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1.
Front Oncol ; 14: 1409273, 2024.
Article in English | MEDLINE | ID: mdl-38947897

ABSTRACT

Objective: This study aims to develop an artificial intelligence model utilizing clinical blood markers, ultrasound data, and breast biopsy pathological information to predict the distant metastasis in breast cancer patients. Methods: Data from two medical centers were utilized, Clinical blood markers, ultrasound data, and breast biopsy pathological information were separately extracted and selected. Feature dimensionality reduction was performed using Spearman correlation and LASSO regression. Predictive models were constructed using LR and LightGBM machine learning algorithms and validated on internal and external validation sets. Feature correlation analysis was conducted for both models. Results: The LR model achieved AUC values of 0.892, 0.816, and 0.817 for the training, internal validation, and external validation cohorts, respectively. The LightGBM model achieved AUC values of 0.971, 0.861, and 0.890 for the same cohorts, respectively. Clinical decision curve analysis showed a superior net benefit of the LightGBM model over the LR model in predicting distant metastasis in breast cancer. Key features identified included creatine kinase isoenzyme (CK-MB) and alpha-hydroxybutyrate dehydrogenase. Conclusion: This study developed an artificial intelligence model using clinical blood markers, ultrasound data, and pathological information to identify distant metastasis in breast cancer patients. The LightGBM model demonstrated superior predictive accuracy and clinical applicability, suggesting it as a promising tool for early diagnosis of distant metastasis in breast cancer.

2.
Poult Sci ; 103(8): 103877, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38843563

ABSTRACT

This study aims to provide new insight on the association between the development of wooden breast myopathy and mitochondrial and glycolytic activity under oxidative stress. Myopathic muscle had higher oxidative stress together with altered glycolytic metabolism and tricarboxylic acid (TCA) cycle. This was evidenced by significantly elevated antioxidant enzyme activities (catalase, superoxide dismutase, and glutathione peroxidase), decreased citrate synthase activity and postmortem glycolytic potential with increasing wooden breast severity. In addition, affected muscles also exhibited higher initial and ultimate pH values as well as reduced total glucose and lactate contents. Citrate synthase activity was negatively correlated to antioxidant enzyme activities. Taken together, we propose that the development of the wooden breast lesion is a chronic process that may be related to the failure of muscle fibers to defend against the excessively generated oxidative products promoted by mitochondrial damage accompanied by impaired TCA cycle. Furthermore, there was a positive correlation between citrate synthase activity and glycolytic potential, which suggests that the wooden breast condition is linked to the overall altered energy metabolism of the muscle, including the oxidative phosphorylation and glycolytic pathways.

3.
Cell Res ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849501

ABSTRACT

Physiologically, the atria contract first, followed by the ventricles, which is the prerequisite for normal blood circulation. The above phenomenon of atrioventricular sequential contraction results from the characteristically slow conduction of electrical excitation of the atrioventricular node (AVN) between the atria and the ventricles. However, it is not clear what controls the conduction of electrical excitation within AVNs. Here, we find that AVN pacemaker cells (AVNPCs) possess an intact intrinsic GABAergic system, which plays a key role in electrical conduction from the atria to the ventricles. First, along with the discovery of abundant GABA-containing vesicles under the surface membranes of AVNPCs, key elements of the GABAergic system, including GABA metabolic enzymes, GABA receptors, and GABA transporters, were identified in AVNPCs. Second, GABA synchronously elicited GABA-gated currents in AVNPCs, which significantly weakened the excitability of AVNPCs. Third, the key molecular elements of the GABAergic system markedly modulated the conductivity of electrical excitation in the AVN. Fourth, GABAA receptor deficiency in AVNPCs accelerated atrioventricular conduction, which impaired the AVN's protective potential against rapid ventricular frequency responses, increased susceptibility to lethal ventricular arrhythmias, and decreased the cardiac contractile function. Finally, interventions targeting the GABAergic system effectively prevented the occurrence and development of atrioventricular block. In summary, the endogenous GABAergic system in AVNPCs determines the slow conduction of electrical excitation within AVNs, thereby ensuring sequential atrioventricular contraction. The endogenous GABAergic system shows promise as a novel intervention target for cardiac arrhythmias.

