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1.
Biomed Res Int ; 2021: 4822383, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337012

RESUMO

Objective: Discectomy remains the classic procedure for treating lumbar intervertebral disc (IVD) herniation, but the occurrence of defects after discectomy is thought to be an important cause generating recurrent and accelerated IVD degeneration. Previous studies attempted suture of the annulus fissure, but the validity of this technique on restraining the degenerative process is controversial. On the other hand, cell therapies have been shown in multiple clinical and basic studies. Our purpose was to investigate the effectiveness of selective retention of autologous Bone Marrow Stromal Cells (BMSCs) with gelatin sponge in combination with annulus fibrosus suture (AFS) for the repair of IVD defects following mobile microendoscopic discectomy (MMED). Methods: This prospective, two-armed, and controlled clinical study was conducted from December 2016 to December 2018. Written informed consent was obtained from each patient. Forty-five patients with typical symptoms, positive signs of radiculopathy, and obvious lumbar disc herniation observed by MRI were enrolled. Patients were divided into 3 groups with different treating methods: MMED (n = 15), MMED+AFS (n = 15), and MMED+AFS+BMSCs (n = 15). A postoperative 2-year follow-up was performed to evaluate the patient-reported outcomes of VAS, ODI, and SF-36. The improvement rate of VAS and ODI was calculated as [(latest-preoperative)/preoperative] to evaluate the therapeutic effect of the three groups. Assessment parameters included Pfirrmann grade, intervertebral disc height (IDH), and disc protrusion size (DPS), as measured by MRI to evaluate the morphological changes. Results: All patients enrolled had a postoperative follow-up at 3, 6, 12, and 24 months. VAS and ODI scores were significantly improved compared to the preoperative status in all three groups with a mean DPS reduction rate over 50%. At the final follow-up, the improvement rate of the VAS score in the MMED+AFS+BMSCs group was significantly higher than the MMED+AFS and MMED groups (80.1% ± 7.6% vs. 71.3% ± 7.0% vs. 70.1% ± 7.8%), while ODI improvement showed a significant change (65.6% ± 8.8% vs. 59.9% ± 5.5% vs. 57.8% ± 8.1%). All participants showed significant improvement in SF-36 PCS and MCS; the differences between each group were not significant. The mean IDH loss rate of the MMED+AFS+BMSCs group was also significantly lower than other groups (-17.2% ± 1.3% vs. -27.6% ± 0.7% vs. -29.3% ± 2.2%). The Pfirrmann grade was aggravated in the MMED and MMED+AFS groups while maintained at the preoperative grade in the MMED+AFS+BMSCs group. No adverse events of cell transplantation or recurrence were found in all patients during the postoperative follow-up period. Conclusions: It is feasible and effective to repair lumbar IVD defects using SCR-enriched BMSCs with gelatin sponges, which warrants further study and development as a cell-based therapy for IVD repair.

2.
Transfus Apher Sci ; : 103201, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34238707

RESUMO

BACKGROUND: Multiple factors contribute to anemia in patients with Hepatitis B virus (HBV)related acute-on-chronic liver failure (ACLF); however, the mechanism is unclear. The purpose of this study was to evaluate the clinical significance of the direct antiglobulin test (DAT) in patients with HBV related ACLF. METHODS: DAT was used to detect immunoglobulins and/or complement proteins on the surface of erythrocytes. RESULTS: We recruited 78 HBV-associated ACLF patients, 30 chronic hepatitis B(CHB)patients and 40 healthy people between October 2015 and May 2016. In HBV related ACLF patients, the hemoglobin concentration, number of erythrocytes, and hematocrit value were significantly lower, while the erythrocyte distribution width was significantly higher, compared to patients with CHB and healthy controls (HCs) (P < 0.001). The rates of DAT positivity in HBV related ACLF patients, CHB patients, and HCs were 62.8 %, 13.3 %, and 0%, respectively. DAT-positive ACLF patients exhibited lower Hb levels, older average age, as well as higher total bilirubin, alanine aminotransferase, and complement component 3 levels compared to DAT-negative patients. CONCLUSIONS: HBV related ACLF patients showed significant alterations in erythrocyte parameters, possibly reflecting disease development and severity. The high presence of erythrocyte autoantibodies suggested that immunologic clearance of erythrocytes contributed to multifactorial anemia in HBV related ACLF patients.

