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1.
Clin Chem ; 69(9): 991-1008, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37478022

RESUMO

BACKGROUND: Harmonization in laboratory medicine is essential for consistent and accurate clinical decision-making. There is significant and unwarranted variation in reference intervals (RIs) used by laboratories for assays with established analytical traceability. The Canadian Society of Clinical Chemists (CSCC) Working Group on Reference Interval Harmonization (hRI-WG) aims to establish harmonized RIs (hRIs) for laboratory tests and support implementation. METHODS: Harnessing the power of big data, laboratory results were collected across populations and testing platforms to derive common adult RIs for 16 biochemical markers. A novel comprehensive approach was established, including: (a) analysis of big data from community laboratories across Canada; (b) statistical evaluation of age, sex, and analytical differences; (c) derivation of hRIs using the refineR method; and (d) verification of proposed hRIs across 9 laboratories with different instrumentation using serum and plasma samples collected from healthy Canadian adults. RESULTS: Harmonized RIs were calculated for all assays using the refineR method, except free thyroxine. Derived hRIs met proposed verification criterion across 9 laboratories and 5 manufacturers for alkaline phosphatase, albumin (bromocresol green), chloride, lactate dehydrogenase, magnesium, phosphate, potassium (serum), and total protein (serum). Further investigation is needed for some analytes due to failure to meet verification criteria in one or more laboratories (albumin [bromocresol purple], calcium, total carbon dioxide, total bilirubin, and sodium) or concern regarding excessively wide hRIs (alanine aminotransferase, creatinine, and thyroid stimulating hormone). CONCLUSIONS: We report a novel data-driven approach for RI harmonization. Findings support feasibility of RI harmonization for several analytes; however, some presented challenges, highlighting limitations that need to be considered in harmonization and big data analytics.


Assuntos
Ciência de Dados , Laboratórios , Adulto , Humanos , Valores de Referência , Canadá , Albuminas
2.
Environ Res ; 219: 114955, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36495962

RESUMO

Hydrocarbon-contaminated soils are considered as one of the major environmental issues that harm human well-being, particularly in arid regions of the world. Phytoremediation is a possible mitigation measure for this issue and has been suggested as it is cost-effective compared with other remediation technologies for soil clean-up, such as soil thermal treatment and soil washing. However, there are still gaps in the literature regarding the behavior of annual and perennial desert plants and their ability to survive in hydrocarbon-contaminated soils in arid ecosystems. Therefore, this study aims to develop an integrated approach using remote sensing techniques to understand the behavior of annual and perennial desert plants over different types of oil-contaminated soils (oil tarcrete, wet-oil lake, bare soil, and vegetation cover) in the Kuwait Desert and to explore the impact of climate and physical soil properties on the regrowth of native desert plants. The Normalized Difference Vegetation Index (NDVI), Normalized Difference Water Index (NDWI), and ferrous iron (Fe2+) index (FI) were used to determine the changes in oil contamination and vegetation cover from 1992 to 2002, and 2013-2020. Subsequently, statistical tests were performed to determine the influence of climatic and soil physical characteristics on changes in hydrocarbon contamination and desert plant behavior. The results showed that hydrocarbon contamination was high at the study sites in the first six years (1992-1997) after contamination, and then decreased in the following years. However, vegetation cover was low in the first six years but significantly increased after 1998, reaching >65%. It was also found that annual plants had the highest distribution rate compared to perennial plants, which mainly depended on the soil type. We concluded that certain annual and perennial plants could successfully grow over tarcrete-contaminated sites, making these sites more suitable for the restoration of native desert plants than hydrocarbon-contaminated sites. We also observed that the succession process of vegetation growth over hydrocarbon-contaminated soils could be associated with vegetation growth on a clean sediment layer covering the oil layer. Additionally, we observed that the remobilization of aeolian sediment over many contaminated sites in Kuwait resulted in the accumulation of organic matter, plant seeds, and dust particles that create layers of nutrient-rich soil for the initial growth of plants.


Assuntos
Ecossistema , Poluentes do Solo , Humanos , Tecnologia de Sensoriamento Remoto , Poluentes do Solo/análise , Solo , Plantas , Biodegradação Ambiental , Hidrocarbonetos
3.
Eur Respir J ; 58(4)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33863738