4.
Food Res Int ; 188: 114440, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823857

ABSTRACT

The emulsification activity of myosin plays a significant role in affecting quality of emulsified meat products. High-density lipoprotein (HDL) possesses strong emulsification activity and stability due to its structural characteristics, suggesting potential for its utilization in developing functional emulsified meat products. In order to explore the effect of HDL addition on emulsification stability, rheological properties and structural features of myosin (MS) emulsions, HDL-MS emulsion was prepared by mixing soybean oil with isolated HDL and MS, with pH adjustments ranging from 3.0 to 11.0. The results found that emulsification activity and stability in two emulsion groups consistently improved as pH increased. Under identical pH, HDL-MS emulsion exhibited superior emulsification behavior as compared to MS emulsion. The HDL-MS emulsion under pH of 7.0-11.0 formed a viscoelastic protein layer at the interface, adsorbing more proteins and retarding oil droplet diffusion, leading to enhanced oxidative stability, compared to the MS emulsion. Raman spectroscopy analysis showed more flexible conformational changes in the HDL-MS emulsion. Microstructural observations corroborated these findings, showing a more uniform distribution of droplet sizes in the HDL-MS emulsion with smaller particle sizes. Overall, these determinations suggested that the addition of HDL enhanced the emulsification behavior of MS emulsions, and the composite emulsions demonstrated heightened responsiveness under alkaline conditions. This establishes a theoretical basis for the practical utilization of HDL in emulsified meat products.


Subject(s)
Emulsions , Lipoproteins, HDL , Myosins , Rheology , Emulsions/chemistry , Hydrogen-Ion Concentration , Lipoproteins, HDL/chemistry , Myosins/chemistry , Meat Products/analysis , Particle Size , Soybean Oil/chemistry , Viscosity , Spectrum Analysis, Raman
5.
Food Res Int ; 188: 114461, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823861

ABSTRACT

Myofibrillar proteins are crucial for gel formation in processed meat products such as sausages and meat patties. Freeze-thaw cycles can alter protein properties, impacting gel stability and product quality. This study aims to investigate the potential of thawed drip and its membrane-separated components as potential antifreeze agents to retard denaturation, oxidation and gel deterioration of myofibrillar proteins during freezing-thawing cycles of pork patties. The thawed drip and its membrane-separated components of > 10 kDa and < 10 kDa, along with deionized water, were added to minced pork at 10 % mass fraction and subjected to increasing freeze-thaw cycles. Results showed that the addition of thawed drip and its membrane separation components inhibited denaturation and structural changes of myofibrillar proteins, evidenced by reduced surface hydrophobicity and carbonyl content, increased free sulfhydryl groups, protein solubility and α-helix, as compared to the deionized water group. Correspondingly, improved gel properties including water-holding capacity, textural parameters and denser network structure were observed with the addition of thawed drip and its membrane separation components. Denaturation and oxidation of myofibrillar proteins were positively correlated with gel deterioration during freezing-thawing cycles. We here propose a role of thawed drip and its membrane separation components as cryoprotectants against myofibrillar protein gel deterioration during freeze-thawing cycles.


Subject(s)
Freezing , Gels , Muscle Proteins , Myofibrils , Animals , Gels/chemistry , Swine , Muscle Proteins/chemistry , Myofibrils/chemistry , Food Handling/methods , Protein Denaturation , Meat Products/analysis , Hydrophobic and Hydrophilic Interactions , Solubility , Water/chemistry , Oxidation-Reduction
6.
Int J Biol Macromol ; 271(Pt 2): 132488, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38763248

