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1.
Anim Biosci ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38665090

RESUMO

Objective: The experiment aimed to determine the standardized ileal digestibility (SID) of crude protein (CP) and amino acids (AA) in 10 brown rice samples fed to pigs, and to construct predictive models for SID of CP and AA based on the physical characteristics and chemical composition of brown rice. Methods: Twenty-two cannulated pigs (initial body weight: 42.0±1.2 kg) were assigned to a replicated 11×3 incomplete Latin square design, including an N-free diet and 10 brown rice diets. Each period included 5 d adaptation and 2 d ileal digesta collection. Chromic oxide was added at 0.3% to all the diets as an indigestible marker for calculating the ileal CP and AA digestibility. Results: The coefficients of variation of all detected indices for physical characteristics and chemical composition, except for bulk weight, dry matter (DM) and gross energy (GE), in 10 brown rice samples were greater than 10%. The SID of CP, lysine (Lys), methionine (Met), threonine (Thr) and tryptophan (Trp) in brown rice was 77.2% (62.6% to 85.5%), 87.5% (80.3% to 94.3%), 89.2% (78.9% to 98.9%), 55.4% (46.1% to 67.6%) and 92.5% (86.3% to 96.3%), respectively. The best prediction equations for the SID of CP, Lys, Thr and Trp were as following, SIDCP=ï¹£664.181+8.484×DM (R2=0.40), SIDLys=53.126+6.031×ether extract (EE) +0.893×thousand-kernel volume (R2=0.66), SIDThr=39.916+7.843×EE (R2=0.41) and SIDTrp=ï¹£361.588+4.891×DM+0.387×total starch (R2=0.85). Conclusion: Overall, a great variation exists among 10 sources of brown rice, and the thousand-grain volume, DM, EE, and total starch can be used as the key predictors for SID of CP and AA.

2.
Drug Resist Updat ; 74: 101080, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38579635

RESUMO

BACKGROUND: Gastric Cancer (GC) characteristically exhibits heterogeneous responses to treatment, particularly in relation to immuno plus chemo therapy, necessitating a precision medicine approach. This study is centered around delineating the cellular and molecular underpinnings of drug resistance in this context. METHODS: We undertook a comprehensive multi-omics exploration of postoperative tissues from GC patients undergoing the chemo and immuno-treatment regimen. Concurrently, an image deep learning model was developed to predict treatment responsiveness. RESULTS: Our initial findings associate apical membrane cells with resistance to fluorouracil and oxaliplatin, critical constituents of the therapy. Further investigation into this cell population shed light on substantial interactions with resident macrophages, underscoring the role of intercellular communication in shaping treatment resistance. Subsequent ligand-receptor analysis unveiled specific molecular dialogues, most notably TGFB1-HSPB1 and LTF-S100A14, offering insights into potential signaling pathways implicated in resistance. Our SVM model, incorporating these multi-omics and spatial data, demonstrated significant predictive power, with AUC values of 0.93 and 0.84 in the exploration and validation cohorts respectively. Hence, our results underscore the utility of multi-omics and spatial data in modeling treatment response. CONCLUSION: Our integrative approach, amalgamating mIHC assays, feature extraction, and machine learning, successfully unraveled the complex cellular interplay underlying drug resistance. This robust predictive model may serve as a valuable tool for personalizing therapeutic strategies and enhancing treatment outcomes in gastric cancer.

3.
Sci Bull (Beijing) ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38614854

RESUMO

Excitatory amino acid transporters (EAATs) are responsible for excitatory amino acid transportation and are associated with auto-immune diseases in the central nervous system and peripheral tissues. However, the subcellular location and function of EAAT2 in macrophages are still obscure. In this study, we demonstrated that LPS stimulation increases expression of EAAT2 (coded by Slc1a2) via NF-κB signaling. EAAT2 is necessary for inflammatory macrophage polarization through sustaining mTORC1 activation. Mechanistically, lysosomal EAAT2 mediates lysosomal glutamate and aspartate efflux to maintain V-ATPase activation, which sustains macropinocytosis and mTORC1. We also found that mice with myeloid depletion of Slc1a2 show alleviated inflammatory responses in LPS-induced systemic inflammation and high-fat diet induced obesity. Notably, patients with type II diabetes (T2D) have a higher level of expression of lysosomal EAAT2 and activation of mTORC1 in blood macrophages. Taken together, our study links the subcellular location of amino acid transporters with the fate decision of immune cells, which provides potential therapeutic targets for the treatment of inflammatory diseases.

