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1.
Colloids Surf B Biointerfaces ; 223: 113150, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36731267

RESUMO

Titanium nitride (TiN) and titanium dioxide (TiO2) are two titanium-based coatings commonly used in cardiovascular stent surface engineering. Generally, TiN has good mechanical properties and endothelial cell (ECs) compatibility but poor anticoagulant properties and cannot modulate cell growth orientation and morphology. TiO2 has excellent corrosion resistance and biosafety. Besides, TiO2 has the photocatalytic anticoagulant property, which can migrate to other materials tens of microns away. Based on the above properties, a striped TiO2-TiN micropattern coating was designed and fabricated in this study, and the coating was photofunctionalized by UV irradiation. The obtained photo-functionalized TiO2-TiN micropattern coating showed anticoagulant properties by the migrating effect of the photocatalytic anticoagulant property of TiO2. Besides, the TiO2-TiN micropattern coatings showed ECs compatibility. Furthermore, the growth orientation and cell shape of ECs on TiO2-TiN samples were effectively regulated by the stripe pattern's contact guidance effect, which was particularly evident on the photo-functionalized TiO2-TiN samples. We envision that this photofunctionalized TiO2-TiN striped micropattern coating has significant potential for the surface engineering of vascular stents.

2.
J Pineal Res ; 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36732033

RESUMO

Increasing carbon dioxide (CO2 ) promotes photosynthesis and mitigates heat stress-induced deleterious effects on plants, but the regulatory mechanisms remain largely unknown. Here, we found that tomato (Solanum lycopersicum L.) plants treated with high atmospheric CO2 concentrations (600, 800 and 1000 µmol mol-1 ) accumulated increased levels of melatonin (N-acetyl-5-methoxy tryptamine) in their leaves and this response is conserved across many plant species, including Arabidopsis, rice, wheat, mustard, cucumber, watermelon, melon and hot pepper. Elevated CO2 (eCO2 , 800 µmol mol-1 ) caused 6.8 fold increase in leaf melatonin content, and eCO2 -induced melatonin biosynthesis preferentially occurred through chloroplast biosynthetic pathways in tomato plants. Crucially, manipulation of endogenous melatonin levels by genetic means affected the eCO2 -induced accumulation of sugar and starch in tomato leaves. Furthermore, net photosynthetic rate, maximum photochemical efficiency of photosystem II and transcript levels of chloroplast- and nuclear-encoded photosynthetic genes, such as rbcL, rbcS, rbcA, psaD, petB and atpA, significantly increased in COMT1 overexpressing (COMT1-OE) tomato plants, but not in melatonin-deficient comt1 mutants at eCO2 conditions. While eCO2 enhanced plant tolerance to heat stress (42°C) in wild-type and COMT1-OE, melatonin deficiency compromised eCO2 -induced thermotolerance in comt1 plants. The expression of heat shock proteins genes increased in COMT1-OE but not in comt1 plants in response to eCO2 under heat stress. Further analysis revealed that eCO2 -induced thermotolerance was closely linked to the melatonin-dependent regulation of reactive oxygen species, redox homeostasis, cellular protein protection and phytohormone metabolism. This study unveiled a crucial mechanism of elevated CO2 -induced thermotolerance in which melatonin acts as an essential endogenous signaling molecule in tomato plants. This article is protected by copyright. All rights reserved.

3.
Adv Biol (Weinh) ; : e2200277, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721069

RESUMO

Efferocytosis, responsible for apoptotic cell clearance, is an essential factor against atherosclerosis. It is reported that efferocytosis is severely impaired in fibroatheroma, especially in vulnerable thin cap fibroatheroma. However, there is a shortage of studies on efferocytosis defects in cell and animal models. Here, the impacts of oxidized low density lipoprotein (ox-LDL) and glut 1 inhibitor (STF31) on efferocytosis of macrophages are studied, and an evaluation system is constructed. Through regulating the cell ratios and stimulus, three types of atherosclerotic spheroids are fabricated, and a necrotic core emerges with surrounding apoptotic cells. Rat models present a similar phenomenon in that substantial apoptotic cells are uncleared in time in vulnerable plaque, and the model period is shortened to 7 weeks. Mechanism studies reveal that ox-LDL, through mRNA and miRNA modulation, downregulates efferocytosis receptor (PPARγ/LXRα/MerTK), internalization molecule (SLC29a1), and upregulates the competitive receptor CD300a that inhibits efferocytosis receptor-ligand binding process. The foam cell differentiation has also confirmed that CD36 and Lp-PLA2 levels are significantly elevated, and macrophages present an interesting transition into prothrombic phenotype. Collectively, the atherosclerotic models featured by efferocytosis defect provide a comprehensive platform to evaluate the efficacy of medicine and biomaterials for atherosclerosis treatment.

