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1.
Microb Pathog ; 150: 104717, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33421608

RESUMO

Helicobacter pylori (H. pylori) is one of the most important pathogenic bacteria associated with various gastrointestinal diseases. At present, its apoptotic or antiapoptotic mechanism on gastric epithelial cells remains unknown and needs further illustrated. In this study, acute infection model (H. pylori and GES-1 cells were co-cultured for 24 h at a multiplicity of infection MOI of 100:1) and chronic infection model (GES-1 cells were infected repeatedly every 24 h at a multiplicity of infection MOI of 100:1 for approximately 8 weeks) were established, respectively. the chronic H. pylori infected GES-1 cells underwent a typically morphological change and Western Blot results showed that there was slight decrease in expression of E-cadherin, and obvious increase in expression of Vimentin. Apoptosis of these two models were analyzed by flow cytometry compared with the control cells, meanwhile, apoptosis associated markers (Bcl-xL, Bcl-2, Bax, etc) were detected by Western blot, additional in clinical H. pylori-positive gastric cancer tissues. Results showed that compared with the control cells, acute infection of H. pylori significantly accelerated the apoptosis of GES-1, increased the expression of Bax and Cleaved caspase-3, down-regulated expression of Bcl-xL and Bcl-2. Moreover, an opposite result was found in chronic infection of model and clinical gastric cancer tissues, and enhanced expression of NF-κB p65. Taken together, these findings suggest that H. pylori infection plays differential effects on apoptosis of gastric epithelial cells.

2.
Food Funct ; 11(11): 9801-9809, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33079125

RESUMO

Panax ginseng was fermented using Lactobacillus fermentum KP-3, and the levels of the minor ginsenosides were measured. Then, the effect of fermented ginseng on alcohol-induced liver injury was investigated. C57BL/6N mice were randomly assigned to 4 groups: pair fed (PF), alcohol fed (AF), alcohol with non-fermented ginseng (AF + NFG) and alcohol with fermented ginseng (AF + FG) groups. After treatment for 8 weeks, fermented ginseng intervention significantly reduced the levels of serum ALT, AST, LPS, TG and TC compared with the AF group. The western-blotting results showed that fermented ginseng activated the adenosine-monophosphate-activated protein kinase (AMPK) pathway to inhibit de novo lipogenesis in the liver and inhibited phosphorylation of p38 through the mitogen-activated protein kinase (MAPK) pathway to alleviate hepatic inflammation, and these effects were superior than those of non-fermented ginseng. Furthermore, fermented ginseng reduced alcohol-induced liver oxidative damage by upregulating the levels of antioxidant enzymes. These findings suggested that the L. fermentum KP-3-fermented ginseng product may be used as a potential dietary nutraceutical for alleviating alcoholic liver injury.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32977520

RESUMO

There is a need for valid and reliable instruments to focus on medication aspects of health literacy and help healthcare professionals address patients' barriers to medication use. This cross-sectional study describes the conceptualization, development, and psychometric properties of the first Chinese Medication Literacy Measurement (ChMLM) to assess the level of health literacy on medication use. The 17-item ChMLM (ChMLM-17) and its short form, 13-item ChMLM (ChMLM-13), consist of four sections (vocabulary, over-the-counter labels, prescription labels, and advertisements) to cover six domains of medication-related health literacy. Multistage stratified quota sampling was attempted to recruit a representative sample in Taiwan. Receiver operating characteristic curves were used to identify the cut-off point for differentiating high and low medication literacy. Psychometric analyses were performed (n = 1410) to assess the reliability and validity separately on all samples and sociodemographic subgroups. The 17- and 13-item versions both had high construct validity among all patients and patients with low medication literacy. The developed ChMLM-17 and ChMLM-13 is expected to help healthcare providers and researchers to accurately measure medication-related health literacy and improve medication use in the real-world practice.

