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1.
Biomedicines ; 12(4)2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38672153

RESUMEN

BACKGROUND: Chronic limb-threatening ischemia (CLTI), the advanced stage of peripheral arterial disease, is diagnosed in the presence of ischemic rest pain, non-healing ulcers, or gangrene. Several studies have demonstrated that inflammation and endothelial dysfunction are some of the main substrates of CLTI. METHODS: A narrative review was conducted and reported according to PRISMA guidelines. Three databases were searched-Web of Science, Medline, and EMBASE-for the studies assessing CLTI and the biological markers related to it. RESULTS: We included 22 studies, and all the markers identified (C-reactive protein, D-dimers, fibrinogen, cytokines, IL-6, TNF-α, ICAM-1 (Intracellular Adhesion Molecule-1), VCAM-1 (Vascular Cell Adhesion Molecule-1), neutrophile-to-lymphocytes ratio (NLR), IL-8, Pentraxin-3, neutrophil gelatinase-associated lipocalin (NGAL), calprotectin, E-selectin, P-selectin, neopterin, High-Mobility Group Box-1 protein (HGMB-1), Osteoprotegerin (OPG) and Sortilin) were positively associated with advanced CLTI, with major limb or major cardiovascular events in these patients. CONCLUSIONS: All the studied markers had increased values in patients with CLTI, especially when associated with diabetes mellitus, proving a very important association between diabetes and major limb or cardiovascular events in these patients. There is a need for more studies to validate these markers in terms of diagnosis or prognosis in CLTI patients and in trying to find new medical strategies that target inflammation or endothelial dysfunction in these patients.

2.
Biomolecules ; 14(4)2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38672515

RESUMEN

Cerebrovascular disease accounts for major neurologic disabilities in patients with type 2 diabetes mellitus (DM). A potential association of mitochondrial DNA (mtDNA) and inflammation with cerebral vessel remodeling in patients with type 2 DM was evaluated. A cohort of 150 patients and 30 healthy controls were assessed concerning urinary albumin/creatinine ratio (UACR), synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), N-acetyl-ß-(D)-glucosaminidase (NAG), interleukins IL-17A, IL-18, IL-10, tumor necrosis factor-alpha (TNFα), intercellular adhesion molecule-1 (ICAM-1). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine by qRT-PCR. Cytochrome b (CYTB) gene, subunit 2 of NADH dehydrogenase (ND2), and beta 2 microglobulin nuclear gene (B2M) were assessed by TaqMan assays. mtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies, through analysis of the CYTB/B2M and ND2/B2M ratio; cerebral Doppler ultrasound: intima-media thickness (IMT)-the common carotid arteries (CCAs), the pulsatility index (PI) and resistivity index (RI)- the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), the breath-holding index (BHI). The results showed direct correlations of CCAs-IMT, PI-ICAs, PI-MCAs, RI-ICAs, RI-MCAs with urinary mtDNA, IL-17A, IL-18, TNFα, ICAM-1, UACR, synaptopodin, podocalyxin, KIM-1, NAG, and indirect correlations with serum mtDNA, IL-10. BHI correlated directly with serum IL-10, and serum mtDNA, and negatively with serum IL-17A, serum ICAM-1, and NAG. In neurologically asymptomatic patients with type 2 DM cerebrovascular remodeling and impaired cerebrovascular reactivity may be associated with mtDNA variations and inflammation from the early stages of diabetic kidney disease.


Asunto(s)
ADN Mitocondrial , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Inflamación , Humanos , ADN Mitocondrial/genética , Masculino , Femenino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Persona de Mediana Edad , Inflamación/genética , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/patología , Anciano , Remodelación Vascular/genética , Estudios de Casos y Controles
3.
Life (Basel) ; 14(4)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38672729

