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Disease Markers 2015The diagnostic value of serum HE4 in patients with lung cancer remains controversial. Thus, we performed a systematic review and meta-analysis to assess the diagnostic... (Meta-Analysis)
Meta-Analysis Review
The diagnostic value of serum HE4 in patients with lung cancer remains controversial. Thus, we performed a systematic review and meta-analysis to assess the diagnostic accuracy of serum HE4 for lung cancer. We conducted a comprehensive literature search in PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and WANFANG databases between Jan. 1966 and Nov. 2014. The diagnostic sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic curve (SROC) were pooled by Meta-DiSc 1.4 software. A total of seven articles including 715 cases and 549 controls were included for analysis. The summary estimates for serum HE4 in the diagnosis of lung cancer in these studies were pooled SEN 0.72 (95% CI: 0.68-0.75), SPE 0.85 (95% CI: 0.81-0.88), PLR 4.68 (95% CI: 3.23-6.78), NLR 0.31 (95% CI: 0.24-0.39), and DOR 17.14 (95% CI: 9.72-30.20), and the area under the curve (AUC) was 0.8557. This meta-analysis indicated that serum HE4 is a potential tool in the diagnosis of lung cancer. In addition, considering the high heterogeneity and potential publication bias, further studies with rigorous design and large sample size are needed in the future.
Topics: Biomarkers, Tumor; Case-Control Studies; Humans; Lung Neoplasms; Proteins; Sensitivity and Specificity; WAP Four-Disulfide Core Domain Protein 2
PubMed: 25873748
DOI: 10.1155/2015/352670 -
Journal of Nanobiotechnology Jan 2024Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins,... (Review)
Review
Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins, lipids, and nucleic acids. Engineered exosomes generated through genetic modification of parent cells show promise as drug delivery vehicles, and they have been demonstrated to have great therapeutic potential for treating cancer, cardiovascular, neurological, and immune diseases, but systematic knowledge is lacking regarding optimization of drug loading and assessment of delivery efficacy. This review summarizes current approaches for engineering exosomes and evaluating their drug delivery effects, and current techniques for assessing exosome drug loading and release kinetics, cell targeting, biodistribution, pharmacokinetics, and therapeutic outcomes are critically examined. Additionally, this review synthesizes the latest applications of exosome engineering and drug delivery in clinical translation. The knowledge compiled in this review provides a framework for the rational design and rigorous assessment of exosomes as therapeutics. Continued advancement of robust characterization methods and reporting standards will accelerate the development of exosome engineering technologies and pave the way for clinical studies.
Topics: Humans; Exosomes; Tissue Distribution; Drug Delivery Systems; Extracellular Vesicles; Neoplasms; Pharmaceutical Preparations
PubMed: 38172932
DOI: 10.1186/s12951-023-02259-6 -
Nucleic Acids Research Jun 2022At the time of writing, although siRNA therapeutics are approved for human use, no official regulatory guidance specific to this modality is available. In the absence of...
At the time of writing, although siRNA therapeutics are approved for human use, no official regulatory guidance specific to this modality is available. In the absence of guidance, preclinical development for siRNA followed a hybrid of the small molecule and biologics guidance documents. However, siRNA differs significantly from small molecules and protein-based biologics in its physicochemical, absorption, distribution, metabolism and excretion properties, and its mechanism of action. Consequently, certain reports typically included in filing packages for small molecule or biologics may benefit from adaption, or even omission, from an siRNA filing. In this white paper, members of the 'siRNA working group' in the IQ Consortium compile a list of reports included in approved siRNA filing packages and discuss the relevance of two in vitro reports-the plasma protein binding evaluation and the drug-drug interaction risk assessment-to support siRNA regulatory filings. Publicly available siRNA approval packages and the literature were systematically reviewed to examine the role of siRNA plasma protein binding and drug-drug interactions in understanding pharmacokinetic/pharmacodynamic relationships, safety and translation. The findings are summarized into two decision trees to help guide industry decide when in vitro siRNA plasma protein binding and drug-drug interaction studies are warranted.