3.
ChemSusChem ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34236142

RESUMO

An important step of the great achievement of organic solar cells in power conversion efficiency is the development of low-band gap polymer donors, PBDB-T derivatives, which present interesting aggregation effects dominating the device performance. The aggregation of polymers can be manipulated by a series of variables from a materials design and processing conditions perspective; however, optimization of film quality is a time- and energy-consuming work. Here, we introduce a robot-based high-throughput platform (HTP) that is offering automated film preparation and optical spectroscopy thin-film characterization in combination with an analysis algorithm. PM6 films are prepared by the so-called spontaneous film spreading (SFS) process, where a polymer solution is coated on a water surface. Automated acquisition of UV/Vis and photoluminescence (PL) spectra and automated extraction of morphological features is coupled to Gaussian Process Regression to exploit available experimental evidence for morphology optimization but also for hypothesis formulation and testing with respect to the underlying physical principles. The integrated spectral modeling workflow yields quantitative microstructure information by distinguishing amorphous from ordered phases and assesses the extension of amorphous versus the ordered domains. This research provides an easy to use methodology to analyze the exciton coherence length in conjugated semiconductors and will allow to optimize exciton splitting in thin film organic semiconductor layers as a function of processing.

4.
Sci Total Environ ; 795: 148926, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34328948

RESUMO

In this paper, a combination of catalyst sample evaluation and vehicle test is used to deeply study the formation mechanism of ammonia in the process of three-way catalytic reaction, and further explore the influence of catalyst formulation and aging on ammonia emissions. The catalytic sample test shows that CO reacts with terminal hydroxyl and bridging hydroxyl on the surface of the catalyst to generate H2 at low temperature, which then reduces NO to generate NH3. At high temperatures, CO reacts with water to generate H2, or hydrocarbon compounds in exhaust react with steam to generate hydrogen, and then H2 reacts with nitrogen oxides to generate NH3. On the one hand, the presence of water vapor can be prompted catalytic hydroxylation of materials and promote the reaction of the hydroxyl and bridging hydroxyl to improve the selectivity of NH3, on the other hand, as the competitive adsorption of H2O molecules and NO on the catalyst surface inhibits the reduction reaction between NH3 and NO, the consumption of NH3 molecules is reduced, and more NH3 vaporizes from the catalyst surface to the gas phase. The combination of Pd/Rh can effectively reduce the NH3 generation compared with the single Pd formulation. Ammonia emission can be effectively reduced by precisely controlling the air-fuel ratio of the engine and combining it with the catalytic converter which optimizes the ratio of precious metals.

5.
J Hazard Mater ; 418: 126355, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34329014

RESUMO

Landfill leachate is produced from garbage decomposition with highly toxic and bio-refractory compounds, which poses serious harm to environmental security and human health. Thus, it is urgent to treat landfill leachate properly. Persulfate (PS) oxidation has attracted extensive attentions in terms of fast reaction speed, non-selectivity to target pollutants and thorough oxidation. In recent years, PS oxidation has been widely adopted for landfill leachate purification. However, the related results have been rarely summarized. In this review, the treatment of landfill leachate by PS oxidation system is discussed systematically including oxidants, activation modes and oxidation mechanisms. In addition, the current situation of PS oxidation system and other coupled systems for landfill leachate treatment is also summarized. Finally, the challenges and future research directions of landfill leachate treatment based on PS oxidation process are proposed. Meaningfully, this review will provide valuable references for the development of landfill leachate treatment process, promoting the application of advanced oxidation technology in landfill leachate treatment.

