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1.
Radiat Res ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38964743

RESUMEN

Preparation for medical responses to major radiation accidents, further driven by increases in the threat of nuclear warfare, has led to a pressing need to understand the underlying mechanisms of radiation injury (RI) alone or in combination with other trauma (combined injury, CI). The identification of these mechanisms suggests molecules and signaling pathways that can be targeted to develop radiation medical countermeasures. Thus far, the United States Food and Drug Administration (U.S. FDA) has approved six countermeasures to mitigate hematopoietic acute radiation syndrome (H-ARS), but no drugs are available for prophylaxis and no agents have been approved to combat the other sub-syndromes of ARS, let alone delayed effects of acute radiation exposure or the effects of combined injury. From its inception, Radiation Research has significantly contributed to the understanding of the underlying mechanisms of radiation injury and combined injury, and to the development of radiation medical countermeasures for these indications through the publication of peer-reviewed research and review articles.

2.
Research (Wash D C) ; 7: 0405, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38952996

RESUMEN

The menace of drought has persistently loomed over global crop production, posing a serious threat to agricultural sustainability. Research on drought stress highlights the important role of the phytohormone abscisic acid (ABA) in orchestrating plant responses to drought conditions. ABA regulates various drought/dehydration-responsive genes, initiates stomatal closure, and influences cellular responses to drought stress. Additionally, plants employ a phosphate starvation response (PSR) mechanism to manage phosphate (Pi) deficiency, with ABA playing a role in its regulation. However, despite intensive research in these fields, the precise connection among PSRs, drought stress, and ABA signaling still needs to be determined. Recently, PSR-related gene induction has been reported to occur before the induction of ABA-responsive genes under progressive mild drought. Mild drought decreases Pi uptake and contents in plants, triggering PSRs, which play an important role in plant growth during mild drought. Both ABA-responsive and PSR-related gene expression could indicate plant perception of external moisture conditions. Thus, integrating the information regarding their associated gene expression with soil moisture contents and thermographic data can enable timely irrigation optimization to mitigate the effect of drought on crop productivity.

3.
Sci Total Environ ; 947: 174705, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39002586

RESUMEN

Groundwater irrigation districts, which play a crucial role in the Earth's critical zone, are confronted with numerous challenges, including water scarcity, pollution, and ecological degradation. These issues come from multiple systems and are linked to a groundwater-dominated water-food-environment-ecosystem nexus problem related to agricultural activities (WFEE). There is a pressing need for the scientific characterization and evaluation of the WFEE nexus in groundwater irrigation districts to assure high-quality, sustainable development. Furthermore, it is critical to provide practical and efficient regulations at the farmer level to uphold the health of this nexus. This paper presents a mapping network that focuses on groundwater irrigation districts. The network aims to convert the restriction indicators utilized to maintain the health of the WFEE nexus (at the irrigation district scale) into the targets employed to manage farmers' living and agricultural activities (at the farmer scale). Additionally, a system dynamics model is created to track and manage the interacting relationships between the WFEE nexus and farmers' living and agricultural activities. This proposed model employs a structured parameter system comprising targets, state parameters, regulatory parameters, and evaluation parameters. This system can get insight into the status of the WFEE nexus at the farmer level using state parameters, induce tailored management and regulation measures using regulatory parameters, assess the effectiveness of various measures using the evaluation parameters, and finally provide decision support to enhance the health of the WFEE nexus. The findings from the research conducted in the Yong'an groundwater irrigation district demonstrated that the model accurately described the relationship between the WFEE nexus and farmers' activities in groundwater irrigation districts. Furthermore, the model responded strongly to a variety of improvement strategies, including adjustments in planting area, optimization of planting pattern, improvement of irrigation method, and implementation of agronomic measures. As a result, it provided farmers with decision support for applying agricultural management methods and addressing the WFEE nexus problem in groundwater irrigation areas.

