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1.
Commun Biol ; 7(1): 800, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956367

RESUMEN

Gastric cancer (GC) is the 5th most prevalent cancer and the 4th primary cancer-associated mortality globally. As the first identified m6A demethylase for removing RNA methylation modification, fat mass and obesity-associated protein (FTO) plays instrumental roles in cancer development. Therefore, we study the biological functions and oncogenic mechanisms of FTO in GC tumorigenesis and progression. In our study, FTO expression is obviously upregulated in GC tissues and cells. The upregulation of FTO is associated with advanced nerve invasion, tumor size, and LNM, as well as the poor prognosis in GC patients, and promoted GC cell viability, colony formation, migration and invasion. Mechanistically, FTO targeted specificity protein 1 and Aurora Kinase B, resulting in the phosphorylation of ataxia telangiectasia mutated and P38 and dephosphorylation of P53. In conclusion, the m6A demethylase FTO promotes GC tumorigenesis and progression by regulating the SP1-AURKB-ATM pathway, which may highlight the potential of FTO as a diagnostic biomarker for GC patients' therapy response and prognosis.


Asunto(s)
Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Proteínas de la Ataxia Telangiectasia Mutada , Aurora Quinasa B , Factor de Transcripción Sp1 , Neoplasias Gástricas , Humanos , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Línea Celular Tumoral , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/genética , Factor de Transcripción Sp1/metabolismo , Factor de Transcripción Sp1/genética , Aurora Quinasa B/metabolismo , Aurora Quinasa B/genética , Masculino , Femenino , Regulación Neoplásica de la Expresión Génica , Progresión de la Enfermedad , Persona de Mediana Edad , Transducción de Señal , Pronóstico , Ratones , Animales
2.
Neural Netw ; 178: 106466, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38968778

RESUMEN

The brain is targeted for processing temporal sequence information. It remains largely unclear how the brain learns to store and retrieve sequence memories. Here, we study how recurrent networks of binary neurons learn sequence attractors to store predefined pattern sequences and retrieve them robustly. We show that to store arbitrary pattern sequences, it is necessary for the network to include hidden neurons even though their role in displaying sequence memories is indirect. We develop a local learning algorithm to learn sequence attractors in the networks with hidden neurons. The algorithm is proven to converge and lead to sequence attractors. We demonstrate that the network model can store and retrieve sequences robustly on synthetic and real-world datasets. We hope that this study provides new insights in understanding sequence memory and temporal information processing in the brain.

3.
Front Endocrinol (Lausanne) ; 15: 1414481, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38978628

RESUMEN

Objective: To determine whether endometrial thickness (EMT) differs between i) clomiphene citrate (CC) and gonadotropin (Gn) utilizing patients as their own controls, and ii) patients who conceived with CC and those who did not. Furthermore, to investigate the association between late-follicular EMT and pregnancy outcomes, in CC and Gn cycles. Methods: Retrospective study. Three sets of analyses were conducted separately for the purpose of this study. In analysis 1, we included all cycles from women who initially underwent CC/IUI (CC1, n=1252), followed by Gn/IUI (Gn1, n=1307), to compare EMT differences between CC/IUI and Gn/IUI, utilizing women as their own controls. In analysis 2, we included all CC/IUI cycles (CC2, n=686) from women who eventually conceived with CC during the same study period, to evaluate EMT differences between patients who conceived with CC (CC2) and those who did not (CC1). In analysis 3, pregnancy outcomes among different EMT quartiles were evaluated in CC/IUI and Gn/IUI cycles, separately, to investigate the potential association between EMT and pregnancy outcomes. Results: In analysis 1, when CC1 was compared to Gn1 cycles, EMT was noted to be significantly thinner [Median (IQR): 6.8 (5.5-8.0) vs. 8.3 (7.0-10.0) mm, p<0.001]. Within-patient, CC1 compared to Gn1 EMT was on average 1.7mm thinner. Generalized linear mixed models, adjusted for confounders, revealed similar results (coefficient: 1.69, 95% CI: 1.52-1.85, CC1 as ref.). In analysis 2, CC1 was compared to CC2 EMT, the former being thinner both before [Median (IQR): 6.8 (5.5-8.0) vs. 7.2 (6.0-8.9) mm, p<0.001] and after adjustment (coefficient: 0.59, 95%CI: 0.34-0.85, CC1 as ref.). In analysis 3, clinical pregnancy rates (CPRs) and ongoing pregnancy rates (OPRs) improved as EMT quartiles increased (Q1 to Q4) among CC cycles (p<0.001, p<0.001, respectively), while no such trend was observed among Gn cycles (p=0.94, p=0.68, respectively). Generalized estimating equations models, adjusted for confounders, suggested that EMT was positively associated with CPR and OPR in CC cycles, but not in Gn cycles. Conclusions: Within-patient, CC generally resulted in thinner EMT compared to Gn. Thinner endometrium was associated with decreased OPR in CC cycles, while no such association was detected in Gn cycles.


