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1.
Inorg Chem ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38950326

ABSTRACT

Inorganic materials doped with chromium (Cr) ions generate remarkable and adjustable broadband near-infrared (NIR) light, offering promising applications in the fields of imaging and night vision technology. However, achieving high efficiency and thermal stability in these broadband NIR phosphors poses a significant challenge for their practical application. Here, we employ crystal field engineering to modulate the NIR characteristics of Cr3+-doped Gd3Ga5O12 (GGG). The Gd3MgxGa5-2xGexO12 (GMGG):7.5% Cr3+ (x = 0, 0.05, 0.15, 0.20, and 0.40) phosphors with NIR emission are developed through the cosubstitution of Mg2+ and Ge4+ for Ga3+ sites. This cosubstitution strategy also effectively reduces the crystal field strength around Cr3+ ions, which results in a significant enhancement of the photoluminescence (PL) full width at half-maximum (fwhm) from 97 to 165 nm, alongside a red shift in the PL peak and an enhancement of the PL intensity up to 2.3 times. Notably, the thermal stability of the PL behaviors is also improved. The developed phosphors demonstrate significant potential in biological tissue penetration and night vision, as well as an exceptional scintillation performance for NIR scintillator imaging. This research paves a new perspective on the development of high-performance NIR technology in light-emitting diodes (LEDs) and X-ray imaging applications.

2.
Inorg Chem ; 62(47): 19350-19357, 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-37960854

ABSTRACT

The visualized dual-modal stress-temperature sensing refers to the ability of a sensor to provide real-time and visible information about both stress and temperature and has indeed attracted significant interest in various fields. However, the development of convenient methods for achieving this capability remains a challenge. In this work, a dual-modal stress-temperature sensor is successfully fabricated using a ZnS/Cu@CsPbBr1.2I1.8 glass ceramics (GCs)/polydimethylsiloxane (PDMS) (ZCP) composite film. The tunable ML color is achieved by modulating the concentration of CsPbBr1.2I1.8 GCs in the ZCP composite films based on the light conversion process from ZnS/Cu to CsPbBr1.2I1.8 GCs. Additionally, the stress and temperature can be visualized simultaneously by integrating the ML intensity and ML color of the ZCP composite film. This feature allows for the real-time monitoring of automotive tire temperature by embedding the ZCP composite film on the tire surface, enabling a strong and stable response to both stress and temperature changes. Overall, this work offers a convenient, efficient, and repeatable approach for achieving visualized dual-modal stress-temperature sensing in the fields of mechanical engineering, structural health monitoring, and intelligent devices.

3.
Inorg Chem ; 62(40): 16485-16492, 2023 Oct 09.
Article in English | MEDLINE | ID: mdl-37738045

ABSTRACT

The current optical anticounterfeit strategies that rely on multimode luminescence in response to the photon or thermal stimuli have significant importance in the field of anticounterfeiting and information encryption. However, the dependence on light and heat sources might limit their flexibility in practical applications. In this work, Er3+ single-doped CaF2 phosphors that show multistimuli-responsive luminescence have been successfully prepared. The as-obtained CaF2:Er3+ phosphor exhibits green photoluminescence (PL) and color-tunable up-conversation (UC) luminescence from red to green due to the cross-relaxation of Er3+ ions. Additionally, as-obtained CaF2:Er3+ phosphors also display green mechano-luminescence behavior, which is induced by the contact electrification between the CaF2 particles and PDMS polymers, enabling the phosphor to flexibly respond to mechanical stimuli. Moreover, feasible anticounterfeiting schemes with the capability of multistimuli-responsive and flexible decryption have been constructed, further expanding the application of optical materials in the field of advanced anticounterfeiting and information encryption.

4.
Folia Histochem Cytobiol ; 60(3): 260-270, 2022.
Article in English | MEDLINE | ID: mdl-36124413

ABSTRACT

INTRODUCTION: Abnormal ovarian angiogenesis is a common feature of polycystic ovary syndrome (PCOS), a typical endocrine disorder affecting women of reproductive age. Histone deacetylase 5 (HDAC5) has been documented as a suppressor of angiogenesis. The aim of this study was to explore the effect of HDAC5 on ovarian angiogenesis in a PCOS mouse model. MATERIAL AND METHODS: PCOS was induced in female C57BL/6 mice by 20-day administration of dehydroepiandrosterone (DHEA). HDAC5 was over-expressed in PCOS mice by corresponding adenovirus injection. In total, 120 mice were used in this study. Western-blotting, real-time PCR, hematoxylin and eosin staining, enzyme-linked immunosorbent assay (ELISA), immunohistochemical staining, flow cytometry, and co-immunoprecipitation were respectively used to evaluate the effect of HDAC5 on PCOS mice. RESULTS: PCOS ovaries showed a compensatory increase in HDAC5 expression, while HDAC5 over-expression alleviated abnormalities in ovarian morphology and serum hormone levels after PCOS modeling. HDAC5 inhibited ovarian angiogenesis in PCOS mice by regulating angiogenesis-related factors, such as VEGFA, platelet-derived growth factors B and D (PDGFB/D), and angiopoietins 1 and 2 (ANGPT1/2) and CD31. HDAC5 over-expression decreased levels of reactive oxygen species (ROS) and malondialdehyde, while promoting activities of catalase and superoxide dismutase in ovaries of PCOS mice, suggesting its suppressive effects on oxidative stress, an inducer of uncontrolled angiogenesis. Moreover, HDAC5 suppressed activation of angiogenesis-related HIF-1α/VEGFA/VEGFR2 signaling in PCOS ovaries partly via inhibiting VEGFR2 acetylation. CONCLUSIONS: This study reveals the protective role of HDAC5 in PCOS by inhibiting ovarian angiogenesis and provides a molecular candidate for PCOS therapy in the future.