4.
Tissue Cell ; 88: 102371, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38593570

RESUMO

BACKGROUND: Paeonol is a representative active ingredient of the traditional Chinese medicinal herbs Cortex Moutan, which has a well-established cardioprotective effect on ischemic heart disease. However, there is little evidence of the protective effect of paeonol, and its pharmacological mechanism is also unclear. This study aims to explore the protective effect and mechanism of Paeonol on myocardial infarction rat and hypoxic H9c2 cells. METHODS: Myocardial ischemia/reperfusion (I/R) was induced by occlusion of the left anterior descending coronary artery for 1 h followed by 3 h of reperfusion, and then gavage with Paeonol for 7 days. H9c2 cells were applied for the in vitro experiments and hypoxia/reoxygenation (H/R) model was established. CKIP-1 expression was evaluated by qPCR and western blot. The expression of genes involved in apoptosis, inflammation and ion channel was measured by western blot. The currents levels of Nav1.5 and Kir2.1 were measured by whole-cell patch-clamp recording. RESULTS: CKIP-1 expression was decreased in H/R-induced H9c2 cells, which was inversely increased after Paeonol treatment. Paeonol treatment could increase the viability of H/R-induced H9c2 cells and diminish the apoptosis and inflammation of H/R-induced H9c2 cells, while si-CKIP-1 treatment inhibited the phenomena. Moreover, the currents levels of Nav1.5 and Kir2.1 were reduced in H/R-induced H9c2 cells, which were inhibited after Paeonol treatment. Intragastric Paeonol can reduce the ventricular arrhythmias in rats with myocardial infarction. CONCLUSIONS: The protective effects of Paeonol on myocardial infarction rats and hypoxic H9c2 cells were achieved by up-regulating CKIP-1.

5.
Adv Mater ; : e2400849, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38567824

RESUMO

Harnessing the spontaneous surface instability of pliable substances to create intricate, well-ordered, and on-demand controlled surface patterns holds great potential for advancing applications in optical, electrical, and biological processes. However, the current limitations stem from challenges in modulating multidirectional stress fields and diverse boundary environments. Herein, this work proposes a universal strategy to achieve arbitrarily controllable wrinkle patterns via the spatiotemporal photochemical boundaries. Utilizing constraints and inductive effects of the photochemical boundaries, the multiple coupling relationship is accomplished among the light fields, stress fields, and morphology of wrinkles in photosensitive polyurethane (PSPU) film. Moreover, employing sequential light-irradiation with photomask enables the attainment of a diverse array of controllable patterns, ranging from highly ordered 2D patterns to periodic or intricate designs. The fundamental mechanics of underlying buckling and the formation of surface features are comprehensively elucidated through theoretical stimulation and finite element analysis. The results reveal the evolution laws of wrinkles under photochemical boundaries and represent a new effective toolkit for fabricating intricate and captivating patterns in single-layer films.