Asunto(s)
Clomifeno , Endometrio , Fármacos para la Fertilidad Femenina , Gonadotropinas , Inseminación Artificial , Humanos , Femenino , Clomifeno/uso terapéutico , Clomifeno/administración & dosificación , Endometrio/efectos de los fármacos , Endometrio/patología , Embarazo , Adulto , Estudios Retrospectivos , Fármacos para la Fertilidad Femenina/uso terapéutico , Fármacos para la Fertilidad Femenina/administración & dosificación , Resultado del Embarazo , Inducción de la Ovulación/métodos , Índice de Embarazo , Infertilidad Femenina/terapia , Infertilidad Femenina/tratamiento farmacológico
4.
Expert Rev Anti Infect Ther ; : 1-12, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38975666

RESUMEN

BACKGROUND: The potential of ursodeoxycholic acid (UDCA) in inhibiting angiotensin-converting enzyme 2 was demonstrated. However, conflicting evidence emerged regarding the association between UDCA and COVID-19 outcomes, prompting the need for a comprehensive investigation. RESEARCH DESIGN AND METHODS: Patients diagnosed with COVID-19 infection were retrospectively analyzed and divided into two groups: the UDCA-treated group and the control group. Kaplan-Meier recovery analysis and Cox proportional hazards models were used to evaluate the recovery time and hazard ratios. Additionally, study-level pooled analyses for multiple clinical outcomes were performed. RESULTS: In the 115-patient cohort, UDCA treatment was significantly associated with a reduced recovery time. The subgroup analysis suggests that the 300 mg subgroup had a significant (adjusted hazard ratio: 1.63 [95% CI, 1.01 to 2.60]) benefit with a shorter duration of fever. The results of pooled analyses also show that UDCA treatment can significantly reduce the incidence of severe/critical diseases in COVID-19 (adjusted odds ratio: 0.68 [95% CI, 0.50 to 0.94]). CONCLUSIONS: UDCA treatment notably improves the recovery time following an Omicron strain infection without observed safety concerns. These promising results advocate for UDCA as a viable treatment for COVID-19, paving the way for further large-scale and prospective research to explore the full potential of UDCA.

6.
Artículo en Inglés | MEDLINE | ID: mdl-39004817

RESUMEN

The large-scale application of aqueous Al-air batteries is highly restricted by the performance of Al anodes. The severe self-corrosion and hydrogen evolution of the Al anode in a concentrated alkaline electrolyte are the main reason. Here, aimed at relieving side reactions and enhancing the utilization of metal Al, we propose a hybrid electrolyte additive of 2-mercaptobenzothiazole (MBT) and ZnO to form a protective film at the anode/electrolyte interface and to decrease the hydrogen evolution active site. The strong absorption capability of MBT on the metal surface, along with the reduced Zn-containing layer, enables a compact protective film with high hydrogen evolution potential on the Al surface. With this benefit, the hydrogen evolution reaction (HER) inhibition efficiency is up to 83.58%, endowing a superior Al-air battery with an energy density of 2376.71 Wh kgAl-1 under a current density of 25 mA cm-2. The conception of constructing a hybrid protective film on the metal surface not only favors the development of metal-air batteries but also facilitates metal corrosion protection.

