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Biomedicines Aug 2022Trastuzumab is a monoclonal antibody used in the treatment of breast cancer in cases where the tumor overexpresses the HER2 receptor, a cell membrane receptor activated... (Review)
Review
Trastuzumab is a monoclonal antibody used in the treatment of breast cancer in cases where the tumor overexpresses the HER2 receptor, a cell membrane receptor activated by the epidermal growth factor. Intravenous and subcutaneous administration of trastuzumab have comparable clinical and pharmacological characteristics, but trastuzumab biosimilars are currently only available in intravenous form. Trastuzumab biosimilars are ultimately preferred by a proportion of patients, especially in cases where co-administration of other chemotherapeutic agents, such as trastuzumab and tucatinib, a small molecule of tyrosine kinase inhibitor, is required in patients with HER-positive metastatic breast cancer. Oncologists should be well-aware of the advantages of intravenously administered trastuzumab biosimilars over subcutaneous administration, certainly also taking into account the patient's preferences. Further cost-effectiveness analyses will be very important, along with expectations regarding successful concomitant subcutaneous administration of trastuzumab with other anticancer drugs, such as pertuzumab. This systematic review describes and analyzes the so-far published studies concerning the use of the available trastuzumab biosimilars in HER-positive early and metastatic breast cancer in terms of efficacy, safety, and cost-benefit ratio. An attempt was also made to draw some conclusions and to comment on future needs and perspectives.
PubMed: 36009592
DOI: 10.3390/biomedicines10082045 -
Mitochondrion Jul 2021Cell-free mitochondrial DNA (cf-mtDNA) is a marker of inflammatory disease and a predictor of mortality, but little is known about cf-mtDNA in relation to psychobiology.... (Review)
Review
Cell-free mitochondrial DNA (cf-mtDNA) is a marker of inflammatory disease and a predictor of mortality, but little is known about cf-mtDNA in relation to psychobiology. A systematic review of the literature reveals that blood cf-mtDNA varies in response to common real-world stressors including psychopathology, acute psychological stress, and exercise. Moreover, cf-mtDNA is inducible within minutes and exhibits high intra-individual day-to-day variation, highlighting the dynamic regulation of cf-mtDNA levels. We discuss current knowledge on the mechanisms of cf-mtDNA release, its forms of transport ("cell-free" does not mean "membrane-free"), potential physiological functions, putative cellular and neuroendocrine triggers, and factors that may contribute to cf-mtDNA removal from the circulation. A review of in vitro, pre-clinical, and clinical studies shows conflicting results around the dogma that physiological forms of cf-mtDNA are pro-inflammatory, opening the possibility of other physiological functions, including the cell-to-cell transfer of whole mitochondria. Finally, to enhance the reproducibility and biological interpretation of human cf-mtDNA research, we propose guidelines for blood collection, cf-mtDNA isolation, quantification, and reporting standards, which can promote concerted advances by the community. Defining the mechanistic basis for cf-mtDNA signaling is an opportunity to elucidate the role of mitochondria in brain-body interactions and psychopathology.
Topics: Brain; Cell-Free Nucleic Acids; DNA, Mitochondrial; Humans; Mitochondria; Signal Transduction
PubMed: 33839318
DOI: 10.1016/j.mito.2021.04.002 -
Brazilian Journal of Otorhinolaryngology 2022SARS-CoV-2 is the pathogen of COVID-19. The virus is composed of the spike, membrane and envelope. On physiological smell, odoriferous substances bind to proteins... (Review)
Review
INTRODUCTION
SARS-CoV-2 is the pathogen of COVID-19. The virus is composed of the spike, membrane and envelope. On physiological smell, odoriferous substances bind to proteins secreted by sustentacular cells in order to be processed by olfactory receptor neurons. Olfactory disorder is one of the main manifestations of COVID-19, however, research is still required to clarify the mechanism involved in SARS-CoV-2 induced anosmia.
OBJECTIVE
This article aims to analyze current scientific evidence intended to elucidate the pathophysiological relationship between COVID-19 and the cause of olfactory disorders.
METHODS
Pubmed, Embase, Scopus and ScienceDirect were used to compose this article. The research was conducted on November 24th, 2020. Original articles with experimental studies in human, animal and in vitro, short communications, viewpoint, published in the English language and between 2019 and 2020 were included, all related to the pathophysiological relationship between olfactory disorders and COVID-19 infection.
