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1.
Mol Plant Pathol ; 25(7): e13491, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38961768

ABSTRACT

Root-knot nematodes (RKNs) are microscopic parasitic worms able to infest the roots of thousands of plant species, causing massive crop yield losses worldwide. They evade the plant's immune system and manipulate plant cell physiology and metabolism to transform a few root cells into giant cells, which serve as feeding sites for the nematode. RKN parasitism is facilitated by the secretion in planta of effector molecules, mostly proteins that hijack host cellular processes. We describe here a conserved RKN-specific effector, effector 12 (EFF12), that is synthesized exclusively in the oesophageal glands of the nematode, and we demonstrate its function in parasitism. In the plant, MiEFF12 localizes to the endoplasmic reticulum (ER). A combination of RNA-sequencing analysis and immunity-suppression bioassays revealed the contribution of MiEFF12 to the modulation of host immunity. Yeast two-hybrid, split luciferase and co-immunoprecipitation approaches identified an essential component of the ER quality control system, the Solanum lycopersicum plant bap-like (PBL), and basic leucine zipper 60 (BZIP60) proteins as host targets of MiEFF12. Finally, silencing the PBL genes in Nicotiana benthamiana decreased susceptibility to Meloidogyne incognita infection. Our results suggest that EFF12 manipulates PBL function to modify plant immune responses to allow parasitism.


Subject(s)
Endoplasmic Reticulum , Tylenchoidea , Animals , Endoplasmic Reticulum/metabolism , Tylenchoidea/physiology , Tylenchoidea/pathogenicity , Helminth Proteins/metabolism , Helminth Proteins/genetics , Plant Immunity , Nicotiana/parasitology , Nicotiana/immunology , Nicotiana/genetics , Solanum lycopersicum/parasitology , Solanum lycopersicum/immunology , Solanum lycopersicum/genetics , Plant Diseases/parasitology , Plant Diseases/immunology , Plant Roots/parasitology , Plant Roots/immunology , Host-Parasite Interactions
2.
Appl Microbiol Biotechnol ; 108(1): 425, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39042328

ABSTRACT

Borrelia, spirochetes transmitted by ticks, are the etiological agents of numerous multisystemic diseases, such as Lyme borreliosis (LB) and tick-borne relapsing fever (TBRF). This study focuses on two surface proteins from two Borrelia subspecies involved in these diseases: CspZ, expressed by Borrelia burgdorferi sensu stricto (also named BbCRASP-2 for complement regulator-acquiring surface protein 2), and the factor H binding A (FhbA), expressed by Borrelia hermsii. Numerous subspecies of Borrelia, including these latter, are able to evade the immune defenses of a variety of potential vertebrate hosts in a number of ways. In this context, previous data suggested that both surface proteins play a role in the immune evasion of both Borrelia subspecies by interacting with key regulators of the alternative pathway of the human complement system, factor H (FH) and FH-like protein 1 (FHL-1). The recombinant proteins, CspZ and FhbA, were expressed in Escherichia coli and purified by one-step metal-affinity chromatography, with yields of 15 and 20 mg or pure protein for 1 L of cultured bacteria, respectively. The purity was evaluated by SDS-PAGE and HPLC and is close to about 95%. The mass of CspZ and FhbA was checked by mass spectrometry (MS). Proper folding of CspZ and FhbA was confirmed by circular dichroism (CD), and their biological activity, namely their interaction with purified FH from human serum (recombinant FH15-20 and recombinant FHL-1), was characterized by SPR. Such a study provides the basis for the biochemical characterization of the studied proteins and their biomolecular interactions which is a necessary prerequisite for the development of new approaches to improve the current diagnosis of LB and TBRF. KEY POINTS: • DLS, CD, SEC-MALS, NMR, HPLC, and MS are tools for protein quality assessment • Borrelia spp. possesses immune evasion mechanisms, including human host complement • CspZ and FhbA interact with high affinity (pM to nM) to human FH and rFHL-1.


