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1.
Cell ; 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35777355

RESUMO

The host-seeking activity of hematophagous arthropods is essential for arboviral transmission. Here, we demonstrate that mosquito-transmitted flaviviruses can manipulate host skin microbiota to produce a scent that attracts mosquitoes. We observed that Aedes mosquitoes preferred to seek and feed on mice infected by dengue and Zika viruses. Acetophenone, a volatile compound that is predominantly produced by the skin microbiota, was enriched in the volatiles from the infected hosts to potently stimulate mosquito olfaction for attractiveness. Of note, acetophenone emission was higher in dengue patients than in healthy people. Mechanistically, flaviviruses infection suppressed the expression of RELMα, an essential antimicrobial protein on host skin, thereby leading to the expansion of acetophenone-producing commensal bacteria and, consequently, a high acetophenone level. Given that RELMα can be specifically induced by a vitamin A derivative, the dietary administration of isotretinoin to flavivirus-infected animals interrupted flavivirus life cycle by reducing mosquito host-seeking activity, thus providing a strategy of arboviral control.

2.
Biotechnol Bioeng ; 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38973176

RESUMO

Biosensors are valuable tools in accelerating the test phase of the design-build-test-learn cycle of cell factory development, as well as in bioprocess monitoring and control. G protein-coupled receptor (GPCR)-based biosensors enable cells to sense a wide array of molecules and environmental conditions in a specific manner. Due to the extracellular nature of their sensing, GPCR-based biosensors require compartmentalization of distinct genotypes when screening production levels of a strain library to ensure that detected levels originate exclusively from the strain under assessment. Here, we explore the integration of production and sensing modalities into a single Saccharomyces cerevisiae strain and compartmentalization using three different methods: (1) cultivation in microtiter plates, (2) spatial separation on agar plates, and (3) encapsulation in water-in-oil-in-water double emulsion droplets, combined with analysis and sorting via a fluorescence-activated cell sorting machine. Employing tryptamine and serotonin as proof-of-concept target molecules, we optimize biosensing conditions and demonstrate the ability of the autocrine screening method to enrich for high producers, showing the enrichment of a serotonin-producing strain over a nonproducing strain. These findings illustrate a workflow that can be adapted to screening for a wide range of complex chemistry at high throughput using commercially available microfluidic systems.

3.
Environ Res ; 251(Pt 1): 118602, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38431072

RESUMO

Short-chain chlorinated paraffins (SCCPs), a class of persistent organic pollutants, have been found to cause diverse organ and systemic toxicity. However, little is known about their neurotoxic effects. In this study, we exposed BV2, a mouse microglia cell line, to environmentally relevant concentration of SCCPs (1 µg/L, 10 µg/L, 100 µg/L) for 24 h to investigate their impacts on the nervous system. Our observations revealed that SCCPs induced the activation of BV2 microglia, as indicated by altered morphology, stimulated cell proliferation, enhanced phagocytic and migratory capabilities. Analysis at the mRNA level confirmed the activation status, with the downregulation of TMEM119 and Tgfbr1, and upregulation of Iba1 and CD11b. The upregulated expression of genes such as cenpe, mki67, Axl, APOE and LPL also validated alterations in cell functions. Moreover, BV2 microglia presented an M2 alternative phenotype upon SCCPs exposure, substantiated by the reduction of NF-κB, TNF-α, IL-1ß, and the elevation of TGF-ß. Additionally, SCCPs caused lipid metabolic changes in BV2 microglia, characterized by the upregulations of long-chain fatty acids and acylcarnitines, reflecting an enhancement of ß-oxidation. This aligns with our findings of increased ATP production upon SCCPs exposure. Intriguingly, cell activation coincided with elevated levels of omega-3 polyunsaturated fatty acids. Furthermore, activated microglial medium remarkably altered the proliferation and differentiation of mouse neural stem cells. Collectively, exposure to environmentally relevant concentrations of SCCPs resulted in activation and lipid metabolic alterations in BV2 microglia, potentially impacting neurogenesis. These findings provide valuable insights for further research on the neurotoxic effect of SCCPs.


