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1.
Cureus ; 16(5): e61347, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38947641

RESUMO

Pulmonary arteriovenous fistula (PAVF) is a rare congenital vascular malformation primarily manifested as dyspnea, migraine, ischemic stroke, hemoptysis, and nervous system complications. However, in our case, an 18-year-old male patient with PAVF presented with sudden onset of ventricular tachycardia and type 2 acute myocardial infarction as initial symptoms. A diagnosis was achieved through pulmonary artery computer tomography angiography (CTA) and three-dimensional (3D) computed tomography (CT) reconstruction, revealing a complex and giant PAVF. Following multidisciplinary team (MDT) consultation, the patient underwent thoracoscopic surgery and experienced a successful recovery during follow-up.

2.
Molecules ; 29(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38999010

RESUMO

Hypochlorite (ClO-) and viscosity both affect the physiological state of mitochondria, and their abnormal levels are closely related to many common diseases. Therefore, it is vitally important to develop mitochondria-targeting fluorescent probes for the dual sensing of ClO- and viscosity. Herein, we have explored a new fluorescent probe, XTAP-Bn, which responds sensitively to ClO- and viscosity with off-on fluorescence changes at 558 and 765 nm, respectively. Because the emission wavelength gap is more than 200 nm, XTAP-Bn can effectively eliminate the signal crosstalk during the simultaneous detection of ClO- and viscosity. In addition, XTAP-Bn has several advantages, including high selectivity, rapid response, good water solubility, low cytotoxicity, and excellent mitochondrial-targeting ability. More importantly, probe XTAP-Bn is successfully employed to monitor the dynamic change in ClO- and viscosity levels in the mitochondria of living cells and zebrafish. This study not only provides a reliable tool for identifying mitochondrial dysfunction but also offers a potential approach for the early diagnosis of mitochondrial-related diseases.


Assuntos
Corantes Fluorescentes , Ácido Hipocloroso , Mitocôndrias , Peixe-Zebra , Ácido Hipocloroso/análise , Corantes Fluorescentes/química , Animais , Mitocôndrias/metabolismo , Viscosidade , Humanos , Imagem Óptica/métodos , Células HeLa
3.
Nat Commun ; 15(1): 5908, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003316

RESUMO

Although Prussian blue nanozymes (PBNZ) are widely applied in various fields, their catalytic mechanisms remain elusive. Here, we investigate the long-term catalytic performance of PBNZ as peroxidase (POD) and catalase (CAT) mimetics to elucidate their lifespan and underlying mechanisms. Unlike our previously reported Fe3O4 nanozymes, which exhibit depletable POD-like activity, the POD and CAT-like activities of PBNZ not only persist but slightly enhance over prolonged catalysis. We demonstrate that the irreversible oxidation of PBNZ significantly promotes catalysis, leading to self-increasing catalytic activities. The catalytic process of the pre-oxidized PBNZ can be initiated through either the conduction band pathway or the valence band pathway. In summary, we reveal that PBNZ follows a dual-path electron transfer mechanism during the POD and CAT-like catalysis, offering the advantage of a long service life.


Assuntos
Catalase , Ferrocianetos , Oxirredução , Peroxidase , Ferrocianetos/química , Catálise , Catalase/química , Catalase/metabolismo , Peroxidase/metabolismo , Peroxidase/química , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Nanoestruturas/química
4.
Artigo em Inglês | MEDLINE | ID: mdl-38976980

