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Current Pollution Reports Sep 2023There is a growing interest in understanding the health effects of exposure to per- and polyfluoroalkyl substances (PFAS) through the study of the human metabolome. In...
PURPOSE OF REVIEW
There is a growing interest in understanding the health effects of exposure to per- and polyfluoroalkyl substances (PFAS) through the study of the human metabolome. In this systematic review, we aimed to identify consistent findings between PFAS and metabolomic signatures. We conducted a search matching specific keywords that was independently reviewed by two authors on two databases (EMBASE and PubMed) from their inception through July 19, 2022 following PRISMA guidelines.
RECENT FINDINGS
We identified a total of 28 eligible observational studies that evaluated the associations between 31 different PFAS exposures and metabolomics in humans. The most common exposure evaluated was legacy long-chain PFAS. Population sample sizes ranged from 40 to 1,105 participants at different stages across the lifespan. A total of 19 studies used a non-targeted metabolomics approach, 7 used targeted approaches, and 2 included both. The majority of studies were cross-sectional ( = 25), including four with prospective analyses of PFAS measured prior to metabolomics.
SUMMARY
Most frequently reported associations across studies were observed between PFAS and amino acids, fatty acids, glycerophospholipids, glycerolipids, phosphosphingolipids, bile acids, ceramides, purines, and acylcarnitines. Corresponding metabolic pathways were also altered, including lipid, amino acid, carbohydrate, nucleotide, energy metabolism, glycan biosynthesis and metabolism, and metabolism of cofactors and vitamins. We found consistent evidence across studies indicating PFAS-induced alterations in lipid and amino acid metabolites, which may be involved in energy and cell membrane disruption.
PubMed: 37753190
DOI: 10.1007/s40726-023-00269-4 -
Cannabis and Cannabinoid Research Aug 2023This systematic review aimed to assess efficacy and safety for skin-applied formulations containing CBD. Bibliographic and clinical trial registries were searched for... (Review)
Review
This systematic review aimed to assess efficacy and safety for skin-applied formulations containing CBD. Bibliographic and clinical trial registries were searched for interventional human trials using cutaneously administered CBD or reported plasma CBD concentrations (any species). Eight of 544 articles fitted the selection criteria: 3 placebo-controlled randomized and 5 single-arm trials. Eleven more studies were found in clinical trial databases but not accessible. Symptoms targeted were dermatopathologies or safety (two studies), pain (two), and behavior (one). Doses were 50-250 mg or 0.075-1.0% CBD, but coformulated with other ingredients. Risk of bias was high and reporting deficiencies further compromised data reliability. Diverse methodologies and formulations hampered syntheses for CBD dose, efficacy, and safety. Plasma CBD levels in dogs and rodents were 0.01-5 μM translating to <100 nM free, unbound CBD in humans. Adverse events were uncommon and mild, but meaningless without CBD's contribution to efficacy data. Achievable CBD plasma concentrations ∼100 nM can interact predominantly with high-affinity CBD targets, for example, TRPA1 and TRPM8 membrane channels that are abundantly expressed in pathological conditions. Even if reached, higher CBD concentrations on less susceptible targets risk complex and unsafe CBD therapy. A conceptual framework is proposed where dermal capillary loops create sinking for topical CBD demonstrating parallels between topical and transdermal CBD administration. Users risk generalizing inadequately designed trials to all CBD preparations. New clinical trials are urgently needed: they must demonstrate that outcomes are solely from CBD pharmacology, are reliable, unbiased, safe, and comparable. Measurements of sustained plasma CBD levels are mandatory, irrespective of administration route for successful translation from systems that express human molecular targets. Placebos must be appropriate. Transcutaneous and topical formulations need preliminary studies to optimize CBD skin penetration. Then, users can rationally balance efficacy against potential harms and cost-effectiveness of CBD formulations.
Topics: Humans; Animals; Dogs; Cannabidiol; Reproducibility of Results; Pain; Administration, Cutaneous; Seizures
PubMed: 35605018
DOI: 10.1089/can.2021.0154 -
Journal of Intensive Care Medicine Jul 2023To summarize the role of therapeutic plasma exchange (TPE) in critically ill adults and children with severe sepsis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To summarize the role of therapeutic plasma exchange (TPE) in critically ill adults and children with severe sepsis.
DATA COLLECTION
A systematic search was performed using the following databases: Medline, EMBASE, CINAHL, and Cochrane from January 1990 till December 2022. Comparative studies of TPE in severe sepsis were selected. Adult and pediatric data were analyzed separately.