4.
BMC Cancer ; 20(1): 603, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600429

RESUMO

BACKGROUND: Modulated electro-hyperthermia (mEHT) is a form of hyperthermia used in cancer treatment. mEHT has demonstrated the ability to activate host immunity by inducing the release of heat shock proteins, triggering apoptosis, and destroying the integrity of cell membranes to enhance cellular uptake of chemo-drugs in tumor cells. Both curcumin and resveratrol are phytochemicals that function as effective antioxidants, immune activators, and potential inhibitors of tumor development. However, poor bioavailability is a major obstacle for use in clinical cancer treatment. METHODS: This purpose of this study was to investigate whether mEHT can increase anti-cancer efficacy of nanosized curcumin and resveratrol in in vitro and in vivo models. The in vitro study included cell proliferation assay, cell cycle, and apoptosis analysis. Serum concentration was analyzed for the absorption of curcumin and resveratrol in SD rat model. The in vivo CT26/BALB/c animal tumor model was used for validating the safety, tumor growth curve, and immune cell infiltration within tumor tissues after combined mEHT/curcumin/resveratrol treatment. RESULTS: The results indicate co-treatment of mEHT with nano-curcumin and resveratrol significantly induced cell cycle arrest and apoptosis of CT26 cells. The serum concentrations of curcumin and resveratrol were significantly elevated when mEHT was applied. The combination also inhibited the growth of CT26 colon cancer by inducing apoptosis and HSP70 expression of tumor cells while recruiting CD3+ T-cells and F4/80+ macrophages. CONCLUSIONS: The results of this study have suggested that this natural, non-toxic compound can be an effective anti-tumor strategy for clinical cancer therapy. mEHT can enable cellular uptake of potential anti-tumor materials and create a favorable tumor microenvironment for an immunological chain reaction that improves the success of combined treatments of curcumin and resveratrol.

5.
Sci Rep ; 10(1): 8936, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32488092

RESUMO

Modulated electro-hyperthermia (mEHT) is a form of mild hyperthermia (HT) used for cancer treatment. The principle utility of HT is the ability not only to increase cell temperature, but also to increase blood flow and associated pO2 to the microenvironment. While investigational evidence has shown the unique ability of mEHT to elicit apoptosis in cancer cells, in vivo and in vitro, the same trait has not been observed with conventional HT. There is dissension as to what allows mEHT to elicit apoptosis despite heating to only mild temperatures, with the predominant opinion in favor of increased temperature at a cellular level as the driving force. For this study, we hypothesized that in addition to temperature, the amount of electrical energy delivered is a major factor in induction of apoptosis by mEHT. To evaluate the impact of electrical energy on apoptosis, we divided generally practiced mEHT treatment into 3 phases: Phase I (treatment start to 10 min. mark): escalation from 25 °C to 37 °C Phase II (10 min. mark to 15 min. mark): escalation from 37 °C to 42 °C Phase III (15 min. mark to 45 min. mark): maintenance at 42 °C Combinations of mEHT at 18 W power, mEHT at 7.5 W power, water bath, and incubator were applied to each of the three phases. Power output was recorded per second and calculated as average power per second. Total number of corresponding Joules emitted per each experiment was also recorded. The biological effect of apoptotic cell death was assayed by annexin-V assay. In group where mEHT was applied for all three phases, apoptosis rate was measured at 31.18 ± 1.47%. In group where mEHT was only applied in Phases II and III, apoptosis rate dropped to 20.2 ± 2.1%. Where mEHT was only applied in Phase III, apoptosis was 6.4 ± 1.7%. Interestingly, when mEHT was applied in Phases I and II, whether Phase III was conducted in either water bath at 42 °C or incubator at 37 °C, resulted in nearly identical apoptosis rates, 26 ± 4.4% and 25.9 ± 3.1%, respectively. These results showed that accumulation of mEHT at high-powered setting (18 W/sec) during temperature escalation (Phase I and Phase II), significantly increased apoptosis of tested cancer cells. The data also showed that whereas apoptosis rate was significantly increased during temperature escalation by higher power (18 W/sec), apoptosis was limited during temperature maintenance with lower power (7.5 W/sec). This presents that neither maintenance of 42 °C nor accumulation of Joules by mEHT has immediate correlating effect on apoptosis rate. These findings may offer a basis for direction of clinical application of mEHT treatment.