Assuntos
Metabolismo dos Lipídeos , Microglia , Neurogênese , Microglia/efeitos dos fármacos , Microglia/metabolismo , Animais , Camundongos , Metabolismo dos Lipídeos/efeitos dos fármacos , Linhagem Celular , Neurogênese/efeitos dos fármacos , Hidrocarbonetos Clorados/toxicidade , Parafina/toxicidade , Poluentes Ambientais/toxicidade , Proliferação de Células/efeitos dos fármacos
4.
Int J Med Sci ; 21(9): 1769-1782, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006834

RESUMO

Dilated cardiomyopathy (DCM) causes heart failure and sudden death. Epigenetics is crucial in cardiomyopathy susceptibility and progression; however, the relationship between epigenetics, particularly DNA methylation, and DCM remains unknown. Therefore, this study identified aberrantly methylated differentially expressed genes (DEGs) associated with DCM using bioinformatics analysis and characterized their clinical utility in DCM. DNA methylation expression profiles and transcriptome data from public datasets of human DCM and healthy control cardiac tissues were obtained from the Gene Expression Omnibus public datasets. Then an epigenome-wide association study was performed. DEGs were identified in both DCM and healthy control cardiac tissues. In total, 3,353 cytosine-guanine dinucleotide sites annotated to 2,818 mRNAs were identified, and 479 DCM-related genes were identified. Subsequently, core genes were screened using logistic, least absolute shrinkage and selection operator, random forest, and support vector machine analyses. The overlapping of these genes resulted in DEGs with abnormal methylation patterns. Cross-tabulation analysis identified 8 DEGs with abnormal methylation. Real-time quantitative polymerase chain reaction confirmed the expression of aberrantly methylated DEGs in mice. In DCM murine cardiac tissues, the expressions of SLC16A9, SNCA, PDE5A, FNDC1, and HTRA1 were higher compared to normal murine cardiac tissues. Moreover, logistic regression model associated with aberrantly methylated DEGs was developed to evaluate the diagnostic value, and the area under the receiver operating characteristic curve was 0.949, indicating that the diagnostic model could reliably distinguish DCM from non-DCM samples. In summary, our study identified 5 DEGs through integrated bioinformatic analysis and in vivo experiments, which could serve as potential targets for further comprehensive investigation.


Assuntos
Cardiomiopatia Dilatada , Biologia Computacional , Metilação de DNA , Perfilação da Expressão Gênica , Cardiomiopatia Dilatada/genética , Metilação de DNA/genética , Humanos , Animais , Camundongos , Epigênese Genética , Transcriptoma/genética , Masculino , Regulação da Expressão Gênica/genética
5.
Proc Natl Acad Sci U S A ; 118(42)2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34620704

RESUMO

Zika virus (ZIKV) caused millions of infections during its rapid and expansive spread from Asia to the Americas from 2015 to 2017. Here, we compared the infectivity of ZIKV mutants with individual stable substitutions which emerged throughout the Asian ZIKV lineage and were responsible for the explosive outbreaks in the Americas. A threonine (T) to alanine (A) mutation at the 106th residue of the ZIKV capsid (C) protein facilitated the transmission by its mosquito vector, as well as infection in both human cells and immunodeficient mice. A mechanistic study showed that the T106A substitution rendered the C a preferred substrate for the NS2B-NS3 protease, thereby facilitating the maturation of structural proteins and the formation of infectious viral particles. Over a complete "mosquito-mouse-mosquito" cycle, the ZIKV C-T106A mutant showed a higher prevalence of mosquito infection than did the preepidemic strain, thus promoting ZIKV dissemination. Our results support the contribution of this evolutionary adaptation to the occasional widespread reemergence of ZIKV in nature.


