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1.
Heliyon ; 10(6): e27346, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38515731

RESUMO

Candida albicans (C. albicans) is one of the most common clinical isolates of systemic fungal infection. Long-term and inappropriate use of antifungal drugs can cause fungal resistance, which poses a great challenge to the clinical treatment of fungal infections. The combination of antifungal drugs and non-antifungal drugs to overcome the problem of fungal resistance has become a research hotspot in recent years. Our previous study found that the combination of rifapentine (RFT) and fluconazole (FLC) has a significant synergistic against FLC-resistant C. albicans. The present study aimed to further verify the synergistic effect between FLC and RFT against the FLC-resistant C. albicans 100, and explore the underlying mechanism. The growth curve and spot assay test not only showed the synergistic effect of FLC and RFT on FLC-resistant C. albicans in vitro but exhibited a dose-dependent effect on RFT, indicating that RFT may play a principal role in the synergic effect of the two drugs. Flow cytometry showed that the combined use of RFT and FLC arrested cells in the G2/M phase, inhibiting the normal division and proliferation of FLC-resistant C. albicans. Transmission electron microscopy (TEM) demonstrated that FLC at a low concentration could still cause a certain degree of damage to the cell membrane in the FLC-resistant C. albicans, as represented by irregular morphologic changes and some defects observed in the cell membrane. When FLC was used in combination with RFT, the nuclear membrane was dissolved and the nucleus was condensed into a mass. Detection of the intracellular drug concentration of fungi revealed that the intracellular concentration of RFT was 31-195 fold that of RFT alone when it was concomitantly used with FLC. This indicated that FLC could significantly increase the concentration of RFT in cells, which may be due to the damage caused to the fungal cell membrane by FLC. In short, the present study revealed a synergistic mechanism in the combined use of RFT and FLC, which may provide a novel strategy for the clinical treatment of FLC-resistant C. albicans.

2.
Curr Issues Mol Biol ; 46(3): 1700-1712, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38534726

RESUMO

Vitamin K2 (MK-7) has been shown to cause significant changes in different physiological processes and diseases, but its role in acute lung injury (ALI) is unclear. Therefore, in this study, we aimed to evaluate the protective effects of VK2 against LPS-induced ALI in mice. The male C57BL/6J mice were randomly divided into six groups (n = 7): the control group, LPS group, negative control group (LPS + Oil), positive control group (LPS + DEX), LPS + VK2 (L) group (VK2, 1.5 mg/kg), and LPS + VK2 (H) group (VK2, 15 mg/kg). Hematoxylin-eosin (HE) staining of lung tissue was performed. Antioxidant superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities, and the Ca2+ level in the lung tissue were measured. The effects of VK2 on inflammation, apoptosis, tight junction (TJ) injury, mitochondrial dysfunction, and autophagy were quantitatively assessed using Western blot analysis. Compared with the LPS group, VK2 improved histopathological changes; alleviated inflammation, apoptosis, and TJ injury; increased antioxidant enzyme activity; reduced Ca2+ overload; regulated mitochondrial function; and inhibited lung autophagy. These results indicate that VK2 could improve tight junction protein loss, inflammation, and cell apoptosis in LPS-induced ALI by inhibiting the mitochondrial dysfunction and excessive autophagy, indicating that VK2 plays a beneficial role in ALI and might be a potential therapeutic strategy.

3.
ACS Nano ; 18(13): 9500-9510, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38477715

RESUMO

Morphing textiles, crafted using electrochemical artificial muscle yarns, boast features such as adaptive structural flexibility, programmable control, low operating voltage, and minimal thermal effect. However, the progression of these textiles is still impeded by the challenges in the continuous production of these yarn muscles and the necessity for proper structure designs that bypass operation in extensive electrolyte environments. Herein, a meters-long sheath-core structured carbon nanotube (CNT)/nylon composite yarn muscle is continuously prepared. The nylon core not only reduces the consumption of CNTs but also amplifies the surface area for interaction between the CNT yarn and the electrolyte, leading to an enhanced effective actuation volume. When driven electrochemically, the CNT@nylon yarn muscle demonstrates a maximum contractile stroke of 26.4%, a maximum contractile rate of 15.8% s-1, and a maximum power density of 0.37 W g-1, surpassing pure CNT yarn muscles by 1.59, 1.82, and 5.5 times, respectively. By knitting the electrochemical CNT@nylon artificial muscle yarns into a soft fabric that serves as both a soft scaffold and an electrolyte container, we achieved a morphing textile is achieved. This textile can perform programmable multiple motion modes in air such as contraction and sectional bending.

