RESUMEN
Acute respiratory distress syndrome (ARDS) is associated with high mortality rates, which are further exacerbated when accompanied by acute kidney injury (AKI). Presently, there is a lack of comprehensive studies thoroughly elucidating the metabolic dysregulation in ARDS patients with AKI leading to poor outcomes. We hypothesized that metabolomics can be a potent tool to highlight the differences in the metabolic profile unraveling unidentified pathophysiological mechanisms of ARDS patients with and without AKI. 1H nuclear magnetic resonance spectroscopy was used to identify key metabolites in the serum samples of 75 patients. Distinct clusters of both groups were obtained as the study's primary outcome using multivariate analysis. Notable alternations in the levels of nine metabolites were identified. Pathway analysis revealed the dysregulation of five significant cycles, which resulted in various complications, such as hyperammonemia, higher energy requirements, and mitochondrial dysfunction causing oxidative stress. Identified metabolites also showed a significant correlation with clinical scores, indicating severity. This study shows the alterations in the metabolite concentration highlighting the difference in the pathophysiology of both patient groups and its association with outcome, pointing in the direction of a personalized medicine approach and holding significant promise for application in critical care settings to improve clinical outcomes.
RESUMEN
The interactions between glycosaminoglycans (GAGs) and proteins are essential in numerous biochemical processes that involve ion-pair interactions. However, there is no evidence of direct and specific interactions between GAGs and collagen proteins in native cartilage. The resolution of solid-state NMR (ssNMR) can offer such information but the detection of GAG interactions in cartilage is limited by the sensitivity of the experiments when 13C and 15N isotopes are at natural abundance. In this communication, this limitation is overcome by taking advantage of dynamic nuclear polarization (DNP)-enhanced magic-angle spinning (MAS) experiments to obtain two-dimensional (2D) 15N-13C and 13C-13C correlations on native samples at natural abundance. These experiments unveiled inter-residue correlations in the aliphatic regions of the collagen protein previously unobserved. Additionally, our findings provide direct evidence of charge-pair salt-bridge interactions between negatively charged GAGs and positively charged arginine (Arg) residues of collagen protein. We also identified potential hydrogen bonding interactions between hydroxyproline (Hyp) and GAGs, offering atomic insights into the biochemical interactions within the extracellular matrix of native cartilage. Our approach may provide a new avenue for the structural characterization of other native systems.
Asunto(s)
Cartílago , Colágeno , Glicosaminoglicanos , Resonancia Magnética Nuclear Biomolecular , Colágeno/química , Colágeno/metabolismo , Glicosaminoglicanos/química , Glicosaminoglicanos/metabolismo , Cartílago/metabolismo , Cartílago/química , Animales , Hidroxiprolina/química , Enlace de Hidrógeno , Sales (Química)/químicaRESUMEN
Body fluids, cells, and tissues contain a wide variety of metabolites that consist of a mixture of various low-molecular-weight compounds, including amino acids, peptides, lipids, nucleic acids, and organic acids, which makes comprehensive analysis more difficult. Quantitative nuclear magnetic resonance (NMR) spectroscopy is a well-established analytical technique for analyzing the metabolic profiles of body fluids, cells, and tissues. It enables fast and comprehensive detection, characterization, a high level of experimental reproducibility, minimal sample preparation, and quantification of various endogenous metabolites. In recent times, NMR-based metabolomics has been appreciably utilized in diverse branches of medicine, including microbiology, toxicology, pathophysiology, pharmacology, nutritional intervention, and disease diagnosis/prognosis. In this review, the utility of NMR-based metabolomics in clinical studies is discussed. The significance of in vitro NMR-based metabolomics as an effective tool for detecting metabolites and their variations in different diseases are discussed, together with the possibility of identifying specific biomarkers that can contribute to early detection and diagnosis of disease.
Asunto(s)
Imagen por Resonancia Magnética , Metabolómica , Reproducibilidad de los Resultados , Espectroscopía de Resonancia Magnética/métodos , Metabolómica/métodos , MetabolomaRESUMEN
Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively, p = 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23-4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 (p = 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641.
