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1.
Int J Gen Med ; 17: 2527-2538, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38841128

RESUMEN

Background: Emerging evidence suggests that systemic inflammatory and nutritional biomarkers, along with derived indices, could serve as predictors for sarcopenia in cancer population. This study aimed to compare these predictors, focusing on the nutritional risk index (NRI) and evaluate its diagnostic value, for sarcopenic patients without cancer. Methods: This cross-sectional retrospective study included 1674 participants. Sarcopenia is defined by skeletal muscle mass index (SMI). Laboratory data reflected the values of systemic inflammatory and nutritional biomarkers, from which the derived indices were calculated. Multiple logistic regression analysis, ROC curve analysis, and the Youden index were utilized to assess the association between these markers and sarcopenia and determine the cutoff value for predicting sarcopenia. Results: Among all participants (1110 men and 564 women, mean age 61.97 ± 9.83 years), 398 individuals were diagnosed with sarcopenia, indicating a prevalence of 23.78% in China's middle-aged and elderly population without cancer. Logistic regression analysis revealed significant associations between all biomarkers and derived indices with sarcopenia. Following adjustment for potential confounders, lower NRI values were significantly associated with a higher incidence of sarcopenia. For sarcopenia diagnosis, the area under the curve (AUC) for NRI was 0.769 ([95% CI, 0.742, 0.796], P < 0.001), with a cutoff value of 106.016, sensitivity of 75.6% and specificity of 66.1%. NRI demonstrated greater predictive advantage for sarcopenia incidence in men compared to women. Conclusion: A lower NRI value was associated with a higher prevalence of sarcopenia. NRI shows promise for early, rapid, and effective sarcopenia screening, particularly in China's middle-aged and elderly male population without cancer.

2.
Gastroenterol Rep (Oxf) ; 12: goae066, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38912038

RESUMEN

During liver ischemia-reperfusion injury, existing mechanisms involved oxidative stress, calcium overload, and the activation of inflammatory responses involve mitochondrial injury. Mitochondrial autophagy, a process that maintains the normal physiological activity of mitochondria, promotes cellular metabolism, improves cellular function, and facilitates organelle renewal. Mitochondrial autophagy is involved in oxidative stress and apoptosis, of which the PINK1-Parkin pathway is a major regulatory pathway, and the deletion of PINK1 and Parkin increases mitochondrial damage, reactive oxygen species production, and inflammatory response, playing an important role in mitochondrial quality regulation. In addition, proper mitochondrial permeability translational cycle regulation can help maintain mitochondrial stability and mitigate hepatocyte death during ischemia-reperfusion injury. This mechanism is also closely related to oxidative stress, calcium overload, and the aforementioned autophagy pathway, all of which leads to the augmentation of the mitochondrial membrane permeability transition pore opening and cause apoptosis. Moreover, the release of mitochondrial DNA (mtDNA) due to oxidative stress further aggravates mitochondrial function impairment. Mitochondrial fission and fusion are non-negligible processes required to maintain the dynamic renewal of mitochondria and are essential to the dynamic stability of these organelles. The Bcl-2 protein family also plays an important regulatory role in the mitochondrial apoptosis signaling pathway. A series of complex mechanisms work together to cause hepatic ischemia-reperfusion injury (HIRI). This article reviews the role of mitochondria in HIRI, hoping to provide new therapeutic clues for alleviating HIRI in clinical practice.

3.
Food Chem ; 456: 140036, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38878538

RESUMEN

1-Aminohydantoin (AHD), the residual marker of nitrofurantoin, is usually detected after derivatisation using the derivatisation reagent 2-nitrobenzaldehyde. Avoiding the antibody recognition of the derivatisation reagent is essential for the accurate detection of AHD residues. In this paper, a novel hapten called hapten D was designed, and then, a monoclonal antibody that did not recognise 2-nitrobenzaldehyde was prepared based on this novel hapten. An ultra-sensitive indirect competitive enzyme linked-immunosorbent assay (icELISA) was established under optimal conditions. The 50% inhibition concentration and limit of detection of AHD were 0.056 and 0.0060 ng/mL, respectively, which improved the sensitivity by 9-37-fold compared with the previously reported icELISA methods. The average recovery rates were 88.1%-97.3%, and the coefficient of variation was <8.6%. The accuracy and reliability of the icELISA were verified using liquid chromatography-tandem mass spectrometry. These results demonstrated that the developed icELISA is a useful and reliable tool.

