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1.
Clin Nutr ; 42(8): 1379-1388, 2023 08.
Article in English | MEDLINE | ID: mdl-37421851

ABSTRACT

BACKGROUND & AIMS: Whether the intake of docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, is beneficial for ovarian cancer (OC) remains controversial and we hope to disentangle this puzzle using genetic data from large-scale populations in European and Asian. METHODS: We employed, for the first time, a systematic Mendelian randomization (MR) design to comprehensively evaluate the causal effect of plasma DHA levels, an objective biomarker of DHA intake, on OC risk in European and then verified the extrapolation of the results in the Asian. Data in the analysis included genetic association data obtained from large-scale genome-wide association studies with 13,499 individuals for plasma DHA measurements and 66,450 individuals for OC in the European population, and 1361 individuals for plasma DHA measurements and 61,457 individuals for OC in the Asian population. The causal relationship between DHA and OC was estimated using the inverse-variance weighted approach, together with extensive validation and sensitivity analyses to verify the main results. RESULTS: In the European population, MR evidence suggested a causal relationship between higher plasma DHA levels and lower OC risk (OR, 0.89 for OC per one-SD increment in DHA; 95% CI, 0.83 to 0.96; P = 0.003). Subgroup analysis by histological type of OC indicated that this observed association was stronger among endometrioid ovarian cancer (EOC) (OR, 0.82; 95% CI, 0.69 to 0.96; P = 0.014). A similar causal association of borderline significance was reached in the Asian replication set. The above results were consistently supported by a series of validation and sensitivity analyses. CONCLUSION: Our study provided robust genetic evidence for a protective association between plasma DHA levels and lower risk of OC, especially EOC, in the European population. These findings may inform prevention strategies and interventions directed towards DHA intake and OC.


Subject(s)
Fatty Acids, Omega-3 , Ovarian Neoplasms , Humans , Female , Docosahexaenoic Acids , Genome-Wide Association Study , Mendelian Randomization Analysis , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/prevention & control , Polymorphism, Single Nucleotide/genetics
3.
Phytomedicine ; 102: 154171, 2022 Jul 20.
Article in English | MEDLINE | ID: mdl-35636165

ABSTRACT

BACKGROUND: Pulmonary hypertension (PH) is a progressive disorder lacking a validated and effective therapy which characterized by elevated pulmonary arterial pressure, vascular remodeling and eventual death. FDA approved sildenafil is being used as a first-line drug for PH, however, neither survival rates nor quality of life have been improved because of side effects and patient noncompliance. Thus, the exploration of novel therapeutic drugs is urgently needed. Astragaloside IV (ASIV) exhibits a protective effect on HPH, but its mechanisms of action is unclear. HYPOTHESIS: CD4+T cell subsets, Tfh and Tfr cells, may contribute to the development of chronic hypoxia-induced PH (HPH). We hypothesized that ASIV could effectively ameliorates pulmonary vascular remodeling of HPH by restraining the Tfh cell response and expanding Tfr cell response. METHODS AND RESULTS: HPH mice model was established by exposure to chronic hypoxia for 21 days. Mice were randomly assigned to six groups: NaCl group, model group, SN group (100 mg/kg of sildenafil), low-dose group (20 mg/kg of ASIV), medium-dose group (40 mg/kg of ASIV) and high-dose group (80 mg/kg of ASIV). Primary culture and identification of distal pulmonary artery smooth muscle cells (PASMCs) in mice were established. Here, we demonstrated that ASIV treatment could significantly ameliorate the increase of mean PAP, RV/ (LV+S) ratio and PAMT in HPH mice. ASIV inhibited Tfh cell differentiation and IL-21 production, but promoted Tfr cell differentiation and TGF-ß, IL-10 production. Chronic hypoxia promoted germinal center B cell responses, which inhibited by ASIV. ASIV regulated Tfh and Tfr cell differentiation by inhibiting the phosphorylation of mTOR signaling pathway, and the effect of ASIV-H was better than that observed in the SN group. ASIV inhibited the proliferation, migration and adhesion of PASMCs in vitro. Moreover, ASIV significantly downregulated the protein level of RhoA and upregulated the protein level of p27 in PASMCs under hypoxic condition. CONCLUSION: Collectively, ASIV may regulate Tfh and Tfr cell responses to subsequently repress pulmonary vascular remodeling and hypoxic pulmonary hypertension.