RESUMO

Molecular dynamics (MD) simulations and first principles calculations were performed to study the tribological behavior of graphene/h-BN (G/h-BN) heterostructures with vacancy and (Stone-Wales) SW defect under uniform normal load, revealing the mechanism of the effect of defect types on friction, and discussing the coupling effect of temperature and interfacial defects on the tribological behavior of G/h-BN heterostructures. Under the normal force of 0.2nN/atom, the friction force of the four systems is 0.0057, 0.0096, 0.0077, and 0.26 nN, respectively. The friction force of SW defect heterostructure is 45 times that of perfect interface heterostructure. The influence of defect type on friction force is SW>SV>DV. By observing the dynamic change of the Z-direction coordinate position of the sliding layer atoms, the slip potential energy curves and the evolution law of the moiré pattern, the relationship between the structural morphology and the energy change of different defective heterostructures and the frictional behavior was investigated comprehensively and intuitively for the first time. From the perspective of atomic strain, the deformation of heterostructures at the atomic level was quantified. The results showed that at 300 K and 0 K, the maximum strain of atoms in the sliding layer was 11.25% and 9.85%, respectively. The thermal perturbation mainly occurs in the out-of-plane direction, which in turn affects the friction. Through density functional theory, it is found that under uniform load, it is difficult to form bonds between the graphene sliding layer and the substrate layer when the defects are in the h-BN substrate layer, which has less influence on the friction of the system, thus making the defective heterostructures also remain superlubricity state. These results provide a new understanding of the interfacial friction of G/h-BN defective heterostructure.

5.
World J Pediatr ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970732

RESUMO

BACKGROUND: Monogenic lupus is defined as systemic lupus erythematosus (SLE)/SLE-like patients with either dominantly or recessively inherited pathogenic variants in a single gene with high penetrance. However, because the clinical phenotype of monogenic SLE is extensive and overlaps with that of classical SLE, it causes a delay in diagnosis and treatment. Currently, there is a lack of early identification models for clinical practitioners to provide early clues for recognition. Our goal was to create a clinical model for the early identification of pediatric monogenic lupus, thereby facilitating early and precise diagnosis and treatment for patients. METHODS: This retrospective cohort study consisted of 41 cases of monogenic lupus treated at the Department of Pediatrics at Peking Union Medical College Hospital from June 2012 to December 2022. The control group consisted of classical SLE patients recruited at a 1:2 ratio. Patients were randomly divided into a training group and a validation group at a 7:3 ratio. A logistic regression model was established based on the least absolute shrinkage and selection operator to generate the coefficient plot. The predictive ability of the model was evaluated using receiver operator characteristic curves and the area under the curve (AUC) index. RESULTS: A total of 41 cases of monogenic lupus patients and 82 cases of classical SLE patients were included. Among the monogenic lupus cases (with a male-to-female ratio of 1:1.05 and ages of onset ranging from birth to 15 years), a total of 18 gene mutations were identified. The variables included in the coefficient plot were age of onset, recurrent infections, intracranial calcifications, growth and developmental delay, abnormal muscle tone, lymphadenopathy/hepatosplenomegaly, and chilblain-like skin rash. Our model demonstrated satisfactory diagnostic performance through internal validation, with an AUC value of 0.97 (95% confidence interval = 0.92-0.97). CONCLUSIONS: We summarized and analyzed the clinical characteristics of pediatric monogenic lupus and developed a predictive model for early identification by clinicians. Clinicians should exercise high vigilance for monogenic lupus when the score exceeds - 9.032299.

6.
J Hazard Mater ; 476: 135049, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38970973

RESUMO

Sulfate-reducing bacteria (SRB) are known to alter methylmercury (MeHg) production in paddy soil, but the effect of SRB on MeHg dynamics in rhizosphere and rice plants remains to be fully elucidated. The present study investigated the impact of SRB on MeHg levels in unsterilized and γ-sterilized mercury-polluted paddy soils, with the aim to close this knowledge gap. Results showed that the presence of SRB reduced MeHg production by ∼22 % and ∼17 % in the two soils, but elevated MeHg contents by approximately 55 % and 99 % in rice grains, respectively. Similar trend at smaller scales were seen in roots and shoots. SRB inoculation exerted the most profound impact on amino acid metabolism in roots, with the relative response of L-arginine positively linking to MeHg concentrations in rhizosphere. The SRB-induced enrichment of MeHg in rice plants may be interpreted by the stronger presence of endophytic nitrogen-related microbes (e.g. Methylocaldum, Hyphomicrobium and Methylocystis) and TGA transcription factors interacting with glutathione metabolism and calmodulin. Our study provides valuable insights into the complex effects of SRB inoculation on MeHg dynamics in rice ecosystems, and may help to develop strategies to effectively control MeHg accumulation in rice grains.