Asunto(s)
COVID-19 , Trasplante de Órganos , Vacunas , Adulto , Humanos , Ad26COVS1 , Vacuna BNT162 , COVID-19/prevención & control , SARS-CoV-2 , Receptores de Trasplantes , Inmunoglobulina G , Anticuerpos AntiviralesRESUMEN
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been raging since the end of 2019 and has shown worse outcomes in solid organ transplant (SOT) recipients. The clinical differences as well as outcomes between respiratory viruses have not been well defined in this population. METHODS: This is a retrospective cohort study of adult SOT recipients with nasopharyngeal swab or bronchoalveolar lavage PCR positive for either SARS-CoV-2, seasonal coronavirus, respiratory syncytial virus (RSV) or influenza virus from January 2017 to October 2020. The follow up period was 3 months. Clinical characteristics and outcomes were evaluated. RESULTS: A total of 377 recipients including 157 SARS-CoV-2, 70 seasonal coronavirus, 50 RSV and 100 influenza infections were identified. The most common transplanted organ was kidney 224/377 (59.4%). Lower respiratory tract infection (LRTI) was found in 210/377 (55.7%) and the risk factors identified with multivariable analysis were SARS-CoV-2 infection, steroid use, and older age. Co- and secondary infections were seen in 77/377 (20.4%) recipients with bacterial pathogens as dominant. Hospital admission was seen in 266/377 (67.7%) recipients without significant statistical difference among viruses, however, ICU admission, mechanical ventilation and mortality were higher with SARS-CoV-2 infection. In the multivariable model, the risk factors for mortality were SARS-CoV-2 infection and older age. CONCLUSIONS: We found higher incidence of ICU admission, mechanical ventilation, and mortality among SARS-CoV-2 infected recipients. Older age was found to be the risk factor for lower respiratory tract infection and mortality for SARS-CoV-2, coronaviruses, RSV and influenza virus groups.
Asunto(s)
COVID-19 , Gripe Humana , Trasplante de Órganos , Infecciones por Virus Sincitial Respiratorio , Infecciones del Sistema Respiratorio , Adulto , Humanos , SARS-CoV-2 , Gripe Humana/etiología , Estudios Retrospectivos , Estaciones del Año , Trasplante de Órganos/efectos adversos , Virus Sincitiales Respiratorios , Receptores de TrasplantesRESUMEN
We present experimental results using a swept-wavelength external cavity quantum cascade laser (swept-ECQCL) diagnostic to measure broadband absorption spectra over a range of 920-1180c m -1 (8.47-10.87 µm) with 2 ms temporal resolution in premixed hydrogen/oxygen flames propagating inside an enclosed chamber. Broadband spectral fits are used to determine time-resolved temperatures and column densities of H 2 O produced during combustion. Modeling of the flowfield within the test chamber under both equilibrium conditions and using a 1D freely propagating flame model is compared with the experiment in terms of temporal dynamics, temperatures, and H 2 O column density. Outputs from the numerical models were used to simulate radiative transport through an inhomogeneous combustion region and evaluate the performance of the spectral fitting model. Simulations show that probing hot-band H 2 O transitions in the high-temperature combustion regions minimizes errors due to spatial inhomogeneity. Good agreement is found between the experimental and modeling results considering experimental uncertainties and model assumptions.
RESUMEN
OBJECTIVE: An early metabolic signature associated with the responsiveness to treatment can be useful in the better management of septic shock patients. This would help clinicians in designing personalized treatment protocols for patients showing non-responsiveness to treatment. METHODS: We analyzed the serum on Day 1 (n = 60), Day 3 (n = 47), and Day 5 (n = 26) of patients with septic shock under treatment using NMR-based metabolomics. Partial least square discriminant analysis (PLS-DA) was performed to generate the list of metabolites that can be identified as potential disease biomarkers having statistical significance (that is, metabolites that had a VIP score > 1, and p value < 0.05, False discovery rate (FDR) < 0.05). RESULTS: Common significant metabolites amongst the three time points were obtained that distinguished the patients being responsive (R) and non-responsive (NR) to treatments, namely 3 hydroxybutyrate, lactate, and phenylalanine which were lower, whereas glutamate and choline higher in patients showing responsiveness. DISCUSSION: The study gave these metabolic signatures identifying patients' responsiveness to treatment. The results of the study will aid in the development of targeted therapy for ICU patients.