6.
Molecules ; 26(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34205154

RESUMO

The genus Curculigo, as a folk herbal medicine, has been used for many years in China, treating impotence, limb limpness, and arthritis of the lumbar and knee joints. The last systematic review of the genus Curculigo was written in 2013, scientifically categorizing the phytochemistry and biological activities. Hitherto, the original compounds and their pharmacological activities were presented as the development of this genus, but there is not an updated review. To conclude the progression of the genus Curculigo, we collected the new literature published from 2013 to 2021 in PubMed, Web of Science, Google Scholar databases, and the Chinese National Knowledge Infrastructure. The novel chlorophenolic glucosides, curculigine, phenolic glycosides, orcinosides and polysaccharides were isolated from Curculigo. The new analyzing methods were established to control the quality of Curculigo as a herbal medicine. In addition, the pharmacological effects of Curculigo focused on anti-diabetes, antibacterial, anti-inflammatory, osteoporosis, antioxidation, etc. The antitumor and neuroprotective activities were newly explored in recent years. The application of herbal medicine was gradually developed in scientific methods. The medicinal value of the genus Curculigo needs to further investigate its pharmacological mechanisms. This new review offers more insights into the exploitation of the pharmacological value of the genus Curculigo.


Assuntos
Curculigo/química , Compostos Fitoquímicos/química , Etnofarmacologia , Glucosídeos/química , Glucosídeos/farmacologia , Lignanas/química , Lignanas/farmacologia , Compostos Fitoquímicos/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia
7.
Exp Biol Med (Maywood) ; : 15353702211027116, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34225474

RESUMO

The soluble form of the suppression of tumorigenicity-2 (sST2) is a biomarker for risk classification and prognosis of heart failure, and its production and secretion in the alveolar epithelium are significantly correlated with the inflammation-inducing in pulmonary diseases. However, the predictive value of sST2 in pulmonary disease had not been widely studied. This study investigated the potential value in prognosis and risk classification of sST2 in patients with community-acquired pneumonia. Clinical data of ninety-three CAP inpatients were retrieved and their sST2 and other clinical indices were studied. Cox regression models were constructed to probe the sST2's predictive value for patients' restoring clinical stability and its additive effect on pneumonia severity index and CURB-65 scores. Patients who did not reach clinical stability within the defined time (30 days from hospitalization) have had significantly higher levels of sST2 at admission (P < 0.05). In univariate and multivariate Cox regression analysis, a high sST2 level (≥72.8 ng/mL) was an independent reverse predictor of clinical stability (P < 0.05). The Cox regression model combined with sST2 and CURB-65 (AUC: 0.96) provided a more accurate risk classification than CURB-65 (AUC:0.89) alone (NRI: 1.18, IDI: 0.16, P < 0.05). The Cox regression model combined with sST2 and pneumonia severity index (AUC: 0.96) also provided a more accurate risk classification than pneumonia severity index (AUC:0.93) alone (NRI: 0.06; IDI: 0.06, P < 0.05). sST2 at admission can be used as an independent early prognostic indicator for CAP patients. Moreover, it can improve the predictive power of CURB-65 and pneumonia severity index score.