DATA SYNTHESIS
Eight randomized control trials and 6 observational studies (n = 50,142 patients) were included. Centrifugal TPE was the most common modality (209/280, 74.6% adults and 952/1026, 92.7% children). Every TPE study utilized different volume exchanges. Most TPE sessions (1173/1306, 89.8%) employed fresh frozen plasma (FFP) as replacement fluid and heparin as anticoagulant. Adults with severe sepsis supported with TPE using FFP had lower mortality (risk ratio, : 0.64 [95% confidence interval, : 0.49, 0.84]) compared to those who did not. In contrast, TPE was associated with increased mortality in septic children without thrombocytopenia-associated multiorgan failure (: 2.23, 95% : 1.93, 2.57). There was no difference in outcomes in patients supported with centrifugal and membrane TPE. In both populations, patients supported on TPE as a continuous regime had poorer outcome.
CONCLUSION
Current evidence indicates that TPE is a potential adjunct therapy in adults with severe sepsis but not in children.
Topics: Adult; Humans; Child; Shock, Septic; Plasma Exchange; Sepsis; Multiple Organ Failure; Plasma
PubMed: 37097910
DOI: 10.1177/08850666231170775 -
Heart Failure Reviews Jan 2024Iron overload increases the production of harmful reactive oxygen species in the Fenton reaction, which causes oxidative stress in the body and lipid peroxidation in the... (Review)
Review
Iron overload increases the production of harmful reactive oxygen species in the Fenton reaction, which causes oxidative stress in the body and lipid peroxidation in the cell membrane, and eventually leads to ferroptosis. Diabetes is associated with increased intracellular oxidative stress, inflammation, autophagy, microRNA alterations, and advanced glycation end products (AGEs), which cause cardiac remodeling and cardiac diastolic contractile dysfunction, leading to the development of diabetic cardiomyopathy (DCM). While these factors are also closely associated with ferroptosis, more and more studies have shown that iron-mediated ferroptosis is an important causative factor in DCM. In order to gain fresh insights into the functions of ferroptosis in DCM, this review methodically summarizes the traits and mechanisms connected with ferroptosis and DCM.
Topics: Humans; Diabetic Cardiomyopathies; Ferroptosis; MicroRNAs; Autophagy; Diastole; Reactive Oxygen Species; Diabetes Mellitus
PubMed: 37555989
DOI: 10.1007/s10741-023-10336-z -
Molecular Biology Reports Nov 2022Angiotensin-converting enzyme 2 (ACE2) is known as the major viral entry site for SARS-CoV-2. However, viral tissue tropism and high rate of infectivity do not directly... (Review)
Review
BACKGROUND
Angiotensin-converting enzyme 2 (ACE2) is known as the major viral entry site for SARS-CoV-2. However, viral tissue tropism and high rate of infectivity do not directly correspond with the level of ACE2 expression in the organs. It may suggest involvement of other receptors or accessory membrane proteins in SARSCoV-2 cell entry.
METHODS AND RESULTS
A systematic search was carried out in PubMed/Medline, EMBASE, and Cochrane Library for studies reporting SARS-CoV-2 cell entry. We used a group of the MeSH terms including "cell entry", "surface receptor", "ACE2", and "SARS-CoV-2". We reviewed all selected papers published in English up to end of February 2022. We found several receptors or auxiliary membrane proteins (including CD147, NRP-1, CD26, AGTR2, Band3, KREMEN1, ASGR1, ANP, TMEM30A, CLEC4G, and LDLRAD3) along with ACE2 that facilitate virus entry and transmission. Expression of Band3 protein on the surface of erythrocytes and evidence of binding with S protein of SARS-CoV-2 may explain asymptomatic hypoxemia during COVID19 infection. The variants of SARS-CoV-2 including the B.1.1.7 (Alpha), B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.617.2+ (Delta+), and B.1.1.529 (Omicron) may have different potency to bond with these receptors.
CONCLUSIONS
The high rate of infectivity of SARS-CoV-2 may be due to its ability to enter the host cell through a group of cell surface receptors. These receptors are potential targets to develop novel therapeutic agents for SARS-CoV-2.