RESUMEN

BACKGROUND: Breast cancer is the most frequently diagnosed cancer among women, responsible for the highest number of cancer-related deaths worldwide. There is limited data available related to serum tumor markers in breast cancer and other blood parameters or other glandular laboratory parameters. This study aims to evaluate the correlation of tumor-specific markers for breast cancer with other blood parameters and how these correlations could impact clinical management. MATERIAL AND METHOD: This retrospective study represents a data analysis from 1 January 2020 to 31 May 2023, in the County Hospital of Timisoara, Romania. We reviewed all the cases where, in the laboratory analyses, the serum tumor specific biomarkers for breast cancer were analyzed. RESULTS: A statistical analysis was performed in order to identify a possible relationship between CA 15-3 and the various biomarkers and blood parameters included in the present study. Values were classified according to reference ranges. The tests revealed no statistically significant associations between CA 15-3 values and the levels of CA125 (χ2(1) = 1.852, p = 0.174), CEA (χ2(1) = 1.139, p = 0.286), AFP (Fisher's exact test, p = 0.341), fT4 (Fisher's exact test, p = 0.310), TSH (Fisher's exact test, p = 0.177), or PTH (Fisher's exact test, p = 0.650). CONCLUSION: The findings indicate a lack of strong correlation between CA 15-3 and CA125, CEA, AFP, thyroid function markers, or PTH within this cohort.

4.
Life (Basel) ; 14(2)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38398724

RESUMEN

Lung cancer (LC) represents one of the most prevalent health issues globally and is a leading cause of tumor-related mortality. Despite being one the most attractive compounds of plant origin due to its numerous biological properties, the therapeutic applications of rutin (RUT) are limited by its disadvantageous pharmacokinetics. Thus, the present study aimed to evaluate in vitro the application of two RUT fatty acids bioconjugates, rutin oleate (RUT-O) and rutin linoleate (RUT-L), as potential improved RUT-based chemotherapeutics in non-small cell lung cancer (NSCLC) treatment. The results indicate that both compounds lacked cytotoxic potential in EpiAirway™ tissues at concentrations up to 125 µM. However, only RUT-L exerted anti-tumorigenic activity in NCI-H23 NSCLC cells after 24 h of treatment by reducing cell viability (up to 47%), proliferation, and neutral red uptake, causing cell membrane damage and lactate dehydrogenase (LDH) leakage, affecting cytoskeletal distribution, inducing cytoplasmic vacuolation, and increasing oxidative stress. The cytopathic effects triggered by RUT-L at 100 and 125 µM are indicators of a non-apoptotic cell death pathway that resembles the characteristics of paraptosis. The novel findings of this study stand as a basis for further investigations on the anti-cancer properties of RUT-L and their underlying mechanisms.

5.
Metabolites ; 13(8)2023 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-37623837

RESUMEN

Complications due to type 2 diabetes mellitus (T2DM) such as diabetic kidney disease (DKD) and cerebral small vessel disease (CSVD) have a powerful impact on mortality and morbidity. Our current diagnostic markers have become outdated as T2DM-related complications continue to develop. The aim of the investigation was to point out the relationship between previously selected metabolites which are potentially derived from gut microbiota and indicators of endothelial, proximal tubule (PT), and podocyte dysfunction, and neurosonological indices. The study participants were 20 healthy controls and 90 T2DM patients divided into three stages: normoalbuminuria, microalbuminuria, and macroalbuminuria. Serum and urine metabolites were determined by untargeted and targeted metabolomic techniques. The markers of endothelial, PT and podocyte dysfunction were assessed by ELISA technique, and the neurosonological indices were provided by an ultrasound device with high resolution (MYLAB 8-ESAOTE Italy). The descriptive statistical analysis was followed by univariable and multivariable linear regression analyses. In conclusion, in serum, arginine (sArg), butenoylcarnitine (sBCA), and indoxyl sulfate (sIS) expressed a biomarker potential in terms of renal endothelial dysfunction and carotid atherosclerosis, whereas sorbitol (sSorb) may be a potential biomarker of blood-brain barrier (BBB) dysfunction. In urine, BCA and IS were associated with markers of podocyte damage, whereas PCS correlated with markers of PT dysfunction.