8.
Gigascience ; 10(7)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34282453

RESUMO

BACKGROUND: Uncovering the genetic architecture of economic traits in pigs is important for agricultural breeding. However, high-density haplotype reference panels are unavailable in most agricultural species, limiting accurate genotype imputation in large populations. Moreover, the infinitesimal model of quantitative traits implies that weak association signals tend to be spread across most of the genome, further complicating the genetic analysis. Hence, there is a need to develop new methods for sequencing large cohorts without large reference panels. RESULTS: We describe a Tn5-based highly accurate, cost- and time-efficient, low-coverage sequencing method to obtain 11.3 million whole-genome single-nucleotide polymorphisms in 2,869 Duroc boars at a mean depth of 0.73×. On the basis of these single-nucleotide polymorphisms, a genome-wide association study was performed, resulting in 14 quantitative trait loci (QTLs) for 7 of 21 important agricultural traits in pigs. These QTLs harbour genes, such as ABCD4 for total teat number and HMGA1 for back fat thickness, and provided a starting point for further investigation. The inheritance models of the different traits varied greatly. Most follow the minor-polygene model, but this can be attributed to different reasons, such as the shaping of genetic architecture by artificial selection for this population and sufficiently interconnected minor gene regulatory networks. CONCLUSIONS: Genome-wide association study results for 21 important agricultural traits identified 14 QTLs/genes and showed their genetic architectures, providing guidance for genetic improvement harnessing genomic features. The Tn5-based low-coverage sequencing method can be applied to large-scale genome studies for any species without a good reference panel and can be used for agricultural breeding.

9.
J BUON ; 26(3): 875-881, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268948

RESUMO

PURPOSE: We aimed to investigate the effect of celecoxib on rats with liver cancer through the extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/p38 pathway. METHODS: Sprague-Dawley rats (n=36) were divided into 3 groups (n=12 per group) randomly. In model group, the liver cancer model was established, and normal saline was intraperitoneally injected. In celecoxib group, the liver cancer model was also established, and celecoxib was intraperitoneally injected. After intervention for 30 d, the samples were taken. The body weight of rats was measured before modeling and before sampling. The morphology of liver tissues was observed via hematoxylin-eosin (HE) staining, the expressions of related proteins and messenger ribonucleic acids (mRNAs) were determined via Western blotting and quantitative polymerase chain reaction (qPCR), respectively, and the protein expressions of cysteinyl aspartate specific proteinase 3 (Caspase3) and Cyclin D1 in liver tissues were detected. RESULTS: Before modeling, there was no difference in t.

10.
Anal Chem ; 93(27): 9549-9558, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34196532

RESUMO

Antibody-drug conjugates (ADCs) are biopharmaceuticals for the targeted delivery of antitumor agents. ADCs can be highly heterogeneous with various drug-to-antibody ratio (DAR) species, conjugation sites, and occupancy levels. The conjugation site can modulate the ADC stability and efficacy and therefore can be considered to be a critical quality attribute (CQA) during development. Traditional mass spectrometry (MS)-based peptide mapping methods cannot accurately quantify site-specific conjugations due to a significant ionization discrepancy between unconjugated native peptides and conjugated peptides. Here, we developed a novel protease-assisted drug deconjugation and linker-like labeling (PADDLL) method to quantify the levels of linker payload at specific conjugation sites. We utilized optimized papain digestion to deconjugate the drug payload and labeled unoccupied conjugation sites with a linker-like structure to provide comparable ionization efficiency for MS-based quantitation. This method was successfully applied on two cysteine-linked, protease-cleavable ADCs, and the method demonstrated good linearity and reliability, reaching a limit of quantitation of below 1%. The calculated DARs were comparable with the results from intact mass analysis. The lot-to-lot variation in conjugation distribution and inferior conjugation stability at HC Cys225 to other interchain cysteines were observed. This method provides a valuable tool for ADC design and product development. To the best of our knowledge, this is the first analytical method developed to accurately quantify site-specific linker-drug payload conjugations for ADCs.


Assuntos
Imunoconjugados , Preparações Farmacêuticas , Anticorpos Monoclonais , Peptídeo Hidrolases , Reprodutibilidade dos Testes
11.
Hum Vaccin Immunother ; : 1-5, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34254894

RESUMO

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has affected billions of lives globally, and the world hopes to end this epidemic by effective vaccination. In this review, we depict the latest panorama of global COVID-19 vaccine research and development based on different technology platforms, and summarize key characteristics and available evidence on vaccines authorized for emergency use, in order to provide insights into improve coordination in the COVID-19 outbreak response for related stakeholders.