7.
J Food Sci ; 89(7): 4109-4122, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38957103

RESUMO

The elucidation of the interaction mechanism between phospholipids and milk proteins within emulsions is pivotal for comprehending the properties of infant formula fat globules. In this study, multispectral methods and molecular docking were employed to explore the relationship between phosphatidylcholine (PC) and whey protein isolate (WPI). Observations indicate that the binding constant, alongside thermodynamic parameters, diminishes as temperature ascends, hinting at a predominantly static quenching mechanism. Predominantly, van der Waals forces and hydrogen bonds constitute the core interactions between WPI and PC. This assertion is further substantiated by Fourier transform infrared spectroscopy, which verifies PC's influence on WPI's secondary structure. A detailed assessment of thermodynamic parameters coupled with molecular docking reveals that PC predominantly adheres to specific sites within α-lactalbumin, ß-lactoglobulin, and bovine serum albumin, propelled by a synergy of hydrophobic interactions, hydrogen bonding, and van der Waals forces, with binding energies noted at -5.59, -6.71, and -7.85 kcal/mol, respectively. An increment in PC concentration is observed to amplify the emulsification properties of WPI whilst concurrently diminishing the zeta potential. This study establishes a theoretical foundation for applying the PC-WPI interaction mechanism in food.


Assuntos
Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Simulação de Acoplamento Molecular , Fosfatidilcolinas , Termodinâmica , Proteínas do Soro do Leite , Proteínas do Soro do Leite/química , Fosfatidilcolinas/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Lactoglobulinas/química , Lactoglobulinas/metabolismo , Emulsões/química , Lactalbumina/química , Lactalbumina/metabolismo , Soroalbumina Bovina/química , Fórmulas Infantis/química
8.
Sensors (Basel) ; 24(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38894241

RESUMO

Eddy current testing (ECT) is commonly used for the detection of defects inside metallic materials. In order to achieve the effective testing of CFRP materials, increasing the operating frequency or improving the coil structure is a common method used by researchers. Higher or wider operating frequencies make the design of the ADC's conditioning circuit complex and difficult to miniaturize. In this paper, an LC resonator based on inductance-to-digital converters (LDCs) is designed to easily detect the resonant frequency response to the state of the material under test. The reasonableness of the coil design is proven by simulation. The high signal-to-noise ratio (SNR) and detection sensitivity of the LC resonator are demonstrated through comparison experiments involving multiple probes. The anti-interference capability of the LC resonator in CFRP defect detection is demonstrated through various interference experiments.

9.
Oncol Rep ; 52(1)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38847277

RESUMO

Ursolic acid (UA), a pentacyclic triterpenoid that has been found in a broad variety of fruits, spices and medicinal plants, has various biological effects such as reducing inflammation, protecting cells from damage, and preserving brain function. However, its impact on ferroptosis in cancer stem­like cells remains unexplored. The present study investigated the effect of UA on MDA­MB­231 and BT­549 cell­derived triple­negative breast CSCs (BCSCs) and its potential ferroptosis pathway. The effects of ferroptosis on BCSCs were demonstrated by the detection of ferroptosis­related indexes including the intracellular level of glutathione, malondialdehyde, reactive oxygen species and iron. The effects of UA on the biological behaviors of BCSCs were analyzed by Cell Counting Kit­8, stemness indexes detection and mammosphere formation assay. The mechanism of UA induction on BCSCs was explored by reverse transcription­quantitative PCR and western blotting. BALB/c­nude mice were subcutaneously injected with MDA­MB­231­derived BCSCs to establish xenograft models to detect the effects of UA in vivo. The results revealed that BCSCs have abnormal iron metabolism and are less susceptible to ferroptosis. UA effectively reduces the stemness traits and proliferation of BCSCs in spheroids and mice models by promoting ferroptosis. It was observed that UA stabilizes Kelch­like ECH­associated protein 1 and suppresses nuclear factor erythroid­related factor 2 (NRF2) activation. These findings suggested that the ability of UA to trigger ferroptosis through the inhibition of the NRF2 pathway could be a promising approach for treating BCSCs, potentially addressing metastasis and drug resistance in triple­negative breast cancer (TNBC). This expands the clinical applications of UA and provides a theoretical basis for its use in TNBC treatment.