RESULTS
Both human cell receptors ACE2 and TMPRSS2 are essential for the SARS-CoV-2 entrance. These receptors are mostly present in the olfactory epithelium cells, therefore, the main hypothesis is that anosmia is caused due to damage to non-neuronal cells which, thereafter, affects the normal olfactory metabolism. Furthermore, magnetic resonance imaging studies exhibit a relationship between a reduction on the neuronal epithelium and the olfactory bulb atrophy. Damage to non-neuronal cells explains the average recovery lasting a few weeks. This injury can be exacerbated by an aggressive immune response, which leads to damage to neuronal cells and stem cells inducing a persistent anosmia. Conductive anosmia is not sufficient to explain most cases of COVID-19 induced anosmia.
CONCLUSION
Olfactory disorders such as anosmia and hyposmia can be caused by COVID-19, the main mechanism is associated with olfactory epithelium damage, targeting predominantly non-neuronal cells. However, neuronal cells can also be affected, worsening the condition of olfactory loss.
Topics: Angiotensin-Converting Enzyme 2; Animals; Anosmia; COVID-19; Humans; Olfaction Disorders; SARS-CoV-2; Smell
PubMed: 33965353
DOI: 10.1016/j.bjorl.2021.04.001 -
International Journal of Molecular... Jul 2023Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various... (Review)
Review
Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various physiological and pathological processes in the brain, including water homeostasis, cell migration, and inflammation, among others. Epileptogenesis is a complex and multifactorial process that involves alterations in the structure and function of neuronal networks. Recent evidence suggests that AQPs may also play a role in the pathogenesis of epilepsy. In animal models of epilepsy, AQPs have been shown to be upregulated in regions of the brain that are involved in seizure generation, suggesting that they may contribute to the hyperexcitability of neuronal networks. Moreover, genetic studies have identified mutations in AQP genes associated with an increased risk of developing epilepsy. Our review aims to investigate the role of AQPs in epilepsy and seizure onset from a pathophysiological point of view, pointing out the potential molecular mechanism and their clinical implications.
Topics: Animals; Aquaporins; Water; Homeostasis; Brain; Seizures
PubMed: 37569297
DOI: 10.3390/ijms241511923 -
Cureus Mar 2022Although the understanding of the pathophysiology of major depressive disorder (MDD) has advanced greatly, this has not been translated into improved outcomes. To date,... (Review)
Review
Although the understanding of the pathophysiology of major depressive disorder (MDD) has advanced greatly, this has not been translated into improved outcomes. To date, no biomarkers have been identified for the diagnosis, prognosis, and therapeutic management of MDD. Thus, we aim to review the biomarkers that are differentially expressed in MDD. A systematic review was conducted in January 2022 in the PubMed/MEDLINE, Scopus, Embase, PsycINFO, and Gale Academic OneFile databases for clinical studies published from January 2001 onward using the following terms: "Depression" OR "Depressive disorder" AND "Metabolomic." Multiple metabolites were found at altered levels in MDD, demonstrating the involvement of cellular signaling metabolites, components of the cell membrane, neurotransmitters, inflammatory and immunological mediators, hormone activators and precursors, and sleep controllers. Kynurenine and acylcarnitine were identified as consistent with depression and response to treatment. The most consistent evidence found was regarding kynurenine and acylcarnitine. Although the data obtained allow us to identify how metabolic pathways are affected in MDD, there is still not enough evidence to propose changes to current diagnostic and therapeutic actions. Some limitations are the heterogeneity of studies on metabolites, methods for detection, analyzed body fluids, and treatments used. The experiments contemplated in the review identified increased or reduced levels of metabolites, but not necessarily increased or reduced the activity of the associated pathways. The information acquired through metabolomic analyses does not specify whether the changes identified in the metabolites are a cause or a consequence of the pathology.
PubMed: 35415046
DOI: 10.7759/cureus.23009 -
International Journal of Molecular... Dec 2023Platelet concentrates are used for cell induction and stimulation in tissue repair processes. The aim of the present systematic review and meta-analysis was to compare... (Meta-Analysis)
Meta-Analysis Review
Platelet concentrates are used for cell induction and stimulation in tissue repair processes. The aim of the present systematic review and meta-analysis was to compare the biological and cellular properties of advanced platelet-rich fibrin (A-PRF) to those of other platelet concentrates. Searches were conducted on the PubMed/Medline, Scopus, Web of Science, Embase and LILACS databases using a search strategy oriented by the guiding question. A total of 589 records were retrieved. Seven articles of in vitro experimental studies were selected for qualitative data analysis and four were selected for meta-analysis. The release of growth factors, distribution of cells in the fibrin membrane, and cell viability, the fibrin network, and fibroblast migration were investigated. In the final analysis, statistically significant differences were found for the A-PRF group with regard to platelet-derived growth factor, transforming growth factor, epidermal growth factor and vascular endothelial growth factor at all assessment times. A difference was found with regard to bone morphogenetic protein only in the later assessment, and no differences among groups were found with regard to platelet-derived growth factor or insulin-like growth factor. The results of this systematic review and meta-analysis suggest that A-PRF has superior cellular properties and better release of growth factors compared to other platelet concentrates.