4.
J Fluoresc ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39037679

RESUMEN

Recently, the 5-HT7 receptor has achieved greater attention in research fraternity due to the involvement of neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) in several neurological disorders. Targeting this neuroreceptor, we have synthesized six compounds named as butyl-benzoxazolone substituted piperazinium derivatives (BBOP) derivatives, abbreviated as L1-L6. These compounds have been evaluated for their binding interaction with BSA through photophysical and in-silico approaches. The UV absorption of these compounds with BSA at λmax = 280 nm, showed an optical density (O.D.) in the range of 0.5-0.9, i.e., 21%-53% (L1max = 1.4, L5min = 0.7385) at varied concentrations (17 µM-114 µM). For fluorescence studies, the Ksv value varied inversely with temperature, which confirmed the static mechanism of quenching with L1 showing maximum quenching. The parameters (ΔH, ΔS) obtained from the thermodynamic study for interaction between BSA and L1-L6 were correlated with in-silico (molecular docking) data. The in-silico docking study showed hydrophobic and the Van der Waals forces were the most significant forces. Amino acid residues ARG 217 & TRP 213 (Sudlow Site I) and LYS 116 & GLU 125 (Sudlow Site II) of BSA were primarily involved in H-bonding.Furthermore, the catalytic activity of BSA for hydrolyzingdifferent chemical entities have monitored in the presence of L1-L6 through esterase-like assay with p-NPA as a substrate, to get more insight about the interaction with catalytic residues (LYS 414, LYS 413, and TYR 411) in BSA at site II. These findings showed the potential of these 5-HT7 markers as promising ligands with appropriate drug likeliness characteristics.

5.
J Phys Condens Matter ; 36(41)2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38959912

RESUMEN

The biosensing industry has seen exponential growth in the past decade. Impact of biosensors in the current scenario cannot be overlooked. Cardiovascular diseases (CvDs) have been recognized as one of the major causes for millions of deaths globally. This mortality can be minimized by early and accurate detection/diagnosis of CvDs with the help of biosensing devices. This also presents a global market opportunity for the development of biosensors for CvDs. A vast variety of biosensing methods and devices have been developed for this problem. Most of commercially available platforms for CvD detection rely on optical (fluorometric and colorimetric analysis) techniques using serum biomarkers since optical testing is the gold standard in medical diagnosis. Field effect transistors-based biosensors, termed as Bio-FETs, are the upcoming devices for blood or serum analyte detection due to excellent sensitivity, low operational voltage, handheld device structure and simple chip-based operation. Further, the discovery of two dimensional (2D) materials and their integration with conventional FETs has improved the overvoltage problem, sensitivity and strict operating conditions as compared to conventional FETs. Graphene-FETs based biosensing devices have been proven as promising candidates due to their attractive properties. Despite the severe threat of CvDs which has further increased in post-covid era, the Bio-FET sensor studies in literature are still rare. In this review, we aim to provide a comprehensive view of all the multidisciplinary concepts related to 2D-BioFETs for CvDs. A critical review of the different platforms has been covered with detailed discussions of related studies to provide a clear concept and present status of 2D-BioFETs based CvD biosensors.


Asunto(s)
Técnicas Biosensibles , Enfermedades Cardiovasculares , Transistores Electrónicos , Enfermedades Cardiovasculares/diagnóstico , Humanos , Técnicas Biosensibles/instrumentación , Grafito/química
6.
RSC Adv ; 14(26): 18777-18786, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38867735

RESUMEN

This study focuses on the synthesis and characterization of Ho3+ doped Ca3(VO4)2 phosphor for potential application in solid-state lighting technology. A citrate-based sol-gel process is optimized to achieve sheet-like morphologies in the phosphor material. The investigation reveals UV absorption at 371 nm, indicating a band gap of 3.28 eV. Emission transitions at (506, 541, and 651) nm are observed when excited at 451 nm, with an optimal Ho3+ concentration of 0.05 mol resulting in robust green emission at 541 nm. The concentration quenching in Ca3(VO4)2:xHo3+ phosphors is discussed in detail with Blesse's and Dexter's models. The concentration quenching effect found in the studied samples is due to the dipole-dipole interactions. Judd-Ofelt intensity parameters were calculated from the excitation bands, and for Ω 2, Ω 4, and Ω 6 are (0.16, 0.17, and 0.36) × 10-20 cm2, respectively. The emission properties for the (5S2 + 5F4) → 5I8 and 5F5 → 5I8 transitions are also estimated with J-O parameters. The higher magnitude of branching ratios (83%) and emission cross-sections (1.6 × 10-21 cm2) suggest that the Ca3(VO4)2:0.05Ho3+ phosphor materials may be suitable for efficient green-emitting device applications. The CIE coordinates confirm the potential of Ho3+-doped phosphors for green emissions, making them suitable for solid-state lighting and display technology.

