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1.
Neural Regen Res ; 18(4): 913-921, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36204863

RESUMO

Successful establishment of reconnection between retinal ganglion cells and retinorecipient regions in the brain is critical to optic nerve regeneration. However, morphological assessments of retinorecipient regions are limited by the opacity of brain tissue. In this study, we used an innovative tissue cleaning technique combined with retrograde trans-synaptic viral tracing to observe changes in retinorecipient regions connected to retinal ganglion cells in mice after optic nerve injury. Specifically, we performed light-sheet imaging of whole brain tissue after a clearing process. We found that pseudorabies virus 724 (PRV724) mostly infected retinal ganglion cells, and that we could use it to retrogradely trace the retinorecipient regions in whole tissue-cleared brains. Unexpectedly, PRV724-traced neurons were more widely distributed compared with data from previous studies. We found that optic nerve injury could selectively modify projections from retinal ganglion cells in the hypothalamic paraventricular nucleus, intergeniculate leaflet, ventral lateral geniculate nucleus, central amygdala, basolateral amygdala, Edinger-Westphal nucleus, and oculomotor nucleus, but not the superior vestibular nucleus, red nucleus, locus coeruleus, gigantocellular reticular nucleus, or facial nerve nucleus. Our findings demonstrate that the tissue clearing technique, combined with retrograde trans-synaptic viral tracing, can be used to objectively and comprehensively evaluate changes in mouse retinorecipient regions that receive projections from retinal ganglion cells after optic nerve injury. Thus, our approach may be useful for future estimations of optic nerve injury and regeneration.

2.
Chemosphere ; 310: 136865, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36244422

RESUMO

Castor cake is a major by-product generated after castor oil extraction and has been widely used as an organic fertilizer. Once applied to soil, a toxic alkaloid ricinine in castor cake may be released into soils and subsequently taken up by crops, which poses a potential threat to food safety and human health. However, the environmental fate of castor cake derived ricinine in agroecosystems remains unclear. In this study, the release and metabolism of ricinine in soils were conducted using soil pot experiments with different castor cake application rates. The analytical methodology of ricinine quantification in soil pore water was first established using solid phase extraction (SPE) coupled with liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). A non-target screening workflow associated with LC-QTOF/MS and SIRIUS platform was further developed to identify ricinine metabolites in soil pore water. After castor cake application, the ricinine concentrations in soil pore water significantly increased to 297-7990 µg L-1 at 1 day and then gradually decreased to 62.1-3460 µg L-1 at 7 days and 1.70-279 µg L-1 at 14 days for the selected two tested soils with castor cake application rates of 2, 10, and 20 g castor cake/kg soil. In addition, two ricinine metabolites R-194 and R-180 were tentatively identified and one ricinine metabolite N-demethyl-ricinin was confirmed through authentic reference standard for the first time by the developed non-target screening workflow. This study highlights the release and metabolism of toxic alkaloid ricinine in soils once applied castor cake as an organic fertilizer. Ricinine could be released into soil pore water in a short-term after castor cake application and then undergo demethylation, hydroxylation, and hydroxylation followed by methylation metabolisms over time in agroecosystems.


Assuntos
Alcaloides , Fertilizantes , Humanos , Fertilizantes/análise , Solo , Óleo de Rícino , Fluxo de Trabalho , Cromatografia Líquida , Alcaloides/análise , Espectrometria de Massas , Água/análise
3.
Chemosphere ; 311(Pt 1): 136792, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36272631