4.
Toxicol In Vitro ; 99: 105867, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38848824

RESUMEN

Pristimerin (Pris), a bioactive triterpenoid compound extracted from the Celastraceae and Hippocrateaceae families, has been reported to exhibit an anti-cancer property on various cancers. However, the effects of Pris on esophageal cancer are poorly investigated. This current study sought to explore the activity and underlying mechanism of Pris against human esophageal squamous cell carcinoma (ESCC) cells. We demonstrated that Pris showed cytotoxicity in TE-1 and TE-10 ESCC cell lines, and significantly inhibited cell viability in a concentration dependent manner. Pris induced G0/G1 phase arrest and triggered apoptosis. It was also observed that the intracellular ROS level was remarkedly increased by Pris treatment. Besides, the function of Pris mediating the activation of ER stress and the inhibition of AKT/GSK3ß signaling pathway in TE-1 and TE-10 cells was further confirmed, which resulted in cell growth inhibition. And moreover, we revealed that all of the above pathways were regulated through ROS generation. In conclusion, our findings suggested that Pris might be considered as a novel natural compound for the developing anti-cancer drug candidate for human esophageal cancer.

5.
Cell Mol Immunol ; 21(7): 674-688, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38740925

RESUMEN

The NLRP3 inflammasome functions as an inflammatory driver, but its relationship with lipid metabolic changes in early sepsis remains unclear. Here, we found that GITR expression in monocytes/macrophages was induced by lysophosphatidylcholine (LPC) and was positively correlated with the severity of sepsis. GITR is a costimulatory molecule that is mainly expressed on T cells, but its function in macrophages is largely unknown. Our in vitro data showed that GITR enhanced LPC uptake by macrophages and specifically enhanced NLRP3 inflammasome-mediated macrophage pyroptosis. Furthermore, in vivo studies using either cecal ligation and puncture (CLP) or LPS-induced sepsis models demonstrated that LPC exacerbated sepsis severity/lethality, while conditional knockout of GITR in myeloid cells or NLRP3/caspase-1/IL-1ß deficiency attenuated sepsis severity/lethality. Mechanistically, GITR specifically enhanced inflammasome activation by regulating the posttranslational modification (PTM) of NLRP3. GITR competes with NLRP3 for binding to the E3 ligase MARCH7 and recruits MARCH7 to induce deacetylase SIRT2 degradation, leading to decreasing ubiquitination but increasing acetylation of NLRP3. Overall, these findings revealed a novel role of macrophage-derived GITR in regulating the PTM of NLRP3 and systemic inflammatory injury, suggesting that GITR may be a potential therapeutic target for sepsis and other inflammatory diseases. GITR exacerbates LPC-induced macrophage pyroptosis in sepsis via posttranslational regulation of NLRP3. According to the model, LPC levels increase during the early stage of sepsis, inducing GITR expression on macrophages. GITR not only competes with NLRP3 for binding to the E3 ligase MARCH7 but also recruits MARCH7 to induce the degradation of the deacetylase SIRT2, leading to decreasing ubiquitination but increasing acetylation of NLRP3 and therefore exacerbating LPC-induced NLRP3 inflammasome activation, macrophage pyroptosis and systemic inflammatory injury.