8.
Sci Rep ; 14(1): 13571, 2024 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-38866887

RESUMEN

The identification and validation of radiation biomarkers is critical for assessing the radiation dose received in exposed individuals and for developing radiation medical countermeasures that can be used to treat acute radiation syndrome (ARS). Additionally, a fundamental understanding of the effects of radiation injury could further aid in the identification and development of therapeutic targets for mitigating radiation damage. In this study, blood samples were collected from fourteen male nonhuman primates (NHPs) that were exposed to 7.2 Gy ionizing radiation at various time points (seven days prior to irradiation; 1, 13, and 25 days post-irradiation; and immediately prior to the euthanasia of moribund (preterminal) animals). Plasma was isolated from these samples and was analyzed using a liquid chromatography tandem mass spectrometry approach in an effort to determine the effects of radiation on plasma proteomic profiles. The primary objective was to determine if the radiation-induced expression of specific proteins could serve as an early predictor for health decline leading to a preterminal phenotype. Our results suggest that radiation induced a complex temporal response in which some features exhibit upregulation while others trend downward. These statistically significantly altered features varied from pre-irradiation levels by as much as tenfold. Specifically, we found the expression of integrin alpha and thrombospondin correlated in peripheral blood with the preterminal stage. The differential expression of these proteins implicates dysregulation of biological processes such as hemostasis, inflammation, and immune response that could be leveraged for mitigating radiation-induced adverse effects.


Asunto(s)
Rayos gamma , Macaca mulatta , Proteómica , Animales , Rayos gamma/efectos adversos , Masculino , Proteómica/métodos , Biomarcadores/sangre , Irradiación Corporal Total/efectos adversos , Síndrome de Radiación Aguda/sangre , Síndrome de Radiación Aguda/etiología , Proteínas Sanguíneas/análisis , Proteínas Sanguíneas/metabolismo , Proteoma/análisis , Proteoma/metabolismo
10.
Multidiscip Respir Med ; 192024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38836339

RESUMEN

BACKGROUND: Pulmonary fibrosis is a chronic, progressive lung condition that involves lung tissue scarring and thickening. The effects of home-based pulmonary rehabilitation (PR) in post-covid pulmonary fibrosis (PCPF) and other forms of fibrosis together have not been evaluated. This study aims to evaluate the effectiveness of home-based pulmonary rehabilitation on pulmonary function, functional capacity, and health-related quality of life in people with pulmonary fibrosis (post-COVID pulmonary fibrosis, pulmonary fibrosis secondary to pulmonary tuberculosis (TB), pulmonary fibrosis secondary to interstitial lung disease (ILD), pulmonary fibrosis secondary to bronchiectasis). METHODS: A single-group pretest-posttest experimental study was performed after recruiting 98 pulmonary fibrosis subjects from K.M.C hospitals. After being screened for the inclusion and exclusion criteria, 45 subjects were analyzed, and 6 subjects were lost to follow-up.  A home-based pulmonary rehabilitation program was carried out for 8 weeks (warm-up, stretching exercises, aerobic exercise, strength training for upper limb and lower limb, breathing exercises mainly involved; others: energy saving techniques, controlled coughing techniques, dyspnea relieving positions). The program was supervised via weekly phone calls. Pulmonary function (Pulmonary function test), exercise capacity (6-minute walk test), dyspnea (modified Borg scale), and health-related quality of life (SF-36) were evaluated before and after the intervention. During the enrollment and after the 6-minute walk test, saturation of peripheral oxygen (SPO2) level was also evaluated pre-intervention and after the 8-weeks program. RESULTS: Pulmonary function [FVC(L) t = -12.52, p<0.05; FEV1(L) t = -2.56, p<0.05; FEV1/FVC t = 7.98, p<0.05 and DLCO (ml/min/mmHg) t = -5.13, p<0.05], 6MWD [MD 88.66; p<0.05] and HRQOL measured by SF-36 scores (p<0.05) were improved significantly. Both the baseline SPO2 level before the 6MWT [MD 1.07, p<0.05] and the SPO2 level after the 6MWT [MD 1.16, p<0.05] showed a significant improvement. The rating of perceived exertion(dyspnea) [MD 1.30, p<0.05] was reduced significantly after the 8-week program. CONCLUSION: Our study shows that home-based pulmonary rehabilitation is an effective option for improving lung function and physical functional capacity by reducing dyspnea perception and improving the saturation of peripheral oxygen (SPO2) level, and enhancing the quality of life in people with pulmonary fibrosis.