Subject(s)
Bacterial Proteins , Recombinant Proteins , Bacterial Proteins/genetics , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , Humans , Borrelia burgdorferi/genetics , Borrelia burgdorferi/metabolism , Borrelia burgdorferi/immunology , Chromatography, Affinity , Escherichia coli/genetics , Escherichia coli/metabolism , Borrelia/genetics , Borrelia/metabolism , Borrelia/immunology , Complement Factor H/metabolism , Complement Factor H/genetics , Lyme Disease/microbiology , Complement C3b Inactivator Proteins/genetics , Complement C3b Inactivator Proteins/metabolism , Gene Expression
3.
EJNMMI Phys ; 11(1): 69, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39052176

ABSTRACT

BACKGROUND: The application of semi-conductor detectors such as cadmium-zinc-telluride (CZT) in nuclear medicine improves extrinsic energy resolution and count sensitivity due to the direct conversion of gamma photons into electric signals. A 3D-ring pixelated CZT system named StarGuide was recently developed and implemented by GE HealthCare for SPECT acquisition. The system consists of 12 detector columns with seven modules of 16 × 16 CZT pixelated crystals, each with an integrated parallel-hole tungsten collimator. The axial coverage is 27.5 cm. The detector thickness is 7.25 mm, which allows acquisitions in the energy range [40-279] keV. Since there is currently no performance characterization specific to 3D-ring CZT SPECT systems, the National Electrical Manufacturers Association (NEMA) NU 1-2018 clinical standard can be tailored to these cameras. The aim of this study was to evaluate the performance of the SPECT/CT StarGuide system according to the NEMA NU 1-2018 clinical standard specifically adapted to characterize the new 3D-ring CZT. RESULTS: Due to the integrated collimator, the system geometry and the pixelated nature of the detector, some NEMA tests have been adapted to the features of the system. The extrinsic measured energy resolution was about 5-6% for the tested isotopes (99mTc, 123I and 57Co); the maximum count rate was 760 kcps and the observed count rate at 20% loss was 917 kcps. The system spatial resolution in air extrapolated at 10 cm with 99mTc was 7.2 mm, while the SPECT spatial resolutions with scatter were 4.2, 3.7 and 3.6 mm in a central, radial and tangential direction respectively. Single head sensitivity value for 99mTc was 97 cps/MBq; with 12 detector columns, the system volumetric sensitivity reached 520 kcps MBq-1 cc-1. CONCLUSIONS: The performance tests of the StarGuide can be performed according to the NEMA NU 1-2018 standard with some adaptations. The system has shown promising results, particularly in terms of energy resolution, spatial resolution and volumetric sensitivity, potentially leading to higher quality clinical images.

4.
Food Res Int ; 191: 114673, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39059905

ABSTRACT

Brown sugar is a natural sweetener obtained by thermal processing, with interesting nutritional characteristics. However, it has significant sensory variability, which directly affects product quality and consumer choice. Therefore, developing rapid methods for its quality control is desirable. This work proposes a fast, environmentally friendly, and accurate method for the simultaneous analysis of sucrose, reducing sugars, minerals and ICUMSA colour in brown sugar, using an innovative strategy that combines digital image processing acquired by smartphone cell with machine learning. Data extracted from the digital images, as well as experimentally determined contents of the physicochemical characteristics and elemental profile were the variables adopted for building predictive regression models by applying the kNN algorithm. The models achieved the highest predictive capacity for the Ca, ICUMSA colour, Fe and Zn, with coefficients of determination (R2) ≥ 92.33 %. Lower R2 values were observed for sucrose (81.16 %), reducing sugars (85.67 %), Mn (83.36 %) and Mg (86.97 %). Low data dispersion was found for all the predictive models generated (RMSE < 0.235). The AGREE Metric assessed the green profile and determined that the proposed approach is superior in relation to conventional methods because it avoids the use of solvents and toxic reagents, consumes minimal energy, produces no toxic waste, and is safer for analysts. The combination of digital image processing (DIP) and the kNN algorithm provides a fast, non-invasive and sustainable analytical approach. It streamlines and improves quality control of brown sugar, enabling the production of sweeteners that meet consumer demands and industry standards.


