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1.
Food Chem ; 368: 130832, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34474242

RESUMO

Piper nigrum L. is commonly used worldwide and its pericarp, stalks, leaves will be major wastes materials. 42 amide alkaloids were identified in black, white pepper and pericarp by UHPLC-LTQ-Orbitrap HRMS method, followed by 40 constituents in stalks and 36 constituents in leaves. 8 amide alkaloids were reported for the first time in P. nigrum. An ultra-high-performance supercritical fluid chromatography (UHPSFC)-MS method was firstly applied to simultaneously determine 9 characteristic constituents (piperine, piperlonguminine, piperanine, pipercallosine, dehydropipernonaline, pipernonatine, retrofractamide B, pellitorine and guineensine). The most abundant compound in each extract was piperine with a concentration from 0.10 to 12.37 mg/g of dry weight. The fruits, pericarp and leaves extracts could improve cell viability in 6-OHDA-induced SK-N-SH and SH-SY5Y cells. The results showed the characteristics of amide alkaloids of different parts of P. nigrum and evaluated their neuroprotective activities.

2.
Int J Biol Macromol ; 192: 498-505, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34619280

RESUMO

Acanthopanax senticosus has been used to extract active products. However, abundant Acanthopanax senticosus residues (ASR), which contain plenty of lignin are discarded after extraction. An appropriate extraction method should be chosen to obtain the lignin with such desirable properties. Thus, this study investigated the effect of alkali, milled wood, deep eutectic solvent and ethanol methods on the lignin. Lignin obtained from different extraction methods were characterized, yields, chemical structure, thermal behavior, molecular weight and phenolic content were evaluated. The results show that the process of lignin acquisition has a great influence on the properties of lignin. Moreover, the multifarious functional groups exist in lignin macromolecules, such as phenolic, ether groups and other chromophores, conferred good UV resistance to lignin. Among them, the lignin from alkali method has the most phenolic-OH groups and smallest molecular weight result in a good UV-resistant, the SPF value achieves 2.39 at 1% AL content, the alkali method was the best way to make sunscreen blended with cream take various factors into consideration. This study used lignin as a bioactive ingredient to provide UV-resistant property to sunscreen formulations. Furthermore, lignin extracted from Acanthopanax senticosus residue provides a new application for the treatment of herb residue waste.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34656487

RESUMO

OBJECTIVES: This study aimed to compare the current 5 investigation strategies to defer cardiac testing in patients with stable chest pain. BACKGROUND: For the clinical management of stable chest pain, the identification of patients unlikely to benefit from further cardiac testing is important, but the most appropriate investigation strategy is unknown. METHODS: A total of 4,207 patients referred to coronary computed tomography angiography for stable chest pain were classified into low- and high-risk groups according to the 2016 National Institute of Health and Care Excellence (NICE) guideline-determined strategy; PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) minimal risk tool-based strategy; 2019 European Society of Cardiology (ESC) guideline-determined strategy; and coronary artery calcium score (CACS), either in isolation (the CACS strategy) or as part of a weighted clinical likelihood model-based strategy (the CACS-CL strategy). The associations of obstructive coronary artery disease on coronary computed tomography angiography, major adverse cardiovascular events, and subsequent clinical management with risk groups according to different strategies were evaluated and compared. RESULTS: The NICE, PROMISE, ESC, CACS, and CACS-CL strategies classified a proportion (22.63%, 29.21%, 41.84%, 46.76%, and 51.41%, respectively) of patients into low-risk groups. Compared with the NICE, PROMISE, ESC, and CACS strategies, the CACS-CL strategy had a stronger association between risk groups and obstructive coronary artery disease (odd ratios: 16.00 vs 2.93, 5.53, 7.94, and 10.39, respectively), major adverse cardiovascular events (HRs: 6.83 vs 1.90, 2.94, 4.23, and 5.13, respectively) and intensive subsequent clinical management as well as better metrics of diagnostic accuracy and positive net reclassification improvement. CONCLUSIONS: Among contemporary strategies used to identify patients with stable chest pain at low risk, the use of CACS, especially when combined with clinical risk features, showed the strongest potential to effectively defer cardiac testing.