11.
Sci Rep ; 14(1): 13315, 2024 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858439

RESUMEN

Exposure to high, marginally lethal doses or higher of ionizing radiation, either intentional or accidental, results in injury to various organs. Currently, there is only a limited number of safe and effective radiation countermeasures approved by US Food and Drug Administration for such injuries. These approved agents are effective for only the hematopoietic component of the acute radiation syndrome and must be administered only after the exposure event: currently, there is no FDA-approved agent that can be used prophylactically. The nutraceutical, gamma-tocotrienol (GT3) has been found to be a promising radioprotector of such exposure-related injuries, especially those of a hematopoietic nature, when tested in either rodents or nonhuman primates. We investigated the nature of injuries and the possible protective effects of GT3 within select organ systems/tissues caused by both non-lethal level (4.0 Gy), as well as potentially lethal level (5.8 Gy) of ionizing radiation, delivered as total-body or partial-body exposure. Results indicated that the most severe, dose-dependent injuries occurred within those organ systems with strong self-renewing capacities (e.g., the lymphohematopoietic and gastrointestinal systems), while in other tissues (e.g., liver, kidney, lung) endowed with less self-renewal, the pathologies noted tended to be less pronounced and less dependent on the level of exposure dose or on the applied exposure regimen. The prophylactic use of the test nutraceutical, GT3, appeared to limit the extent of irradiation-associated pathology within blood forming tissues and, to some extent, within the small intestine of the gastrointestinal tract. No distinct, global pattern of bodily protection was noted with the agent's use, although a hint of a possible radioprotective benefit was suggested not only by a lessening of apparent injury within select organ systems, but also by way of noting the lack of early onset of moribundity within select GT3-treated animals.


Asunto(s)
Suplementos Dietéticos , Protectores contra Radiación , Animales , Protectores contra Radiación/farmacología , Vitamina E/farmacología , Vitamina E/análogos & derivados , Síndrome de Radiación Aguda/prevención & control , Síndrome de Radiación Aguda/tratamiento farmacológico , Síndrome de Radiación Aguda/patología , Cromanos/farmacología , Masculino , Traumatismos Experimentales por Radiación/prevención & control , Traumatismos Experimentales por Radiación/patología , Macaca mulatta , Hígado/efectos de los fármacos , Hígado/efectos de la radiación , Hígado/patología
12.
J Contam Hydrol ; 265: 104385, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38878553

RESUMEN

This study aims to develop a multi-objective quantitative-qualitative reservoir operation model (MOQQROM) by a simulation-optimization approach. However, the main challenge of these models is their computational complexity. The simulation-optimization method used in this study consists of CE-QUAL-W2 as a hydrodynamic and water quality simulation model and a multi-objective firefly algorithm-k nearest neighbor (MOFA-KNN) as an optimization algorithm which is an efficient algorithm to overcome the computational burden in simulation-optimization approaches by decreasing simulation model calls. MOFA-KNN was expanded for this study, and its performance was evaluated in the MOQQROM. Three objectives were considered in this study, including (1) the sum of the squared mass of total dissolved solids (TDS), (2) the sum of the squared temperature difference between reservoir inflow and outflow as water quality objectives, and (3) the vulnerability index as a water quantity objective. Aidoghmoush reservoir was employed as a case study, and the model was investigated under three scenarios, including the normal, wet, and dry years. Results showed the expanded MOFA-KNN reduced the number of original simulation model calls compared to the total number of simulations in MOQQROM by more than 99%, indicating its efficacy in significantly reducing execution time. The three most desired operating policies for meeting each objective were selected for investigation. Results showed that the operation policy with the best value for the second objective could be chosen as a compromise policy to balance the two conflicting goals of improving quality and supplying the demand in normal and wet scenarios. In terms of contamination mass, this policy was, on average, 16% worse than the first policy and 40% better than the third policy in the normal scenario. In the wet scenario, it was, on average, 55% worse than the first policy and 16% better than the third policy. The outflow temperature of this policy was, on average, only 8.35% different from the inflow temperature in the normal scenario and 0.93% different in the wet scenario. The performance of the developed model is satisfactory.