Topics: Biological Products; Blood Proteins; Decision Trees; Drug Interactions; Humans; Protein Binding; RNA, Small Interfering
PubMed: 35687098
DOI: 10.1093/nar/gkac456 -
Pharmacogenomics Apr 2023To analyze roles of single nucleotide variants (SNVs) on weight loss with US FDA-approved medications. We searched the literature up until November 2022. Preferred... (Meta-Analysis)
Meta-Analysis Review
To analyze roles of single nucleotide variants (SNVs) on weight loss with US FDA-approved medications. We searched the literature up until November 2022. Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. 14 studies were included in qualitative analysis and seven in meta-analysis. SNVs in , , , , , , and were evaluated relative to weight loss with glucagon-like peptide-1 agonists (13 studies) or naltrexone-bupropion (one study). gene (rs1049353), gene (rs6923761, rs10305420), gene (rs7903146) were associated with weight loss in at least one study involving glucagon-like peptide-1 agonist(s). The meta-analysis did not identify any consistent effect of SNVs. Pharmacogenetic interactions for exenatide, liraglutide, naltrexone-bupropion and weight loss were identified, but the directionality was inconsistent.
Topics: Adult; Humans; Hypoglycemic Agents; Pharmacogenetics; Naltrexone; Bupropion; Peptides; Venoms; Glucagon-Like Peptide 1; Weight Loss; Glucagon-Like Peptide-1 Receptor; Diabetes Mellitus, Type 2; Protein Serine-Threonine Kinases
PubMed: 36999540
DOI: 10.2217/pgs-2022-0192 -
Advances in Clinical and Experimental... May 2024Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and... (Review)
Review
Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and calcification. One of the pathomechanisms of atherosclerosis is the upregulation of Wnt signaling. This study aimed to summarize the current knowledge regarding the role of Wnt signaling and sclerostin in atherosclerosis, vascular calcification, aneurysms, and mortality based on the PubMed database. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendation and identified 160 papers that were included in this systematic review. The published data highlight that the upregulation of Wnt components facilitates the initiation and progression of atherosclerosis, arterial remodeling, VSMCs proliferation and phenotypic transition to the osteoblastic lineage in the arterial wall. This results in protein secretion, cell migration, calcification, fibrosis and aneurysm formation. The transformation of VSMCs into osteoblast-like cells that is observed in atherosclerosis results in sclerostin expression inhibiting the Wnt pathway. Furthermore, it was shown that sclerostin, expressed in atherosclerotic plaques, inhibits aneurysm formation in a mouse model. However, in humans, while the antisclerostin antibody romosozumab inhibits bone resorption, biochemical parameters of endothelial activation and inflammation are not affected, and the incidence of aneurysms is not increased. It was suggested that detecting sclerostin in the calcified aortic atherosclerotic plaques reflects a defense mechanism against Wnt activation and inhibition of atherosclerosis, although this has only been shown in animal models. Moreover, an increased number of vascular cells converted to osteogenic phenotypes results in increased plasma sclerostin concentrations. Therefore, plasma sclerostin derived from bone limits its importance as a global marker of vascular calcification.
Topics: Humans; Vascular Calcification; Atherosclerosis; Animals; Wnt Signaling Pathway; Adaptor Proteins, Signal Transducing; Genetic Markers
PubMed: 37676098
DOI: 10.17219/acem/169567 -
Neurology India 2018Sepsis is a leading cause of death in medical and surgical intensive care units (ICUs). Disturbance of consciousness of varying severity is an early warning sign of... (Review)
Review
Sepsis is a leading cause of death in medical and surgical intensive care units (ICUs). Disturbance of consciousness of varying severity is an early warning sign of developing sepsis in the majority of cases. Sepsis-associated encephalopathy (SAE) is the most frequent type of encephalopathy in the ICU and is defined as a state of diffuse cerebral dysfunction caused by the inflammatory response of the body to various infections, where the inflammatory process does not affect the central nervous system (CNS) directly and the primary symptom is a disturbed level of consciousness. The aim of this comprehensive review was to collect the latest scientific knowledge regarding the epidemiology, clinical aspects, pathogenesis, diagnosis, and possible prevention strategies related to SAE.