Assuntos
Evolução Molecular , Mosquitos Vetores/genética , Mutação , Zika virus/genética , Animais , Genoma Viral , Humanos , Camundongos , Filogenia
6.
Small ; : e2310444, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38050927

RESUMO

Topical antibiotics can be utilized to treat periodontitis, while their delivery stratagems with controlled release and long-lasting bactericidal inhibition are yet challenging. Herein, inspired by the defensive behavior of cuttlefish expelling ink, this work develops innovative thermal-responsive melanin-integrated porous microparticles (MPs) through microfluidic synthesis for periodontitis treatment. These MPs are composed of melanin nanoparticles (NPs), poly(N-isopropylacrylamide) (PNIPAM), and agarose. Benefiting from the excellent biocompatibility and large surface area ratio of MPs, they can deliver abundant melanin NPs. Under near-infrared irradiation, the melanin NPs can convert photo energy into thermal energy. This leads to agarose melting and subsequent shrinkage of the microspheres induced by pNIPAM, thereby facilitating the release of melanin NPs. In addition, the released melanin NPs can serve as a highly effective photothermal agent, displaying potent antibacterial activity against porphyromonas gingivalis and possessing natural anti-inflammatory properties. These unique characteristics are further demonstrated through in vivo experiments, showing the antibacterial effects in the treatment of infected wounds and periodontitis. Therefore, the catfish-inspired photo-responsive antibacterial MPs with controlled-release drug delivery hold tremendous potential in clinical antibacterial applications.

7.
Brief Bioinform ; 22(4)2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-33313676

RESUMO

The genus Culicoides includes biting midges, some of which are vectors for viruses that cause diseases in humans and animals. Knowledge of the roles of Culicoides in viral ecology is inadequate. We collected ~300 000 samples of Culicoides and mosquitoes in 15 representative regions within Yunnan, China. Using mosquitoes as reference vectors, we designed a comparative virome strategy to study the viral composition, diversity, hosts and spatiotemporal distribution of Culicoides. A map of viromes in Culicoides and mosquitoes in Yunan province, China, was constructed. At the same locations, Culicoides and mosquitoes usually share a similar viral diversity. At least 10 important pathogenic viruses were detected from Culicoides. Many novel viruses were discovered, including 21 segmented viruses of Flaviviridae, 180 viruses of Monjiviricetes and 130 viruses of Bunyavirales. The findings demonstrate that Culicoides is an important part of viral ecology and should be studied and monitored for potentially emerging viruses.


Assuntos
Ceratopogonidae/virologia , Culicidae/virologia , Vírus de RNA de Cadeia Positiva/classificação , Viroma , Animais
8.
J Med Virol ; 95(10): e29187, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37877809

RESUMO

Chronic infection of hepatitis B virus (HBV) is the major cause of hepatocellular carcinoma (HCC). Notably, 90% of HBV-positive HCC cases exhibit detectable HBV integrations, hinting at the potential early entanglement of these viral integrations in tumorigenesis and their subsequent oncogenic implications. Nevertheless, the precise chronology of integration events during HCC tumorigenesis, alongside their sequential structural patterns, has remained elusive thus far. In this study, we applied whole-genome sequencing to multiple biopsies extracted from six HBV-positive HCC cases. Through this approach, we identified point mutations and viral integrations, offering a blueprint for the intricate tumor phylogeny of these samples. The emergent narrative paints a rich tapestry of diverse evolutionary trajectories characterizing the analyzed tumors. We uncovered oncogenic integration events in some samples that appear to happen before and during the initiation stage of tumor development based on their locations in reconstituted trajectories. Furthermore, we conducted additional long-read sequencing of selected samples and unveiled integration-bridged chromosome rearrangements and tandem repeats of the HBV sequence within integrations. In summary, this study revealed premalignant oncogenic and sequential complex integrations and highlighted the contributions of HBV integrations to HCC development and genome instability.