Topics: Platelet-Rich Fibrin; Vascular Endothelial Growth Factor A; Cell Movement; Platelet-Derived Growth Factor; Fibrin
PubMed: 38203653
DOI: 10.3390/ijms25010482 -
Movement Disorders : Official Journal... Aug 2021Dopamine receptors are abundant along the central nigrostriatal tract and are expressed as 5 subtypes in two receptor families. In PD, compensatory changes in dopamine... (Meta-Analysis)
Meta-Analysis Review
Dopamine receptors are abundant along the central nigrostriatal tract and are expressed as 5 subtypes in two receptor families. In PD, compensatory changes in dopamine receptors emerge as a consequence of the loss of dopamine nerve terminals or dopaminergic pharmacotherapy. We performed a systematic review and meta-analysis of the available PET and single-photon emission computed tomography studies that have investigated dopamine receptors in PD, PSP and MSA. The inclusion criteria were studies including human PET or single-photon emission computed tomography imaging; dopamine receptor tracers (D1-like or D2-like) and idiopathic PD, PSP, or MSA patients compared with healthy controls. The 67 included D2-like studies had 1925 patients. Data were insufficient for an analysis of D1-like studies. PD patients had higher striatal binding early in the disease, but after a disease duration of 4.36 years, PD patients had lower binding values than healthy controls. Striatal D2R binding was highest in unmedicated early PD patients and in the striatum contralateral to the predominant motor symptoms. PSP and MSA-P patients had lower striatal D2R binding than PD patients (14.2% and 21.8%, respectively). There is initial upregulation of striatal D2Rs in PD, which downregulate on average 4 years after motor symptom onset, possibly because of agonist-induced effects. The consistent upregulation of D2Rs in the PD striatum contralateral to the predominant motor symptoms indicates that receptor changes are driven by neurodegeneration and loss of striatal neuropil. Both PSP and MSA patients have clearly lower striatal D2R binding values than PD patients, which offers an opportunity for differential diagnostics. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Humans; Parkinson Disease; Receptors, Dopamine D2; Tomography, Emission-Computed, Single-Photon
PubMed: 33955044
DOI: 10.1002/mds.28632 -
Cancer Management and Research 2019Thyroid cancer (TC) is an important common endocrine malignancy, and its incidence has increased in the past decades. The current TC diagnosis and classification tools... (Review)
Review
INTRODUCTION
Thyroid cancer (TC) is an important common endocrine malignancy, and its incidence has increased in the past decades. The current TC diagnosis and classification tools are fine-needle aspiration (FNA) and histological examination following thyroidectomy. The metabolite profile alterations of thyroid cells (oncometabolites) can be considered for current TC diagnosis and management protocols.
METHODS
This systematic review focuses on metabolite alterations within the plasma, FNA specimens, and tissue of malignant TC contrary to benign, goiter, or healthy TC samples. A systematic search of MEDLINE (PubMed), Scopus, Embase, and Web of Science databases was conducted, and the final 31 studies investigating metabolite biomarkers of TC were included.
RESULTS
A total of 15 targeted studies and 16 untargeted studies revealed several potential metabolite signatures of TC such as glucose, fructose, galactose, mannose, 2-keto-d-gluconic acid and rhamnose, malonic acid and inosine, cholesterol and arachidonic acid, glycosylation (immunoglobulin G [IgG] Fc-glycosylation), outer mitochondrial membrane 20 (TOMM20), monocarboxylate transporter 4 (MCT4), choline, choline derivatives, myo-/scyllo-inositol, lactate, fatty acids, several amino acids, cell membrane phospholipids, estrogen metabolites such as 16 alpha-OH E1/2-OH E1 and catechol estrogens (2-OH E1), and purine and pyrimidine metabolites, which were suggested as the TC oncometabolite.
CONCLUSION
Citrate was suggested as the first most significant biomarker and lactate as the second one. Further research is needed to confirm these biomarkers as the TC diagnostic oncometabolite.