Subject(s)
Color , Image Processing, Computer-Assisted , Machine Learning , Minerals , Image Processing, Computer-Assisted/methods , Minerals/analysis , Sucrose/analysis , Algorithms , Sugars/analysis , Smartphone , Sweetening Agents/analysis , Food Analysis/methods
5.
Food Res Int ; 191: 114702, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39059909

ABSTRACT

Sterilization of Northern shrimp (Pandalus borealis) is a key tool to ensure their freshness for post-production transportation. However, in the face of the specific problem of quality deterioration caused by the increase of storage environment temperature due to unexpected circumstances or the prolongation of temporary storage time, it is still a technical challenge to realize intelligent decision-making and higher sterilization efficiency. In this paper, we propose an intelligent UV-Ozone sterilization system suitable for cold chain transportation of Northern shrimp (Pandalus borealis). Using hierarchical analysis, equipartition method and the prediction method of generalized linear model, combined with the technology of intelligent control and remote control, we realized the automatic control of the system's UV irradiance from 324 âˆ¼ 1620 J/m2, and ozone concentration from21.4 ∼ 107 mg/cm3 in a graded manner. The accuracy of the predicted structure was verified using a combination of direct measurement and simulation. In addition, the key model of the system, the intensity level decision model, was tested, and the test results showed that the decision model was able to accurately make decisions during the sterilization of Northern shrimp (Pandalus borealis), and the system was able to achieve a sterilization effect of 1-3 orders of magnitude. This reduces quality loss due to unexpected conditions, facilitates real-time monitoring of transported samples by staff, extends the shelf life of the samples, and improves the accuracy of sterilization, increasing the economic value of Northern shrimp (Pandalus borealis).


Subject(s)
Food Storage , Ozone , Pandalidae , Sterilization , Ultraviolet Rays , Animals , Sterilization/methods , Food Storage/methods , Food Preservation/methods , Shellfish , Refrigeration
6.
J Pharm Biomed Anal ; 249: 116349, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39029352

ABSTRACT

In this study we analyzed drug recall data from the U.S. Food and Drug Administration (FDA) over the period 2012-2023. We identified trends in the number of recalls initiated annually and their underlying causes. On average, 330 drug recalls are initiated each year, showing an overall increasing trend. The average duration of a recall, from initiation to termination date, was 1.3 years and each recall involved on average 400 000 product units, implying considerable resource demands and consequences for all stakeholders. The most frequent cause of these recalls was found to be impurities and contaminants (37 %), followed by control (28 %) and labeling/packaging (19 %) issues. Recalls of medicines causing serious health problems or death (class I), accounted for 14 % of the recall events. Continuous evaluation of recalls is expected to reduce their number, mitigate their impact on the healthcare system and improve drug safety.

7.
Antioxidants (Basel) ; 13(7)2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39061890

ABSTRACT

Nutritional interventions are one focus of sarcopenia treatment. As medium-chain fatty acids (MCFAs) are oxidized in the mitochondria and produce energy through oxidative phosphorylation (OXPHOS), they are key parts of nutritional interventions. We investigated the in vitro effects of three types of MCFA, caprylic acid (C8), capric acid (C10), and lauric acid (C12), in skeletal muscle cells. Compared with C10 and C12, C8 promoted mitophagy through the phosphatase and tensin homolog (PTEN)-induced kinase 1-Parkin pathway and increased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-α and dynamin-related protein 1 to reduce mitochondrial oxidative stress and promote OXPHOS. Furthermore, the expression of myogenic differentiation 1 and myosin heavy chain increased in myotubes, thus promoting muscle differentiation and maturation. These results suggest that C8 improves mitochondrial quality and promotes skeletal muscle maturation; in contrast, C10 and C12 poorly promoted mitochondrial quality control and oxidative stress and suppressed energy production. Future animal experiments are required to establish the usefulness of C8 for nutritional interventions for sarcopenia.

8.
Cell Rep ; 43(8): 114473, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39024102

ABSTRACT

Mitochondria require the constant import of nuclear-encoded proteins for proper functioning. Impaired protein import not only depletes mitochondria of essential factors but also leads to toxic accumulation of un-imported proteins outside the organelle. Here, we investigate the consequences of impaired mitochondrial protein import in human cells. We demonstrate that un-imported proteins can clog the mitochondrial translocase of the outer membrane (TOM). ATAD1, a mitochondrial ATPase, removes clogged proteins from TOM to clear the entry gate into the mitochondria. ATAD1 interacts with both TOM and stalled proteins, and its knockout results in extensive accumulation of mitochondrial precursors as well as decreased protein import. Increased ATAD1 expression contributes to improved fitness of cells with inefficient mitochondrial protein import. Overall, we demonstrate the importance of the ATAD1 quality control pathway in surveilling protein import and its contribution to cellular health.