7.
Adv Mater ; : e2405433, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39007283

RESUMEN

Collective excitations including plasmons, magnons, and layer-breathing vibration modes emerge at an ultralow frequency (<1 THz) and are crucial for understanding van der Waals materials. Strain at the nanoscale can drastically change the property of van der Waals materials and create localized states like quantum emitters. However, it remains unclear how nanoscale strain changes collective excitations. Herein, ultralow-frequency tip-enhanced Raman spectroscopy (TERS) with sub-10 nm resolution under ambient conditions is developed to explore the localized collective excitation on monolayer semiconductors with nanoscale strains. A new vibrational mode is discovered at around 12 cm-1 (0.36 THz) on monolayer MoSe2 nanobubbles and it is identified as the radial breathing mode (RBM) of the curved monolayer. The correlation is determined between the RBM frequency and the strain by simultaneously performing deterministic nanoindentation and TERS measurement on monolayer MoSe2. The generality of the RBM in nanoscale curved monolayer WSe2 and bilayer MoSe2 is demonstrated. Using the RBM frequency, the strain of the monolayer MoSe2 on the nanoscale can be mapped. Such an ultralow-frequency vibration from curved van der Waals materials provides a new approach to study nanoscale strains and points to more localized collective excitations to be discovered at the nanoscale.

8.
Artículo en Inglés | MEDLINE | ID: mdl-39013587

RESUMEN

BACKGROUND AND AIM: Helicobacter pylori infection is linked to various gastrointestinal conditions, such as chronic active gastritis, peptic ulcers, and gastric cancer. Traditional treatment options encounter difficulties due to antibiotic resistance and adverse effects. Therefore, the aim of this study was to explore the effectiveness of a new treatment plan that combines vonoprazan (VPZ), amoxicillin, and bismuth for the eradication of H. pylori. METHODS: A total of 600 patients infected with H. pylori were recruited for this multicenter randomized controlled trial. Patients treated for H. pylori elimination were randomly assigned at a 1:1 ratio to receive 14 days of vonoprazan-based triple therapy (vonoprazan + amoxicillin + bismuth, group A) or standard quadruple therapy (esomeprazole + clarithromycin + amoxicillin + bismuth, group B). Compliance and adverse effects were tracked through daily medication and side effect records. All patients underwent a 13C/14C-urea breath test 4 weeks after treatment completion. RESULTS: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed no substantial differences in H. pylori eradication rates between groups A and B (ITT: 83.7% vs 83.2%; PP: 90.9% vs 89.7%). However, significant differences were observed in the assessment of side effects (13.7% vs 28.6%, P < 0.001). Specifically, group A had significantly fewer "bitter mouths" than group B did (3.7% vs 16.2%, P < 0.001). CONCLUSION: Triple therapy comprising vonoprazan (20 mg), amoxicillin (750 mg), and bismuth potassium citrate (220 mg) achieved a PP eradication rate ≥90%, paralleling standard quadruple therapy, and had fewer adverse events and lower costs (¥306.8 vs ¥645.8) for treatment-naive patients.

9.
Dig Liver Dis ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39043537

RESUMEN

BACKGROUND: Liver fibrosis is a pathological feature of biliary atresia (BA). However, both histological fibrosis stage and existing biomarkers fail to predict prognosis at the time of hepatoportonterostomy (HPE). AIMS: To explore the role of collagen triple- helix repeat containing-1 (CTHRC1) in BA. METHODS: CTHRC1 expression levels were detected and its association with liver fibrosis stage was analyzed in patients with BA. Immunohistochemistry and immunofluorescent analyses were performed to detect the expression and localization of CTHRC1. Epithelial-mesenchymal transition (EMT) and proliferation were analyzed in cholangiocytes treated with recombinant human CTHRC1 protein. Survival analyses were performed to assess the prognostic value of CTHRC1 in patients with BA. RESULTS: CTHRC1 was upregulated in BA, and its expression level was positively correlated with fibrosis-related markers and the severity of liver fibrosis. In liver tissue CTHRC1 was co-localized with CK19 and highly expressed in patients with severe liver fibrosis. Further experiments revealed that CTHRC1 promoted cholangiocyte EMT and proliferation. Additionally, CTHRC1 expression levels at HPE could predict the 2-year native liver survival (NLS). CONCLUSIONS: CTHRC1 promotes the EMT and proliferation of cholangiocytes and indicate the stage of liver fibrosis. The CTHRC1 expression levels can predict outcomes of BA.