RESUMO

Chronic lung allograft dysfunction (CLAD) is the major cause of death after lung transplantation. Angiotensin II (AngII), the main effector of the renin-angiotensin system, elicits fibrosis in both kidney and lung. We identified six AngII-regulated proteins (Ras homolog family member B (RHOB), bone marrow stromal cell antigen 1 (BST1), lysophospholipase 1 (LYPA1), glutamine synthetase (GLNA), thrombospondin 1 (TSP1) and laminin subunit ß2 (LAMB2)) that were increased in urine of patients with kidney allograft fibrosis. We hypothesised that the renin-angiotensin system is active in CLAD and that AngII-regulated proteins are increased in bronchoalveolar lavage fluid (BAL) of CLAD patients.We performed immunostaining of AngII receptors (AGTR1 and AGTR2), TSP1 and GLNA in 10 CLAD lungs and five controls. Using mass spectrometry, we quantified peptides corresponding to AngII-regulated proteins in BAL of 40 lung transplant recipients (stable, acute lung allograft dysfunction (ALAD) and CLAD). Machine learning algorithms were developed to predict CLAD based on BAL peptide concentrations.Immunostaining demonstrated significantly more AGTR1+ cells in CLAD versus control lungs (p=0.02). TSP1 and GLNA immunostaining positively correlated with the degree of lung fibrosis (R2=0.42 and 0.57, respectively). In BAL, we noted a trend towards higher concentrations of AngII-regulated peptides in patients with CLAD at the time of bronchoscopy, and significantly higher concentrations of BST1, GLNA and RHOB peptides in patients that developed CLAD at follow-up (p<0.05). The support vector machine classifier discriminated CLAD from stable and ALAD patients at the time of bronchoscopy (area under the curve (AUC) 0.86) and accurately predicted subsequent CLAD development (AUC 0.97).Proteins involved in the renin-angiotensin system are increased in CLAD lungs and BAL. AngII-regulated peptides measured in BAL may accurately identify patients with CLAD and predict subsequent CLAD development.


Assuntos
Transplante de Pulmão , Sistema Renina-Angiotensina , Aloenxertos , Humanos , Pulmão , Receptor Tipo 2 de Angiotensina
4.
J Environ Manage ; 288: 112416, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33831641

RESUMO

This study focused on evaluating factors influencing the growth of perennial shrubs by integrating field-based experiments and spatial analysis using unmanned aerial vehicles (UAVs) to identify ecological indicators that can help detect potential locations for restoration and revegetation of native plants. The experiment was implemented in the Al-Abduli protected area in Kuwait, which is mainly dominated by a Rhanterium epapposum community (desert shrub). Aerial imagery of the study site was acquired using UAVs during the growing season to estimate the desert shrub biomass and carbon stock. Then, soil samples were collected based on vegetation density to determine the impact of the soil's physical and chemical properties on vegetation biomass, growth, and distribution. It was found that shrub biomass was significantly correlated with crown area and shrub volume. We also observed that annual plants support the growth of perennial shrubs, as the mean shrub height and crown area (CA) are significantly higher, with averages of 0.7 m and 3 cm, respectively, in the presence of high annual plant density. However, shrubs in plots with low annual density had an average shrub height of 0.5 m and CA of 1.4 cm. Annual plants also enhance the soil by providing approximately 50% higher soil moisture, phosphorous (P), organic matter (OM), and carbon dioxide (CO2) sequestration. In addition, annual plants are mainly supported by loamy soils in the deeper soil layers. We concluded that locations covered with annual plants represent suitable soils and that this can be considered a biological indicator for convenient locations for restoration and revegetation of native perennial shrubs. Remote sensing technologies could be utilized for initial assessments to detect sites that may support annual plant growth over a large scale for classification as potential restoration and revegetation areas.


Assuntos
Ecossistema , Biomarcadores Ambientais , Biomassa , Clima Desértico , Fósforo , Solo
5.
J Pathol ; 239(4): 411-25, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27135434

RESUMO

Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been associated with fibrotic lung disease, although exactly how they modulate this process remains unclear. Here we investigated the role of GRP78, the main UPR regulator, in an experimental model of lung injury and fibrosis. Grp78(+/-) , Chop(-/-) and wild type C57BL6/J mice were exposed to bleomycin by oropharyngeal intubation and lungs were examined at days 7 and 21. We demonstrate here that Grp78(+/-) mice were strongly protected from bleomycin-induced fibrosis, as shown by immunohistochemical analysis, collagen content and lung function measurements. In the inflammatory phase of this model, a reduced number of lung macrophages associated with an increased number of TUNEL-positive cells were observed in Grp78(+/-) mice. Dual immunohistochemical and in situ hybridization experiments showed that the macrophage population from the protected Grp78(+/-) mice was also strongly positive for cleaved caspase-3 and Chop mRNA, respectively. In contrast, the administration of bleomycin to Chop(-/-) mice resulted in increased quasi-static elastance and extracellular matrix deposition associated with an increased number of parenchymal arginase-1-positive macrophages that were negative for cleaved caspase-3. The data presented indicate that the UPR is activated in fibrotic lung tissue and strongly localized to macrophages. GRP78- and CHOP-mediated macrophage apoptosis was found to protect against bleomycin-induced fibrosis. Overall, we demonstrate here that the fibrotic response to bleomycin is dependent on GRP78-mediated events and provides evidence that macrophage polarization and apoptosis may play a role in this process. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Apoptose/genética , Proteínas de Choque Térmico/metabolismo , Macrófagos Alveolares/metabolismo , Fibrose Pulmonar/metabolismo , Fator de Transcrição CHOP/metabolismo , Animais , Bleomicina , Caspase 3/metabolismo , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/genética , Proteínas de Choque Térmico/genética , Macrófagos Alveolares/patologia , Camundongos , Camundongos Knockout , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia , Fator de Transcrição CHOP/genética , Resposta a Proteínas não Dobradas/genética
6.
J Am Soc Nephrol ; 26(8): 1839-54, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25398788

