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BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is a prevalent and severe issue among ICU patients. Resistance training and beta-hydroxy-beta-methylbutyrate (HMB) intervention have demonstrated the potential to enhance muscle function in patients with sarcopenia and in older adults. The purpose of this study was to determine whether resistance training and/or HMB administration would improve physical function, muscle strength, and quality of life in medical ICU patients. METHODS: In this multicentre, four-arm, single-blind randomised control trial, a total of 112 adult patients with internal medical diagnoses admitted to the ICU were enrolled. These participants were then randomly assigned to one of four treatment groups: the resistance training group received protocol-based multilevel resistance exercise, the HMB group received 3 g/day of HMBCa, combination group and control groups received standard care, from the ICU to the general ward until discharge. The primary outcomes assessed at discharge included six-minute walking distance (6MWD) and short physical performance battery (SPPB). Secondary outcomes measured included muscle mass, MRC score, grip strength, and health reports quality of life at different time points. Data analysis was performed using a generalised linear mixed model, adhering to the principles of intention-to-treat analysis. RESULTS: Resistance training and combination treatment groups exhibited significant increases in SPPB scores (3.848 and 2.832 points, respectively) compared to the control group and substantial improvements in 6WMD (99.768 and 88.577 m, respectively) (all with P < 0.01). However, no significant changes were observed in the HMB group. Muscle strength, as indicated by MRC and grip strength tests conducted at both ICU and hospital discharge, showed statistically significant improvements in the resistance training and combination groups (P < 0.05). Nevertheless, no significant differences were found between the treatment groups and usual care in terms of 60-day mortality, prevalence of ICU-AW, muscle mass, quality of life, or other functional aspects. CONCLUSIONS: Resistance training with or without beta-hydroxy-beta-methylbutyrate during the entire hospitalisation intervention improves physical function and muscle strength in medical ICU patients, but muscle mass, quality of life, and 60-day mortality were unaffected. TRIAL REGISTRATION: ChiCTR2200057685 was registered on March 15th, 2022.
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Entrenamiento de Fuerza , Humanos , Suplementos Dietéticos , Unidades de Cuidados Intensivos , Fuerza Muscular , Músculo Esquelético/fisiología , Alta del Paciente , Calidad de Vida , Método Simple Ciego , AdultoRESUMEN
Background and aim: Xianglian Wan (XLW) as a classic prescription of traditional Chinese medicine protects digestive function; however, few studies have investigated its anti-colorectal cancer effects. This study verified that the effective monomer berberine of XLW plays an antitumo r role by regulating the acetyl-CoA carboxylase (ACC)/fatty acid synthase (FASN) lipid metabolism-related signaling pathway. Experimental procedure: The connection between XLW and FASN was identified through literature mining, bioinformatics and structural biology. In vivo experiments verified the rationality of the antitumor effect of berberine by regulating the ACC/FASN pathway, and in vitro experiments verified the regulatory relationship between berberine and FASN. Results and conclusion: The most frequent Chinese medicine component in XLW was Coptis chinensis. Berberine, the active ingredient of XLW, has a FASN binding site. FASN expression is higher in tumor tissues than in normal tissues. FASN is related to colorectal adenocarcinoma occurrence and patient survival time. Experiments showed that XLW, berberine and orlistat (FASN inhibitor) can cooperate with palmitic acid (PA) to inhibit tumors in mice. Berberine can downregulate FASN and ACC expression in tumor tissues and inhibit the increase in acetyl-CoA, the intermediate product of exogenous PA intake. The mechanism by which berberine inhibits colon cancer cell proliferation by lowering lipids is related to its downregulation of FASN protein expression. The ACC/FASN signaling pathway is a critical pathway through which berberine, the effective monomer of XLW, plays an antitumor role in colon cancer.