Assuntos
Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Humanos , Vírus da Hepatite B/genética , Carcinogênese , Transformação Celular Neoplásica
9.
FASEB J ; 36(10): e22552, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36111987

RESUMO

Among the more than 170 known RNA modifications, methylation modification is the most frequent and well-studied. Depending on where the methylation occurs, RNA methylation can be classified as N6 -methyladenosine, N1 -methyladenosine, 5-methylcytosine, N7 -methylguanosine, and others. The methylation of RNA is constantly and dynamically modified in the complex microenvironment by methyltransferases, demethylases, and methylation reading proteins. These changes affect the proliferation and differentiation of immune cells as well as their effector activities by affecting RNA location, activity, stability, and translation efficiency. This review outlines how diverse RNA methylation alterations affect immune cell development and biological activity, as well as the role of RNA methylation in health and disease, to provide a molecular basis for future immunotherapies.


Assuntos
5-Metilcitosina , Adenosina , Adenosina/genética , Adenosina/metabolismo , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo , RNA/genética , RNA/metabolismo
10.
Virus Genes ; 59(2): 223-233, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36441333

RESUMO

In July 2019, a novel viral strain (JH2019C603) was isolated from sentinel cattle in Jinghong City, in the subtropical region of Yunnan Province, China. The virus replicated and caused cytopathological effects in both Aedes albopictus (C6/36) and Baby Hamster Syrian Kidney (BHK-21) cells. Agarose gel electrophoresis analysis revealed a viral genome comprised of 10 segments of double-stranded RNA, with a 1-2-2-1-1-1-1-1 migration pattern. Complete genome sequences of the JH2019C603 virus were determined through full-length cDNA amplification. Phylogenetic analysis based on the amino acid (aa) sequences of RNA-dependent RNA Polymerase (Pol), Major subcore (T2) and Major core-surface (T13) showed that JH2019C603 clustered with Yonaguni orbivirus (YONOV) from Japan, with aa identities relative to YONOV of 97.7% (Pol), 99.0% (T2) and 98.5% (T13). However, phylogenetic analysis based on the aa sequences of the outer capsid protein one and two (OC1 and OC2) showed that JH2019C603 formed an independent branch in the phylogenetic tree, and its aa identity with YONOV was only 55.4% (OC1) and 80.8% (OC2), respectively. Compared with the prototype of YONOV, a notable sequence deletion was observed in the 3' non-coding region of NS1, with the NS1 of JH2019C603 encoded within segment 7 (Seg-7), in contrast to YONOV, which contains NS1 in Seg-6. These results indicate that JH2019C603 belongs to the YONOV lineage and might be a novel serotype or a highly variant strain of YONOV. These findings will facilitate the identification of new isolates and clarify their geographical distribution, epidemiology, genetic diversity and possible disease associations.


Assuntos
Orbivirus , Cricetinae , Bovinos , Animais , China , Filogenia , Sorogrupo , Sequência de Aminoácidos , Genoma Viral/genética , RNA Viral/genética
11.
Acta Pharmacol Sin ; 44(1): 19-31, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35840658

RESUMO

Inflammatory bowel disease (IBD) is a global health burden whose existing treatment is largely dependent on anti-inflammatory agents. Despite showing some therapeutic actions, their clinical efficacy and adverse events are unacceptable. Resolution as an active and orchestrated phase of inflammation involves improper inflammatory response with three key triggers, specialized pro-resolving mediators (SPMs), neutrophils and phagocyte efferocytosis. The formyl peptide receptor 2 (FPR2/ALX) is a human G protein-coupled receptor capable of binding SPMs and participates in the resolution process. This receptor has been implicated in several inflammatory diseases and its association with mouse model of IBD was established in some resolution-related studies. Here, we give an overview of three reported FPR2/ALX agonists highlighting their respective roles in pro-resolving strategies.