7.
Orthop Surg ; 12(3): 997-1004, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32324329

RESUMO

To evaluate the curative effect of one-stage posterior debridement and osteotomy parallel to the endplates for reconstruction, deformity correction, and tuberculosis control on treating the spinal tuberculosis of graded GATA III. From July of 2012 to December of 2017, there were 36 cases from the Second Hospital of Shanxi Medical University with thoracic and lumbar tuberculosis graded GATA III, in which we used osteotomy parallel to the endplates and reconstruction for treatment,16 for males and 20 for females. The local Cobb angles of kyphosis of all patients are greater than or equal to 20.The age varied from 28 months to 72 years with an average of 38.8 years. There were 15 cases of thoracic segment, 12 cases of thoracolumbar segment (T11 -L2 ), 9 cases of lumbar segment. Preoperative results of ASIA were 3 cases of grade C,5 cases of grade D and 28 cases of grade E with an average kyphosis Cobb angle of 37.21 ± 3.28. The visual analogue scale(VAS) scores preoperatively were 0-8 points (averaged 5.58 ± 1.66 points). All the patients had paraspinal abscesses. After completing the preoperative examinations and evaluations, the osteotomy parallel to the endplates and reconstruction were executed. We made a statistical analysis of the Cobb angles, visual analogue scale(VAS) scores, erythrocyte sedimentation rate (ESR), C-reaction protein(CRP), and ASIA grades before and after the surgery. The following-up time varied from 12 to 24 months, with an average of 18 months. The VAS score improved from 5.58 ± 1.66 before the surgery to 3.25 ± 0.92 one month after the surgery and 2.12 ± 0.73 at the last follow-up. The Cobb angles decreased from 37.21° ± 3.28° before the surgery to 5.72°± 2.66° one month later and 5.99° ± 1.92° at the last follow-up. The ESR decreased from 55.34 ± 1.72 mm/1 h before the surgery to 28.22 ± 3.76 mm/1 h one month later and 11.54 ± 0.46 mm/1 h at the last follow-up. The CRP decreased from 35.22 ± 2.46 mg/L before to 12.67 ± 2.82 mg/L and 4.50 ± 2.11 mg/L at the last follow-up. The results of the last ASIA grades were 1 case of grade D and 35 cases of grade E. The one-stage posterior debridement and osteotomy parallel to the endplates for patients with spinal tuberculosis of graded GATA III are not only beneficial to spinal reconstruction, but also obtain ideal reconstuction effects.

8.
Front Oncol ; 10: 254, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32211319

RESUMO

Purpose: True abscopal responses from radiation therapy are extremely rare; the combination of immune checkpoint inhibitors with radiation therapy has led to more reports of the abscopal effect, but even in this setting, the genuine magnitude remains unknown and is still considered generally uncommon. We report the occurrence of what appears to be putative, durable abscopal tumor responses with associated auto-immune systemic reactions resulting from the combination of local radiotherapy (RT) and modulated electrohyperthermia (mEHT). Materials and Methods: Data from advanced cancer patients treated palliatively with RT and mEHT between January and December 2017 were collected as part of a post-marketing safety monitoring program of mEHT therapy. We specified a minimum RT dose of 30 Gy and at least four mEHT treatments for reporting toxicities, which was the primary aim of the larger study. Results: Thirty-three patients treated with RT and mEHT, both applied to the same lesion, were included. The median RT dose was 45.5 Gy in 20 fractions (fxs) and the median number of mEHT treatments was 12 (range, 4-20). Most patients had subsequent systemic therapy after one course of RT and mEHT. Three patients (9.1%) developed autoimmune toxicities. Case number 1 received RT and mEHT only; case number 2 had two cycles of concurrent low dose chemotherapy during RT; and case number 3 received concurrent immune checkpoint inhibitors. None of the three patients received any further systemic treatment due to obvious treatment-related autoimmune reactions which occurred rapidly after RT; one had autoimmune hepatitis, one had dermatitis herpetiformis and the third developed severe myasthenia gravis. Interestingly, what we surmise to be long-lasting abscopal responses outside the irradiated area, were noted in all three patients. Conclusion: RT combined with mEHT could putatively result in enhancing immune responsiveness. These preliminary observational findings lead to the generation of a hypothesis that this combination induces both an in-situ, tumor-specific immune reaction and an anti-self-autoimmune reaction, in at least a small proportion of patients, and of those who experience the auto-immune response, tumor response is a concomitant finding. Mechanisms underlying this phenomenon need to be investigated further.