ABSTRACT

Nanoparticles are used as fillers to improve the properties of biopolymers, and their particle size is an important parameter. This work aims to investigate the effect of particle size of isoreticular metal-organic framework-3 (IRMOF-3) on the mechanical, physical, and release properties of sodium alginate (SA)-based composite active film. In our study, IRMOF-3 with six different particle sizes was synthesized by introducing additives. IRMOF-3 loading with carvacrol (IRMOF-3/CA nanoparticles) was incorporated into the SA matrix to prepare the composite film. The characterization and testing results of films showed that the particle size of nanoparticles affected the physical morphology and chemical structure of the film. Especially smaller nanoparticles uniformly dispersed into the SA matrix more easily, forming a denser and more stable spatial network structure with SA, which could more significantly improve the tensile strength, water vapor barrier, and hydrophobic properties of the film (P < 0.05). In addition, the CA release rate from the active film could be significantly reduced by about 33.90 % even when the smallest particle size of the IRMOF-3/CA nanoparticles was added. Therefore, when IRMOF-3/CA is used as the nano-filler to develop SA-based active film, its particle size has a potential influence on the properties of the film.


Subject(s)
Alginates , Metal-Organic Frameworks , Nanocomposites , Particle Size , Alginates/chemistry , Nanocomposites/chemistry , Metal-Organic Frameworks/chemistry , Tensile Strength , Cymenes/chemistry , Hydrophobic and Hydrophilic Interactions , Steam
7.
Curr Mol Med ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38778614

ABSTRACT

Ribosomal DNA (rDNA) is important in the nucleolus and nuclear organization of human cells. Defective rDNA repeat maintenance has been reported to be closely associated with neurological disorders, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, depression, suicide, etc. However, there has not been a comprehensive review on the role of rDNA in these disorders. In this review, we have summarized the role of rDNA in major neurological disorders to sort out the correlation between rDNA and neurological diseases and provided insights for therapy with rDNA as a target.

8.
Int J Biol Macromol ; 268(Pt 2): 131786, 2024 May.
Article in English | MEDLINE | ID: mdl-38657927

ABSTRACT

This study investigated impact of high-density lipoprotein (HDL) on thermal aggregation and gelling behavior of myosin in relation to varied pHs. Results revealed that HDL modified myosin structure before and after heating, with distinct effects observed at varied pH. Under pH 5.0, both myosin and HDL-MS exhibited larger aggregates and altered microstructure; at pH 7.0 and 9.0, HDL inhibited myosin aggregation, resulting in enhanced solubility, reduced turbidity and particle size. Comparative analysis of surface hydrophobicity, free sulfhydryl groups and secondary structure highlighted distinct thermal aggregation behavior between MS and HDL-MS, with the latter showing inhibitory effects under neutral or alkaline conditions. Gelation behavior was enhanced at pH 7.0 with maximum strength, hardness, water-holding capacity and rheological properties. Under acidic pH, excessive protein aggregation resulted in increased whiteness and rough microstructure with granular aggregates. Under alkaline pH, gel network structure was weaker, possibly due to higher thermal stability of protein molecules. Scanning electron microscopy revealed expanded HDL protein particles at pH 7.0, accounting for decreased gel strength and altered rheological properties compared with myosin gel. Overall, the results indicated a positive role of HDL at varied pH in regulating thermal aggregation of myosin and further impacting heat-induced gel characteristics.


Subject(s)
Gels , Hot Temperature , Lipoproteins, HDL , Myosins , Protein Aggregates , Rheology , Hydrogen-Ion Concentration , Myosins/chemistry , Myosins/metabolism , Lipoproteins, HDL/chemistry , Gels/chemistry , Hydrophobic and Hydrophilic Interactions , Solubility , Animals , Particle Size
9.
Food Chem ; 447: 138979, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-38518617

