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1.
J Diabetes ; 16(4): e13526, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38584148

RESUMO

BACKGROUND: Bexagliflozin and dapagliflozin are sodium-glucose cotransporter-2 (SGLT2) inhibitors. No direct comparison of SGLT2 inhibitors in a randomized controlled trial has been reported to date. METHODS: This was a multicenter, randomized, double-blind, active-controlled trial comparing bexagliflozin to dapagliflozin for the treatment of type 2 diabetes mellitus in adults with disease inadequately controlled by metformin. Subjects (n = 406) were randomized to receive bexagliflozin (20 mg) or dapagliflozin (10 mg) plus metformin. The primary endpoint was noninferiority of bexagliflozin to dapagliflozin for the change in glycated hemoglobin (HbA1c) from baseline to week 24. Secondary endpoints included intergroup differences in fasting plasma glucose (FPG), 2-h-postprandial glucose (PPG), body weight, and systolic blood pressure (SBP) from baseline to week 24. The trial also evaluated the safety profiles. RESULTS: The model-adjusted mean change from baseline to week 24 HbA1c was -1.08% for bexagliflozin and -1.10% for dapagliflozin. The intergroup difference of 0.03% (95% confidence interval [CI] -0.14% to 0.19%) was below the prespecified margin of 0.4%, confirming the noninferiority of bexagliflozin. The changes from baseline in FPG, PPG, body weight, and SBP were -1.95 mmol/L, -3.24 mmol/L, -2.52 kg, and -6.4 mm Hg in the bexagliflozin arm and -1.87 mmol/L, -3.07 mmol/L, -2.22 kg, and -6.3 mm Hg in the dapagliflozin arm. Adverse events were experienced in 62.6% and 65.0% and serious adverse events affected 4.4% and 3.5% of subjects in the bexagliflozin and dapagliflozin arm, respectively. CONCLUSIONS: Bexagliflozin showed nearly identical effects and a similar safety profile to dapagliflozin when used in Chinese patients on metformin.


Assuntos
Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Glucosídeos , Metformina , Piranos , Adulto , Humanos , Metformina/efeitos adversos , Hipoglicemiantes/efeitos adversos , Hemoglobinas Glicadas , Peso Corporal , Método Duplo-Cego , Quimioterapia Combinada , Glucose , China , Glicemia , Resultado do Tratamento
2.
Chem Commun (Camb) ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38572692

RESUMO

L/D-Phenylglycine amphiphiles and metal ions with peroxidase-like activity self-assembled into chiral nanoribbons, which act as efficient chiral supramolecular nanozymes for catalyzing the 3,4-dihydroxy-L/D-phenylalanine (L/D-DOPA) oxidation reactions. The catalytic efficiency and enantioselectivity are dominated by the chirality transfer and the synergistic effect between the metal ions and chiral nanoribbons.

3.
PeerJ ; 12: e16988, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560459

RESUMO

Background: Myeloid-derived suppressor cells (MDSCs) have crucial immunosuppressive role in T cell dysfunction in various disease processes. However, the role of MDSCs and their impact on Tregs in COPD have not been fully understood. The aim of the present study is to investigate the immunomodulatory role of MDSCs and their potential impact on the expansion and function of Tregs in COPD patients. Methods: Peripheral blood samples were collected to analyze circulating MDSCs, Tregs, PD-1/PD-L1 expression to assess the immunomodulatory role of MDSC and their potential impact on the expansion and function of Treg in COPD. A total of 54 COPD patients and 24 healthy individuals were enrolled in our study. Flow cytometric analyses were performed to identify granulocytic MDSCs (G-MDSCs), monocytic MDSCs (M-MDSCs), Tregs, and the expression of PD-1/PD-L1(L2) on MDSCs and Tregs in peripheral blood. Results: Our results revealed a significantly higher percentage of G-MDSCs and M-MDSCs (p < 0.001) in COPD patients compared to the healthy controls. Additionally, a significantly higher proportion of peripheral blood Tregs was observed in COPD patients. Furthermore, an increased expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on Tregs (p < 0.01) was detected in COPD patients. The expression of PD-1 on CD4+ Tcells and Tregs, but not CD8+Tcells, was found to be increased in patients with COPD compared to controls. Furthermore, an elevated expression of PD-L1 on M-MDSCs (p < 0.01) was also observed in COPD patients. A positive correlation was observed between the accumulation of M-MDSCs and Tregs in COPD patients. Additionally, the percentage of circulating M-MDSCs is positively associated with the level of PD-1 (r = 0.51, p < 0.0001) and CTLA-4 (r = 0.42, p = 0.0014) on Tregs in COPD. Conclusion: The recruitment of MDSCs, accumulation of Tregs, and up-regulation of CTLA-4 on Treg in COPD, accompanied by an increased level of PD-1/PD-L1, suggest PD-1/PD-L1 axis may be potentially involved in MDSCs-induced the expansion and activation of Treg at least partially in COPD.