RESUMO

BACKGROUND: Human exposure to cadmium has various effects on health, especially on male reproductive organs. Although it is widely known that prenatal maternal cadmium exposure can affect birth outcomes, the effect of paternal exposure to cadmium remains unclear. OBJECTIVES: This study aimed to evaluate the effect of paternal cadmium exposure on fetal growth by considering maternal cadmium exposure and exposure to other heavy metals, namely mercury and lead. METHODS: The Mothers and Children's Environmental Health (MOCEH) study is a prospective birth cohort study in Korea. Overall, 1313 families (father-mother-child triple) without child abnormalities and who completed paternal whole blood cadmium assessments were included in this study. Families were divided into two subgroups based on the blood sampling periods, namely early and late pregnancy. Subjects were selected as follows: one family triple with a high level of paternal cadmium and two triples with low levels of paternal cadmium, using the method of propensity score matching. And linear regression analyses were performed. RESULTS: The group with high paternal cadmium exposure (80% or more; 1.93 µg/L) had lower birth weight infants compared to the group with low cadmium concentrations (ß(se) = -0.21(0.10); p-value = 0.0283). After stratification by infant sex, prenatal paternal cadmium exposure significantly reduced the birth weight of females in subgroups of different sampling times, namely early pregnancy (ß(se) = -0.52 (0.22); p-value = 0.0170) and late pregnancy (ß(se) = -0.43 (0.18); p-value = 0.0160). Finally, after performing propensity score matching in the early pregnancy measurement group, it was found that the prenatal exposure of father to cadmium significantly reduced birth weight in females (ß(se) = -0.72(0.25); p-value = 0.0047). CONCLUSION: This study assessed the effect of paternal cadmium exposure on birth outcomes in family units consisting of a father, mother, and child. Prenatal paternal cadmium exposure negatively affected birth weight, especially that of female, considering covariates and other heavy metals exposure, namely mercury and lead.


Assuntos
Mercúrio , Metais Pesados , Efeitos Tardios da Exposição Pré-Natal , Lactente , Gravidez , Masculino , Feminino , Humanos , Cádmio , Peso ao Nascer , Estudos de Coortes , Estudos Prospectivos , Pontuação de Propensão , Exposição Materna , Pai
4.
Front Public Health ; 10: 994712, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339215

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic can be effectively controlled by rapid and accurate identification of SARS-CoV-2-infected cases through large-scale screening. Hypercube pooling polymerase chain reaction (PCR) is frequently used as a pooling technique because of its high speed and efficiency. We attempted to implement the hypercube pooling strategy and found it had a large quantization effect. This raised two questions: is hypercube pooling with edge = 3 actually the optimal strategy? If not, what is the best edge and dimension? We used a C++ program to calculate the expected number of PCR tests per patient for different values of prevalence, edge, and dimension. The results showed that every edge had a best performance range. Then, using C++ again, we created a program to calculate the optimal edge and dimension required for pooling samples when entering prevalence into our program. Our program will be provided as freeware in the hope that it can help governments fight the SARS-CoV-2 pandemic.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Teste para COVID-19 , COVID-19/diagnóstico , Pandemias , Reação em Cadeia da Polimerase
5.
FEBS Open Bio ; 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36345604

RESUMO

Nasopharyngeal carcinoma (NPC) is a highly metastatic and invasive malignant tumor that originates in the nasopharynx. The DNA-binding protein WD repeat and HMG-box DNA-binding protein 1 (WDHD1) is highly expressed in a variety of tumors, but its expression and mechanism of action in NPC have not been reported to date. To investigate the involvement of WDHD1 in NPC, we first mined databases for the gene expression profile of NPC. Immunohistochemistry (IHC) was performed on 338 cases of NPC and 112 non-NPC samples to verify the results. We report that the expression of WDHD1 is significantly elevated in NPC. ChIP-seq was used to show that integrin alpha V (ITGAV) and WDHD1 exhibit a significant binding peak in the promoter region of the ITGAV gene. The expression levels of ITGAV and WDHD1 exhibit a significant positive correlation, and IHC was performed to show that ITGAV is highly expressed in NPC. Expression of ITGAV increased after overexpression of WDHD1, suggesting that ITGAV may be a potential target gene of WDHD1. Pathway analysis showed that both genes were closely related to cell cycle, and flow cytometry was used to further confirm that decreased expression of WDHD1 significantly increased the number of apoptotic cells. In conclusion, our results suggest that expression of WDHD1 is increased in NPC and is likely to be associated with the NPC cell cycle; thus, we propose that WDHD1 may have potential as a target gene for primary screening and treatment of NPC.