RESUMO

Angiotensin II is an important mediator of CKD of diverse etiology. A common pathologic feature of CKD is glomerular fibrosis, a central mediator of which is the profibrotic cytokine TGF-ß. The mechanisms underlying the induction of TGF-ß and matrix by angiotensin II are not completely understood. Recent studies showed that overexpression of the transcription factor SREBP-1 induces glomerular sclerosis and that angiotensin II can activate SREBP-1 in tubular cells. We thus studied whether SREBP-1 is activated by angiotensin II and mediates angiotensin II-induced profibrogenic responses in primary rat mesangial cells. Treatment of cells with angiotensin II induced the upregulation and activation of SREBP-1. Angiotensin II-induced activation of SREBP-1 required signaling through the angiotensin II type I receptor and activation of PI3K/Akt in addition to the chaperone SCAP and protease S1P. Notably, angiotensin II-induced endoplasmic reticulum stress was identified as a key mediator of Akt-SREBP-1 activation, and inhibition of endoplasmic reticulum stress or SREBP-1 prevented angiotensin II-induced SREBP-1 binding to the TGF-ß promoter, TGF-ß upregulation, and downstream fibronectin upregulation. Endoplasmic reticulum stress alone, however, did not induce TGF-ß upregulation despite activating SREBP-1. Although not required for SREBP-1 activation by angiotensin II, EGF receptor signaling was necessary for activation of the SREBP-1 cotranscription factor Sp1, which provided a required second signal for TGF-ß upregulation. In vivo, endoplasmic reticulum stress and SREBP-1-dependent effects were induced in glomeruli of angiotensin II-infused mice, and administration of the SREBP inhibitor fatostatin prevented angiotensin II-induced TGF-ß upregulation and matrix accumulation. SREBP-1 and endoplasmic reticulum stress thus provide potential novel therapeutic targets for the treatment of CKD.


Assuntos
Angiotensina II/metabolismo , Estresse do Retículo Endoplasmático , Células Mesangiais/metabolismo , Insuficiência Renal Crônica/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Animais , Células Cultivadas , Receptores ErbB/metabolismo , Fibronectinas/biossíntese , Fibrose , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Rim/patologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridinas , Ratos Endogâmicos Dahl , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/metabolismo , Insuficiência Renal Crônica/patologia , Serina Proteases/metabolismo , Fator de Transcrição Sp1/metabolismo , Tiazóis , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima
7.
Integr Pharm Res Pract ; 13: 51-60, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736676

RESUMO

Background: Cow's milk protein allergy is the most frequent type of food allergy in newborns and young children. It affects numerous body systems. A community pharmacist possessing adequate knowledge and appropriate practices is crucial for the management of the disease. Objectives: : This study aimed to assess the knowledge and attitude of community pharmacists toward the complications and treatment of cow milk protein allergy. Methods: A descriptive cross-sectional study was conducted among 332 randomly selected community pharmacists in the Capital of Sudan (Khartoum state). Data were collected using a validated and internally consistent (Cronbach Alpha = 0.712) self-administered questionnaire Descriptive statistics and Chi-square analysis were conducted using Statistical Package for the Social Sciences version 25. Results: The response rate was 95.8%, and about 47.8% of the population had 1-5 years of experience as community pharmacists, and 37.4% of them had a post-graduate degree. Only 30.8% of respondents had good knowledge, while 40.6% had poor knowledge, and 28.6% had scored as having fair knowledge of complications of Cow's milk protein allergy. Regarding knowledge toward treatment, 65.1% of respondents had a poor knowledge, 24.5% had fair knowledge, and only 10.4% had good knowledge. Overall, 39.62% of participants had a positive attitude, and 60.38% had a negative attitude toward this disease. Data analysis showed no significant association between the sociodemographic characteristics of respondents and their knowledge and attitude. Conclusion: Community pharmacists in Khartoum State had inadequate knowledge and attitude about the complications and treatment of cow milk protein allergy. As a result, we recommend the implementation of strategies to raise pharmacists' knowledge and attitude.