9.
Med Phys ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-39031758

ABSTRACT

BACKGROUND: Adequate image enhancement of organs and blood vessels of interest is an important aspect of image quality in contrast-enhanced computed tomography (CT). There is a need for an objective method for evaluation of vessel contrast that can be automatically and systematically applied to large sets of CT exams. PURPOSE: The purpose of this work was to develop a method to automatically segment and measure attenuation Hounsfield Unit (HU) in the portal vein (PV) in contrast-enhanced abdomen CT examinations. METHODS: Input CT images were processed by a vessel enhancing filter to determine candidate PV segmentations. Multiple machine learning (ML) classifiers were evaluated for classifying a segmentation as corresponding to the PV based on segmentation shape, location, and intensity features. A public data set of 82 contrast-enhanced abdomen CT examinations was used to train the method. An optimal ML classifier was selected by training and tuning on 66 out of the 82 exams (80% training split) in the public data set. The method was evaluated in terms of segmentation classification accuracy and PV attenuation measurement accuracy, compared to manually determined ground truth, on a test set of the remaining 16 exams (20% test split) held out from public data set. The method was further evaluated on a separate, independently collected test set of 21 examinations. RESULTS: The best classifier was found to be a random forest, with a precision of 0.892 in the held-out test set to correctly identify the PV from among the input candidate segmentations. The mean absolute error of the measured PV attenuation relative to ground truth manual measurement was 13.4 HU. On the independent test set, the overall precision decreased to 0.684. However, the PV attenuation measurement remained relatively accurate with a mean absolute error of 15.2 HU. CONCLUSIONS: The method was shown to accurately measure PV attenuation over a large range of attenuation values, and was validated in an independently collected dataset. The method did not require time-consuming manual contouring to supervise training. The method may be applied to systematic quality control of contrast-enhanced CT examinations.

10.
Article in English | MEDLINE | ID: mdl-38964136

ABSTRACT

The production of biogenic amines (BAs), which are markers of both quality and safety in fish and fishery products, is influenced by the harvesting technique, handling, and other operations including those carried out on board the vessel. Scombroid dark-meat fish (e.g. tuna) are the fish species most frequently linked to histamine poisoning. The most commonly found BAs in fish are histamine, tyramine, putrescine, and cadaverine, which are produced when microbes decarboxylate the corresponding free amino acids. In this study, a rapid and cost-effective HILIC-MS/MS method was developed and validated for the determination of putrescine, cadaverine, histamine and tyramine in tuna samples. A simple sample preparation procedure was followed using the solvent mixture MeOH/H2O (50/50, v/v), 0.1 % acetic acid for protein precipitation and analyte extraction. Intra- and inter-day accuracy, expressed as %Recovery (%R), ranged from 88.0 % (Cad) to 102.7 % (Tyr) and from 85.0 % (Cad) to 99.8 % (Tyr), respectively. Intra- and inter-day precision, expressed as %Relative Standard Deviation (%RSD), ranged from 0.4 % (Tyr, Put) to 3.3 % (His) and from 0.7 % (Tyr) to 5.0 % (Cad), respectively. Limits of detection (LOD) and quantification (LOQ) varied from 0.0009 to 0.0940 mg/kg and from 0.0030 mg/kg to 0.3100 mg/kg, respectively, depending on the analyte. Regarding the potential toxic effects linked to biogenic amines in foods, samples examined in this study showed no risk. The proposed method is an important analytical tool for routine analysis of BAs in fish products.


Subject(s)
Biogenic Amines , Limit of Detection , Tandem Mass Spectrometry , Tuna , Animals , Tandem Mass Spectrometry/methods , Biogenic Amines/analysis , Reproducibility of Results , Linear Models , Chromatography, Liquid/methods , Seafood/analysis , Chromatography, High Pressure Liquid/methods
11.
Sci Total Environ ; 946: 174313, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-38964406

