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24 pages, 935 KB  
Review
Cancer-Associated Fibroblasts Arising from Endothelial-to-Mesenchymal Transition: Induction Factors, Functional Roles, and Transcriptomic Evidence
by Junyeol Han, Eung-Gook Kim, Bo Yeon Kim and Nak-Kyun Soung
Biology 2025, 14(10), 1403; https://doi.org/10.3390/biology14101403 - 13 Oct 2025
Viewed by 903
Abstract
Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME) that influence cancer progression via extracellular matrix (ECM) remodeling and secretion of growth factors and cytokines. Endothelial-to-mesenchymal transition (EndMT) is emerging as an important axis among the heterogeneous origins of CAFs. This [...] Read more.
Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME) that influence cancer progression via extracellular matrix (ECM) remodeling and secretion of growth factors and cytokines. Endothelial-to-mesenchymal transition (EndMT) is emerging as an important axis among the heterogeneous origins of CAFs. This review introduces the diverse methods used to induce EndMT in cancer—mouse tumor models, conditioned-medium treatment, co-culture, targeted gene perturbation, ligand stimulation, exosome exposure, irradiation, viral infection, and three-dimensional (3D) culture systems—and summarizes EndMT cell-type evidence uncovered using transcriptomic and proteomic technologies. Hallmark EndMT features include spindle-like morphology, increased motility, impaired angiogenesis and barrier function, decreased endothelial markers (CD31, VE-cadherin), and increased mesenchymal markers (α-SMA, FN1). Reported mechanisms include signaling via TGF-β, cytoskeletal/mechanical stress, reactive oxygen species, osteopontin, PAI-1, IL-1β, GSK-3β, HSP90α, Tie1, TNF-α, HSBP1, and NOTCH. Cancer-induced EndMT affects tumors and surrounding TME—promoting tumor growth and metastasis, expanding cancer stem cell-like cells, driving macrophage differentiation, and redistributing pericytes—and is closely associated with poor survival and therapy resistance. Finally, we indicate each study’s stance: some frame cancer-induced EndMT as a source of CAFs, whereas others, from an endothelial perspective, emphasize barrier weakening and promotion of metastasis. Full article
(This article belongs to the Special Issue Recent Advances in Tumor Microenvironment Biology)
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17 pages, 4073 KB  
Systematic Review
Efficacy and Safety of Esaxerenone for Essential Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
by Abdelrahman Hafez, Ahmed Abdelaziz, Ahmed Mansour, Ibrahim Kamal, Ali Bakr, Ahmed Farid Gadelmawla, Hanaa Elsayed, Mohamed Reyad Mohamed, Karim Ali and Mohamed Elhelw
J. Clin. Med. 2025, 14(16), 5663; https://doi.org/10.3390/jcm14165663 - 11 Aug 2025
Cited by 1 | Viewed by 1321
Abstract
Background/Objectives: Esaxerenone, a novel non-steroidal mineralocorticoid receptor antagonist, has shown promising results in the treatment of essential hypertension (HTN). This study aims to comprehensively analyze the effectiveness of esaxerenone to control BP in patients with essential HTN. Methods: A systematic search was performed [...] Read more.
Background/Objectives: Esaxerenone, a novel non-steroidal mineralocorticoid receptor antagonist, has shown promising results in the treatment of essential hypertension (HTN). This study aims to comprehensively analyze the effectiveness of esaxerenone to control BP in patients with essential HTN. Methods: A systematic search was performed on PubMed, Scopus, Web of Science (WOS), and Cochrane Library from inception until January 2025 for randomized controlled trials (RCTs) comparing esaxerenone with standard HTN usual care. The primary outcome of interest was mean changes in sitting systolic (SBP) and diastolic blood pressure (DBP). Other secondary outcomes were mean changes in 24 h-SBP and 24 h-DBP, and target BP achievement. Safety outcomes, such as adverse events and increased levels of potassium/uric acid, were also assessed. Results: Our meta-analysis included four studies with a total of 1981 patients, all conducted in Japan. Esaxerenone demonstrated dose-dependent blood pressure reductions. At 5 mg, sitting DBP decreased by 4.22 mmHg (95% CI −8.72 to 0.29; p = 0.07) and SBP by 9.07 mmHg (95% CI −17.69 to −0.45; p = 0.04), while the 1.25 mg dose showed smaller, non-significant reductions. For 24 h measurements, only the 5 mg dose achieved significant reductions. Target BP achievement increased by 48% overall (RR 1.48, 95% CI 1.11 to 1.96; p = 0.007), with stronger effects at 5 mg (RR 2.05, 95% CI 1.03 to 4.08; p = 0.04). Esaxerenone significantly reduced nocturnal SBP by 10.62 mmHg (95% CI −14.01 to −7.23; p < 0.001). Conclusions: In patients with essential HTN, esaxerenone was shown to be safe and well-tolerated compared with usual care. Long-term data on safety is warranted. Full article
(This article belongs to the Special Issue Hypertension: Clinical Treatment and Management)
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21 pages, 5005 KB  
Article
A Machine Learning-Based Risk Assessment Study of Unsafe Behavior of Workers in Nuclear Power Plants Under Construction
by Xueqiang Shan, Weibo Yang, Xia Liu, Kai Yu and Hui Cui
Processes 2025, 13(2), 340; https://doi.org/10.3390/pr13020340 - 26 Jan 2025
Cited by 1 | Viewed by 931
Abstract
Most accidents during the construction of nuclear power plants are caused by human unsafe behavior. How to scientifically determine the risk management priority of human unsafe behaviors is the basis for effectively preventing accidents in under-construction nuclear power plants. Although employees are adopted [...] Read more.