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Inflammatory bowel disease (IBD) mainly includes Crohn's disease (CD) and ulcerative colitis (UC). Immune disorders play an essential role in the pathogenesis of these two IBDs, but the differences in the immune microenvironment of the colon and their underlying mechanisms remain poorly investigated. Here we examined the immunological features and metabolic microenvironment of untreated individuals with IBD by multiomics analyses. Modulation of CD-specific metabolites, particularly reduced selenium, can obviously shape type 1 T helper (Th1) cell differentiation, which is specifically enriched in CD. Selenium supplementation suppressed the symptoms and onset of CD and Th1 cell differentiation via selenoprotein W (SELW)-mediated cellular reactive oxygen species scavenging. SELW promoted purine salvage pathways and inhibited one-carbon metabolism by recruiting an E3 ubiquitin ligase, tripartite motif-containing protein 21, which controlled the stability of serine hydroxymethyltransferase 2. Our work highlights selenium as an essential regulator of T cell responses and potential therapeutic targets in CD.
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Antioxidantes/farmacología , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/inmunología , Selenio/farmacología , Selenoproteína W/metabolismo , Células TH1/citología , Diferenciación Celular/inmunología , Polaridad Celular , Colon/inmunología , Colon/patología , Glicina Hidroximetiltransferasa/metabolismo , Humanos , Especies Reactivas de Oxígeno/metabolismo , Ribonucleoproteínas/metabolismo , Células TH1/inmunología , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
[This corrects the article DOI: 10.1155/2017/1871298.].
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BACKGROUND: Sleep disturbance is a frequent and significant problem challenge for family caregivers of patients with cancer. A previously tested 6-week auricular acupressure intervention was found to reduce symptom burden in women with cancer. It is possible that such an intervention has a concomitant benefit for family caregivers. OBJECTIVES: The aim of this study was to explore if the effects of an auricular acupressure intervention on major symptoms experienced by women with ovarian cancer improves the sleep quality of family caregivers. METHODS: A quasi-randomized controlled trial with a repeated-measures design was used. Family caregivers (n = 68) of cancer patients were recruited and completed the Pittsburgh Sleep Quality Index on 4 occasions. Demographic information included age, sex, duration of caring role, and relationship to the patient. RESULTS: Family members with a longer duration of caregiving reported more sleep disturbance at baseline. As the symptom burden of treated women decreased, their family caregivers reported improved Pittsburgh Sleep Quality Index scores at 4 weeks (time 2; Cohen d = 1.075) and 6 weeks (time 3; Cohen d = 1.022). CONCLUSIONS: Reducing the symptom burden of patients with cancer can improve the sleep quality of family caregivers. IMPLICATIONS FOR PRACTICE: Auricular acupressure is a noninvasive and easy-to-apply intervention that can be applied by caregivers to assist their family member. Nursing staff can implement and test the acupressure intervention into their clinical practice and better support family-based strategies and interventions. Further studies with larger samples are needed to confirm our findings.
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Acupresión , Neoplasias Ováricas , Trastornos del Sueño-Vigilia , Cuidadores , Femenino , Humanos , Sueño , Trastornos del Sueño-Vigilia/etiología , Trastornos del Sueño-Vigilia/prevención & controlRESUMEN
The Ruanjian Sanjie Decoction (RSD) is a traditional Chinese medicine (TCM) formulation consisting of Spica Prunellae, Pseudobulbus Cremastrae Seu Pleiones, Concha Ostreae and Semen Coicis, and widely used as an adjuvant in anti-cancer therapy. The aim of this study was to determine the effects of RSD on the extracellular matrix (ECM) of tumors, and on the efficacy of anti-cancer nano-formulations in a tumor-bearing mouse model. The mice were treated with triptolide encapsulated in PEG-modified liposomes (TP-PEG-LPs), either alone or in combination with RSD. The combination treatment significantly retarded tumor growth relative to the untreated controls, indicating the potent adjuvant effect of RSD in targeted anti-cancer therapy. In addition, RSD also reduced the amount of total collagen and collagen I and increased that of collagen III in the tumor ECM, along with decreasing the expression of the pro-angiogenic VEGF. Finally, even high doses of RSD did not significantly affect the liver and kidney function or body weight, indicating low toxicity.