Asunto(s)
Modelos Teóricos , Calidad del Agua , Abastecimiento de Agua , Algoritmos , Simulación por Computador
13.
mBio ; 15(7): e0129224, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38860823

RESUMEN

Sepsis and chronic infections with Pseudomonas aeruginosa, a leading "ESKAPE" bacterial pathogen, are associated with increased morbidity and mortality and skeletal muscle atrophy. The actions of this pathogen on skeletal muscle remain poorly understood. In skeletal muscle, mitochondria serve as a crucial energy source, which may be perturbed by infection. Here, using the well-established backburn and infection model of murine P. aeruginosa infection, we deciphered the systemic impact of the quorum-sensing transcription factor MvfR (multiple virulence factor regulator) by interrogating, 5 days post-infection, its effect on mitochondrial-related functions in the gastrocnemius skeletal muscle and the outcome of the pharmacological inhibition of MvfR function and that of the mitochondrial-targeted peptide, Szeto-Schiller 31 (SS-31). Our findings show that the MvfR perturbs adenosine triphosphate generation, oxidative phosphorylation, and antioxidant response, elevates the production of reactive oxygen species, and promotes oxidative damage of mitochondrial DNA in the gastrocnemius muscle of infected mice. These impairments in mitochondrial-related functions were corroborated by the alteration of key mitochondrial proteins involved in electron transport, mitochondrial biogenesis, dynamics and quality control, and mitochondrial uncoupling. Pharmacological inhibition of MvfR using the potent anti-MvfR lead, D88, we developed, or the mitochondrial-targeted peptide SS-31 rescued the MvfR-mediated alterations observed in mice infected with the wild-type strain PA14. Our study provides insights into the actions of MvfR in orchestrating mitochondrial dysfunction in the skeletal murine muscle, and it presents novel therapeutic approaches for optimizing clinical outcomes in affected patients. IMPORTANCE: Skeletal muscle, pivotal for many functions in the human body, including breathing and protecting internal organs, contains abundant mitochondria essential for maintaining cellular homeostasis during infection. The effect of Pseudomonas aeruginosa (PA) infections on skeletal muscle remains poorly understood. Our study delves into the role of a central quorum-sensing transcription factor, multiple virulence factor regulator (MvfR), that controls the expression of multiple acute and chronic virulence functions that contribute to the pathogenicity of PA. The significance of our study lies in the role of MvfR in the metabolic perturbances linked to mitochondrial functions in skeletal muscle and the effectiveness of the novel MvfR inhibitor and the mitochondrial-targeted peptide SS-31 in alleviating the mitochondrial disturbances caused by PA in skeletal muscle. Inhibiting MvfR or interfering with its effects can be a potential therapeutic strategy to curb PA virulence.


Asunto(s)
Proteínas Bacterianas , Músculo Esquelético , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Percepción de Quorum , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/fisiología , Animales , Ratones , Músculo Esquelético/microbiología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/tratamiento farmacológico , Percepción de Quorum/efectos de los fármacos , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Modelos Animales de Enfermedad , Factores de Virulencia/metabolismo , Factores de Virulencia/genética , Masculino , Fosforilación Oxidativa/efectos de los fármacos , Mitocondrias Musculares/metabolismo , Mitocondrias Musculares/efectos de los fármacos , Ratones Endogámicos C57BL , Oligopéptidos/farmacología , Adenosina Trifosfato/metabolismo , Antibacterianos/farmacología
14.
Food Chem ; 456: 140062, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-38876073

RESUMEN

Differences in moisture and protein content impact both nutritional value and processing efficiency of corn kernels. Near-infrared (NIR) spectroscopy can be used to estimate kernel composition, but models trained on a few environments may underestimate error rates and bias. We assembled corn samples from diverse international environments and used NIR with chemometrics and partial least squares regression (PLSR) to determine moisture and protein. The potential of five feature selection methods to improve prediction accuracy was assessed by extracting sensitive wavelengths. Gradient boosting machines (GBMs), particularly CatBoost and LightGBM, were found to effectively select crucial wavelengths for moisture (1409, 1900, 1908, 1932, 1953, 2174 nm) and protein (887, 1212, 1705, 1891, 2097, 2456 nm). SHAP plots highlighted significant wavelength contributions to model prediction. These results illustrate GBMs' effectiveness in feature engineering for agricultural and food sector applications, including developing multi-country global calibration models for moisture and protein in corn kernels.