Asunto(s)
Proteína Relacionada con TNFR Inducida por Glucocorticoide , Lisofosfatidilcolinas , Macrófagos , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Procesamiento Proteico-Postraduccional , Piroptosis , Sepsis , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Animales , Sepsis/inmunología , Macrófagos/metabolismo , Macrófagos/inmunología , Lisofosfatidilcolinas/metabolismo , Ratones , Proteína Relacionada con TNFR Inducida por Glucocorticoide/metabolismo , Inflamasomas/metabolismo , Masculino , Ratones Noqueados , Humanos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Sirtuina 2/metabolismo , Sirtuina 2/genética , Acetilación
6.
Foods ; 13(10)2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38790878

RESUMEN

Liquid fermentation is an efficient culture for obtaining polysaccharides from edible mushrooms. In this study, the polysaccharide content and biomass were examined by introducing microorganisms into the Wolfiporia cocos fermentation system. Three edible mushroom co-fermentation systems were established, among which the Wolfiporia cocos-Ganoderma lucidum co-fermentation system significantly increased the mycelial biomass of the system by 57.71% compared to Wolfiporia cocos alone and 91.22% compared to Ganoderma lucidum alone, and the intracellular polysaccharide content was significantly increased. Physiological activities of polysaccharides showed that mycelial polysaccharides in the Wolfiporia cocos-Ganoderma lucidum system had stronger anti-tumor cell value-adding and anti-tumor cell migration activities compared with Wolfiporia cocos and Ganoderma lucidum fermentation alone. The transcriptomic study of Wolfiporia cocos mycelium induced by exogenous substances suggested that the exogenous substances could enhance the intracellular polysaccharide content of Wolfiporia cocos through the upregulation of the expression of α-glycosyltransferase encoded by ALG10 and the downregulation of α-glycosidases encoded by MAN1B in the glycolytic metabolism of Wolfiporia cocos. This study provides a new direction for the transformation of polysaccharides from Wolfiporia cocos and Ganoderma lucidum into functional foods and new product development, and provides an experimental basis.

7.
ACS Appl Bio Mater ; 7(6): 3981-3990, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38781457

RESUMEN

Polyetheretherketone (PEEK), particularly its sulfonated form (SPEEK), has emerged as a promising synthetic biomaterial for artificial bone implants, providing an alternative to conventional titanium metal. However, postoperative infections pose a critical challenge, driven by diverse and antibiotic-resistant bacteria. To address this issue, we propose the modification of the SPEEK surface using a thin graphene oxide (GO) film containing silver (Ag) ions. The resulting coating exhibits substantial antibacterial effects against various pathogens, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans. Experimental assessments elucidate the coating's impact on bacterial adhesion, biofilm formation, and morphology. The results suggest that hindered bacterial growth stems from reduced biofilm production and the controlled release of Ag ions facilitated by the GO coating. The Ag/GO-SPEEK material holds promise as a bioactive implant, addressing the challenges associated with bacterial targeting in bone tissue engineering applications.


Asunto(s)
Antibacterianos , Benzofenonas , Grafito , Ensayo de Materiales , Pruebas de Sensibilidad Microbiana , Polietilenglicoles , Polímeros , Plata , Grafito/química , Grafito/farmacología , Plata/química , Plata/farmacología , Benzofenonas/química , Benzofenonas/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Polímeros/química , Polímeros/farmacología , Polietilenglicoles/química , Polietilenglicoles/farmacología , Staphylococcus aureus/efectos de los fármacos , Cetonas/química , Cetonas/farmacología , Tamaño de la Partícula , Candida albicans/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Biopelículas/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos
8.
Cancer Cell Int ; 24(1): 172, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750489