PubMed: 30881111
DOI: 10.2147/CMAR.S188661 -
European Review For Medical and... Jul 2023Bisphosphonates, the most common anti-resorptive medications, are internalized by osteoclasts, where they inhibit the macrophage colony-stimulating factor (M-CSF)...
OBJECTIVE
Bisphosphonates, the most common anti-resorptive medications, are internalized by osteoclasts, where they inhibit the macrophage colony-stimulating factor (M-CSF) pathway, preventing their differentiation, inhibiting anchorage to the cell membrane, and inducing apoptosis. In patients undergoing oral bisphosphonate therapy, oral surgery involves a high risk of developing drug-related osteonecrosis of the jaws (BRONJ/MRONJ), among the possible complications.
MATERIALS AND METHODS
A systematic search was carried out on the PubMed, Scopus and Cochrane Library search engines, using the keywords "oral bisphosphonates AND tooth extraction", "third molar extraction AND oral bisphosphonates". In addition, we manually evaluated the articles included in references from other sources and an analysis of the Gray Literature was performed. A secondary outcome was to evaluate the assessment of pharmacological (antibiotics) use in the BRONJ/MRONJ management. The revision protocol followed the indications of the Cochrane Handbook, and was registered in the INPLASY database, while the drafting of the manuscript was based on PRISMA.
RESULTS
The results of the systematic review, after the study identification and selection process, included a total of 7 studies: 4 retrospective studies, 2 prospective studies and 1 case report. The main complication was represented by osteonecrosis of the jaws, which appears to be related to the duration of treatment with bisphosphonates; in addition, data regarding the anatomical location of post-extraction sites, the sex and age of patients, comorbidities and various systemic risk factors were extrapolated. The most frequent post-extraction complication in patients treated with oral bisphosphonates is osteonecrosis of the jaws, with a significant prevalence in the posterior region of the mandible. In some cases, delayed healing of the surgical wound was also found; moreover, the duration of exposure to oral bisphosphonates influences the onset of complications.
CONCLUSIONS
Ongoing studies continue to unravel the role of the oral environment response in alveolar bone homeostasis and how it might contribute to the induction of BRONJ/MRONJ. Approaching the problem from this perspective could provide new directions for the prevention of BRONJ/MRONJ and expand our understanding of the unique oral microenvironment.
Topics: Humans; Bone Density Conservation Agents; Prospective Studies; Retrospective Studies; Bisphosphonate-Associated Osteonecrosis of the Jaw; Diphosphonates; Osteonecrosis; Tooth Extraction
PubMed: 37458653
DOI: 10.26355/eurrev_202307_32996 -
Ecotoxicology and Environmental Safety Jul 2023Membrane-based separation processes has been recently of significant global interest compared to other conventional separation approaches due to possessing undeniable... (Review)
Review
The roles of artificial intelligence techniques for increasing the prediction performance of important parameters and their optimization in membrane processes: A systematic review.
Membrane-based separation processes has been recently of significant global interest compared to other conventional separation approaches due to possessing undeniable advantages like superior performance, environmentally-benign nature and simplicity of application. Computational simulation of fluids has shown its undeniable role in modeling and simulation of numerous physical/chemical phenomena including chemical engineering, chemical reaction, aerodynamics, drug delivery and plasma physics. Definition of fluids can be occurred using the Navier-Stokes equations, but solving the equations remains an important challenge. In membrane-based separation processes, true perception of fluid's manner through disparate membrane modules is an important concern, which has been significantly limited applying numerical/computational procedures such s computational fluid dynamics (CFD). Despite this noteworthy advantage, the optimization of membrane processes using CFD is time-consuming and expensive. Therefore, combination of artificial intelligence (AI) and CFD can result in the creation of a promising hybrid model to accurately predict the model results and appropriately optimize membrane processes and phase separation. This paper aims to provide a comprehensive overview about the advantages of commonly-employed ML-based techniques in combination with the CFD to intelligently increase the optimization accuracy and predict mass transfer and the unfavorable events (i.e., fouling) in various membrane processes. To reach this objective, four principal strategies of AI including SL, USL, SSL and ANN were explained and their advantages/disadvantages were discussed. Then after, prevalent ML-based algorithm for membrane-based separation processes. Finally, the application potential of AI techniques in different membrane processes (i.e., fouling control, desalination and wastewater treatment) were presented.
Topics: Artificial Intelligence; Computer Simulation; Algorithms; Water Purification; Hydrodynamics
PubMed: 37262969
DOI: 10.1016/j.ecoenv.2023.115066