors play prominent roles. Vulnerable individuals may often be drawn towards drug-addiction to combat stress. This systematic review critically appraises the relationship of various genetic factors linked with the incidences of ADA development. For coherence, we focused solely on cocaine as a substance of abuse in this study. Online scholarly databases were used to screen pertinent literature using apt keywords; and the final retrieval included 42 primary-research articles. The major conclusion drawn from this systematic analysis states that there are 51 genes linked with the development of ADA; and 3 (BDNF, PERIOD2 and SLC6A4) of them are common to all the three aspects of ADA. Further, inter-connectivity analyses of the 51 genes further endorsed the central presence of BDNF and SLC6A4 genes in the development of ADA disorders. The conclusions derived from this systematic study pave the way for future studies for the identification of diagnostic biomarkers and drug targets; and for the development of novel and effective therapeutic regimens against ADA.
Topics: Humans; Cocaine-Related Disorders; Depression; Brain-Derived Neurotrophic Factor; Anxiety; Anxiety Disorders; Cocaine; Serotonin Plasma Membrane Transport Proteins
PubMed: 37271299
DOI: 10.1016/j.neubiorev.2023.105270 -
European Journal of Clinical... Feb 2024Calprotectin is a calcium-binding-S100-protein synthetized mainly in neutrophils which has been demonstrated to be an accurate biomarker of the presence of these cells.... (Review)
Review
BACKGROUND
Calprotectin is a calcium-binding-S100-protein synthetized mainly in neutrophils which has been demonstrated to be an accurate biomarker of the presence of these cells. Gut barrier dysfunction in patients with advanced chronic liver disease (ACLD), in addition to the lack of noninvasive tools for diagnosis and prognosis of cirrhosis decompensations, has raised interest in this biomarker.
AIMS
Our aim is to summarize the current evidence regarding the role of calprotectin in terms of its diagnostic and prognostic utility in ACLD.
METHODS
We performed a systematic search (PROSPERO registration no. CRD42023389069) of original articles published without any restrictions on the publication date until January 2023 providing information about calprotectin for the prognosis or diagnosis of ACLD and its decompensations in adult patients.
RESULTS
A total 227 articles were identified, and 26 observational studies finally met the inclusion criteria. In 14 studies, calprotectin was measured in ascitic fluid, all of which reported higher calprotectin values in spontaneous bacterial peritonitis, while cut-off points for its diagnosis were proposed in nine studies. Three studies reported higher faecal calprotectin levels in patients with hepatic encephalopathy and portal hypertension. Four studies evaluated faecal calprotectin and one plasma calprotectin as biomarkers for gut barrier integrity and bacterial translocation.
CONCLUSIONS
Calprotectin is emerging as a promising biomarker in ACLD, particularly for the management of bacterial infections and alcohol-related liver disease. Further research with better study designs should help to determine the feasibility of calprotectin measurement in routine clinical practice.
Topics: Adult; Humans; Biomarkers; Hypertension, Portal; Leukocyte L1 Antigen Complex; Liver Cirrhosis; Prognosis
PubMed: 37849372
DOI: 10.1111/eci.14111 -
Seminars in Nuclear Medicine Sep 2023Fibroblast activation protein inhibitor (FAPI) is a promising tracer in oncologic positron emission tomography/computed tomography (PET/CT). Numerous studies have... (Review)
Review
Fibroblast activation protein inhibitor (FAPI) is a promising tracer in oncologic positron emission tomography/computed tomography (PET/CT). Numerous studies have demonstrated the superior sensitivity of FAPI PET/CT over fluorodeoxyglucose (FDG) PET/CT in several types of cancer. However, the cancer specificity of FAPI uptake remains understudied, and several cases of false-positive FAPI PET/CT findings have been reported. A systematic search of PubMed, Embase, and Web of Science was conducted for studies published prior to April 2022 reporting nonmalignant FAPI PET/CT findings. We included original peer-reviewed articles of studies in humans using FAPI tracers radiolabeled with Ga or F that were published in English. Papers without original data and studies with insufficient information were excluded. Nonmalignant findings were presented on a per-lesion basis and grouped according to the type of organ or tissue involved. The search identified a total of 1.178 papers, of which 108 studies were eligible. Eighty studies were case reports (74%), and the remaining 28 were cohort studies (26%). A total of 2.372 FAPI-avid nonmalignant findings were reported, with the most frequent being uptake in the arteries, e.g., related to plaques (n = 1178, 49%). FAPI uptake was also frequently related to degenerative and traumatic bone and joint lesions (n = 147, 6%) or arthritis (n = 92, 4%). For organs, diffuse or focal uptake was often seen in cases of inflammation, infection, fibrosis, and IgG4-related disease (n = 157, 7%). FAPI-avid inflammatory/reactive lymph nodes (n = 121, 5%) and tuberculosis lesions (n = 51, 2%) have been reported and could prove to be potential pitfalls in cancer staging. Periodontitis (n = 76, 3%), hemorrhoids (n = 47, 2%), and scarring/wound healing (n = 35, 2%) also presented as focal uptake on FAPI PET/CT. The present review provides an overview of the reported FAPI-avid nonmalignant PET/CT findings to date. A large number of benign clinical entities may show FAPI uptake and should be kept in mind when interpreting FAPI PET/CT findings in patients with cancer.