4.
J Alzheimers Dis ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34657881

RESUMO

BACKGROUND: Studies suggest that general anesthetics like isoflurane and sevoflurane may aggravate Alzheimer's disease (AD) neuropathogenesis, e.g., increased amyloid-ß (Aß) protein aggregation resulting in synaptotoxicity and cognitive dysfunction. Other studies showed neuroprotective effects, e.g., with xenon. OBJECTIVE: In the present study, we want to detail the interactions of inhalational anesthetics with Aß-derived pathology. We hypothesize xenon-mediated beneficial mechanisms regarding Aß oligomerization and Aß-mediated neurotoxicity on processes related to cognition. METHODS: Oligomerization of Aß 1-42 in the presence of anesthetics has been analyzed by means of TR-FRET and silver staining. For monitoring changes in neuronal plasticity due to anesthetics and Aß 1-42, Aß 1-40, pyroglutamate-modified amyloid-(AßpE3), and nitrated Aß (3NTyrAß), we quantified long-term potentiation (LTP) and spine density. We analyzed network activity in the hippocampus via voltage-sensitive dye imaging (VSDI) and cognitive performance and Aß plaque burden in transgenic AD mice (ArcAß) after anesthesia. RESULTS: Whereas isoflurane and sevoflurane did not affect Aß 1-42 aggregation, xenon alleviated the propensity for aggregation and partially reversed AßpE3 induced synaptotoxic effects on LTP. Xenon and sevoflurane reversed Aß 1-42-induced spine density attenuation. In the presence of Aß 1-40 and AßpE3, anesthetic-induced depression of VSDI-monitored signaling recovered after xenon, but not isoflurane and sevoflurane removal. In slices pretreated with Aß 1-42 or 3NTyrAß, activity did not recover after washout. Cognitive performance and plaque burden were unaffected after anesthetizing WT and ArcAß mice. CONCLUSION: None of the anesthetics aggravated Aß-derived AD pathology in vivo. However, Aß and anesthetics affected neuronal activity in vitro, whereby xenon showed beneficial effects on Aß 1-42 aggregation, LTP, and spine density.

5.
Ying Yong Sheng Tai Xue Bao ; 32(9): 3053-3060, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34658189

RESUMO

Fine roots play an important role in energy flow and substance cycling in forests. How-ever, the estimates of biomass, production and turnover of fine roots remain large uncertainties, and the mechanism underlying local-scale spatial variation in fine roots is still unclear. In a temperate secondary forest in the Maoer Mountain in Northeast China, we investigated the vertical distribution of fine root biomass and necromass at the 0-100 cm profile and the dynamics, production and turnover rate of fine root in 0-20 cm soil layer. The sequential coring (including the Decision Matrix and the Maximum-Minimum formula) and the ingrowth core (3 cm diameter and 5 cm diameter) were compared in estimating production and turnover rate of fine roots. Forest stand variables that might affect fine roots were also explored. The results showed that 76.8% of fine root biomass and 62.9% of necromass concentrated in the 0-20 cm soil layer, and that both decreased exponentially with increa-sing soil depth. The seasonal variation in both fine root biomass and necromass was not significant in 0-20 cm soil layer, which might be related to the negligible snowfall in winter and the extremely high precipitation in summer. There was no significant difference in the results of the estimated fine root production between two diameter ingrowth cores. After log-transformed, fine root production and turnover rate estimated by the Decision Matrix, the Maximum-Minimum formula and ingrowth cores were significantly different among methods. With the increases of soil nutrient concentrations, fine root biomass/fine root necromass ratio significantly increased, fine root necromass significantly decreased, whereas fine root biomass, productivity, and turnover rate were not related to soil nutrient. There was a significant positive correlation between fine root production and aboveground woody biomass increment in the previous-year but not current-year.