6.
Medicine (Baltimore) ; 103(9): e37289, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38428860

RESUMO

Adenocarcinoma of the esophagogastric junction (AEG) has a high incidence, and the extent of lymph node dissection (LND) and its impact on prognosis remain controversial. This study aimed to explore the risk factors for lymph node metastasis (LNM) and prognosis in Siewert II/III AEG patients. A retrospective review of 239 Siewert II/III AEG patients surgically treated at Beijing Friendship Hospital from July 2013 to December 2022 was conducted. Preoperative staging was conducted via endoscopy, ultrasound gastroscopy, CT, and biopsy. Depending on the stage, patients received radical gastrectomy with LND and chemotherapy. Clinicopathological data were collected, and survival was monitored semiannually until November 2023. Utilizing logistic regression for data analysis and Cox regression for survival studies, multivariate analysis identified infiltration depth (OR = 0.038, 95% CI: 0.011-0.139, P < .001), tumor deposit (OR = 0.101, 95% CI: 0.011-0.904, P = .040), and intravascular cancer embolus (OR = 0.234, 95% CI: 0.108-0.507, P < .001) as independent predictors of LNM. Lymph nodes No. 1, 2, 3, 4, 7, 10, and 11 were more prone to metastasis in the abdominal cavity. Notably, Siewert III AEG patients showed a higher metastatic rate in nodes No. 5 and No. 6 compared to Siewert II. Mediastinal LNM was predominantly found in nodes No. 110 and No. 111 for Siewert II AEG, with rates of 5.45% and 3.64%, respectively. A 3-year survival analysis underscored LNM as a significant prognostic factor (P = .001). Siewert II AEG patients should undergo removal of both celiac and mediastinal lymph nodes, specifically nodes No. 1, 2, 3, 4, 7, 10, 11, 110, and 111. Dissection of nodes No. 5 and No. 6 is not indicated for these patients. In contrast, Siewert III AEG patients do not require mediastinal LND, but pyloric lymphadenectomy for nodes No. 5 and No. 6 is essential. The presence of LNM is associated with poorer long-term prognosis. Perioperative chemotherapy may offer a survival advantage for AEG patients.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Metástase Linfática/patologia , Neoplasias Gástricas/patologia , Neoplasias Esofágicas/patologia , Prognóstico , Excisão de Linfonodo , Adenocarcinoma/patologia , Junção Esofagogástrica/patologia , Fatores de Risco
7.
Angew Chem Int Ed Engl ; : e202402171, 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38494450

RESUMO

Design the electrocatalysts without noble metal is still a challenge for oxygen evolution reaction (OER) in acid media. Herein, we reported the manganese (Mn) doping method to decrease the concentration of oxygen vacancy (VO) and form the Mn-O structure adjacent octahedral sites in spinel NiCo2O4-δ (NiMn1.5Co3O4-δ), which highly enhanced the activity and stability of spinel NiCo2O4-δ with a low overpotential (η) of 280 mV at j=10 mA cm-2 and long-term stability of 80 h in acid media. The isotopic labelling experiment based on differential electrochemical mass spectrometry (DEMS) clearly demonstrated the lattice oxygen in NiMn1.5Co3O4-δ is more stable due to strong Mn-O bond and shows synergetic adsorbate evolution mechanism (SAEM) for acid OER. Density functional theory (DFT) calculations reveal highly increased oxygen vacancy formation energy (EVO) of NiCo2O4-δ after Mn doping. More importantly, the highly hydrogen bonding between Mn-O and *OOH adsorbed on adjacent Co octahedral sites promote the formation of *OO from *OOH due to the greatly enhanced charge density of O in Mn substituted sites.

8.
Micromachines (Basel) ; 15(3)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38542643

RESUMO

The plasma rotating electrode process (PREP) is an ideal method for the preparation of metal powders such as nickel-based, titanium-based, and iron-based alloys due to its low material loss and good degree of sphericity. However, the preparation of silver alloy powder by PREP remains challenging. The low hardness of the mould casting silver alloy leads to the bending of the electrode rod when subjected to high-speed rotation during PREP. The mould casting silver electrode rod can only be used in low-speed rotation, which has a negative effect on particle refinement. This study employed continuous casting (CC) to improve the surface hardness of S800 Ag (30.30% higher than mould casting), which enables a high rotation speed of up to 37,000 revolutions per minute, and silver alloy powder with an average sphericity of 0.98 (5.56% higher than gas atomisation) and a sphericity ratio of 97.67% (36.28% higher than gas atomisation) has been successfully prepared. The dense S800 Ag was successfully fabricated by laser powder bed fusion (LPBF), which proved the feasibility of preparing high-quality powder by the "CC + PREP" method. The samples fabricated by LPBF have a Vickers hardness of up to 271.20 HV (3.66 times that of mould casting), leading to a notable enhancement in the strength of S800 Ag. In comparison to GA, the S800 Ag powder prepared by "CC + PREP" exhibits greater sphericity, a higher sphericity ratio and less satellite powder, which lays the foundation for dense LPBF S800 Ag fabrication.