10.
bioRxiv ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38948734

RESUMEN

Comprehensive molecular and cellular phenotyping of human islets can enable deep mechanistic insights for diabetes research. We established the Human Islet Data Analysis and Sharing (HI-DAS) consortium to advance goals in accessibility, usability, and integration of data from human islets isolated from donors with and without diabetes at the Alberta Diabetes Institute (ADI) IsletCore. Here we introduce HumanIslets.com, an open resource for the research community. This platform, which presently includes data on 547 human islet donors, allows users to access linked datasets describing molecular profiles, islet function and donor phenotypes, and to perform various statistical and functional analyses at the donor, islet and single-cell levels. As an example of the analytic capacity of this resource we show a dissociation between cell culture effects on transcript and protein expression, and an approach to correct for exocrine contamination found in hand-picked islets. Finally, we provide an example workflow and visualization that highlights links between type 2 diabetes status, SERCA3b Ca2+-ATPase levels at the transcript and protein level, insulin secretion and islet cell phenotypes. HumanIslets.com provides a growing and adaptable set of resources and tools to support the metabolism and diabetes research community.

11.
Artículo en Inglés | MEDLINE | ID: mdl-39027976

RESUMEN

Quercetin is kown for its antihypertensive effects. However, its role on hypertensive renal injury has not been fully eucidated. In this study, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining, and Annexin V staining were used to assess the pathological changes and cells apoptosis in the renal tissues of Ang II-infused mice and Ang II- stimulated renal tubular epithelial cell line (NRK-52E). A variety of technologies, including network pharmacology, RNA-sequencing, immunohistochemistry, and Western blotting were performed to investigate its underlying mechanisms. Network pharmacology analysis identified multiple potential candidate targets (including TP53, Bcl-2 and Bax) and enriched signaling pathways (including apoptosis and p53 signaling pathway). Quercetin treatment significantly alleviated the pathological changes in renal tissues of Ang II-infused mice and reversed 464 differentially expressed transcripts (DETs), as well as enriched several signaling pathways, including those related apoptosis and p53 pathway. Furthermore, quercetin treatment significantly inhibited the cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Additionally, quercetin treatment inhibited the upregulation of p53, Bax, cleaved-caspase-9, and cleaved-caspase-3 protein expression and the downregulation of Bcl-2 protein expression in both renal tissue of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Moreover, the molecular docking results indicated a potential binding interaction between quercetin and TP53. Quercetin treatment significantly attenuated hypertensive renal injury and cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells, and by targeting p53 may be one of the potential underlying mechanisms.

12.
Eur J Radiol ; 178: 111622, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39018648

RESUMEN

PURPOSE: To investigate the value of microstructural characteristics derived from time-dependent diffusion MRI in distinguishing high-grade serous ovarian cancer (HGSOC) from serous borderline ovarian tumor (SBOT) and the associations of immunohistochemical markers with microstructural features. METHODS: Totally 34 HGSOC and 12 SBOT cases who received preoperative pelvic MRI were retrospectively included in this study. Two radiologists delineated the tumors to obtain the regions of interest (ROIs). Time-dependent diffusion MRI signals were fitted by the IMPULSED (imaging microstructural parameters using limited spectrally edited diffusion) model, to extract microstructural parameters, including fraction of the intracellular component (fin), cell diameter (d), cellularity and extracellular diffusivity (Dex). Apparent diffusion coefficient (ADC) values were obtained from standard diffusion-weighted imaging (DWI). The parameters of HGSOCs and SBOTs were compared, and the diagnostic performance was evaluated. The associations of microstructural indexes with immunopathological parameters were assessed, including Ki-67, P53, Pax-8, ER and PR. RESULTS: In this study, fin, cellularity, Dex and ADC had good diagnostic performance levels in differentiating HGSOC from SBOT, with AUCs of 0.936, 0.909, 0.902 and 0.914, respectively. There were no significant differences in diagnostic performance among these parameters. Spearman analysis revealed in the HGSOC group, cellularity had a significant positive correlation with P53 expression (P = 0.028, r = 0.389) and Dex had a significant positive correlation with Pax-8 expression (P = 0.018, r = 0.415). ICC showed excellent agreement for all parameters. CONCLUSION: Time-dependent diffusion MRI had value in evaluating the microstructures of HGSOC and SBOT and could discriminate between these tumors.