6.
Int J Mol Sci ; 24(12)2023 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-37372951

RESUMEN

Mitochondrial dysfunction is an important mechanism contributing to the development and progression of diabetic kidney disease (DKD). Mitochondrial DNA (mtDNA) levels in blood and urine were evaluated in relation to podocyte injury and proximal tubule (PT) dysfunction, as well as to a specific inflammatory response in normoalbuminuric DKD. A total of 150 type 2 diabetes mellitus (DM) patients (52 normoalbuminuric, 48 microalbuminuric, and 50 macroalbuminuric ones, respectively) and 30 healthy controls were assessed concerning the urinary albumin/creatinine ratio (UACR), biomarkers of podocyte damage (synaptopodin and podocalyxin), PT dysfunction (kidney injury molecule-1 (KIM-1) and N-acetyl-ß-(D)-glucosaminidase (NAG)), and inflammation (serum and urinary interleukins (IL-17A, IL-18, and IL-10)). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine via qRT-PCR. MtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies via analysis of the CYTB/B2M and ND2/B2M ratio. Multivariable regression analysis provided models in which serum mtDNA directly correlated with IL-10 and indirectly correlated with UACR, IL-17A, and KIM-1 (R2 = 0.626; p < 0.0001). Urinary mtDNA directly correlated with UACR, podocalyxin, IL-18, and NAG, and negatively correlated with eGFR and IL-10 (R2 = 0.631; p < 0.0001). Mitochondrial DNA changes in serum and urine display a specific signature in relation to inflammation both at the podocyte and tubular levels in normoalbuminuric type 2 DM patients.


Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Interleucina-10 , Interleucina-17 , Interleucina-18/genética , ADN Mitocondrial/genética , Albuminuria/orina , Inflamación/genética , Mitocondrias/genética , Biomarcadores/orina
7.
Infect Drug Resist ; 15: 7001-7014, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36478964

RESUMEN

Purpose: Critically ill patients hospitalized in the intensive care unit (ICU) have an increased infection risk. The aim of this study was to determine the bacterial and fungal superinfections rate in Coronavirus disease 2019 (COVID-19) patients stationed in the ICU, identify risk factors associated with their development and to determine whether superinfection plays a role in patients' outcome in this population. Patients and Methods: In this retrospective, non-interventional, single centre, cohort study, medical records of 302 consecutive patients with SARS-COV-2 pneumonia admitted into the COVID-19 ICU of the largest university hospital from Western Romania between October 2020 and May 2021, were reviewed, of whom 236 patients met the inclusion criteria. Results: One hundred and nineteen patients developed a superinfection ≥48 h after being admitted to the hospital. Superinfection rate in the ICU was 50.42%. Coagulase-negative Staphylococci (CoNS) and Enterococcus spp. were predominantly isolated from blood cultures, while Acinetobacter baumannii, Staphylococcus aureus and Candida spp. from tracheobronchial aspirates. Significant independent risk factors regarding bacterial/fungal superinfection in COVID-19 patients were obtained for the following variables: number of days of central venous catheter (HR = 1.13 [1.07-1.20], p < 0.001) and prior administration of corticosteroids (HR = 2.80 [1.33-5.93], p = 0.007). Four independent predictive risk factors were associated with unfavorable outcome: age (HR = 1.07 [95% CI 1.03-1.12], p = 0.001); Carmeli Score (HR = 6.09 [1.18-31.50], p = 0.031); body mass index (HR = 1.11 [1.02-1.21], p = 0.011) and the presence of a central venous catheter (HR = 6.49 [1.93-21.89], p = 0.003). Conclusion: The superinfection rate in COVID-19 patients was high in this study group. Exogenous risk factors were associated with superinfection more than endogenous factors. Only a small percentage of uninfected COVID-19 patients were not prescribed antibiotics during their hospitalization, raising serious concerns regarding the judicious prescribing of antibiotics in viral infections.