Assuntos
Proliferação de Células , Ferroptose , Fator 2 Relacionado a NF-E2 , Células-Tronco Neoplásicas , Neoplasias de Mama Triplo Negativas , Triterpenos , Ácido Ursólico , Ensaios Antitumorais Modelo de Xenoenxerto , Ferroptose/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Triterpenos/farmacologia , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Camundongos , Feminino , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
10.
Methods Enzymol ; 699: 59-87, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38942516

RESUMO

Structural biology research of terpene synthases (TSs) has provided a useful basis to understand their catalytic mechanisms in producing diverse terpene products with polycyclic ring systems and multiple chiral centers. However, compared to the large numbers of>95,000 terpenoids discovered to date, few structures of TSs have been solved and the understanding of their catalytic mechanisms is lagging. We here (i) introduce the basic catalytic logic, the structural architectures, and the metal-binding conserved motifs of TSs; (ii) provide detailed experimental procedures, in gene cloning and plasmid construction, protein purification, crystallization, X-ray diffraction data collection and structural elucidation, for structural biology research of TSs; and (iii) discuss the prospects of structure-based engineering and de novo design of TSs in generating valuable terpene molecules, which cannot be easily achieved by chemical synthesis.


Assuntos
Alquil e Aril Transferases , Alquil e Aril Transferases/química , Alquil e Aril Transferases/metabolismo , Alquil e Aril Transferases/genética , Cristalografia por Raios X/métodos , Terpenos/metabolismo , Terpenos/química , Clonagem Molecular/métodos , Modelos Moleculares , Conformação Proteica
11.
Micromachines (Basel) ; 15(6)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38930708

RESUMO

Under certain circumstances, a high-speed railway may require constant acceleration or emergency braking, in which case the inverter may experience short-term overload conditions and the current passing through the IGBT will go beyond the rated design tolerance. Under overload conditions, the IGBT loss will increase instantly, raising the power semiconductor device's junction temperature in the process. This research examines the boosting-gate-voltage-driven IGBT control technology. It increases the gate drive voltage and the IGBT current capacity and decreases the conduction voltage drop of IGBT under short-term overload conditions, reducing the instantaneous loss and temperature rise undulation of IGBT. The working characteristics of IGBT devices are studied, and the influence of gate drive voltage on device loss and temperature rise fluctuations is analyzed. Based on the emergency acceleration and brake conditions of the actual train operation, the short-term overload characteristics of the inverter are analyzed. The optimization analysis of the boosting gate voltage under emergency conditions is carried out, and the IGBT drive circuit with gate voltage pumping function is designed. The effectiveness of the driving circuit is verified through PSpice simulation and actual switching characteristic test. According to the analysis of experimental data, it can be verified that increasing the gate voltage technology can reduce IGBT losses.