9.
Brain Res ; 1726: 146492, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31586626

RESUMO

Ischemic stroke arising from the sudden blockage of arteries in the brain, is a common and serious brain damaging problem worldwide, often leading to disability or death. The oxygen glucose deprivation (OGD) model was created to improve understanding of hypoxia- and hypoglycemia-induced neuronal cell injury, and provide an in vitro surrogate to assess novel treatments for cerebral hypoxia-ischemia. AMP-activated protein kinase (AMPK) is a critical neuroprotective regulator of energy homeostasis, metabolism and cell survival. However, the neuroprotective mechanisms by which AMPK achieves these beneficial effects in human SH-SY5Y neural cells exposed to OGD are still not well understood. Resveratrol is a potent activator of AMPK suggesting it may have therapeutic potential as a neuroprotective agent. Therefore, we hypothesized the AMPK activator resveratrol protects against OGD-mediated impairment of human SH-SY5Y neuronal cells. The novelty of the experiment using a 3D gelatin scaffold cell culture assay, we have tested the potential of 3D systems to mimic the endogenous neuronal environment and have applied these systems to study the effect of OGD on neuronal cells with/without resveratrol. Here we show resveratrol reverses, via AMPK-dependent downregulation of caspase 3 and 9 activity, the OGD-mediated decreases in SH-SY5Y cell viability on a 3D gelatin scaffold. In addition, treatment with OGD decreases mRNA levels of AMPK and the neuroprotective genes (Bcl-2 and CREB); however, co-treatment with resveratrol significantly normalizes these effects. Importantly, resveratrol improves the expression of AMPK and p-AMPK in OGD-exposed SH-SY5Y cells. Resveratrol also significantly rescues SH-SY5Y cells from OGD-mediated mitochondrial deficiency (lower D-loop level, mitochondrial mass, maximal respiratory function, COX activity, and mitochondrial membrane potential). Resveratrol also rescues the transcript expression levels of PGC1α and mitochondrial genes (NRF-1 and Tfam) in OGD-treated SH-SY5Y cells. These findings extend our mechanistic understanding of the central role of AMPK in OGD-related neuronal impairment, and may serve as basis for implementing new therapeutic strategies in the treatment of ischemic stroke.

10.
Cancer Cell Int ; 19: 296, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807118

RESUMO

Background: Endometrial cancer (EC) is one of the three major gynecological malignancies. Numerous biomarkers that may be associated with survival and prognosis have been identified through database mining in previous studies. However, the predictive ability of single-gene biomarkers is not sufficiently specific. Genetic signatures may be an improved option for prediction. This study aimed to explore data from The Cancer Genome Atlas (TCGA) to identify a new genetic signature for predicting the prognosis of EC. Methods: mRNA expression profiling was performed in a group of patients with EC (n = 548) from TCGA. Gene set enrichment analysis was performed to identify gene sets that were significantly different between EC tissues and normal tissues. Cox proportional hazards regression models were used to identify genes significantly associated with overall survival. Quantitative real-time-PCR was used to verify the reliability of the expression of selected mRNAs. Subsequent multivariate Cox regression analysis was used to establish a prognostic risk parameter formula. Kaplan-Meier survival estimates and the log-rank test were used to validate the significance of risk parameters for prognosis prediction. Result: Nine genes associated with glycolysis (CLDN9, B4GALT1, GMPPB, B4GALT4, AK4, CHST6, PC, GPC1, and SRD5A3) were found to be significantly related to overall survival. The results of mRNA expression analysis by PCR were consistent with those of bioinformatics analysis. Based on the nine-gene signature, the 548 patients with EC were divided into high/low-risk subgroups. The prognostic ability of the nine-gene signature was not affected by other factors. Conclusion: A nine-gene signature associated with cellular glycolysis for predicting the survival of patients with EC was developed. The findings provide insight into the mechanisms of cellular glycolysis and identification of patients with poor prognosis in EC.

11.
Food Sci Nutr ; 7(5): 1685-1694, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31139381

RESUMO

Previous studies have demonstrated that 27-hydroxycholesterol (27-OHC), a cholesterol metabolite, was involved in the inflammatory process of Alzheimer's disease (AD). The present study aimed to investigate the 27-OHC-induced inflammatory damage to neurons and astrocytes and the underlying mechanism(s) accounting for this damage. Human neuroblastoma cells (SH-SY5Y cells) and rat glioma cells (C6 cells) were treated with vehicle or 27-OHC (5, 10, or 20 µM) for 24 hr. The levels of secreted interleukin-1ß (IL-1ß), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α), and inducible nitric oxide synthase (iNOS) were determined by using an enzyme-linked immunosorbent assay (ELISA). Immunofluorescence staining was used to determine the cellular expression of toll-like receptor 4 (TLR4) and transforming growth factor-ß (TGF-ß). The mRNA and protein expression levels of nuclear factor-κB p65 (NF-κB p65), nuclear factor-κB p50 (NF-κB p50) and cyclooxygenase-2 (COX-2) in both SH-SY5Y and C6 cells were also detected by real-time PCR and Western blot, respectively. The results of this study showed that 27-OHC treatment increased secretion of TNF-α and iNOS and decreased secretion of IL-10, upregulated expression of TGF-ß, NF-κB p65 and p50, and downregulated expression of COX-2 in SH-SY5Y cells. In C6 cells, treatment with 27-OHC resulted in decreased secretion of IL-1ß, IL-10, TNF-α, and iNOS, and increased expression of TLR4 and TGF-ß. These results suggest that 27-OHC may cause inflammatory damage to neurons by activating the TGF-ß/NF-κB signaling pathway and to astrocytes by activating the TLR4/TGF-ß signaling, which results in the subsequent release of inflammatory cytokines.