9.
Med Eng Phys ; 125: 104135, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38508796

RESUMO

Traditional treatment methods have certain limitations. In recent years, the technique of internal fixation with double-plane double-supported screws based on X-ray images has been proposed to improve the therapeutic effect. The main objective of this research was to examine the effectiveness of the X-ray image-based bi-planar double-braced screw internal fixation technique . During surgery, the procedure was determined based on X-ray images, followed by an open reduction procedure at the fracture site, and finally internal fixation using bi-planar double-support screws. All patients were successfully treated with X-ray image-based bi-planar double support screw fixation. After surgery, X-ray images showed a good reduction of the fracture site without significant loosening or failure of the internal fixation. At the postoperative follow-up, the patient's pain symptoms were significantly relieved, and no significant complications occurred during recovery.


Assuntos
Fraturas do Colo Femoral , Humanos , Raios X , Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas/métodos , Parafusos Ósseos , Tecnologia , Resultado do Tratamento
10.
Phytomedicine ; 128: 155258, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38522318

RESUMO

BACKGROUND: Traditional Chinese Medicine (TCM), renowned for its holistic approach with a 2000-year history of utilizing natural remedies, offers unique advantages in disease prevention and treatment. Berberine, found in various Chinese herbs, has been employed for many years, primarily for addressing conditions such as diarrhea and dysentery. Berberine has recently become a research focus owing to its pharmacological activities and benefits to human bodies. However, little is known about the anti-inflammatory mechanism of berberine. PURPOSE: To summarize recent findings regarding the pharmacological effects and mechanisms of berberine anti-inflammation and highlight and predict the potential therapeutic effects and systematic mechanism of berberine. METHODS: Recent studies (2013-2023) on the pharmacological effects and mechanisms of berberine anti-inflammation were retrieved from Web of Science, PubMed, Google Scholar, and Scopus up to July 2023 using relevant keywords. Network pharmacology and bioinformatics analysis were employed to predict the therapeutic effects and mechanisms of berberine against potential diseases. RESULTS: The related pharmacological mechanisms of berberine anti-inflammation include the inhibition of inflammatory cytokine production (e.g., IL-1ß, IL-6, TNF-α), thereby attenuating the inflammatory response; Inhibiting the activation of NF-κB signaling pathway and IκBα degradation; Inhibiting the activation of MAPK signaling pathway; Enhancing the activation of the STAT1 signaling pathway; Berberine interacts directly with cell membranes through a variety of pathways, thereby influencing cellular physiological activities. Berberine enhances human immunity and modulates immune system function, which is integral to addressing certain autoimmune and tumour-related health concerns. CONCLUSION: This study expounds on the correlation between berberine and inflammatory diseases, encapsulating the mechanisms through which berberine treats select typical inflammatory ailments. Furthermore, it delves into a deeper understanding of berberine's effectiveness by integrating network pharmacology and molecular docking techniques in the context of treating inflammatory diseases. It provides guidance and reference for berberine's subsequent revelation of the modern scientific connotation of Chinese medicine.

11.
Medicine (Baltimore) ; 103(11): e37506, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489708

RESUMO

Poly-L-lactin acid (PLLA) has been widely used in the field of bio-medicine. In 2004, as an injectable material, PLLA was approved by the FDA to treat AIDS-related facial atrophy. Since then, several injectable stuffs containing PLLA have been approved for marketing in various countries and regions. Recently, PLLA has often been used to treat facial rejuvenation problems like cutaneous depressions and static wrinkles which always induce unsatisfactory facial expression. This review introduces the physicochemical properties, regeneration stimulating mechanism, applications in aesthetics and injectable comorbidity of PLLA.