RESUMEN

BACKGROUND: Cervical cancer is a human papillomavirus (HPV)-related disease. HPV type 16 (HPV16), which is the predominant cause of cervical cancer, can encode miRNAs (HPV16-miRNAs). However, the role of HPV16-miRNAs in the pathogenesis of cervical cancer remains unclear. METHODS: Human cervical cancer cell lines SiHa (HPV16-positive) and C33A (HPV-negative), and cervical cancer tissues were collected to investigate the expression levels of two HPV16-miRNAs (HPV16-miR-H1 and HPV16-miR-H6). The overexpression and knockdown of HPV16-miR-H1 and HPV16-miR-H6 were performed using the lentiviral vector system and miRNA inhibitors, respectively. RNA-sequencing (RNA-seq) analysis and H3K27ac chromatin immunoprecipitation and sequencing (CHIP-seq) experiments were utilized to explore the roles of HPV16-miR-H1 and HPV16-miR-H6 facilitated by enhancers. CCK8, EdU, transwell, and wound healing assays were performed to verify the effects of HPV16-miR-H1 and HPV16-miR-H6 on cell proliferation and migration. RESULTS: HPV16-miR-H1 and HPV16-miR-H6 were highly expressed in both SiHa cells and tissue samples from HPV16-positive cervical cancer patients. RNA-seq analysis showed that HPV16-miR-H1 and HPV16-miR-H6 induced the upregulation of numerous tumor progression-associated genes. H3K27ac CHIP-seq experiments further revealed that HPV16-miR-H1 and HPV16-miR-H6 modulated the expression of critical genes by regulating their enhancer activity. The functional study demonstrated that HPV16-miR-H1 and HPV16-miR-H6 increased the migratory capacity of SiHa cells. CONCLUSIONS: Our data shed light on the role of HPV16-encoded miRNAs in cervical cancer, particularly emphasizing their involvement in the miRNA-enhancer-target gene system. This novel regulatory mechanism of HPV16-miRNAs provides new insights and approaches for the development of therapeutic strategies by targeting HPV16-positive cervical cancer.

9.
Ultrason Sonochem ; 105: 106871, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38599129

RESUMEN

The research on developing a purification technology for 2,4-dichlorophenol (2,4-DCP) polluted water with high efficiency and the low energy consumption is crucial for achieving several Sustainable Development Goals (SDGs). In order to achieve these goals, MWCNTs-Pd/Fe nanocomposites were prepared by Fe nanoparticles modified with multi-walled carbon nanotubes (MWCNTs) and palladium (Pd) in the presence of ultrasonic irradiation. The MWCNTs-Pd/Fe nanocomposites were characterized by using Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and X-Ray Diffraction (XRD), and others. Characterization results confirmed that the MWCNTs-Pd/Fe was successfully prepared, with the particle size of 80 nm and the specific surface area of 89.5 m2/g confirmed. We studied the reductive dechlorination of 2,4-Dichlorophenol (2,4-DCP) by MWCNTs-Pd/Fe nanocomposites under different conditions, and the optimized experimental results were found when the Pd loading was 0.4 %, the pH was 3, and the temperature was 30 °C. The phenol yield increased from 76.5 % (without ultrasonic irradiation) to 92.3 % (with ultrasonic irradiation) in 300 min and the 2,4-DCP removal rate reached 98.7 % under the optimal conditions. Therefore, ultrasonic irradiation enhanced the performance of MWCNTs-Pd/Fe nanocomposites for 2,4-DCP removal. We also established the degradation mechanism of chlorophenol by analyzing the intermediates, and proposed the degradation kinetics model. The degradation of 2,4-DCP followed the pseudo-first-order kinetics with the rate constant of 0.05988 min-1. Also, this study demonstrated the potential of using ultrasonic irradiation to improve the properties and recovery of MWCNTs-Pd/Fe nanocomposites, contributing to achievement of the Sustainable Development Goals (SDGs), including SDG-3, SDG-6.

10.
Sensors (Basel) ; 24(5)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38475163

RESUMEN

Angle-of-arrival (AOA) measurements are often used in underwater acoustical localization. Different from the traditional AOA model based on azimuth and elevation measurements, the AOA model studied in this paper uses bearing measurements. It is also often used in the Ultra-Short Baseline system (USBL). However, traditional acoustical localization needs additional range information. If the range information is unavailable, the closed-form solution is difficult to obtain only with bearing measurements. Thus, a localization closed-form solution using only bearing measurements is explored in this article. A pseudo-linear measurement model between the source position and the bearing measurements is derived, and considering the nonlinear relationship of the parameters, a weighted least-squares optimization equation based on multiple constraints is established. Different from the traditional two-step least-squares method, the semidefinite programming (SDP) method is designed to obtain the initial solution, and then a bias compensation method is proposed to further minimize localization errors based on the SDP result. Numerical simulations show that the performance of the proposed method can achieve Cramer-Rao lower bound (CRLB) accuracy. The field test also proves that the proposed method can locate the source position without range measurements and obtain the highest positioning accuracy.