Asunto(s)
Choque Séptico , Humanos , Choque Séptico/metabolismo , Pronóstico , Biomarcadores , Unidades de Cuidados Intensivos , Ácido LácticoRESUMEN
Bone is a living tissue made up of organic proteins, inorganic minerals, and water. The organic component of bone (mainly made up of Type-I collagen) provides flexibility and tensile strength. Solid-state nuclear magnetic resonance (ssNMR) is one of the few techniques that can provide atomic-level structural insights of such biomaterials in their native state. In the present article, we employed the variable contact time cross-polarization (1 H-13 C CP) kinetics experiments to study the hydration-dependent atomic-level structural changes in the bone extracellular matrix (ECM). The natural abundant 13 C CP intensity of the bone ECM is measured by varying CP contact time and best fitted to the nonclassical kinetic model. Different relaxation parameters were measured by the best-fit equation corresponding to the different hydration conditions of the bone ECM. The associated changes in the measured parameters due to varying levels of hydration observed at different sites of collagen protein have provided its structural arrangements and interaction with water molecules in bone ECM. Overall, the present study reveals a better understanding of the kinetics of the organic part inside the bone ECM that will help in comprehending the disease-associated pathways.
Asunto(s)
Huesos , Matriz Extracelular , Cinética , Matriz Extracelular/metabolismo , Colágeno/química , Agua/químicaRESUMEN
BACKGROUND: Growth retardation, malnutrition, and failure to thrive are some of the consequences associated with congenital heart diseases. Several metabolic factors such as hypoxia, anoxia, and several genetic factors are believed to alter the energetics of the heart. Timely diagnosis and patient management is one of the major challenges faced by the clinicians in understanding the disease and provide better treatment options. Metabolic profiling has shown to be potential diagnostic tool to understand the disease. OBJECTIVE: The present experiment was designed as a single center observational pilot study to classify and create diagnostic metabolic signatures associated with the energetics of congenital heart disease in cyanotic and acyanotic groups. METHODS: Metabolic sera profiles were obtained from 35 patients with cyanotic congenital heart disease (TOF) and 23 patients with acyanotic congenital heart disease (ASD and VSD) using high resolution 1D 1H NMR spectra. Univariate and multivariate statistical analysis were performed to classify particular metabolic disorders associated with cyanotic and acyanotic heart disease. RESULTS: The results show dysregulations in several metabolites in cyanotic CHD patients versus acyanotic CHD patients. The discriminatory metabolites were further analyzed with area under receiver operating characteristic (AUROC) curve and identified four metabolic entities (i.e. mannose, hydroxyacetone, myoinositol, and creatinine) which could differentiate cyanotic CHDs from acyanotic CHDs with higher specificity. CONCLUSION: An untargeted metabolic approach proved to be helpful for the detection and distinction of disease-causing metabolites in cyanotic patients from acyanotic ones and can be useful for designing better and personalized treatment protocol.
Asunto(s)
Cardiopatías Congénitas , Humanos , Cianosis/etiología , Cianosis/metabolismo , Hipoxia/complicaciones , Biomarcadores/metabolismo , MetabolomaRESUMEN
Metabolic reprogramming, a key hallmark of cancer, plays a pivotal role in fulfilling the accelerated biological demands of tumor cells. Such metabolic changes trigger the production of several proinflammatory factors, thereby inciting cancer development and its progression. Serine protease inhibitor Kazal Type 1 (SPINK1), well known for its oncogenic role and its upregulation via acute-phase reactions, is highly expressed in multiple cancers including colorectal cancer (CRC). Here, we show accumulation of lipid droplets in CRC cells stained with Oil Red O upon SPINK1 silencing. Furthermore, NMR spectroscopy analysis revealed an accretion of monounsaturated fatty acids (MUFAs) and phosphatidylcholine in these CRC cells, while the levels of polyunsaturated fatty acids remained unaltered. This alteration indicates the presence of MUFAs with the triglycerides in the lipid droplets as observed in SPINK1-silenced CRC cells. Considering the role of MUFAs in the anti-inflammatory response, our data hint that suppression of SPINK1 in CRC leads to activation of an anti-inflammatory signaling milieu. Conclusively, our study uncovers a connection between lipid metabolism and SPINK1-mediated CRC progression, hence paving the way for further exploration and better prognosis of SPINK1-positive CRC patients.