Asunto(s)
Proteínas de Plantas , Espectroscopía Infrarroja Corta , Agua , Zea mays , Zea mays/química , Espectroscopía Infrarroja Corta/métodos , Proteínas de Plantas/análisis , Proteínas de Plantas/química , Análisis de los Mínimos Cuadrados , Agua/química , Agua/análisis , Semillas/química
15.
Int Endod J ; 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38703070

RESUMEN

AIM: The success of vital pulp treatment (VPT) procedures is dependent on an accurate diagnosis of the pulpal inflammatory condition. Compared with current subjective pulpal diagnostic tests, inflammatory molecular biomarkers involved in the pathogenesis of pulpitis represent potential objective indicators of the degree of pulpal inflammation. Therefore, the aim of this study was to quantify level of inflammatory biomarkers - Interleukin 8 (IL-8) and TNF-α in patients diagnosed with reversible pulpitis (RP), irreversible pulpitis (IR) and normal pulp (NP) and investigate their diagnostic accuracy in differentiating between healthy and inflamed conditions. METHODOLOGY: This prospective, cross-sectional study enrolled 72 patients aged 14-53 years with extremely deep carious lesions after establishing a clinical diagnosis of RP (n = 42), symptomatic IR (n = 22) and NP (n = 8). 50 µL of pulpal blood sample was collected from all the patients using a micropipette after pulpal exposure. The level of IL-8 and TNF-α was assessed in pg/mL using enzyme-linked immunosorbent assays. Mann-Whitney U test was applied to establish the association between IL-8/TNF-α level and degree of pulp inflammation. Receiver operating curve (ROC) analysis was carried out to calculate area under the curve (AUC) for RP versus IR. Cut-off values were established using Youden's index. RESULTS: IL-8 and TNF-α levels differed significantly between RP and IR groups (p ≤ .001). The median value of IL-8 in RP and IP groups was 259.8 pg/mL [187.5-310.0] and 1357.8 pg/mL [1036.7-2177.6] respectively. The AUC-ROC curve for RP versus IR was 0.997 with 95.5% sensitivity and 99.76% specificity. The median value of TNF-α in RP and IR groups was 75.4 pg/mL [62.7-95.8] and 157.6 pg/mL [94.1-347.3]. The AUC-ROC curve for TNF-α was 0.812 with a sensitivity and specificity of 59.1% and 92.1%, respectively. IL-8 and TNF-α levels were below detection levels for all NP samples. CONCLUSION: This study showed that pulpal blood could provide an excellent medium for establishing pulpal diagnosis under extremely deep carious lesions. The selected cytokines, IL-8 and TNF-α, demonstrated excellent discriminatory performance for reversible and irreversible pulpitis. Future studies should correlate the IL-8/TNF-α levels with VPT treatment outcomes.

16.
bioRxiv ; 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38746243

RESUMEN

Sepsis and chronic infections with Pseudomonas aeruginosa, a leading "ESKAPE" bacterial pathogen, are associated with increased morbidity and mortality and skeletal muscle atrophy. The actions of this pathogen on skeletal muscle remain poorly understood. In skeletal muscle, mitochondria serve as a crucial energy source, which may be perturbed by infection. Here, using the well-established backburn and infection model of murine P. aeruginosa infection, we deciphered the systemic impact of the quorum sensing (QS) transcription factor MvfR by interrogating five days post-infection its effect on mitochondrial-related functions in the gastrocnemius skeletal muscle and the outcome of the pharmacological inhibition of MvfR function and that of the mitochondrial-targeted peptide, Szeto-Schiller 31 (SS-31). Our findings show that the MvfR perturbs ATP generation, oxidative phosphorylation (OXPHOS), and antioxidant response, elevates the production of reactive oxygen species, and promotes oxidative damage of mitochondrial DNA in the gastrocnemius muscle of infected mice. These impairments in mitochondrial-related functions were corroborated by the alteration of key mitochondrial proteins involved in electron transport, mitochondrial biogenesis, dynamics and quality control, and mitochondrial uncoupling. Pharmacological inhibition of MvfR using the potent anti-MvfR lead, D88, we developed, or the mitochondrial-targeted peptide SS-31 rescued the MvfR- mediated alterations observed in mice infected with the wild-type strain PA14. Our study provides insights into the actions of MvfR in orchestrating mitochondrial dysfunction in the skeletal murine muscle, and it presents novel therapeutic approaches for optimizing clinical outcomes in affected patients.