ABSTRACT

Traditional Beijing roast duck often suffers from uneven color and high sugar content after roasting. Water-in-oil (W/O) nanoemulsion is a promising alternative to replace high concentration of sugar solution used in sugaring process according to similarity-intermiscibility theory. Herein, 3% of xylose was embedded in the aqueous phase of W/O emulsion to replace 15% maltose solution. W/O emulsions with different ratios of lecithin (LEC) and polyglycerol polyricinoleate (PGPR) were constructed by high-speed homogenization and high-pressure homogenization. Distribution and penetration extent of solutions and emulsions through the duck skin, as well as the color uniformity of Beijing roast duck were analyzed. Emulsions with LEC:PGPR ratios of 1:3 and 2:2 had better stability. Stable interfacial film and spatial structure were important factors influencing emulsion stabilization. The stable W/O emulsions could more uniformly distribute onto the surface of duck skin and longitudinally penetrate through the skin than solutions.


Subject(s)
Ducks , Glycerol/analogs & derivatives , Lecithins , Ricinoleic Acids , Animals , Lecithins/chemistry , Emulsions/chemistry , Sugars , Water/chemistry , Beijing
10.
Diabetes Metab Syndr Obes ; 17: 633-646, 2024.
Article in English | MEDLINE | ID: mdl-38343583

ABSTRACT

Objective: Gestational diabetes mellitus (GDM) is a condition of glucose intolerance, which may be accompanied with inflammation. The levels of hematological parameters during pregnancy can reflect inflammatory conditions in pregnant women. This study aims to describe the dynamic change of blood cell parameters from the first trimester (6-12 weeks of gestation) to the second trimester (24-28 weeks of gestation) and to investigate the associations of these biomarkers with the risk of GDM. Methods: This study was a prospective double-center study conducted in Beijing, China (clinical trial number: NCT03246295). Hematological parameters were tested four times during the follow-up. Logistic regression analysis and Receiver Operating Characteristic (ROC) curve analysis were used to explore the association and predictive ability of hematological parameters for GDM. Results: There were 258 of 1027 pregnant women in our study developed GDM. Among the 1027 pregnant women, white blood cells (WBC) gradually increased, and red blood cells (RBC), hemoglobin (HGB), and platelet (PLT) tended to decrease from the first trimester to second trimester. After adjusting for confounding factors, higher levels of RBC, HGB, and PLT in both early and middle pregnancy were positively associated with GDM risk, whereas the level of WBC was associated with GDM risk only in early pregnancy. WBC, RBC, HGB, and PLT in early and middle pregnancy were all correlated with fasting insulin (FINS) in early pregnancy. Conclusion: Higher levels of hematological parameters in early and middle pregnancy were associated with glucose metabolism in early pregnancy and the subsequent risk of GDM.

11.
Foods ; 13(2)2024 Jan 11.
Article in English | MEDLINE | ID: mdl-38254528

ABSTRACT

Two fermenters, Lactobacillus acidophilus (LA) and the active dry yellow wine yeast (HY), were utilized to ferment cattle bones in order to release calcium. The influences of fermenters and the fermentation process on the calcium release capacity, particle properties, morphology, and chemical composition of bone powders were assessed, and the underlying mechanism was discussed. The results showed that LA had a better capacity of acid production than yeast, and therefore released more calcium during the fermentation of bone powders. The released calcium in the fermentation broth mainly existed in the forms of free Ca2+ ions, organic acid-bound calcium and a small amount of calcium-peptide chelate. For bone powders, the fermentation induced swollen bone particles, increased particle size, and significant changes of the internal chemical structure. Therefore, fermentation has a great potential in the processing of bone-derived products, particularly to provide new ideas for the development of calcium supplement products.