Asunto(s)
Neoplasias Colorrectales , Metabolismo de los Lípidos , Inhibidor de Tripsina Pancreática de Kazal , Neoplasias Colorrectales/patología , Ácidos Grasos Monoinsaturados/metabolismo , Humanos , Espectroscopía de Resonancia Magnética , Inhibidor de Tripsina Pancreática de Kazal/metabolismoRESUMEN
Solid organ transplant (SOT) recipients are at high risk for severe disease with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Emerging variants of concern have disproportionately affected this population. Data on severity and outcomes with the Omicron variant in SOT recipients are limited. Thus we conducted this single-center, retrospective cohort study of SOT recipients diagnosed with SARS-CoV-2 infection from December 18, 2021 to January 18, 2022, when prevalence of the Omicron variant was more than 80%-95% in the community. Univariate and multivariate logistic regression analysis was performed to identify risk factors for hospital admission. We identified 166 SOT patients: 112 (67.5%) kidney, 22 (13.3%) liver, 10 (6.0%) lung, seven (4.2%) heart, and 15 (9.0%) combined transplants. SARS-CoV-2 vaccine series was completed in 59 (35.5%) recipients. Ninety-nine (59.6%) and 13 (7.8%) recipients received casirivimab/imdevimab and sotrovimab, respectively. Fifty-three (32%) recipients required hospital admission, of which 19 (35.8%) required intensive care unit level of care. Median follow-up was 50 (interquartile range, 25-59) days, with mortality reported in six (3.6%) patients. Risk factors identified for hospital admission were African American race (p < .001, odds ratio [OR] 4.00, 95% confidence interval [CI] 1.84-8.70), history of coronary artery disease (p = .031, OR 3.50, 95% CI 1.12-10.87), and maintenance immunosuppression with corticosteroids (p = .048, OR 2.00, 95% CI 1.01-4.00). In conclusion, contrary to that in the general population, we found a higher hospital admission rate in SOT recipients with omicron variant infection. Further studies to investigate the efficacy of newer treatments are necessary, even as outcomes continue to improve.
Asunto(s)
COVID-19 , Trasplante de Órganos , Humanos , COVID-19/epidemiología , Vacunas contra la COVID-19 , Estudios Retrospectivos , SARS-CoV-2 , Trasplante de Órganos/efectos adversos , Receptores de TrasplantesRESUMEN
Complications of the bronchial anastomosis in lung transplantation, once the Achilles heel of the procedure, have become quite rare. The surgical technique is well established and safe. Risks contributing to anastomotic complications are primarily related to patients pre-existing conditions. The key factor is good blood flow to the bronchial stump. Postoperative infection can also contribute to the breakdown of the anastomosis. This may be the reason why different immunosuppressive regimes lead to differences in the incidence of bronchial dehiscence.
Asunto(s)
Trasplante de Pulmón , Anastomosis Quirúrgica/métodos , Bronquios/cirugía , Humanos , Inmunosupresores , Trasplante de Pulmón/efectos adversos , Trasplante de Pulmón/métodos , Factores de RiesgoRESUMEN
BACKGROUND: Visualizing and quantifying cellular heterogeneity is of central importance to study tissue complexity, development, and physiology and has a vital role in understanding pathologies. Mass spectrometry-based methods including imaging mass cytometry (IMC) have in recent years emerged as powerful approaches for assessing cellular heterogeneity in tissues. IMC is an innovative multiplex imaging method that combines imaging using up to 40 metal conjugated antibodies and provides distributions of protein markers in tissues with a resolution of 1 µm2 area. However, resolving the output signals of individual cells within the tissue sample, i.e., single cell segmentation, remains challenging. To address this problem, we developed MATISSE (iMaging mAss cyTometry mIcroscopy Single cell SegmEntation), a method that combines high-resolution fluorescence microscopy with the multiplex capability of IMC into a single workflow to achieve improved segmentation over the current state-of-the-art. RESULTS: MATISSE results in improved quality and quantity of segmented cells when compared to IMC-only segmentation in sections of heterogeneous tissues. Additionally, MATISSE enables more complete and accurate identification of epithelial cells, fibroblasts, and infiltrating immune cells in densely packed cellular areas in tissue sections. MATISSE has been designed based on commonly used open-access tools and regular fluorescence microscopy, allowing easy implementation by labs using multiplex IMC into their analysis methods. CONCLUSION: MATISSE allows segmentation of densely packed cellular areas and provides a qualitative and quantitative improvement when compared to IMC-based segmentation. We expect that implementing MATISSE into tissue section analysis pipelines will yield improved cell segmentation and enable more accurate analysis of the tissue microenvironment in epithelial tissue pathologies, such as autoimmunity and cancer.