5.
Fitoterapia ; 173: 105771, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38070780

RESUMO

To establish a quality evaluation method for Patrinia scabiosaefolia Fisch (PS), as well as to study the anti-inflammatory and hepatoprotective effects of the aqueous extract of Patrinia scabiosaefolia Fisch (APS). We used ultra performance liquid chromatography (UPLC) to establish fingerprint and content determination method for PS. The alcoholic liver injury model was prepared by feeding Lieber-DeCarli alcohol liquid feed to mice. We determined the levels of ALT, AST, TC, TG in serum, as well as GSH, MDA in the liver. The mRNA relative expression levels of TNF-α, IL-6, IL-1ß, INOS and COX-2 were detected by qRT-PCR, and liver tissues were taken for pathological examination. The fingerprints of 16 batches of PS were established, and 3 component peaks were identified, which were chlorogenic acid (CA), isochlorogenic acid A (ICAA) and isochlorogenic acid C (ICAC). The similarity of the 6 common peaks was between 0.924 and 1.000. A mice model of alcoholic liver injury was successfully made by mixing alcohol liquid feed. The levels of ALT, AST, TC and TG in serum and MDA, TNF-α, IL-1ß, LL-6, COX-2 and INOS mRNA in liver were effectively reduced in the drug administration group. The levels of GSH in mouse liver tissue were increased in the drug administration group. The method has good repeatability, stability and feasibility, and it meets the requirements for Quality evaluation. APS exhibits a protective effect against alcoholic liver injury (ALI) in mice.


Assuntos
Patrinia , Camundongos , Animais , Patrinia/química , Fator de Necrose Tumoral alfa , Cromatografia Líquida de Alta Pressão , Ciclo-Oxigenase 2 , Estrutura Molecular , Fígado , Etanol/farmacologia , RNA Mensageiro/farmacologia
6.
Hematology ; 28(1): 2288475, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38038045

RESUMO

This study delves into the emerging role of ferroptosis in Myelodysplastic Neoplasms (MDS) and aims to identify a prognostic ferroptosis-related gene signature for MDS. Utilizing RNA-seq data and clinical information from the Gene Expression Omnibus database, the researchers extracted ferroptosis-related genes from the FerrDb website and conducted differential expression analysis using the 'limma' package in R. Hub ferroptosis-related genes in MDS were screened using the "RandomForest" and "carat" R packages. Kaplan -Meier and Cox regression analyses were employed to assess the prognostic role of three identified hub genes (BNIP3, MDM2, and RRM2). Receiver operator characteristic curve analysis confirmed the diagnostic efficacy of these genes. The study delved further into immune infiltration correlations, ncRNA-transcription factor coregulatory network analysis, and the identification of potential therapeutic drugs targeting hub ferroptosis-related genes in MDS. The researchers constructed a 3-gene signature-based risk score using datasets GSE58831 and GSE19429, demonstrating high accuracy (AUC > 0.75) in both datasets for survival prediction in MDS. A nomogram analysis reinforced the prognostic value of the risk-scoring model. Immunological analysis revealed an association between the risk score and immune infiltration. Quantitative reverse transcription polymerase chain reaction (qPCR) data indicated significant expression differences in MDM2, RRM2, and BNIP3 between MDS and healthy bone marrow samples. Notably, MDM2 and RRM2 showed decreased expression, while BNIP3 exhibited increased expression in MDS samples. This comprehensive study concludes that BNIP3, MDM2, and RRM2 hold diagnostic and prognostic significance in MDS and provide valuable insights into immune cell landscapes and potential therapeutic avenues for this condition.


