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1.
Food Chem ; 400: 134032, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36055145

RESUMO

The formation mechanism of heat-induced egg yolk granules (EYGs)/sodium alginate (SA) emulsion gel was studied under pH 6.2 and 7.5. Particle size, water holding capacity, LF NMR, and protein solubility revealed that pH 7.5 increased the surface charge of EYGs and enhanced non-covalent interaction with SA, and hydrogen bonding dominated of the gel formation process. Microscopy and rheological analysis indicated that samples with 0.75% SA had the smallest particle size and highest G', with chain-like oil droplets. Excess SA (1%) led to depletion flocculation due to SA structural rearrangements around oil droplets caused by the increase in negatively charged, causing uneven network structure. The in vitro release property and storage stability of ß-carotene loaded in the EYGs/SA emulsion gel showed that SA increased storage stability and decreased bioaccessibility of ß-carotene with delayed digestion rate. These results provide a theoretical basis for the nutrient delivery system in gel foods.

2.
Food Chem ; 399: 133991, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36037681

RESUMO

Fish oil develops particular off-odors, mainly fishy odor, from the oxidation of its characteristic fatty acids, docosahexaenoic (DHA) and eicosapentaenoic (EPA). Anchovy oil (AO) was taken as representative of fish oils. This was compared to three vegetable oils with different fatty acid compositions, i.e. camellia, sunflower and linseed oil, and differential volatile compounds were identified by static-headspace gas-chromatography ion-mobility-spectrometry (SHS-GC-IMS) and orthogonal partial-least-squares discriminant analysis (OPLS-DA) during oxidation at 60 °C. Three groups of differential volatile compounds detected at higher concentrations in the AO were screened out and two compounds, identified as 5-methylfurfural and 2-acetylfuran, were characteristic to the AO and not found in the vegetable oils. They were formed from both EPA and DHA, only present in the AO, and their formation mechanisms were proposed. The contents of 5-methylfurfural and 2-acetylfuran increased linearly with the oxidation time and consequently they could be used as oxidative markers of fish oils.


Assuntos
Quimiometria , Óleos de Peixe , Ácidos Graxos/análise , Óleos de Peixe/química , Furaldeído/análogos & derivados , Furanos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Óleos Vegetais
3.
Bioanalysis ; 14(5): 307-316, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35195039

RESUMO

Aim: HCP002, a phosphate-modified derivative of voriconazole, can improve solubility without using the nephrotoxic solubilizer, sulfobutylether-ß-cyclodextrin. To study pharmacokinetics in humans, LC-MS/MS methods to quantify HCP002 in human plasma and urine were developed and validated. Method: After protein precipitation by acetonitrile containing voriconazole-d3, HCP002 was separated on a ZORBAX SB-Aq column, and LCMS/MS analysis was performed in multi-response monitoring mode. Results: The analytical run time was 3 min. Linearity was observed over the ranges of 0.100-40.0 and 0.400-200 µg/ml in plasma and urine, respectively. Precision and accuracy were within acceptable limits. Sample stability was confirmed. Conclusion: Rapid and reproducible methods quantified HCP002 in urine, and plasma samples were established.


Assuntos
Plasma , Espectrometria de Massas em Tandem , Cromatografia Líquida/métodos , Humanos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
4.
Artigo em Inglês | MEDLINE | ID: mdl-36074968