6.
Hypertension ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36345830

RESUMO

BACKGROUND: Previous EWASs (Epigenome-Wide Association Studies) have reported hundreds of blood pressure (BP) associated 5'-cytosine-phosphate-guanine-3' (CpG) sites. However, their results were inconsistent. Longitudinal observations on the temporal relationship between DNA methylation and BP are lacking. METHODS: A candidate CpG site association study for BP was conducted on 1072 twins in the Chinese National Twin Registry. PubMed and EMBASE were searched for candidate CpG sites. Cross-lagged models were used to assess the temporal relationship between BP and DNA methylation in 308 twins who completed 2 surveys in 2013 and 2018. Then, the significant cross-lagged associations were validated by adopting the Inference About Causation From Examination of Familial Confounding approach. Finally, to evaluate the cumulative effects of DNA methylation on the progression of hypertension, we established methylation risk scores based on BP-associated CpG sites and performed Markov multistate models. RESULTS: 16 and 20 CpG sites were validated to be associated with systolic BP and diastolic BP, respectively. In the cross-lagged analysis, we detected that methylation of 2 CpG sites could predict subsequent systolic BP, and systolic BP predicted methylation at another 3 CpG sites. For diastolic BP, methylation at 3 CpG sites had significant cross-lagged effects for predicting diastolic BP levels, while the prediction from the opposite direction was observed at one site. Among these, 3 associations were validated in the Inference About Causation From Examination of Familial Confounding analysis. Using the Markov multistate model, we observed that methylation risk scores were associated with the development of hypertension. CONCLUSIONS: Our findings suggest the significance of DNA methylation in the development of hypertension.

7.
Sensors (Basel) ; 22(21)2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36365864

RESUMO

Graph Neural Networks (GNNs) are neural networks that learn the representation of nodes and associated edges that connect it to every other node while maintaining graph representation. Graph Convolutional Neural Networks (GCNs), as a representative method in GNNs, in the context of computer vision, utilize conventional Convolutional Neural Networks (CNNs) to process data supported by graphs. This paper proposes a one-stage GCN approach for 3D object detection and poses estimation by structuring non-linearly distributed points of a graph. Our network provides the required details to analyze, generate and estimate bounding boxes by spatially structuring the input data into graphs. Our method proposes a keypoint attention mechanism that aggregates the relative features between each point to estimate the category and pose of the object to which the vertices of the graph belong, and also designs nine degrees of freedom of multi-object pose estimation. In addition, to avoid gimbal lock in 3D space, we use quaternion rotation, instead of Euler angle. Experimental results showed that memory usage and efficiency could be improved by aggregating point features from the point cloud and their neighbors in a graph structure. Overall, the system achieved comparable performance against state-of-the-art systems.


Assuntos
Gráficos por Computador , Imageamento Tridimensional , Redes Neurais de Computação
8.
Front Surg ; 9: 1033453, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353614

RESUMO

Introduction: For patients undergoing THR, measuring the postoperative acetabular anteversion precisely plays a pivotal role in the prognosis. However, using elliptical methods mandates computerized equipment that is frequently in shortage in remote areas and developing countries. We invented a laser projector utilizing the ellipse method to measure the acetabular anteversion directly. The aim is to examine the consistency and validity of the laser projector as compared to our original software, Elliversion. Materials and Methods: We retrospectively collected 50 postoperative pelvis radiographs including acetabulum from our institution. One investigator first measured the anteversion of included radiographs through Elliversion software as the control group. Subsequently, two operators independently used the laser projector for measurements in two separate periods with 1-day intervals as the experimental group. Our analysis was comprised of intra- and inter-observer comparisons and reliability, which investigated both the consistency and validity, by using two-sample student's t-test and intraclass correlation coefficient. Results: There was no significant difference in measuring the anteversion through laser projectors between two operators (p = 0.54), with excellent inter-observer reliability (ICC, 0.967). The estimated effect in the anteversion measurement between the Elliversion and laser projector was also comparable, with the ICC level of 0.984, indicating excellent reliability. Conclusion: Our study reported the consistency and validity of this laser projector as there is no significant difference between Elliversion and Laser projector, notably with excellent intra- and inter-observer reliability. We look forward to helping elevate clinical acumen when doctors provide care to patients after THR, especially in remote areas.