Asunto(s)
Citometría de Imagen , Biomarcadores , Espectrometría de Masas , Microscopía FluorescenteRESUMEN
BACKGROUND: Several computational methods have been developed that integrate transcriptomics data with genome-scale metabolic reconstructions to increase accuracy of inferences of intracellular metabolic flux distributions. Even though existing methods use transcript abundances as a proxy for enzyme activity, each method uses a different hypothesis and assumptions. Most methods implicitly assume a proportionality between transcript levels and flux through the corresponding function, although these proportionality constant(s) are often not explicitly mentioned nor discussed in any of the published methods. E-Flux is one such method and, in this algorithm, flux bounds are related to expression data, so that reactions associated with highly expressed genes are allowed to carry higher flux values. RESULTS: Here, we extended E-Flux and systematically evaluated the impact of an assumed proportionality constant on model predictions. We used data from published experiments with Escherichia coli and Saccharomyces cerevisiae and we compared the predictions of the algorithm to measured extracellular and intracellular fluxes. CONCLUSION: We showed that detailed modelling using a proportionality constant can greatly impact the outcome of the analysis. This increases accuracy and allows for extraction of better physiological information.
Asunto(s)
Fenómenos Bioquímicos , Modelos Biológicos , Escherichia coli/genética , Redes y Vías Metabólicas/genética , Saccharomyces cerevisiae/genética , TranscriptomaRESUMEN
Recent advances in technology have led to significantly greater use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation with better outcomes. The novel ProtekDuo veno-venous ECMO (CardiacAssist, Inc.) has gained significance as it facilitates effective decompression of the right heart in patients with acute decompensation, while also providing consistent and effective gas exchange by eliminating recirculation. Here, we report two cases of effectively using ProtekDuo veno-venous ECMO: one case as a bridge to lung transplantation and another case as a bridge to heart-lung transplantation.
Asunto(s)
Oxigenación por Membrana Extracorpórea , Trasplante de Corazón-Pulmón , Trasplante de Pulmón , Humanos , Resultado del TratamientoRESUMEN
Solid-state nuclear magnetic resonance is a promising technique to probe bone mineralization and interaction of collagen protein in the native state. However, many of the developments are hampered due to the low sensitivity of the technique. In this article, we report solid-state nuclear magnetic resonance (NMR) experiments using the newly developed BioSolids CryoProbe™ to access its applicability for elucidating the atomic-level structural details of collagen protein in native state inside the bone. We report here approximately a fourfold sensitivity enhancement in the natural abundance 13 C spectrum compared with the room temperature conventional solid-state NMR probe. With the advantage of sensitivity enhancement, we have been able to perform natural abundance 15 N cross-polarization magic angle spinning (CPMAS) and two-dimensional (2D) 1 H-13 C heteronuclear correlation (HETCOR) experiments of native collagen within a reasonable timeframe. Due to high sensitivity, 2D 1 H/13 C HETCOR experiments have helped in detecting several short and long-range interactions of native collagen assembly, thus significantly expanding the scope of the method to such challenging biomaterials.