Topics: Blood-Brain Barrier; Critical Care; Cytokines; Humans; Incidence; Mitochondrial Diseases; Oxidative Stress; Sepsis-Associated Encephalopathy
PubMed: 29547154
DOI: 10.4103/0028-3886.227299 -
Acta Histochemica Jan 2023Epithelial membrane protein 2 (EMP2) is a cell surface protein composed of approximately 160 amino acids and encoded by the growth arrest-specific 3 (GAS3)/peripheral... (Review)
Review
OBJECTIVES
Epithelial membrane protein 2 (EMP2) is a cell surface protein composed of approximately 160 amino acids and encoded by the growth arrest-specific 3 (GAS3)/peripheral myelin protein 22 kDa (PMP22) gene family. Although EMP2 expression has been investigated in several diseases, much remains unknown regarding its mechanism of action and the extent of its role in pathogenesis. Our aim was to perform a systematic review on the involvement of EMP2 in disease processes and the current usage of anti-EMP2 therapies.
METHODS
A Boolean search of the English-language medical literature was performed. PubMed, Scopus, Cochrane, and Web of Science were used to identify relevant citations. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
52 studies met the inclusion criteria for qualitative analysis. Of those, 28 (53.8%) were human-only studies, 11 (21.2%) were animal-only studies, and 13 (25%) studies included both human and animal models. Furthermore, 34 (65.4%) studies focused on EMP2's role in neoplasms, while the remaining 18 (34.6%) articles evaluated its role in other pathologies.
CONCLUSION
Overall, the evidence suggests the mechanisms of action of EMP2 are context dependent. Promising results have been produced by utilizing EMP2 as a biomarker and therapeutic target. More studies are warranted to better understand the mechanism and comprehend the role of EMP2 in the pathogenesis of diseases.
Topics: Animals; Humans; Membrane Glycoproteins; Membrane Proteins
PubMed: 36455339
DOI: 10.1016/j.acthis.2022.151976 -
Cardiovascular Diabetology Dec 2022Apolipoprotein C1 (apoC1) is a small size apolipoprotein whose exact role is not totally clarified but which seems to modulate significantly the metabolism of... (Review)
Review
Apolipoprotein C1 (apoC1) is a small size apolipoprotein whose exact role is not totally clarified but which seems to modulate significantly the metabolism of lipoproteins. ApoC1 is involved in the metabolism of triglyceride-rich lipoproteins by inhibiting the binding of very low density lipoproteins (VLDL) to VLDL-receptor (VLDL-R), to low density lipoprotein receptor (LDL-R) and to LDL receptor related protein (LRP), by reducing the activity of lipoprotein lipase (LPL) and by stimulating VLDL production, all these effects leading to increase plasma triglycerides. ApoC1 takes also part in the metabolism of high density lipoproteins (HDL) by inhibiting Cholesterol Ester Transfer Protein (CETP). The functionality of apoC1 on CETP activity is impaired in diabetes that might account, at least in part, for the increased plasma CETP activity observed in patients with diabetes. Its different effects on lipoprotein metabolism with a possible role in the modulation of inflammation makes the net impact of apoC1 on cardiometabolic risk difficult to figure out and apoC1 might be considered as pro-atherogenic or anti-atherogenic depending on the overall metabolic context. Making the link between total plasma apoC1 levels and the risk of cardio-metabolic diseases is difficult due to the high exchangeability of this small protein whose biological effects might depend essentially on its association with VLDL or HDL. The role of apoC1 in humans is not entirely elucidated and further studies are needed to determine its precise role in lipid metabolism and its possible pleiotropic effects on inflammation and vascular wall biology. In this review, we will present data on apoC1 structure and distribution among lipoproteins, on the effects of apoC1 on VLDL metabolism and HDL metabolism and we will discuss the possible links between apoC1, atherosclerosis and diabetes.
Topics: Humans; Apolipoprotein C-I; Atherosclerosis; Cholesterol Ester Transfer Proteins; Diabetes Mellitus; Inflammation; Lipoproteins, HDL; Lipoproteins, VLDL; Triglycerides
PubMed: 36471375
DOI: 10.1186/s12933-022-01703-5 -
BMC Immunology Oct 2023This systematic review aimed to map the evidence evaluated the relationship between vitamin D and redox and inflammatory status during gestation.