Most accidents during the construction of nuclear power plants are caused by human unsafe behavior. How to scientifically determine the risk management priority of human unsafe behaviors is the basis for effectively preventing accidents in under-construction nuclear power plants. Although employees are adopted for control in under-construction nuclear power plants, the records of unsafe behaviors are mostly recorded by inspectors, and the records of behaviors may have missing values. To overcome the above problems, this paper applies machine learning algorithms to construct an employee behavioral risk assessment model. Firstly, by analyzing the influencing factors of unsafe behaviors, the assessment indexes are proposed, then the Random Forest algorithm is used to obtain the characteristic importance of the proposed indexes and exclude those with smaller characteristic importance. Finally, the harmony search (HS) algorithm is used to optimize the back propagation (BP) neural network to construct an assessment model and compare with the BP evaluation model. The results show that the HS-BP model is more accurate and efficient. The results show that the method can comprehensively and effectively analyze workers‘ unsafe behaviors, and the BP neural network is optimized to construct the assessment model using the Harmonic Search algorithm, which is more accurate than the original model. The use of the machine learning method to assess workers’ behaviors can objectively output the risk level and overcome the one-sidedness and subjectivity of the traditional expert evaluation method. Full article
(This article belongs to the Special Issue Risk Assessment and System Safety in the Process Industry)
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17 pages, 4526 KB  
Article
Differential Regulations of Antioxidant Metabolism and Cold-Responsive Genes in Three Bermudagrass Genotypes under Chilling and Freezing Stress
by Zhou Li, Cheng Huang and Liebao Han
Int. J. Mol. Sci. 2023, 24(18), 14070; https://doi.org/10.3390/ijms241814070 - 14 Sep 2023
Cited by 3 | Viewed by 1714
Abstract
As a typical warm-season grass, bermudagrass growth and turf quality begin to decrease when the environmental temperature drops below 20 °C. The current study investigated the differential responses of three bermudagrass genotypes to chilling stress (8/4 °C) for 15 days and then freezing [...] Read more.
As a typical warm-season grass, bermudagrass growth and turf quality begin to decrease when the environmental temperature drops below 20 °C. The current study investigated the differential responses of three bermudagrass genotypes to chilling stress (8/4 °C) for 15 days and then freezing stress (2/−2 °C) for 2 days. The three genotypes exhibited significant variation in chilling and freezing tolerance, and Chuannong-3, common bermudagrass 001, and Tifdwarf were ranked as cold-tolerant, -intermediate, and -sensitive genotypes based on evaluations of chlorophyll content, the photochemical efficiency of photosystem II, oxidative damage, and cell membrane stability, respectively. Chuannong-3 achieved better tolerance through enhancing the antioxidant defense system to stabilize cell membrane and reactive oxygen species homeostasis after being subjected to chilling and freezing stresses. Chuannong-3 also downregulated the ethylene signaling pathway by improving CdCTR1 expression and suppressing the transcript levels of CdEIN3-1 and CdEIN3-2; however, it upregulated the hydrogen sulfide signaling pathway via an increase in CdISCS expression under cold stress. In addition, the molecular basis of cold tolerance could be associated with the mediation of key genes in the heat shock pathway (CdHSFA-2b, CdHSBP-1, CdHSP22, and CdHSP40) and the CdOSMOTIN in Chuannong-3 because the accumulation of stress-defensive proteins, including heat shock proteins and osmotin, plays a positive role in osmoprotection, osmotic adjustment, or the repair of denatured proteins as molecular chaperones under cold stress. The current findings give an insight into the physiological and molecular mechanisms of cold tolerance in the new cultivar Chuannong-3, which provides valuable information for turfgrass breeders and practitioners. Full article
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9 pages, 263 KB  
Article
Predictors of Preeclampsia in the First Trimester in Normotensive and Chronic Hypertensive Pregnant Women
by Susana Vázquez, Julio Pascual, Xavier Durán-Jordà, Jose Luís Hernández, Marta Crespo and Anna Oliveras
J. Clin. Med. 2023, 12(2), 579; https://doi.org/10.3390/jcm12020579 - 11 Jan 2023
Cited by 3 | Viewed by 2975
Abstract
Preeclampsia (PE) is characterized by the new onset of hypertension (HT) and proteinuria beyond the 20th week of gestation. We aimed to find the best predictor of PE and find out if it is different in women with or without HT. Consecutively attended [...] Read more.