Assuntos
Doenças Inflamatórias Intestinais , Receptores de Formil Peptídeo , Animais , Camundongos , Humanos , Receptores de Formil Peptídeo/metabolismo , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/metabolismo , Neutrófilos/metabolismo , Doenças Inflamatórias Intestinais/tratamento farmacológico
12.
Environ Res ; 239(Pt 1): 117245, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37774999

RESUMO

The squeezed liquid from fruit and vegetable waste (LW) presents a unique wastewater challenge, marked by recalcitrance in treatment and amplified design risks with the application of conventional processes. Following coagulation of the squeezed liquid, the majority of particulate matter precipitates. The resulting precipitated floc (LWF) is reclaimed and subsequently utilized for the synthesis of biochar. The present study primarily explores the viability of repurposing LWF as biochar to enhance soil quality and mitigate N2O emissions. Findings indicate that the introduction of a 2% proportion of LWFB led to a remarkable 99.5% reduction in total N2O emissions in contrast to LWF. Concurrently, LWFB substantially enhanced nutrients content by elevating soil organic carbon (SOC) and nitrogen levels. Utilizing high-throughput sequencing in conjunction with qPCR, the investigation unveiled that the porous structure and substantial specific surface area of LWFB potentially fostered microbial adhesion and heightened diversity within the soil microbial community. Furthermore, LWFB notably diminished the relative abundance of AOB (Nitrosospira, Nitrosomonas), and NOB (Candidatus_Nitrotoga), thereby curbing the conversion of NH4+ into NO3-. The pronounced elevation in nosZ abundance implies that LWFB holds the potential to mitigate N2O emissions through a conversion to N2.


Assuntos
Microbiota , Solo , Solo/química , Carbono , Verduras , Frutas/química , Óxido Nitroso , Microbiologia do Solo
13.
J Nanobiotechnology ; 21(1): 95, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36932366

RESUMO

Clostridium perfringens ε-toxin (ETX) is the main toxin leading to enterotoxemia of sheep and goats and is classified as a potential biological weapon. In addition, no effective treatment drug is currently available in clinical practice for this toxin. We developed membrane-camouflaged nanoparticles (MNPs) with different membrane origins to neutralize ETX and protect the host from fatal ETX intoxication. We evaluated the safety and therapeutic efficacy of these MNPs in vitro and in vivo. Compared with membranes from karyocytes, such as Madin-Darby canine kidney (MDCK) cells and mouse neuroblastoma N2a cells (N2a cells), membrane from erythrocytes, which do not induce any immune response, are superior in safety. The protective ability of MNPs was evaluated by intravenous injection and lung delivery. We demonstrate that nebulized inhalation is as safe as intravenous injection and that both modalities can effectively protect mice against ETX. In particular, pulmonary delivery of nanoparticles more effectively treated the challenge of inhaled toxins than intravenously injected nanoparticles. Moreover, MNPs can alter the biological distribution of ETX among different organs in the body, and ETX was captured, neutralized and slowly delivered to the liver and spleen, where nanoparticles with ETX could be phagocytized and metabolized. This demonstrates how MNPs treat toxin infections in vivo. Finally, we injected the MNPs into mice in advance to find out whether MNPs can provide preventive protection, and the results showed that the long-cycle MNPs could provide at least a 3-day protection in mice. These findings demonstrate that MNPs provide safe and effective protection against ETX intoxication, provide new insights into membrane choices and delivery routes of nanoparticles, and new evidence of the ability of nanoparticles to provide preventive protection against infections.