12.
Biom J ; 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34272887

RESUMO

In biomedical studies it is common to collect data on multiple biomarkers during study follow-up for dynamic prediction of a time-to-event clinical outcome. The biomarkers are typically intermittently measured, missing at some event times, and may be subject to high biological variations, which cannot be readily used as time-dependent covariates in a standard time-to-event model. Moreover, they can be highly correlated if they are from in the same biological pathway. To address these issues, we propose a flexible joint model framework that models the multiple biomarkers with a shared latent reduced rank longitudinal principal component model and correlates the latent process to the event time by the Cox model for dynamic prediction of the event time. The proposed joint model for highly correlated biomarkers is more flexible than some existing methods since the latent trajectory shared by the multiple biomarkers does not require specification of a priori parametric time trend and is determined by data. We derive an expectation-maximization (EM) algorithm for parameter estimation, study large sample properties of the estimators, and adapt the developed method to make dynamic prediction of the time-to-event outcome. Bootstrap is used for standard error estimation and inference. The proposed method is evaluated using simulations and illustrated on a lung transplant data to predict chronic lung allograft dysfunction (CLAD) using chemokines measured in bronchoalveolar lavage fluid of the patients.

13.
Foodborne Pathog Dis ; 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34314613

RESUMO

National foodborne pathogen surveillance is a system that collects data regarding food contamination by pathogenic bacteria, viruses, parasites, and other harmful microbial factors. The surveillance data are used to understand the potential microbial risks in different categories of food and to provide science-based data for risk assessment and development of reference standards in the form of maximum limits. This review introduces stepwise expansion of the foodborne pathogen surveillance in China, relevant policies, function and duties of different organizations and institutions, surveillance plans, and quality control. Achievements of the surveillance system and future challenges are also presented.

14.
Se Pu ; 39(6): 578-587, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34227318

RESUMO

The incidence of breast cancer, one of the most common malignancies affecting women, is increasing significantly worldwide. Given the rapid development of medical technology, early and effective diagnostic methods should be able to improve the survival rate and quality of life of patients suffering from disease. However, although existing treatment options, including chemotherapy and endocrine therapies, have greatly improved the survival of patients, disease recurrence in the long term remains a challenge. Because breast cancer is a heterogeneous and complex disease, which includes several subtypes with different responses to treatment, the continual acquisition of spatial information on related biomolecules is important for accurate tracking of the tumor heterogeneity and microenvironment. At present, prognostic and predictive biomarkers, such as human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), Ki-67, progesterone receptor (PR), and programmed death-ligand 1 (PD-L1), are validated for use in the decision-making over breast cancer therapies. Mass spectrometry imaging (MSI) is a useful technique for acquiring molecular information about biological tissues, including qualitative, quantitative, and spatial distribution information, because it is based on the ion mass-to-charge ratio of the biomolecules and avoids the need for their labeling and staining. MSI can also acquire molecular information on drugs and their metabolites, as well as that on molecules related to endogenous metabolism, such as lipids, peptides, and proteins. Of the various ion sources available for MSI, the most popular are matrix-assisted laser desorption ionization, secondary ion mass spectrometry, and desorption electrospray ionization, and modifications or derivatives of these sources are still emerging. MSI-based techniques provide new ideas and directions for the molecular typing of tumors, as well as knowledge on the metabolism of related antitumor drugs. The process of MSI analysis generally involves tissue acquisition, section preparation, mass spectrometry ionization, map acquisition, and data analysis, with the most crucial step being sample handling to preserve the original chemical and location information of the analytes. The sample preparation steps are sample collection, storage, and slicing, tissue pretreatment, and matrix spraying. This review focuses mainly on the preparation of biological specimens for MSI analysis and the recent progress made in breast cancer research with this technology. With regard to sample preparation, four aspects are discussed: small-molecule samples, macromolecular samples, paraffin-embedded samples, and matrix spraying methods. To solve the difficulties associated with small-molecule sample processing, including the low extraction efficiency for certain lipids and matrix interference in the low-molecular-weight region, the addition of a cationic reagent to the extractant, the use of a new matrix, and tissue derivatization have been used. In the review of macromolecular sample processing, several different washing protocols are summarized. With regard to paraffin-embedded samples, the solutions to several common problems are reviewed. Additionally, the application of MSI to three models associated with breast cancer research is discussed, viz. cell models, animal models, and clinical tumor samples. For these models, MSI technology is used to evaluate the penetration and metabolism of antitumor agents in breast cancer, which can better reflect the malignant transformation of cells and changes in the microenvironment. With regard to lipid molecules, the use of MSI to study differences in their spatial distribution may provide a better understanding of the relationship between lipid metabolism and cancer. This review also provides important information for accurate molecular typing and drug screening in cancer research. Analytically, the tissue preparation method, tissue storage conditions, instrumentation choice, and experimental parameters have all been associated with variability in the imaging and mass-spectral qualities of MSI, thereby affecting the performance of the method. Large-scale studies using diverse sample cohorts are therefore needed to properly evaluate the robustness of MSI molecular markers and workflows for the clinical diagnosis and characterization of breast cancer variants. Our review provides strong evidence that MSI is a reliable, highly reproducible, and rapid technique for the diagnosis of breast cancer biopsies and may be useful in clinical application.