Assuntos
Técnicas Cosméticas , Poliésteres , Polímeros , Humanos , Polímeros/uso terapêutico , Rejuvenescimento , Ácido Láctico , Estética , Reprodução
12.
J Biomol Struct Dyn ; : 1-14, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38529923

RESUMO

Mutations near allosteric sites can have a significant impact on the function of KRAS. Three specific mutations, K104Q, G12D/K104Q, and G12D/G75A, which are located near allosteric positions, were selected to investigate the molecular mechanisms behind mutation-induced influences on the activity of KRAS. Gaussian accelerated molecular dynamics (GaMD) simulations followed by the principal component analysis (PCA) were performed to improve the sampling of conformational states. The results revealed that these mutations significantly alter the structural flexibility, correlated motions, and dynamic behavior of the switch regions that are essential for KRAS binding to effectors or regulators. Furthermore, the mutations have a significant impact on the hydrogen bonding interactions between GDP and the switch regions, as well as on the electrostatic interactions of magnesium ions (Mg2+) with these regions. Our results verified that these mutations strongly influence the binding of KRAS to its effectors or regulators and allosterically regulate the activity. We believe that this work can provide valuable theoretical insights into a deeper understanding of KRAS function.Communicated by Ramaswamy H. Sarma.

13.
J Colloid Interface Sci ; 662: 160-170, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38340515

RESUMO

Developing a highly efficient strategy for the stabilization of the solid-liquid interface is a persistent pursuit for researchers. Herein, porous ionic liquids based on UiO-66 (Zr) porous materials were synthesized and applied to the selective desulfurization catalysis, which integrates the permanent pores of porous solids with the exceptional properties of ionic liquids. Results show that porous ionic liquids possess high activity and selectivity for dibenzothiophene. Experimental analysis and density functional theory calculations revealed that the ionic liquids moiety served as an extractant to enrich dibenzothiophene into the porous ionic liquids phase through the π···π and CH···π interactions. Additionally, the electrostatic solvent effect in the porous ionic liquids contributes to the stabilization solid-liquid interface, which was favorable for UiO-66 moiety to catalytically activate hydrogen peroxide (H2O2) to generate ·OH radicals, and subsequently oxidized dibenzothiophene to the corresponding sulfone. It is hoped that the development of porous ionic liquids could pave a new route to the stabilization of the solid-liquid interface for catalytic oxidation.

14.
Proc Natl Acad Sci U S A ; 121(10): e2309957121, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38422022

RESUMO

Hypoxia signaling influences tumor development through both cell-intrinsic and -extrinsic pathways. Inhibiting hypoxia-inducible factor (HIF) function has recently been approved as a cancer treatment strategy. Hence, it is important to understand how regulators of HIF may affect tumor growth under physiological conditions. Here we report that in aging mice factor-inhibiting HIF (FIH), one of the most studied negative regulators of HIF, is a haploinsufficient suppressor of spontaneous B cell lymphomas, particular pulmonary B cell lymphomas. FIH deficiency alters immune composition in aged mice and creates a tumor-supportive immune environment demonstrated in syngeneic mouse tumor models. Mechanistically, FIH-defective myeloid cells acquire tumor-supportive properties in response to signals secreted by cancer cells or produced in the tumor microenvironment with enhanced arginase expression and cytokine-directed migration. Together, these data demonstrate that under physiological conditions, FIH plays a key role in maintaining immune homeostasis and can suppress tumorigenesis through a cell-extrinsic pathway.


Assuntos
Linfoma de Células B , Proteínas Repressoras , Animais , Camundongos , Hipóxia/metabolismo , Oxigenases de Função Mista/metabolismo , Proteínas Repressoras/metabolismo , Microambiente Tumoral
15.
Vet Parasitol ; 327: 110143, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38325134