Assuntos
Ferroptose , Síndromes Mielodisplásicas , Neoplasias , Humanos , Prognóstico , Ferroptose/genética , Nomogramas , Bases de Dados Factuais , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética
7.
Food Funct ; 14(24): 10770-10783, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37975193

RESUMO

Green tea is one of the main types of tea in China, and it has been widely consumed in the world. This study aims to investigate the potential mechanism by which the water extract of green tea (GTWE) may be effective in the treatment of alcohol-related hepatitis (ARH), utilizing a combination of network pharmacology, molecular docking, and experimental validation. Through network pharmacology analysis, seven active components and 45 potential targets were identified, with TLR4 being confirmed as the central target. Experimental findings demonstrate that GTWE exhibits significant efficacy in mitigating alcohol-induced liver inflammation and steatosis. Furthermore, the administration of GTWE has demonstrated significant efficacy in mitigating alcohol-induced intestinal inflammation and microbiota disturbance while concurrently restoring intestinal barrier function. Consequently, GTWE exhibits considerable potential as a pharmacological intervention and warrants further research and development as a lead compound for the treatment of ARH. Moreover, the prospective utilization of green tea in prolonged intakes exhibits potential as a prophylactic nutritive regimen against ARH.


Assuntos
Microbioma Gastrointestinal , Hepatite , Camundongos , Animais , Chá , Simulação de Acoplamento Molecular , Estudos Prospectivos , Extratos Vegetais/farmacologia , Inflamação
8.
PLoS One ; 18(11): e0294763, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38011192

RESUMO

Acute lung injury (ALI) is a life-threatening disease that has received considerable critical attention in the field of intensive care. This study aimed to explore the role and mechanism of vitamin K2 (VK2) in ALI. Intraperitoneal injection of 7 mg/kg LPS was used to induce ALI in mice, and VK2 injection was intragastrically administered with the dose of 0.2 and 15 mg/kg. We found that VK2 improved the pulmonary pathology, reduced myeloperoxidase (MPO) activity and levels of TNF-α and IL-6, and boosted the level of IL-10 of mice with ALI. Moreover, VK2 played a significant part in apoptosis by downregulating and upregulating Caspase-3 and Bcl-2 expressions, respectively. As for further mechanism exploration, we found that VK2 inhibited P38 MAPK signaling. Our results also showed that VK2 inhibited ferroptosis, which manifested by reducing malondialdehyde (MDA) and iron levels, increasing glutathione (GSH) level, and upregulated and downregulated glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HO-1) expressions, respectively. In addition, VK2 also inhibited elastin degradation by reducing levels of uncarboxylated matrix Gla protein (uc-MGP) and desmosine (DES). Overall, VK2 robustly alleviated ALI by inhibiting LPS-induced inflammation, apoptosis, ferroptosis, and elastin degradation, making it a potential novel therapeutic candidate for ALI.


Assuntos
Lesão Pulmonar Aguda , Ferroptose , Camundongos , Animais , Lipopolissacarídeos/efeitos adversos , Vitamina K 2/efeitos adversos , Elastina , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Apoptose , Pulmão/patologia
9.
Int Immunopharmacol ; 124(Pt A): 110890, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37688914

RESUMO

While The World Health Organization (WHO) has announced that COVID-19 is no longer a public health emergency of international concern(PHEIC), the risk of reinfection and new emerging variants still makes it crucial to study and work towards the prevention of COVID-19. Stem cell and stem cell-like derivatives have shown some promising results in clinical trials and preclinical studies as an alternative treatment option for the pulmonary illnesses caused by the COVID-19 and can be used as a potential vaccine. In this review, we will systematically summarize the pathophysiological process and potential mechanisms underlying stem cell-based therapy in COVID-19, and the registered COVID-19 clinical trials, and engineered extracellular vesicle as a potential vaccine for preventing COVID-19.