Assuntos
Neoplasias da Mama , Espectrometria de Massas/métodos , Animais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Qualidade de Vida , Tecnologia , Microambiente Tumoral
15.
Molecules ; 26(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34299424

RESUMO

The gut epithelium is a mechanical barrier that protects the host from the luminal microenvironment and interacts with the gut microflora, which influences the development and progression of ulcerative colitis (UC). Licochalcone A (LA) exerts anti-inflammatory effects against UC; however, whether it also regulates both the gut barrier and microbiota during colitis is unknown. The current study was conducted to reveal the regulatory effects of LA on the intestinal epithelium and gut microflora in C57BL/6 mice subjected to dextran sodium sulfate (DSS). Sulfasalazine (SASP) was used as the positive control. Results of clinical symptoms evaluation, hematoxylin, and eosin (H&E) staining, and enzyme-linked immunosorbent (ELISA) assays showed that LA significantly inhibited DSS-induced weight loss, disease activity index (DAI) increase, histological damage, and gut inflammation. Additionally, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and immunohistochemical (IHC) analysis showed that LA maintained the integrity of the intestinal barrier by suppressing cell apoptosis and preserving the expression of tight junction (TJ) proteins. Notably, the optimal dose of LA for gut barrier preservation was low, while that for anti-inflammatory effects was high, indicating that LA might preserve gut barrier integrity via direct effects on the epithelial cells (ECs) and TJ proteins. Furthermore, 16S rRNA analysis suggested that the regulatory effect of LA on the gut microbiota differed distinctly according to dose. Correlation analysis indicated that a low dose of LA significantly modulated the intestinal barrier-associated bacteria as compared with a moderate or high dose of LA. Western blot (WB) analysis indicated that LA exhibited anti-UC activity partly by blocking the mitogen-activated protein kinase (MAPK) pathway. Our results further elucidate the pharmacological activity of LA against UC and will provide valuable information for future studies regarding on the regulatory effects of LA on enteric diseases.