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Astragalus membranaceus (Radix Astragali, RA) and Atractylodes macrocephala (Rhizoma Atractylodis Macrocephalae, RAM) are often used to treat gastrointestinal diseases. In the present study, we determined the effects of polysaccharides extracts from these two herbs on IEC-6 cell migration and explored the potential underlying mechanisms. A migration model with IEC-6 cells was induced using a single-edged razor blade along the diameter of cell layers in six-well polystyrene plates. The cells were grown in control media or media containing spermidine (5 µmol·L-1, SPD), alpha-difluoromethylornithine (2.5 mmol·L-1, DFMO), 4-Aminopyridine (40 µmol·L-1, 4-AP), the polysaccharide extracts of RA or RAM (50, 100, or 200 mg·L-1), DFMO plus SPD, or DFMO plus polysaccharide extracts of RA or RAM for 12 or 24 h. Next, cytosolic free Ca2+ ([Ca2+]cyt) was measured using laser confocal microscopy, and cellular polyamine content was quantified with HPLC. Kv1.1 mRNA expression was assessed using RT-qPCR and Kv1.1 and RhoA protein expressions were measured with Western blotting analysis. A cell migration assay was carried out using Image-Pro Plus software. In addition, GC-MS was introduced to analyze the monosaccharide composition of both polysaccharide extracts. The resutls showed that treatment with polysaccharide extracts of RA or RAM significantly increased cellular polyamine content, elevated [Ca2+]cyt and accelerated migration of IEC-6 cells, compared with the controls (P < 0.01). Polysaccharide extracts not only reversed the inhibitory effects of DFMO on cellular polyamine content and [Ca2+]cyt, but also restored IEC-6 cell migration to control level (P < 0.01 or < 0.05). Kv1.1 mRNA and protein expressions were increased (P < 0.05) after polysaccharide extract treatment in polyamine-deficient IEC-6 cells and RhoA protein expression was increased. Molar ratios of D-ribose, D-arabinose, L-rhamnose, D-mannose, D-glucose, and D-galactose was 1.0 : 14.1 : 0.3 : 19.9 : 181.3 : 6.3 in RA and 1.0 : 4.3 : 0.1 : 5.7 : 2.8 : 2.2 in RAM. In conclusion, treatment with RA and RAM polysaccharide extracts stimulated migration of intestinal epithelial cells via a polyamine-Kv1.1 channel activated signaling pathway, which facilitated intestinal injury healing.
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Astragalus propinquus/química , Atractylodes/química , Medicamentos Herbarios Chinos/farmacología , Células Epiteliales/efectos de los fármacos , Intestinos/efectos de los fármacos , Canal de Potasio Kv.1.1/metabolismo , Poliaminas/metabolismo , Polisacáridos/farmacología , Animales , Línea Celular , Movimiento Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Células Epiteliales/citología , Células Epiteliales/metabolismo , Intestinos/citología , Canal de Potasio Kv.1.1/genética , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Ratas , Rizoma/química , Transducción de Señal/efectos de los fármacos , Proteína de Unión al GTP rhoA/metabolismoRESUMEN
Background. Yiqi Huayu Jiedu Decoction (YHJD) can obviously improve the quality of life of those patients with gastric cancer and prolong their survival. Methods. In vitro experiments, we observe YHJD's effect on the cells' proliferation by MTT assay. Cell adhesion assay, wound-healing assay, and Transwell invasion assay serve to detect its influence on cells' adhesion, migration, and invasion, respectively. Inhibitor (10 µM/L of SB431542) and activator (10 ng/mL of TGF-ß) of TGF-ß/Smad pathway were used to estimate whether YHJD's impact on the biological behavior of gastric cancer cells was related to TGF-ß/Smad pathway. In in vivo studies, YHJD was administered to the nude mice transplanted with gastric cancer to observe its effect on the tumor. Western blotting and immunohistochemical assay were used to test relevant cytokines of TGF-ß/Smad pathway and epithelial-mesenchymal transition (EMT) in MGC-803 cells and the tumor bearing nude mice. Results. YHJD inhibited proliferation, adhesion, migration, and invasion of MGC-803 gastric cancer cells in vitro. In in vivo studies, YHJD reduced the volume of the transplanted tumors. It also enhanced the expression of E-cadherin and decreased the levels of N-cadherin, TGF-ß, Snail, and Slug in both MGC-803 cells and the transplanted tumor by western blot assay. The immunohistochemical assay revealed that YHJD raised E-cadherin in the tumors of the mice; on the contrary, the expression of N-cadherin, Twist, vimentin, TGF-ßR I, p-Smad2, p-Smad3, Snail, and Slug reduced. Conclusion. YHJD can effectively inhibit the invasion and metastasis of gastric cancer cells. The mechanism may be related to TGF-ß/Smad pathway.