12.
Int J Nanomedicine ; 14: 1269-1279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863059

RESUMO

Purpose: Modulated electro-hyperthermia (mEHT) stands to be a significant technological advancement in the hyperthermia field, utilizing autofocusing electromagnetic power on the cell membrane to create massive apoptosis. Since mEHT possesses the unique ability to excite cell membranes, we hypothesized that mEHT could enhance the uptake of liposomal drugs by enhancing phagocytic activity. Materials and methods: Water bath control and mEHT were used to compare the enhancement of liposome-encapsulated doxorubicin (Lipodox®) uptake by cancer cells. Cancer cells were made visible by doxorubicin fluorescence to investigate drug uptake. Viable cell yield was determined via the Trypan Blue exclusion method. Various substrates were used to investigate the mechanism of drug-uptake enhancement. The murine colon carcinoma model, CT26, was used to confirm the tissue infiltration of Lipodox® and its therapeutic effect. Results: mEHT treatment showed a significant enhancement of Lipodox® uptake of doxorubicin fluorescence compared with 37°C or 42°C water bath treatment. Tumor tissue sections also confirmed that mEHT treatment achieved the highest doxorubicin concentration in vivo (1.44±0.32 µg/g in mEHT group and 0.79±0.32 µg/g in 42°C water bath). Wortmannin was used to inhibit the macropinocytosis effect and 70 kDa dextran-FITC served as uptake substance. The uptake of dextran-FITC by cancer cells significantly increased after mEHT treatment whereas such enhancement was significantly inhibited by wortmannin. Conclusion: The result showed mEHT-induced particle-uptake through macropinocytosis. mEHT-enhanced uptake of Lipodox® may amplify the therapeutic effect of liposomal drugs. This novel finding warrants further clinical investigation.


Assuntos
Doxorrubicina/análogos & derivados , Hipertermia Induzida , Neoplasias/tratamento farmacológico , Células A549 , Animais , Antibióticos Antineoplásicos , Apoptose , Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Células Hep G2 , Humanos , Camundongos Endogâmicos BALB C , Neoplasias/patologia , Tamanho da Partícula , Pinocitose , Polietilenoglicóis/farmacologia , Polietilenoglicóis/uso terapêutico , Transdução de Sinais
13.
J Nanobiotechnology ; 17(1): 25, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30728015

RESUMO

BACKGROUND: A cationic liposome-PEG-PEI complex (LPPC) was employed as a carrier for achieving targeted delivery of drug to human epidermal growth factor receptor-2 (HER2/neu)-expressing breast cancer cells. LPPC can be easily loaded with an anti-tumor drug and non-covalently associated with an anti-tumor antibody such as Herceptin that is clinically used to rapidly form immunoparticles within 1 h. RESULTS: Drug-loaded LPPC have an average size about 250 nm and a zeta potential of about 40 mV. Herceptin was complexed onto surface of the LPPC to form the drug/LPPC/Herceptin complexes. The size of curcumin/LPPC/Herceptin complexes were 280 nm and the zeta potentials were about 23 mV. Targeting ability of this delivery system was demonstrated through specific binding on surface of cells and IVIS images in vivo, which showed specific binding in HER2-positive SKBR3 cells as compared to HER2-negative Hs578T cells. Only the drug/LPPC/Herceptin complexes displayed dramatically increased the cytotoxic activity in cancer cells. Both in vitro and in vivo results indicated that Herceptin adsorbed on LPPC directed the immunocomplex towards HER2/neu-positive cells but not HER2/neu-negative cells. The complexes with either component (curcumin or doxorubicin) used in the LPPC-delivery system provided a better therapeutic efficacy compared to the drug treatment alone and other treatment groups, including clinical dosages of Herceptin and LipoDox, in a xenografted model. CONCLUSIONS: LPPC displays important clinical implications by easily introducing a specific targeting characteristic to drugs utilized for breast cancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Polietilenoglicóis/química , Polietilenoimina/análogos & derivados , Receptor ErbB-2/metabolismo , Trastuzumab/administração & dosagem , Animais , Antineoplásicos/imunologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/administração & dosagem , Doxorrubicina/administração & dosagem , Liberação Controlada de Fármacos , Feminino , Xenoenxertos , Humanos , Lipossomos , Células MCF-7 , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Polietilenoimina/química , Propriedades de Superfície , Trastuzumab/imunologia
14.
Food Funct ; 9(11): 6020-6028, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30397690