10.
ACS Nano ; 17(13): 12809-12819, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37338135

RESUMO

Similar to natural muscle fibers, coiled artificial muscle fibers provide a straightforward contraction. However, unlike natural muscle fibers, their recovery from the contracted state to the initial state requires high stress, resulting in almost zero work during a full actuation cycle. Herein, a self-recoverable coiled artificial muscle fiber was prepared by conformally coating an elastic carbon nanotube (CNT) fiber with a very thin liquid crystal elastomer (LCE) sheath. The as-obtained muscle fiber demonstrated excellent actuation properties comprising 56.9% contractile stroke, 1522%/s contraction rate, 7.03 kW kg-1 power density, and 32,000 stable cycles. The LCE chains were helically aligned in a nematic phase, and the phase change of the LCE caused by Joule heating drove the actuation process. Moreover, the LCE/CNT fiber had a well-separated, torsionally stable, and elastic coiled structure, which permitted large contractile strokes and acted as an elastic template for external-stress-free recovery. Thus, the use of self-recoverable muscle fibers to mimic the natural muscles for object dragging, multidirectional bending, and quick striking was demonstrated.


Assuntos
Cristais Líquidos , Nanotubos de Carbono , Fibras Musculares Esqueléticas , Elastômeros/química , Fibra de Carbono , Nanotubos de Carbono/química , Cristais Líquidos/química
11.
Mol Med ; 29(1): 59, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37098464

RESUMO

BACKGROUND: Myofibroblasts (MFB), one of the major effectors of pathologic fibrosis, mainly derived from the activation of fibroblast to myofibroblast transition (FMT). Although MFBs were historically considered terminally differentiated cells, their potential for de-differentiation was recently recognized and implied with therapeutic value in treating fibrotic diseases, for instance, idiopathic pulmonary fibrosis (IPF) and post allogeneic hematopoietic stem cell transplantation bronchiolitis obliterans (BO). During the past decade, several methods were reported to block or reverse MFB differentiation, among which mesenchymal stem cells (MSC) have demonstrated potential but undetermined therapeutic values. However, the MSC-mediated regulation of FMT and underlying mechanisms remained largely undefined. METHOD: By identifying TGF-ß1 hypertension as the pivotal landmark during the pro-fibrotic FMT, TGF-ß1-induced MFB and MSC co-culture models were established and utilized to investigate regulations by MSC on FMT in vitro. Methods including RNA sequencing (RNA-seq), Western blot, qPCR and flow cytometry were used. RESULT: Our data revealed that TGF-ß1 readily induced invasive signatures identified in fibrotic tissues and initiated MFB differentiation in normal FB. MSC reversibly de-differentiated MFB into a group of FB-like cells by selectively inhibiting the TGF-ß-SMAD2/3 signaling. Importantly, these proliferation-boosted FB-like cells remained sensitive to TGF-ß1 and could be re-induced into MFB. CONCLUSION: Our findings highlighted the reversibility of MSC-mediated de-differentiation of MFB through TGF-ß-SMAD2/3 signaling, which may explain MSC's inconsistent clinical efficacies in treating BO and other fibrotic diseases. These de-differentiated FB-like cells are still sensitive to TGF-ß1 and may further deteriorate MFB phenotypes unless the pro-fibrotic microenvironment is corrected.


Assuntos
Células-Tronco Mesenquimais , Miofibroblastos , Humanos , Diferenciação Celular , Fibroblastos/metabolismo , Fibrose , Células-Tronco Mesenquimais/metabolismo , Miofibroblastos/metabolismo , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Proteína Smad3/metabolismo
12.
Ther Hypothermia Temp Manag ; 13(3): 120-125, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36951663