ABSTRACT

Nervous system diseases are a global health problem, and with the increase in the elderly population around the world, their incidence will also increase. Harmful substances in the environment are closely related to the occurrence of nervous system diseases. China is a large agricultural country, and thus the insecticide cyfluthrin has been widely used. Cyfluthrin is neurotoxic, but the mechanism of this injury is not clear. Inflammation is an important mechanism for the occurrence of nervous system diseases. Mitochondria are the main regulators of the inflammatory response, and various cellular responses, including autophagy, directly affect the regulation of inflammatory processes. Mitochondrial damage is related to mitochondrial quality control (MQC) and PTEN-induced kinase 1 (PINK1). As an anti-inflammatory factor, stimulator of interferon genes (STING) participates in the regulation of inflammation. However, the relationship between STING and mitochondria in the process of cyfluthrin-induced nerve injury is unclear. This study established in vivo and in vitro models of cyfluthrin exposure to explore the role of MQC and to clarify the mechanism of action of STING and PINK1. Our results showed that cyfluthrin can increase the reactive oxygen species (ROS) level, resulting in mitochondrial damage and inflammation. In this process, an imbalance in MQC leads to the aggravation of mitochondrial damage, and high STING expression drives the occurrence of inflammation. We established a differential expression model of STING and PINK1 to further determine the underlying mechanism and found that the interaction between STING and PINK1 regulates MQC to affect the levels of mitochondrial damage and inflammation. When STING and PINK1 expression are downregulated, mitochondrial damage and STING-induced inflammation are significantly alleviated. In summary, a synergistic effect between STING and PINK1 on cyfluthrin-induced neuroinflammation may exist, which leads to an imbalance in MQC by inhibiting mitochondrial biogenesis and division/fusion, and PINK1 can reduce STING-driven inflammation.


Subject(s)
Mitochondria , Nitriles , Protein Kinases , Pyrethrins , Pyrethrins/toxicity , Mitochondria/drug effects , Animals , Nitriles/toxicity , Protein Kinases/metabolism , Protein Kinases/genetics , Neuroinflammatory Diseases/chemically induced , Insecticides/toxicity , Mice , Reactive Oxygen Species/metabolism , Inflammation/chemically induced , Membrane Proteins/metabolism , Membrane Proteins/genetics
12.
J Sep Sci ; 47(13): e2400308, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38982562

ABSTRACT

Jiawei Huoxiang Zhengqi Pill (JHZP) is a commonly used Chinese patent medicine for the clinical treatment of headache, dizziness, chest tightness as well as abdominal distension, and pain caused by wind-cold flu. In this study, a comprehensive strategy combining ultra-high performance liquid chromatography with diode array detector (UHPLC-DAD) fingerprinting and multi-component quantitative analysis was established and validated for quality evaluation of JHZP. A total of 49 characteristic common peaks were selected in a chromatographic fingerprinting study to assess the similarity of 15 batches of JHZP. Furthermore, 109 compounds were identified or preliminarily identified from JHZP by coupling with an advanced hybrid linear ion trap-Orbitrap mass spectrometer. For quantification, the optimized ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was employed for the simultaneous determination of 13 target compounds within 12 min. The sensitivity, precision, reproducibility, and accuracy of the method were satisfactory. This validated UPLC-MS/MS method was successfully applied to analyzing 15 batches of JHZP. The proposed comprehensive strategy combining UHPLC-DAD fingerprinting and multi-component UPLC-MS/MS analysis proved to be highly efficient, accurate, and reliable for the quality evaluation of JHZP, which can be considered as a reference for the overall quality evaluation of other Chinese herbal formulations.


Subject(s)
Drugs, Chinese Herbal , Quality Control , Tandem Mass Spectrometry , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/chemistry
14.
Electrophoresis ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38973474

ABSTRACT

An imaged capillary isoelectric focusing (icIEF)-based method was developed and validated as a multi-attribute method for a bispecific antibody (BsAb). First, as the traditional application of the icIEF method, it serves as an identity assay and purity assay for the BsAb. Second, the method can also be used as an impurity assay for the homodimer monoclonal antibodies generated during BsAb assembly. The homodimer impurity analysis for BsAb is usually done by hydrophobic interaction chromatography methods in the industry. The icIEF method has good sensitivity (down to 4 µg/mL in a limit of quantitation) when UV fluorescence detection is used, which detects the native fluorescence of proteins. This is the first report that an icIEF method has been applied as impurity assay.