9.
J Exp Bot ; 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36398724

RESUMO

Boron (B) is an essential element for plant growth. Many agricultural soils around the globe have either insufficient or excessive amounts of available B, with major implications for crop production. Understanding major limitations imposed by B nutritional disorders may allow breeding crops for improved B use efficiency as well as make them more resilient to excessive B, thus reducing yield penalties. It has become apparent that B-related physiological disorders are mediated in large part by their impact on plant hormonal production and signaling. The aim of this review is to summarize the current knowledge of the roles of hormones in plant responses to B and their impact on plant growth and development. The most significant effect of B deficiency is the inhibition of root elongation. B deficiency promotes the redistribution of auxin in the root elongation zone. Together with cytokinin signals and ethylene, this redistribution and modulation of auxin content triggers inhibition of the root cell elongation. Under B deficiency, root development is also regulated by brassinosteroids and jasmonic acid. Excess B can induce the production of reactive oxygen species (ROS). Abscisic acid and salicylic acid are both produced in response to B toxicity, and both can induce the antioxidant defense system to detoxify ROS. Another adaptation to B toxicity involves changes in the expression levels and activity of aquaporins in roots, thus reducing the uptake of water and delivery of B into the transpiration stream. In addition, abscisic acid mediates stomatal closure to further limit transpiration and the consequent accumulation of B in leaves.

10.
J Thorac Dis ; 14(10): 3983-3991, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36389322

RESUMO

Background: As a novel alternative to the conventional minimally invasive esophagectomy (MIE), more minimally invasive single-port laparoscopic retrograde 3-step gastric mobilization (SLRM) for esophageal reconstruction during MIE to treat esophageal cancer was attempted by our department. This study explored the preliminary clinical outcomes and feasibility of this innovative surgery. Methods: The data of 120 patients who had undergone SLRM combined with 4-port thoracoscopic McKeown esophagectomy for their esophageal cancers from March 2020 to November 2021 were reviewed. Gastric mobilization with abdominal lymph node dissection was performed via SLRM. The clinical characteristics and short-term outcomes were retrospectively analyzed. The data of operating time, blood loss, harvested lymph nodes, postoperative hospital stay and complications are presented as the mean and standard deviation. Results: A total of 120 patients underwent R0 resection without conversion to open surgery. The mean times for the thoracic procedure, abdominal procedure, and total operation were 43±6, 60±18, and 195±20 min, respectively. The numbers of mediastinal and abdominal lymph nodes harvested were 13.2±2.7, and 10.2±2.5, respectively. Postoperative pneumonia occurred in 10 patients (8.3%). Anastomotic leakage occurred in 3 patients (2.5%). Temporary vocal cord paralysis was reported in 20 patients (16.6%). The mean length of hospital stay was 8.5±4.6 days. Conclusions: SLRM is a technically feasible and safe treatment for patients with esophageal cancer. It can be considered an alternative method for patients, especially those with obesity and gastric distension.