8.
Biomed Pharmacother ; 177: 116899, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38889636

RESUMO

Neurodegenerative diseases that include Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS) that arise due to numerous causes like protein accumulation and autoimmunity characterized by neurologic depletion which lead to incapacity in normal physiological function such as thinking and movement in these patients. Glial cells perform an important role in protective neuronal function; in the case of neuroinflammation, glial cell dysfunction can promote the development of neurodegenerative diseases. miRNA that participates in gene regulation and plays a vital role in many biological processes in the body; in the central nervous system (CNS), it can play an essential part in neural maturation and differentiation. In neurodegenerative diseases, miRNA dysregulation occurs, enhancing the development of these diseases. In this review, we discuss neurodegenerative disease (Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)) and how miRNA is preserved as a diagnostic biomarker or therapeutic agent in these disorders. Finally, we highlight miRNA as therapy.

9.
Diseases ; 12(5)2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38785754

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an incurable disease. There are vigorous attempts to develop treatments to reduce the effects of this disease, and among these treatments is the transplantation of stem cells. This study aimed to retrospectively evaluate a mesenchymal stem cell (MSC) therapy cohort as a promising novel treatment modality by estimating some additional new parameters, such as immunological and biochemical factors. METHODS: This study was designed as an open-label, one-arm cohort retrospective study to evaluate potential diagnostic biomarkers of repeated infusions of autologous-bone marrow-derived mesenchymal stem cells (BM-MSCs) in 15 confirmed patients with ALS, administered at a dose of 1 × 106 cells/kg BW with a one-month interval, in equal amounts in both an intravenous (IV) and intrathecal (IT) capacity simultaneously, via various biochemical (iron (Fe), ferritin, total-iron-binding capacity (TIBC), transferrin, and creatine kinase (CK)) and immunological parameters (tumor necrosis factor-alpha (TNF-α), neurofilament light chain (NFL), and glial-cell-derived neurotrophic factor (GDNF) levels, evaluated during the three-month follow-up period in serum and cerebrospinal fluid (CSF). RESULTS: Our study indicated that, in the case of immunological biomarkers, TNF-α levels in the CSF showed a significant decrease at month three after transplantation compared with levels at month zero, and the p-value was p < 0.01. No statistically significant changes were observed for other immunological as well as biochemical parameters and a p-value of p > 0.05. CONCLUSIONS: These results can indicate the potential benefit of stem cell transfusion in patients with ALS and suggest some diagnostic biomarkers. Several studies are required to approve these results.

10.
J Biol Chem ; 287(10): 7603-14, 2012 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-22215680

RESUMO

The integrated stress response mediated by eukaryotic translation initiation factor 2α (eIF2α) phosphorylation maintains cellular homeostasis under endoplasmic reticulum (ER) stress. eIF2α phosphorylation induces activating transcription factor 4 (ATF4), a basic leucine zipper transcription factor that regulates the expression of genes responsible for amino acid metabolism, cellular redox state, and anti-stress responses. Cystathionine γ-lyase (CSE) and cystathionine ß-synthase are critical enzymes in the transsulfuration pathway, which also regulate cellular redox status by modulating glutathione (GSH) levels. To determine the link between the integrated stress response and the transsulfuration pathway, we used homocysteine (Hcy) as an inducer of eIF2α phosphorylation and ATF4 gene induction. Mouse embryonic fibroblasts (MEFs) lacking ATF4 (ATF4(-/-)) had reduced GSH levels and increased reactive oxygen species and were susceptible to apoptotic cell death under normal culture conditions. Further, ATF4(-/-) MEFs were more sensitive to Hcy-induced cytotoxicity and showed significantly reduced intracellular GSH levels associated with apoptosis. ATF4(-/-) MEFs could be rescued from l-Hcy-induced apoptosis by ß-mercaptoethanol medium supplementation that increases cysteine levels and restores GSH synthesis. ATF4(-/-) MEFs showed little or no CSE protein but did express cystathionine ß-synthase. Further, ER stress-inducing agents, including tunicamycin and thapsigargin, induced the expression of CSE in ATF4(+/+) MEFs. Consistent with ATF4(-/-) MEFs, CSE(-/-) MEFs showed significantly greater apoptosis when treated with tunicamycin, thapsigargin, and l-Hcy, compared with CSE(+/+) MEFs. Liver and kidney GSH levels were also reduced in CSE(-/-) mice, suggesting that CSE is a critical factor in GSH synthesis and may act to protect the liver and kidney from a variety of conditions that cause ER stress.