8.
Biomed Res Int ; 2022: 6028045, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35734346

RESUMEN

Background: The bacterial membrane plays a critical role in the survival of bacteria and the effectiveness of antimicrobial peptides in protecting the host. The lipid constituents of the bacterial membrane are not evenly distributed, and they could be affected by clustering anionic lipids with cationic peptides with multiple positive charges. That could be harmful to bacteria because it prevents lipids from interacting with other molecular components of the cell membrane, disrupts existing natural domains, or creates phase boundary defects between the clustered lipids and the bulk of the membrane. This preliminary quantitative study is aimed at assembling a correlation between antibiotic resistance and bacterial lipid composition in E. coli, based on the function and arrangement of the bilipid coating of the bacterial cell, intimately associated with the path of antimicrobials through membranes. Methods: Fifteen multiresistant E. coli samples are collected from swine with enterocolitis tested for resistance levels using the disc diffusimetric method (Kirby-Bauer disc diffusion). Pathogen identification completed using the API 20E multitest system revealed the E. coli presence in 11 samples. In these samples, bacterial membrane detection of fatty acid methyl esters (FAME) operating a 240 MS Ion Trap (Varian) GC/MS (Agilent Technologies, Santa Clara, CA, USA) was performed, using the MIDI Sherlock recognition software model. Results: Interpreting the descriptive statistical method, the correlation matrix, and regression curves and after ANOVA analysis, we ascertained that the studied E. coli population statistically confirmed different degrees of resistance in most of the samples analyzed in this test. Conclusions: In one case, the methyl-(Z)-11-tetradecenoate acid was observed to have a relationship with the susceptibility evaluation by using the disc diffusimetric method, which has revealed the lowest rate of antimicrobial resistance, so it has importance in further resistance evaluation studies.


Asunto(s)
Infecciones por Escherichia coli , Lípidos de la Membrana , Animales , Antibacterianos/química , Bacterias , Farmacorresistencia Bacteriana , Farmacorresistencia Microbiana , Escherichia coli , Lípidos de la Membrana/metabolismo , Pruebas de Sensibilidad Microbiana , Porcinos
9.
Pathogens ; 11(5)2022 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-35631037

RESUMEN

With the onset of the COVID-19 pandemic, enormous efforts have been made to understand the genus SARS-CoV-2. Due to the high rate of global transmission, mutations in the viral genome were inevitable. A full understanding of the viral genome and its possible changes represents one of the crucial aspects of pandemic management. Structural protein S plays an important role in the pathogenicity of SARS-CoV-2, mutations occurring at this level leading to viral forms with increased affinity for ACE2 receptors, higher transmissibility and infectivity, resistance to neutralizing antibodies and immune escape, increasing the risk of infection and disease severity. Thus, five variants of concern are currently being discussed, Alpha, Beta, Gamma, Delta and Omicron. In the present review, a comprehensive summary of the following critical aspects regarding SARS-CoV-2 has been made: (i) the genomic characteristics of SARS-CoV-2; (ii) the pathological mechanism of transmission, penetration into the cell and action on specific receptors; (iii) mutations in the SARS-CoV-2 genome; and (iv) possible implications of mutations in diagnosis, treatment, and vaccination.

10.
Vector Borne Zoonotic Dis ; 22(4): 267-270, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35384727

RESUMEN

Limited data are available regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in children. In this study, we assessed for the first time the seroprevalence of SARS-CoV-2 in children from Romania. Serum samples of 379 children were investigated for the presence of SARS-CoV-2 total antibodies. Serologic tests were performed using Elecsys Anti-SARS-CoV-2 electrochemiluminiscence immunoassay that targets the nucleocapsid protein of the virus. The overall seroprevalence of SARS-CoV-2 total antibodies was 46.70%. No significant difference was observed between seropositive and seronegative children according to age groups, gender, and area of residence. Our findings revealed a high SARS-CoV-2 seroprevalence in Romanian children at the end of the third COVID-19 pandemic wave. Results suggest that children, regardless of age, gender, or area of residence, are susceptible to infection with SARS-CoV-2. Seroprevalence in children was similar to the seroprevalence reported in the adult population from Western Romania during the same period of time, March to June 2021.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Anticuerpos Antivirales , COVID-19/epidemiología , COVID-19/veterinaria , Humanos , Pandemias , Rumanía/epidemiología , Estudios Seroepidemiológicos
11.
Materials (Basel) ; 15(3)2022 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-35161136

RESUMEN

Malocclusion is a global health problem, mainly affecting children and adolescents. For this reason, orthodontic treatment must be, on the one hand, safe, non-toxic, and effective and, on the other hand, it must have the best possible esthetic profile. Thus, the use of orthodontic appliances is addressed to all age groups, including young children, for a long period of time, which is why their safety profile is a matter of real interest. For this reason, the purpose of the present study was to evaluate the safety and biocompatibility of an acrylic removable orthodontic appliance made of polymethylmethacrylate and stainless steel alloy made by our team of researchers. To verify the biocompatibility of the medical device, it was immersed in artificial saliva with three different pHs (3, 7, and 10) for a period of ten days. Subsequently, the three types of saliva were tested on human keratinocytes (HaCaT cell line) in terms of viability and modification of cell morphology. Finally, the use of 3D reconstructed human epidermis verified the cytotoxic and irritating potential of the medical device, thus providing relevant information regarding its biocompatibility. The results revealed that by maintaining the orthodontic device in the saliva there is no release of substances with a toxic effect on the human keratinocytes and on the 3D reconstructed human epidermis. There were also no significant changes in cell morphology. In conclusion, it is suggested that the acrylic removable appliance has a safety profile recommended for in vivo use.