11.
Gut Microbes ; 16(1): 2320283, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38444395

RESUMEN

Chronic obstructive pulmonary disease (COPD), a condition primarily linked to oxidative stress, poses significant health burdens worldwide. Recent evidence has shed light on the association between the dysbiosis of gut microbiota and COPD, and their metabolites have emerged as potential modulators of disease progression through the intricate gut-lung axis. Here, we demonstrate the efficacy of oral administration of the probiotic Pediococcus pentosaceus SMM914 (SMM914) in delaying the progression of COPD by attenuating pulmonary oxidative stress. Specially, SMM914 induces a notable shift in the gut microbiota toward a community structure characterized by an augmented abundance of probiotics producing short-chain fatty acids and antioxidant metabolisms. Concurrently, SMM914 synthesizes L-tryptophanamide, 5-hydroxy-L-tryptophan, and 3-sulfino-L-alanine, thereby enhancing the tryptophan-melatonin pathway and elevating 6-hydroxymelatonin and hypotaurine in the lung environment. This modulation amplifies the secretion of endogenous anti-inflammatory factors, diminishes macrophage polarization toward the M1 phenotype, and ultimately mitigates the oxidative stress in mice with COPD. The demonstrated efficacy of the probiotic intervention, specifically with SMM914, not only highlights the modulation of intestine microbiota but also emphasizes the consequential impact on the intricate interplay between the gastrointestinal system and respiratory health.


Asunto(s)
Microbioma Gastrointestinal , Melatonina , Probióticos , Enfermedad Pulmonar Obstructiva Crónica , Animales , Ratones , Antioxidantes , Pediococcus pentosaceus , Melatonina/farmacología , Triptófano
12.
Antioxidants (Basel) ; 13(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38539841

RESUMEN

Premature ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction characterized by the abnormal alteration of hormone levels such as FSH and E2. POI causes infertility, severe daily life disturbances, and long-term health risks. However, the underlying mechanism remains largely unknown. In this study, we found that POI is associated with the cellular senescence of ovarian granulosa cells, and TRIM28 mediates oxidative stress (OS)-induced cellular senescence in granulosa cells. Mechanistically, OS causes a decrease in TRIM28 protein levels in KGN cells. Subsequently, it triggers an increase in the levels of autophagy marker proteins ATG5 and LC3B-II, and the downregulation of P62. Abnormal autophagy induces an increase in the levels of cellular senescence markers γ-H2A.X, P16, and P21, provoking cellular senescence in vitro. The overexpression of ovarian TRIM28 through a microinjection of lentivirus attenuated autophagy, cellular senescence, and follicular atresia in the ovaries of POI mice and improved mouse fertility in vivo. Our study highlights the triggers for POI, where the reduction of TRIM28, which is regulated by reactive oxygen species, causes follicular atresia and POI via triggering autophagy and inducing granulosa cell senescence. Shedding light on TRIM28 may represent a potential intervention strategy for POI.

13.
Carbohydr Polym ; 334: 122031, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38553230

RESUMEN

The efficacy of cancer therapies is significantly compromised by the immunosuppressive tumor milieu. Herein, we introduce a previously unidentified therapeutic strategy that harnesses the synergistic potential of chitosan-coated bacterial vesicles and a targeted chemotherapeutic agent to activate dendritic cells, thereby reshaping the immunosuppressive milieu for enhanced cancer therapy. Our study focuses on the protein-mediated modification of bacterium-derived minicells with chitosan molecules, facilitating the precise delivery of Doxorubicin to tumor sites guided by folate-mediated homing cues. These engineered minicells demonstrate remarkable specificity in targeting lung carcinomas, triggering immunogenic cell death and releasing tumor antigens and damage-associated molecular patterns, including calreticulin and high mobility group box 1. Additionally, the chitosan coating, coupled with bacterial DNA from the minicells, initiates the generation of reactive oxygen species and mitochondrial DNA release. These orchestrated events culminate in dendritic cell maturation via activation of the stimulator of interferon genes signaling pathway, resulting in the recruitment of CD4+ and CD8+ cytotoxic T cells and the secretion of interferon-ß, interferon-γ, and interleukin-12. Consequently, this integrated approach disrupts the immunosuppressive tumor microenvironment, impeding tumor progression. By leveraging bacterial vesicles as potent dendritic cell activators, our strategy presents a promising paradigm for synergistic cancer treatment, seamlessly integrating chemotherapy and immunotherapy.