4.
Langmuir ; 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36623173

RESUMO

The application of graphitic carbon nitride (g-C3N4) in photocatalytic NO oxidation was limited due to severe recombination of photogenerated carriers and low concentration of oxidizing species. In this work, K and B were introduced into the interlayer and in-plane framework of g-C3N4 to address this challenge through the thermal polymerization process. The synthesized K-doped B-g-C3N4 nanosheets exhibited expanded light absorption and low charge recombination efficiency. In addition, the doping of K and B reduced the band gap of g-C3N4, which corresponded to enhanced light absorption. B was introduced into the in-plane structure by replacing C atoms, which adjusted the in-plane electron distribution. K was inserted into the interlayer by binding to the N and C atoms of adjacent layers. K-derived electron transfer channels were constructed, which increased electron delocalization and expanded the π-conjugate system. More electrons were transferred through the interlayer channels and were involved in the reaction process. The severe carrier recombination and weak transfer were improved due to the synergistic effect of K and B doping. K-doped B-g-C3N4 nanosheets exhibited enhanced generation of superoxide radicals and hydroxyl radicals, which played a key role during NO oxidation. The photocatalytic NO oxidation efficiency of codoped g-C3N4 nanosheets reached 61%, which was 2.1 and 1.2 times of that of pristine g-C3N4 and B-doped g-C3N4, respectively. The codoped g-C3N4 sample still exhibited stable photocatalytic NO oxidation efficiency after five cycles. This result provided a potential idea for improving the charge distribution and transfer of layered materials by codoping metallic and nonmetallic elements and for photocatalytic NO oxidation.

5.
Antimicrob Agents Chemother ; 67(1): e0162422, 2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36622172

RESUMO

Vancomycin is recommended for the treatment of skin and soft tissue infections (SSTI) and bone and joint infections (BJI). However, a detailed investigation of the pharmacokinetic profile and optimal dosing regimens of vancomycin in pediatric patients with SSTI and BJI is lacking. We successfully developed a new PopPK model of vancomycin in this population by using scavenged blood samples with the typical values for clearance (CL) of 0.14 L/h/kg and volume of distribution (V) of 0.5 L/kg. Body weight was confirmed as the significant covariate on CL and V. The optimal dosing regimens of 75 mg/kg/day and 80 mg/kg/day were recommended for this specific population.


Assuntos
Infecções dos Tecidos Moles , Vancomicina , Humanos , Criança , Antibacterianos/farmacocinética , Infecções dos Tecidos Moles/tratamento farmacológico , Modelos Biológicos
6.
Biologicals ; : 101661, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36621353

RESUMO

The Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) collected historical data from 20 biopharmaceutical industry members on their experience with the in vivo adventitious virus test, the in vitro virus test, and the use of next generation sequencing (NGS) for viral safety. Over the past 20 years, only three positive in vivo adventitious virus test results were reported, and all were also detected in another concurrent assay. In more than three cases, data collected as a part of this study also found that the in vivo adventitious virus test had given a negative result for a sample that was later found to contain virus. Additionally, the in vivo adventitious virus test had experienced at least 21 false positives and had to be repeated an additional 21 times all while using more than 84,000 animals. These data support the consideration and need for alternative broad spectrum viral detection tests that are faster, more sensitive, more accurate, more specific, and more humane. NGS is one technology that may meet this need. Eighty one percent of survey respondents are either already actively using or exploring the use of NGS for viral safety. The risks and challenges of replacing in vivo adventitious virus testing with NGS are discussed. It is proposed to update the overall virus safety program for new biopharmaceutical products by replacing in vivo adventitious virus testing approaches with modern methodologies, such as NGS, that maintain or even improve the final safety of the product.