11.
Plant Cell Physiol ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36355785

RESUMO

A comparative investigation was conducted to evaluate transcriptional changes in guard cells (GCs) of closely related halophytic (Chenopodium quinoa) and glycophytic (Spinacia oleracea) species. Plants were exposed to three weeks of 250 mM NaCl treatment and GC-enriched epidermal fragments were mechanically prepared. In both species salt-responsive genes were mainly related to categories of protein metabolism, secondary metabolites, signal transduction, and transport systems. Genes related to ABA signaling and ABA biosynthesis were strongly induced in quinoa but not in spinach GCs. Also, expression of the genes encoding transporters of amino acids, proline, sugars, sucrose, and potassium increased in quinoa GCs under salinity stress. Analysis of cell-wall-related genes suggests that genes involved in lignin synthesis (e.g., lignin biosynthesis LAC4) were highly upregulated by salt in spinach GCs. In contrast, transcripts related to cell wall plasticity (e.g., PM3) were highly induced in quinoa. Faster stomatal response to light and dark measured by observing kinetics of changes in stomatal conductance in quinoa might be associated with higher plasticity of the cell wall regulated by PME3. Furthermore, genes involving in inhibition of stomatal development and differentiation were highly expressed by salt in quinoa, but not in spinach. These changes correlated with reduced stomatal density and index in quinoa thus improving its water use efficiency. The fine modulation of transporters, cell wall modification and controlling stomatal development in GCs of quinoa may have resulted in high K+/Na+ ratio, lower stomatal conductance and higher stomatal speed for better adaptation to salinity stress in quinoa.

12.
Food Chem ; 405(Pt A): 134850, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36368100

RESUMO

Extruded glutelin/rice starch composites were prepared using twin-screw extrusion at various specific mechanical energies (SME), and the interaction mechanism of glutelin and rice starch was investigated at the molecular level. The results indicated that the structure of glutelin was destroyed, hydrophobic interactions and hydrogen bonds between rice starch and glutelin were formed and enhanced as the SME increased, and new hydrogen bonds were formed at the carbonyl (δ- and γ-carbons of glutelin) and C-1 of Tyr. Molecular docking studies confirmed that SME promoted the simultaneous occurrence of the Millard reaction and non-covalent reaction between glutelin and small molecular sugars produced by starch degradation, providing information on binding sites. Additionally, scanning electron microscopy (SEM) revealed dense and uniform flake-like structures induced by these binding interactions. Overall, insights into the interaction mechanism of rice starch and glutelin provide theoretical references for generating reconstituted rice products using extrusion processing.

13.
Int J Mol Sci ; 23(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36362062

RESUMO

Programmed death-ligand 1 (PD-L1) is an immune checkpoint molecule that can regulate immune responses in the tumor microenvironment (TME); however, the clinical applications of PD-L1 in early-stage colorectal cancer (CRC) remain unclear. In this study, we aimed to investigate the relationship between PD-L1 expression and survival outcome and explore its relevant immune responses in CRC. PD-L1 expression was evaluated by immunohistochemical staining to determine the tumor proportion score and combined positive score (CPS) in a Taiwanese CRC cohort. The oncomine immune response research assay was conducted for immune gene expression analyses. CRC datasets from the TCGA database were reappraised for PD-L1-associated gene enrichment analyses using GSEA. The high expression of PD-L1 (CPS ≥ 5) was associated with longer recurrence-free survival (p = 0.031) and was an independent prognostic factor as revealed by multivariate analysis. High PD-L1 expression was related to six immune-related gene signatures, and CXCL9 is the most significant overexpressed gene in differential analyses. High CXCL9 expression correlated with increased infiltration levels of immune cells in the TME, including CD8+ T lymphocytes and M1 macrophages. These findings suggest that high PD-L1 expression is a prognostic factor of early-stage CRC, and CXCL9 may play a key role in regulating PD-L1 expression.


Assuntos
Antígeno B7-H1 , Neoplasias Colorretais , Humanos , Antígeno B7-H1/metabolismo , Linfócitos do Interstício Tumoral , Microambiente Tumoral/genética , Neoplasias Colorretais/patologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-36400408