6.
Eur J Med Chem ; 226: 113795, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34597896

RESUMO

P-glycoprotein (P-gp; ABCB1)-mediated drug efflux causes multidrug resistance in cancer. Previous synthetic methylated epigallocatechin (EGC) possessed promising P-gp modulating activity. In order to further improve the potency, we have synthesized some novel stereoisomers of methylated epigallocatechin (EGC) and gallocatechin (GC) as well as epicatechin (EC) and catechin (C). The (2R, 3S)-trans-methylated C derivative 25 and the (2R, 3R)-cis-methylated EC derivative 31, both containing dimethyoxylation at ring B, tri-methoxylation at ring D and oxycarbonylphenylcarbamoyl linker between ring D and C3, are the most potent in reversing P-gp mediated drug resistance with EC50 ranged from 32 nM to 93 nM. They are non-toxic to fibroblast with IC50 > 100 µM. They can inhibit the P-gp mediated drug efflux and restore the intracellular drug concentration to a cytotoxic level. They do not downregulate surface P-gp protein level to enhance drug retention. They are specific for P-gp with no or low modulating activity towards MRP1- or BCRP-mediated drug resistance. In summary, methylated C 25 and EC 31 derivatives represent a new class of potent, specific and non-toxic P-gp modulator.

7.
Photodiagnosis Photodyn Ther ; : 102581, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34648994

RESUMO

BACKGROUND: Rationally designed nanostructured materials can produce ideal drug carriers that plays an increasingly important role in cancer treatment. In comparison with conventional drug combination approaches, using co-delivery systems of multiple drugs achieves sophisticated targeting strategies and multifunctionality. METHODS: First, a nano-co-delivery of chitosan/tripolyphosphate (CS-TPP) was synthesized and characterized combining 5-aminolevulinic acid photodynamic therapy (ALA-PDT) with methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) shRNA. In this report, we investigated the efficacy of the simultaneous delivery of shRNA/photosensitizer on the gene expression of oral squamous cell carcinoma (OSCC) cells. The efficacy of CS-TPP-(shMTHFD1L-ALA)-PDT in inducing apoptosis and in generating of reactive oxygen species (ROS) in vitro was then assessed by Annexin V-PI and DCFH-DA assays respectively. In vivo therapeutic experiments were conducted in well-established orthotopic animal models of HNSCC. RESULTS: The results showed that the CS-TPP-(shMTHFD1L-ALA) nanoparticles (NPs) were approximately 145 nm in size. The cytotoxicity of OSCC cells was significantly increased by co-delivery of MTHFD1L shRNA and ALA-PDT compared with other groups. Furthermore, individual and combined therapies revealed remarkable pro-apoptotic, ROS and anti-tumorigenesis effects, and CS-TPP-(shMTHFD1L-ALA)-PDT had additive effects in vitro and in vivo. CONCLUSION: These observations indicate that CS-TPP-(shMTHFD1L-ALA) NPs may be an ideal candidate for gene/photosensitizer delivery.

8.
Clin Rheumatol ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642881

RESUMO

INTRODUCTION: Biomarkers of bone and cartilage metabolism were proposed as early diagnosis indicators for knee osteoarthritis (OA), however, which were influenced by disease stage, age, and menopause state. Accurate diagnosis indicators are eagerly awaited. The current study aims to investigate associations of joint metabolism biomarkers and bone mineral density (BMD) with early knee OA in males and premenopausal females before age 50 years. METHOD: A total of 189 patients aged before 50 years with early knee OA and 152 healthy participants were enrolled. Levels of bone biomarkers (PINP, OC, and CTX-I) and cartilage biomarkers (PIIANP, COMP, CTX-II, and MMP-3) were assessed. BMD was measured at the lumbar, femoral neck, and hip. Multivariate regression analyses were performed to evaluate the relationship between biomarkers, BMD, and early knee OA. RESULTS: Serum COMP, urine CTX-II and BMD at femoral neck and hip were increased in premenopausal patients as compared to control; with serum PINP and OC reduced. Meanwhile, serum COMP, urine CTX-II, and BMD at femoral neck and hip showed positive associations with premenopausal early knee OA, while serum PINP had negative association. However, in male patients, only serum COMP was higher than control, and no association of biomarkers or BMD was found with early knee OA. CONCLUSIONS: The joint metabolism biomarkers and BMD showed multiple associations with early knee OA in premenopausal females, but not in males aged before 50 years. It was suggested that sex differences should be taken into account when evaluating cartilage and bone metabolism in early knee OA. Key Points • The joint metabolism biomarkers and BMD are associated with early knee OA in premenopausal females, but not in males aged before 50 years. • Sex differences should be taken into account when evaluating cartilage and bone metabolism in early knee OA.