Subject(s)
Polycystic Ovary Syndrome , Angiogenesis Inducing Agents , Angiopoietins , Animals , Catalase , Dehydroepiandrosterone , Disease Models, Animal , Eosine Yellowish-(YS) , Female , Hematoxylin , Histone Deacetylases , Humans , Malondialdehyde , Mice , Mice, Inbred C57BL , Polycystic Ovary Syndrome/chemically induced , Polycystic Ovary Syndrome/drug therapy , Proto-Oncogene Proteins c-sis , Reactive Oxygen Species , Superoxide Dismutase
5.
Article in English | MEDLINE | ID: mdl-35754690

ABSTRACT

Background: Exercise is one of the recommended interventions for polycystic ovary syndrome (PCOS), and current evidence has shown that Tai chi may have favorable effects. The objective of this randomized controlled pilot trial was to study the feasibility and potential effects of Tai chi for overweight/obese adolescents and young women with PCOS, so a future definitive randomized controlled trial (RCT) can be well designed and implemented. Materials and Methods: This study recruited 50 patients who were randomly assigned to two groups (Tai chi and self-monitored exercise) at a ratio of 3 : 2. The intervention lasted for 3 months, and the feasibility and effectiveness outcomes were measured. Results: A total of 42 patients completed the study, including 24 in the Tai chi group and 18 in the control group. Compared with the self-monitored exercise group, there was a significantly decreased body mass index (BMI) in the Tai chi group adjusted for baseline BMI. The testosterone level and lipid profile were also decreased compared to controls; the same tendency was also observed for the homeostasis model assessment of insulin resistance (HOMA-IR), but the difference did not achieve statistical significance. Twenty-four (out of 30, 80%) patients in the Tai chi group and 18 (out of 20, 90%) patients in the self-monitored exercise group completed the data collection. A total of 36 exercise sessions were held in both groups. Patients in the Tai chi group took a mean of 34.0 ± 2.21 classes (93.06%), and those in the self-monitored exercise group engaged in 32 ± 3.06 exercise sessions (88.27%) out of the 36 required exercise sessions. Conclusions: The present pilot study was feasible to deliver; there was a decrease in BMI, testosterone level, and lipid profile for PCOS patients in the Tai chi group at 3 months. In a future definitive trial, lower recruitment rate and outcome measurements lead to poor patient acceptance such as the 5-time point oral glucose tolerance test need to be considered and one fixed type of aerobic exercise and supervision from the investigator for the control group are also needed. Trial registration: ClinicalTrials.gov, NCT02608554.

6.
Pharmaceuticals (Basel) ; 14(7)2021 Jul 14.
Article in English | MEDLINE | ID: mdl-34358098

ABSTRACT

Site-specific antibody conjugations generate homogeneous antibody-drug conjugates with high therapeutic index. However, there are limited examples for producing the site-specific conjugates with a drug-to-antibody ratio (DAR) greater than two, especially using engineered cysteines. Based on available Fc structures, we designed and introduced free cysteine residues into various antibody CH2 and CH3 regions to explore and expand this technology. The mutants were generated using site-directed mutagenesis with good yield and properties. Conjugation efficiency and selectivity were screened using PEGylation. The top single cysteine mutants were then selected and combined as double cysteine mutants for expression and further investigation. Thirty-six out of thirty-eight double cysteine mutants display comparable expression with low aggregation similar to the wild-type antibody. PEGylation screening identified seventeen double cysteine mutants with good conjugatability and high selectivity. PEGylation was demonstrated to be a valuable and efficient approach for quickly screening mutants for high selectivity as well as conjugation efficiency. Our work demonstrated the feasibility of generating antibody conjugates with a DAR greater than 3.4 and high site-selectivity using THIOMABTM method. The top single or double cysteine mutants identified can potentially be applied to site-specific antibody conjugation of cytotoxin or other therapeutic agents as a next generation conjugation strategy.