RESUMO

Context: Severe acute pancreatitis (SAP) is a common critical illness, and stress hyperglycemia is the greatest independent risk factor for poor prognoses in critically ill patients. Enteral nutrition can not only provide an essential energy source for the body and improve a patient's intestinal micro-ecology but also can play a critical role in blood glucose management, especially for blood glucose variability. Objective: The study intended to investigate the effects of different enteral nutrition preparations, including a slow-release starch, on blood glucose variability, nutritional status, inflammatory indexes, and prognosis for patients with SAP with stress hyperglycemia. Design: The research team designed a retrospective analysis of SAP patients' data. Setting: The study took place in the Department of Critical Care Medicine at Ruijin Hospital of the Shanghai Jiao Tong University School of Medicine in Shanghai, China. Participants: Participants were 129 SAP patients with stress hyperglycemia, who had a random blood glucose of ≥11.1 mmol/L and who had been admitted to the department at the hospital between January 2013 and December 2018. Intervention: After the recovery of intestinal function, Patients were inserted a nasointestinal feeding tube below the ligament of Treitz to deliver enteral nutrition. According to the presence or absence of enteral nutrition preparations containing slow-release starch in the nutritional therapy, the research team divided patients into an intervention group (n = 63) that received a protein-based, enteral nutrition preparation containing slow-release starch and a control group (n = 66) that received a protein- or short-peptide-based, enteral nutrition preparation containing no slow-release starch. Outcome Measures: Postintervention for both groups, the research team measured the total amount of insulin used. At baseline and postintervention, the team measured for both groups: (1) the blood glucose variability: the average value of blood glucose (GLU AVE), standard deviation of blood glucose (GLU SD), coefficient of variation of blood glucose (GLU CV), large amplitude of glycemic excursions (GLU LAGE), and nutrition indicators-serum albumin (ALB), serum pre-albumin (PA), serum total protein (TP), and hemoglobin (HB); (2) the inflammatory markers: total amount of white blood cells (WBC), C-reactive protein (CRP), and procalcitonin (PCT); and (3) prognostic indicators: the length of ICU stay, total length of hospital stay, and 60-day and 90-day mortality. Results: The intervention group used significantly less insulin than the control group did, at 12.23 ± 6.74 and 35.31 ± 12.79 IU/d, respectively (P ≤ .05). Postintervention for 2 weeks, the blood glucose variability in the intervention group showed a decline. Between baseline and postintervention, the following significant decreases in blood glucose variability occurred for the group (P ≤ .05): (1) the GLU AVE from 14.27 ± 2.27 to 10.84 ± 1.97, (2) the GLU SD from 2.76 ± 1.48 to 2.15 ± 0.88, (3) the GLU CV from 20.1 ± 8.93 to 16.2 ± 3.61, and (4) the GLU LAGE from 7.9 ± 4.3 to 6.2 ± 2.5. Between baseline and postintervention, the following significant increases in blood glucose variability occurred for the control group (P ≤ .05): (1) the GLU AVE from 11.2 ± 2.3 to 12.1 ± 1.9, (2) the GLU SD from 1.9 ± 1.09 to 3.2 ± 1.0, (3) the GLU CV from 16.2 ± 6.2 to 19.6 ± 7.8, and (4) the GLU LAGE from 4.6 ± 2.6 to 5.0 ± 2.6. Postintervention, the GLU AVE, GLU SD, and GLU CV in the intervention group were significantly lower than those in the control group (p≤0.05). For nutritional indicators, the levels of ALB, PA, and TP in both groups significantly increased between baseline and postintervention (P ≤ .05), but HB didn't increase. However, no statistically significant differences existed between the groups (P > .05). For inflammatory markers, the total WBCs, CRP, and PCT in both groups significantly declined between baseline and postintervention (P ≤ .05). However, the decline in CRP in the intervention group was greater, from 154.5 ± 64.8 to 8.4 ± 6.8, than that of the control group, from 155.2 ± 88.4 to 15.6 ± 13.4, but no statistically significant differences existed between the groups (P > .05). The length of ICU stay and total length of hospital stay in the intervention group, from 53.9 ± 5.21 d and 74.7 ± 9.18 d, respectively, were significantly shorter than those in the control group, at 25.9 ± 4.89 and 43.6 ± 7.98 , respectively (P ≤ .05). The 60-day and 90-day mortality in the intervention group were significantly lower than those in the control group, at 0% and 0% compared to 2.8% and 6.9%, respectively (P ≤ .05). Conclusions: The application of enteral nutrition preparation containing sustained-release starch in treatment of SAP patients with stress hyperglycemia, may increase nutrition indicators quickly, significantly reduce blood glucose variability, improve inflammatory markers, shorten the length of ICU stay and hospital stay, and decrease the mortality.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36083369

RESUMO

Low-density polyethylene (LDPE) is a major cause of persistent and long-term environmental pollution. In this study, we report the successful isolation of an efficient LDPE degrading bacterial strain from the wastewater sediment of an agricultural land film recycling plant and identified and designated it as Acinetobacter sp. LW-1, respectively. The surface analyses including scanning electron microscopy (SEM) and atomic force microscopy (AFM) of LW-1-treated samples revealed the existence of appreciable pits and cavities on the facet of PE film, while the formation of carbonyl group was also verified by XPS and FTIR. Moreover, water contact angle assay substantiated the chemical transformation of the LDPE film from hydrophobic to hydrophilic transition after treatment with LW-1. In addition, co-incubation of LDPE film and Acinetobacter sp. LW-1 at 35 °C for 90 days significantly decreased the weight of LDPE film with an optimal weight loss of 15 ± 0.85%. This work enriches the LDPE degradation bacterial library and shows the tremendous potential of Acinetobacter sp. LW-1 to be used in the degradation of LDPE waste.