Asunto(s)
Quitosano , Neoplasias Pulmonares , Neoplasias , Humanos , Quitosano/uso terapéutico , Inmunomodulación , Neoplasias/tratamiento farmacológico , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Línea Celular Tumoral , Células Dendríticas , Microambiente Tumoral
14.
Biomedicines ; 12(2)2024 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-38397968

RESUMEN

BACKGROUND: This study aimed to develop a simple predictive model for early identification of the risk of adverse outcomes in kidney transplant-associated Pneumocystis carinii pneumonia (PCP) patients. METHODS: This study encompassed 103 patients diagnosed with PCP, who received treatment at our hospital between 2018 and 2023. Among these participants, 20 were categorized as suffering from severe PCP, and, regrettably, 13 among them succumbed. Through the application of machine learning techniques and multivariate logistic regression analysis, two pivotal variables were discerned and subsequently integrated into a nomogram. The efficacy of the model was assessed via receiver operating characteristic (ROC) curves and calibration curves. Additionally, decision curve analysis (DCA) and a clinical impact curve (CIC) were employed to evaluate the clinical utility of the model. The Kaplan-Meier (KM) survival curves were utilized to ascertain the model's aptitude for risk stratification. RESULTS: Hematological markers, namely Procalcitonin (PCT) and C-reactive protein (CRP)-to-albumin ratio (CAR), were identified through machine learning and multivariate logistic regression. These variables were subsequently utilized to formulate a predictive model, presented in the form of a nomogram. The ROC curve exhibited commendable predictive accuracy in both internal validation (AUC = 0.861) and external validation (AUC = 0.896). Within a specific threshold probability range, both DCA and CIC demonstrated notable performance. Moreover, the KM survival curve further substantiated the nomogram's efficacy in risk stratification. CONCLUSIONS: Based on hematological parameters, especially CAR and PCT, a simple nomogram was established to stratify prognostic risk in patients with renal transplant-related PCP.

15.
Open Res Eur ; 4: 7, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38313675

RESUMEN

The rapidly evolving field of Digital Finance necessitates a new, interdisciplinary approach to doctoral training. This manuscript presents a comprehensive curriculum designed to equip early-stage researchers with the skills and knowledge required to navigate the complexities of modern finance. The curriculum is structured around four pillars: Training through Research and Mandatory Scientific Training, Advanced Scientific Training, Transferable Skills Training, and Training through Secondments. Together, these pillars provide a balanced mix of theoretical knowledge, practical experience, and soft skills. The program also emphasizes international collaboration through conferences and offers online courses for accessibility and sustainability. By addressing key challenges such as data quality, deployment of complex models, trust in AI-supported products, and labor shortages, the program aims to foster innovation and competitiveness in the European Finance industry. The curriculum's alignment with the European Digital Finance Package and integration with leading institutions ensures its relevance and potential for significant impact.