Subject(s)
Hypertension, Pulmonary , Animals , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/etiology , Hypoxia/complications , Hypoxia/drug therapy , Mice , Pulmonary Artery , Quality of Life , Saponins , Sildenafil Citrate/metabolism , Sildenafil Citrate/pharmacology , Sildenafil Citrate/therapeutic use , T Follicular Helper Cells , Triterpenes , Vascular Remodeling
4.
Phytother Res ; 35(10): 5720-5733, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34411362

ABSTRACT

Tumor resistance is the main cause of treatment failure and is associated with many tumor factors. Jaridon 6, a new diterpene extracted from Rabdosia rubescens (Hemsl.) Hara, which has been previously extracted by our research team, has been tested having more obvious advantages in resistant tumor cells. However, its mechanism is unclear. In this study, we studied the effect and the specific mechanism of Jaridon 6 in resistant gastric cancer cells. Cytotoxicity test, colony test, western blotting, and nude test verified the anti-drug resistance ability of Jaridon 6 in the MGC803/PTX and MGC803/5-Fu cells. Jaridon 6 has shown obvious inhibitory effects in the sirtuin 1 (SIRT1) enzyme test. Transmission electron microscopy and immunofluorescence tests further proved the autophagic action of Jaridon 6. Jaridon 6 could inhibit the proliferation of the resistant gastric cancer cell in vivo and in vitro. Jaridon 6 inhibited SIRT1 enzyme and induced autophagy by inhibiting the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway. Thus, it may be considered for treating gastric cancer resistance by individual or combined administration, as an SIRT1 inhibitor and autophagy inducer.


Subject(s)
Diterpenes, Kaurane , Isodon , Stomach Neoplasms , Apoptosis , Autophagy , Cell Line, Tumor , Cell Proliferation , Humans , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Sirtuin 1 , Stomach Neoplasms/drug therapy
5.
Biochem Biophys Res Commun ; 522(4): 862-868, 2020 02 19.
Article in English | MEDLINE | ID: mdl-31806372

ABSTRACT

Ebola virus (EBOV), pathogen of Ebola hemorrhagic fever (EHF), is an enveloped filamental RNA virus. Recently, the EHF crisis occurred in the Democratic Republic of the Congo again highlights the urgency for its clinical treatments. However, no Food and Drug Administration (FDA)-approved therapeutics are currently available. Drug repurposing screening is a time- and cost-effective approach for identifying anti-EBOV therapeutics. Here, by combinatorial screening using pseudovirion and minigenome replicon systems we have identified several FDA-approved drugs with significant anti-EBOV activities. These potential candidates include azithromycin, clomiphene, chloroquine, digitoxin, epigallocatechin-gallate, fluvastatin, tetrandrine and tamoxifen. Mechanistic studies revealed that fluvastatin inhibited EBOV pseudovirion entry by blocking the pathway of mevalonate biosynthesis, while the inhibitory effect of azithromycin on EBOV maybe due to its intrinsic cationic amphiphilic structure altering the homeostasis of later endosomal vesicle similar as tamoxifen. Moreover, based on structure and pathway analyses, the anti-EBOV activity has been extended to other family members of statins, such as simvastatin, and multiple other cardiac glycoside drugs, some of which exhibited even stronger activities. More importantly, in searching for drug interaction, we found various synergy between several anti-EBOV drug combinations, showing substantial and powerful synergistic against EBOV infection. In conclusion, our work illustrates a successful and productive approach to identify new mechanisms and targets for treating EBOV infection by combinatorial screening of FDA-approved drugs.


Subject(s)
Antiviral Agents/analysis , Antiviral Agents/pharmacology , Combinatorial Chemistry Techniques , Drug Approval , Drug Evaluation, Preclinical , Ebolavirus/drug effects , Azithromycin/pharmacology , Cardiac Glycosides/pharmacology , Cell Line , Cholesterol/biosynthesis , Drug Synergism , Ebolavirus/physiology , Fluvastatin/pharmacology , Humans , Mevalonic Acid/metabolism , Models, Biological , Surface-Active Agents/chemistry , Virion/drug effects , Virion/physiology , Virus Internalization/drug effects , Virus Replication/drug effects
6.
J Thorac Dis ; 11(9): 3785-3793, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31656651