Assuntos
Toxinas Bacterianas , Clostridium perfringens , Animais , Cães , Camundongos , Ovinos , Clostridium perfringens/metabolismo , Toxinas Bacterianas/metabolismo , Células Madin Darby de Rim Canino
14.
Int J Mol Sci ; 24(6)2023 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-36982489

RESUMO

Epsilon toxin (ETX), produced by type B and D strains of Clostridium perfringens, can cause fatal enterotoxaemia in ruminant animals, particularly sheep, cattle, and goats. Previous studies show that the cytotoxicity of ETX is dependent on the integrity of lipid rafts, the maintenance of which is ensured by cholesterol. Zaragozic acid (ZA) is a statin drug that reduces the synthesis of squalene, which is responsible for cholesterol synthesis. In this study, ZA significantly reduced the toxicity of ETX in Madin-Darby canine kidney (MDCK) cells. We show that ZA does not affect the binding of ETX to MDCK cells, but propidium iodide staining (PI) and Western blotting confirmed that ZA significantly disrupts the ability of ETX to form pores or oligomers in MDCK cells. Additionally, ZA decreased the phosphatidylserine exposure on the plasma membrane and increased the Ca2+ influx of the cells. Results of density gradient centrifugation suggest that ZA decreased the number of lipid rafts in MDCK membranes, which probably contributed to the attenuation of pore-formation. Moreover, ZA protected mice against ETX in vivo. All mice pre-treated with ZA for 48 h before exposure to an absolute lethal dose of ETX (6400 ng/kg) survived. In summary, these findings provide an innovative method to prevent ETX intoxication. Considering many pore-forming toxins require lipid rafts, we tested and found ZA also inhibited the toxicity of other toxins such as Clostridium perfringens Net B and ß-toxin (CPB) and Staphylococcus aureus α-hemolysin (Hla). We expect ZA can thus be developed as a broad-spectrum medicine for the treatment of multiple toxins. In addition, other statins, such as lovastatin (LO), also reduced the toxicity of ETX. These findings indicate that statin medicines are potential candidates for preventing and treating multiple toxin-induced diseases.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Animais , Cães , Camundongos , Ovinos , Bovinos , Inibidores de Hidroximetilglutaril-CoA Redutases/metabolismo , Células Madin Darby de Rim Canino , Membrana Celular/metabolismo , Clostridium perfringens/metabolismo
15.
J Proteome Res ; 21(2): 507-518, 2022 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-34969243

RESUMO

Targeted analysis of data-independent acquisition (DIA) data needs a spectral library, which is generated by data-dependent acquisition (DDA) experiments or directly from DIA data. A comparison of the DDA library and DIA library in analyzing DIA data has been reported. However, the effects of different spectral libraries on the analysis of diaPASEF data have not been investigated. Here, we generate different spectral libraries with varying proteome coverage to analyze parallel accumulation-serial fragmentation (diaPASEF) data. Besides, we also employ the library-free strategy. The library, constructed by extensive fractionation DDA experiments, produces the highest numbers of precursors and proteins but with a high percentage of missing values. The library-free strategy identifies 10-20% fewer proteins than the library-based method but with a high degree of data completeness. A further study shows that the library-free strategy, although it identifies fewer proteins than the library-based method, leads to similar biological conclusions as the library-based method.


Assuntos
Proteoma , Proteômica , Biblioteca de Peptídeos , Proteômica/métodos
16.
J Biol Chem ; 296: 100283, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33450224

RESUMO

Metabolic reprogramming provides transformed cells with proliferative and/or survival advantages. Capitalizing on this therapeutically, however, has been only moderately successful because of the relatively small magnitude of these differences and because cancers may further adapt their metabolism to evade metabolic pathway inhibition. Mice lacking the peroxisomal bifunctional enzyme enoyl-CoA hydratase/3-hydroxyacyl CoA dehydrogenase (Ehhadh) and supplemented with the 12-carbon fatty acid lauric acid (C12) accumulate the toxic metabolite dodecanedioic acid (DDDA), which causes acute hepatocyte necrosis and liver failure. We noted that, in a murine model of pediatric hepatoblastoma (HB) and in primary human HBs, downregulation of Ehhadh occurs in association with the suppression of mitochondrial ß- and endosomal/peroxisomal ω-fatty acid oxidation pathways. This suggested that HBs might be more susceptible than normal liver tissue to C12 dietary intervention. Indeed, HB-bearing mice provided with C12- and/or DDDA-supplemented diets survived significantly longer than those on standard diets. In addition, larger tumors developed massive necrosis following short-term DDDA administration. In some HBs, the eventual development of DDDA resistance was associated with 129 transcript differences, ∼90% of which were downregulated, and approximately two-thirds of which correlated with survival in numerous human cancers. These transcripts often encoded extracellular matrix components, suggesting that DDDA resistance arises from reduced Ehhadh uptake. Lower Ehhadh expression was also noted in murine hepatocellular carcinomas and in subsets of certain human cancers, supporting the likely generality of these results. Our results demonstrate the feasibility of C12 or DDDA dietary supplementation that is nontoxic, inexpensive, and likely compatible with more standard chemotherapies.