15.
Hum Reprod ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38970367

ABSTRACT

Recent advances in preimplantation genetic testing for aneuploidy (PGT-A) have significantly enhanced its application in ART, providing critical insights into embryo viability, and potentially reducing both the time spent in fertility treatments and the risk of pregnancy loss. With the integration of next-generation sequencing, PGT-A now offers greater diagnostic precision, although challenges related to segmental aneuploidies and mosaicism remain. The emergence of non-invasive PGT-A (niPGT-A), which analyzes DNA in spent embryo culture media, promises a simpler aneuploidy screening method. This mini review assesses the methodological criteria for test validation, the current landscape of PGT-A, and the potential of niPGT-A, while evaluating its advantages and potential pitfalls. It underscores the importance of a robust three-phase validation process to ensure the clinical reliability of PGT-A. Despite initial encouraging data, niPGT-A not only confronts issues of DNA amplification failure and diagnostic inaccuracies but also has yet to meet the three-prong criteria required for appropriate test validation, necessitating further research for its clinical adoption. The review underscores that niPGT-A, like traditional PGT-A, must attain the high standards of precision and reliability expected of any genetic testing platform used in clinical settings before it can be adopted into routine ART protocols.

16.
Article in English | MEDLINE | ID: mdl-38970800

ABSTRACT

The multiattribute method (MAM) has emerged as a powerful tool for simultaneously screening multiple product quality attributes of therapeutic antibodies. One such potential critical quality attribute (CQA) is glycation, a common modification that can impact the heterogeneity, functional activity, and immunogenicity of therapeutic antibodies. However, current methods for monitoring glycation levels in MAM are rare and not sufficiently rapid and accurate. In this study, an improved mass spectrometry (MS)-based MAM was developed to simultaneously monitor glycation and other quality attributes including afucosylation. The method was evaluated using two therapeutic antibodies with different glycosylation site numbers. Treatment with IdeS, Endo F2, and dithiothreitol generated three distinct subunits, and the glycation results obtained were similar to those treated with PNGase F, which is routinely used to release glycans; the sample processing time was greatly reduced while providing additional quality attribute information. The MS-based MAM was also employed to assess the glycation progression following forced glycation in various buffer solutions. A significant increase in oxidation was observed when forced glycation was conducted in an ammonium bicarbonate buffer solution, and a total of 23 potential glycation sites and 4 significantly oxidized sites were identified. Notably, we found that ammonium bicarbonate was found to specifically stimulate oxidation, while glycation had a synergistic effect on oxidation. These findings establish this study as a novel methodology for achieving a technologically advanced platform and concept that enhances the efficacy of product development and quality control, characterized by its broad-spectrum, rapid, and accurate nature.

17.
Intern Emerg Med ; 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38971910

ABSTRACT

Autophagy is an evolutionarily conserved process that plays a pivotal role in the maintenance of cellular homeostasis and its impairment has been implicated in the pathogenesis of various metabolic diseases including obesity, type 2 diabetes (T2D), and metabolic dysfunction-associated steatotic liver disease (MASLD). This review synthesizes the current evidence from human studies on autophagy alterations under these metabolic conditions. In obesity, most data point to autophagy upregulation during the initiation phase of autophagosome formation, potentially in response to proinflammatory conditions in the adipose tissue. Autophagosome formation appears to be enhanced under hyperglycemic or insulin-resistant conditions in patients with T2D, possibly acting as a compensatory mechanism to eliminate damaged organelles and proteins. Other studies have proposed that prolonged hyperglycemia and disrupted insulin signaling hinder autophagic flux, resulting in the accumulation of dysfunctional cellular components that can contribute to ß-cell dysfunction. Evidence from patients with MASLD supports autophagy inhibition in disease progression. Nevertheless, given the available data, it is difficult to ascertain whether autophagy is enhanced or suppressed in these conditions because the levels of autophagy markers depend on the overall metabolism of specific organs, tissues, experimental conditions, or disease duration. Owing to these constraints, determining whether the observed shifts in autophagic activity precede or result from metabolic diseases remains challenging. Additionally, autophagy-modulating strategies are shortly discussed. To conclude, more studies investigating autophagy impairment are required to gain a more comprehensive understanding of its role in the pathogenesis of obesity, T2D, and MASLD and to unveil novel therapeutic strategies for these conditions.