ABSTRACT

BACKGROUND: According to several phase III studies, tiotropium [a long-acting muscarinic antagonist (LAMA)] is a well-tolerated add-on therapy to inhaled corticosteroids (ICS) for asthmatics with or without the addition of long-acting beta2-agonists (LABAs). However, real-world studies based on clinical phenotypes to predict the long-term need of tiotropium as an add-on therapy for asthmatics are limited. METHODS: This is a retrospective study conducted at a single medical center in Taiwan from July 2016 to July 2018. An asthma control test (ACT) is applied to uncontrolled asthmatics to evaluate the effectiveness of tiotropium as an add-on therapy. Asthmatic subgroups with different clinical phenotypes and needing long-term tiotropium as a maintenance treatment are identified. The effectiveness of tiotropium add-on therapy is defined as an improvement of ACT score ≥3 points 3 months after the treatment (vs. baseline), while the long-term requirement of tiotropium is defined as tiotropium dependency >1 year. RESULTS: The study analyzed a total of 160 uncontrolled asthmatics regardless of low- or medium-to-high-dose ICS plus LABA. One hundred and twelve patients responded well (ACT score increased ≥3 points) to tiotropium. These patients were further divided into two subgroups: one with tiotropium add-on therapy for ≥1 year due to patients' difficulties in stepping down from tiotropium; the other with tiotropium add-on therapy for <1 year due to successful step-down treatment according to Global Initiative for Asthma (GINA) score. All clinical characteristics of these two groups were collected and analyzed. Univariate and multivariate analyses showed that asthma-and-chronic obstructive pulmonary disease (COPD)-overlap (ACO), initial forced expiratory volume-one second (FEV1) % predicted <80%, or body mass index (BMI) >30 kg/m2 were predictors for asthmatics requiring long-term tiotropium add-on therapy. CONCLUSIONS: Tiotropium add-on therapy is effective for uncontrolled asthmatics. Moreover, patients with ACO, initial FEV1% predicted <80%, or BMI >30 kg/m2 require long-term tiotropium add-on therapy for asthma control.

7.
Nat Commun ; 9(1): 4280, 2018 10 15.
Article in English | MEDLINE | ID: mdl-30323200

ABSTRACT

Textiles that are capable of harvesting biomechanical energy via triboelectric effects are of interest for self-powered wearable electronics. Fabrication of conformable and durable textiles with high triboelectric outputs remains challenging. Here we propose a washable skin-touch-actuated textile-based triboelectric nanogenerator for harvesting mechanical energy from both voluntary and involuntary body motions. Black phosphorus encapsulated with hydrophobic cellulose oleoyl ester nanoparticles serves as a synergetic electron-trapping coating, rendering a textile nanogenerator with long-term reliability and high triboelectricity regardless of various extreme deformations, severe washing, and extended environmental exposure. Considerably high output (~250-880 V, ~0.48-1.1 µA cm-2) can be attained upon touching by hand with a small force (~5 N) and low frequency (~4 Hz), which can power light-emitting diodes and a digital watch. This conformable all-textile-nanogenerator is incorporable onto cloths/skin to capture the low output of 60 V from subtle involuntary friction with skin, well suited for users' motion or daily operations.


Subject(s)
Electric Power Supplies , Electricity , Nanoparticles/chemistry , Phosphorus/chemistry , Skin/anatomy & histology , Textiles , Touch/physiology , Biomechanical Phenomena , Friction , Humans , Motion
8.
Zhongguo Zhen Jiu ; 38(6): 575-9, 2018 Jun 12.
Article in Chinese | MEDLINE | ID: mdl-29971997

ABSTRACT

OBJECTIVE: To compare the effect differences between auricular intradermal needling combined with erjian (HX6,7i) bloodletting and oral administration of western medicine, and to explore the efficacy of neuroendocrine level in patients with perimenopausal insomnia. METHODS: Ninety patients were randomized into an observation group and a control group, 45 cases in each one. In the observation group, auricular intradermal needling combined with erjian (HX6,7i) bloodletting were adopted alternately in the two ears. The auricular points were shen (CO10), xin (CO15), gan (CO12), shenmen (TF4), jiaogan (AH6a), neifenmi (CO18) and erjian (HX6,7i). The treatment was required once 3 days on the auricular points of one side alternatively. Oral administration of estazolam (1mg each day) was applied in the control group for 2 courses, 4 weeks as 1 course, once a day. The scores of Pittsburgh sleep quality index (PSQI), the levels of serum estrogen (E2), 5-hydroxy tryptamine (5-HT) and norepinephrine (NE) were valuated in the two groups before and after treatment. RESULTS: After treatment, the total scores of PSQI reduced in the two groups (both P<0.05), and the improvements of sleeping quality, sleeping time, sleeping difficulty, daytime dysfunction and the total PSQI score in the observation group were superior to those in the control group (all P<0.05). There was no significant difference in serum E2 before and after treatment in the two groups,and between the two groups after treatment (all P>0.05). After treatment, 5-HT contents increased and NE levels decreased in the two groups (all P<0.05), with better results in the observation group (both P<0.05). The total effective rate was 95.6% (43/45) in the observation group, which was higher than 82.2% (37/45) in the control group (P<0.05). CONCLUSION: Auricular intradermal needling combined with erjian (HX6,7i) bloodletting can improve the sleep quality of patients with perimenopausal insomnia, and adjust the neurotransmitter level, which achieves better effect than western medication.