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To explore the role of CWP in invasion and migration of gastric cancer cells and its underlying molecular mechanism, we performed the experiment in SGC-7901 cells both in vitro and in vivo. In the cell experiment, we evaluated cell proliferation by MTT assay. The results showed that CWP can inhibit the growth of SGC-7901 cells. The influence on cell migration and invasion was detected by wound-healing and Transwell invasion assays. The results showed that the abilities of invasion and migration are restrained in CWP group. Western blot showed that CWP can decrease the expression of Cox-2 and inhibit the PI3K/AKT/GSK3ß/ß-catenin signaling pathway. In the animal experiment, we observed that CWP had an inhibitory effect on the growth of xenograft tumors of nude mice. IHC assay, ELISA, RT-PCR assay, and Western blot assay were used to test relevant cytokines of Cox-2/PGE2-PI3K/AKT/GSK3ß/ß-catenin pathway. The results showed that CWP can suppress relevant cytokines of Cox-2/PGE2-PI3K/AKT/GSK3ß/ß-catenin pathway. In conclusion, we suggest that CWP inhibits the invasion and metastasis of SGC-7901 cells via Cox-2/PGE2-PI3K/AKT/GSK3ß/ß-catenin signaling pathway.
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Objective To observe the clinical effects of Bushen Quyu Recipe (BQR) combined with acupuncture in treatment of clomiphene-resistant polycystic ovary syndrome (PCOS) infertility pa- tients after cold needle puncture drainage operation. Methods Totally 170 clomiphene-resistant PCOS in- fertility patients were recruited from March 2011 to October 2013, who were assigned to the control group and the observation group according to random blocking method, 85 cases in each group. Patients in the control group received cold needle puncture drainage operation alone, while those in the observation group additionally took BQR and received acupuncture after cold needle puncture drainage operation. Clinical efficacy was observed in the two groups before and after treatment. The spontaneous ovulation rate and the pregnancy rate were followed-up. The levels of serum sex hormones and hermodynamic indicators of ovarian blood flow were detected in the two groups before and after treatment. Results Successful pregnancy occurred in 63 cases of the observation group, significantly better than that of the con- trol group (52 cases; x² =7. 63, P <0. 05). The spontaneous ovulation rate was 75. 29% at month 3 of follow-ups and 88. 24% at month 6 of follow-ups in the observation group, significantly higher than those of the control group [56. 47% , 67. 06%; x² =6. 70, X² =10. 98, P <0. 05). In the observation group the total pregnancy rate was 74. 12% , higher than that of the control group [61. 18% ; X² =4. 46, P <0. 05). Compared with before treatment in the same group, levels of luteinizing hormone (LH) , testesterone (T) , estradiol (E2) significantly decreased in the two groups after treatment; levels of follicular stimulating hormone (FSH) , peak systolic velocity (PSV) , end diastolic volume (EDV) obviously increased in the two groups after treatment (P <0. 05). The decrement of T, LH, E2 levels and the increment of FSH, PSV, EDV levels were obviously higher in the observation group than in the control group (P <0. 05). Conclusion BQR combined with acupuncture in treatment of clomiphene-resistant PCOS infertility pa- tients after cold needle puncture drainage operation could effectively promote the recovery of menstruation, elevate the success rate of pregnancy, and was helpful to improving levels of sex hormones and ovarian blood perfusion.