16.
J Agric Food Chem ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34323067

RESUMO

Upregulated de novo lipogenesis (DNL) plays a pivotal role in the progress of the nonalcoholic fatty liver disease (NAFLD). Cytoplasmic citrate flux, mediated by plasma membrane citrate transporter (SLC13A5), mitochondrial citrate carrier (SLC25A1), and ATP-dependent citrate lyase (ACLY), determines the central carbon source for acetyl-CoA required in DNL. Curcumin, a widely accepted dietary polyphenol, can attenuate lipid accumulation in NAFLD. Here, we first investigated the lipid-lowering effect of curcumin against NAFLD in oleic and palmitic acid (OPA)-induced primary mouse hepatocytes and high-fat plus high-fructose diet (HFHFD)-induced mice. Curcumin profoundly attenuated OPA- or HFHFD-induced hyperlipidemia and aberrant hepatic lipid deposition via modulating the expression and function of SLC13A5 and ACLY. The possible mechanism of curcumin on the citrate pathway was investigated using HepG2 cells, HEK293T cells transfected with human SLC13A5, and recombinant human ACLY. In OPA-stimulated HepG2 cells, curcumin rectified the dysregulated expression of SLC13A5/ACLY possibly via the AMPK-mTOR signaling pathway. Besides, curcumin also functionally inhibited both citrate transport and metabolism mediated by SLC13A5 and ACLY, respectively. These findings confirm that curcumin improves the lipid accumulation in the liver by blocking citrate disposition and hence may be used to prevent NAFLD.

17.
Toxicol In Vitro ; 76: 105220, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34271082

RESUMO

Recently, more and more attention has been focused on silica nanoparticles (SiNPs) as they are increasingly used in various fields. Yet, their biological effects, especially on human beings, largely remain unknown. This study was implanted to assess the biological responses in vitro elicited by human macrophages exposed to the SiNPs and to explore its toxicity and fibrosis biomarker. We found that SiNPs suppressed the viability of THP-1 cells in a dose-dependent manner while they triggered apoptosis and promoted the secretion of inflammatory factors. Next, SiNPs-induced macrophage supernatant was used to act on fibroblast (MRC-5), indicating that the expression of hydroxyproline (Hyp), α-SMA, and collagonIin MRC-5 increased after SiNPs treatment. To further explore the biomarker of fibrosis, Liquid-mass spectrometry facilitated quantitative proteomics, identified 3247 proteins, of which 791 proteins were expressed differentially in human embryonic lung fibroblasts after treated with SiNPs. In conclusion, our observations suggest that SiNPs induced THP-1-derived macrophage damage and apoptosis. Moreover, SiNPs induced macrophages to secrete cytokines that promote fibroblasts' proliferation and differentiation and changed protein expression in MRC-5 cells, regulating biological processes such as apoptosis, protein synthesis, and cell growth. Among these results, our findings could provide a basis for determining fibrosis biomarkers of silica nanoparticle exposure.

18.
Chemosphere ; 286(Pt 1): 131552, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34320440

RESUMO

Bioaugmented biotrickling filter (BTF) seeded with Piscinibacter caeni MQ-18, Pseudomonas oleovorans DT4, and activated sludge was established to investigate the treatment performance and biodegradation kinetics of the gaseous mixtures of tetrahydrofuran (THF) and methyl tert-butyl ether (MTBE). Experimental results showed an enhanced startup performance with a startup period of 9 d in bioaugmented BTF (25 d in control BTF seeded with activated sludge). The interaction parameter I2,1 of control (7.462) and bioaugmented BTF (3.267) obtained by the elimination capacity-sum kinetics with interaction parameter (EC-SKIP) model indicated that THF has a stronger inhibition of MTBE biodegradation in the control BTF than in the bioaugmented BTF. Similarly, the self-inhibition EC-SKIP model quantified the positive effects of MTBE on THF biodegradation, as well as the negative effects of THF on MTBE biodegradation and the self-inhibition of MTBE and THF. Metabolic intermediate analysis, real-time quantitative polymerase chain reaction, biofilm-biomass determination, and high-throughput sequencing revealed the possible mechanism of the enhanced treatment performance and biodegradation interactions of MTBE and THF.