13.
J Clin Nurs ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39021041

RESUMEN

AIM: To evaluate the effectiveness and safety of nutritional interventions (i.e. nutritional support, dietary patterns and dietary supplements) on cognitive function in cancer survivors. DESIGN: Systematic review. METHODS: A systematic and comprehensive search of PubMed, Web of Science, the Cochrane Library, Embase, and CINAHL was conducted from the inception until March 10, 2023. The last search was conducted on December 10, 2023. REPORTING METHOD: PRISMA. RESULTS: A total of 59 randomized controlled trials were included for analysis. Nutritional support, dietary patterns and dietary supplements improved cognitive function in cancer survivors with no apparent safety concerns. The anti-inflammatory diet, the fasting-mimicking diet and the web-based diet significantly improved cognitive function. Whereas the ketogenic diet or dietary advice to consume more soluble dietary fibres and less insoluble dietary fibres and lactose could not. There was evidence from dietary supplements to support the beneficial effects of polyunsaturated fatty acid supplements, traditional herbal medicines and other supplements. CONCLUSIONS: Nutritional interventions have great promise for improving cognitive function in adult cancer survivors. Further validation of the nutritional interventions supported in this study in other survivors and exploration of more effective nutritional interventions are needed. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This work can support the construction of nutritional support interventions and dietary guidance programs to prevent cancer-related cognitive decline. IMPACT: This work filled a gap in preventive strategies for cancer-related cognitive decline from a nutritional perspective. Nutritional support, dietary patterns, and dietary supplements can prevent cancer-related cognitive decline without serious safety concerns. This work highlighted nutritional interventions that have the potential to improve cognitive function in cancer survivors, benefiting the further construction of evidence-based nutritional intervention programs. PROTOCOL REGISTRATION: PROSPERO. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

14.
Huan Jing Ke Xue ; 45(7): 3911-3918, 2024 Jul 08.
Artículo en Chino | MEDLINE | ID: mdl-39022939

RESUMEN

Microplastics (MPs) are ubiquitous in the marine environment and have become an emerging pollutant that is attracting great attention. To reveal the pollution characteristics of MPs in surface seawater of coastal waters in Guangdong Province, nine bays (estuaries) were selected from Jiangmen to Shantou. The distribution and compositional characteristics of MPs were investigated through field sampling, oxidation digestion, and visual and compositional identification, and their potential sources were analyzed. The ecological risks were assessed by combining the pollution load index and the polymer risk index. The results showed that MPs were detected in all 30 surface seawater samples from the coastal waters of Guangdong Province, with an abundance range of 70-920 n·m-3 and an average abundance of (295.3 ±175.3) n·m-3. The highest MPs abundance was found in the Pearl River estuary, and the lowest abundance was found in Shenquan bay. The distribution patterns were mainly influenced by human activities and ocean currents. The dominant polymer types included polypropylene (31.2%), phenol resin (16.0%), polyethylene terephthalate (15.3%), and polyethylene (10.9%). The main shape, color, and size categories of MPs were fiber (57.5%), transparent (72.0%), and 0.5-1 mm (32.8%), respectively. The possible sources of MPs mainly included aquaculture, fishing, navigation, tourism, municipal sewage discharge, and ocean current transportation. The model assessment results showed that the pollution load risk of MPs was relatively low, but the polymer risk was at a medium-high level. This study provides a data basis for the action plan of plastic pollution control in Guangdong Province and supports the prevention and control of marine MPs pollution.