RESUMO

OBJECTIVES: The socioeconomic and clinical burden of multidrug-resistant organisms (MDRO), including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug-resistant Acinetobacter baumannii (MRAB), multidrug-resistant Pseudomonas aeruginosa (MRPA) and carbapenem-resistant Enterobacteriaceae (CRE) have not yet been adequately addressed. METHODS: We prospectively searched for MDROs bacteremia cases with matched controls from 10 hospitals across Korea during a 6-month period in 2017. Patients were classified into the MDRO, susceptible organism and no-infection groups. The corresponding susceptible or no-infection controls had been selected according to predefined criteria. We collected clinical information and estimated the total additional medical cost due to MDRO infections using the multistate model. RESULTS: During the 6-month period, a total of 486 MDRO bacteremia cases (260, 87, 18, 20 and 101 cases of MRSA, MRAB, MRPA, CRE and VRE, respectively) were identified. The 90-day mortality rates were 30.4%, 63.2%, 16.7%, 55.0% and 47.5%, respectively. The additional costs caused by bacteremia were $15,768, $35,682, $39,908, $72,051 and $33,662 per MDRO type, respectively. Based on these 6-month data, the estimated annual number of bacteremia cases due to these five MDRO in Korea were 7979 (4070, 1396, 218, 461 and 1834 cases, respectively). Overall, this caused an estimated 3280 (1237, 882, 36, 254, 871, respectively) deaths and costing $294,505,002 ($84,707,359, $74,387,364, $10,344,370, $45,850,215 and $79,215,694, respectively) (range $170,627,020 to $416,094,679) in socioeconomic loss. CONCLUSIONS: A tremendous clinical and economic burden is caused by MDRO bacteremia compared with antibiotic-susceptible and no-infection groups. Substantial investment and efforts by related government agencies and medical staffs are needed.

15.
Comput Math Methods Med ; 2022: 3545712, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388160

RESUMO

Tongue diagnosis, a noninvasive examination, is an essential step for syndrome differentiation and treatment in traditional Chinese medicine (TCM). Sublingual vein (SV) is examined to determine the presence of blood stasis and blood stasis syndrome. Many studies have shown that the degree of SV stasis positively correlates with disease severity. However, the diagnoses of SV examination are often subjective because they are influenced by factors such as physicians' experience and color perception, resulting in different interpretations. Therefore, objective and scientific diagnostic approaches are required to determine the severity of sublingual varices. This study aims at developing a computer-assisted system based on machine learning (ML) techniques for diagnosing the severity of sublingual varicose veins. We conducted a comparative study of the performance of several supervised ML models, including the support vendor machine, K-neighbor, decision tree, linear regression, and Ridge classifier and their variants. The main task was to differentiate sublingual varices into mild and severe by using images of patients' SVs. To improve diagnostic accuracy and to accelerate the training process, we proposed using two model reduction techniques, namely, the principal component analysis in conjunction with the slice inverse regression and the convolution neural network (CNN), to extract valuable features during the preprocessing of data. Our results showed that these two extraction methods can reduce the training time for the ML methods, and the Ridge-CNN method can achieve an accuracy rate as high as 87.5%, which is similar to that of experienced TCM physicians. This computer-aided tool can be used for reference clinical diagnosis. Furthermore, it can be employed by junior physicians to learn and to use in clinical settings.


Assuntos
Medicina Tradicional Chinesa , Varizes , Humanos , Medicina Tradicional Chinesa/métodos , Aprendizado de Máquina , Redes Neurais de Computação , Língua , Varizes/diagnóstico por imagem
16.
Oxid Med Cell Longev ; 2022: 1603469, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388170