7.
J Pharm Biomed Anal ; 226: 115247, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36657347

RESUMO

LC-MS has been a widely used analytical technique for identification of natural compounds. However, sophisticated and laborious data analysis is required to identify chemical components, especially new compounds, from a large LC-MS dataset. The aim of this study is to develop an integrated data-mining strategy that combines molecular networking (MN), in-house polygonal mass defect filtering (MDF), and diagnostic fragment ion filtering (DFIF) to identify phytochemicals in Stephania tetrandra based on LC-MS data. S. tetrandra samples were prepared by matrix solid-phase dispersion extraction methods and then raw MS spectra were acquired using LC-QTOF-MS/MS. MN and in-house polygonal MDF classified the compounds roughly. Modified DFIF were then used in succession to place each spectrum into a specific class. Finally, the exact structures were deduced by fragmentation pathways and related botanical biogenesis, with the help of the narrowed classification from MN and MDF. The total workflow was a combination of data filtering and identification methods for rapid characterization of known compounds (dereplication) and discovery of new compounds. Consequently, 144 compounds were identified or tentatively identified in the aerial parts and roots of S. tetrandra, including 11 potentially new compounds and 63 compounds first identified in this species. Among 144 compounds, 61 were from the aerial parts exclusively, 8 were from the roots exclusively, and 75 were found in both parts. Furthermore, two new biflavonoids were isolated with the guide of LC-MS analysis and structurally elucidated by spectroscopic methods. In conclusion, the proposed data-mining strategy based on LC-MS can be used to profile chemical constituents with high efficiency and guide the isolation of new compounds from medicinal plants. The comparison of the components of the aerial parts and roots of S. tetrandra would be helpful for the rational utilization of the medicinal plant.

8.
Colloids Surf B Biointerfaces ; 223: 113141, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36682296

RESUMO

Dopamine is a small molecule inspired by the dopamine motif of mussel foot proteins, and PDA is formed by the self-polymerization of dopamine. Under the UV-irradiation,PDA would be oxidized by reactive oxygen species (ROS) which were produced by photocatalytic reactions on TiO2 surfaces,thus regulating the adhesion behavior of endothelial cells (ECs) TiO2 inhibited platelet (Plt) adhesion after UV exposure. Polydopamine (PDA)-TiO2 micropatterns (P-PDA-TiO2) were prepared by magnetron sputtering and photolithography. This micropatterns successfully achieves selective adhesion of Plt and ECs. The selective adhesion of ECs disappears after vacuum reduction. In contrast to conventional cell patterning strategies, P-PDA-TiO2 can easily achieve pattern separation of ECs and Plts and provide a new concept for building complex blood-contacting devices.

9.
Exp Ther Med ; 25(2): 74, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36684656

RESUMO

Periodontitis is the chronic inflammation of the periodontal tissue. The present study aimed to investigate the role of baricitinib, a Janus kinase (JAK)1/2 inhibitor, in periodontitis by using a lipopolysaccharide (LPS)-induced human periodontal ligament stem cell (PDLSC) model. The viability of PDLSCs stimulated by LPS was assessed in the presence of baricitinib by Cell Counting Kit-8 assay. The induction of oxidative stress was evaluated by detecting the intracellular reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity and glutathione (GSH) content. ELISA and reverse transcription-quantitative PCR were used to determine the levels of inflammatory factors TNF-α, IL-1ß and IL-6. Alkaline phosphatase (ALP) activity and alizarin red staining were used to assess the osteogenic differentiation of PDLSCs. The expression levels of osteogenic differentiation- and JAK/signal transducer and activator of transcription (STAT) signaling-associated proteins were estimated with western blotting. RO8191, an agonist of the JAK/STAT pathway, was used to treat PDLSCs to investigate the regulatory mechanism of baricitinib. The results indicated that baricitinib elevated the LPS-induced decrease in cell viability. LPS-triggered oxidative stress and inflammation were inhibited by baricitinib, as demonstrated by the decreased levels of ROS, TNF-α, IL-1ß, IL-6 and increased levels of SOD and GSH. In addition, baricitinib caused a marked elevation in ALP activity and mineralization ability of PDLSCs, as determined by the upregulated osteocalcin and Runt-related transcription factor 2 expression. Moreover, the expression levels of phosphorylated (p)-JAK1, p-JAK2 and p-STAT3 were downregulated by baricitinib in a dose-dependent manner. Furthermore, addition of RO8191 restored the effect of baricitinib on the induction of oxidative stress, inflammation and osteogenic differentiation of PDLSCs exposed to LPS. Collectively, these findings suggested that baricitinib alleviated oxidative stress and inflammation and promoted osteogenic differentiation of LPS-induced PDLSCs by inhibiting JAK/STAT signaling.

