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Biochimica Et Biophysica Acta.... Nov 2023This study aims to explore the potential biomarkers in the development of diabetes mellitus (DM) into diabetic retinopathy (DR).
Integration of systematic review, lipidomics with experiment verification reveals abnormal sphingolipids facilitate diabetic retinopathy by inducing oxidative stress on RMECs.
OBJECTIVE
This study aims to explore the potential biomarkers in the development of diabetes mellitus (DM) into diabetic retinopathy (DR).
METHODS
Systematic review of diabetic metabolomics was used to screen the differential metabolites and related pathways during the development of DM. Non-targeted lipidomics of rat plasma was performed to explore the differential metabolites in the development of DM into DR in vivo. To verify the effects of differential metabolites in inducing retinal microvascular endothelial cells (RMECs) injury by increasing oxidative stress, high glucose medium containing differential metabolites was used to induce rat RMECs injury and cell viability, malondialdehyde (MDA) contents, superoxide dismutase (SOD) activities, reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were evaluated in vitro. Network pharmacology was performed to explore the potential mechanism of differential metabolites in inducing DR.
RESULTS
Through the systematic review, 148 differential metabolites were obtained and the sphingolipid metabolic pathway attracted our attention. Plasma non-targeted lipidomics found that sphingolipids were accompanied by the development of DM into DR. In vitro experiments showed sphinganine and sphingosine-1-phosphate aggravated rat RMECs injury induced by high glucose, further increased MDA and ROS levels, and further decreased SOD activities and MMP. Network pharmacology revealed sphinganine and sphingosine-1-phosphate may induce DR by regulating the AGE-RAGE and HIF-1 signaling pathways.
CONCLUSIONS
Integrated systematic review, lipidomics and experiment verification reveal that abnormal sphingolipid metabolism facilitates DR by inducing oxidative stress on RMECs. Our study could provide the experimental basis for finding potential biomarkers for the diagnosis and treatment of DR.
Topics: Rats; Animals; Diabetic Retinopathy; Reactive Oxygen Species; Sphingolipids; Lipidomics; Endothelial Cells; Oxidative Stress; Glucose; Superoxide Dismutase; Biomarkers; Diabetes Mellitus
PubMed: 37659619
DOI: 10.1016/j.bbalip.2023.159382 -
The Science of the Total Environment Dec 2022The spread of microbial antibiotic resistance has seriously threatened public health globally. Non-antibiotic stressors have significantly contributed to the evolution... (Review)
Review
The spread of microbial antibiotic resistance has seriously threatened public health globally. Non-antibiotic stressors have significantly contributed to the evolution of bacterial antibiotic resistance. Although numerous studies have been conducted on the potential risk of pesticide pollution for bacterial antibiotic resistance, a systematic review of these concerns is still lacking. In the present study, we elaborate the mechanism underlying the effects of pesticides on bacterial antibiotic resistance acquisition as well as the propagation of antimicrobial resistance. Pesticide stress enhanced the acquisition of antibiotic resistance in bacteria via various mechanisms, including the activation of efflux pumps, inhibition of outer membrane pores for resistance to antibiotics, and gene mutation induction. Horizontal gene transfer is a major mechanism whereby pesticides influence the transmission of antibiotic resistance genes (ARGs) in bacteria. Pesticides promoted the conjugation transfer of ARGs by increasing cell membrane permeability and increased the proportion of bacterial mobile gene elements, which facilitate the spread of ARGs. This review can improve our understanding regarding the pesticide-induced generation and spread of ARGs and antibiotic resistant bacteria. Moreover, it can be applied to reduce the ecological risks of ARGs in the future.
Topics: Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial; Gene Transfer, Horizontal; Pesticides
PubMed: 35977623
DOI: 10.1016/j.scitotenv.2022.158057 -
Hormones (Athens, Greece) Jun 2019Thyroid incidentaloma is defined as a thyroid lesion incidentally and newly detected by imaging techniques performed for an unrelated purpose and especially for a...
INTRODUCTION
Thyroid incidentaloma is defined as a thyroid lesion incidentally and newly detected by imaging techniques performed for an unrelated purpose and especially for a non-thyroid disease. The aim of this review is to evaluate the prevalence and clinical significance of focal incidental radiolabelled prostate-specific membrane antigen (PSMA) uptake in the thyroid gland [PSMA thyroid incidentaloma (PTI)] revealed by PET/CT or PET/MRI.
METHODS
A comprehensive literature search of the PubMed/MEDLINE, Scopus, and Embase databases was conducted to find relevant published articles about the prevalence and clinical significance of PTIs detected by PET/CT or PET/MRI in patients studied for other oncologic purposes.
RESULTS
Twelve articles were included in the systematic review. Among 23 PTIs, 6 were malignant (5 primary thyroid tumors and one metastasis from renal cell carcinoma), one was a follicular lesion of undetermined significance, and the rest were benign.