Assuntos
Estresse do Retículo Endoplasmático/fisiologia , Fibroblastos/metabolismo , Glutationa/metabolismo , Homocisteína/metabolismo , Liases/metabolismo , Compostos de Sulfidrila/metabolismo , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Animais , Apoptose/fisiologia , Células Cultivadas , Cistationina gama-Liase , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Fibroblastos/citologia , Glutationa/genética , Homocisteína/genética , Rim/metabolismo , Fígado/metabolismo , Liases/genética , Camundongos , Camundongos Knockout , Oxirredução
11.
Int J Emerg Med ; 16(1): 89, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102544

RESUMO

BACKGROUND: The role of the clinical pharmacist in medication reconciliation is well established. Upon patients' admission, the reconciliation service mainly focuses on achieving an accurate and full drug history. This will achieve the best treatment plan and reduce medication discrepancies. Upon the recent implementation of clinical pharmacy services in the emergency department at Alexandria Main University Hospital, medication reconciliation was one of the most important duties that needed to be focused on. We hypothesized that clinical pharmacists are able to achieve patients' drug history lists with higher accuracy than emergency physicians. RESULTS: A total number of 161 patients were included. Age was 58.59 ± (13.78) years, number of comorbidities was 2.39 ± (1.22) and number of home medications was 4.51 ± (2.72). Clinical pharmacists' fulfillment of patients' drug history was significantly more accurate than the emergency physicians (75.16% and 50.3% of the total number of revised patients' profiles respectively). The clinical pharmacists could put a written copy of the accurate patients' drug history list in only 50.93% of the revised patients' profiles. Five hundred eighty-five medication discrepancies were detected which represent an average of 3.63 discrepancies/medication sheet. Medications at Transitions and Clinical Handoffs (MATCH) Toolkit for medication reconciliation and the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) index were used to categorize discrepancies. Categories A, B, and C represented (66.5%), while categories D, E, and F represented (33.5%) of the total discrepancies. There was a significant direct relationship between the total number of discrepancies and both the number of comorbidities and the number of drugs administered before hospital admission. CONCLUSION: The clinical pharmacists are the main members of the emergency health care team. One of their fundamental services is medication reconciliation. The establishment of a complete drug history list and physicians' discussion about the current treatment plan can obviously detect and reduce medication errors. TRIAL REGISTRATION: NCT04395443. Registered 16 May 2020.

12.
Am J Physiol Renal Physiol ; 303(3): F467-81, 2012 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-22592641

RESUMO

Epithelial-to-mesenchymal transition (EMT) contributes to renal fibrosis in chronic kidney disease. Endoplasmic reticulum (ER) stress, a feature of many forms of kidney disease, results from the accumulation of misfolded proteins in the ER and leads to the unfolded protein response (UPR). We hypothesized that ER stress mediates EMT in human renal proximal tubules. ER stress is induced by a variety of stressors differing in their mechanism of action, including tunicamycin, thapsigargin, and the calcineurin inhibitor cyclosporine A. These ER stressors increased the UPR markers GRP78, GRP94, and phospho-eIF2α in human proximal tubular cells. Thapsigargin and cyclosporine A also increased cytosolic Ca(2+) concentration and T cell death-associated gene 51 (TDAG51) expression, whereas tunicamycin did not. Thapsigargin was also shown to increase levels of active transforming growth factor (TGF)-ß1 in the media of cultured human proximal tubular cells. Thapsigargin induced cytoskeletal rearrangement, ß-catenin nuclear translocation, and α-smooth muscle actin and vinculin expression in proximal tubular cells, indicating an EMT response. Subconfluent primary human proximal tubular cells were induced to undergo EMT by TGF-ß1 treatment. In contrast, tunicamycin treatment did not produce an EMT response. Plasmid-mediated overexpression of TDAG51 resulted in cell shape change and ß-catenin nuclear translocation. These results allowed us to develop a two-hit model of ER stress-induced EMT, where Ca(2+) dysregulation-mediated TDAG51 upregulation primes the cell for mesenchymal transformation via Wnt signaling and then TGF-ß1 activation leads to a complete EMT response. Thus the release of Ca(2+) from ER stores mediates EMT in human proximal tubular epithelium via the induction of TDAG51.


Assuntos
Epitélio/metabolismo , Túbulos Renais Proximais/metabolismo , Mesoderma/metabolismo , Fatores de Transcrição/fisiologia , Animais , Cálcio/metabolismo , Linhagem Celular , Forma Celular , Células Cultivadas , Quelantes/farmacologia , Citosol/efeitos dos fármacos , Citosol/metabolismo , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Eletroforese em Gel de Poliacrilamida , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Chaperona BiP do Retículo Endoplasmático , Ensaio de Imunoadsorção Enzimática , Fibrose , Humanos , Indicadores e Reagentes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia de Fluorescência , Plasmídeos/genética , Espectrometria de Fluorescência , Fatores de Transcrição/genética , Transfecção , Fator de Crescimento Transformador beta1/biossíntese , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia , beta Catenina/metabolismo
13.
Pathol Res Pract ; 239: 154132, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36183439