9.
Front Bioeng Biotechnol ; 9: 734688, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660555

RESUMO

Bone regeneration or replacement has been proved to be one of the most effective methods available for the treatment of bone defects caused by different musculoskeletal disorders. However, the great contradiction between the large demand for clinical therapies and the insufficiency and deficiency of natural bone grafts has led to an urgent need for the development of synthetic bone graft substitutes. Bone tissue engineering has shown great potential in the construction of desired bone grafts, despite the many challenges that remain to be faced before safe and reliable clinical applications can be achieved. Graphene, with outstanding physical, chemical and biological properties, is considered a highly promising material for ideal bone regeneration and has attracted broad attention. In this review, we provide an introduction to the properties of graphene and its derivatives. In addition, based on the analysis of bone regeneration processes, interesting findings of graphene-based materials in bone regenerative medicine are analyzed, with special emphasis on their applications as scaffolds, membranes, and coatings in bone tissue engineering. Finally, the advantages, challenges, and future prospects of their application in bone regenerative medicine are discussed.

10.
Thyroid ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605662

RESUMO

Background Adipogenesis, glycosaminoglycan hyaluronan (HA) production, inflammation, and fibrosis are the main pathogenic mechanisms responsible for Graves' orbitopathy (GO). We hypothesized that disulfiram (DSF), an aldehyde dehydrogenase (ALDH) inhibitor used to treat alcoholism, would have therapeutic effects on orbital fibroblasts (OFs) in GO. This study aimed to determine the therapeutic effects and underlying mechanisms of DSF on these parameters. Methods Primary cultures of OFs from 6 GO patients and 6 control subjects were established. OFs were allowed to differentiate into adipocytes and treated with various concentrations of DSF. Lipid accumulation within the cells was evaluated by Oil Red O staining. Real-time PCR and Western blotting were used to measure the expression of key adipogenic transcription factors, ALDH1A1, ALDH2, and mitogen-activated protein kinase (MAPK) signaling proteins. Apoptosis assays and reactive oxygen species (ROS) levels were evaluated by flow cytometry. HA production was measured using an ELISA kit. The mRNA levels of proinflammatory molecules were measured using real-time PCR after interleukin (IL)-1ß stimulation with or without DSF. The mRNA expression of markers associated with fibrosis was examined using real-time PCR after transforming growth factor (TGF)-ß1 stimulation with or without DSF. The wound-healing assay was assessed by phase-contrast microscopy. Results Under identical adipogenesis conditions, GO OFs effectively differentiated, while NC OFs did not. DSF dose-dependently suppressed lipid accumulation during adipogenesis in GO OFs. The expression of key adipogenic transcription factors, such as perilipin-1 (PLIN1), PPARγ (PPARG), FABP4, and c/EBPα (CEBPA), was downregulated. Furthermore, DSF inhibited the phosphorylation of ERK by inhibiting ALDH1A1. In addition, DSF attenuated HA production and suppressed inflammatory molecule expression induced by IL-1ß in GO OFs and NC OFs. The antifibrotic effects of DSF on TGF-ß1 were also observed in GO OFs. Conclusions In the current study, we provide evidence of the inhibitory effect of DSF on GO OFs adipogenesis, HA production, inflammation, and fibrosis in vitro. The results of this study are noteworthy and indicate the potential use of DSF as a therapeutic agent for the treatment of GO.