Asunto(s)
Matriz Ósea/química , Colágeno/química , Animales , Isótopos de Carbono/química , Fémur/química , Cabras , Isótopos de Nitrógeno/química , Resonancia Magnética Nuclear Biomolecular/métodosRESUMEN
Acute respiratory distress syndrome (ARDS), manifested by intricate etiology and pathophysiology, demands careful clinical surveillance due to its high mortality and imminent life support measures. NMR based metabolomics provides an approach for ARDS which culminates from a wide spectrum of illness thereby confounding early manifestation and prognosis predictors. 1 H NMR with its manifold applications in critical disease settings can unravel the biomarker of ARDS thus holding potent implications by providing surrogate endpoints of clinical utility. NMR metabolomics which is the current apogee platform of omics trilogy is contributing towards the possible panacea of ARDS by subsequent validation of biomarker credential on larger datasets. In the present review, the physiological derangements that jeopardize the whole metabolic functioning in ARDS are exploited and the biomarkers involved in progression are addressed and substantiated. The following sections of the review also outline the clinical spectrum of ARDS from the standpoint of NMR based metabolomics which is an emerging element of systems biology. ARDS is the main premise of intensivists textbook, which has been thoroughly reviewed along with its incidence, progressive stages of severity, new proposed diagnostic definition, and the preventive measures and the current pitfalls of clinical management. The advent of new therapies, the need for biomarkers, the methodology and the contemporary promising approaches needed to improve survival and address heterogeneity have also been evaluated. The review has been stepwise illustrated with potent biometrics employed to selectively pool out differential metabolites as diagnostic markers and outcome predictors. The following sections have been drafted with an objective to better understand ARDS mechanisms with predictive and precise biomarkers detected so far on the basis of underlying physiological parameters having close proximity to diseased phenotype. The aim of this review is to stimulate interest in conducting more studies to help resolve the complex heterogeneity of ARDS with biomarkers of clinical utility and relevance.
Asunto(s)
Biomarcadores/metabolismo , Espectroscopía de Resonancia Magnética , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/metabolismo , Animales , Cuidados Críticos , Humanos , Metabolómica , Análisis Multivariante , Síndrome de Dificultad Respiratoria/epidemiología , Síndrome de Dificultad Respiratoria/fisiopatologíaRESUMEN
Coronary artery disease (CAD) is a pathology often found in patients with end-stage lung disease. Although in the past CAD might have been considered an absolute contraindication, modern revascularization techniques have helped increase the number of transplants performed in this population. However, discrepancies in the guidelines for perioperative evaluation and risk mitigation strategies for the ischemic cardiac burden are present in the current literature. This is a review of the available data regarding perioperative evaluation, revascularization tactics, postoperative management, and survival rate that patients with different grades of coronary artery disease present after lung transplantation.
Asunto(s)
Enfermedad de la Arteria Coronaria , Trasplante de Pulmón , Contraindicaciones , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/cirugía , Humanos , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The study of structural and dynamical properties of lipid and its associated interaction with different components of bone is essential to understand its role at a different level of bone homeostasis such as bone mineralization and bone metabolism. In this article, we present water-dependent dynamical changes observed in lipids (triglycerides) in its absolute native environment inside bone by high-resolution 1H solid-state nuclear magnetic resonance spectroscopy (ssNMR). Relaxation measurement (T2 measurement) ssNMR experiments were performed at different levels of water network induced by dehydration and H/D exchange in native bone. Our measurements reflect the changes in the local environment and dynamical properties of triglyceride due to different hydration levels. The present study explains the role of water in stabilizing the structural properties of triglycerides in bone hence will help understand its pathological role associated with bone physiology and bone disorders.
Asunto(s)
Fémur/metabolismo , Metabolismo de los Lípidos , Espectroscopía de Resonancia Magnética , Agua/metabolismo , Animales , CabrasRESUMEN
Hydroxychloroquine and chloroquine are medications that have been used for a long time. Their most common use is for the treatment and prophylaxis of malaria. However, these antimalarial drugs are known to also have anti-inflammatory and antiviral effects and are used for several chronic diseases such as systemic lupus erythematosus with low adverse effects. The antiviral action of hydroxychloroquine and chloroquine has been a point of interest to different researchers due to its mechanism of action. Several in vitro studies have proven their effectiveness on severe acute respiratory syndrome virus and currently both in vitro and in vivo studies have been conducted on 2019 novel coronavirus (covid-19). The purpose of this article is to review the history and mechanism of actions of these drugs and the potential use they can have on the current covid-19 pandemic.