Topics: Humans; Biological Transport; Fluorodeoxyglucose F18; Gallium Radioisotopes; Inflammation; Positron Emission Tomography Computed Tomography
PubMed: 36813670
DOI: 10.1053/j.semnuclmed.2023.02.001 -
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 -
Mutation Research. Reviews in Mutation... 2023The development of resistance by tumor cells to various types of therapy is a significant problem that decreases the effectiveness of oncology treatments. For more than... (Review)
Review
The development of resistance by tumor cells to various types of therapy is a significant problem that decreases the effectiveness of oncology treatments. For more than two decades, comparative transcriptomic studies of tumor cells with different sensitivities to ionizing radiation and chemotherapeutic agents have been conducted in order to identify the causes and mechanisms underlying this phenomenon. However, the results of such studies have little in common and often contradict each other. We have assumed that a systematic analysis of a large number of such studies will provide new knowledge about the mechanisms of development of therapeutic resistance in tumor cells. Our comparison of 123 differentially expressed gene (DEG) lists published in 98 papers suggests a very low degree of consistency between the study results. Grouping the data by type of genotoxic agent and tumor type did not increase the similarity. The most frequently overexpressed genes were found to be those encoding the transport protein ABCB1 and the antiviral defense protein IFITM1. We put forward a hypothesis that the role played by the overexpression of the latter in the development of resistance may be associated not only with the stimulation of proliferation, but also with the limitation of exosomal communication and, as a result, with a decrease in the bystander effect. Among down regulated DEGs, BNIP3 was observed most frequently. The expression of BNIP3, together with BNIP3L, is often suppressed in cells resistant to non-platinum genotoxic chemotherapeutic agents, whereas it is increased in cells resistant to ionizing radiation. These observations are likely to be mediated by the binary effects of these gene products on survival, and regulation of apoptosis and autophagy. The combined data also show that even such obvious mechanisms as inhibition of apoptosis and increase of proliferation are not universal but show multidirectional changes.
Topics: Humans; Gene Expression Profiling; Transcriptome; RNA; Apoptosis; DNA Damage
PubMed: 37657754
DOI: 10.1016/j.mrrev.2023.108467 -
Journal of Oral Pathology & Medicine :... Nov 2023CTNNB1 gene encodes beta catenin, a transcriptional activator of Wnt pathway involved in the pathogenesis of odontogenic lesions. Though located intramembranously, its... (Review)
Review
BACKGROUND
CTNNB1 gene encodes beta catenin, a transcriptional activator of Wnt pathway involved in the pathogenesis of odontogenic lesions. Though located intramembranously, its translocation into cytoplasm and nucleus could trigger cell proliferation, inhibition of apoptosis, invasion and migration of the tumour cell.
MATERIALS AND METHODS
Five electronic databases including MEDLINE by PubMed, Google scholar, Scopus, Trip, Cochrane library and EMBASE until 1 January 2023 without period restriction were thoroughly searched. Those articles that identified CTNNB1 mutation and beta catenin in odontogenic lesions were included for review. Risk of bias was analysed for each study using QUADAS 2 tool and Review Manager 5.3 was used to output its result.
RESULTS
Thirty four published articles were included for data synthesis. A total of 1092 cases of odontogenic lesions were assessed for both CTNNB1 mutation and beta catenin expression. CTNNB1 mutation was observed in ameloblastoma, calcifying odontogenic cyst, calcifying cystic odontogenic tumour and all malignant odontogenic tumours. The beta catenin expression (nuclear and cytoplasmic) was maximum in odontogenic keratocyst and calcifying odontogenic cyst. The expression was variable in ameloblastomas, membranous in odontomas, calcifying cystic odontogenic tumour and nuclear in all malignant tumours.
DISCUSSION AND CONCLUSION
High recurrence of odontogenic keratocyst and aggressiveness of solid ameloblastoma and malignant odontogenic tumours could be associated with the nuclear translocation of beta catenin. Disparity between CTNNB1 mutation and beta catenin expression within odontogenic lesions suggests alternate routes of beta catenin activation. The review results support the unique localisation of beta catenin as a helpful diagnostic factor in the pathogenesis of odontogenic lesions.
Topics: Humans; Ameloblastoma; beta Catenin; Odontogenic Cyst, Calcifying; Odontogenic Cysts; Odontogenic Tumors
PubMed: 37840228
DOI: 10.1111/jop.13487 -
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