OBJECTIVE
This systematic review aimed to map the evidence evaluated the relationship between vitamin D and redox and inflammatory status during gestation.
METHODS
Three databases (PubMed/MEDLINE, Scopus, and Web of Science (WoS)) and reference list of included documents were searched for related observational studies published until 2nd October 2023. To determine the quality of the selected observational studies, the Newcastle-Ottawa Scale (NOS) was used.
RESULTS
After a primary search of three databases, 19492records were appeared. When duplicates and irrelevant documents were removed, 14 articles were found to have eligible criteria. The design of the identified studies was cross-sectional, case-control and cohort. Evidence showed an adverse association between 25(OH)D and the biomarkers of inflammation, such as high-sensitivity C-reactive protein (hs-CRP), Interleukin-1beta (IL-1β), Interleukin-6 (IL-6), and tumor necrosis factor- alfa (TNF-α) during pregnancy. On the contrary, some studies represented that 25(OH)D positively correlated with hs-CRP in the cord blood. One study suggested a direct association between serum concentrations of 25(OH)D and Interleukin-8 (IL-8), macrophage inflammatory protein (MIP), and TNF-α levels in mothers with gestational diabetes mellitus (GDM). A case-control study showed that lower serum concentration of 25(OH)D positively correlated with total antioxidant capacity (TAC) levels in participants.
CONCLUSIONS
Evidence confirmed the supposition of the direct relationship between vitamin D levels and biomarkers with anti-inflammatory and anti-oxidative properties. However, the Existence of inconsistent evidence confirms the need for further studies in mothers with GDM and hypertensive disorders.
PROSPERO REGISTRATION CODE
CRD42020202600.
Topics: Pregnancy; Female; Humans; Vitamin D; Pregnant Women; C-Reactive Protein; Tumor Necrosis Factor-alpha; Cross-Sectional Studies; Case-Control Studies; Vitamins; Biomarkers; Inflammation; Interleukin-6; Oxidative Stress
PubMed: 37891486
DOI: 10.1186/s12865-023-00577-w -
International Journal of Molecular... Oct 2023Bisphenols such as bisphenol A (BPA), S (BPS), C (BPC), F (BPF), AF (BPAF), tetrabromobisphenol, nonylphenol, and octylphenol are plasticizers used worldwide to... (Meta-Analysis)
Meta-Analysis Review
Bisphenols such as bisphenol A (BPA), S (BPS), C (BPC), F (BPF), AF (BPAF), tetrabromobisphenol, nonylphenol, and octylphenol are plasticizers used worldwide to manufacture daily-use articles. Exposure to these compounds is related to many pathologies of public health importance, such as infertility. Using a protector compound against the reproductive toxicological effects of bisphenols is of scientific interest. Melatonin and vitamins have been tested, but the results are not conclusive. To this end, this systematic review and meta-analysis compared the response of reproductive variables to melatonin and vitamin administration as protectors against damage caused by bisphenols. We search for controlled studies of male rats exposed to bisphenols to induce alterations in reproduction, with at least one intervention group receiving melatonin or vitamins (B, C, or E). Also, molecular docking simulations were performed between the androgen (AR) and estrogen receptors (ER), melatonin, and vitamins. About 1234 records were initially found; finally, 13 studies were qualified for review and meta-analysis. Melatonin plus bisphenol improves sperm concentration and viability of sperm and increases testosterone serum levels compared with control groups; however, groups receiving vitamins plus bisphenols had lower sperm concentration, total testis weight, and testosterone serum levels than the control. In the docking analysis, vitamin E had the highest negative MolDock score, representing the best binding affinity with AR and ER, compared with other vitamins and melatonin in the docking. Our findings suggest that vitamins could act as an endocrine disruptor, and melatonin is most effective in protecting against the toxic effects of bisphenols.
Topics: Male; Rats; Animals; Melatonin; Vitamins; Molecular Docking Simulation; Semen; Benzhydryl Compounds; Reproduction; Receptors, Estrogen; Vitamin A; Vitamin K; Testosterone; Endocrine Disruptors
PubMed: 37834378
DOI: 10.3390/ijms241914930