Assuntos
Células Supressoras Mieloides , Doença Pulmonar Obstrutiva Crônica , Humanos , Antígeno B7-H1/metabolismo , Antígeno CTLA-4 , Células Supressoras Mieloides/metabolismo , Receptor de Morte Celular Programada 1 , Linfócitos T Reguladores/metabolismo
4.
Front Surg ; 11: 1279194, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601877

RESUMO

Purpose: We prospectively evaluate the short-term clinical and radiographic outcomes of the only Chinese domestically produced trabecular titanium acetabular cup(3D ACT™ cup) in primary total hip arthroplasty (THA), aiming to provide evidence-based support for its clinical application. Methods: A total of 236 patients, who underwent primary THA using 3D ACT™ cup in the Department of Joint Surgery at our hospital between January 2017 and June 2019, were included in this study. General patient data, imaging information, functional scores, and complications were collected to evaluate the early clinical efficacy. Results: All patients were followed up for 33-52 months, with an average of (42.2 ± 9.2) months. At the last follow-up, the preoperative HHS score increased significantly from 43.7 ± 6.8 to 85.6 ± 9.3 points (P < 0.01). Similarly, the preoperative WOMAC scores showed significant improvement from 59.2 ± 5.8 to 13.1 ± 3.5 points (P < 0.01). 92.3% of the patients expressed satisfaction or high satisfaction with the clinical outcome. Furthermore, 87.7% of the acetabular cups were positioned within the Lewinnek safe zone, achieving successful reconstruction of the acetabular rotation center. The cup survival rate at the last follow-up was 100%. Conclusions: The utilization of the only Chinese domestically manufactured 3D printing trabecular titanium acetabular cup in primary THA demonstrated favorable short-term clinical and radiographic outcomes. The acetabular cup exhibits excellent initial stability, high survival rate, and favorable osseointegration, leading to a significant enhancement in pain relief and functional improvement. In the future, larger sample sizes and multicenter prospective randomized controlled trials will be required to validate the long-term safety and effectiveness of this 3D ACT™ cup.

5.
Sci Adv ; 10(10): eadk3854, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38446880

RESUMO

Liquid crystal elastomers (LCEs) have garnered attention for their remarkable reversible strains under various stimuli. Early studies on LCEs mainly focused on basic dimensional changes in macrostructures or quasi-three-dimensional (3D) microstructures. However, fabricating complex 3D microstructures and cross-scale LCE-based structures has remained challenging. In this study, we report a compatible method named melt electrowriting (MEW) to fabricate LCE-based microfiber actuators and various 3D actuators on the micrometer to centimeter scales. By controlling printing parameters, these actuators were fabricated with high resolutions (4.5 to 60 µm), actuation strains (10 to 55%), and a maximum work density of 160 J/kg. In addition, through the integration of a deep learning-based model, we demonstrated the application of LCE materials in temperature field sensing. Large-scale, real-time, LCE grid-based spatial temperature field sensors have been designed, exhibiting a low response time of less than 42 ms and a high precision of 94.79%.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38462931