12.
Anal Chem ; 96(25): 10170-10181, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38862388

RESUMO

The diversity of cannabinoid isomers and complexity of Cannabis products pose significant challenges for analytical methodologies. In this study, we developed a method to analyze 14 different cannabinoid isomers in diverse samples within milliseconds by leveraging the unique adduct-forming behavior of silver ions in advanced cyclic ion mobility spectrometry-mass spectrometry. The developed method achieved the separation of isomers from four groups of cannabinoids: Δ3-tetrahydrocannabinol (THC) (1), Δ8-THC (2), Δ9-THC (3), cannabidiol (CBD) (4), Δ8-iso-THC (5), and Δ(4)8-iso-THC (6) (all MW = 314); 9α-hydroxyhexahydrocannabinol (7), 9ß-hydroxyhexahydrocannabinol (8), and 8-hydroxy-iso-THC (9) (all MW = 332); tetrahydrocannabinolic acid (THCA) (10) and cannabidiolic acid (CBDA) (11) (both MW = 358); Δ8-tetrahydrocannabivarin (THCV) (12), Δ8-iso-THCV (13), and Δ9-THCV (14) (all MW = 286). Moreover, experimental and theoretical traveling wave collision cross section values in nitrogen (TWCCSN2) of cannabinoid-Ag(I) species were obtained for the first time with an average error between experimental and theoretical values of 2.6%. Furthermore, a workflow for the identification of cannabinoid isomers in Cannabis and Cannabis-derived samples was established based on three identification steps (m/z and isotope pattern of Ag(I) adducts, TWCCSN2, and MS/MS fragments). Afterward, calibration curves of three major cannabinoids were established with a linear range of 1-250 ng·ml-1 for Δ8-THC (2) (R2 = 0.9999), 0.1-25 ng·ml-1 for Δ9-THC (3) (R2 = 0.9987), and 0.04-10 ng·ml-1 for CBD (4) (R2 = 0.9986) as well as very low limits of detection (0.008-0.2 ng·ml-1). Finally, relative quantification of Δ8-THC (2), Δ9-THC (3), and CBD (4) in eight complex acid-treated CBD mixtures was achieved without chromatographic separation. The results showed good correspondence (R2 = 0.999) with those obtained by gas chromatography-flame ionization detection/mass spectrometry.


Assuntos
Canabinoides , Cannabis , Dronabinol , Espectrometria de Mobilidade Iônica , Espectrometria de Massas , Cannabis/química , Canabinoides/análise , Canabinoides/química , Dronabinol/análise , Dronabinol/análogos & derivados , Espectrometria de Mobilidade Iônica/métodos , Espectrometria de Massas/métodos , Extratos Vegetais/química , Extratos Vegetais/análise , Isomerismo
13.
Nat Commun ; 15(1): 5398, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926348

RESUMO

Ionotropic gelation is widely used to fabricate targeting nanoparticles (NPs) with polysaccharides, leveraging their recognition by specific lectins. Despite the fabrication scheme simply involves self-assembly of differently charged components in a straightforward manner, the identification of a potent combinatory formulation is usually limited by structural diversity in compound collections and trivial screen process, imposing crucial challenges for efficient formulation design and optimization. Herein, we report a diversity-oriented combinatory formulation screen scheme to identify potent gene delivery cargo in the context of precision cardiac therapy. Distinct categories of cationic compounds are tested to construct RNA delivery system with an ionic polysaccharide framework, utilizing a high-throughput microfluidics workstation coupled with streamlined NPs characterization system in an automatic, step-wise manner. Sequential computational aided interpretation provides insights in formulation optimization in a broader scenario, highlighting the usefulness of compound library diversity. As a result, the out-of-bag NPs, termed as GluCARDIA NPs, are utilized for loading therapeutic RNA to ameliorate cardiac reperfusion damages and promote the long-term prognosis. Overall, this work presents a generalizable formulation design strategy for polysaccharides, offering design principles for combinatory formulation screen and insights for efficient formulation identification and optimization.


Assuntos
Nanopartículas , Polissacarídeos , Polissacarídeos/química , Nanopartículas/química , Animais , Humanos , Camundongos , Técnicas de Transferência de Genes , Terapêutica com RNAi/métodos , Interferência de RNA , Masculino , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/química , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/terapia
14.
Small ; : e2401400, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38881184