6.
Nano Lett ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36083803

RESUMO

Two dimensional Dion-Jacobson (2D DJ) perovskite has emerged as a potential photovoltaic material because of its unique optoelectronic characteristics. However, due to its low structural flexibility and high formation energy, extra assistance is needed during crystallization. Herein, we study the solvent effect on film formation and trap states of 2D DJ perovskite. It is found that the nucleation process of 2D DJ perovskite can be retarded by extra coordination, which is proved by in situ optical spectra. As a benefit, out-of-plane oriented crystallization and ordered phase distribution are realized. Finally, in 1,5-pentanediammonium (PeDA) based 2D DJ perovskite solar cells (PSCs), one of the highest reported open-circuit voltage (VOC) values of 1.25 V with state-of-the-art efficiency of 18.41% is obtained due to greatly shallowed trap states and suppressed nonradiative recombination. The device also exhibits excellent heat tolerance, which maintains 80% of its initial efficiency after being kept under 85 °C after 3000 h.

7.
Pathol Oncol Res ; 28: 1610401, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061145

RESUMO

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-mediated senescence-associated secretory phenotype (SASP) pathway has recently been identified in the suppression and promotion of cancers. However, its practical role in carcinogenesis remains to be comprehensively elucidated. Here, we describe an investigation analysing SASP activity and its correlations with DNA damage response (DDR), genomic mutations, and cell proliferation in gastric carcinogenesis among 30 cases with available endoscopic submucosal dissection (ESD) specimens of early neoplastic lesions (including low-grade dysplasia [LGD], high-grade dysplasia [HGD], and intramucosal carcinoma). The positive cells of senescence-associated ß-galactosidase staining and cGAS, STING, interferon-regulatory factor 3 (IRF3), and signal transducer and activator of transcription 6 (STAT6) expression levels using immunostaining were elevated in HGD and in cancers. Similarly, increased expression of the Fanconi anemia group D2 (FANCD2) protein, tumour suppressor p53 binding protein 1 (TP53BP1), and replication protein A (RPA2) (i.e., primary DDR factors) was detected in HGD and in cancers; these increased expression levels were closely correlated with high expression of Ki67 and minichromosome maintenance complex component 7 (MCM7) proteins. Moreover, genomic mutations in TP53 gene were detected in 56.67% of the evaluated cases (17/30) using next-generation sequencing, and positive staining was verified in HGD and in cancers. Statistical analysis revealed that cell proliferation closely correlated with the expression of DDR factors, of which TP53BP1 was positively associated with SASP factors and IRF3 was positively correlated with cell proliferation. In addition, an analysis evaluating clinical features demonstrated that STAT6-positive cases showed a longer progression-free survival time than STAT6-negative cases. Our evaluation, conducted using a limited number of specimens, suggests SASP may be prevalent in early gastric neoplastic lesions and could be activated by accelerated cell proliferation-induced DDR. The clinical significance of SASP still needs to be determined.


Assuntos
Senescência Celular , Neoplasias , Carcinogênese , Proliferação de Células/genética , Senescência Celular/genética , Dano ao DNA/genética , Humanos , Proteínas de Membrana , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo
8.
Front Nutr ; 9: 926429, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36071934