RESUMO

We investigated the vulnerable fish species Schizothorax argentatus Kessler, 1874, using low-coverage whole genome sequencing data. The assembled 16,587 bp mitochondrial genome has a nucleotide composition of A = 29.8%, T = 25.3%, G = 17.9%, and C = 27.0%, containing 13 protein-coding genes, two ribosomal RNA genes, and 22 transfer RNA genes with a gene arrangement identical to other cofamilial species. Phylogenetic analyses of 71 schizothoracine fishes suggest a close relationship between S. argentatus and Schizothorax eurystomus, sharing a common ancestor with Schizothorax pseudoaksaiensis. Our study supports dividing extant schizothoracine fishes into two tribes, Schizothoracini and Schizopygopsini. The estimated time to most recent common ancestor (tMRCA) and their distribution imply geological and climatic events during the Miocene around the Qinghai-Tibet Plateau as significant evolutionary drivers explaining the diversification of main clades in schizothoracine fishes.

7.
BMC Cardiovasc Disord ; 24(1): 155, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481127

RESUMO

BACKGROUND: Hyperuricemia and low level of high-density lipoprotein cholesterol (HDL-C) are both risk factors for coronary artery disease (CAD). The uric acid to HDL-C ratio (UHR) has recently been identified as a new inflammatory and metabolic biomarker. However, the relationship between the UHR and coronary culprit plaques has not been fully investigated in patients with acute coronary syndrome (ACS). METHODS: A total of 346 patients with ACS were enrolled in this study. Culprit lesion characteristics were assessed by optical coherence tomography (OCT). Logistic regression and linear correlation analyses were performed to assess the association between the UHR and culprit plaques. The predictive value of the UHR was investigated by receiver operating characteristic (ROC) curve analysis. RESULTS: The percentages of typical culprit plaques, including ruptures, erosions and thrombi, were greater in the high-UHR subgroup than those in the low-UHR subgroup. A positive relationship was also found between the UHR and diameter stenosis (r = 0.160, P = 0.003) and between the UHR and area stenosis (r = 0.145, P = 0.007). The UHR was found to be independently associated with plaque rupture, erosion and thrombus. Furthermore, ROC analysis suggested that the UHR had a better predictive value than low-density lipoprotein cholesterol. CONCLUSIONS: An elevated UHR level was independently related to the occurrence rate of culprit plaques. The UHR is a simple and easily acquired parameter for detecting culprit plaques in patients with ACS.


Assuntos
Síndrome Coronariana Aguda , Placa Aterosclerótica , Humanos , Síndrome Coronariana Aguda/diagnóstico por imagem , Ácido Úrico , HDL-Colesterol , Constrição Patológica , Angiografia Coronária/métodos , Placa Aterosclerótica/patologia , Tomografia de Coerência Óptica/métodos , Vasos Coronários/patologia
8.
ESC Heart Fail ; 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38520316

RESUMO

Left ventricular assist device (LVAD) implantation is an effective alternative treatment to heart transplantation, especially for end-stage heart failure patients who are ineligible for or unable to await a heart transplant. This report describes a complex and innovative surgery where LVAD implantation was performed alongside multiple concomitant cardiac and aortic procedures. A 62-year-old male patient with complicated comorbidities developed acute myocardial infarction and subsequent refractory advanced heart failure. Given his critically ill condition and intractable anatomical malformations, the CH-VAD left ventricular assist system implantation was performed concomitantly with the Bentall procedure, coronary artery bypass grafting, tricuspid valvuloplasty, and foramen ovale closure. The patient was successfully discharged. This case details the medical decision-making process and surgical strategy and demonstrates the feasibility of LVAD implantation combined with multiple additional cardiac and aortic procedures in expert cardiac centres. Success relies on experienced cardiac surgeons and a multidisciplinary LVAD Heart Team, ensuring excellence in surgical techniques, preoperative evaluation, post-operative care, and rehabilitation.