Preeclampsia (PE) is characterized by the new onset of hypertension (HT) and proteinuria beyond the 20th week of gestation. We aimed to find the best predictor of PE and find out if it is different in women with or without HT. Consecutively attended pregnant women were recruited in the first trimester of pregnancy and followed-up. Laboratory and office and 24 h-ambulatory blood pressure (BP) data were collected. PE occurred in 6.25% of normotensives (n = 124). Both office mean BP and 24 h-systolic BP in the first trimester were higher in women with versus those without PE (p ≤ 0.001). In women with chronic hypertension (cHT), PE occurred in 55%; office SBP (p = 0.769) and 24 h-SBP (p = 0.589) were similar between those with and those without PE. Regarding biochemistry, in cHT, plasma urea and creatinine were higher in PE women than in those without cHT (p = 0.001 and p = 0.004 for the differences in both parameters). These differences were not observed in normotensives. In normotensives, mean BP was the best predictor of PE [ROC curve = 0.91 (95%CI 0.82–0.99)], best cut-off = 80.3 mmHg. In cHT, plasma urea and creatinine were the best predictors of PE, with ROC curves of 0.94 (95%CI 0.84–1.00) and 0.93 (95%CI 0.83–1.00), respectively. In the first trimester of pregnancy, the strongest predictor of PE in normotensive women is office mean BP, while in cHT, renal parameters are the strongest predictors. Otherwise, office BP is non-inferior to 24 h ambulatory BP to predict PE. Full article
(This article belongs to the Topic Biomarkers in Cardiovascular Disease—Chances and Risks)
15 pages, 1446 KB  
Article
Effects of a Phytogenic Supplement Containing Olive By-Product and Green Tea Extracts on Growth Performance, Lipid Metabolism, and Hepatic Antioxidant Capacity in Largemouth Bass (Micropterus salmoides) Fed a High Soybean Meal Diet
by Jiacheng Liu, Min Xue, Sofia Morais, Maolong He, Hao Wang, Jie Wang, Jose J. Pastor, Rui A. Gonçalves and Xiaofang Liang
Antioxidants 2022, 11(12), 2415; https://doi.org/10.3390/antiox11122415 - 7 Dec 2022
Cited by 23 | Viewed by 3575
Abstract
A 10-week growth trial was conducted to investigate the effects of a phytogenic feed additive (PFA) containing olive by-products and green tea extracts supplemented to a reduced fishmeal/high soybean meal diet on the growth performance, hepatic antioxidant capacity, lipid metabolism, and liver health [...] Read more.