RESUMO

Fatty acid (FA) in breast milk is beneficial to the growth and neurodevelopment of infants. However, the structure profiles of breast milk FAs and the influencing factors which are crucial for normal function have not been fully elucidated. This study aimed to characterize the profiles of total and sn-2 FAs in human mature milk based on two representative urban areas in China and explore potential sociodemographic determinants. Mothers (n = 70) at 40-100 d postpartum from Beijing and Danyang were recruited according to unified inclusion and exclusion criteria. Total and sn-2 FA compositions were examined by gas chromatography and quantified. Using the Spearman correlation and multiple regression model, we found that the location and maternal education level were the most conspicuous correlated factor. The milk of mothers from Beijing had higher levels of the n-6 series of long-chain polyunsaturated fatty acids (LCPUFA) (C20:2, C20:3n-6, C20:4n-6, n-6PUFA/n-3PUFA, LA/ALA, and ARA/DHA) than that of Danyang, while the opposite was observed in the n-3 series of LCPUFA (C18:3n-3 and Total n-3PUFA). Compared to the milk of mothers with a high school degree or below, those with a bachelor's degree or above had lower SFAs (C10:0, C12:0, C14:0, and Total SFA), n-3 series of LCPUFA (C18:3n-3 and Total n-3PUFA), C18:1n-9t, and higher n-6 series of LCPUFA (C18:2n-6c, C20:2, C20:4n-6, Total n-6PUFA, and n-6PUFA/n-3PUFA). Maternal age, infant gender, pre-conception body mass index (BMI), parity, delivery mode, and gestational weight gain were also associated with total FAs. However, fewer associations were found between the above factors and sn-2 FAs. This study will promote an understanding of human breast milk's lipid profile and help develop a formula more suitable for infants.

10.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(4): 678-685, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36065702

RESUMO

MicroRNAs,a group of short non-coding RNAs that regulate gene expression at post-transcriptional level,play a role in a variety of cell activities.Methylation is an essential topic in the study of transcriptional regulation at the genomic level.It is associated with diverse diseases such as tumor and aging by regulating gene expression and silencing.Studies have demonstrated that the abnormal methylation of miRNA can regulate the expression of miRNA and affect the expression and function of the target genes,which is a key signal for the occurrence and development of hepatocellular carcinoma.This research achievement provides a new idea for deciphering the molecular mechanism of the pathogenesis of hepatocellular carcinoma and exploring the therapeutic targets.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Regulação da Expressão Gênica , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Metilação , MicroRNAs/genética , MicroRNAs/metabolismo
11.
Mol Med Rep ; 26(5)2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36069225

RESUMO

Tanshinone IIA (Tan 2A) is a lipid­soluble compound extracted from the Chinese herb Danshen (Salvia miltiorrhiza Bunge). It protects neuron and microvascular endothelial cells against hypoxia/ischemia both in vitro and in vivo however the mechanism is not fully known. Glucose transporter 1 (GLUT­1) is ubiquitously expressed in all types of tissue in the human body and serves important physiological functions due to its glucose uptake ability. The present study evaluated the role of Tan 2A in regulating GLUT­1 expression and its potential mechanism. RT­PCR and western Blot were used to detect the expression of GLUT­1. Si RNA mediated knockdown and CHIP assay were used to explore the mechanism of Tan 2A on GLUT­1expression. Tan 2A treatment induced expression of GLUT­1 and subsequently increased glucose uptake in endothelial cells (ECs). Furthermore, mRNA expression levels of vascular endothelial cell growth factor, BCL2 interacting protein 3 and enolase 2, which are target genes for hypoxia­inducible factor­1α (HIF­1α), were significantly upregulated by Tan 2A. Co­immunoprecipitation demonstrated that Tan 2A markedly increased the association of HIF­1α with recombination signal­binding protein for immunoglobulin κJ region (RBPJκ). Moreover, knockdown of HIF­1α and RBPJκ significantly reversed the regulatory effect of Tan 2A on mRNA expression levels of these genes in ECs. The results of the present study suggested that HIF­1α partially mediated the regulatory effect of Tan 2A on GLUT­1 expression in ECs. Therefore, GLUT­1 may be a potential therapeutic target for Tan 2A.


Assuntos
Células Endoteliais , Salvia miltiorrhiza , Abietanos , Células Endoteliais/metabolismo , Glucose/metabolismo , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Humanos , RNA Mensageiro/metabolismo , Salvia miltiorrhiza/química , Transdução de Sinais , Triacetonamina-N-Oxil/metabolismo , Triacetonamina-N-Oxil/farmacologia
12.
Front Oncol ; 12: 929037, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052258

RESUMO

Breast cancer is the most common female malignancy, but the mechanisms regulating gene expression leading to its development are complex. In recent years, as epigenetic research has intensified, RNA-binding proteins (RBPs) have been identified as a class of posttranscriptional regulators that can participate in regulating gene expression through the regulation of RNA stabilization and degradation, intracellular localization, alternative splicing and alternative polyadenylation, and translational control. RBPs play an important role in the development of normal mammary glands and breast cancer. Functional inactivation or abnormal expression of RBPs may be closely associated with breast cancer development. In this review, we focus on the function and regulatory mechanisms of RBPs in breast cancer, as well as the advantages and challenges of RBPs as potential diagnostic and therapeutic targets in breast cancer, and discuss the potential of RBPs in clinical treatment.