RESUMO

This study compared the pregnancy and neonatal outcomes between fresh embryo transfer and frozen-thawed embryo transfer (FET). These patients were split into two groups: the fresh embryo transfer group and the FET group. The general conditions, pregnancy outcomes, and neonatal outcomes between these groups were compared. The influencing factors of fetal macrosomia occurrence were explored as well. Compared with the fresh embryo transfer group, the FET group had a significantly higher mean age (32.59 ± 4.77 vs. 31.90 ± 4.71, p < 0.05) and lower multiple pregnancy rate (21.2% vs. 26.9%, p < 0.05). There was no significant difference in the incidence of congenital anomalies of neonates between the two groups (1.32% vs. 0.37%, p > 0.05). In the FET group, compared with the fresh embryo transfer group, the mean birth weight of singleton live births, the cesarean section rate, and the incidence of fetal macrosomia were significantly increased, while the incidence of low birth weight was significantly decreased. The logistic analysis showed that the occurrence of fetal macrosomia was primarily associated with the embryo transfer protocol (odds ratio [OR] = 2.769, 95% confidence interval [CI]: 1.246-6.154, p < 0.05), endometrial thickness (OR = 1.144, 95% CI: 1.043-1.256, p < 0.05), and gestational age (OR = 1.710, 95% CI: 1.338-2.184, p < 0.05). Macrosomia (OR = 2.938, 95% CI: 1.436-6.010, p = 0.003) and multiple pregnancy (OR = 3.574, 95% CI: 2.616-4.882, p < 0.001) significantly increased the cesarean section rate. The risk of fetal macrosomia and congenital anomalies in the offspring of the fresh embryo transfer group was lower than that in the offspring of the FET group, we preferred to fresh embryo transfer for patients with assisted reproductive technologies. FET should be used as supplementary therapeutic strategy with strengthened pregnancy management and screening to reduce the occurrence of birth defects in newborns.


Assuntos
Macrossomia Fetal , Hipotermia Induzida , Humanos , Recém-Nascido , Gravidez , Feminino , Macrossomia Fetal/epidemiologia , Macrossomia Fetal/etiologia , Fertilização In Vitro/efeitos adversos , Cesárea/efeitos adversos , Criopreservação/métodos , Estudos Retrospectivos , Hipotermia Induzida/efeitos adversos , Transferência Embrionária/efeitos adversos , Transferência Embrionária/métodos
13.
J Hazard Mater ; 451: 131141, 2023 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-36921413

RESUMO

At present, the most available pyrethroid (PYR) detection methods still suffer from a narrow detection spectrum, low sensitivity, and less portability. Herein, a novel magnetic relaxation switching (MRS) sensor was elaboratively designed to detect multiple PYRs, combining a novel broad-spectrum antibody CL-CN/1D2 and synthesized immune gold-functionalized magnetic nanoparticles, with the inherent response of the sensor. A series of antibodies and the immune gold-functionalized magnetic nanoparticles were designed and synthesized. The broad-spectrum antibody CL-CN/1D2 and high-performance gold-functionalized magnetic nanoprobe were further selected. The target analytes were effectively captured by the gold-functionalized magnetic nanoparticles in 20% (v/v) ethanol, resulting in the number increase of the signaling probes in the supernatant after magnetic separation. This sensor can detect multiple PYRs with a detection limit of 2.72 µg/L for cypermethrin, 3.58 µg/L for ß-cypermethrin, 4.07 µg/L for cyfluthrin, 3.66 µg/L for λ-cyhalothrin, 4.42 µg/L for ß-cyhalothrin, 3.51 µg/L for fenpropathrin, 4.41 µg/L for fenvalerate, and 4.12 µg/L for deltamethrin in lake water and milk within 35 min. This study not only achieves broad-spectrum PYRs detection at a trace amount but also provides an effective and universal strategy for enhancing the sensitivity and stability of the portable MRS sensor when detecting hydrophobic analytes in the environment.


Assuntos
Técnicas Biossensoriais , Piretrinas , Técnicas Biossensoriais/métodos , Ouro/química , Imunoensaio/métodos , Piretrinas/química , Anticorpos , Fenômenos Magnéticos
14.
Small ; 19(27): e2300589, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36970836

RESUMO

The advancement in thermosensitive active hydrogels has opened promising opportunities to dynamic full-thickness skin wound healing. However, conventional hydrogels lack breathability to avoid wound infection and cannot adapt to wounds with different shapes due to the isotropic contraction. Herein, a moisture-adaptive fiber that rapidly absorbs wound tissue fluid and produces a large lengthwise contractile force during the drying process is reported. The incorporation of hydroxyl-rich silica nanoparticles in the sodium alginate/gelatin composite fiber greatly improves the hydrophilicity, toughness, and axial contraction performance of the fiber. This fiber exhibits a dynamic contractile behavior as a function of humidity, generating ≈15% maximum contraction strain or ≈24 MPa maximum isometric contractile stress. The textile knitted by the fibers features excellent breathability and generates adaptive contraction in the target direction during the natural desorption of tissue fluid from the wounds. In vivo animal experiments further demonstrate the advantages of the textiles over traditional dressings in accelerating wound healing.