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Terapia por Acupuntura , Clomifeno , Fármacos para la Fertilidad Femenina , Síndrome del Ovario Poliquístico , Clomifeno/uso terapéutico , Drenaje , Femenino , Fármacos para la Fertilidad Femenina/uso terapéutico , Humanos , Infertilidad Femenina , Inducción de la Ovulación , Síndrome del Ovario Poliquístico/terapia , Embarazo , PuncionesRESUMEN
Peroxisome proliferators activated receptors (PPARs) are closely related to human chronic disease, such as diabetes mellitus and the other metabolic diseases. In this study, a cell-based PPARs (PPAR α/ß/γ) model was developed for the screening of PPARs agonists from Alismatis Rhizoma (AR). Firstly, 293T cells were transfected with the reconstructed plasmid pBind-PPAR (α, ß, or γ)-LBD and reporter gene pGL4.35, and the known PPARs agonists were used as the positive control (fenofibrate for PPARα, L165041 for PPARß, and rosiglitazone for PPARγ). The ability of activation for PPARs was evaluated by analyzing the expression value of luciferase. Afterward, the 14 pure triterpenoids isolate from AR were analyzed on the developed PPARα, PPARß and PPARγ screening assay method. The results showed that the compounds 5, 6, 7, 8, 13 and 14 from AR have the ability of activation for PPARα. The compounds 5 and 7 from AR have the ability of activation for PPARß. The compounds 6, 7, 8 and 12 from RA have the ability of activation for PPARγ.In this study, the compound 12 from AR were found to display significant activation on PPARγ for the first time. AR triterpenoids extracts had the ability of activation for PPARα, PPARß and PPARγ. The results suggested that triterpenoids extracts from AR were PPARα, PPARß and PPARγ agonists. The results will help to provide reference for clinical application of AR, and establish a model for PPARs on 293T cell, which can be used to screen and evaluate PPARs natural agonists.
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Alismatales/química , Medicamentos Herbarios Chinos/farmacología , Receptores Activados del Proliferador del Peroxisoma/agonistas , Triterpenos/farmacología , Genes Reporteros , Células HEK293 , Humanos , PPAR alfa , PPAR gamma , PPAR-beta , Rizoma/químicaRESUMEN
Head-and-neck cancer is a major form of the disease worldwide. Treatment consists of surgery, radiation therapy and chemotherapy, but these have not resulted in improved survival rates over the past few decades. Versatile nanoparticles, with selective tumor targeting, are considered to have the potential to improve these poor outcomes. Application of nanoparticle-based targeted therapeutics has extended into many areas, including gene silencing, chemotherapeutic drug delivery, radiosensitization, photothermal therapy, and has shown much promise. In this review, we discuss recent advances in the field of nanoparticle-mediated targeted therapeutics for head-and-neck cancer, with an emphasis on the description of targeting points, including future perspectives.
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Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/terapia , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Terapia Genética , Humanos , Nanopartículas/uso terapéutico , FototerapiaRESUMEN
Geniposide, Geniposide, the main active component in extracts of Gardenia jasminoides ELLIS., is one of the main components of Huanglian-Jiedu-Tang (HJT). This study aimed to validate an indirect competitive enzyme-linked immunosorbent assay (icELISA) based on monoclonal antibodies (mAb) against geniposide (anti-geniposide mAb), which was developed by our lab, and apply the assay to study the pharmacokinetics of geniposide in HJT in mice. Blood samples were drawn from mice at predetermined time points after oral administration of HJT in three dosages. A linear correlation was obtained for geniposide concentrations in the range from 1.17 to 37.50 µg/mL. The intra-day and inter-day precision values of the icELISA method were well within the recommended range (≤10%). The recovery rates ranged from 99.74 to 102.40%. Stability studies showed that geniposide sample solutions were intact for 12 h. The Tmax and mean residence time (MRT) of geniposide of the three groups were consistent with previous data. The results suggest that a reliable and effective method was established and could be applied to the study of the pharmacokinetics of geniposide in HJT.