RESUMO

Coccidiosis is one of the leading morbidity causes in chickens, causing a reduction of body weight and egg production. Backyard chickens are at risk of developing clinical and subclinical coccidiosis due to outdoor housing and scavenging behaviour, jeopardizing food security in households. The objectives of this study were to estimate clinical prevalence of coccidiosis at country and regional levels in the Horn of Africa in extensive backyard chickens. A binomial random effects model was developed to impute prevalence of coccidiosis. Previously gathered prevalence data (n = 40) in backyard chickens was used to define the model. Precipitation (OR: 1.09 (95% CI: 1.05-1.13) and the presence of seasonal rainfall (OR: 1.85, 95% CI: 1.27-2.70) significantly increase prevalence. Results showed an overall prevalence of coccidiosis in the Horn of Africa of 0.21 (95% CI: 0.15-0.29). Ethiopia, the Republic of South Sudan and Kenya showed the highest prevalence and Djibouti the lowest. Significant differences between Djibouti and the countries with highest prevalence were found. However, no evidence of a significant difference between the rest of the countries. Kenya and Ethiopia showed larger prevalence differences between regions. Results could assist with the targeting of testing for coccidiosis, the observation for clinical disease of chickens living in specific regions and as a baseline for the evaluation of future control measures.


Assuntos
Coccidiose , Eimeria , Doenças das Aves Domésticas , Animais , Galinhas , Prevalência , Habitação , Doenças das Aves Domésticas/epidemiologia , Coccidiose/epidemiologia , Coccidiose/veterinária , Etiópia/epidemiologia
16.
Obes Rev ; 25(5): e13701, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38311366

RESUMO

Melatonin appears to be a promising supplement for obesity treatment. The antiobesity effects of melatonin on obese rodents are influenced by various factors, including the species, sex, the dosage of melatonin, treatment duration, administration via, daily treatment time, and initial body weight (IBW). Therefore, we conducted a meta-analysis and machine learning study to evaluate the antiobesity effect of melatonin on obese mice or rats from 31 publications. The results showed that melatonin significantly reduced body weight, serum glucose (GLU), triglycerides (TGs), low-density lipoprotein (LDL), and cholesterol (TC) levels in obese mice or rats but increased high-density lipoprotein (HDL) levels. Melatonin showed a slight positive effect on clock-related genes, although the number of studies was limited. Meta-regression analysis and machine learning indicated that the dosage of melatonin was the primary factor influencing body weight, with higher melatonin dosages leading to a stronger weight reduction effect. Together, male obese C57BL/6 mice and Sprague-Dawley rats with an IBW of 100-200 g showed better body weight reduction when supplemented with a dose of 10-30 mg/kg melatonin administered at night via injection for 5-8 weeks.


Assuntos
Melatonina , Camundongos , Ratos , Masculino , Animais , Melatonina/farmacologia , Melatonina/uso terapêutico , Roedores , Camundongos Obesos , Ratos Sprague-Dawley , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Peso Corporal , Triglicerídeos , Redução de Peso , Aprendizado de Máquina
17.
Clin Transl Med ; 14(2): e1587, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38372484

RESUMO

Metastasis is responsible for at least 90% of colon cancer (CC)-related deaths. Lipid metabolism is a critical factor in cancer metastasis, yet the underlying mechanism requires further investigation. Herein, through the utilisation of single-cell sequencing and proteomics, we identified sulfotransferase SULT2B1 as a novel metastatic tumour marker of CC, which was associated with poor prognosis. CC orthotopic model and in vitro assays showed that SULT2B1 promoted lipid metabolism and metastasis. Moreover, SULT2B1 directly interacted with SCD1 to facilitate lipid metabolism and promoted metastasis of CC cells. And the combined application of SCD1 inhibitor CAY with SULT2B1- konockout (KO) demonstrated a more robust inhibitory effect on lipid metabolism and metastasis of CC cells in comparison to sole application of SULT2B1-KO. Notably, we revealed that lovastatin can block the SULT2B1-induced promotion of lipid metabolism and distant metastasis in vivo. Further evidence showed that SMC1A transcriptionally upregulated the expression of SULT2B1. Our findings unveiled the critical role of SULT2B1 in CC metastasis and provided a new perspective for the treatment of CC patients with distant metastasis.