RESUMO

Stem cell-related therapeutic technologies have garnered significant attention of the research community for their multi-faceted applications. To promote the therapeutic effects of stem cells, the strategies for cell microencapsulation in hydrogel microparticles have been widely explored, as the hydrogel microparticles have the potential to facilitate oxygen diffusion and nutrient transport alongside their ability to promote crucial cell-cell and cell-matrix interactions. Despite their significant promise, there is an acute shortage of automated, standardized, and reproducible platforms to further stem cell-related research. Microfluidics offers an intriguing platform to produce stem cell-laden hydrogel microparticles (SCHMs) owing to its ability to manipulate the fluids at the micrometer scale as well as precisely control the structure and composition of microparticles. In this review, the typical biomaterials and crosslinking methods for microfluidic encapsulation of stem cells as well as the progress in droplet-based microfluidics for the fabrication of SCHMs are outlined. Moreover, the important biomedical applications of SCHMs are highlighted, including regenerative medicine, tissue engineering, scale-up production of stem cells, and microenvironmental simulation for fundamental cell studies. Overall, microfluidics holds tremendous potential for enabling the production of diverse hydrogel microparticles and is worthy for various stem cell-related biomedical applications.

15.
J Phys Condens Matter ; 36(37)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38843804

RESUMO

Super microgenerator (SMG) refers to a generator that can efficiently convert extremely weak external stimuli into electrical energy and has a small size, high power density and long lifespan, offer ground-breaking solutions for powering wearable devices, wireless distributed sensors and implanted medical equipment. However, the friction and wear between the interfaces of ordinary microgenerator results in an extremely low lifespan. Here, we present a prototype of SMGs based on a 2D-2D (graphite-MoS2) Schottky contact in the state of structural superlubricity (no wear and nearly zero friction between two contacted solid surfaces). What is even more interesting is when the graphite flake is slid from the bulk to the edge of MoS2, the output current will enhance from 31 to 56 A m-2. Through the I-V curve measurement, we found that the conductive channel across the junction can be activated and further enhanced at the edge of MoS2compare to bulk, which provide the explanation for the above-mentioned edge enhancement of power generation. Above results provide the design principles of high-performance SMGs based on 2D-2D Schottky junctions.

16.
Oncogene ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914663

RESUMO

Gemcitabine resistance is a major obstacle to the effectiveness of chemotherapy in pancreatic ductal adenocarcinoma (PDAC). Therefore, new strategies are needed to sensitize cancer cells to gemcitabine. Here, we constructed gemcitabine-resistant PDAC cells and analyzed them with RNA-sequence. Employing an integrated approach involving bioinformatic analyses from multiple databases, TGFB2 is identified as a crucial gene in gemcitabine-resistant PDAC and is significantly associated with poor gemcitabine therapeutic response. The patient-derived xenograft (PDX) model further substantiates the gradual upregulation of TGFB2 expression during gemcitabine-induced resistance. Silencing TGFB2 expression can enhance the chemosensitivity of gemcitabine against PDAC. Mechanistically, TGFB2, post-transcriptionally stabilized by METTL14-mediated m6A modification, can promote lipid accumulation and the enhanced triglyceride accumulation drives gemcitabine resistance by lipidomic profiling. TGFB2 upregulates the lipogenesis regulator sterol regulatory element binding factor 1 (SREBF1) and its downstream lipogenic enzymes via PI3K-AKT signaling. Moreover, SREBF1 is responsible for TGFB2-mediated lipogenesis to promote gemcitabine resistance in PDAC. Importantly, TGFB2 inhibitor imperatorin combined with gemcitabine shows synergistic effects in gemcitabine-resistant PDAC PDX model. This study sheds new light on an avenue to mitigate PDAC gemcitabine resistance by targeting TGFB2 and lipid metabolism and develops the potential of imperatorin as a promising chemosensitizer in clinical translation.

17.
Acta Pharmacol Sin ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719954

RESUMO

Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.