RESUMO

Lactobacillus fermentum KP-3 was isolated from Korean pickle and used to ferment ginseng. The changes in the minor ginsenosides in the fermented ginseng were analyzed and the material was evaluated in high fat diet-fed mice. Total ginsenosides increased from 0.746 mg g-1 to 0.939 mg g-1 after fermentation, and the levels of minor ginsenosides (Rg2, Rg3, Rh1, Rh2, F2, and Ro) increased from 0.186 mg g-1 to 0.704 mg g-1. In an animal study, the serum TC and LDL levels in the HFD group were significantly higher than those of the control group. Compared with the HFD group, the probiotic-fermented ginseng significantly decreased the serum TC and LDL levels. In addition, the serum and liver ALT and AST levels were dramatically increased in the HFD group, but these increases were significantly inhibited by treatment with the probiotic-fermented ginseng. Furthermore, fermented ginseng reduced high fat diet-induced liver lipid accumulation. Overall, fermentation with L. fermentum KP-3 enhanced minor ginsenosides in ginseng and this probiotic-fermented ginseng ameliorated hyperlipidemia and liver injury induced by a high fat diet.


Assuntos
Ginsenosídeos/farmacologia , Hiperlipidemias/tratamento farmacológico , Lactobacillus fermentum/metabolismo , Hepatopatias/tratamento farmacológico , Panax/química , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Glicemia/metabolismo , Colesterol/sangue , Dieta Hiperlipídica , Fermentação , Microbiologia de Alimentos , Hiperlipidemias/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatias/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/farmacologia , Probióticos , Triglicerídeos/sangue
15.
Mol Genet Genomic Med ; 6(6): 982-992, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30296009

RESUMO

BACKGROUND: The aim of this study was to use the liquid chromatography/tandem mass spectrometry (LC-MS/MS) method to quantitate levels of three urinary glycosaminoglycans (GAGs; dermatan sulfate [DS], heparan sulfate [HS], and keratan sulfate [KS]) to help make a correct diagnosis of mucopolysaccharidosis (MPS). METHODS: We analyzed the relationships between phenotypes and levels of urinary GAGs of 79 patients with different types of MPS. RESULTS: The patients with mental retardation (n = 21) had significantly higher levels of HS than those without mental retardation (n = 58; 328.8 vs. 3.2 µg/ml, p < 0.001). The DS levels in the patients with hernia, hepatosplenomegaly, claw hands, coarse face, valvular heart disease, and joint stiffness were higher than those without. Twenty patients received enzyme replacement therapy (ERT) for 1-12.3 years. After ERT, the KS level decreased by 90% in the patients with MPS IVA compared to a 31% decrease in the change of dimethylmethylene blue (DMB) ratio. The DS level decreased by 79% after ERT in the patients with MPS VI compared to a 66% decrease in the change of DMB ratio. CONCLUSIONS: The measurement of GAG fractionation biomarkers using the LC-MS/MS method is a more sensitive and reliable tool than the DMB ratio for MPS high-risk screening, diagnosis, subclass identification, and monitoring the efficacy of ERT.


Assuntos
Dermatan Sulfato/urina , Heparitina Sulfato/urina , Sulfato de Ceratano/urina , Mucopolissacaridoses/urina , Adolescente , Biomarcadores/urina , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Mucopolissacaridoses/classificação , Mucopolissacaridoses/patologia , Fenótipo
16.
Huan Jing Ke Xue ; 39(9): 4132-4141, 2018 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-30188054