CONCLUSION
Despite being very rare, though probably underestimated, PTIs frequently signal the presence of unexpected lesions in the thyroid which differ from the indicated reason for which the patient was initially scanned and concerning which the risk of malignancy is not negligible.
Topics: Adenoma; Edetic Acid; Gallium Isotopes; Gallium Radioisotopes; Humans; Incidental Findings; Male; Oligopeptides; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Thyroid Neoplasms
PubMed: 30989578
DOI: 10.1007/s42000-019-00106-8 -
The Spine Journal : Official Journal of... Feb 2022There are limited treatments for discogenic low back pain. Intradiscal injections of biologic agents such as platelet-rich plasma (PRP) or stem cells (SC) are theorized... (Review)
Review
BACKGROUND CONTEXT
There are limited treatments for discogenic low back pain. Intradiscal injections of biologic agents such as platelet-rich plasma (PRP) or stem cells (SC) are theorized to have regenerative properties and have gained increasing interest as a possible treatment, but the evidence supporting their use in clinical practice is not yet well-defined.
PURPOSE
Determine the effectiveness of intradiscal biologics for treating discogenic low back pain.
STUDY DESIGN
PRISMA-compliant systematic review.
PATIENT SAMPLE
Patients with discogenic low back pain confirmed by provocation discography or clinical and imaging findings consistent with discogenic pain.
OUTCOME MEASURES
The primary outcome was the proportion of individuals with ≥50% pain relief after intradiscal biologic injection at 6 months. Secondary outcomes included ≥2-point pain score reduction on NRS; patient satisfaction; functional improvement; decreased use of other health care, including analgesics and surgery; and structural disc changes on MRI.
METHODS
Comprehensive literature search performed in 2018 and updated in 2020. Interventions included were biologic therapies including mesenchymal stem cells, platelet rich plasma, microfragmented fat, amniotic membrane-based injectates, and autologous conditioned serum. Any other treatment (sham or active) was considered for comparative studies. Studies were independently reviewed.
RESULTS
The literature search yielded 3,063 results, 37 studies were identified for full-text review, and 12 met established inclusion criteria for review. The quality of evidence on effectiveness of intradiscal biologics was very low. A single randomized controlled trial evaluating platelet-rich plasma reported positive outcomes but had significant methodological flaws. A single trial that evaluated mesenchymal stem cells was negative. Success rates for platelet-rich plasma injectate in aggregate were 54.8% (95% Confidence Interval: 40%-70%). For mesenchymal stem cells, the aggregate success rate at six months was 53.5% (95% Confidence Interval: 38.6%-68.4%), though using worst-case analysis this decreased to 40.7% (95% Confidence Interval: 28.1%-53.2%). Similarly, ≥30% functional improvement was achieved in 74.3% (95% Confidence Interval: 59.8%-88.7%) at six months but using worst-case analysis, this decreased to 44.1% (95% Confidence Interval: 28.1%-53.2%).
CONCLUSION
Limited observational data support the use of intradiscal biologic agents for the treatment of discogenic low back pain. According to the Grades of Recommendation, Assessment, Development and Evaluation System, the evidence supporting use of intradiscal mesenchymal stem cells and platelet-rich plasma is very low quality.
Topics: Analgesics; Biological Products; Humans; Intervertebral Disc Displacement; Low Back Pain; Pain Management; Platelet-Rich Plasma; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34352363
DOI: 10.1016/j.spinee.2021.07.015 -
Cornea May 2015Ex vivo cultured limbal epithelial transplantation (CLET) with amniotic membrane (AM) as the substrate is a relatively new type of surgical therapy in treating limbal... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Ex vivo cultured limbal epithelial transplantation (CLET) with amniotic membrane (AM) as the substrate is a relatively new type of surgical therapy in treating limbal stem cell deficiency (LSCD). We summarize available evidence for determining the efficiency of this technique by a systematic review and meta-analysis.
METHODS
Searching the following electronic databases, MEDLINE, EMBASE, and the Cochrane Library, we analyzed the selected articles in 5 main aspects: donor screening, culture methods, evidence of cultivated stem cells, subjective symptoms, and adverse events through systematic review. Specifically, meta-analysis was used in evaluating improvements in ocular surface and visual acuity.
RESULTS
A total of 18 articles involving 572 eyes of 562 patients were available. The rate of success and 2-line improvement in best-corrected visual acuity (BCVA) was 67% [95% confidence interval (CI), 0.59-0.75; I = 60%] and 62% (95% CI, 0.57-0.66; I = 37.7%), respectively; and no difference was found both in success rate [odds ratio (OR), 1.35; 95% CI, 0.63-2.89; I = 46%] and visual acuity outcome (OR, 1.53; 95% CI, 0.67-3.45; I = 42.1%) between autograft and allograft.
CONCLUSIONS
CLET is efficacious in patients with LSCD, and no difference both in success rate and visual acuity outcome between autograft and allograft was found. Overall safety profile was good, with most side effects being transient and amenable to subsequent treatments. The long-term results of autograft and allograft will inform future treatment algorithms and techniques with random control trials and better-designed analysis.