11.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(5): 832-838, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34622601

RESUMO

Objective: To study the distributional characteristics of allergens in children with allergic diseases in Shaanxi province. Methods: A total of 4 622 children diagnosed with allergic diseases in the Asthma Center, Department of Pediatrics, Xijing Hospital from March 2015 to February 2019 were selected. Serum allergen-specific immunoglobulin E (sIgE) of 19 common kinds of allergens were examined with enzyme-linked immunosorbent assay (ELISA). The children were divided into different groups according to sex, age and geographical regions, and the distributional characteristics of allergens of the different groups were compared. Results: The overall positive rate for the 19 allergens of the 4 622 children was 62.8%. The ranking of the positive rates for individual allergens from high to low were as follows: 24.2% for milk, 18.0% for mold mix, 16.7% for dog dander, 16.4% for house dust mite, 11.7% for cat dander, 10.7% for cashew, 10.6% for weed pollen, 8.8% for egg white, 7.8% for house dust, 7.7% for tree pollen, 5.6% for amaranth, 4.9% for mulberry tree, 3.6% for mango, 3.2% for beef, 2.8% for cockroach, 2.1% for crab, 1.5% for shrimp, 0.8% for pineapple, and 0.3% for shellfish. Analysis based on sex showed that the allergen positive rates in boys were higher than those in girls. Analysis by age difference showed that generally the positive rates for inhaled allergens increased along with the increase in patient age, while the positive rates for ingested allergens decreased along with the increase in patient age. Analysis by geographical regions showed that the positive rate of house dust mite in the patients from the southern part of Shaanxi, the positive rate of weed pollen in the patients from the northern part of Shaanxi and the positive rates of milk and egg white in the patients from the central part of Shaanxi were higher than those in other areas. The cluster analysis and correlation analysis showed that the 19 allergens could be roughly divided into 4 categories. There were moderate correlations among tree pollen, mulberry tree and amaranth. There were moderate correlations among mulberry tree, mango and amaranth. There was moderate correlation between shrimp and crab, and there were mild or weak correlations among most of the other allergens. Conclusion: Among the 4 622 children with allergic diseases in Shaanxi Province who were treated in the Asthma Center, Department of Pediatrics, Xijing Hospital, male patients showed higher sensitivity to allergens. The positive rates of inhaled allergens increased, while the positive rates of ingested allergens decreased with increase in patient age. There were regional differences in the distribution of allergens. Some allergens were correlated with each other, which may be related to cross-reaction.


Assuntos
Asma , Hipersensibilidade , Alérgenos , Animais , Asma/epidemiologia , Gatos , Bovinos , Criança , Cães , Poeira , Humanos , Imunoglobulina E , Masculino
12.
Biomacromolecules ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34636237

RESUMO

Developing safe and efficient delivery vehicles for chemotherapeutic drugs has been a long-standing demanding. Amino acid-based polymers are promising candidates to address this challenge due to their excellent biocompatibility and biodegradation. Herein, a series of well-defined amphiphilic block copolymers were prepared by PET-RAFT polymerization of N-acryloyl amino acid monomers. By altering monomer types and the block ratio of the copolymers, the copolymers self-assembled into nanostructures with various morphologies, including spheres, rod-like, fibers, and lamellae via hydrophobic and hydrogen bonding interactions. Significantly, the nanoparticles (NPs) assembled from amphiphilic block copolymers poly(N-acryloyl-valine)-b-poly(N-acryloyl-aspartic acid) (PV-b-PD) displayed an appealing cargo loading efficiency (21.8-32.6%) for a broad range of drugs (paclitaxel, doxorubicin (DOX), cisplatin, etc.) due to strong interactions. The DOX-loaded PV-b-PD NPs exhibited rapid cellular uptake (within 1 min) and a great therapeutic performance. These drug delivery systems provide new insights for regulating the controlled morphologies and improving the efficiency of drug delivery.

13.
Food Funct ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34636388

RESUMO

Gestational diabetes mellitus (GDM) has become a global health concern as the main result of its contribution to the high risk of adverse pregnancy outcomes for both the mother and fetus. However, there is absence of an ideal and widely acceptable therapy. Nuciferine has previously been shown to exert beneficial effects in various metabolic diseases. This study aimed to investigate the potential therapeutic efficacy of nuciferine on GDM in C57BL/6J mice induced by a high-fat diet (HFD), which has not been reported before. The results showed that nuciferine improved glucose intolerance, reduced lipid accumulation and increased the glycogen content within hepatocytes, and decreased placental lipid and glycogen deposition, thus ameliorating glycolipid disorders in GDM mice. Additionally, nuciferine protected against histological degeneration of metabolism-associated critical organs including the liver, pancreas, and abdominal adipose tissue. Most interestingly, nuciferine could correct intestinal dysbacteriosis in GDM mice, as evidenced by the elevation of probiotic abundances consisting of Akkermansia, Lactobacillus, and Bifidobacterium, which were all negatively correlated with serum and liver triglyceride (TG) and positively associated with hepatic glycogen, and the reduction of conditional pathogen abundances including Escherichia-Shigella and Staphylococcus, and the latter was positively related to serum and liver TG and negatively linked with liver glycogen. Collectively, these findings suggest that nuciferine as a food-borne strategy played important roles in the management of GDM.