RESUMO

In order to discern temporal variations, sources, and controlling factors of river water chemistry in the Malian River Basin, time series samples were collected from the Yuluoping hydrological station in 2016. The compositions of major cations and anions were analyzed and a forward model was used to calculate the weathering rates of evaporite, silicate, and carbonate. Results showed that river water was brackish with average total dissolved solids of 1154.0 mg·L-1, indicating significant differences from other main rivers in China. Na+, Ca2+, Mg2+, and SO42- were the major ions present in water, with mean concentrations of 202.8, 86.0, 78.6, and 431.2 mg·L-1 respectively. Water chemistry exhibited distinct seasonal variations, with major ions gradually declining during the pre-monsoon period and increasing in the post-monsoon period. An abrupt rise in concentrations of major ions during the ice melting interval was observed, as well as a sharp drop during stormy events. Dissolved loads were mainly derived from chemical weathering, with the contribution ratios of evaporite, silicate, and carbonate being 67.1%, 13.7%, and 19.2% respectively. Chemical processes showed different responses to climate forcing, attributed to variations in mineral content in the watershed and dissolution kinetics. The dominant contribution of evaporite in the monsoon season was due to its rapid dissolution, while silicate weathering increased during the pre-monsoon period, with longer water rock interaction times when water discharge was lower. During the post-monsoon season, carbonate weathering was enhanced due to its high content in loess and due to more CO2 absorption by rain from soil. The average chemical weathering rates of evaporite, silicate, and carbonate were 30.6, 6.2, and 8.7 kg·(km2·d)-1, respectively. A strong correlation between evaporite weathering rates and river discharge was evident; a correlation was also observed between carbonate weathering rates and river discharge, indicating that water discharge played a dominant role in chemical weathering, rather than temperature or precipitation.

17.
BMC Immunol ; 19(1): 27, 2018 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-30075754

RESUMO

BACKGROUND: The natural killer cell line, NK-92MI, is cytotoxic against various types of cancer. The aim of this study was to develop chimeric antigen receptor-modified (CAR) NK-92MI cells targeting carcinoembryonic antigen-expressing (CEA) tumours and increase killing efficacy by pharmacologically modifying CEA-expression. RESULT: We generated anti-CEA-CAR NK-92MI cells by retroviral vector transduction. This genetically-modified cell line recognised and lysed high CEA-expressing tumour cell lines (LS174T) at 47.54 ± 12.60% and moderate CEA-expressing tumour cell lines (WiDr) at 31.14 ± 16.92% at a 5:1 effector: target (E/T) ratio. The cell line did not lyse low CEA-expressing tumour cells (HCT116) as they did their parental cells (NK-92MI cells). The histone deacetylase-inhibitor (HDAC) sodium butyrate (NaB) and the methylation-inhibitor 5-azacytidine (5-AZA), as epigenetic modifiers, induced CEA-expression in HCT116 and WiDr cells. Although the IC50 of 5 fluorouracil (5-FU) increased, both cell lines showed collateral sensitivity to anti-CEA-CAR NK-92MI cells. The cytolytic function of anti-CEA-CAR NK-92MI cells was increased from 22.99 ± 2.04% of lysis background to 69.20 ± 11.92% after NaB treatment, and 69.70 ± 9.93% after 5-AZA treatment, at a 10:1 E/T ratio in HCT116 cells. The WiDr cells showed similar trend, from 22.99 ± 4.01% of lysis background to 70.69 ± 10.19% after NaB treatment, and 59.44 ± 10.92% after 5-AZA treatment, at a 10:1 E/T ratio. CONCLUSIONS: This data indicates that the effector-ability of anti-CEA-CAR NK-92MI increased in a CEA-dependent manner. The combination of epigenetic-modifiers like HDAC-inhibitors, methylation-inhibitors, and adoptive-transfer of ex vivo-expanded allogeneic-NK cells may be clinically applicable to patients with in 5-FU resistant condition.


Assuntos
Antígeno Carcinoembrionário/imunologia , Neoplasias Colorretais/terapia , Citotoxicidade Imunológica , Imunoterapia Adotiva/métodos , Células Matadoras Naturais/transplante , Receptores de Antígenos Quiméricos/imunologia , Antígeno Carcinoembrionário/genética , Linhagem Celular Tumoral , Expressão Gênica , Células HCT116 , Humanos , Células Matadoras Naturais/imunologia , Receptores de Antígenos Quiméricos/genética , Regulação para Cima
18.
Oncotarget ; 9(6): 6883-6896, 2018 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-29467937