13.
Front Pediatr ; 10: 972032, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052359

RESUMO

Objective: Hydrocephalus in bacterial meningitis (BM) is a devastating infectious neurological disease and the proteins and pathways involved in its pathophysiology are not fully understood. Materials and methods: Label-free quantitative (LFQ) proteomics analyses was used to identify differentially expressed proteins (DEPs) in cerebrospinal fluid (CSF) samples from infants with hydrocephalus and bacterial meningitis (HBM group, N = 8), infants with bacterial meningitis (BM group, N = 9); and healthy infants (N group, N = 11). Bioinformatics analysis was subsequently performed to investigate Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enriched signaling pathways of these DEPs. Six proteins (AZU1, COX4I1, EDF1, KRT31, MMP12, and PRG2) were selected for further validation via enzyme-linked immunosorbent assay (ELISA). Results: Compared with BM group and N group, HBM group had a higher whole CSF protein level (5.6 ± 2.7 vs. 1.7 ± 1.0 vs. 1.2 ± 0.5 g/l) and lower whole CSF glucose level (0.8 ± 0.6 vs. 1.8 ± 0.7 vs. 3.3 ± 0.8 mmol/l) (both P < 0.05). Over 300 DEPs were differentially expressed in HBM group compared with BM group and BM compared with N group, of which 78% were common to both. Cluster analysis indicated that the levels of 226 proteins were increased in BM group compared with N group and were decreased in HBM group compared with BM group. Bioinformatics analysis indicated the involvement of the cell adhesion, immune response and extracellular exosome signaling were significantly enriched in HBM compared with BM group and BM compared with N group. 267 DEPs were identified between HBM group with N group, KEGG analysis indicated that DEPs mainly involved in filament cytoskeleton and immune response. The ELISA results further verified that the expression levels of AZU1 were significantly different from among three groups (both P < 0.05). Conclusion: This is the first reported characterization of quantitative proteomics from the CSF of infants with HBM. Our study also demonstrated that AZU1 could be a potential biomarker for the diagnosis of hydrocephalus in bacterial meningitis.

14.
Adv Nutr ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36083999

RESUMO

Reported breast milk lipid concentrations may vary with geographical region, postnatal age and year of sample collection. In this review, we summarized data on the concentrations of total fat, total phospholipids, cholesterol and fatty acids in human milk worldwide and their variation according to lactation stage, study area and sample collection year. A systematic literature search was performed using the PubMed, Embase, Web of Science and Medline databases for English language papers and Wanfang and China National Knowledge Infrastructure databases for Chinese language papers. A total of 186 studies evaluating the human milk lipid profiles were included. According to random effects models based on worldwide data, the summarized means (95% confidence intervals) as percentages of total fat were 42.2% (41.1%, 43.3%) for saturated fatty acids (SFAs), 36.6% (35.6%, 37.5%) for monounsaturated fatty acids (MUFAs) and 21.0% (19.3%, 22.7%) for polyunsaturated fatty acids (PUFAs). However, the study heterogeneity was high for most types of fatty acids (I2 > 99%). Human milk from western countries had higher concentrations of MUFAs and 18:1n-9, but lower concentrations of PUFAs, 18:2n-6, 20:4n-6, 18:3n-3, 20:5n-3, 22:6n-3 and total n-6PUFA in compared with those from non-western countries (P: <0.001-0.011). Significant lactation stage differences were observed for total fat and some individual fatty acids. The concentrations of SFAs and 16:0 were significantly negatively correlated with sampling year (P < 0.001-0.028). In contrast, a significant positive correlation between the concentrations of 18:2n-6 and 18:3n-3 and sampling year was observed (P < 0.001-0.035). Our results suggest that the pooling of data on human milk lipid profiles in different studies should be done with caution due to the high between-study heterogeneity. The concentration of lipids, including total fat, cholesterol and specific fatty acids, differs in human milk according to lactation stage, geographical region and year of sample collection.