10.
Pharmaceuticals (Basel) ; 16(1)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36678620

RESUMO

Multiple myeloma is a hematological malignancy characterized by the unrestricted proliferation of plasma cells that secrete monoclonal immunoglobulins in the bone marrow. Alpha-momorcharin (α-MMC) is a type I ribosome-inactivating protein extracted from the seeds of the edible plant Momordica charantia L., which has a variety of biological activities. This study aimed to investigate the inhibitory effect of α-MMC on the proliferation of multiple myeloma MM.1S cells and the molecular mechanism of MM.1S cell death induced through the activation of cell signal transduction pathways. The cell counting kit-8 (CCK-8) assay was used to determine the inhibitory effect of α-MMC on the proliferation of MM.1S cells and its toxic effect on normal human peripheral blood mononuclear cells (PBMCs). The effect of α-MMC on the MM.1S cells' morphology was observed via inverted microscope imaging. The effects of α-MMC on the MM.1S cell cycle, mitochondrial membrane potential (MMP), and apoptosis were explored using propidium iodide, JC-1, annexin V- fluorescein isothiocyanate/propidium iodide fluorescence staining, and flow cytometry (FCM) analysis. Western blot was used to detect the expressions levels of apoptosis-related proteins and MAPK-signaling-pathway-related proteins in MM.1S cells induced by α-MMC. The results of the CCK-8 showed that in the concentration range of no significant toxicity to PBMCs, α-MMC inhibited the proliferation of MM.1S cells in a time-dependent and concentration-dependent manner, and the IC50 value was 13.04 and 7.518 µg/mL for 24 and 48 h, respectively. Through inverted microscope imaging, it was observed that α-MMC induced a typical apoptotic morphology in MM.1S cells. The results of the FCM detection and analysis showed that α-MMC could arrest the MM.1S cells cycle at the G2 phase, decrease the MMP, and induce cell apoptosis. Western blot analysis found that α-MMC upregulated the expression levels of Bax, Bid, cleaved caspase-3, and cleaved PARP, and downregulated the expression levels of Mcl-1. At the same time, α-MMC decreased the expression levels of p-c-Raf, p-MEK1/2, p-ERK1/2, p-MSK1, and p-P90RSK, and increased the expression levels of p-p38, p-SPAK/JNK, p-c-Jun, and p-ATF2. The above results suggest that α-MMC can inhibit the proliferation of multiple myeloma MM.1S cells. MAPK cascade signaling is involved in the growth inhibition effect of α-MMC on MM.1S cells via cycle arrest and mitochondrial-pathway-dependent apoptosis.

11.
Microsyst Nanoeng ; 9: 9, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36644333

RESUMO

With the increasing demand for multidirectional vibration measurements, traditional triaxial accelerometers cannot achieve vibration measurements with high sensitivity, high natural frequency, and low cross-sensitivity simultaneously. Moreover, for piezoresistive accelerometers, achieving pure axial deformation of the piezoresistive beam can greatly improve performance, but it requires the piezoresistive beam to be located in a specific position, which inevitably makes the design more complex and limits the performance improvement. Here, a monolithically integrated triaxial high-performance accelerometer with pure axial stress piezoresistive beams was designed, fabricated, and tested. By controlling synchronous displacements at both piezoresistive beam ends, the pure axial stress states of the piezoresistive beams could be easily achieved with position independence without tedious calculations. The measurement unit for the z-axis acceleration was innovatively designed as an interlocking proof mass structure to ensure a full Wheatstone bridge for sensitivity improvement. The pure axial stress state of the piezoresistive beams and low cross-sensitivity of all three units were verified by the finite element method (FEM). The triaxial accelerometer was fabricated and tested. Results showing extremely high sensitivities (x axis: 2.43 mV/g/5 V; y axis: 2.44 mv/g/5 V; z axis: 2.41 mV/g/5 V (without amplification by signal conditioning circuit)) and high natural frequencies (x/y axes: 11.4 kHz; z-axis: 13.2 kHz) were obtained. The approach of this paper makes it simple to design and obtain high-performance piezoresistive accelerometers.