19.
Int J Surg ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38742842

RESUMO

BACKGROUND: Robot-assisted kidney transplantation (RAKT) surgery is an advanced minimally invasive technique, albeit with extended surgical and kidney ischemia time. To safeguard kidney function, we have devised a continuous surface cooling method (CSCT) for intraoperative kidney cooling. MATERIALS AND METHODS: Patients receiving RAKT were divided into CSCT group and conventional group. The CSCT is a custom-designed apparatus composed of a single-layer plastic bag, featuring an inflow and an outflow that create a closed circuit for the continuous flow of cooling saline. The conventional group utilized ice slush for kidney graft cooling (Vattikuti Urology Institute-Medanta Technique, VUIMT). Patients who underwent open renal transplantation during the same period were also included in the study. All patients were subject to a minimum 2-month follow-up. And 1:3 propensity score matching was used to minimize selection bias. RESULTS: A total of 144 patients underwent CSCT, 47 underwent VUIMT, and 196 underwent open surgery were included in the study, while after matching, 129, 43, 129 patients were included in the three groups, respectively. The median follow-up time was 19 months. None of the patients experienced delayed graft function, patient mortality, or graft loss. After introducing the kidney into the abdominal cavity for 20 minutes, the surface temperature of the kidney in the CSCT group was notably lower compared to the VUIMT group (15.42±0.88 vs. 21.74±2.53°C, P=0.001). This temperature disparity became more pronounced at 65 minutes (19.74±1.61 vs. 29.82±1.63°C, P<0.001). At both 3 and 7 days post-transplantation, creatinine levels in the VUIMT group were significantly higher than those in the CSCT and open surgery groups (at 3 d, 244.13±45.61 vs. 182.51±55.47 in CSCT group, P<0.001, or vs. 182.77±61.32 in the open surgery group, P<0.001; at 7 d, 162.42±54.86 vs. 143.11±44.32 in the CSCT group, P<0.001, or vs. 135.23±45.27 in the open surgery group, P<0.001). No differences were observed in blood creatinine, estimated glomerular filtration rate, and perioperative complications between the CSCT and open surgery groups. CONCLUSION: The CSCT presents a significant advantage over the traditional VUIMT method in terms of kidney cooling and early postoperative kidney function preservation. Additional research is required to ascertain whether the CSCT can enhance the long-term prognosis of kidney transplant recipients.

20.
Technol Health Care ; 32(S1): 351-359, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38759060

RESUMO

BACKGROUND: A growing body of evidence has shown that activating spinal cord glial cells (typically astrocytes and microglial cells) is closely related to hyperpathia and persistent pain. OBJECTIVE: To investigate the expression of GFAP and CR3/CD11b in cornu dorsale medullae spinalis of rats with nonbacterial prostatitis, to explore the therapeutic efficacy and action mechanism of intrathecal injection of BNP alleviating chronic neuropathic pain. METHODS: Eighteen male SPF SD rats were randomly divided into sham operation control group, nonbacterial prostatitis group (NBP) and intrathecal injection BNP group, the NBP model was established by intraprostatic injection of CFA, and the spinal cord of L6-S1 segment was extracted seven days after intrathecal injection of BNP; The expression of GFAP and CR3/CD11b in dorsal horn of spinal cord were detected by immunofluorescence and Western blot. RESULTS: The cumulative optical density values of GFAP and CR3/CD11b immunofluorescence assay in the NBP group were higher than those in the sham operation group, with statistical significance (p⁢ï⁢»â¢ 0.01); The expression of GFAP and CR3/CD11b in intrathecal injection BNP group were lower than those in NBP group, the differences were statistically significant (p⁢ï⁢»â¢ 0.01). Western blot results showed that the expression of GFAP and CR3/CD11B in NBP group were higher than those in sham operation group, with statistical significance (p⁢ï⁢»â¢ 0.05). The expression of GFAP and CR3/CD11B in intrathecal injection BNP group were lower than those in NBP group, the differences were statistically significant (p⁢ï⁢»â¢ 0.05). CONCLUSION: Intrathecal injection of BNP can down-regulate the expressions of GFAP and CR3/CD11b in L6-S1 spinal cord of NBP rat model and to further inhibit chronic pain caused by NBP.


Assuntos
Proteína Glial Fibrilar Ácida , Peptídeo Natriurético Encefálico , Prostatite , Ratos Sprague-Dawley , Medula Espinal , Animais , Masculino , Ratos , Prostatite/metabolismo , Medula Espinal/metabolismo , Peptídeo Natriurético Encefálico/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Antígeno CD11b/metabolismo , Modelos Animais de Doenças , Injeções Espinhais , Neuralgia
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