Subject(s)
Acupuncture Therapy , Sleep Initiation and Maintenance Disorders , Acupuncture Points , Bloodletting , Humans , Perimenopause , Sleep Initiation and Maintenance Disorders/therapy , Treatment Outcome
9.
Menopause ; 24(3): 299-307, 2017 03.
Article in English | MEDLINE | ID: mdl-27760084

ABSTRACT

OBJECTIVE: This study aims to evaluate the effectiveness and safety of Gua sha therapy on perimenopausal symptoms, quality of life, and serum female hormones in participants with perimenopausal syndrome. METHODS: A prospective, randomized, controlled clinical trial was conducted at the First Affiliated Hospital of Nanjing University of Chinese Medicine in China. Eighty women with perimenopausal syndrome were recruited and randomized into an intervention group or a control group. Participants in the intervention group received 15-minute Gua sha treatment sessions once a week plus conventional treatment for 8 weeks, whereas participants in the control group received conventional treatment alone. The primary outcome was the change in perimenopausal symptoms and quality of life as obtained through the modified Kupperman Index (KI) and the Menopause-Specific Quality of Life. The secondary outcome was the change of serum female hormones including estrogen, follicle-stimulating hormone, and luteinizing hormone. RESULTS: Seventy-five out of 80 participants (93.8%) completed the study-38 in the intervention group and 37 in the control group. The baseline levels of demographic and outcome measurements were comparable between the two groups. After eight sessions of intervention, the reduction in the total modified KI score was, however, 16.32 ±â€Š4.38 in the intervention group and 11.46 ±â€Š5.96 in the control group, with a difference of 4.86 ±â€Š6.15 (P < 0.01) between the two groups. Also the reductions of hot flash/sweating, paresthesia, insomnia, nervousness, melancholia, fatigue, and headache were greater in the intervention group than in the control group (P < 0.05). The reduction in the total Menopause-Specific Quality of Life score was 17.87 ±â€Š3.84 in the intervention group and 13.62 ±â€Š7.40 in the control group, with a difference of 4.46 ±â€Š7.52 (P < 0.01) between the two groups. And the scores for vasomotor, psychosocial, and physical domains in the intervention group were significantly lower than those in the control group (P < 0.05). There were no significant differences in serum estrogen, follicle-stimulating hormone, and luteinizing hormone between the two groups. CONCLUSIONS: The results of this study suggest that Gua sha therapy was effective and safe in relieving perimenopausal symptoms and improving the quality of life in participants with perimenopausal syndrome. The therapy may serve as a promising, effective, nondrug treatment for perimenopausal syndrome in clinical work. Additional research is needed to better understand its effectiveness and examine its mechanism for treating perimenopausal syndrome.


Subject(s)
Medicine, Chinese Traditional/methods , Perimenopause , Physical Therapy Modalities , Adult , Estrogens/blood , Female , Follicle Stimulating Hormone/blood , Hot Flashes/blood , Hot Flashes/therapy , Humans , Luteinizing Hormone/blood , Middle Aged , Prospective Studies , Quality of Life , Syndrome , Treatment Outcome
10.
Zhongguo Zhen Jiu ; 36(12): 1257-1262, 2016 Dec 12.
Article in Chinese | MEDLINE | ID: mdl-29231362