RESUMO

Testicular torsion/detorsion-induced ischemia/reperfusion injury is partly due to the overgeneration of reactive oxygen species. Baicalein, a main bioactive constituent derived from the dried root of Scutellaria baicalensis Georgi, possesses powerful antioxidative and anti-inflammatory properties. Therefore, we designed the research to explore the possible protective effect of baicalein against testicular ischemia-reperfusion injury. Sprague-Dawley rats were randomized into 4 groups, including control, testicular ischemia-reperfusion, testicular ischemia-reperfusion+vehicle injection, and testicular ischemia-reperfusion+baicalein therapy groups. The control group received surgical exposure of the left testis without torsion-detorsion. In the testicular ischemia-reperfusion group, the left testis underwent 720° counterclockwise torsion for two hours and then was allowed detorsion. Rats in the testicular ischemia-reperfusion+vehicle injection group received intraperitoneal injection of the vehicle at detorsion. In the baicalein-treated group, the intraperitoneal administration of baicalein dissolved in the vehicle was performed at detorsion. At four hours or three months following testicular detorsion, testicular tissues were removed to detect the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1ß) which can recruit neutrophils into the testis, myeloperoxidase activity (an index of neutrophil infiltration in the testis), protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in neutrophils which can catalyze reactive oxygen species production, malondialdehyde concentration (a common marker of reactive oxygen species), and spermatogenesis. Both testicular ischemia-reperfusion and testicular ischemia-reperfusion+vehicle injection significantly increased the TNF-α and IL-1ß levels, myeloperoxidase activity, NADPH oxidase protein expression, and malondialdehyde concentration, while decreased spermatogenesis in ipsilateral testes. In contrast, baicalein administration remarkably reduced TNF-α and IL-1ß levels, myeloperoxidase activity, NADPH oxidase protein expression, and malondialdehyde concentration and also elevated spermatogenesis in ipsilateral testes. The results of our experiment demonstrate that baicalein alleviates testicular ischemia-reperfusion injury by inhibiting TNF-α and IL-1ß secretion, neutrophil infiltration in the testis, and NADPH oxidase protein expression in neutrophils to reduce reactive oxygen species production.


Assuntos
Traumatismo por Reperfusão , Torção do Cordão Espermático , Masculino , Humanos , Ratos , Animais , Torção do Cordão Espermático/complicações , Torção do Cordão Espermático/tratamento farmacológico , Torção do Cordão Espermático/metabolismo , Testículo/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Peroxidase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Malondialdeído/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , NADPH Oxidases/metabolismo , Isquemia/metabolismo
17.
J Am Heart Assoc ; 11(22): e027578, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36346048

RESUMO

Background Dilated cardiomyopathy (DCM), characterized by progressive left ventricular enlargement and systolic dysfunction, is the most common type of cardiomyopathy and a leading cause of heart failure and cardiac death. Accumulating evidence underscores the critical role of genetic defects in the pathogenesis of DCM, and >250 genes have been implicated in DCM to date. However, DCM is of substantial genetic heterogeneity, and the genetic basis underpinning DCM remains elusive in most cases. Methods and Results By genome-wide scan with microsatellite markers and genetic linkage analysis in a 4-generation family inflicted with autosomal-dominant DCM, a new locus for DCM was mapped on chromosome 15q13.1-q13.3, a 4.77-cM (≈3.43 Mbp) interval between markers D15S1019 and D15S1010, with the largest 2-point logarithm of odds score of 5.1175 for the marker D15S165 at recombination fraction (θ)=0.00. Whole-exome sequencing analyses revealed that within the mapping chromosomal region, only the mutation in the KLF13 gene, c.430G>T (p.E144X), cosegregated with DCM in the family. In addition, sequencing analyses of KLF13 in another cohort of 266 unrelated patients with DCM and their available family members unveiled 2 new mutations, c.580G>T (p.E194X) and c.595T>C (p.C199R), which cosegregated with DCM in 2 families, respectively. The 3 mutations were absent from 418 healthy subjects. Functional assays demonstrated that the 3 mutants had no transactivation on the target genes ACTC1 and MYH7 (2 genes causally linked to DCM), alone or together with GATA4 (another gene contributing to DCM), and a diminished ability to bind the promoters of ACTC1 and MYH7. Add, the E144X-mutant KLF13 showed a defect in intracellular distribution. Conclusions This investigation indicates KLF13 as a new gene predisposing to DCM, which adds novel insight to the molecular pathogenesis underlying DCM, implying potential implications for prenatal prevention and precision treatment of DCM in a subset of patients.