19.
J Am Med Dir Assoc ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34324873

RESUMO

OBJECTIVE: A prescription cascade is a subsequent event that occurs when an adverse drug event is misinterpreted as a new medical condition, resulting in the prescription of a potentially unnecessary medication to treat this new condition. This study was designed to test the hypothesis of whether prescribing cascades exist and their magnitude among older individuals by using prescription sequence symmetry analysis (PSSA). DESIGN: A retrospective population-based cohort study based on data from Taiwan's National Health Insurance Research Database (NHIRD), a nationwide claims-based database that covers 99% of the population in Taiwan. SETTING AND PARTICIPANTS: Patients receiving newly initiated index and marker drugs in the outpatient setting between 2014 and 2016 were included. Those who received index and marker drugs on the same date were excluded. MEASURES: PSSA measures the propensity for a marker drug (eg, thyroxine) to be prescribed after an index drug (eg, amiodarone) has been initiated, where the index drug is suspected of inducing a side effect (eg, hypothyroidism) and the marker drug is used to treat the side effect. We evaluated 14 PSSA sets as potential prescription cascade-related drug pairs (index and marker drug), including 2 confirmatory analyses (eg, amiodarone and thyroxin), to check the validity of the PSSA results and 12 exploratory analyses of cardiovascular medication-related prescribing cascades (eg, statins and antidepressants). The observation periods for sequences of incident marker drug use were 1 year before and 1 year after the use of the incident index drug, and the symmetry of prescriptions filled for the 2 periods was examined. The results of the PSSA were performed as the crude sequence ratio (SR), defined as the ratio of patients initiating the marker drug after the index drug (causal group) to those initiating the marker drug before the index drug (noncausal group), and the adjusted SR (aSR) with 95% confidence intervals (CIs). RESULTS: Among 12 potential prescription cascade-related drug pairs in exploratory analysis, 9 of them reached statistical significance, and aSR ranged from 1.02 to 1.46. Dihydropyridine calcium channel blocker-induced edema showed the highest aSR (1.46, 95% CI 1.45-1.48), and statin-induced muscle pain showed the lowest aSR (1.02, 95% CI 1.02-1.03). CONCLUSIONS AND IMPLICATIONS: Our study supported the application of PSSA in detecting prescribing cascades using a nationwide claims database. Nevertheless, most previously reported prescribing cascades among cardiovascular medications were shown to have a low effect size of sequence ratios among older individuals.

20.
Arch Gerontol Geriatr ; 97: 104475, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34304112

RESUMO

BACKGROUND: Older adults with multiple complex care needs tend to receive fragmented care that may jeopardize their quality of life (QoL) and health outcomes. This study evaluated the determinants of improved QoL among integrated outpatient service recipients with multimorbidity. METHODS: We conducted a retrospective cohort study of integrated geriatric outpatient services (IGOS) at a tertiary medical center in Taiwan. Data from 2018 to 2019 were retrieved. All patients underwent comprehensive geriatric assessment, which included demographic information, serial functional assessments, and assessment for QoL. QoL was reassessed through a telephone survey 6 months after the patients' first visit to IGOS. Factors associated with the interval changes in QoL were identified using multivariate logistic regression. RESULTS: Data from 995 patients receiving IGOS (mean age: 82.21 ± 7.96 years, 54.5% males) were analyzed. An overall mean improvement in QoL was noted (EQ-5D index: +0.055±0.26, p <0.001) while 747 recipients reported maintained or improved QoL. The results of the multivariate logistic regression showed that poorer nutritional status (OR = 1.56, 95% CI: 1.07-2.28), depressive symptoms (OR = 1.99, 95% CI: 1.38-2.86), and frailty (OR = 1.66, 95% CI: 1.10-2.52) were independent risk factors for poorer QoL after adjustment for baseline QoL. CONCLUSIONS: Integrated outpatient services improved the quality of life of older adults with multimorbidity. Those with poorer nutritional status, depressive symptoms and frailty were less likely to show improvement in their QoL.

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