ABSTRACT

OBJECTIVE: To compare the difference in the therapeutic effect on post-infectious cough differentiated as wind-cold retention in the lung between the combined therapy of scraping and xuanfei zhisou decoction and the simple application of xuanfei zhisou decoction. METHODS: Eighty patients were randomized into a combined therapy group and a Chinese herbal medicine group, 40 cases in each one. In the Chinese herbal medicine group, the oral administration of xuanfei zhisou decoction was used. The main ingredients included roasted herba ephedrae, amygdalus communis vas, rhizoma zingiberis recens, platycodon grandiflorum, flos farfarae, pinellia temata, radix stemonae, herba periliae, etc., one dose a day, twice a day. In the combined therapy group, on the basis of the treatment as the Chinese herbal medicine group, scraping therapy was added and applied to the bladder meridian of foot-taiyang, the lung meridian of hand-taiyin, the conception vessel and the governor vessel, focusing on Tiantu (CV 22), Baihui (GV 20), Dazhui (GV 14), Feishu (BL 13), Fengmen (BL 12), Taiyuan (LU 9), Lieque (LU 7) and Fengchi (GB 20), once a week and one-week treatment as one session. Totally, the continuous two sessions were required in the two groups. The cough symptom score, cough remission time, relapse, TCM syndrome score, the score of Leicester cough questionnaire (LCQ), SP concentration in the supernatant of the induced sputum before and after treatment as well as clinical efficacy were observed in the two groups. RESULTS: The cough symptom score, TCM symptom score and SP concentration in the supernatant of the induced sputum were all apparently reduced after treatment in the patients of the two groups (all P<0.01). The scores in the combined therapy group were reduced in the higher amplitude as compared with those in the Chinese herbal medicine group (all P<0.01). The total effective rate was 95.0% (38/40) in the combined therapy group, better than 87.5% (35/40) in the Chinese herbal medicine group (P<0.05). Regarding the cough remission time and relapse rate, the results in the combined therapy group were better than those in the Chinese herbal medicine group[(5.3±1.2) d vs (7.4±1.5) d, P<0.01; 0% (0/19) vs 62.5% (5/8), P<0.01]. The scoreo of LCQ was all apparently improved in the patients of the two groups (both P<0.01), and the score in the combined therapy group was higher than that in the Chinese herbal medicine group (P<0.01). CONCLUSIONS: Scraping therapy combined with xuanfei zhisou decoction and the simple application of xuanfei zhisou decoction all relieve the symptoms of post-infectious cough and improves the living quality. The therapeutic effects of the combined therapy are superior to the oral administration of xuanfei zhisou decoction.


Subject(s)
Acupuncture Therapy/methods , Cough/therapy , Drugs, Chinese Herbal/therapeutic use , Lung Diseases/therapy , Acupuncture Points , Combined Modality Therapy/methods , Cough/etiology , Drugs, Chinese Herbal/chemistry , Humans , Lung Diseases/etiology , Wind
11.
Zhongguo Zhen Jiu ; 36(8): 821-826, 2016 Aug 12.
Article in Chinese | MEDLINE | ID: mdl-29231567

ABSTRACT

OBJECTIVE: To observe the efficacy difference between scrapping therapy combined with Qingxin Zishen Decoction and the single application of Qingxin Zishen Decoction for perimenopausal syndrome (PMS) with pattern of fire excess from yin deficiency. METHODS: Eighty patients were assinged into an observation group and a control group, 40 cases in each one. Patients in the control group were treated with oral administration of Qingxin Zishen Decoction to clear heart heat and nourish kidney. One dose of the decoction was taken by two times within one day. Based on the treatment of the control group, patients in the observation group were additionally treated with scrapping therapy along the urinary bladder meridian of foot-taiyang, heart meridian of hand-shaoyin and kidney meridian of foot-shaoyin; the scrapping therapy was performed at Back-shu points, Shenmen (HT 7), Yongquan (KI 1), Taixi (KI 3), Zhaohai (KI 6), Sanyinjiao (SP 6), Zusanli (ST 36), etc.; the treatment was given once every week. Four weeks of treatment were taken as one course in two groups, and totally 2 courses were given. The modified Kupperman score, menopausal quality of life (MENQOL), level of serum estrogen (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH) before and after treatment as well as the clinical efficacy were valuated between the two groups. RESULTS: After treatment, each item score and total score of modified Kupperman were reduced apparently in the two groups (P<0.01,P<0.05) except dyspareunia score in the control group. The score of hot flash and sweating, paresthesia, depression, fatigue, arthralgia, palpitation, formication, urinary symptoms and total score in the observation group were superior to those in the control group (P<0.01, P<0.05). After treatment, the total score and each dimension score of MENQOL were obviously decreased in the two groups (all P<0.01), and the scores of vasomotor symptoms, psychosocial condition and physical condition in the observation group were significantly lower than those in the control group (P<0.01, P<0.05). There were no significant differences of serum hormone levels before and after treatment between the two groups (all P>0.05), however, after treatment, the serum E2 level had the tendency to raise and serum LH, FSH levels had the tendency to decrease in the observation group. The total effective rate was 97.4% (37/38) in the observation group, which was higher apparently than 81.1% (30/37) in the control group (P<0.01). CONCLUSIONS: The scrapping therapy combined with Qingxin Zishen Decoction or the simple application of Qingxin Zishen Decoction can both improve PMS symptoms and the quality of life, delay the ovary recession; the combination of scrapping therapy and Qingxin Zishen Decoction achieve superior efficacy on PMS syndrome to the simple application of Qingxin Zishen Decoction.