Assuntos
Ácidos Graxos/metabolismo , Hepatoblastoma/metabolismo , Neoplasias Hepáticas/metabolismo , Enzima Bifuncional do Peroxissomo/genética , Animais , Ácidos Dicarboxílicos/efeitos adversos , Ácidos Dicarboxílicos/farmacologia , Ácidos Graxos/genética , Hepatoblastoma/genética , Hepatoblastoma/patologia , Humanos , Fígado/enzimologia , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Metabolismo/genética , Camundongos , Camundongos Knockout , Mitocôndrias/genética , Mitocôndrias/metabolismo , Oxirredução , Peroxissomos/genética , Peroxissomos/metabolismo
17.
Small ; 18(36): e2200858, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35411651

RESUMO

Mesenchymal stem cells (MSCs) have a demonstrated value for acute liver failure (ALF) regeneration, while their delivery stratagems with long-term biological functions, low immune response, and high biocompatibility are still a challenge. Here, a lipopolysaccharide (LPS)-loaded photoresponsive cryogel porous microcarrier (CPM) for MSCs delivery and colonization is presented to promote defect liver regeneration. The CPMs are fabricated with graphene oxide, poly(N-isopropylacrylamide), and gelatin methacrylate (GelMA) via droplet microfluidic technology and a gradient-cooling procedure. Benefitting from the biocompatible GelMA component and the porous microstructure of the CPMs, MSCs can be nondestructively captured and abundantly delivered. Because the LPS can be released from the CPMs under NIR irradiation, the delivered MSCs are imparted with the feature of "trained immunity." Thus, when the MSCs-laden CPMs are tailored into the liver matched patches by bioprinting and applied in ALF rats, they display superior anti-inflammatory and more significant liver regeneration properties than the untrained MSCs. These features make the CPMs an excellent MSCs delivery system for clinical applications in tissue repair.


Assuntos
Bioimpressão , Falência Hepática Aguda , Células-Tronco Mesenquimais , Animais , Bioimpressão/métodos , Gelatina/química , Lipopolissacarídeos , Falência Hepática Aguda/terapia , Ratos
18.
Support Care Cancer ; 30(9): 7261-7269, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35596014

RESUMO

PURPOSE: China is currently one of the countries with the largest increased number of new cancer cases in the world, but cancer pain management (CPM) is still inadequate. This study uses a questionnaire to demonstrate the status and differences in knowledge, attitude and practice (KAP) of CPM among healthcare workers (HCWs) in developed regions of China, to find deficiencies and priorities for improvement, from which areas and advantages of the role of pharmacists and mobile devices can be explored. METHODS: This study used data from a questionnaire on CPM from March to June 2019. The study population consisted of a total of 515 HCWs in four first-tier developed cities in China. The questionnaire has four major components, analysis of differences in KAP of different occupations through one-way analysis of variance (ANOVA). RESULTS: Among the respondents, the physicians had the highest knowledge scores toward CPM, pharmacists had the lowest practice scores. Around half of the respondents indicated that their hospital or department have a pharmacist participating in CPM. Physicians and nurses were more likely to expect pharmacists to provide drug counseling. The HCWs interviewed most expect that the mobile-based pain management system can automatically screen and mark patients with pain. CONCLUSION: From this study, it can be suggested that pharmacists and nurses in the CPM team should actively promote relevant knowledge. Besides, pharmacists should focus on improving practical ability such as increasing the frequency of pain assessment. Multidisciplinary collaboration and the introduction of mobile devices can improve and refine the CPM.