9.
Med Sci Monit ; 30: e942661, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38520116

RESUMO

BACKGROUND Body mass index (BMI) and endoscopists' experiences can be associated with cecal intubation time (CIT), but such associations are controversial. This study aimed to clarify the association between BMI and CIT during unsedated colonoscopy at 3 learning stages of a single endoscopist. MATERIAL AND METHODS A total of 1500 consecutive patients undergoing unsedated colonoscopy by 1 endoscopist at our department from December 11, 2020, to August 21, 2022, were reviewed. They were divided into 3 learning stages according to the number of colonoscopies performed by 1 endoscopist, including intermediate (501-1000 colonoscopies), experienced (1001-1500 colonoscopies), and senior stages (1501-2000 colonoscopies). Variables that significantly correlated with CIT were identified by Spearman rank correlation analyses and then included in multiple linear regression analysis. RESULTS Overall, 1233 patients were included. Among them, 392, 420, and 421 patients were divided into intermediate, experienced, and senior stages, respectively. Median CIT was 7.83, 6.38, and 5.58 min at intermediate, experienced, and senior stages, respectively (P.


Assuntos
Ceco , Colonoscopia , Humanos , Colonoscopia/métodos , Índice de Massa Corporal , Modelos Lineares , Competência Clínica
10.
J Colloid Interface Sci ; 665: 1-9, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38513403

RESUMO

The cancer therapeutic efficacy of the peroxidase (POD)-mimicking nanozyme-based monotherapy is significantly hindered due to insufficient intratumoral hydrogen peroxide (H2O2) and glutathione (GSH) consumption effect on reactive oxygen species (ROS). In this study, we present the development of poly(o-phenylenediamine)@gold nanoparticles (AuNPs) (PoPD@Au) nanocomposites for multifunctional catalytic-photothermal therapy. These nanocomposites exhibit triple distinct nanozymatic activities, i.e., POD-like activity that catalyzes H2O2 to ROS, glucose oxidase (GOx)-like activity that supplements endogenous H2O2, and GSH depleting activity that decreases the ROS consumption efficiency. This open source and reduce expenditure strategy for ROS generation allows for the amplification of tumor oxidative stress, thereby enhancing anti-tumor efficiency. Additionally, the PoPD@Au nanocomposites demonstrate outstanding photothermal conversion efficiency, contributing to the synergistic effect between PoPD and AuNPs. Moreover, we reveal the improved photothermal performance of PoPD@Au triggered by the tumor microenvironment pH, which provides additional benefits for targeted catalytic-photothermal therapy. This "four-in-one" design of PoPD@Au enables efficient anti-tumor effects both in vitro and in vivo, making it a universal strategy for engineering catalytic-photothermal therapeutic nanoagents.

11.
Materials (Basel) ; 17(6)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38541470

RESUMO

The microstructure, corrosion resistance, and phase-transition process of micro-arc oxidation (MAO) coatings prepared on LaFe11.6Si1.4 alloy surfaces in different electrolyte systems were systematically investigated. Research has demonstrated that various electrolyte systems do not alter the main components of the coatings. However, the synergistic action of Na2CO3 and Na2B4O7 more effectively modulated the ionization and chemical reactions of the MAO process and accelerated the formation of α-Al2O3. Moreover, the addition of Na2CO3 and Na2B4O7 improved the micromorphology of the coating, resulting in a uniform coating thickness and good bonding with the LaFe11.6Si1.4 substrate. The dynamic potential polarization analysis was performed in a three-electrode system consisting of a LaFe11.6Si1.4 working electrode, a saturated calomel reference electrode, and a platinum auxiliary electrode. The results showed that the self-corrosion potential of the LaFe11.6Si1.4 alloy without surface treatment was -0.68 V, with a current density of 8.96 × 10-6 A/cm2. In contrast, the presence of a micro-arc electrolytic oxidation coating significantly improved the corrosion resistance of the LaFe11.6Si1.4 substrate, where the minimum corrosion current density was 1.32 × 10-7 A/cm2 and the corrosion potential was -0.50 V. Similarly, after optimizing the MAO electrolyte with Na2CO3 and Na2B4O7, the corrosion resistance of the material further improved. Simultaneously, the effect of the coatings on the order of the phase transition, latent heat, and temperature is negligible. Therefore, micro-arc oxidation technology based on the in situ growth coating of the material surface effectively improves the working life and stability of La(Fe, Si)13 materials in the refrigeration cycle, which is an excellent alternative as a protection technology to promote the practical process of magnetic refrigeration technology.