Subject(s)
Acupuncture Points , Drugs, Chinese Herbal/therapeutic use , Hot Flashes/therapy , Perimenopause , Yin Deficiency/therapy , Case-Control Studies , Female , Humans , Meridians , Quality of Life
12.
Article in Chinese | WPRIM | ID: wpr-495497

ABSTRACT

Objectives To observe the clinical significance and application value of autologous blood transfusion in neurosurgery of primary hospital. Methods Four hundred and fourteen patients who underwent the neurosurgery operation and were subjected to intraoperative blood transfusion were selected, among whom 97 patients were subjected to autologous blood transfusion (observation group), and 317 patients were subjected to heterogenous blood transfusion (control group). The condition of intraoperative blood transfusion, changes of hemoglobin and hematocrit, blood transfusion related cost were compared between 2 groups. Results There were no statistical differences in operation time, infusion volume, rate of transfusion related complications and postoperation hemoglobin, hematocrit between observation group and control group (P>0.05). The patients in control group were infused with 189 000 ml, and the transfusion liquid volume proportion of total blood transfusion was 79.22%(189 000/238 580);13 patients in observation group were used the heterogenous blood transfusion with 5 400 ml, and the transfusion liquid volume proportion of total blood transfusion was 10.30%(5 400/52 430). Eighty-six patients (88.66%, 86/97) in observation group performed autologous blood collection and transfusion, the volume of autologous collection was 80 650 ml, and the volume of transfusion was 47 020 ml. Eleven patients in observation group did not perform autologous blood transfusion, among whom 6 patients was because of operational and mechanical reasons, and 5 patients performed collection but did not transfuse. The cost of heterogenous concentrated suspension red blood cell over 6 U was significantly higher than the cost of disposable material and injection of autologous blood:(2 287.06 ± 243.52) yuan vs. (1 595.08 ± 133.95) yuan, and there was statistical difference (P<0.05). The rate of heterogenous concentrated suspension red blood cell 6 U in control group was 14.83%(47/317), and the rate of over 6 U was 6.62%(21/317). Conclusions The autologous blood transfusion is safe and effective, and it is worth popularizing in neurosurgery of primary hospital. But in the process of its application, it is necessary to strengthen the user′s operating skills and ensure the quality of autologous blood transfusion.

13.
Neuropharmacology ; 67: 419-31, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23231807

ABSTRACT

Quercetin has demonstrated protective effects against Aß-induced toxicity on both neurons and endothelial cells. However, whether or not quercetin has an effect on the neurovascular coupling is unclear. In the present study, we aim to investigate the anti-amnesic effects of quercetin and to explore the underlying mechanisms. Aß(25-35) (10 nmol) was administrated to mice i.c.v. Quercetin was administrated orally for 8 days after injection. Learning and memory behaviors were evaluated by measuring spontaneous alternation in Morris Water Maze test and the step-through positive avoidance test. The regional cerebral blood flow was monitored before the Aß(25-35) injection and on seven consecutive days after injection. Mice were sacrificed and cerebral cortices were isolated on the last day. The effects of quercetin on the neurovascular unit (NVU) integrity, microvascular function and cholinergic neuronal changes, and the modification of signaling pathways were tested. Our results demonstrate that quercetin treatment for Aß(25-35)-induced amnesic mice improved the learning and memory capabilities and conferred robust neurovascular coupling protection, involving maintenance of the NVU integrity, reduction of neurovascular oxidation, modulation of microvascular function, improvement of cholinergic system, and regulation of neurovascular RAGE signaling pathway and ERK/CREB/BDNF pathway. In conclusion, in Aß(25-35)-induced amnesic mice, optimal doses of quercetin administration were beneficial. Quercetin protected the NVU likely through reduction of oxidative damage, inactivation of RAGE-mediated pathway and preservation of cholinergic neurons, offering an alternative medication for Alzheimer's disease.