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Medicamentos Herbarios Chinos/farmacocinética , Iridoides/sangre , Administración Oral , Animales , Anticuerpos Monoclonales/inmunología , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/química , Ensayo de Inmunoadsorción Enzimática , Iridoides/análisis , Iridoides/inmunología , Masculino , Ratones Endogámicos BALB C , Reproducibilidad de los ResultadosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Yaotongning Capsule (YTNC) is a Traditional Chinese Medicinal (TCM) formula that has been demonstrated to be effective for osteoarthritis (OA) treatment in clinical use. Many compounds and 10 component medicinal materials (CMMs for short, i.e., the fundamental elements used in TCM formulas) in YTNC are challenging to study the pharmacological effects and interactions of the CMMs. Besides, it is difficult to know whether the YTNC formula is reasonable, and if YTNC formula could be improved without comparing YTNC with other TCM formulas of treating OA. Based on different combinations of the active fractions from the 10 CMMs of YTNC and eight additional herbs frequently used in the TCM formulas of treating OA, the present study evaluated systematically the in vitro effects of these active fractions and the interactions among the active fractions from YTNC on rat chondrocytes to find possible solutions of the above questions. MATERIALS AND METHODS: Based on the formulation of YTNC and the concept of combinatorial chemistry, the active fractions were applied to form the whole YTNC prescription (i.e., the combination of all YTNC active fractions and the extract of YTNC׳s vehicle), five disassembled formulas of YTNC (i.e., the combinations of some active fractions in YTNC) and 21 TCM samples consisted of different kinds of active fractions. The degenerated chondrocytes were induced with interleukin-1ß (IL-1ß), and then the half-effective concentration (EC50) value of the proliferation activity was analyzed to evaluate the 27 TCM samples. Nine samples were screened for the following evaluation on glycosaminoglycan (GAG) synthesis. Rat articular cartilage was obtained from six Sprague-Dawley rats (seven days of age), and then chondrocytes were isolated through enzymatic digestion with 0.2% Collagenase II. Proliferations of chondrocytes were examined through Cell Counting Kit-8 assay, when the intracellular levels of GAG were detected by 1,9-Dimethylmethylene blue staining. The interactions between the active fractions in YTNC were evaluated by comparing experimental EC50 values of the YTNC formulas with their additive EC50 values. The effects of every active fraction were estimated by comparing the EC50 values of the TCM sample containing the active fraction with that of the initial sample without the active fraction. RESULTS: The whole formula of YTNC was very good at promoting the proliferation and GAG synthesis among all the 27 TCM samples. The vehicle of YTNC (Chinese rice wine) strengthened the two activities of YTNC. Refer to promoting the proliferation in chondrocytes, Davallia mariesii flavonoids (not belong to YTNC) were more potent than Glycyrrhiza uralensis flavonoids in YTNC, while the saponins, volatile oils and polysaccharides of YTNC were more potent than those from the eight additional herbs. Some samples including fewer active fractions were as good as YTNC. The YTNC formula and its disassembled formulas exhibited good activities both in promoting the proliferation and GAG synthesis, and the whole formula was most potent among the six YTNC formulas. CONCLUSIONS: The YTNC formula is reasonable and has advantage in promoting the proliferation and GAG synthesis in IL-1ß induced chondrocytes. YTNC׳s vehicle Chinese rice wine plays an important role in strengthening the activity of YTNC. YTNC may have the potential activity on treating chondrocytes degeneration caused by OA. However, the formula still can be simplified based on the combination of alkaloids, flavonoids and 50% of saponins from Glycyrrhiza uralensis to improve its quality controllability and safety. The present study can be a quite purposeful work for developing new YTNC-based formulas with maximal therapeutic efficacy and minimal adverse effects.