12.
Small ; : e2309654, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38530064

RESUMO

Aligned carbon nanotube (A-CNT) with high semiconducting purity and high-density have been considered as one of the most promising active channels for field-effect transistors (FETs), but conjugated polymer dispersant residues on the surface of A-CNT have become the main obstacle for its further development in electronics applications. In this work, a series of removable conjugated polymers (CPs) are designed and synthesized to achieve favorable purification and alignment for CNT arrays with a high density of ≈360 CNTs/µm. Furthermore, a removal process of CPs on the CNT array film is developed. Raman spectra show that the CNTs in array film are almost not damaged after the removal process, and the G/D ratio is as high as 35. The field-effect transistors (FETs) are fabricated with a saturation current density up to 600 µA µm-1 and a current on-off ratio of ≈105, even with a relatively long channel length of ≈3 µm.

13.
Theriogenology ; 221: 9-17, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38521007

RESUMO

Semen cryopreservation represents a promising technology utilized for preserving high-quality chicken varieties in husbandry practices. However, the efficacy of this methodology is significantly impeded by the diminished quality of sperm. Metabolites, as the end products of metabolic reactions, serve as indicators of biological processes and offer insights into physiological conditions. In this study, we investigaged the sperm quality and alteration in metabolic profiles during the cryopreservation of Longyou Partridge Chicken semen. Following artificial semen collection, four groups of semen samples were established based on four points of the cryopreservation process (Ⅰ, fresh semen; Ⅱ, semen added extender and chilled at 4 °C for 30 min; Ⅲ, semen added cryoprotectants; Ⅳ, semen gradient freezed and stored in liquid nitrogen). Semen cryopreservation has a negative effect on the percentage of sperm in a straight-line trajectory (LIN), has no significant effect on total motile sperms (TM) or the proportion of sperm with typical morphology (NM). Metabolites were identified using LC-MS technique and analyses including Principal Component Analysis (PCA), Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), Univariate statistical analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were employed to identify metabolites. A total of 2471 metabolites had been identified, with the majority of the list being made up of amino acids and their metabolites as well as benzene and substituted derivatives. Group II exhibits 882 metabolites with significantly elevated abundance relative to Group I, alongside 37 metabolites displaying decreased abundance. In Group III, 836 metabolites demonstrate notably augmented abundance compared to Group II, while 87 metabolites exhibit reduced abundance. Furthermore, Group IV showcases 513 metabolites with markedly heightened abundance in comparison to Group III, and 396 metabolites with decreased abundance. Specific metabolites such as 5-Hydroxylysine, Phosphocholine, and alpha-d-glucose-6-phosphate exhibited a progressive decline during the cryopreservation process, correlating with either dilution and chilling, cryoprotectant addition, or freezing. In conclusion, our investigation systematically examined the changes of seminal metabolome and sperm quality throughout the cryopreservation process of rooster semen.


Assuntos
Preservação do Sêmen , Sêmen , Masculino , Animais , Sêmen/fisiologia , Galinhas/fisiologia , Motilidade dos Espermatozoides , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos , Criopreservação/veterinária , Criopreservação/métodos , Espermatozoides/fisiologia , Análise do Sêmen/veterinária , Crioprotetores/farmacologia , Crioprotetores/metabolismo
14.
Angew Chem Int Ed Engl ; : e202400177, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488857

RESUMO

Mn(I)-catalyzed enantioselective C-C bond-forming reactions represent a great challenge in homogeneous catalysis primarily due to a limited understanding of its mechanistic principles. Herein, we have developed an interesting catalytic strategy that leverages a synergistic combination of a dimeric manganese(I) catalyst and a chiral aminocatalyst to address this issue. A range of conjugated dienals and trienals can exclusively proceed 1,4-hydroalkenylation by using readily available aromatic and aliphatic alkenyl boronic acids as coupling partners, producing a rich library of skipped diene aldehydes in synthetically useful yields and high levels of enantioselectivities. Notably, downstream transformations of these products can not only afford a concise approach to construct enantioenriched skipped trienes but also realize enantioselective total synthesis of analogues to (-)-Blepharocalyxin D in four steps. DFT calculations suggest the 1,4-hydroalkenylation is kinetically more favorable than 1,6-hydroalkenylation.