Assuntos
Neoplasias do Colo , Metabolismo dos Lipídeos , Humanos , Metabolismo dos Lipídeos/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Sulfotransferases/genética , Sulfotransferases/metabolismo , Estearoil-CoA Dessaturase/metabolismo
18.
Cancer Lett ; 587: 216657, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38336289

RESUMO

Metastatic colonization by circulating cancer cells is a highly inefficient process. To colonize distant organs, disseminating cancer cells must overcome many obstacles in foreign microenvironments, and only a small fraction of them survives this process. How these disseminating cancer cells cope with stress and initiate metastatic process is not fully understood. In this study, we report that the metastatic onset of prostate cancer cells is associated with the dynamic conversion of metabolism signaling pathways governed by the energy sensors AMPK and mTOR. While in circulation in blood flow, the disseminating cancer cells display decreased mTOR and increased AMPK activities that protect them from stress-induced death. However, after metastatic onset, the mTOR-AMPK activities are reversed, enabling mTOR-dependent tumor growth. Suppression of this dynamic conversion by co-targeting of AMPK and mTOR signaling significantly suppresses prostate cancer cell and tumor organoid growth in vitro and experimental metastasis in vivo, suggesting that this can be a therapeutic approach against metastasizing prostate cancer.


Assuntos
Proteínas Quinases Ativadas por AMP , Neoplasias da Próstata , Masculino , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais , Neoplasias da Próstata/patologia , Microambiente Tumoral
19.
Front Cardiovasc Med ; 11: 1253554, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38374993

RESUMO

Purpose: This study aimed to investigate the effect of Marshall ethanol infusion (VOM-Et) in the vein on mitral isthmus (MI) ablation. Methods: Patients with persistent atrial fibrillation (AF) were grouped into vein of VOM-Et combined with radiofrequency (RF) ablation (VOM-Et-RF) and RF groups. The primary outcome was MI block immediate block rate after surgery. Stratified analysis was also performed for factors affecting the outcome measures. Results: A total of 118 consecutive patients underwent AF ablation at Taizhou Hospital of Zhejiang Province from January 2018 to December 2021. Successful bidirectional perimitral block was achieved in 96% of patients in VOM-Et-RF (69 of 72) and in 76% of patients in the RF group (35 of 46) (P < 0.01). In the subgroup analysis, male sex, elder than 60 years, Left atrial diameter <55 mm, and AF duration <3 years were associated with the benefits of VOM-Et in AF Patients. Conclusion: The vein of Marshall ethanol infusion for catheter ablation can improve the MI block rate. Male sex, elder age, smaller Left atrial diameter and shorter AF duration may have significant benefits for VOM-Et.

20.
Biochem Biophys Rep ; 37: 101655, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38333051

RESUMO

Background: Previous studies have shown that the nicotinamide adenine dinucleotide (NAD+) precursors, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), protect against endogenously or exogenously induced DNA damage. However, whether the two compounds have the same or different efficacy against DNA damage is not clear. In the current study, we systematically compared the effects of NMN and NR on cisplatin-induced DNA damage in HeLa cells. Methods: To evaluate the protective effects of NMN or NR, HeLa cells were pretreated with different doses of NMN or NR followed with 10 µM of cisplatin treatment. Cell viability was examined by Trypan blue staining assay. For observing the DNA damage repair process, HeLa cells were treated with 10 µM of cisplatin for 12 h, followed with 10 mM NMN or NR treatment for another 8, 16, 24, or 32 h, DNA damage levels were assessed for each time point by immunofluorescent staining against phosphor-H2AX (γH2AX) and alkaline comet assay. The effects of NMN and NR on intracellular NAD+ and reactive oxygen species (ROS) levels were also determined. Results: NMN and NR treatment alone did not have any significant effects on cell viability, however, both can protect HeLa cells from cisplatin-induced decrease of cell viability with similar efficacy in a dose-dependent manner. On the other hand, while both can reduce the DNA damage levels in cisplatin-treated cells, NR exhibited better protective effect. However, both appeared to boost the DNA damage repair process with similar efficacy. NMN or NR treatment alone could increase cellular NAD+ levels, and both can reverse cisplatin-induced decrease of NAD+ levels. Finally, while neither NMN nor NR affected cellular ROS levels, both inhibited cisplatin-induced increase of ROS with no significant difference between them. Conclusion: NR have a better protective effect against cisplatin-induced DNA damage than NMN.

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