Assuntos
Cardiomiopatia Dilatada , Humanos , Cardiomiopatia Dilatada/metabolismo , Mutação , Linhagem , Proteínas Repressoras/genética , Proteínas de Ciclo Celular/genética , Fatores de Transcrição Kruppel-Like/genética
18.
Artigo em Inglês | MEDLINE | ID: mdl-36429812

RESUMO

Exercise stress testing (EST) has limited power in diagnosing obstructive coronary artery disease (CAD). The heart rate variability (HRV) analysis might increase the sensitivity of CAD detection. This study aimed to evaluate the correlation between short-term HRV and myocardial ischemia during EST, including the acceleration, maximum, and recovery stages of heart rate (HR). The HRV during EST from 19 healthy (RHC) subjects and 35 patients with CAD (25 patients with insignificant CAD (iCAD), and 10 patients with significant CAD (sCAD)) were compared. As a result, all HRV indices decreased at the maximum stage and no significant differences between iCAD and sCAD were found. The low-frequency power of heart rate signal (LF) of the RHC group recovered relatively quickly from the third to the sixth minutes after maximum HR, compared with that of the sCAD group. The relative changes of most HRV indices between maximum HR and recovery stage were lower in the sCAD group than in the RHC group, especially in LF, the standard deviation of all normal to normal intervals (SDNN), and the standard deviation in the long axis direction of the Poincaré plot analysis (SD2) indices (p < 0.05). The recovery slope of LF was significantly smaller in the sCAD group than in the RHC group (p = 0.02). The result suggests that monitoring short-term HRV during EST provides helpful insight into the cardiovascular autonomic imbalance in patients with significant CAD. The relative change of autonomic tone, especially the delayed sympathetic recovery, could be an additional marker for diagnosing myocardial ischemia.

19.
Food Sci Anim Resour ; 42(6): 942-952, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36415580

RESUMO

To establish a pre-plating method of chicken satellite cells with high purity, pre-plating was performed under culture conditions of 37°C and 41°C, and the pre-plating time was set from a total of 3 hours to 6 hours in consideration of the cell attachment time. The purity of the cells was confirmed by staining paired box protein 7 (Pax7) after proliferation, and Pax7 expression was the highest in culture flasks shaken for 2 hours after incubation at 41°C for 2 hours to prevent the attachment of satellite cells (p<0.05). Also, when pre-plating and proliferation were performed at 37°C and 41°C, the Pax7 expression rate was higher at 41°C. The differentiation capabilities of the three groups (T3, T6, and T7) with high Pax7 expression were compared and the fusion index (%) and myotube formation area (%) determined by myosin heavy chain (MHC) staining was calculated. The T6 and T7 groups, which were cultured at 41°C, showed significantly higher values than the T3 group (p<0.05). There was no significant difference in the expression of Pax7 and MHC between the T6 and T7 groups (p>0.05). These results suggest that pre-plating at 41°C for a total of 4 hours was the most efficient in terms of cost and time for purifying chicken satellite cells for cultured meat.

20.
Eur J Med Chem ; 244: 114888, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36334453

RESUMO

ESKAPE pathogens, as priority 1 and 2 pathogens, are prevalent infectious agents associated with high morbidity and mortality. ESKAPE can cause broad-spectrum diseases with increasing tendency of resistance acquisition to antibiotics and have enhanced the urge for the development of alternate therapeutics. 1,2,3-Triazole, a highly privileged moiety for the discovery of novel drugs, not only can act as a linker to tether different pharmacophores, but also can serve as a pharmacophore. Notably, several 1,2,3-triazole-containing hybrids which are exemplified by cefatrizine, radezolid and tazobactam have already approved as antibiotics to treat infections caused by various organisms including ESKAPE pathogens and their drug-resistant forms, revealing that 1,2,3-triazole-containing hybrids are useful prototypes for clinical deployment in the control of bacterial infections. The purpose of the present review article is to provide an emphasis on the current scenario (2018-2022) of 1,2,3-triazole-containing hybrids with potential antibacterial activity against ESKAPE pathogens to facilitate further rational design of more effective candidates.


Assuntos
Infecções Bacterianas , Triazóis , Humanos , Testes de Sensibilidade Microbiana , Triazóis/farmacologia , Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico
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