16.
J Ovarian Res ; 17(1): 35, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38317224

RESUMEN

PURPOSE: PAQR7 plays a key role in cell apoptosis as a progesterone membrane receptor. The physiological mechanism of PAQR7 in ovarian function and its anti-apoptotic action in mammals remain poorly understood. METHODS: We first added 0.2 µM aminoglutethimide (AG), an inhibitor of endogenous progesterone (P4) secretion, and transfected siPAQR7 co-incubated with P4 in human KGN cells to identify granulosa cell apoptosis, respectively. Additionally, we used Paqr7 knockout (PAQR7 KO) mice to assess the role of PAQR7 in the ovary. RESULTS: The PAQR7 deficiency significantly increased apoptosis of KGN cells, and this significant difference disappeared following P4 supplementation. The Paqr7-/- female mice showed a prolonged estrous cycle, reduced follicular growth, increased the number of atresia follicles, and decreased the concentrations of E2 and AMH. The litters, litter sizes, and spontaneous ovulation in the Paqr7-/- mice were significantly decreased compared with the Paqr7+/+ mice. In addition, we also found low expression of PAQR7 in GCs from human follicular fluids of patients diagnosed with decreased ovarian reserve (DOR) and ovaries of mice with a DOR-like phenotype, respectively. CONCLUSIONS: The present study has identified that PAQR7 is involved in mouse ovarian function and fertilization potential. One possible mechanism is mediating the anti-apoptotic effect of P4 on GC apoptosis via the BCL-2/BAX/CASPASE-3 signaling pathway. The mechanism underlying the effect of PAQR7 on ovarian development and aging remains to be identified.


Asunto(s)
Progesterona , Receptores Acoplados a Proteínas G , Receptores de Progesterona , Animales , Femenino , Humanos , Ratones , Apoptosis , Células de la Granulosa/metabolismo , Folículo Ovárico/metabolismo , Ovario/metabolismo , Progesterona/metabolismo , Receptores de Progesterona/metabolismo , Receptores Acoplados a Proteínas G/metabolismo
17.
Heliyon ; 10(1): e23056, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38163170

RESUMEN

Objectives: To analyse the pathogenic genes in a patient with hypohidrotic ectodermal dysplasia (HED) and explore the relationship between pathogenic genes and the oligodontia phenotype. Methods: Clinical data and peripheral blood were collected from a patient with HED. Pathogenic genes were analysed by whole-exon sequencing (WES) and verified by Singer sequencing. The secondary and tertiary structures of the variant proteins were predicted to analyse their toxicity. Results: The patient exhibited a severe oligodontia phenotype, wherein only two deciduous canines were left in the upper jaw. WES revealed a hemizygous EDA variant c.466C > T p.(Arg156Cys) and a novel heterozygous EVC2 variant c.1772T > C p.(Leu591Ser). Prediction of the secondary and tertiary structures of the EDA variant p.(Arg156Cys) and EVC2 variant p.(Leu591Ser) indicated impaired function of both molecules. Conclusion: The patient demonstrated a more severe oligodontia phenotype when compared with the other patients caused by the EDA variant c.466C > T. Since Evc2 is a positive regulator of the Sonic Hedgehog (Shh) signal pathway, we speculated that the EVC2 variant p.(Leu591Ser) may play a synergistic role in the oligodontia phenotype of HED, thereby exacerbating the oligodontia phenotype. Knowledge of oligodontia caused by multiple gene variants is of great significance for understanding individual differences in oligodontia phenotypes.

18.
Transpl Immunol ; 82: 101961, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38184216

RESUMEN

BACKGROUND: The kidney donor profile index (KDPI) evaluates kidney donor's age, height, weight, ethnicity, cause of death, high blood pressure, diabetes, exposure to hepatitis C and estimated glomerular filtration (eGFR). Kidneys with lower KDPI scores are expected to function longer that those with higher KPDI values. The applicability of KDPI score in Chinese kidney transplant donation has not yet been validated. This study evaluated the prognostic value of KDPI score in Chinese kidney transplant patients. METHODS: A retrospective analysis was conducted on 184 deceased donors and 353 corresponding kidney transplant patients at the Organ Transplantation Department of Renmin Hospital of Wuhan University between 2018 and 2021. The donors and recipients were stratified into four groups based on their KDPI score: KDPI 85-100, KDPI 60-84, KDPI 21-59, and KDPI 0-20. RESULTS: As expected, the KDPI 85-100 group was associated with a poor short-term renal function (both postoperative creatinine and eGFR with P > 0.05), a higher incidence of delayed graft function (DGF; 25.5% for KDPI 85-100 group vs. 10.2% for KDPI 60-84 group vs. 5.4% for KDPI 21-59 group vs. 0 for KDPI 0-20 group, all P > 0.05). Furthermore, the same groups showed worse 3-year patient survival rate: 86.3% for KDPI 85-100 group vs. 97.01% for KDPI 60-84 group vs. 97.83% for KDPI 21-59 group vs. 100% for KDPI 0-20 group, all P > 0.05); and renal survival rate: 82.6% for KDPI 85-100 group vs. 92.99% KDPI 60-84 group vs.97.83% for KDPI 21-59 group vs. 100% for KDPI 0-20 group, all P > 0.05). Our analysis showed that the KDPI score had a good predictive value for the survival of kidney transplants and patients in our center (area under the curve: 0.728 and 0.76, P > 0.05). CONCLUSION: We recommend that the KDPI scoring system can be employed as an effective tool to predict kidney transplantation outcomes in deceased donation in China.