12.
Circ Res ; 134(3): 290-306, 2024 02 02.
Article in English | MEDLINE | ID: mdl-38197258

ABSTRACT

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disorder. However, the pathogenesis of HCM, especially its nongenetic mechanisms, remains largely unclear. Transcription factors are known to be involved in various biological processes including cell growth. We hypothesized that SP1 (specificity protein 1), the first purified TF in mammals, plays a role in the cardiomyocyte growth and cardiac hypertrophy of HCM. METHODS: Cardiac-specific conditional knockout of Sp1 mice were constructed to investigate the role of SP1 in the heart. The echocardiography, histochemical experiment, and transmission electron microscope were performed to analyze the cardiac phenotypes of cardiac-specific conditional knockout of Sp1 mice. RNA sequencing, chromatin immunoprecipitation sequencing, and adeno-associated virus experiments in vivo were performed to explore the downstream molecules of SP1. To examine the therapeutic effect of SP1 on HCM, an SP1 overexpression vector was constructed and injected into the mutant allele of Myh6 R404Q/+ (Myh6 c. 1211C>T) HCM mice. The human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with HCM were used to detect the potential therapeutic effects of SP1 in human HCM. RESULTS: The cardiac-specific conditional knockout of Sp1 mice developed a typical HCM phenotype, displaying overt myocardial hypertrophy, interstitial fibrosis, and disordered myofilament. In addition, Sp1 knockdown dramatically increased the cell area of hiPSC-CMs and caused intracellular myofibrillar disorganization, which was similar to the hypertrophic cardiomyocytes of HCM. Mechanistically, Tuft1 was identified as the key target gene of SP1. The hypertrophic phenotypes induced by Sp1 knockdown in both hiPSC-CMs and mice could be rescued by TUFT1 (tuftelin 1) overexpression. Furthermore, SP1 overexpression suppressed the development of HCM in the mutant allele of Myh6 R404Q/+ mice and also reversed the hypertrophic phenotype of HCM hiPSC-CMs. CONCLUSIONS: Our study demonstrates that SP1 deficiency leads to HCM. SP1 overexpression exhibits significant therapeutic effects on both HCM mice and HCM hiPSC-CMs, suggesting that SP1 could be a potential intervention target for HCM.


Subject(s)
Cardiomyopathy, Hypertrophic , Induced Pluripotent Stem Cells , Humans , Mice , Animals , Induced Pluripotent Stem Cells/metabolism , Cardiomyopathy, Hypertrophic/metabolism , Myofibrils/metabolism , Myocytes, Cardiac/metabolism , Cardiomegaly/metabolism , Transcription Factors/metabolism , Mammals
13.
Biochem Biophys Rep ; 37: 101639, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38288281

ABSTRACT

Ovarian cancer is among the most prevalent gynecological malignancies around the globe. Nonetheless, chemoresistance continues to be one of the greatest obstacles in the treatment of ovarian cancer. Therefore, understanding the mechanisms of chemoresistance and identifying new treatment options for ovarian cancer patients is urgently required. In this study, we found that the mRNA and protein expression levels of PRDX1 were significantly increased in cisplatin resistant A2780/CDDP cells. Cell survival assays revealed that PRDX1 depletion substantially increased ovarian cancer cell sensitivity to cisplatin, docetaxel, and doxorubicin. Additionally, PRDX1 significantly increased GSTP1 activity, resulting in multidrug resistance. Biochemical experiments showed that PRDX1 interacted with GSTP1 through Cysteine 83, which regulated GSTP1 activity as well as chemotherapy resistance in ovarian cancer cells. Our findings indicate that the molecular chaperone activity of PRDX1 is a promising new therapeutic target for ovarian cancer.