15.
J Environ Manage ; 356: 120684, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38531133

RESUMO

Microbial biotransformation is a recommended and reliable method in face of formidable tetracycline (TC) with broad-spectrum antibacterial activity. Herein, comprehensive characteristics of a newfound strain and its molecular mechanism in process of TC bioremediation were involved in this study. Specifically, Serratia marcescens MSM2304 isolated from pig manure sludge grew well in presence of TC and achieved optimal removal efficiency of 61% under conditions of initial TC concentration of 10 mg/L, pH of 7.0, cell inoculation amount of 5%, and tryptone of 10 g/L as additional carbon. The pathways of biotransformation include EPS biosorption, cell surface biosorption and biodegradation, which enzymatic processes of biodegradation were occurred through TC adsorbed by biofilms was firstly broken down by extracellular enzymes and part of TC migrated towards biofilm interior and degraded by intracellular enzymes. Wherein extracellular polysaccharides in extracellular polymeric substances (EPS) from biofilm of strain MSM2304 mainly performed extracellular adsorption, and changes in position and intensity of CO, =CH and C-O-C/C-O of EPS possible further implied TC adsorption by it. Biodegradation accounting for 79.07% played a key role in TC biotransformation and could be fitted well by first-order model that manifesting rapid and thorough removal. Potential biodegradation pathway including demethylation, dihydroxylation, oxygenation, and ring opening possibly involved in TC disposal process of MSM2304, TC-degrading metabolites exhibited lower toxicity to indicator bacteria relative to parent TC. Whole genome sequencing as underlying molecular evidence revealed that TC resistance genes, dehydrogenases-encoding genes, monooxygenase-encoding genes, and methyltransferase-encoding genes of strain MSM2304 were positively related to TC biodegradation. Collectively, these results favored a theoretical evaluation for Serratia marcescens MSM2304 as a promising TC-control agent in environmental bioremediation processes.


Assuntos
Serratia marcescens , Tetraciclina , Animais , Suínos , Serratia marcescens/genética , Antibacterianos/análise , Biotransformação , Genômica
16.
Proc Natl Acad Sci U S A ; 121(13): e2320386121, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38513101

RESUMO

Stimuli-responsive soft robots offer new capabilities for the fields of medical and rehabilitation robotics, artificial intelligence, and soft electronics. Precisely programming the shape morphing and decoupling the multiresponsiveness of such robots is crucial to enable them with ample degrees of freedom and multifunctionality, while ensuring high fabrication accuracy. However, current designs featuring coupled multiresponsiveness or intricate assembly processes face limitations in executing complex transformations and suffer from a lack of precision. Therefore, we propose a one-stepped strategy to program multistep shape-morphing soft millirobots (MSSMs) in response to decoupled environmental stimuli. Our approach involves employing a multilayered elastomer and laser scanning technology to selectively process the structure of MSSMs, achieving a minimum machining precision of 30 µm. The resulting MSSMs are capable of imitating the shape morphing of plants and hand gestures and resemble kirigami, pop-up, and bistable structures. The decoupled multistimuli responsiveness of the MSSMs allows them to conduct shape morphing during locomotion, perform logic circuit control, and remotely repair circuits in response to humidity, temperature, and magnetic field. This strategy presents a paradigm for the effective design and fabrication of untethered soft miniature robots with physical intelligence, advancing the decoupled multiresponsive materials through modular tailoring of robotic body structures and properties to suit specific applications.