RESUMO

Triple-negative breast cancer (TNBC) is considered about 12-24 % of all breast cancer cases. Patients experience poor overall survival, high recurrence rate, and distant metastasis compared to other breast cancer subtypes. Numerous studies have highlighted the crucial roles of non-coding RNAs (ncRNAs) in carcinogenesis and proliferation, migration, and metastasis of tumor cells in TNBC. Recent research has demonstrated that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play a role in the regulation of the immune system by affecting the tumor microenvironment, the epithelial-mesenchymal transition, the regulation of dendritic cells and myeloid-derived stem cells, and T and B cell activation and differentiation. Immune-related miRNAs and lncRNAs, which have been established as predictive markers for various cancers, are strongly linked to immune cell infiltration and could be a viable therapeutic target for TNBC. In the current review, we discuss the recent updates of ncRNAs, including miRNAs and lncRNAs in TNBC, including their biogenesis, target genes, and biological function of their targets, which are mostly involved in the immune response.


Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/patologia , RNA Longo não Codificante/genética , MicroRNAs/genética , RNA não Traduzido , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica/genética , Microambiente Tumoral
14.
Sci Total Environ ; 806(Pt 4): 151295, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34736754

RESUMO

Food security and water sustainability in arid and semiarid regions are threatened by rapid population growth, declining natural resources, and global climate change. Countries in the arid regions compensate meat import by raising domestic livestock with cultivated green fodder, which diminishes lands for other crops and depletes precious water resources. This study presents for the first time an in-depth integrated food water ecosystem (FWEco) nexus modeling on the feasibility of restoring 10% of Kuwait's desert as grazing rangeland to alleviate water consumption from fodder production. Our results showed that revegetating 10% of the country's land with native species could support up to 23% of domestic livestock through natural grazing at optimal coverage (70%) and high productivity, and decrease water consumption by up to 90%. However, depending solely on natural rainfall is unlikely to achieve the optimal coverage. Strategic supplemental irrigation in the fall season (e.g., October and November) is required to maximize vegetation coverage and enhance food security and water sustainability. Significantly, strategic irrigation results in much lower net water consumption because irrigating native species requires much less water than green fodder cultivation. Therefore, revegetating desert lands with native species to restore their natural grazing service can be a sustainable approach to simultaneously improve food security and water sustainability in arid landscapes.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Produtos Agrícolas , Clima Desértico , Segurança Alimentar , Água
15.
Clin Biochem ; 108: 14-19, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35772500

RESUMO

In this study, we compared the DiaSorin LiaisonXL IGF-1 immunoassay to both the Roche Elecsys IGF-1 immunoassay and to the liquid chromatography-high resolution mass spectrometry (LC-MS) IGF-1 assay. Our study shows a constant positive bias in DiaSorin compared to the Roche immunoassay (mean 42 µg/L, 24%), and a proportional positive bias in DiaSorin compared to the LC-MS method (mean 49 µg/L, 29%). Further, we demonstrate the potential clinical impact of this bias by evaluating 43 adult samples, collected over a 2-month period, which were shown to be discrepant based on a chart review. Despite the positive analytical bias in the Diasorin assay compared to the LC-MS assay, the Diasorin assay upper reference limits were lower than those of the LC-MS assay. This effect caused nine out of forty-three samples to show falsely elevated results when they were clinically diagnosed as negative for acromegaly. Discussed in the context of previous literature, our findings emphasize the importance of adjusting reference intervals for IGF-1 assays based on the clinical needs of a patient population.


Assuntos
Espectrometria de Massas em Tandem , Vitamina D , Adulto , Cromatografia Líquida/métodos , Humanos , Imunoensaio/métodos , Fator de Crescimento Insulin-Like I , Laboratórios Clínicos , Espectrometria de Massas em Tandem/métodos
16.
JAMA Netw Open ; 5(2): e2146798, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35171263