18.
Heliyon ; 10(12): e33015, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39027461

ABSTRACT

Japanese encephalitis (JE) vaccination is the most effective way to prevent JE. Plaque reduction neutralization test (PRNT) as the standard method for potency testing for inactivated JE vaccine could not provide the exact potency value. Envelope (E) protein of JE virus induces the body to create neutralizing antibodies. There is a potential for using the determination of E protein to assess the immunogenicity and efficacy of JE vaccine. In this study, an automatic time-resolved fluoroimmunoassay for detection of E protein in JE vaccine was established as a simple and rapid in vitro potency assay to complement PRNT, including the expression and paired screening of monoclonal antibodies, the establishment of assay method and performance verification. A pair of anti-E protein neutralizing antibodies (L022 and L034) were screened to construct the sandwich detection pattern. After pre-treating the vaccine sample, the entire analysis was performed using a fully automated machine, which had a little detection time and eliminated manual error. The results of the validation experiment met the requirements for quality control. The linear range was from 0.78125 U/mL to 25 U/mL, the sensitivity was 0.01 U/mL, the intra-assay coefficient of variation was less than 5 %, and the inter-assay coefficient of variation was less than 10 %. The recovery from the dilution was between 90 % and 110 %. This present TRFIA shown good stability and effectiveness in quality control for samples related to JE vaccine production. The outcomes demonstrated that the present TRFIA could be an alternative in vitro potency assay in quality control for inactivated JE vaccine.

19.
Heliyon ; 10(13): e32683, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39027520

ABSTRACT

The compounding of injectable cancer drugs for clinical trials often requires specific procedures, with limited access to the starting materials and especially the active compound. These characteristics prevent the application of qualitative or quantitative analyses and quality control techniques. Hence, for some very complex compounding operations, double visual inspection is considered to be less reliable, more time-consuming and more human-resource-intensive than other methods. The compounding team at Lille University Hospital (Lille, France) has equipped one of its preparation areas with a new device: augmented reality (AR) eyewear connected to an oncology drug management system, as a support tool for compounding and quality control. The tool has been tested, adapted and improved within the unit and is now used for investigational drug compounding on a routine basis. In a prospective, single-centre study, we evaluated the feasibility of the implementation of this novel AR approach for the compounding of injectable investigational cancer drugs. During the 6-month study period, 564 clinical trial compounding operations were performed with the AR eyewear. The proportion of poor-quality photos taken with the AR eyewear fell over time, as users became more familiar with the tool. A user satisfaction survey highlighted a very high level of uptake and a wish to broaden the scope of the compounding performed with AR support. The AR eyewear constitutes an innovative, cost-effective tool that increased the level of safety without disrupting the unit's operating procedures. The tool's flexibility enabled its integration into a variety of working environments. The various improvements now being developed should help to further boost the added value of this novel device.

20.
BMC Nurs ; 23(1): 493, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39026330

ABSTRACT

BACKGROUND: ICU nurses provide critical care and meticulously document electronic medical records (EMRs), tracking vital signs, interventions, and medication hourly. Despite China's ICUs effectively integrating real-time monitor and ventilator data into EMRs, challenges persist. Patient movements can introduce inaccuracies, and the demands of critical care may lead nurses to miss assessments like pain and nutrition. Traditional manual EMR verification is inefficient and error-prone, highlighting the urgent need for standardized, technology-aided EMR practices in ICU nursing. OBJECTIVE: This study aimed to describe the development and evaluation of an electronic medical records quality control system implemented in a Chinese tertiary care ICU setting, where current practices impact the accuracy of electronic medical records. METHODS: A prospective controlled trial was conducted with 600 ICU patients in Zhejiang Province from January to December 2023. An automated EMR quality control system was implemented in July 2023, facilitating real-time data collection and quality control for vital signs, medication management, and nursing evaluations. RESULTS: After implementing the ICU nursing electronic medical record quality control system, the prevalence of false data on vital signs decreased from 9 to 1.33%. Additionally, the incidence of incomplete medication administration dropped from 3.33 to 1.67%, and the rate of missing evaluations of assessment items in EMRs was reduced from 8 to 1.33%. Besides, the average time spent on quality control of the electronic medical records was 62 (48,76) seconds per record, which was significantly lower than the 264 (195.5,337.5) seconds using the traditional method. The nurses' satisfaction with the nursing electronic medical record quality control was (105.73 ± 9.31). CONCLUSIONS: The ICU nursing electronic medical record quality control system has led to substantial improvements in the quality and reliability of EMRs. The reduction in false data on vital signs, instances of incomplete medication administration, and missing evaluations of assessment items demonstrates the system's positive impact on nursing documentation practices. These improvements not only enhance the accuracy of patient records but also contribute to better patient care and safety within the ICU setting.

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