14.
Food Funct ; 12(19): 9178-9187, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606546

RESUMO

Background: Basic studies have found that xanthine oxidase inhibitors extracted from mushrooms have inhibitory effects on hyperuricemia. However, the association between mushroom consumption and hyperuricemia is unknown in humans. Objective: We therefore designed a large-scale cohort study to examine whether mushroom consumption is a protective factor for developing hyperuricemia in adults. Methods: This prospective cohort study investigated 19 830 participants (mean age: 39.4 years; and 9906 [50.0%] men) who were free of hyperuricemia, cardiovascular disease, and cancer at the baseline. Mushroom consumption was measured at the baseline using a validated food frequency questionnaire. Hyperuricemia is defined as serum uric acid levels >420 µmol L-1 in men and >350 µmol L-1 in women. Cox proportional hazards regression models were used to examine the association of mushroom consumption with incident hyperuricemia. Restricted cubic spline regression was used to estimate the dose-response relationship between mushroom consumption and risk of hyperuricemia. Results: A total of 4260 first incident cases of hyperuricemia occurred during 61 421 person-years of follow-up (median follow-up of 4.2 years). After adjusting for demographic characteristics, lifestyle factors, dietary intake, and inflammatory markers, the multivariable hazard ratios (95% confidence intervals) for incident hyperuricemia were 1.00(reference) for <1.76 g per 1000 kcal per day, 0.93(0.86, 1.01) for 1.76-2.84 g per 1000 kcal per day, 0.93(0.85, 1.01) for 2.85-5.52 g per 1000 kcal per day, and 0.88 (0.80, 0.96) for >5.52 g per 1000 kcal per day, respectively (P for trend = 0.007). Conclusions: This population-based prospective cohort study has firstly demonstrated that higher mushroom consumption is significantly associated with lower incidence of hyperuricemia among general adults.

15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1394-1402, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627416

RESUMO

OBJECTIVE: To investigate the effect of glycolytic enzyme pyruvate kinase type 2 (PKM2) on the proliferation and apoptosis of human leukemia HL-60 cells. METHODS: si-PKM2 plasmid was transfected into HL-60 cells (set as si-PKM2 group), and blank vector transfected cells were set as control group (si-Ctl group). The expression levels of PKM2 mRNA and protein in si-Ctl group and si-PKM2 group were detected by RT-qPCR and Western blot. CCK-8 cell detection kit was used to detect the proliferation ability of the cells in the two groups. Flow cytometry was used to detect the changes of cell cycle and apoptosis. Western blot and RT-qPCR were used to detect the changes of p-Akt and p-mTOR protein levels in PI3K/Akt/mTOR signaling pathway and the changes of glycolysis-related mRNA levels of the cells in the two groups. The changes in glucose consumption and lactic acid production of the cells were assayed. Over expressed PKM2, HL-60 cells were treated with PI3K inhibitor LY294002 or galactose, the changes in cell proliferation ability, cell cycle and apoptosis, as well as changes in glucose consumption and lactic acid production were detected. RESULTS: Interfered by si-PKM2, mRNA and protein levels of PKM2 in si-PKM2 group significantly decreased, and proliferation ability of the cells was also reduced (P<0.05). After PKM2 knockdown, the cells were significantly blocked at G1 phase, and cell apoptosis was obviously induced (P<0.05). p-Akt and p-mTOR levels were lower in si-PKM2 group than those in si-Ctl group. The glucose consumption and lactic acid production significantly decreased in si-PKM2 cells. Overexpressed PKM2, HL-60 cells were treated with PI3K inhibitor LY294002. The glucose consumption and lactate acid production induced by overexpressed PKM2 were reduced. Overexpressed PKM2, HL-60 cells showed no significant changes in cell proliferation, cycle and apoptosis when cultured with galactose. CONCLUSION: PKM2 knockdown can inhibit the proliferation and induce apoptosis of HL-60 cells, and its molecular mechanism may be related to the PKM2-mediated PI3K/Akt/mTOR-glycolysis, which suggesting that PKM2 may serve as a molecular target for the prevention and treatment of leukemia.