Assuntos
Neoplasias , Médicos , Atitude do Pessoal de Saúde , Cidades , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Humanos , Manejo da Dor/psicologia , Farmacêuticos , Inquéritos e Questionários
19.
Sensors (Basel) ; 22(9)2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35591151

RESUMO

Ricin and abrin are phytotoxins that can be easily used as biowarfare and bioterrorism agents. Therefore, developing a rapid detection method for both toxins is of great significance in the field of biosecurity. In this study, a novel nanoforest silicon microstructure was prepared by the micro-electro-mechanical systems (MEMS) technique; particularly, a novel microfluidic sensor chip with a capillary self-driven function and large surface area was designed. Through binding with the double antibodies sandwich immunoassay, the proposed sensor chip is confirmed to be a candidate for sensing the aforementioned toxins. Compared with conventional immunochromatographic test strips, the proposed sensor demonstrates significantly enhanced sensitivity (≤10 pg/mL for both toxins) and high specificity against the interference derived from juice or milk, while maintaining good linearity in the range of 10-6250 pg/mL. Owing to the silicon nanoforest microstructure and improved homogeneity of the color signal, short detection time (within 15 min) is evidenced for the sensor chip, which would be helpful for the rapid tracking of ricin and abrin for the field of biosecurity.


Assuntos
Abrina , Ricina , Toxinas Biológicas , Abrina/análise , Microfluídica , Silício
20.
Saudi Pharm J ; 30(8): 1088-1094, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36164572

RESUMO

Introduction: Post-transplant diabetes mellitus (PTDM) is a known side effect in transplant recipients administered immunosuppressant drugs, such as tacrolimus. This study aimed to investigate the risk factors related to PTDM, and establish a risk prediction model for PTDM. In addition, we explored the effect of PTDM on the graft survival rate of kidney transplantation recipients. Methods: Patients with pre-diabetes mellitus before kidney transplant were excluded, and 495 kidney transplant recipients were included in our study, who were assigned to the non-PTDM and PTDM groups. The cumulative incidence was calculated at 3 months, 6 months, 1 year, 2 years, and 3 years post-transplantation. Laboratory tests were performed and the tacrolimus concentration, clinical prognosis, and adverse reactions were analyzed. Furthermore, binary logistic regression analysis was used to identify the independent risk factors of PTDM. Results: Age ≥ 45 years (adjusted odds ratio [aOR] 2.25, 95% confidence interval [CI] 1.14-3.92; P = 0.015), body mass index (BMI) > 25 kg/m2 (aOR 3.12, 95% CI 2.29-5.43, P < 0.001), tacrolimus concentration > 10 ng/mL during the first 3 months post-transplantation (aOR 2.46, 95%CI 1.41-7.38; P < 0.001), transient hyperglycemia (aOR 4.53, 95% CI 1.86-8.03; P < 0.001), delayed graft function (DGF) (aOR 1.31, 95% CI 1.05-2.39; P = 0.019) and acute rejection (aOR 2.16, 95% CI 1.79-4.69; P = 0.005) were identified as independent risk factors of PTDM. The PTDM risk prediction model was developed by including the above six risk factors, and the area under the receiver operating characteristic curve was 0.916 (95% CI 0.862-0.954, P < 0.001). Furthermore, the cumulative graft survival rate was significantly higher in the non- PTDM group than in the PTDM group. Conclusions: Risk factors related to PTDM were age ≥ 45 years, BMI > 25 kg/m2, tacrolimus concentration > 10 ng/mL during the first 3 months post-transplantation, transient hyperglycemia, DGF and acute rejection.

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