Asunto(s)
Trasplante de Riñón , Humanos , Estudios Retrospectivos , Supervivencia de Injerto , Donantes de Tejidos , Riñón , Factores de Riesgo
19.
Phys Chem Chem Phys ; 26(6): 4922-4928, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38263876

RESUMEN

Pure rotational transitions of the ClSO radical have been observed by Fourier-transform microwave spectroscopy. a-type and b-type transitions, for both 35Cl and 37Cl isotopologues, were detected, and the observed very complicated fine and hyperfine components were assigned well. The intensities of the observed spectra of the two isotopologues correspond to the ratio of the isotope abundances of 35Cl and 37Cl. A total of 21 molecular constants were determined precisely for both 35ClSO and 37ClSO, including the rotational constants, centrifugal distortion constants, electronic spin-rotation constants, nuclear spin-rotation constants, magnetic hyperfine constants, and quadrupole coupling constants of chlorine. The molecular constants show ClSO to have the 2A'' electronic ground state with an out-of-plane unpaired electron. The spin density of the chlorine atom is about 10.6%, which is similar to that of the fluorine atom for FSO, about 8%. Results of the ClSO radical are compared with those of other triatomic radicals with similar structures, the XSS, XSO, and XOO radicals with X = H, F, and Cl, leading to a conclusion that the ClSO radical is more like FSO, but fairly different from the FOO and ClOO radicals.

20.
Anal Chim Acta ; 1287: 342101, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38182383

RESUMEN

BACKGROUND: Haemophilus parasuis (H. parasuis) is a gram-negative bacterial pathogen that causes severe infections in swine, resulting in substantial economic losses. Currently, the majority of H. parasuis detection methods are impractical for on-site application due to their reliance on large instruments or complex procedures. Thus, there is an urgent need to develop a rapid, visually detectable, and highly sensitive detection method, especially under resource-limited environments and field conditions. RESULTS: In this study, we established a naked eye assay for highly sensitive detection by combining recombinase polymerase amplification (RPA) with CRISPR/Cas12a technology. Positive samples exhibited a clear red color visible to the naked eye, while negative samples appeared blue. We achieved a remarkable sensitivity, detecting H. parasuis down to a single copy, with no cross-reactivity with other bacteria. In a mouse model, our assay detected H. parasuis infection nearly 8 h earlier than traditional PCR. Compared to qPCR, our detection results were 100 % accurate. To enhance point-of-care applicability and mitigate the risk of aerosol contamination from uncapping, we consolidated RPA and CRISPR/Cas12a cleavage into a single-tube reaction system. This integrated approach was validated with 20 clinical lung samples, yielding results consistent with those obtained from qPCR. The entire procedure, from DNA extraction to detection, was completed in 35 min. SIGNIFICANCE: We present an RPA-CRISPR/Cas12a assay suitable for the early and resource-efficient diagnosis of H. parasuis infections. Its simplicity and visual detection are advantageous for field diagnostics, representing a substantial develpoment in the diagnosis of H. parasuis.


Asunto(s)
Haemophilus parasuis , Recombinasas , Ratones , Animales , Porcinos , Haemophilus parasuis/genética , Sistemas CRISPR-Cas , Bioensayo , Reacciones Cruzadas
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