RESUMO

Importance: The incidence of infection during SARS-CoV-2 viral waves, the factors associated with infection, and the durability of antibody responses to infection among Canadian adults remain undocumented. Objective: To assess the cumulative incidence of SARS-CoV-2 infection during the first 2 viral waves in Canada by measuring seropositivity among adults. Design, Setting, and Participants: The Action to Beat Coronavirus study conducted 2 rounds of an online survey about COVID-19 experience and analyzed immunoglobulin G levels based on participant-collected dried blood spots (DBS) to assess the cumulative incidence of SARS-CoV-2 infection during the first and second viral waves in Canada. A sample of 19 994 Canadian adults (aged ≥18 years) was recruited from established members of the Angus Reid Forum, a public polling organization. The study comprised 2 phases (phase 1 from May 1 to September 30, 2020, and phase 2 from December 1, 2020, to March 31, 2021) that generally corresponded to the first (April 1 to July 31, 2020) and second (October 1, 2020, to March 1, 2021) viral waves. Main Outcomes and Measures: SARS-CoV-2 immunoglobulin G seropositivity (using a chemiluminescence assay) by major geographic and demographic variables and correlation with COVID-19 symptom reporting. Results: Among 19 994 adults who completed the online questionnaire in phase 1, the mean (SD) age was 50.9 (15.4) years, and 10 522 participants (51.9%) were female; 2948 participants (14.5%) had self-identified racial and ethnic minority group status, and 1578 participants (8.2%) were self-identified Indigenous Canadians. Among participants in phase 1, 8967 had DBS testing. In phase 2, 14 621 adults completed online questionnaires, and 7102 of those had DBS testing. Of 19 994 adults who completed the online survey in phase 1, fewer had an educational level of some college or less (4747 individuals [33.1%]) compared with the general population in Canada (45.0%). Survey respondents were otherwise representative of the general population, including in prevalence of known risk factors associated with SARS-CoV-2 infection. The cumulative incidence of SARS-CoV-2 infection among unvaccinated adults increased from 1.9% in phase 1 to 6.5% in phase 2. The seropositivity pattern was demographically and geographically heterogeneous during phase 1 but more homogeneous by phase 2 (with a cumulative incidence ranging from 6.4% to 7.0% in most regions). The exception was the Atlantic region, in which cumulative incidence reached only 3.3% (odds ratio [OR] vs Ontario, 0.46; 95% CI, 0.21-1.02). A total of 47 of 188 adults (25.3%) reporting COVID-19 symptoms during phase 2 were seropositive, and the OR of seropositivity for COVID-19 symptoms was 6.15 (95% CI, 2.02-18.69). In phase 2, 94 of 444 seropositive adults (22.2%) reported having no symptoms. Of 134 seropositive adults in phase 1 who were retested in phase 2, 111 individuals (81.8%) remained seropositive. Participants who had a history of diabetes (OR, 0.58; 95% CI, 0.38-0.90) had lower odds of having detectable antibodies in phase 2. Conclusions and Relevance: The Action to Beat Coronavirus study found that the incidence of SARS-CoV-2 infection in Canada was modest until March 2021, and this incidence was lower than the levels of population immunity required to substantially reduce transmission of the virus. Ongoing vaccination efforts remain central to reducing viral transmission and mortality. Assessment of future infection-induced and vaccine-induced immunity is practicable through the use of serial online surveys and participant-collected DBS.


Assuntos
Teste Sorológico para COVID-19/estatística & dados numéricos , COVID-19/epidemiologia , Imunoglobulina G/sangue , Adolescente , Adulto , Idoso , COVID-19/imunologia , Canadá/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Inquéritos e Questionários
17.
Talanta ; 234: 122695, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364491

RESUMO

In this study, we aim to develop an antibiotic-based biosensor platform 'Antibiotsensor' for the specific detection of gram-positive bacteria using vancomycin modified Screen Printed Gold Electrodes (SPGEs). Through this pathway, vancomycin molecules were first functionalized with thiol groups and characterized with quadrupole time of flight (q-TOF) mass spectroscopy analysis. Immobilization of thiolated vancomycin molecules (HS-Van) onto SPGEs was carried out based on self-assembled monolayer (SAM) phenomenon. Electrochemical impedance spectroscopy (EIS) was employed to test the detection and showed a considerable change in impedance value upon the binding of HS-Van molecules onto the electrode surface. Atomic Force Microscopy analysis indicated that SPGE was successfully modified upon the treatment with HS-Van molecules based on the shift in surface roughness from 173 ± 2 nm to 301 ± 3 nm. Fourier Transform Infrared Spectroscopy (FTIR) spectroscopy proved the EIS and AFM results as well by showing characteristic peaks of immobilized HS-Van molecule. As a proof-of-concept, EIS-based susceptibility testing was performed using Escherichia coli, Staphylococcus aureus and Mycobacterium smegmatis bacteria to prove the specificity of obtained SPGE-Van. EIS data showed that the charge transfer resistance (Rct) values changed from 1.08, 1.18 to 26.5, respectively, indicating that vancomycin susceptible S. aureus was successfully attached onto SPGE-Van surface strongly, while vancomycin resistance E. coli and M. smegmatis did not show any significant attachment properties. In addition, different concentration (108-10 CFU/mL) of S. aureus was performed to investigate sensitivity of proposed sensor platform. Limit of detection and limit of quantitation was calculated as 101.58 and 104.81 CFU/mL, respectively. Scanning electron microscopy (SEM) analysis also confirmed that only S. aureus bacteria was attached to the surface in a dense monolayer distribution. We believe that the proposed approach is selective and sensitive towards the whole-cell detection of vancomycin-susceptible bacteria and can be modified for different purposes in the future.