17.
Radiat Res ; 202(1): 26-37, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38714310

RESUMEN

BBT-059, a long-acting PEGylated interleukin-11 (IL-11) analog that is believed to have hematopoietic promoting and anti-apoptotic properties, is being developed as a potential radiation medical countermeasure (MCM) for hematopoietic acute radiation syndrome (H-ARS). This agent has been shown to improve survival in lethally irradiated mice. To further evaluate the drug's toxicity and safety profile, 12 naïve nonhuman primates (NHPs, rhesus macaques) were administered one of three doses of BBT-059 subcutaneously and were monitored for the next 21 days. Blood samples were collected throughout the study to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of the drug as well as its effects on complete blood counts, cytokines, vital signs, and to conduct metabolomic studies. No adverse effects were detected in any treatment group during the study. Short-term changes in metabolomic profiles were present in all groups treated with BBT-059 beginning immediately after drug administration and reverting to near normal levels by the end of the study period. Several pathways and metabolites, particularly those related to inflammation and steroid hormone biosynthesis, were activated by BBT-059 administration. Taken together, these observations suggest that BBT-059 has a good safety profile for further development as a radiation MCM for regulatory approval for human use.


Asunto(s)
Macaca mulatta , Metabolómica , Polietilenglicoles , Protectores contra Radiación , Animales , Protectores contra Radiación/farmacología , Protectores contra Radiación/farmacocinética , Polietilenglicoles/farmacocinética , Polietilenglicoles/farmacología , Polietilenglicoles/química , Masculino , Interleucina-11 , Femenino , Metaboloma/efectos de los fármacos , Metaboloma/efectos de la radiación , Síndrome de Radiación Aguda/tratamiento farmacológico , Síndrome de Radiación Aguda/prevención & control
18.
Planta ; 259(6): 144, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38709333

RESUMEN

MAIN CONCLUSION: Silicon application mitigates phosphate deficiency in barley through an interplay with auxin and nitric oxide, enhancing growth, photosynthesis, and redox balance, highlighting the potential of silicon as a fertilizer for overcoming nutritional stresses. Silicon (Si) is reported to attenuate nutritional stresses in plants, but studies on the effect of Si application to plants grown under phosphate (Pi) deficiency are still very scarce, especially in barley. Therefore, the present work was undertaken to investigate the potential role of Si in mitigating the adverse impacts of Pi deficiency in barley Hordeum vulgare L. (var. BH902). Further, the involvement of two key regulatory signaling molecules--auxin and nitric oxide (NO)--in Si-induced tolerance against Pi deficiency in barley was tested. Morphological attributes, photosynthetic parameters, oxidative stress markers (O2·-, H2O2, and MDA), antioxidant system (enzymatic--APX, CAT, SOD, GR, DHAR, MDHAR as well as non-enzymatic--AsA and GSH), NO content, and proline metabolism were the key traits that were assessed under different treatments. The P deficiency distinctly declined growth of barley seedlings, which was due to enhancement in oxidative stress leading to inhibition of photosynthesis. These results were also in parallel with an enhancement in antioxidant activity, particularly SOD and CAT, and endogenous proline level and its biosynthetic enzyme (P5CS). The addition of Si exhibited beneficial effects on barley plants grown in Pi-deficient medium as reflected in increased growth, photosynthetic activity, and redox balance through the regulation of antioxidant machinery particularly ascorbate-glutathione cycle. We noticed that auxin and NO were also found to be independently participating in Si-mediated improvement of growth and other parameters in barley roots under Pi deficiency. Data of gene expression analysis for PHOSPHATE TRANSPORTER1 (HvPHT1) indicate that Si helps in increasing Pi uptake as per the need of Pi-deficient barley seedlings, and also auxin and NO both appear to help Si in accomplishing this task probably by inducing lateral root formation. These results are suggestive of possible application of Si as a fertilizer to correct the negative effects of nutritional stresses in plants. Further research at genetic level to understand Si-induced mechanisms for mitigating Pi deficiency can be helpful in the development of new varieties with improved tolerance against Pi deficiency, especially for cultivation in areas with Pi-deficient soils.