RESUMO

Glioblastoma (GBM) cells are characterized by high phagocytosis, lipogenesis, exocytosis activities, low autophagy capacity and high lysosomal demand are necessary for survival and invasion. The lysosome stands at the cross roads of lipid biosynthesis, transporting, sorting between exogenous and endogenous cholesterol. We hypothesized that three already approved drugs, the autophagy inducer, sirolimus (rapamycin, Rapa), the autophagy inhibitor, chloroquine (CQ), and DNA alkylating chemotherapy, temozolomide (TMZ) could synergize against GBM. This repurposed triple therapy combination induced GBM apoptosis in vitro and inhibited GBM xenograft growth in vivo. Cytotoxicity is caused by induction of lysosomal membrane permeabilization and release of hydrolases, and may be rescued by cholesterol supplementation. Triple treatment inhibits lysosomal function, prevents cholesterol extraction from low density lipoprotein (LDL), and causes clumping of lysosome associated membrane protein-1 (LAMP-1) and lipid droplets (LD) accumulation. Co-treatment of the cell lines with inhibitor of caspases and cathepsin B only partially reverse of cytotoxicities, while N-acetyl cysteine (NAC) can be more effective. A combination of reactive oxygen species (ROS) generation from cholesterol depletion are the early event of underling mechanism. Cholesterol repletion abolished the ROS production and reversed the cytotoxicity from QRT treatment. The shortage of free cholesterol destabilizes lysosomal membranes converting aborted autophagy to apoptosis through either direct mitochondria damage or cathepsin B release. This promising anti-GBM triple therapy combination severely decreases mitochondrial function, induces lysosome-dependent apoptotic cell death, and is now poised for further clinical testing and validation.

19.
Chronic Dis Transl Med ; 3(2): 129-134, 2017 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-29063066

RESUMO

OBJECTIVE: Stroke is the leading cause of death and disability, and is closely related to a lack of exercise. Currently, most Chinese medical staff members lack exercise and may be at risk for stroke. We sought to determine the risk factors for stroke and study the significance of health-related physical fitness testing in stroke prevention among Chinese medical staff members. METHODS: A total of 627 subjects from Urumqi, Xinjiang, China, were included in the study and a survey was conducted from 1st January 2016 to 1st February 2016. Stroke screening and health-related physical fitness testing were completed according to the standard protocol, and the related data were analyzed. RESULTS: Based on the screening, 27.6% (n = 173) of the subjects were at high risk for stroke. The top risk factors for stroke in these subjects were dyslipidemia, lack of exercise or mild physical activity, being overweight or obese, and high blood pressure. Body weight, body mass index, body fat, visceral fat area, body fat percentage, and basal metabolic rate were significantly higher (P < 0.01) in subjects at high risk for stroke than in subjects who were not at high risk. Lung capacity, step index, grip test, vertical jump, and sit-up/push-up index were significantly lower (P < 0.01) in subjects at high risk for stroke than in subjects who were not at high risk. CONCLUSIONS: A large proportion of China's on-the-job medical personnel is at high risk for stroke. This may be related to the nature of the profession and warrants more attention from the society. The health-related physical fitness measurement parameters in subjects at high risk for stroke were significantly different from those in subjects who were not at high risk. Screening and health-related physical fitness testing in medical staff members may contribute to stroke prevention. More rigorous controlled clinical trials will be needed in the future.

20.
Oncotarget ; 8(36): 60046-60059, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28947953

RESUMO

7,7″-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from Taxus × media cv. Hicksii, induces apoptotic and autophagic cell death. However, whether DMGF suppresses tumor metastasis is unclear. The aim of this study was to investigate the anti-metastatic activities of DMGF on the metastatic processes of melanoma cells in vivo and in vitro. A transwell assay showed that DMGF could effectively attenuate the motility of B16F10 cells, and the results of real-time PCR revealed that DMGF also suppressed the expressions of matrix metalloproteinase-2 (MMP-2). Moreover, DMGF did not influence tube formation but inhibited the migration of endothelial cells. Furthermore, animal models were used to monitor the effects of DMGF on tumor metastasis, and all models showed that DMGF significantly suppressed the metastatic behaviors of B16F10 cells, including intravasation, colonization, and invasion of the lymphatic duct. In addition, DMGF could also reduce the densities of the blood vessels in the tumor area in vivo. Further investigation of the molecular mechanisms of anti-metastatic activity revealed that DMGF can down-regulate the levels of key modulators of the Cdc42/Rac1 pathway to interfere in F-actin polymerization and suppress the formation of lamellipodia by reducing the phosphorylation of CREB. These data suggested that DMGF presents anti-metastatic activities in B16F10 melanoma cells. Here, we demonstrated that DMGF can inhibit the metastasis of highly invasive melanoma cancer cells through the down-regulation of F-actin polymerization. Considering these findings, DMGF may be further developed to serve as a chemoprevention drug for patients with metastatic melanoma.

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