14.
Microbiol Res ; 280: 127588, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38163390

ABSTRACT

Fungi play a crucial role in decomposing litter and facilitating the energy flow between aboveground plants and underground soil in forest ecosystems. However, our understanding how the fungal community involved in litter decomposition responds during forest succession, particularly in disease-driven succession, is still limited. This study investigated the activity of degrading enzyme, fungal community, and predicted function in litter after one year of decomposition in different types of forests during a forest succession gradient from coniferous to deciduous forest, induced by pine wilt disease. The results showed that the weight loss of needles/leaves and twigs did not change along the succession process, but twigs degraded faster than needles/leaves in both pure pine forest and mixed forest. In pure pine forest, peak activities of enzymes involved in carbon degradation (ß-cellobiosidase, ß-glucosidase, ß-D-glucuronidase, ß-xylosidase), nitrogen degradation (N-acetyl-glucosamidase), and organic phosphorus degradation (phosphatase) were observed in needles, which subsequently declined. The fungal diversity and evenness (Shannon's diversity and Shannon's evenness) dropped in twig from coniferous forest to mixed forest during the succession. The dominant phyla in needle/leaf and twig litters were Ascomycota (46.9%) and Basidiomycota (38.9%), with Lambertella pruni and Chalara hughesii identified as the most abundant indicator species. Gymnopus and Desmazierella showed positively correlations with most measured enzyme activities. Functionally, saprotrophs constituted the main trophic mode (47.65%), followed by Pathotroph-Saprotroph-Symbiotroph (30.95%) and Saprotroph-Symbiotroph (10.57%). The fungal community and predicted functional structures in both litter types shifted among different forest types along the succession. These findings indicate that the fungal community in litter decomposition responds differently to disease-induced succession, leading to significant shifts in both the fungal community structure and function.


Subject(s)
Agaricales , Mycobiome , Pinus , Ecosystem , Fungi/metabolism , Forests , Soil/chemistry , Soil Microbiology
15.
Endocrine ; 83(3): 636-647, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37782356

ABSTRACT

PURPOSE: The association between serum uric acid (UA) and gestational diabetes mellitus (GDM) was still unclear. Serum UA levels in pregnancy differed from that in non-pregnancy. This study aimed to investigate the changes of serum UA in early pregnancy, and to explore the association of serum UA with the risk of GDM. METHODS: A prospective double-center study including 873 singleton pregnant women was conducted in Beijing, China since 2019 (clinical trial number: NCT03246295). Seventy-eight healthy non-pregnant women were selected to compare the changes of biomarkers in pregnancy. Spearman correlation and logistic regression analysis were performed to measure the relationship between serum UA in early pregnancy and GDM. RESULTS: The incidence of GDM in our cohort was 20.27%(177/873). Compared with non-pregnant women, serum UA and creatinine decreased significantly during early pregnancy. Serum UA concentration in early pregnancy was significantly higher in GDM women than that in normal glucose tolerance (NGT) women [217.0(192.9, 272.0) µmol/l vs. 201.9(176.0, 232.0) µmol/l, p < 0.001]. After adjusted for confounding factors, elevated serum UA remained as an independent risk factor for GDM. The risk of GDM increased when serum UA was above 240 µmol/l (adjusted OR 1.964, 95% CI 1.296-2.977, p < 0.001), and stronger relationships between serum UA and GDM were observed in pregnant women aged over 35 years old and preBMI ≥ 24 kg/m2. CONCLUSION: The normal range of serum UA and creatinine in pregnant women were lower than those in non-pregnant women. It is essential to monitor serum UA concentrations since early pregnancy to alert and prevent GDM, especially in older and heavier pregnant women. CLINICAL TRIAL NUMBER: NCT03246295.


Subject(s)
Diabetes, Gestational , Pregnancy , Female , Humans , Aged , Adult , Diabetes, Gestational/epidemiology , Uric Acid , Prospective Studies , Creatinine , Glucose Tolerance Test
16.
Mol Metab ; 79: 101839, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37979657