Subject(s)
Amnesia/metabolism , Amnesia/prevention & control , Amyloid beta-Peptides/toxicity , Neuroprotective Agents/administration & dosage , Peptide Fragments/toxicity , Quercetin/administration & dosage , Receptors, Immunologic/metabolism , Amnesia/chemically induced , Amyloid beta-Peptides/administration & dosage , Animals , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Injections, Intraventricular , Male , Mice , Neural Pathways/drug effects , Neural Pathways/physiology , Peptide Fragments/administration & dosage , Plant Extracts/administration & dosage , Receptor for Advanced Glycation End Products , Receptors, Immunologic/antagonists & inhibitors
14.
Zhonghua Yi Xue Za Zhi ; 91(20): 1388-92, 2011 May 31.
Article in Chinese | MEDLINE | ID: mdl-21756809

ABSTRACT

OBJECTIVE: To compare the chemosensitivity of pirarubicin (THP) and epirubicin (EPI) in primary breast cancer (PBC) cells so as to examine their differential chemosensitivity to THP and EPI by CD-DST (collagen gel droplet embedded culture-drug sensitivity test) system; To detect the differences in the short-term clinical efficacy and side effects between TAC (docetaxel + pirarubicin + cyclophosphamide) and TEC (docetaxel + epirubicin + cyclophosphamide) as the neoadjuvant chemotherapy regimens and the long-term clinical efficacy of CAF (cyclophosphamide + pirarubicin + fluorouracil) and CEF (cyclophosphamide + epirubicin + fluorouracil) as the chemotherapy regimens in breast cancer; To evaluate the feasibility of THP as an adjuvant chemotherapeutic regimen in the treatment of breast cancer. METHODS: From January 2008 to January 2009, a total of 129 fresh breast cancer samples were collected. The differential chemosensitivity of cultured PBC cells to THP and EPI was measured by CD-DST test. And 139 cases of PBC patients inIIb-IIIc phase were randomly divided into two groups: TAC and TEC groups. After 4-6 cycles of neoadjuvant chemotherapy, the primary lesion, axillary lymph nodes and side effects were assessed; The clinical data and survival status of 1241 cases of PBC patients treated at our hospital from 2003 to 2006 were collected and divided into CAF and CEF groups according to their chemotherapeutic regimens. Long-term prognosis was compared between two groups. RESULTS: There was no significant difference of chemosensitivity between THP and EPI in PBC cells (P = 0.743); The overall response rate (RR) of neoadjuvant chemotherapy was 87.8%; the clinical objective responses, pathologic complete remission (pCR), clinical complete remission (cCR), clinical partial remission (cPR) and stable disease (SD) of groups TAC and TEC were 88.7%, 11.3%, 28.2%, 60.6%, 11.3% vs 86.8%, 10.3%, 26.5%, 60.3%, 13.2% respectively. There was no significant difference between two groups (P > 0.05). No significant differences existed between two groups in such side effects as leukopenia, thrombocytopenia, constipation, cardiotoxity and hepatorenal dysfunction (P > 0.05). The gastrointestinal reactions of nausea and vomiting was less frequent in the TAC group than that in the TEC group (46.5% vs 66.2%, P = 0.019); There was no significant difference in 5-year disease-free survival rate (79% vs 78%) and overall survival rate between two groups (85% vs 82%, P > 0.05). CONCLUSION: There were no significant differences in chemosensitivity, clinical efficacy of neoadjuvant chemotherapy, side effects or long-term efficacy between THP and EPI. Both pirarubicin and epirubicin may be used as conventional chemotherapy in breast cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Doxorubicin/analogs & derivatives , Epirubicin/therapeutic use , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Female , Fluorouracil/therapeutic use , Humans , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Retrospective Studies , Tamoxifen/therapeutic use , Young Adult
15.
Zhongguo Zhong Yao Za Zhi ; 32(19): 2058-62, 2007 Oct.
Article in Chinese | MEDLINE | ID: mdl-18161305