15.
Front Optoelectron ; 17(1): 23, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39014042

RESUMEN

This study presents a high-accuracy, all-fiber mode division multiplexing (MDM) reconstructive spectrometer (RS). The MDM was achieved by utilizing a custom-designed 3 × 1 mode-selective photonics lantern to launch distinct spatial modes into the multimode fiber (MMF). This facilitated the information transmission by increasing light scattering processes, thereby encoding the optical spectra more comprehensively into speckle patterns. Spectral resolution of 2 pm and the recovery of 2000 spectral channels were accomplished. Compared to methods employing single-mode excitation and two-mode excitation, the three-mode excitation method reduced the recovered error by 88% and 50% respectively. A resolution enhancement approach based on alternating mode modulation was proposed, reaching the MMF limit for the 3 dB bandwidth of the spectral correlation function. The proof-of-concept study can be further extended to encompass diverse programmable mode excitations. It is not only succinct and highly efficient but also well-suited for a variety of high-accuracy, high-resolution spectral measurement scenarios.

17.
J Agric Food Chem ; 72(28): 16018-16031, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38960914

RESUMEN

Flow-injection spin-trapping electron paramagnetic resonance (FI-EPR) methods that involve the use of 5,5-dimethyl-pyrroline-N-oxide (DMPO) as a spin-trapping reagent have been developed for the kinetic study of the O2•- radical scavenging reactions occurring in the presence of various plant-derived and synthetic phenolic antioxidants (Aox), such as flavonoid, pyrogallol, catechol, hydroquinone, resorcinol, and phenol derivatives in aqueous media (pH 7.4 at 25 °C). The systematically estimated second-order rate constants (ks) of these phenolic compounds span a wide range (from 4.5 × 10 to 1.0 × 106 M-1 s-1). The semilogarithm plots presenting the relationship between ks values and oxidation peak potential (Ep) values of phenolic Aox are divided into three groups (A1, A2, and B). The ks-Ep plots of phenolic Aox bearing two or three OH moieties, such as pyrogallol, catechol, and hydroquinone derivatives, belonged to Groups A1 and A2. These molecules are potent O2•- radical scavengers with ks values above 3.8 × 104 (M-1 s-1). The ks-Ep plots of all phenol and resorcinol derivatives, and a few catechol and hydroquinone derivatives containing carboxyl groups adjacent to the OH groups, were categorized into the group poor scavengers (ks < 1.6 × 103 M-1 s-1). The ks values of each group correlated negatively with Ep values, supporting the hypothesis that the O2•- radical scavenging reaction proceeds via one-electron and two-proton processes. The processes were accompanied by the production of hydrogen peroxide at pH 7.4. Furthermore, the correlation between the plots of ks and the OH proton dissociation constant (pKa•) of the intermediate aroxyl radicals (ks-pKa• plots) revealed that the second proton transfer process could potentially be the rate-determining step of the O2•- radical scavenging reaction of phenolic compounds. The ks-Ep plots provide practical information to predict the O2•- radical scavenging activity of plant-derived phenolic compounds based on those molecular structures.


Asunto(s)
Depuradores de Radicales Libres , Oxidación-Reducción , Fenoles , Superóxidos , Espectroscopía de Resonancia por Spin del Electrón , Cinética , Fenoles/química , Depuradores de Radicales Libres/química , Superóxidos/química , Detección de Spin
18.
J Steroid Biochem Mol Biol ; : 106579, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39032671