ABSTRACT

OBJECTIVE: G-protein-signaling modulator 1 (GPSM1) has been proved the potential role in brain tissues, however, whether GPSM1 in hypothalamic nuclei, especially in POMC neurons is essential for the proper regulation of whole-body energy balance remains unknown. The aim of our current study was to explore the role of GPSM1 in POMC neurons in metabolic homeostasis. METHODS: We generated POMC neuron specific GPSM1 deficiency mice and subjected them to a High Fat Diet to monitor metabolic phenotypes in vivo. By using various molecular, biochemical, immunofluorescent, immunohistochemical analyses, and cell culture studies to reveal the pathophysiological role of GPSM1 in POMC neurons and elucidate the underlying mechanisms of GPSM1 regulating POMC neurons activity. RESULTS: We demonstrated that mice lacking GPSM1 in POMC neurons were protected against diet-induced obesity, glucose dysregulation, insulin resistance, and hepatic steatosis. Mechanistically, GPSM1 deficiency in POMC neurons induced enhanced autophagy and improved leptin sensitivity through PI3K/AKT/mTOR signaling, thereby increasing POMC expression and α-MSH production, and concurrently enhancing sympathetic innervation and activity, thus resulting in decreased food intake and increased brown adipose tissue thermogenesis. CONCLUSIONS: Our findings identify a novel function of GPSM1 expressed in POMC neurons in the regulation of whole-body energy balance and metabolic homeostasis by regulating autophagy and leptin sensitivity, which suggests that GPSM1 in the POMC neurons could be a promising therapeutic target to combat obesity and obesity-related metabolic disorders.


Subject(s)
Adipose Tissue, Brown , Adrenal Insufficiency , Leptin , Animals , Mice , Adipose Tissue, Brown/metabolism , Diet, High-Fat/adverse effects , Leptin/metabolism , Neurons/metabolism , Obesity/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Pro-Opiomelanocortin/genetics , Pro-Opiomelanocortin/metabolism , Thermogenesis/genetics
17.
Diabetes Ther ; 14(12): 2143-2157, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37843770

ABSTRACT

INTRODUCTION: This study aimed to develop a simplified screening model to identify pregnant Chinese women at risk of gestational diabetes mellitus (GDM) in the first trimester. METHODS: This prospective study included 1289 pregnant women in their first trimester (6-12 weeks of gestation) with clinical parameters and laboratory data. Logistic regression was performed to extract coefficients and select predictors. The performance of the prediction model was assessed in terms of discrimination and calibration. Internal validation was performed through bootstrapping (1000 random samples). RESULTS: The prevalence of GDM in our study cohort was 21.1%. Maternal age, prepregnancy body mass index (BMI), a family history of diabetes, fasting blood glucose levels, the alanine transaminase to aspartate aminotransferase ratio (ALT/AST), and the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) were selected for inclusion in the prediction model. The Hosmer-Lemeshow goodness-of-fit test showed good consistency between prediction and actual observation, and bootstrapping indicated good internal performance. The area under the receiver operating characteristic curve (ROC-AUC) of the multivariate logistic regression model and the simplified clinical screening model was 0.825 (95% confidence interval [CI] 0.797-0.853, P < 0.001) and 0.784 (95% CI 0.750-0.818, P < 0.001), respectively. The performance of our prediction model was superior to that of three other published models. CONCLUSION: We developed a simplified clinical screening model for predicting the risk of GDM in pregnant Chinese women. The model provides a feasible and convenient protocol to identify women at high risk of GDM in early pregnancy. Further validations are needed to evaluate the performance of the model in other populations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03246295.

18.
Int Immunopharmacol ; 123: 110793, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37582311

ABSTRACT

ß-defensin-1 (BD-1) is a rich source of disulfide bonds and antibacterial peptides that exhibit direct bactericidal function. The expression of BD-1 is primarily induced by external stimulation and is known to correlate with TLR-mediated inflammation, suggesting its association with innate immune responses. Equine ß-defensin-1 (eBD-1) belongs to the BD-1 family. Our previous study demonstrated that eBD-1 enhances cytokine expression and promotes macrophage phagocytosis of S. aureus, although the underlying mechanism remains unknown. In this study, we utilized a PI-3K inhibitor (PKI-402) to treat eBD-1 -treated S. aureus-infected macrophages in vitro. Our results revealed that PKI-402 decreased the expression of eBD-1-promoted TNF-α, IL-6, CXCL10, CD40, RANTES, and p65 mRNA. To further investigate the relationship between eBD-1 and phagocytosis, we examined the expression of paxillin and FcγRIII (CD16 receptor) using western blot and immunofluorescence techniques. Our findings demonstrated that eBD-1 enhanced CD16 and paxillin expression in S. aureus -infected macrophages. Considering the correlation between paxillin expression and focal adhesion kinase (FAK), we transfected FAK siRNA into macrophages and evaluated paxillin expression using western blot analysis. Additionally, we quantified the number of S. aureus phagocytosed by macrophages. The results indicated a reduction in both paxillin expression and the number of S. aureus phagocytosed by macrophages upon FAK siRNA treatment. Our study showed the eBD-1 promotes cytokine mRNA expression in S. aureus-infected macrophages regulated by PI-3K-NF-κB pathway, and it increases macrophage phagocytosis of S. aureus associated with the FAK-paxillin signaling pathway.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , beta-Defensins , Mice , Animals , Horses , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Paxillin/metabolism , Staphylococcus aureus , Phosphatidylinositol 3-Kinases/metabolism , Cytokines/metabolism , Monocytes/metabolism , beta-Defensins/genetics , beta-Defensins/metabolism , Macrophages/metabolism , Phagocytosis , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Phosphorylation
19.
Food Chem ; 429: 136836, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37453331