12.
Med Oncol ; 40(2): 78, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635412

RESUMO

Cervical cancer is a heterogeneous malignancy mainly caused by human papillomavirus (HPV). While a few studies have revealed heterogeneity of cervical cancer in chromosome levels, the correlation between genetic heterogeneity and HPV integration in cervical cancer remains unknown. Here, we applied multi-region whole-exome sequencing and HPV integration analysis to explore intratumor heterogeneity in cervical cancer. We sequenced 20 tumor regions and 5 adjacent normal tissues from 5 cervical cancer patients, analysis based on somatic mutations and somatic copy number alterations (SCNAs) levels were performed. Variable heterogeneity was observed between the five patients with different tumor stages and HPV infection statuses. We found HPV integration has a positive effect on somatic mutation burden, but the relation to SCNAs remains unclear. Frequently mutated genes in cervical cancer were identified as trunk events, such as FBXW7, PIK3CA, FAT1 in somatic mutations and TP63, MECOM, PIK3CA, TBL1XR1 in SCNAs. New potential driver genes in cervical cancer were summarized including POU2F2, TCF7 and UBE2A. The SCNAs level has potential relation with tumor stage, and Signature 3 related to homologous recombination deficiency may be the appropriate biomarker in advanced cervical cancer. Mutation signature analysis also revealed a potential pattern that APOBEC-associated signature occurs in early stage and signatures associated with DNA damage repair arise at the later stage of cervical cancer evolution. In a conclusion, our study provides insights into the potential relationship between HPV infection and tumor heterogeneity. Those results enhanced our understanding of tumorigenesis and progression in cervical cancer.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Classe I de Fosfatidilinositol 3-Quinases/genética , Evolução Clonal/genética , Variações do Número de Cópias de DNA , Mutação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia
13.
J Neuroimmunol ; 376: 578035, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36716560

RESUMO

Neuromyelitis optica spectrum disorders (NMOSD) is an autoimmune demyelinating disease with IgG against aquaporin 4 (AQP4) in more than two thirds of patients. Anti-myelin-oligodendrocyte glycoprotein (MOG) antibody is found in some AQP4-negative NMOSD patients and MOG antibody-associated disease (MOGAD) is thought to be distinct from NMOSD. Due to the high disabling nature of NMOSD, treatment strategy on first attack is crucial for good prognosis. Rituximab (RTX), an anti-CD20 monoclonal antibody (mAb), is the first-line treatment for NMOSD. However, RTX can be limited by the relatively high rate of systemic allergic reaction. Herein, we reported a rare case of AQP4 and MOG-IgG double positive NMOSD patient effectively and safely treated with ofatumumab (OFA), a novel fully humanized anti-CD20 mAb.

14.
Microbiol Spectr ; : e0278622, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36719204

RESUMO

Klebsiella pneumoniae is capable of acquiring various exogenous genetic elements and subsequently conferring high antimicrobial resistance. Recently, a plasmid-mediated RND family multidrug efflux pump gene cluster, tmexCD1-toprJ1, was discovered in K. pneumoniae. In this study, we analyzed tigecycline-resistant K. pneumoniae isolates from patients from surveillance from 2017 to 2021. In addition to phenotype detection, including growth curves, plasmid transferability and stability, hypermucoviscosity, biofilm formation, and serum survival, by whole-genome sequencing, we analyzed the phylogenetic relationships of the isolates harboring tmexCD1-toprJ1 and discovered the composition of plasmids carrying tmexCD1-toprJ1. In total, we discovered that 12 tigecycline-resistant isolates from 5 patients possessed tmexCD1-toprJ1, designated sequence type 22 (ST22) and ST3691. An ST11 isolate harbored a partial tmexD1, and a complete toprJ1 (tmexC1 was lost) was tigecycline sensitive. All the ST22 tigecycline-resistant isolates coharbored tmexCD1-toprJ1, blaNDM-1, and blaKPC-2. tmexCD1-toprJ1 was encoded by a novel IncU plasmid in ST22 and an IncFIB/HI1B plasmid in ST3691, which presented differences in mobility and stability. Interestingly, isolates from the same patients presented heteroresistance to tigecycline, not only among isolates from different specimens but also those from the same sample, which might be attributed to the differential expression of tmexCD1-toprJ1 due to the dynamic genetic heterogeneity caused by relocating tmexCD1-toprJ1 close to the replication origin of plasmid. Here, we reported the emergence of K. pneumoniae isolates coharboring tmexCD1-toprJ1, blaNDM-1, and blaKPC-2. The results highlight the impact of in vivo genetic heterogeneity of tmexCD1-toprJ1-carrying elements on the in vivo variation of tigecycline resistance, which might have notable influences on antimicrobial treatment. IMPORTANCE Pandrug-resistant (PDR) Klebsiella pneumoniae poses a great challenge to public health, and tigecycline is an essential choice for antimicrobial treatment. In this study, we reported the emergence of PDR K. pneumoniae coharboring tmexCD1-toprJ1, blaNDM-1, and blaKPC-2, which belongs to ST22 and ST3691. By whole-genome analysis, we reconstructed the evolutionary map of the ST22 ancestor to become the PDR superbug by acquiring multiple genetic elements encoding tmexCD1-toprJ1 or blaNDM-1. Importantly, the genetic contexts of tmexCD1-toprJ1 among the ST22 isolates are different and present with various mobilities and stabilities. Furthermore, we also discovered the heterogeneity of tigecycline resistance during long-term infection of ST22, which might be attributed to the differential expression of tmexCD1-toprJ1 due to the dynamic genetic heterogeneity caused by relocating tmexCD1-toprJ1 close to the replication origin of plasmid. This study tracks the inter- and intrahost microevolution of the superbug PDR K. pneumoniae and highlights the importance of timely monitoring of the variation of pathogens during antimicrobial treatment.