17.
Artigo em Inglês | MEDLINE | ID: mdl-38504574

RESUMO

BACKGROUND AND PURPOSE: Emodin, a compound derived from rhubarb and various traditional Chinese medicines, exhibits a range of pharmacological actions, including antiinflammatory, antiviral, and anticancer properties. Nevertheless, its pharmacological impact on bladder cancer (BLCA) and the underlying mechanism are still unclear. This research aimed to analyze the pharmacological mechanisms of Emodin against BLCA using network pharmacology analysis and experimental verification. METHODS: Initially, network pharmacology was employed to identify core targets and associated pathways affected by Emodin in bladder cancer. Subsequently, the expression of key targets in normal bladder tissues and BLCA tissues was assessed by searching the GEPIA and HPA databases. The binding energy between Emodin and key targets was predicted using molecular docking. Furthermore, in vitro experiments were carried out to confirm the predictions made with network pharmacology. RESULTS: Our analysis identified 148 common genes targeted by Emodin and BLCA, with the top ten target genes including TP53, HSP90AA1, EGFR, MYC, CASP3, CDK1, PTPN11, EGF, ESR1, and TNF. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated a significant correlation between Emodin and the PI3KAKT pathway in the context of BLCA. Molecular docking investigations revealed a strong affinity between Emodin and critical target proteins. In vitro experiments demonstrated that Emodin inhibits T24 proliferation, migration, and invasion while inducing cell apoptosis. The findings also indicated that Emodin reduces both PI3K and AKT protein and mRNA expression, suggesting that Emodin may mitigate BLCA by modulating the PI3K-AKT signaling pathway. CONCLUSION: This study integrates network pharmacology with in vitro experimentation to elucidate the potential mechanisms underlying the action of Emodin against BLCA. The results of this research enhance our understanding of the pharmacological mechanisms by which Emodin may be employed in treating BLCA.

18.
J Orthop Translat ; 45: 168-177, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38549808

RESUMO

Background: Recently, the osteogenic potential of Adiponectin-labeled adipogenic lineage progenitors (Adipoq-lineage progenitors) in bone marrow has been observed to support bone maintenance and repair. However, little is known about the function of Schnurri-3 (SHN3, also known as HIVEP3) in other mesenchymal lineage cells, apart from its negative regulation of bone formation on osteoblasts. Method: In this study, we used single-cell RNA sequencing (scRNA-seq) profiling to demonstrate that Adipoq-lineage progenitors express higher levels of Shn3 compared to other mesenchymal cell populations in mice and humans. To investigate the role of SHN3 in Adipoq-lineage progenitors, we generated a murine model specifically harboring a Shn3-deficient allele in Adipoq-expressing cells. Information of mice body weight was collected weekly to generate body weight curve. Bone phenotype was analyzed using micro-CT and histomorphometric studies. To eliminate the role of peripheral adipose tissue on bone, we collected adipose wet weight, performed intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and conducted a fat-transplantation study. Osteoblast and osteoclast functions were assessed through toluidine blue staining and TRAP staining, respectively. We further investigated the effect of Shn3 depletion on the differentiation of Adipoq-lineage progenitors through immunostaining and in vitro differentiation assays. Finally, we evaluated whether Shn3 deficiency in Adipoq-lineage progenitors affects the fracture healing process by generating bi-cortical femoral fracture models. Results: Depletion of Shn3 in Adipoq-lineage progenitors resulted in a significant increase in trabecular bone mass and bone formation in vivo, without disrupting whole-body energy metabolism and skeletal development. Consistent with these findings, both cell-lineage tracing and functional assays revealed that Shn3 ablation effectively shifted the cell fate of Adipoq-lineage progenitors towards an osteogenic phenotype in the bone marrow. Furthermore, in vivo studies demonstrated that the lack of Shn3 in Adipoq-lineage progenitors also enhanced bone fracture healing under pathological conditions. Conclusion: Overall, our findings provide a novel strategy for targeting the osteoanabolic potential of bone marrow Adipoq-lineage progenitors as a potential treatment for bone loss-related disorders. Translational potential of this article: We have identified a novel gene target that directs the cell fate of a previously identified non-osteogenic cell population under physiological conditions. This study not only expands the therapeutic value of Shn3 ablation in treating osteoporotic or traumatic bone diseases but also provides new insights into the contribution of bone marrow Adipoq-lineage progenitors to osteogenesis. Thus, this article further supports Shn3 silencing as a valuable approach to treat osteopenia and accelerate fracture healing (see graphical abstract).