Topics: Amnion; Cells, Cultured; Corneal Diseases; Epithelial Cells; Humans; Limbus Corneae; Stem Cell Transplantation; Stem Cells; Tissue Scaffolds; Transplantation, Autologous
PubMed: 25789694
DOI: 10.1097/ICO.0000000000000398 -
Oxidative Medicine and Cellular... 2018Mitochondria are metabolically active organelles that produce significant reactive oxygen species, linked with aging and degenerative diseases. In recent years,... (Meta-Analysis)
Meta-Analysis Review
Mitochondria are metabolically active organelles that produce significant reactive oxygen species, linked with aging and degenerative diseases. In recent years, particular focus has been put on mitochondria-targeted antioxidants, to decrease the concentration of reactive oxygen species and help alleviate the accumulation of oxidative damage and associated aging. MitoQ is a mitochondria-targeted antioxidant of which is reported to support healthy aging. The aim of this systematic review is to investigate the effects of MitoQ on oxidative outcomes related to the aging process. A predeveloped search strategy was run against MEDLINE (Ovid), EMBASE (Ovid), and CINAHL databases, which identified 10,255 articles of interest, with 27 of these finalised for use after screening. Three outcomes had sufficient data to meta-analyse nitrotyrosine concentration (190 animals, SMD -0.67, 95% CI (-1.30, -0.05), = 0.04), membrane potential (63 animals, MD 11.44, 95% CI (1.28-21.60), = 0.03), and protein carbonyl concentration (182 animals, SMD -0.13, 95% CI (-0.44, 0.18), = 0.41). MitoQ intervention produced a statistically significant reduction in nitrotyrosine concentration and increased membrane potential. MitoQ may be of some benefit in alleviating oxidative stress related to aging.
Topics: Aging; Biomarkers; Humans; Mitochondria; Organophosphorus Compounds; Ubiquinone
PubMed: 30116495
DOI: 10.1155/2018/8575263 -
Mitochondrion May 2022Mitochondrial permeability transition pore (mPTP) is a channel that opens at the inner mitochondrial membrane under conditions of stress. Sirtuin 3 (Sirt3) is a... (Review)
Review
Mitochondrial permeability transition pore (mPTP) is a channel that opens at the inner mitochondrial membrane under conditions of stress. Sirtuin 3 (Sirt3) is a mitochondrial deacetylase known to play a major role in stress resistance and a regulatory role in cell death. This systematic review aims to elucidate the role of Sirt3 in mPTP inhibition. Electronic databases, including PubMed, EMBASE, Web of Science and Cochrane Library were searched up to May 2020. Original studies that investigated the relationship between Sirt3 and mPTP were included. Two reviewers independently extracted data on study characteristics, methods and outcomes. A total of 194 articles were found. Twenty-nine articles, which met criteria were included in the systematic review. Twenty-three studies provided evidence of the inhibitory effect of Sirt3 on the mPTP aperture. This review summarizes up-to-date evidence of the protective and inhibitory role of Sirt3 through deacetylating Cyclophilin D (CypD) on the mPTP aperture. Furthermore, we discuss the implications of this effect in disease.
Topics: Peptidyl-Prolyl Isomerase F; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Sirtuin 3
PubMed: 35346868
DOI: 10.1016/j.mito.2022.03.004 -
International Journal of Molecular... Mar 2023Seminal plasma contains numerous extracellular vesicles (sEVs). Since sEVs are apparently involved in male (in)fertility, this systematic review focused on studies... (Review)
Review
Seminal plasma contains numerous extracellular vesicles (sEVs). Since sEVs are apparently involved in male (in)fertility, this systematic review focused on studies specifically investigating such relationship. Embase, PubMed, and Scopus databases were searched up to 31 December 2022, primarily identifying a total of 1440 articles. After processing for screening and eligibility, 305 studies were selected as they focused on sEVs, and 42 of them were considered eligible because they included the word fertility or a related word such as infertility, subfertility, fertilization, and recurrent pregnancy loss in the title, objective(s), and/or keywords. Only nine of them met the inclusion criteria, namely (a) conducting experiments aimed at associating sEVs with fertility concerns and (b) isolating and adequately characterizing sEVs. Six studies were conducted on humans, two on laboratory animals, and one on livestock. The studies highlighted some sEV molecules, specifically proteins and small non-coding RNAs, that showed differences between fertile and subfertile or infertile males. The content of sEVs was also related to sperm fertilizing capacity, embryo development, and implantation. Bioinformatic analysis revealed that several of the highlighted sEV fertility-related proteins would be cross-linked to each other and involved in biological pathways related to (i) EV release and loading and (ii) plasma membrane organization.
Topics: Pregnancy; Animals; Female; Male; Humans; Semen; Fertility; Infertility, Male; Spermatozoa; Extracellular Vesicles
PubMed: 36902244
DOI: 10.3390/ijms24054818 -
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 -
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