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Condrocitos/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Animales , Cartílago Articular/citología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Condrocitos/citología , Condrocitos/metabolismo , Glicosaminoglicanos/metabolismo , Interleucina-1beta/farmacología , Medicina Tradicional China , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To explore the effects of folate on the expression of DNA methyltransferase 1 (DNMT1) and methyl-CpG-binding protein 2 (MeCP2) in cervical cancer cell lines. METHODS: Experimental study was carried out in vitro. Human cervical cancer cell lines, including C33A cell with HPV negative and Caski cell with HPV16 positive, were treated with different concentration of folate. The expression of DNMT1 and MeCP2 protein (by Western blot) and mRNA (by real-time PCR) were then detected in the two cell lines. RESULTS: It was found that supplement of folate was able to reduce the cell proliferation in C33A cell (r = 0.984, P < 0.001) and Caski cell (r = 0.978, P = 0.002), as well as induced the cell apoptosis (C33A: r = 0.989, P < 0.001; Caski: r = 0.994, P < 0.001). RESULTS: showed that the expression levels of DNMT1 protein (C33A: r = -0.914, P < 0.001; Caski: r = -0.859, P = 0.003) and MeCP2 protein (C33A: r = -0.830, P = 0.005; Caski: r = -0.981, P < 0.001) decreased gradually with the increase of folate concentrations, but the expression of DNMT1 and MeCP2 mRNA was not observed in Caski or C33A cell. When at the same levels of folate, the expression of DNMT1 protein or mRNA was higher in Caski cell than in C33A cell. However, the expression of MeCP2 protein or mRNA was higher in C33A cell than in Caski cell. CONCLUSION: Our finding indicated that adequate folate could effectively inhibit the proliferation of cervical cancer cells and facilitate their apoptosis in vitro, thus would reverse the aberration protein expression of DNMT1 and MeCP2. That there might be a synergistic action between HPV16 infection and parafunction of DNMT1 in cervical cancer, being noticed.
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ADN (Citosina-5-)-Metiltransferasas/metabolismo , Ácido Fólico/farmacología , Proteína 2 de Unión a Metil-CpG/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Línea Celular Tumoral , ADN (Citosina-5-)-Metiltransferasa 1 , Femenino , HumanosRESUMEN
OBJECTIVES: To investigate the effects of loading dose of atorvastatin on periprocedural myocardial injury and inflammatory reaction in patients with non-ST segment elevation (NSTE) acute coronary syndromes (unstable angina or NSTE acute myocardial infarction). METHODS: A total of 81 patients with NSTE-acute coronary syndromes were randomly divided into the pretreatment with atorvastatin group [80 mg 12 h before percutaneous coronary intervention (PCI), with a further 40 mg preprocedure dose] (n=41) or the placebo group (n=40). The main end point was a 30-day incidence of major adverse cardiac events (cardiac death, nonfatal acute myocardial infarction, or revascularization with either PCI or coronary artery bypass grafting). Creatine kinase-MB, cardiac troponin I, and high-sensitivity C-reactive protein levels were measured at the baseline and at 8 and 24 h after the procedure. RESULTS: Major adverse cardiac events occurred in 2.4% of patients in the atorvastatin group and 22.5% of those in the placebo group (P=0.0161). This difference was mostly because of reduction in the incidence of myocardial infarction (2.4 vs. 20.0%; P=0.0307). Markers of the two groups were elevated after PCI; however, the higher values of creatine kinase-MB, cardiac troponin I, and high-sensitivity C-reactive protein in the atorvastatin treatment group were significantly lower than those in the placebo group (P<0.01). CONCLUSION: Short-term pretreatment with a high dose of atorvastatin significantly reduces procedural myocardial injury in early PCI.