12.
Exp Ther Med ; 23(1): 76, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34934447

RESUMEN

Therapeutic plasma exchange (TPE) has been proposed as a rescue therapy in critically ill COVID-19 patients. The aim of the present study was to determine whether combining TPE with convalescent plasma (CVP) transfusion early in the intensive care unit (ICU) stay improves survival among this heterogeneous population. The primary endpoint was survival at 30 days. Secondary endpoints included assessing the evolution of biomarkers, such as the partial pressure of arterial oxygen to fractional inspired oxygen ratio, and C reactive protein (CRP), lactate dehydrogenase (LDH) and ferritin levels at the 7-day follow-up. This single centre, prospective, non-randomized controlled trial was conducted in an 8-bed COVID-19 ICU and included patients with severe COVID-19 pneumonia requiring intensive care treatment. A total of 19 patients were treated by performing TPE followed by CVP transfusion, in addition to standard treatment, while for another 19 patients, only standard treatment according to hospital protocols was used. TPE was initiated during the first 24 h after ICU admission, followed immediately by transfusion of CVP. Survival at 30 days was 47.37% in the TPE CVP group and 26.32% in the control group (P=0.002). Patients in the TPE CVP group also showed better oxygenation and a reduction in inflammation, with decreased CRP, LDH and ferritin levels compared with those in the control group. Overall, the study indicated that early initiation of TPE followed by CVP transfusion may be a valid rescue therapy in severe and critically ill COVID-19 patients, with a statistically significant survival benefit, improved oxygenation and a reduction in inflammatory markers. The trial was registered in the ClinicalTrials.gov database (trial registration number: NCT04973488) on July 22, 2021 (retrospectively registered).

13.
Exp Ther Med ; 22(5): 1215, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34584560

RESUMEN

Clostridioides difficile (C. difficile) is a common cause of nosocomial diarrhea. The multi-modal infection control strategies designed to contain the COVID-19 pandemic have had an unintended positive effect on other hospital-acquired infections. The aim of the present study was to analyze the impact of the COVID-19 prevention measures on healthcare-associated C. difficile infections in a large regional acute care center. Electronic databases were reviewed from the start of the pandemic (March) up to November 2020. Average values from the same months from 2019 and 2018 were used as controls. Using the ICD-10 discharge coding, 65 C. difficile cases per 25,124 patients were identified in 2020 compared to 151/43,126 from the 2018 and 2019 averages (P=0.0484). The C. difficile cases were found to be decreased after the implementation of COVID-19 infection control strategies compared to previous years, despite an increase in antibiotic use. Subset analysis during lockdown showed a clear decrease but the difference was not statistically significant. For the months of recovery after lockdown, the number of cases was comparable to previous years.

14.
Biomolecules ; 11(6)2021 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-34070757

RESUMEN

Cardiovascular disorders are leading mortality causes worldwide, often with a latent evolution. Vascular health depends on endothelial function, arterial stiffness, and the presence of atherosclerotic plaques. Preventive medicine deserves special attention, focusing on modifiable cardiovascular risk factors, including diet. A diet rich in fruits and vegetables has well-known health benefits, especially due to its polyphenolic components. Anthocyanins, water-soluble flavonoid species, responsible for the red-blue color in plants and commonly found in berries, exert favorable effects on the endothelial function, oxidative stress, inhibit COX-1, and COX-2 enzymes, exert antiatherogenic, antihypertensive, antiglycation, antithrombotic, and anti-inflammatory activity, ameliorate dyslipidemia and arterial stiffness. The present review aims to give a current overview of the mechanisms involved in the vascular protective effect of anthocyanins from the human diet, considering epidemiological data, in vitro and in vivo preclinical research, clinical observational, retrospective, intervention and randomized studies, dietary and biomarker studies, and discussing preventive benefits of anthocyanins and future research directions.