Assuntos
Apoptose , Fosfatidilinositol 3-Quinases , Proliferação de Células , Glicólise , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Piruvato Quinase
16.
Int J Mol Sci ; 22(19)2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34639156

RESUMO

BACKGROUND: Patients with psoriasis have an increased risk of atherosclerotic cardiovascular disease (CVD). The molecular mechanisms behind this connection are not fully understood, but the involvement of neutrophils have drawn attention as a shared inflammatory factor. METHODS: RNA sequencing using the Illumina platform was performed on blood from 38 patients with moderate to severe psoriasis; approximately half had prior CVD. The neutrophil to lymphocyte ratio (NLR) was obtained from blood samples. Subclinical atherosclerosis was assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and ultrasound imaging. Transcriptomic analysis for differential expression and functional enrichment were performed, followed by correlation analyses of differentially expressed genes (DEGs), NLR and subclinical measurers of CVD. RESULTS: 291 genes were differentially expressed between patients with psoriasis with and without CVD. These included 208 upregulated and 83 downregulated DEGs. Neutrophil degranulation was identified as the most significant process related to the upregulated DEGs. Genes for the neutrophil-associated markers MPO, MMP9, LCN2, CEACAM1, CEACAM6 and CEACAM8 were identified as being of special interest and their mRNA levels correlated with NLR, high-sensitive C-reactive protein and markers of subclinical CVD. CONCLUSIONS: Patients with psoriasis and CVD had an increased expression of genes related to neutrophil degranulation in their blood transcriptome compared with patients with psoriasis without CVD. NLR may be a potential biomarker of subclinical CVD in psoriasis.

17.
BMC Oral Health ; 21(1): 517, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34641832

RESUMO

BACKGROUND: To investigate the related risk factors of periodontal health status among Chinese middle school students. METHODS: This study is a part of the Fourth National Oral Health Epidemiological Survey, which is by far the largest oral epidemiological survey in China, including all provinces, municipalities and autonomous regions in mainland China. A multi-stage stratified sampling method was used to select middle school students aged 12-15 from the sampled middle school for investigation. The survey consisted of two parts: oral examination and questionnaire survey. The oral examination included gingival bleeding and calculus. The questionnaire included sociodemographic information, oral health knowledge, attitudes and behaviors. Logistic regression and generalized linear mixed model were used to investigate the risk factors of gingival bleeding and calculus. RESULTS: A total of 118,514 middle-school students has been examined. Less gingival bleeding (OR = 0.746, CI 0.718-0.774) and calculus (OR = 0.550, CI 0.529-0.527) were found in 12-year-old group compared to 15-year-old group. The periodontal health status of males was worse than that of females (gingival bleeding OR = 1.102, CI 1.074-1.132, calculus OR = 1.258, CI 1.223-1.295). Besides age and gender, region, living place, ethnic groups, family structure, parent's education level, oral health knowledge and behavior were also related to gingival bleeding and calculus. CONCLUSIONS: Gingival bleeding and calculus occurred most of 12-15 years old adolescents in China. Several related factors, such as gender, age, ethnicity, father's education level, oral health knowledge and behavior, were found in multi-factorial models. The impact of province should arouse people's attention.