Assuntos
Pele , Cicatrização , Animais , Pele/lesões , Bandagens , Biopolímeros , Hidrogéis
15.
Int Immunopharmacol ; 117: 109746, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36827923

RESUMO

BACKGROUND: Chronic graft-versus-host disease (cGVHD) is the most common cause of non-relapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). CD4+ follicular helper T (Tfh) cells, specialized providers of T cell help to B cells, play a vital role in GVHD pathogenesis. B-cell lymphoma-6 (Bcl-6) transcription factor has been shown to be required for Tfh-mediated germinal center reactions. In this study, we would like to evaluate the effect of Bcl-6 on Tfh function in sclerodermatous cGVHD and the efficacy of Bcl-6 inhibitors (Bcl-6i) for treating a minor histocompatibility complex (miHC) mismatch model of sclerodermatous cGVHD (scl-cGVHD). METHODS: A minor histocompatibility haploidentical model of scl-cGVHD was established and received intraperitoneal injection of 79-6, a small-molecule inhibitor of Bcl-6. The clinical manifestations and survival times of cGVHD mice were recorded. The histological assessment was performed by hematoxylin-eosin (HE) and Masson's trichrome staining on the skin and lung tissues. Tfh cells and germinal center B cells in the spleen and peripheral blood were detected by flow cytometry. The cellular markers were immunostained in different organs. ELISA was performed to detect cytokine secretion. RESULTS: Bcl-6 inhibition by 79-6 improved the clinical manifestation of scl-cGVHD mice and prolonged their survival. The histopathologic damage, particular the fibrotic changes of scl-cGVHD mice was significantly relieved after 79-6 treatment. Furthermore, 79-6 treatment not only suppressed the development and function of Tfh and Tph cells in the peripheral blood, but also reduced the survival of Tfh cells in the spleen. Moreover, 79-6 decreased the frequency of GC plasmocytes accompanied by a reduction in IL-21. CONCLUSIONS: Our study demonstrates that Bcl-6 inhibitor could prevent murine sclerodermatous chronic graft-versus-host disease by abrogating T follicular helper differentiation and suppressing the function of GC B cells, indicating that Bcl-6 inhibition may be a potential treatment for patients with cGVHD.


Assuntos
Síndrome de Bronquiolite Obliterante , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Camundongos , Animais , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/patologia , Linfócitos T Auxiliares-Indutores , Diferenciação Celular , Doença Crônica
16.
Acta Biomater ; 158: 759-768, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36638945

RESUMO

Biofilm of oral pathogenic microorganisms induced by their multiplication and coaggregation would lead to periodontitis. In biofilms, the extracellular polymeric substances (EPS) as a protective shield encapsulates the individual bacteria, protecting them against attack. To alleviate periodontal disease, disrupting the EPS of pathogenic bacteria is crucial and challenging. Based on the sufficient capacity of disorganizing EPS of our designed cationic dextrans, we hypothesized that these polymers could be competent in relieving periodontitis. We validated that cationic dextrans could induce the phase transition of EPS in biofilms, especially the Porphyromonas gingivalis (P. gingivalis), a keystone periodontal pathogen, thus effectively destroying biofilm in vitro. More importantly, satisfactory in vivo treatment was achieved in a rat periodontal disease model. In summary, the study exploited a practical and effective strategy to treat periodontitis with cationic dextrans' powerful biofilm-controlling potential. STATEMENT OF SIGNIFICANCE: Periodontal disease is closely related to dental plaque biofilms on the tooth surface. The biofilm forms gel structures and shields the bacteria underneath, thus protecting oral pathogens from traditional anti-bacterial reagents. Due to limited penetration into gel, the efficacy of these reagents in biofilm elimination is restricted. Our designed cationic dextran could wipe out the coverage of gel-like EPS to disperse encapsulated bacteria. Such superior capacity endowed them with satisfactory effect in disrupting biofilm. Notably, in a rat periodontitis model, cationic dextrans dramatically suppressed alveolar bone loss and alleviated periodontal inflammation by controlling dental plaque. Given the increasing global concerns about periodontal disease, it's worth expanding the application of cationic dextrans both scientifically and clinically.