ABSTRACT

OBJECTIVE: To evaluate the inhibitory effect of quercetin, rutin and puerarin on the LDL oxidation induced by Cu2+ and to investigate their action on the prevention and treatment of atherosclerosis. METHOD: The serum LDL was isolated by the one step density gradient ultracentrifugation. The LDL oxidation was induced by Cu2+ in vitro for different time periods. Quercetin, rutin and puerarin at 5 micromol x L(-1) were added respectively, as the experimental groups, 3 hours before oxidation. The oxidation of LDL in experimental and control groups was identified by measuring A234, REM, TBARS and protein carbonyls content, and the values were compared between the two groups. RESULT: (1) The values of A234, REM, TBARS and protein carbonyls formation increased gradually during LDL oxidation induced by Cu2+ in vitro. (2) During LDL oxidation induced by Cu2+ in vitro and incubation with each of quercetin, rutin and puerarin, the kinetic changes of A234, REM, TBARS and protein carbonyls formation showed lag phases of 2-6 h, 2 h and 2 h respectively, and the corresponding values for each of the agents treated group were reduced by 27.7%-49.6%, 24.1%-38.6%, 19.8%-34.3% and 36.4%-56.8%; 12.8%-39.3%, 15.7%-32.0%, 19.0%-28.1% and 12.8%-50.3%; and 3.3%-19.2%, 7.0%-22.5%, 19.5%-22.8% and 8.6%-47.0%, respectively. CONCLUSION: These results suggest that quercetin, rutin and puerarin can substantially inhibit LDL oxidation, and quercetin has antioxidation ability stronger than rutin and puerarin.


Subject(s)
Antioxidants/pharmacology , Isoflavones/pharmacology , Lipoproteins, LDL/metabolism , Quercetin/pharmacology , Rutin/pharmacology , Copper/pharmacology , Humans , Lipoproteins, LDL/blood , Lipoproteins, LDL/chemistry , Oxidation-Reduction/drug effects , Protein Carbonylation/drug effects , Thiobarbituric Acid Reactive Substances/metabolism , Time Factors
16.
Zhong Yao Cai ; 30(6): 677-81, 2007 Jun.
Article in Chinese | MEDLINE | ID: mdl-17918439

ABSTRACT

OBJECTIVE: To evaluate the inhibitory effect of Isorhamnetin and Hesperidin on the LDL oxidation induced by Cu2+. METHODS: The serum LDL was isolated by the one step density gradient ultracentrifugation. The LDL oxidation was induced by Cu2+ in vitro for different time periods. Isorhamnetin and Hesperidin at 5 micromol/L were added respectively, as the experimental groups, 3 hours before oxidation. The oxidation of LDL in experimental and control groups was identified by measuring A234 , REM, TBARS and protein carbonyls content. RESULTS: The values of A234, REM, TBARS and protein carbonyls formation increased gradually during LDL oxidation induced by Cu2+ in vitro. During LDL oxidation induced by Cu2+ in vitro and incubation with each of Isorhamnetin and Hesperidin, the kinetic changes of A234 , REM, TBARS and protein carbonyls formation showed lag phases of 2-4 h and 2 h respectively, and the corresponding values for each of the agents treated group were reduced by 23.5%-40.4%, 20.5%-37.7%, 18.6-30.3% and 20.1%-52.4% (P < 0.001); and 11.1%-21.2%, 9.2%-28.3%, 13.7%-21.3% and 5.0%-43.8% respectively (P < 0.001, P < 0.01, P < 0.001 and P < 0.05). CONCLUSION: It suggests that Isorhamnetin and Hesperidin can substantially inhibit LDL oxidation, and Isorhamnetin has antioxidation ability stronger than Hesperidin.


Subject(s)
Antioxidants/pharmacology , Copper/pharmacology , Flavonols/pharmacology , Hesperidin/pharmacology , Lipoproteins, LDL/metabolism , Copper/chemistry , Drugs, Chinese Herbal/pharmacology , Humans , Kinetics , Lipid Peroxidation/drug effects , Lipoproteins, LDL/blood , Lipoproteins, LDL/chemistry , Oxidation-Reduction/drug effects , Protein Carbonylation/drug effects , Quercetin/analogs & derivatives , Thiobarbituric Acid Reactive Substances/chemistry , Thiobarbituric Acid Reactive Substances/metabolism , Time Factors
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