19.
Heliyon ; 10(5): e26651, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38434312

RESUMO

Background: The correlation between acute ischemic stroke (AIS) and gut microbiota has opened a promising avenue for improving stroke prognosis through the utilization of specific gut bacterial species. This study aimed to identify gut bacterial species in AIS patients and their correlation with stroke severity, 3-month prognosis, and inflammatory markers. Methods: We enrolled 59 AIS patients (from June 2021 to July 2022) and 31 age-matched controls with similar cerebrovascular risk profiles but no stroke history. Fecal samples were analyzed using 16 S rDNA V3-V4 sequencing to assess α and ß diversity and identify significant microbiota differences. AIS cases were categorized based on the National Institute of Health Stroke Scale (NIHSS) scores and 3-month modified Rankin Scale (mRS) scores. Subgroup analyses were performed, and correlation analysis was used to examine associations between flora abundance, inflammatory markers and stroke outcome. Results: Significant differences in ß-diversity were observed between case and control groups (P < 0.01). Bacteroides dominated AIS samples, while Clostridia, Lachnospirales, Lachnospiraceae, Ruminococcaceae, Faecalibacterium, and Faecalibacterium prausnitzii were prominent in controls. Faecalibacterium and Faecalibacterium prausnitzii were significantly reduced in non-minor stroke and 3-month poor prognosis groups compared to controls, while this difference was less pronounced in patients with minor stroke and 3-month good prognosis. Both Faecalibacterium and Faecalibacterium prausnitzii were negatively correlated with the NIHSS score on admission (r = -0.48, -0.48, P < 0.01) and 3-month mRS score (r = -0.48, -0.44, P < 0.01). Additionally, they showed negative correlations with pro-inflammatory factors and positive correlations with anti-inflammatory factors (both P < 0.01). Conclusions: Faecalibacterium prausnitzii is negatively associated with stroke severity, impaired prognosis, and pro-inflammatory markers, highlighting its potential application in AIS treatments.

20.
BMC Pharmacol Toxicol ; 25(1): 24, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443996

RESUMO

BACKGROUND: This study aimed to evaluate the long-term risk of CKD and renal function declines using a combination of diuretics and SGLT2i. METHODS: We selected the data of subjects who had at least two outpatient records or at least one inpatient record for DM treatment as the DM group from the National Health Insurance Research Database (NHIRD). Patients receiving versus not receiving SGLT2i were defined as the SGLT2i and non-SGLT2i cohorts, respectively. The patients in the two groups were matched 1:1 through propensity score matching based on age, sex, year of index date, and comorbidities. RESULTS: The diuretics-only group had a higher risk of CKD (aHR, 2.46; 95% CI, 1.68-3.61) compared to the neither SGLT2i nor diuretics group, while the both SGLT2i and diuretics group and the SGLT2i only group had lower risks (aHR, 0.45, 95% CI, 0.32-0.63; aHR, 0.26, 95% CI, 0.17-0.40) than the diuretics-only group. The SGLT2i-only group had a lower risk (aHR, 0.58, 95% CI, 0.36-0.94) than the both SGLT2i and diuretics group. CONCLUSION: This study indicates that diuretics could raise the risk of CKD in diabetic patients, but when used in combination with SGLT2i, they continue to offer protection against CKD.


Assuntos
Pacientes Internados , Insuficiência Renal Crônica , Humanos , Taiwan/epidemiologia , Estudos Retrospectivos , Diuréticos/efeitos adversos , Insuficiência Renal Crônica/epidemiologia
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