A 10-week growth trial was conducted to investigate the effects of a phytogenic feed additive (PFA) containing olive by-products and green tea extracts supplemented to a reduced fishmeal/high soybean meal diet on the growth performance, hepatic antioxidant capacity, lipid metabolism, and liver health of largemouth bass (Micropterus salmoides). Three experimental diets were tested: (1) a control high fishmeal (40%) and low soybean meal (15.57%) diet (named HFM), (2) a reduced fishmeal (30%) and high soybean meal (30.97%) diet (named HSB), and (3) a HSB diet supplemented with the PFA at 500 mg/kg (named HSB+P). Each diet was assigned to four replicate tanks, each containing 30 largemouth bass (initial body weight, IBW = 48.33 ± 0.01 g). The results showed that increasing the soybean meal content in the diet did not negatively affect growth performance, whereas supplementation with PFA significantly increased weight gain and specific growth rate of largemouth bass compared to both HFM and HSB groups. Reducing fishmeal and increasing soybean meal in the diet caused oxidative stress with a higher content of ROS in the liver. However, the hepatic antioxidant capacity was enhanced, with reduced ROS and increased GSH-Px levels in the HSB+P group. Moreover, the decrease of plasma TG, LDL-C, and LDL-C/TC, and downregulation of lipogenesis and cholesterol synthesis gene expression in liver, indicated that supplementation with the PFA improved fish lipid metabolism. Protein retention efficiency was also significantly increased in largemouth bass fed the diet with PFA supplementation, which regulated (enhanced) AKT-mTOR phosphorylation. These results clearly indicated that a PFA containing olive by-product and green tea extracts can positively improve growth performance, protein retention efficiency, antioxidant capacity, and lipid metabolism of largemouth bass fed a reduced fishmeal/high soybean meal diet. Full article
(This article belongs to the Special Issue Antioxidant Defenses in Fish)
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11 pages, 582 KB  
Article
Impact of Isolated High Home Systolic Blood Pressure and Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus: A 5-Year Prospective Cohort Study
by Nobuko Kitagawa, Noriyuki Kitagawa, Emi Ushigome, Hidetaka Ushigome, Isao Yokota, Naoko Nakanishi, Masahide Hamaguchi, Mai Asano, Masahiro Yamazaki and Michiaki Fukui
J. Clin. Med. 2021, 10(9), 1929; https://doi.org/10.3390/jcm10091929 - 29 Apr 2021
Cited by 3 | Viewed by 2341
Abstract
Background: A previous 2-year cohort study has shown that isolated high home systolic blood pressure (IH-HSBP) may increase the risk of diabetic nephropathy, using normal HBP as a reference. However, this association has not been previously assessed in the medium to long term. [...] Read more.
Background: A previous 2-year cohort study has shown that isolated high home systolic blood pressure (IH-HSBP) may increase the risk of diabetic nephropathy, using normal HBP as a reference. However, this association has not been previously assessed in the medium to long term. Methods: This prospective 5-year cohort study of 424 patients, with normal or mildly increased albuminuria, investigated the effect of IH-HSBP on the risk of diabetic nephropathy in patients with type 2 diabetes mellitus. Diabetic nephropathy was defined as an advancement from normal or mildly increased albuminuira to moderate or severely increased albuminuria. Results: Among 424 patients, 75 developed diabetic nephropathy during the study period. The adjusted odds ratio for developing diabetic nephropathy given IH-HSBP was 2.39 (95% confidence interval, 1.15–4.96, p = 0.02). The odds ratio for developing nephropathy in patients with IH-HSBP younger than 65 years was higher than that in patients with IH-HSBP older than 65 years. Conclusion: IH-HSBP was associated with an increased risk of diabetic nephropathy among type 2 diabetes mellitus patients with normal or mildly increased albuminuria in the medium to long term. The results support and strengthen previous reports. These findings suggest that IH-HSBP might be a useful marker in disease prognostication. Full article
(This article belongs to the Special Issue Current Challenges and Advances in Atherosclerosis)
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13 pages, 2088 KB  
Article
Prevalence of Arterial Hypertension and Characteristics of Nocturnal Blood Pressure Profile of Asthma Patients According to Therapy and Severity of the Disease: The BADA Study
by Domenico Di Raimondo, Gaia Musiari, Alida Benfante, Salvatore Battaglia, Giuliana Rizzo, Antonino Tuttolomondo, Nicola Scichilone and Antonio Pinto
Int. J. Environ. Res. Public Health 2020, 17(18), 6925; https://doi.org/10.3390/ijerph17186925 - 22 Sep 2020
Cited by 12 | Viewed by 4442
Abstract
Background: several studies report an increased risk for asthmatic subjects to develop arterial hypertension and the relationship between these two diseases, frequently co-existing, still has some unclear aspects. Methods: The BADA (blood pressure levels, clinical features and markers of subclinical cardiovascular damage of [...] Read more.