15.
ACS Appl Mater Interfaces ; 15(4): 4959-4972, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36650085

RESUMO

Hydrogel dressings not only have basic functions such as swelling, water retention, gas permeability, and good biocompatibility but also can be endowed with advanced functions such as antibacterial, antioxidant, adhesion, hemostasis, and anti-inflammation, which make hydrogels have great application potential in clinical trauma. However, the complexity of the wound healing process makes the development of multifunctional wound dressings a great challenge. In this work, based on the thiol-ene photoclickable PEG hydrogel, the inclusion complex of the hydrophobic drug ellagic acid (EA) with mono-(6-mercapto-6-deoxy)-ß-cyclodextrin (SH-ß-CD) participated in the formation of a hydrogel as a crosslinker. The drug EA with antioxidant, antibacterial, and anti-inflammatory activities was introduced into the hydrogel. This strategy increases the loading capacity of the hydrogel for EA and endows the hydrogel with multifunctional properties. Then, dithiothreitol was added to adjust the mechanical stiffness of the hydrogel to meet the requirements of the wound dressing. Our results demonstrated that this wound dressing has excellent cytocompatibility, antioxidant, antibacterial, and anti-inflammatory activities. Furthermore, the results of the infected wound healing model experiment in rats confirmed that the hydrogel has the ability to rapidly shrink the wound area, prevent wound infection, and promote angiogenesis and collagen deposition. All these results suggest that this hydrogel could be a candidate for the treatment of infected wounds and shed new light on the development of multifunctional wound dressings.


Assuntos
Antioxidantes , Ciclodextrinas , Ratos , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Ácido Elágico/farmacologia , Hidrogéis/farmacologia , Hidrogéis/química , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química , Anti-Inflamatórios/farmacologia
16.
Cell Rep ; 42(1): 111904, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36662616

RESUMO

TEAD1 and the mammalian Hippo pathway regulate cellular proliferation and function, though their regulatory function in ß cells remains poorly characterized. In this study, we demonstrate that while ß cell-specific TEAD1 deletion results in a cell-autonomous increase of ß cell proliferation, ß cell-specific deletion of its canonical coactivators, YAP and TAZ, does not affect proliferation, suggesting the involvement of other cofactors. Using an improved split-GFP system and yeast two-hybrid platform, we identify VGLL4 and MENIN as TEAD1 corepressors in ß cells. We show that VGLL4 and MENIN bind to TEAD1 and repress the expression of target genes, including FZD7 and CCN2, which leads to an inhibition of ß cell proliferation. In conclusion, we demonstrate that TEAD1 plays a critical role in ß cell proliferation and identify VGLL4 and MENIN as TEAD1 corepressors in ß cells. We propose that these could be targeted to augment proliferation in ß cells for reversing diabetes.