Asunto(s)
Antocianinas/uso terapéutico , Aterosclerosis/tratamiento farmacológico , Dislipidemias/tratamiento farmacológico , Endotelio Vascular/metabolismo , Estrés Oxidativo/efectos de los fármacos , Placa Aterosclerótica/tratamiento farmacológico , Rigidez Vascular/efectos de los fármacos , Antocianinas/química , Antocianinas/metabolismo , Aterosclerosis/metabolismo , Aterosclerosis/mortalidad , Dislipidemias/metabolismo , Dislipidemias/mortalidad , Humanos , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/mortalidad
15.
Exp Ther Med ; 22(1): 672, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33986837

RESUMEN

Ionic liquids (ILs) exhibit cytotoxic effects on prokaryotic and eukaryotic cells. In this study, the antibacterial and antiproliferative activities of tetrahexylammonium bromide-based ILs were investigated. In order to evaluate the therapeutic potential of these ionic liquids, firstly microbiological assay using both Gram-positive and Gram-negative bacteria were conducted by employing Disk-Diffusion and 2,3,5-triphenyltetrazolium chlorine (TTC) methods to assess the antimicrobial effects. Likewise, the antitumor effects on 2D and 3D cell culture systems were assessed using the human colon cancer Caco-2 cell line and cytotoxic activity was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Alamar blue assays. Results obtained showed that [CH3(CH2)5]4N(Br) possesses an antibacterial potential, particularly in the case of two bacteria, S. aureus (Gram+) and H. influenzae (Gram-). Preliminary screening of antiproliferative activity showed moderate activity, except for the concentration of 10 mM. Furthermore, regarding the effect of [CH3(CH2)5]4N(Br) on tumor cell aggregation, positive outcomes were noted. [CH3(CH2)5]4N(Br) presents promising and under-explored potential to improve antibacterial or anticancer therapies.

16.
Int J Med Sci ; 18(10): 2093-2101, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33859515

RESUMEN

Aims: Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aims of the study were to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients in relation to a particular miRNAs profile. Methods: A total of 136 patients with type 2 DM and 25 healthy subjects were assessed in a cross-sectional study concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and of proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), urinary miRNA21, 124, 93, 29a. Results: Multivariable regression analysis showed that urinary lncMALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.727); urinary lncNEAT1 correlated directly with synaptopodin, KIM-1, NAG, miRNA21, 124, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.702); urinary lncMIAT correlated directly with miRNA93 and 29a, eGFR (p<0.0001; R2=0.671) and negatively with synaptopodin, KIM-1, NAG, UACR, miRNA21, 124 (p<0.0001; R2=0.654); urinary lncTUG1 correlated directly with eGFR, miRNA93, 29a, and negatively with synaptopodin, podocalyxin, NAG, miRNA21, 124 (p<0.0001; R2=0.748). Conclusions: In patients with type 2 DM lncRNAs exert either deleterious or protective functions within glomeruli and PT. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/genética , Túbulos Renales Proximales/fisiopatología , Podocitos/fisiología , ARN Largo no Codificante/metabolismo , Adulto , Anciano , Biomarcadores/metabolismo , Biomarcadores/orina , Estudios Transversales , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/orina , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/orina , Femenino , Regulación de la Expresión Génica/fisiología , Humanos , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Factores Protectores , ARN Largo no Codificante/orina , Factores de Riesgo , Adulto Joven
17.
Medicina (Kaunas) ; 58(1)2021 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-35056343