Background: several studies report an increased risk for asthmatic subjects to develop arterial hypertension and the relationship between these two diseases, frequently co-existing, still has some unclear aspects. Methods: The BADA (blood pressure levels, clinical features and markers of subclinical cardiovascular damage of asthma patients) study is aimed to evaluate the prevalence of the cardiovascular comorbidities of asthma and their impact on the clinical outcome. The main exclusion criteria were the presence of other respiratory diseases, current smoking, any contraindication to ambulatory blood pressure monitoring (ABPM). Results: The overall percentage of asthmatics having also hypertension was 75% (30 patients) vs. 45% (18 patients) of the control group (p: 0.012). Reduced level of FEV1 (but not inhaled steroid therapy) was associated to newly-diagnosed hypertension (p: 0.0002), higher day SBP levels (p: 0.003), higher day DBP levels (p: 0.03), higher 24 h-SBP levels (p: 0.005) and higher 24h-DBP levels (p: 0.03). The regression analysis performed taking into account sex, age, diabetes, fasting glucose, and body mass index confirms the independent role played by asthma: odds ratio (OR): 3.66 (CI: 1.29–11.1). Conclusions: hypertension is highly prevalent in asthma; the use of ABPM has allowed the detection of a considerable number of unrecognized hypertensives. Full article
(This article belongs to the Special Issue New Insights in Prevention and Treatment of Cardiovascular Disease)
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17 pages, 3762 KB  
Article
Identification and Characterization of a Thermotolerant TILLING Allele of Heat Shock Binding Protein 1 in Tomato
by Dominik Marko, Asmaa El-shershaby, Filomena Carriero, Stephan Summerer, Angelo Petrozza, Rina Iannacone, Enrico Schleiff and Sotirios Fragkostefanakis
Genes 2019, 10(7), 516; https://doi.org/10.3390/genes10070516 - 7 Jul 2019
Cited by 28 | Viewed by 5582
Abstract
The identification of heat stress (HS)-resilient germplasm is important to ensure food security under less favorable environmental conditions. For that, germplasm with an altered activity of factors regulating the HS response is an important genetic tool for crop improvement. Heat shock binding protein [...] Read more.
The identification of heat stress (HS)-resilient germplasm is important to ensure food security under less favorable environmental conditions. For that, germplasm with an altered activity of factors regulating the HS response is an important genetic tool for crop improvement. Heat shock binding protein (HSBP) is one of the main negative regulators of HS response, acting as a repressor of the activity of HS transcription factors. We identified a TILLING allele of Solanum lycopersicum (tomato) HSBP1. We examined the effects of the mutation on the functionality of the protein in tomato protoplasts, and compared the thermotolerance capacity of lines carrying the wild-type and mutant alleles of HSBP1. The methionine-to-isoleucine mutation in the central heptad repeats of HSBP1 leads to a partial loss of protein function, thereby reducing the inhibitory effect on Hsf activity. Mutant seedlings show enhanced basal thermotolerance, while mature plants exhibit increased resilience in repeated HS treatments, as shown by several physiological parameters. Importantly, plants that are homozygous for the wild-type or mutant HSBP1 alleles showed no significant differences under non-stressed conditions. Altogether, these results indicate that the identified mutant HSBP1 allele can be used as a genetic tool in breeding, aiming to improve the thermotolerance of tomato varieties. Full article
(This article belongs to the Special Issue TILLING and CRISPR to design the varieties of tomorrow)
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25 pages, 7163 KB  
Article
A Novel Approach for Microgrid Protection Based upon Combined ANFIS and Hilbert Space-Based Power Setting
by Ali Hadi Abdulwahid and Shaorong Wang
Energies 2016, 9(12), 1042; https://doi.org/10.3390/en9121042 - 10 Dec 2016
Cited by 20 | Viewed by 5076
Abstract
Nowadays, the use of distributed generation (DG) has increased because of benefits such as increased reliability, reduced losses, improvement in the line capacity, and less environmental pollution. The protection of microgrids, which consist of generation sources, is one of the most crucial concerns [...] Read more.
Nowadays, the use of distributed generation (DG) has increased because of benefits such as increased reliability, reduced losses, improvement in the line capacity, and less environmental pollution. The protection of microgrids, which consist of generation sources, is one of the most crucial concerns of basic distribution operators. One of the key issues in this field is the protection of microgrids against permanent and temporary failures by improving the safety and reliability of the network. The traditional method has a number of disadvantages. The reliability and stability of a power system in a microgrid depend to a great extent on the efficiency of the protection scheme. The application of Artificial Intelligence approaches was introduced recently in the protection of distribution networks. The fault detection method depends on differential relay based on Hilbert Space-Based Power (HSBP) theory to achieve fastest primary protection. It is backed up by a total harmonic distortion (THD) detection method that takes over in case of a failure in the primary method. The backup protection would be completely independent of the main protection. This is rarely attained in practice. This paper proposes a new algorithm to improve protection performance by adaptive network-based fuzzy inference system (ANFIS). The protection can be obtained in a novel way based on this theory. An advantage of this algorithm is that the protection system operates in fewer than two cycles after the occurrence of the fault. Another advantage is that the error detection is not dependent on the selection of threshold values, and all types of internal fault can identify and show that the algorithm operates correctly for all types of faults while preventing unwanted tripping, even if the data were distorted by current transformer (CT) saturation or by data mismatches. The simulation results show that the proposed circuit can identify the faulty phase in the microgrid quickly and correctly. Full article
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