Asunto(s)
Hordeum , Ácidos Indolacéticos , Óxido Nítrico , Estrés Oxidativo , Fosfatos , Fotosíntesis , Raíces de Plantas , Silicio , Hordeum/metabolismo , Hordeum/genética , Hordeum/efectos de los fármacos , Hordeum/crecimiento & desarrollo , Hordeum/fisiología , Silicio/farmacología , Silicio/metabolismo , Ácidos Indolacéticos/metabolismo , Fosfatos/deficiencia , Fosfatos/metabolismo , Óxido Nítrico/metabolismo , Raíces de Plantas/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/genética , Fotosíntesis/efectos de los fármacos , Antioxidantes/metabolismo , Plantones/crecimiento & desarrollo , Plantones/metabolismo , Plantones/genética , Plantones/efectos de los fármacos , Plantones/fisiología
19.
Global Spine J ; : 21925682241256350, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38798232

RESUMEN

STUDY DESIGN: Randomized Control Trial. OBJECTIVE: DCM refers to compression of spinal cord either due to static/dynamic causes or commonly, a result of combination of both. Number of variables exist, which determine prognosis post-surgery. Role of intra-operative blood pressure has not been analyzed in depth in current literature. Elevating MAP post SCI is widely practiced and forms a recommendation of AANS/CNS Joint Committee Guidelines. This led us to investigate role played by elevated MAP during surgery for DCM, in order to optimize outcomes. METHODS: This prospective randomized comparative pilot study was conducted at a tertiary care spine centre. 84 patients were randomly divided in two groups. Group 1 had intra-operative MAP in normal range. Group 2, had intra-operative BP 20 mmHg higher than preoperative average MAP with a variation of + 5 mmHg. Outcomes were recorded at 3 months, 6 months and 1 year by mJOA, VAS and ASIA scale. RESULTS: Neurological improvement was documented in 19/30 (63.3%) patients of hypertensive group compared to 16/30 (53.3%) patients of normotensive group. Improvements in mJOA scores were better for hypertensive group during the 1-year follow-up. Improvement in VAS scores were comparable between two groups, but at 1-year follow-up the VAS score of hypertensive groups was significantly lower. CONCLUSION: MAP should be individualized according to preoperative average blood pressure assessment of patient. Keeping intraoperative MAP at higher level (preoperative MAP + 20 mmHg) during surgery for DCM can result in better outcomes.

20.
ScientificWorldJournal ; 2024: 8825476, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38799378

RESUMEN

Background: In most settings, patients receive phase 1 cardiac rehabilitation in CTVS ICU at the hospital, but there are several barriers to follow-up after patients are discharged from the hospital. Physiotherapists play an important role in the enrolment and continuation of cardiac rehabilitation. Thus, we aim to study the knowledge, attitude, and practice of physiotherapists about CR program adherence among patients discharged from the hospital after cardiac surgery. Objectives: (i) To study the knowledge of physiotherapists about the importance of cardiac rehabilitation after discharge; (ii) to know the attitude of physiotherapists towards cardiac surgery patients after discharge; and (iii) to know what approach various centres are applying for patients after discharge to ensure adherence to cardiac rehabilitation. Methods: A questionnaire was developed with reference to the objectives of the study, which was answered by a total of 127 physiotherapists. Results: The overall response rate was 42.3%; nearly 35.4% of the participants indicated that they knew a lot about CR, while 5.5% said they knew very little. Regarding the program's content, 36.2% of participants reported having a medium degree of awareness of the diverse CR components, while 8.6% reported having very little knowledge of them. Only about one-third, 35.7% stated that CR in India is effective and 95% believed that CR will have an added value for the country. Approximately 80% of respondents thought that it would be challenging for a physiotherapist to recommend patients to a CR in the nation. Nearly 35% of respondents believed that they, "themselves as physios," needed to commence CR, and slightly less than 70% thought that doctors were required to choose and refer the patients when asked who should take the initiative to start this kind of programme in the country. A little over 40% of respondents said that insurance firms are also involved in starting a CR programme. Conclusion: Physiotherapists have good knowledge of cardiac rehabilitation. However, their attitude and practice towards adherence to exercise protocols are confounded by various clinician- and patient-level factors.


Asunto(s)
Rehabilitación Cardiaca , Procedimientos Quirúrgicos Cardíacos , Conocimientos, Actitudes y Práctica en Salud , Alta del Paciente , Fisioterapeutas , Humanos , India , Femenino , Masculino , Procedimientos Quirúrgicos Cardíacos/rehabilitación , Encuestas y Cuestionarios , Adulto , Persona de Mediana Edad , Cooperación del Paciente , Actitud del Personal de Salud
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