RESUMEN

Background and Objectives: The extent of SARS-CoV-2 infection among a population may be assessed by the presence of serum SARS-CoV-2 antibodies, which indicates previous exposure. The aim of this study was to determine the seroprevalence of SARS-CoV-2 infection in the adult population from Western Romania. Materials and Methods: Samples of 2443 consecutive individuals, referred for routine laboratory investigations, were tested for SARS-CoV-2 antibodies using the Elecsys immunoassay that targets the nucleocapsid protein, for identifying the presence of the total antibodies against SARS-CoV-2. Results: The overall SARS-CoV-2 seroprevalence was 45.60%. SARS-CoV-2 seroprevalence was significantly higher in age group 30-49 years (53.94%) compared to age groups 50-69 years (43.53%) and 70-91 years (30.79%) (p < 0.001, p < 0.001, respectively). No significant difference in seroprevalence was observed between females (44.83%) and males (47.05%). Conclusions: Our data revealed a high seroprevalence of SARS-CoV-2 infection in the adult population from Western Romania and indicate the rapid and significant spread of the virus. The estimated prevalence of 45.60% was 6 times higher than the rate of confirmed COVID-19 cases reported in the study area. This indicates the magnitude of virus transmission in the community.


Asunto(s)
COVID-19 , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas de la Nucleocápside , Rumanía/epidemiología , Estudios Seroepidemiológicos
18.
Medicine (Baltimore) ; 99(48): e23356, 2020 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-33235104

RESUMEN

This study investigates for the first time the influence of four doses of rosuvastatin on total fatty acids (TFA) and free fatty acids (FFA) in human plasma and correlates their changes in concentration with changes in the concentration of other lipids involved in cholesterol homeostasis.This study was a placebo-controlled, randomized, double-blind, crossover experiment. The study used a single group of 16 men and consisted of 5 treatment periods lasting 4 weeks each with placebo and 4 doses of rosuvastatin (5, 10, 20, and 40 mg). Each subject changed 5 medical treatments and received in each new treatment different tablets of rosuvastatin or placebo compared to those taken in previous treatments, in a random order. Between treatment periods there was a wash-out period of 2 weeks, without treatment.Changes in TFA and FFA were significant compared to placebo and between different doses of rosuvastatin. We found a continuous logarithmic decrease in levels of TFA, FFA, low-density lipoprotein (LDL)-cholesterol, total cholesterol, triglycerides, phospholipids, and apolipoprotein B-100, and a continuous increase in levels of high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-1 by increases the dose of rosuvastatin. Analysis of the correlation of TFA and FFA with the main lipids and lipoproteins in cholesterol homeostasis indicated a linear regression with high correlation coefficients and all P-values were less than .05 level.The concentrations of TFA and FFA are significantly influenced by the dose of rosuvastatin. They are strongly correlated with those of other lipids and lipoproteins involved in cholesterol homeostasis. The mechanisms of cholesterol homeostasis regulation are involved in changing the concentrations of TFA and FFA.


Asunto(s)
Colesterol/metabolismo , Ácidos Grasos/sangre , Rosuvastatina Cálcica/farmacología , Anciano , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Ácidos Grasos no Esterificados/sangre , Humanos , Lípidos/sangre , Masculino
19.
Biochem Biophys Rep ; 24: 100822, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33072892

RESUMEN

Each fatty acid (FA) or class of FAs has a different behavior in the pathologies of atherosclerosis. The aim of this study was to investigate changes in the concentration of each fatty acid in the fraction of free fatty acids (FFAs) and total lipids in human plasma after short-term therapy with rosuvastatin as a cholesterol-lowering statin drug. Six hypercholesterolemic men on a habitual diet were studied in a randomized, double-blind, and crossover process. They received 20 mg rosuvastatin or placebo in random order, each for 4 weeks and after 2 weeks of washout period, they received another medication (placebo or rosuvastatin) for another period of 4 weeks. Rosuvastatin treatment significantly decreased the absolute concentrations of saturated and monounsaturated FAs in the total FAs as well as in FFAs. Long chain polyunsaturated fatty acids with 20 and 22 carbon atoms in the molecule had no significant change in the fraction of FFAs. Rosuvastatin is directly involved in cholesterol biosynthesis and indirectly through cholesterol homeostasis in the biosynthesis of other plasma lipids. In conclusion, our findings show that rosuvastatin treatment leads to significant changes in the concentration of each fatty acid, except for long-chain polyunsaturated fatty acids in FFAs. Our observations indicate that cholesterol homeostasis through its regulatory mechanisms appears to be the main cause of changes in the concentration of each plasma fatty acid during rosuvastatin treatment. These changes can be a source of beneficial consequences, in addition to lowering low-density lipoprotein cholesterol in cardiovascular diseases.

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