17.
J Colloid Interface Sci ; 636: 646-656, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36680955

RESUMO

Construction of Z-scheme heterojunctions has been considered one superb method in promoting solar-assisted charge carrier separation of carbon-based materials to achieve efficient utilization of solar energy in hydrogen production and CO2 reduction. One interesting concept in nanofabrication that has become trend recent years is nanoarchitectonics. A heterostructure photocatalyst constructed based on the idea of nanoarchitectonics using the combination of g-C3N4, metal and an additional semiconducting nanocomposite is investigated in this paper. Z-scheme tungsten oxide incorporated copper modified graphitic carbon nitride (WOx/Cu-g-C3N4) heterostructures are fabricated via immobilization of WOx on Cu nanoparticles modified superior thin g-C3N4 nanosheets. Mechano-chemical pre-reaction and a two-step high-temperature thermal polymerization process are the keys in attaining homogeneous distribution of Cu nanoparticles in g-C3N4 nanosheets. The horizontal growth of homogeneously distributed WOx nanobelts on Cu modified g-C3N4 (Cu-g-C3N4) base via solvothermal synthesis is achieved. The photocatalytic performances of the heterostructures are evaluated through water splitting and CO2 photoreduction measurements in full solar spectrum irradiation condition. The presence of Cu nanoparticles in the composite system improves charge transport between g-C3N4 and WOx and thus enhances the photocatalytic performances (H2 generation and CO2 photoreduction) of the composite material, while the presence of WOx nanocomposites enhances light absorption of the composite material in the near infrared range. The synthesized heterostructure with optimized WOx to Cu-g-C3N4 ratio and in case of no co-catalyst addition exhibits enhanced photocatalytic H2 evolution (4560 µmolg-1h-1) as well as excellent CO2 reduction rate (5.89 µmolg-1h-1 for CO generation).

18.
Curr Mol Pharmacol ; 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36635928

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a usual head and neck malignancy. Guggulsterone (GS) has potential in cancer chemoprophylaxis and treatment, but its therapeutic effect on NPC is unknown. We aimed to explore whether GS could promote the secretion of exosomal circFIP1L1 from NPC cells and its regulatory mechanism. METHODS: NPC tissues and adjacent tissues were collected from NPC patients. Human nasopharyngeal epithelial cell lines (NP69) and NPC lines (5-8F, CNE1, and HNE1) were used for in vitro experiments. HNE1 cells were treated with GS (20, 40, 60 µmol/L). The expressions of miR-125a-5p and circFIP1L1 were evaluated by qRT-PCR. Cell proliferation and apoptosis abilities were measured by CCK-8 and flow cytometry. HNE1 cell exosomes were extracted and identified, and the levels of VEGFA and VEGFR2 were detected by ELISA. Then miR-125a-5p was knocked down and overexpressed. HUVECs angiogenesis was determined by the tube formation assay. qRT-PCR and Western blot were utilized to evaluate the expressions of VEGFA, MMP-2, MMP-9, and ICAM-1 in HUVECs. RESULTS: miR-125a-5p was highly expressed in NPC tissues and cells. GS promoted the secretion of exosomal circFIP1L1 from HNE1 cells to affect HUVECs proliferation and angiogenesis. Overexpression of miR-125a-5p accelerated HUVECs proliferation and angiogenesis. Knocking down miR-125a-5p inhibited VEGFA expression. In addition, exosomal circFIP1L1 sponged miR-125a-5p, inhibiting the VEGFA pathway to repress HUVECs angiogenesis. CONCLUSIONS: GS promoted exosomal circFIP1L1 in NPC cells to mediate miR-125a-5p/VEGFA axis affecting tumor angiogenesis.

20.
Radiat Res ; 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36630584

RESUMO

Radiation-induced skin injury (RISI) is a serious concern for nuclear accidents and cancer radiotherapy, which seriously affects the quality of life of patients. This injury differs from traditional wounds due to impaired healing and the propensity to recurrence and is divided into acute and chronic phases on the basis of the injury time. Unfortunately, there are few effective therapies for preventing or mitigating this injury. Over the last few decades, various studies have focused on the effects of stem cell-based therapies to address the tissue repair and regeneration of irradiated skin. These stem cells modulate inflammation and instigate tissue repair by differentiating into specific kinds of cells or releasing paracrine factors. Stem cell-based therapies, including bone marrow-derived stem cells (BMSCs), adipose-derived stem cells (ADSCs) and stromal vascular fraction (SVF), have been reported to facilitate wound healing after radiation exposure. Moreover, stem cell-derived exosomes have recently been suggested as an effective and cell-free approach to support skin regeneration, circumventing the concerns respecting direct application of stem cells. Based on the literature on stem cell-based therapies for radiation-induced skin injury, we summarize the characteristics of different stem cells and describe their latest animal and clinical applications, as well as potential mechanisms. The promise of stem-cell based therapies against radiation-induced skin injury contribute to our response to nuclear events and smooth progress of cancer radiotherapy.

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