15.
Semin Cancer Biol ; 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36084815

RESUMO

Brain cancer is an aggressive type of cancer with poor prognosis. While the immune system protects against cancer in the early stages, the tumor exploits the healing arm of inflammatory reactions to accelerate its growth and spread. Various immune cells penetrate the developing tumor region, establishing a pro-inflammatory tumor milieu. Additionally, tumor cells may release chemokines and cytokines to attract immune cells and promote cancer growth. Inflammation and its associated mechanisms in the progression of cancer have been extensively studied in the majority of solid tumors, especially brain tumors. However, treatment of the malignant brain cancer is hindered by several obstacles, such as the blood-brain barrier, transportation inside the brain interstitium, inflammatory mediators that promote tumor growth and invasiveness, complications in administering therapies to tumor cells specifically, the highly invasive nature of gliomas, and the resistance to drugs. To resolve these obstacles, nanomedicine could be a potential strategy that has facilitated advancements in diagnosing and treating brain cancer. Due to the numerous benefits provided by their small size and other features, nanoparticles have been a prominent focus of research in the drug-delivery field. The purpose of this article is to discuss the role of inflammatory mediators and signalling pathways in brain cancer as well as the recent advances in understanding the nano-carrier approaches for enhancing drug delivery to the brain in the treatment of brain cancer.

16.
Phytother Res ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36086852

RESUMO

Resveratrol (Resv) has antitumorigenic and antimetastatic activities; however, the molecular mechanisms underlying the inhibitory effects of Resv on the invasion and metastasis of breast cancer cells are still a subject of debate. In our study, we demonstrated that Resv inhibited tumor cell proliferation and tumor growth. It also suppressed invasion and pulmonary metastasis of breast cancer by reversing the transforming growth factor beta 1 (TGF-ß1)-mediated EMT process. Meanwhile, the anticarcinogenic effects of Resv were abolished by the autophagy blocker 3-methyladenine (3-MA) or Beclin 1 small interfering RNA. Moreover, Resv upregulated autophagy-related genes and protein levels and induced the formation of autophagosomes in 4T1 breast cancer cells and xenograft mice, suggesting that autophagy was involved in the anticarcinogenic activities of Resv in both models. In addition, Resv-induced autophagy by increasing the expression of SIRT3 and phosphorylated AMPK. SIRT3 knockdown reduced AMPK phosphorylation and autophagy-related proteins levels, and suppressed the anticancer effects of Resv, demonstrating that the inhibitory effects of Resv on tumor progression were mediated via the SIRT3/AMPK/autophagy pathway. Taken together, our study provided novel insight into the anticancer effects of Resv and revealed that targeting the SIRT3/AMPK/autophagy pathway can serve as a new therapeutic target against breast cancer.

17.
Kidney Int ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36087808

RESUMO

IgA nephropathy (IgAN) is characterized by deposition of galactose-deficient IgA1 (Gd-IgA1) in glomerular mesangium associated with mucosal immune disorders. Since environmental pollution has been associated with the progression of chronic kidney disease in the general population, we specifically investigated the influence of exposure to fine particulate matter less than 2.5µm in diameter (PM2.5) on IgAN progression. Patients with biopsy-proven primary IgAN were recruited from seven Chinese kidney centers. PM2.5 exposure from 1998 to 2016 was derived from satellite aerosol optical depth data and a total of 1,979 patients with IgAN, including 994 males were enrolled. The PM2.5 exposure levels for patients from different provinces varied but, in general, the PM2.5 exposure levels among patients from the north were higher than those among patients from the south. The severity of PM2.5 exposure in different regions was correlated with regional kidney failure burden. In addition, each 10 µg/m3 increase in annual average concentration of PM2.5 exposure before study entry (Hazard Ratio, 1.14; 95% confidence interval, 1.06-1.22) or time-varying PM2.5 exposure after study entry (1.10; 1.01-1.18) were associated with increased kidney failure risk after adjustment for age, gender, estimated glomerular filtration rate, urine protein, uric acid, hemoglobin, mean arterial pressure, Oxford classification, glucocorticoid and renin-angiotensin system blocker therapy. The associations were robust when the time period, risk factors of cardiovascular diseases or city size were further adjusted on the basis of the above model. Thus, our results suggest PM2.5 is an independent risk factor for kidney failure in patients with IgAN but these findings will require validation in more diverse populations and other geographic regions.