18.
CNS Drugs ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34661872

RESUMO

BACKGROUND: The effects of tranexamic acid on spontaneous intracerebral hemorrhage in reducing hematoma expansion and mortality as well as its role in thromboembolic complications and in the improvement of functional outcomes remain substantially uncertain. OBJECTIVE: The objective of this systematic review was to evaluate the efficacy and safety of tranexamic acid in patients with spontaneous intracerebral hemorrhage. METHODS: Several databases were searched from inception up to 20 June, 2021. We included randomized controlled trials that compared tranexamic acid with placebo or no treatment for the management of intracerebral hemorrhage. The primary outcomes were hematoma expansion and 90-day mortality. The secondary outcomes were hemorrhagic volume change, thromboembolic complications, and functional outcomes. RESULTS: Overall, six trials with 2800 patients were included in this meta-analysis. Tranexamic acid was associated with a reduced risk of hematoma expansion (relative risk 0.87, 95% confidence interval [CI] 0.77-0.99, p = 0.03, I2 = 0%, six trials with 2800 participants) and a lessening of hematoma volume change (mean difference - 1.28, 95% CI - 2.44 to - 0.12; p = 0.03; I2 = 0%, four trials with 2626 participants), without a corresponding higher rate of major thromboembolic complications (relative risk 1.20, 95% CI 0.85-1.69; p = 0.80; I2 = 0%, five trials with 2759 participants). The present analysis also demonstrated that tranexamic acid had no effect on reducing 90-day mortality (relative risk 1.02, 95% CI 0.88-1.19; p = 0.80; I2 = 0%, five trials with 2770 participants). CONCLUSIONS: In adults with spontaneous intracerebral hemorrhage, tranexamic acid reduced the risk of intracerebral hemorrhage growth compared with the control. The effects on 90-day mortality remained inconclusive. Further studies should report death within 24 h and death due to bleeding whenever possible.

19.
Vet Res ; 52(1): 122, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535180

RESUMO

Mastitis is a complex inflammatory disease caused by pathogenic infection of mammary tissue in dairy cows. The molecular mechanism behind its occurrence, development, and regulation consists of a multi-gene network including microRNA (miRNA). Until now, there is no report on the role of miR-125b in regulating mastitis in dairy cows. This study found that miR-125b expression is significantly decreased in lipopolysaccharide (LPS)-induced MAC-T bovine mammary epithelial cells. Also, its expression is negatively correlated with the expression of NF-κB inhibitor interacting Ras-like 2 (NKIRAS2) gene. MiR-125b target genes were identified using a double luciferase reporter gene assay, which showed that miR-125b can bind to the 3' untranslated region (3' UTR) of the NKIRAS2, but not the 3'UTR of the TNF-α induced protein 3 (TNFAIP3). In addition, miR-125b overexpression and silencing were used to investigate the role of miR-125b on inflammation in LPS-induced MAC-T. The results demonstrate that a reduction in miR-125b expression in LPS-induced MAC-T cells increases NKIRAS2 expression, which then reduces NF-κB activity, leading to low expression of the inflammatory factors IL-6 and TNF-α. Ultimately, this reduces the inflammatory response in MAC-T cells. These results indicate that miR-125b is a pro-inflammatory regulator and that its silencing can alleviate bovine mastitis. These findings lay a foundation for elucidating the molecular regulation mechanism of cow mastitis.

20.
Br J Nutr ; : 1-20, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34544523

RESUMO

High dietary fiber intake has been associated with a lower risk of diabetes, but the association of dietary fiber with prediabetes is only speculative, especially in China, where the supportive data from prospective studies is lacking. This study aimed to examine the association between dietary fiber intake and risk of incident prediabetes among Chinese adults. We performed a prospective analysis in 18,085 participants of the TCLSIH cohort study who were free of diabetes, prediabetes, cancer, and cardiovascular disease at baseline. Dietary data were collected using a validated 100-item food frequency questionnaire. Prediabetes was defined based on the American Diabetes Association diagnostic criteria. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During 63,175 person-years of follow-up, 4,139 cases of incident prediabetes occurred. The multivariable HRs (95% CIs) of prediabetes for the highest versus lowest quartiles were 0.85 (0.75, 0.98) (P for trend =0.02) for total dietary fiber, 0.84 (0.74, 0.95) (P for trend <0.01) for soluble fiber, and 1.05 (0.93, 1.19) (P for trend =0.38) for insoluble fiber. Fiber from fruits, but not from cereals, beans, and vegetables was inversely associated with prediabetes. Our results indicate that intakes of total dietary fiber, soluble fiber, and fiber derived from fruit sources were associated with a lower risk of prediabetes.

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