RESUMEN

Chronic stress refers to the activation of the hypothalamic-pituitary-adrenal (HPA) axis and elevated blood contents of ACTH and corticosterone (CORT), exhibiting significant adverse effects on health outcomes. Currently, natural polyphenol compounds are increasingly being explored as potential therapeutic agents and have been considered as a treatment option for a variety of stress-induced diseases. Curcumin (CUR) is the main substance in Curcuma longa (Zingiberacea) rhizome that has strong health-beneficial properties. The study aimed to assess the potential protective effects of CUR on hepatic oxidative stress damage and abnormal lipid deposition in a chronic CORT-induced stress (CCIS) model in broilers. One hundred and twenty experimental broilers were randomly divided into 1) control group (CON), 2) CUR group (200mg/kg feed), 3) CORT group (4mg/kg BW CORT) and 4) CORT+CUR group (200mg/kg feed plus 4mg/kg BW CORT). The liver histology, glycolipid metabolism and oxidative stress were determined. In addition, qPCR was performed to identify shifts in genes expression. Compared with CON group, broilers under CCIS showed a decreased body weight, body weight gain and average daily gain, while dietary CUR significantly reversed these adverse effects. Furthermore, the plasma contents of TCH, TG, HDL-C, LDL-C, TP, GLB and AST were all significantly increased in CCIS broilers, while dietary CUR obviously alleviated the increase of TCH, HDL-C, LDL-C and AST, and relieved the hepatic lipid deposition disorder and liver injury. Moreover, CCIS significantly increased the contents of MDA in both liver and plasma, and decreased the content of plasma SOD, while CUR obviously reversed these changes, showing reduced oxidative stress damage. Finally, the mRNA expressions of FAS, ACC, SCD and the protein level of PPAR-γ were significantly increased, meanwhile the mRNA expression of lipolytic genes ACOX1, ATGL and CPT as well as two major intracellular antioxidant enzymes SOD1 and GPX1 were obviously decreased, while CUR effectively reversed these effects. These results showed that dietary CUR effectively alleviated CCIS-induced body weight loss, hepatic oxidative damage and lipid deposition disorder, suggesting the possible therapeutic effectiveness of CUR against hepatic damage and function abnormality caused by CCIS.

19.
Ear Nose Throat J ; : 1455613241261457, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877652

RESUMEN

Pleomorphic adenoma (PA) represents the most frequently occurring benign tumor within both major and minor salivary glands. However, in rare instances, nasal PA is an epithelial-derived borderline tumor, often originating from the nasal septum. Diagnosis usually relies on histopathological analysis. Under general anesthesia, these rare nasal tumors can be completely resected via endoscopic surgery. This article reports a case of PA originating from the nasal septum in a 49-year-old patient presenting with nasal congestion, along with a brief review of the current literature. The diagnostic nasal endoscopic examination showed a pink neoplastic mass in the left nasal cavity. Subsequent radiologic examination demonstrated a soft tissue mass in the anterior part of the nasal septum. After complete resection under nasal endoscopy, histopathological examination confirmed it as PA. Fortunately, no related complications occurred perioperatively and postoperatively. After surgery, performing a thorough examination with nasal endoscopy and scheduling regular follow-ups are crucial steps to prevent local recurrence.

20.
Int J Mol Sci ; 25(11)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38892221

RESUMEN

Chronic kidney disease (CKD) presents a significant global health challenge, characterized by complex pathophysiology. This study utilized a multi-omic approach, integrating genomic data from the CKDGen consortium alongside transcriptomic, metabolomic, and proteomic data to elucidate the genetic underpinnings and identify therapeutic targets for CKD and kidney function. We employed a range of analytical methods including cross-tissue transcriptome-wide association studies (TWASs), Mendelian randomization (MR), summary-based MR (SMR), and molecular docking. These analyses collectively identified 146 cross-tissue genetic associations with CKD and kidney function. Key Golgi apparatus-related genes (GARGs) and 41 potential drug targets were highlighted, with MAP3K11 emerging as a significant gene from the TWAS and MR data, underscoring its potential as a therapeutic target. Capsaicin displayed promising drug-target interactions in molecular docking analyses. Additionally, metabolome- and proteome-wide MR (PWMR) analyses revealed 33 unique metabolites and critical inflammatory proteins such as FGF5 that are significantly linked to and colocalized with CKD and kidney function. These insights deepen our understanding of CKD pathogenesis and highlight novel targets for treatment and prevention.


Asunto(s)
Simulación del Acoplamiento Molecular , Insuficiencia Renal Crónica , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/tratamiento farmacológico , Humanos , Estudio de Asociación del Genoma Completo , Riñón/metabolismo , Riñón/patología , Transcriptoma , Proteómica/métodos , Análisis de la Aleatorización Mendeliana , Predisposición Genética a la Enfermedad , Metabolómica/métodos , Proteoma/metabolismo , Metaboloma , Multiómica
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