Assuntos
Placa Dentária , Doenças Periodontais , Periodontite , Animais , Ratos , Dextranos/farmacologia , Doenças Periodontais/microbiologia , Biofilmes , Periodontite/tratamento farmacológico , Periodontite/microbiologia , Porphyromonas gingivalis
17.
18.
Front Oncol ; 12: 1057153, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408189

RESUMO

Identifying subgroups of T-cell acute lymphoblastic leukemia (T-ALL) with poor survival will significantly influence patient treatment options and improve patient survival expectations. Current efforts to predict T-ALL survival expectations in multiple patient cohorts are lacking. A deep learning (DL)-based model was developed to determine the prognostic staging of T-ALL patients. We used transcriptome sequencing data from TARGET to build a DL-based survival model using 265 T-ALL patients. We found that patients could be divided into two subgroups (K0 and K1) with significant difference (P< 0.0001) in survival rate. The more malignant subgroup was significantly associated with some tumor-related signaling pathways, such as PI3K-Akt, cGMP-PKG and TGF-beta signaling pathway. DL-based model showed good performance in a cohort of patients from our clinical center (P = 0.0248). T-ALL patients survival was successfully predicted using a DL-based model, and we hope to apply it to clinical practice in the future.

19.
J Control Release ; 352: 540-555, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36323363

RESUMO

The stomach acid degradation, mucus clearance and intestinal epithelial impermeability severely limit the oral delivery of polypeptide drugs. To simultaneously address the three major barriers, novel self-assembled core-shell nanosystems (CA-NPs) were designed. The fabricated shell of citric acid cross-linked carboxymethyl cellulose (CA-CMC) wrapped on core nanoparticles (HA-NPs) maintained the integrity of CA-NPs in the stomach. When CA-NPs passed through the stomach, the CA-CMC shell was gradually degraded to release the core HA-NPs in the intestine. HA-NPs with numerous hydrophilic groups and mannose side chains rapidly penetrated through the mucus layer and efficiently transcellular transported via the glucose transporter (GLUT)-mediated and paracellular transport through reversible opening of tight junctions (TJs) by CA-CMC. The oral bioavailability and therapeutic effects of CA-NPs-loaded polypeptide colistin against Escherichia coli (E. coli) bacteremia in mice were significantly increased compared with the native colistin, respectively. Good safety was observed following oral daily delivery for 14 consecutive days. Thus, CA-NPs may offer a promising strategy for the oral delivery of polypeptide drugs.


Assuntos
Quitosana , Nanopartículas , Camundongos , Animais , Portadores de Fármacos/química , Insulina/farmacologia , Administração Oral , Colistina , Escherichia coli/metabolismo , Nanopartículas/química , Quitosana/química
20.
Sci Adv ; 8(46): eabq7703, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36383669

RESUMO

Integrating sense in a thin artificial muscle fiber for environmental adaption and actuation path tracing, as a snail tentacle does, is highly needed but still challenging because of the interfacing mismatch between the fiber's actuation and sensing components. Here, we report an artificial neuromuscular fiber by wrapping a carbon nanotube (CNT) fiber core in sequence with an elastomer layer, a nanofiber network, and an MXene/CNT thin sheath, achieving the ingenious sense-judge-act intelligent system in an elastic fiber. The CNT/elastomer components provide actuation, and the sheath enables touch/stretch perception and hysteresis-free cyclic actuation tracing due to its strain-dependent resistance. As a whole, the coaxial structure builds a dielectric capacitor that enables sensitive touchless perception. The key to seamless integration is to use a nanofiber interface that allows the sensing layer to adaptively trace but not restrict actuation. This work provides promising solutions for closed-loop control for future intelligent soft robots.

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