18.
Mikrochim Acta ; 189(10): 368, 2022 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057018

RESUMO

Upconversion nanoparticles (UCNPs) represent a group of NPs that can convert near-infrared (NIR) light into ultraviolet and visible light, thus possess deep tissue penetration power with less background fluorescence noise interference, and do not induce damage to biological tissues. Due to their unique optical properties and possibility for surface modification, UCNPs can be exploited for concomitant antigen delivery into dendritic cells (DCs) and monitoring by molecular imaging. In this study, we focus on the development of a nano-delivery platform targeting DCs for immunotherapy and simultaneous imaging. OVA 254-267 (OVA24) peptide antigen, harboring a CD8 T cell epitope, and Pam3CysSerLys4 (Pam3CSK4) adjuvant were chemically linked to the surface of UCNPs by amide condensation to stimulate DC maturation and antigen presentation. The OVA24-Pam3CSK4-UCNPs were thoroughly characterized and showed a homogeneous morphology and surface electronegativity, which promoted a good dispersion of the NPs. In vitro experiments demonstrated that OVA24-Pam3CSK4-UCNPs induced a strong immune response, including DC maturation, T cell activation, and proliferation, as well as interferon gamma (IFN-γ) production. In vivo, highly sensitive upconversion luminescence (UCL) imaging of OVA24-Pam3CSK4-UCNPs allowed tracking of UCNPs from the periphery to lymph nodes. In summary, OVA24-Pam3CSK4-UCNPs represent an effective tool for DC-based immunotherapy.


Assuntos
Nanopartículas , Células Dendríticas , Luz , Luminescência , Imagem Molecular , Nanopartículas/química
19.
Nat Commun ; 13(1): 5278, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36075892

RESUMO

Polygenic risk scores (PRS) have been successfully developed for the prediction of human diseases and complex traits in the past years. For drug response prediction in randomized clinical trials, a common practice is to apply PRS built from a disease genome-wide association study (GWAS) directly to a corresponding pharmacogenomics (PGx) setting. Here, we show that such an approach relies on stringent assumptions about the prognostic and predictive effects of the selected genetic variants. We propose a shift from disease PRS to PGx PRS approaches by simultaneously modeling both the prognostic and predictive effects and further make this shift possible by developing a series of PRS-PGx methods, including a novel Bayesian regression approach (PRS-PGx-Bayes). Simulation studies show that PRS-PGx methods generally outperform the disease PRS methods and PRS-PGx-Bayes is superior to all other PRS-PGx methods. We further apply the PRS-PGx methods to PGx GWAS data from a large cardiovascular randomized clinical trial (IMPROVE-IT) to predict treatment related LDL cholesterol reduction. The results demonstrate substantial improvement of PRS-PGx-Bayes in both prediction accuracy and the capability of capturing the treatment-specific predictive effects while compared with the disease PRS approaches.


Assuntos
Estudo de Associação Genômica Ampla , Farmacogenética , Teorema de Bayes , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Humanos , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco
20.
BMC Genomics ; 23(1): 638, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36076187

RESUMO

BACKGROUND: The strawberry fleshy fruit is actually enlarged receptacle tissue, and the successful development of the embryo and endosperm is essential for receptacle fruit set. MicroRNAs (miRNAs) and phased small interfering RNAs (phasiRNAs) play indispensable regulatory roles in plant growth and development. However, miRNAs and phasiRNAs participating in the regulation of strawberry embryo and endosperm development have yet to be explored. RESULTS: Here, we performed genome-wide identification of miRNA and phasiRNA-producing loci (PHAS) in strawberry seeds with a focus on those involved in the development of the early embryo and endosperm. We found that embryos and endosperm have different levels of small RNAs. After bioinformatics analysis, the results showed that a total of 404 miRNAs (352 known and 52 novel) and 156 PHAS genes (81 21-nt and 75 24-nt genes) could be found in strawberry seed-related tissues, of which four and nine conserved miRNA families displayed conserved expression in the endosperm and embryo, respectively. Based on refined putative annotation of PHAS loci, some auxin signal-related genes, such as CM3, TAR2, AFB2, ASA1, NAC and TAS3, were found, which demonstrates that IAA biosynthesis is important for endosperm and embryo development during early fruit growth. Additionally, some auxin signal-related conserved (miR390-TAS3) and novel (miR156-ASA1) trigger-PHAS pairs were identified. CONCLUSIONS: Taken together, these results expand our understanding of sRNAs in strawberry embryo and endosperm development and provide a genomic resource for early-stage fruit development.


Assuntos
Fragaria , MicroRNAs , Endosperma/genética , Endosperma/metabolismo , Regulação da Expressão Gênica de Plantas , Humanos , Ácidos Indolacéticos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Interferente Pequeno/genética
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