ABSTRACT

During storage and processing, muscle proteins, e.g. myosin and myoglobin, will inevitably undergo degeneration, which is thus accompanied by quality deterioration of muscle foods. Some exogenous additives have been widely used to interact with muscle proteins to stabilize the quality of muscle foods. Molecular docking and molecular dynamics simulation (MDS) are regarded as promising tools for recognizing dynamic molecular information at atomic level. Molecular docking and MDS can explore chemical bonds, specific binding sites, spatial structure changes, and binding energy between additives and muscle proteins. Development and workflow of molecular docking and MDS are systematically summarized in this review. Roles of molecular simulations are, for the first time, comprehensively discussed in recognizing the interaction details between muscle proteins and exogenous additives aimed for stabilizing color, texture, flavor, and other properties of muscle foods. Finally, research directions of molecular docking and MDS for improving the qualities of muscle foods are discussed.


Subject(s)
Molecular Dynamics Simulation , Muscle Proteins , Molecular Docking Simulation , Binding Sites , Protein Binding
20.
Sci Rep ; 13(1): 10131, 2023 06 22.
Article in English | MEDLINE | ID: mdl-37349531

ABSTRACT

Our objective was to provide a method for selecting reference beam model and evaluating the dosimetric accuracy of volumetric modulated arc therapy (VMAT) plans delivered on three Elekta beam-matched linacs during radiation oncology. Beam data was measured on three beam-matched linacs including Synergy1, Synergy2 and VersaHD. For eighteen lung and esophagus cases, fifty-four plans were generated using VMAT technique with three linac beam models respectively for point dose measurement and three-dimensional dose measurement. Each VMAT plan was executed sequentially on three linacs respectively. Measurement results were compared with treatment planning system (TPS) calculation results for all VMAT plans. Among three beam-matched linacs, discrepancy in beam output factor, percentage depth dose at 5 cm, 10 cm, 20 cm depth and MLC leaf offset are all within 1% except 20 × 20 cm2 and 30 × 30 cm2 field sizes, and discrepancy in beam profile is all within 2%. With comparison between measurement result and TPS calculation result, the absolute dose deviations are within the range of ± 3%, and the gamma passing rates are all over 95% for all VMAT plans, which are within the tolerance of clinical acceptability. Compared with all plans delivered on Synegy1 and VersaHD, the point dose discrepancy between measured results and TPS calculated results for plans delivered on Synergy2 is smallest, and the gamma passing rate between measured results and TPS calculated results for plans delivered on Synergy2 is highest. The beam-matched linacs demonstrate good agreement between measurement result and TPS calculation result for VMAT plans. The method can be used for selecting reference beam model for VMAT plans.


Subject(s)
Radiation Oncology , Radiotherapy, Intensity-Modulated , Radiotherapy, Intensity-Modulated/methods , Radiotherapy Planning, Computer-Assisted/methods , Phantoms, Imaging , Radiotherapy Dosage , Particle Accelerators
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