Topics: Humans; Angiotensin-Converting Enzyme 2; Asialoglycoprotein Receptor; COVID-19; Protein Binding; Receptors, Virus; SARS-CoV-2; Spike Glycoprotein, Coronavirus
PubMed: 35754059
DOI: 10.1007/s11033-022-07700-x -
Pediatric Nephrology (Berlin, Germany) Jul 2022Observing biomarkers that affect alternative pathway dysregulation components may be effective in obtaining a new and more rapid diagnostic portrayal of atypical... (Review)
Review
BACKGROUND AND OBJECTIVES
Observing biomarkers that affect alternative pathway dysregulation components may be effective in obtaining a new and more rapid diagnostic portrayal of atypical hemolytic uremic syndrome. We have conducted a systematic review on the aHUS biomarkers: C3, C5a, C5b-9, factor B, complement factor B, H, and I, CH50, AH50, D-dimer, as well as anti-CFH antibodies.
METHODS
An exhaustive literature search was conducted for aHUS patient population plasma/serum, collected/reported at the onset of diagnosis. A total of 60 studies were included with the data on 837 aHUS subjects, with at least one biomarker reported.
RESULTS
The biomarkers C3 [mean (SD): 72.1 (35.0), median: 70.5 vs. reference range: 75-175 mg/dl, n = 752]; CH50 [28.3 (32.1), 24.3 vs. 30-75 U/ml, n = 63]; AH50 [27.6% (30.2%), 10% vs. ≥ 46%, n = 23]; and CFB [13.1 (6.6), 12.4, vs. 15.2-42.3 mg/dl, n = 19] were lower among aHUS subjects as compared with the reference range. The biomarkers including C4 [mean (SD): 20.4 (9.5), median: 20.5 vs. reference range: 14-40 mg/dl, n = 343]; C4d [7.2 (6.5), 4.8 vs. ≤ 9.8 μg/ml, n = 108]; CFH [40.2 (132.3), 24.5 vs. 23.6-43.1 mg/dl, n = 123 subjects]; and CFI [8.05 (5.01), 6.55 mg/dl vs. 4.4-18.1 mg/dl, n = 38] were all observed to be within the reference range among aHUS subjects. The biomarkers C5a [mean (SD): 54.9 (32.9), median: 48.8 vs. reference range: 10.6-26.3 mg/dl, n = 117]; C5b-9 [466.0 (401.4), 317 (186-569.7) vs. ≤ 250 ng/ml, n = 174]; Bb [2.6 (2.1), 1.9 vs. ≤ 1.6 μg/ml, n = 77] and D-dimer [246 (65.05), 246 vs. < 2.2 ng/ml, 2, n = 2 subjects] were higher among patients with aHUS compared with the reference range.
CONCLUSION
If a comprehensive complement profile were built using our data, aHUS would be identified by low levels of C3, CH50, AH50, and CFB along with increased levels of C5a, C5b-9, Bb, anti-CFH autoantibodies, and D-dimer. A higher resolution version of the Graphical abstract is available as Supplementary information.
Topics: Atypical Hemolytic Uremic Syndrome; Autoantibodies; Biomarkers; Complement Factor B; Complement Factor H; Complement Membrane Attack Complex; Humans
PubMed: 35118546
DOI: 10.1007/s00467-022-05451-2 -
American Journal of Ophthalmology Jan 2023To compare the efficacy and safety of ultrathin Descemet stripping (automated) endothelial keratoplasty (UT-DS(A)EK) versus Descemet membrane endothelial keratoplasty... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To compare the efficacy and safety of ultrathin Descemet stripping (automated) endothelial keratoplasty (UT-DS(A)EK) versus Descemet membrane endothelial keratoplasty (DMEK) for the treatment of Fuchs endothelial dystrophy (FED) and bullous keratopathy (BK).
DESIGN
Systematic review and meta-analysis.
METHODS
Literature containing DMEK and UT-DSAEK were searched in the Cochrane Database of Systematic Reviews, PubMed, EMBASE, LILACS, and through manual reference searching. Studies were included that measured the outcome of interventions-including best corrected visual acuity (BCVA), endothelial cell density (ECD), and postoperative complications, especially graft detachment with the need of re-bubbling, graft rejection, graft failure, and postoperative elevated intraocular pressure (IOP)-in patients with FED and BK. Included outcomes were pooled as standardized mean differences (SMD) or risk ratios (RR) using random effects models. Inter-study heterogeneity was assessed using the Q-test and I statistic.