Assuntos
Técnicas Biossensoriais , Vancomicina , Bactérias , Eletrodos , Escherichia coli , Ouro , Staphylococcus aureus , Vancomicina/farmacologia
18.
MethodsX ; 8: 101399, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34430295

RESUMO

Unmanned Aerial Vehicles (UAVs) have started to receive more attention in the ecological field in the past 15 years, as they provide very high-resolution imagery that ranges from meters to millimeters. Very high-resolution multispectral imagery obtained from UAVs can help in assessing and monitoring native desert vegetation. Thus, this study use UAVs to develop a method to estimate the biomass and carbon stock of native desert shrubs. The method integrates different techniques and software to monitor native plants' coverage, biomass, and carbon stock. The techniques used in this work are also applicable for other native desert shrubs in the region and could support ecosystem managers in assessing and monitoring arid ecosystems and restoration and revegetation programs. A three-stage image and data management are discussed, including: (1) fieldwork and image acquisition using UAVs, (2) image pre-processing, and (3) image processing using different techniques and software.•Determining shrub biomass is not restricted to multispectral data only but could be applicable for RGB data since it mainly depends on the DSM and DTM.•Allometric parameters could help in estimating desert shrub biomass which could be measured easily and rapidly using UAV imagery.•SVM Supervised classification could help in distinguishing between native shrubs and grasses.

19.
Plants (Basel) ; 10(5)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068447

RESUMO

The rapid assessment and monitoring of native desert plants are essential in restoration and revegetation projects to track the changes in vegetation patterns in terms of vegetation coverage and structure. This work investigated advanced vegetation monitoring methods utilizing UAVs and remote sensing techniques at the Al Abdali protected site in Kuwait. The study examined the effectiveness of using UAV techniques to assess the structure of desert plants. We specifically examined the use of very-high-resolution aerial imagery to estimate the vegetation structure of Rhanterium epapposum (perennial desert shrub), assess the vegetation cover density changes in desert plants after rainfall events, and investigate the relationship between the distribution of perennial shrub structure and vegetation cover density of annual plants. The images were classified using supervised classification techniques (the SVM method) to assess the changes in desert plants after extreme rainfall events. A digital terrain model (DTM) and a digital surface model (DSM) were also generated to estimate the maximum shrub heights. The classified imagery results show that a significant increase in vegetation coverage occurred in the annual plants after rainfall events. The results also show a reasonable correlation between the shrub heights estimated using UAVs and the ground-truth measurements (R2 = 0.66, p < 0.01). The shrub heights were higher in the high-cover-density plots, with coverage >30% and an average height of 77 cm. However, in the medium-cover-density (MD) plots, the coverage was <30%, and the average height was 52 cm. Our study suggests that utilizing UAVs can provide several advantages to critically support future ecological studies and revegetation and restoration programs in desert ecosystems.

20.
Remote Sens Appl ; 23: 100557, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36568404

RESUMO

Law enforcement and massive media awareness, limiting the anthropogenic disturbance, is the way to go for implementing successful desert native vegetation recovery plans. A lesson learned on the resiliency of desert ecosystems throughout studying the native vegetation coverage in the Wadi Al-Batin desert ecosystem during the COVID-19 pandemic. Wadi Al-Batin tri-state desert (89,315 km2) covers the South-western part of Iraq, State of Kuwait, and the North-eastern part of Saudi Arabia. In this study, the spatiotemporal changes in vegetation coverage was detected, by using Sentinel-2A imageries, during the period from 2017 to 2020. For better understanding the impact of associated law enforcement and media practices during COVID-19 pandemic, native vegetation coverage of years with relevant rainfall records were compared. The results revealed that despite receiving the least amount of rain of the three years (≤93 mm), the COVID-19 year (2020) had the highest native vegetation coverage at 28.5% compared with 6% in 2017, and 2% in 2018. These results prove that the main drivers of desert vegetation deterioration are anthropogenic activities, such as quarrying, overgrazing, distractive camping, and off-road vehicle movements. Moreover, the estimated 63% vegetation coverage in Wadi Al-Batin desert in 2019 assures the significant role of precipitation in desert vegetation recovery. This bulk increase in vegetation coverage detected during COVID-19 pandemic shows that the desert vegetation adapts to harsh environments (low rainfall) and rapidly recovers once the source of the disturbance was removed by enforcing the environmental rules. Thus, the protection of natural resources and ecosystems can be achieved through the synergy between governments and civil communities, including intensive awareness of environmental impacts via media, enforcing environmental regulations, and promoting regional collaboration.

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