RESULTS
Seven (of 163) studies met all the inclusion and exclusion criteria. Meta-analysis showed a significantly better BCVA 12 months postoperatively, but an increased re-bubbling rate in eyes after DMEK compared with eyes after UT-DS(A)EK (BCVA: SMD = 0.50 [95% CI 0.27-0.74] and re-bubbling rate: RR = 0.33 [95% CI 0.16-0.67]). All other parameters did not differ significantly between both interventions, although estimates were imprecise (graft failure: RR = 0.65 [95% CI 0.18-2.30], graft rejection: RR = 1.40 [95% CI 0.27-7.30], and postoperative intraocular pressure elevation: RR = 1.14 [95% CI 0.60-2.18]). Postoperative SMDs of ECD could not be evaluated due to significant heterogeneity between studies.
CONCLUSIONS
Although the improvement in BCVA was higher after UT-DS(A)EK than after conventional DS(A)EK, the BCVA after DMEK was still superior. The complication rates were comparable for both procedures, except for the higher rate of re-bubbling after DMEK.
Topics: Humans; Cell Count; Corneal Edema; Descemet Membrane; Descemet Stripping Endothelial Keratoplasty; Endothelium, Corneal; Fuchs' Endothelial Dystrophy; Retrospective Studies; Visual Acuity
PubMed: 36220351
DOI: 10.1016/j.ajo.2022.09.013 -
Obesity Science & Practice Jun 2022Inositol is a sugar-alcohol and recognized as a key component of cell membrane phospholipids. It has crucial role in the cell signaling pathways and contribute to... (Review)
Review
BACKGROUND
Inositol is a sugar-alcohol and recognized as a key component of cell membrane phospholipids. It has crucial role in the cell signaling pathways and contribute to improving glycemic responses. Although some earlier studies have revealed the effect of inositol mediating glucose uptake by improving insulin sensitivity, the benefit of inositol supplementation in patients with overweight and obesity is not completely understood. This study aimed to assess the impact of inositol supplementation on body mass index (BMI) through a systematic review and meta-analysis of controlled clinical trials.
METHODS
A systematic search was performed to August 2021 in the following databases: PubMed-Medline, Embase, Web of Science and Scopus. Fifteen controlled clinical trials investigating the effect of inositol on adult's BMI were finally included in the study. A random-effects model was employed to estimate the effect size. Subgroup analysis was performed by dose, duration, age, type of inositol. Meta-regression was used to investigate presence of any linear relationship. Begg's and Egger's tests were carried out to detect small study effect.
RESULTS
The results of pooled analysis showed that inositol supplementation significantly decreased BMI scores (WMD = -0.41 kg/m; 95% CI: -0.78, -0.04; = 0.028). Subgroup analysis was performed to identify the source of heterogeneity among studies ( = 73.9%, < 0.001), demonstrating supplementation duration, baseline BMI, mean age of participants, type of inositol and dosage were potential sources of heterogeneity. The effect of intervention was more clinically significant in participants with polycystic ovary syndrome (PCOS) and overweight/obesity. Inositol in the form of myo-inositol (MI) had stronger effect on BMI reduction.
CONCLUSION
The meta-analysis suggests that oral inositol supplementation has positive effect on BMI reduction. Inositol supplementation could be considered as an adjunct treatment to improve body mass index.
PubMed: 35664247
DOI: 10.1002/osp4.569 -
Frontiers in Genetics 2022Exosomes are nano-extracellular vesicles secreted by a variety of cells. They are composed of a double-layer membrane that can transport a variety of proteins, coding...
Exosomes are nano-extracellular vesicles secreted by a variety of cells. They are composed of a double-layer membrane that can transport a variety of proteins, coding and non-coding genes, and bioactive substances. Exosomes participate in information transmission between cells and regulate processes such as cell proliferation, migration, angiogenesis, and phenotypic transformation. They have broad prospects in the occurrence, development, and treatment of many diseases including orthopedics. Exosomes derived from different types of bone cells such as mesenchymal stem cells, osteoblasts, osteoclasts, and their precursors are recognized to play pivotal roles in bone remodeling processes including osteogenesis, osteoclastogenesis, and angiogenesis. This articlesummarizes the characteristics of exosomes and their research progress in bone remodeling, bone tumors, vascular skeletal muscle injury, spinal cord injury, degenerative disc diseases, cartilage degeneration, osteoarthritis, necrosis of the femoral head, and osteoporosis.
PubMed: 36081990
DOI: 10.3389/fgene.2022.915141 -
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