7.
Front Endocrinol (Lausanne) ; 12: 659268, 2021.
Article in English | MEDLINE | ID: mdl-34149613

ABSTRACT

Background: Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine disorder. And metabolic syndrome (MS) is an important bridge for PCOS patients to develop other diseases, such as diabetes and coronary heart disease. Our aim was to study the potential metabolic characteristics of PCOS-MS and identify sensitive biomarkers so as to provide targets for clinical screening, diagnosis, and treatment. Methods: In this study, 44 PCOS patients with MS, 34 PCOS patients without MS, and 32 healthy controls were studied. Plasma samples of subjects were tested by ultraperformance liquid chromatography (UPLC) system combined with LTQ-orbi-trap mass spectrometry. The changes of metabolic characteristics from PCOS to PCOS-MS were systematically analyzed. Correlations between differential metabolites and clinical characteristics of PCOS-MS were assessed. Differential metabolites with high correlation were further evaluated by the receiver operating characteristic (ROC) curve to identify their sensitivity as screening indicators. Results: There were significant differences in general characteristics, reproductive hormone, and metabolic parameters in the PCOS-MS group when compared with the PCOS group and healthy controls. We found 40 differential metabolites which were involved in 23 pathways when compared with the PCOS group. The metabolic network further reflected the metabolic environment, including the interaction between metabolic pathways, modules, enzymes, reactions, and metabolites. In the correlation analysis, there were 11 differential metabolites whose correlation coefficient with clinical parameters was greater than 0.4, which were expected to be taken as biomarkers for clinical diagnosis. Besides, these 11 differential metabolites were assessed by ROC, and the areas under curve (AUCs) were all greater than 0.7, with a good sensitivity. Furthermore, combinational metabolic biomarkers, such as glutamic acid + leucine + phenylalanine and carnitine C 4: 0 + carnitine C18:1 + carnitine C5:0 were expected to be sensitive combinational biomarkers in clinical practice. Conclusion: Our study provides a new insight to understand the pathogenesis mechanism, and the discriminating metabolites may help screen high-risk of MS in patients with PCOS and provide sensitive biomarkers for clinical diagnosis.


Subject(s)
Metabolic Syndrome/diagnosis , Metabolic Syndrome/prevention & control , Polycystic Ovary Syndrome/complications , Adolescent , Adult , Biomarkers/blood , Carnitine/blood , Female , Glutamic Acid/blood , Humans , Leucine/blood , Metabolic Syndrome/blood , Metabolic Syndrome/etiology , Metabolomics , ROC Curve , Young Adult
8.
Fertil Steril ; 113(6): 1275-1285.e2, 2020 06.
Article in English | MEDLINE | ID: mdl-32482257

ABSTRACT

OBJECTIVE: To investigate the placental morphology alterations and identify the clinical characteristics of women with polycystic ovary syndrome (PCOS) and their newborns. Pregnant women with PCOS (n = 12) and pregnant women without PCOS (n = 11) were recruited. Then, the placenta, maternal blood and cord blood were collected after delivery. DESIGN: Clinical observational study. SETTING: Not applicable. PATIENT(S): In the present study, pregnant women with PCOS and healthy pregnant women were recruited from the clinic of the Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, China, between February 2015 and October 2015. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): A proteomic analysis was performed on the placenta in women with PCOS and healthy women. RESULT(S): The maternal testosterone, androstenedione, dehydroepiandrosterone sulfate, free androgen index, cholesterol, apolipoprotein B, and apolipoprotein B/apolipoprotein A-I levels were significantly higher in the PCOS group than in the control group, and the offspring in the PCOS group had higher dehydroepiandrosterone sulfate, high-density lipoprotein, and cholesterol levels, when compared with the control group. The placenta in the PCOS group demonstrated infarction, calcification, and a greater intervillous space, when compared with the control group. A higher level of estrogen receptor-ß protein was observed in the placenta of women with PCOS, when compared with women without PCOS. A total of 258 proteins in the placenta were identified to be significantly different, when the PCOS and control groups were compared, and fibronectin 1 exhibited the closest relationship with other differential proteins. CONCLUSION(S): The overexposure to hyperandrogenism and hyperlipidemia affects the functions of the placenta, which are associated with the development of metabolic disorders in newborns.


Subject(s)
Androgens/blood , Fetal Blood/metabolism , Infant, Newborn, Diseases/etiology , Lipids/blood , Placenta/metabolism , Polycystic Ovary Syndrome/complications , Adult , Biomarkers/blood , Case-Control Studies , Female , Humans , Hyperandrogenism/blood , Hyperandrogenism/etiology , Hyperandrogenism/physiopathology , Hyperlipidemias/blood , Hyperlipidemias/etiology , Hyperlipidemias/physiopathology , Infant, Newborn , Infant, Newborn, Diseases/blood , Infant, Newborn, Diseases/physiopathology , Placenta/physiopathology , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/physiopathology , Pregnancy , Risk Factors , Up-Regulation
9.
Zhongguo Zhong Yao Za Zhi ; 44(20): 4350-4353, 2019 Oct.
Article in Chinese | MEDLINE | ID: mdl-31872644

ABSTRACT

Kangfu Xiaoyan Suppository is widely used in the treatment of gynecological inflammatory diseases. Long-term clinical application and a certain amount of research evidences show that Kangfu Xiaoyan Suppository can alleviate the clinical symptoms of pelvic inflammatory diseases,reduce the recurrence rate,and relieve sequelae,with a better safety and economic characteristics. As a type of nationally protected traditional Chinese medicine and type B medicine included in medical insurance,it has been selected as a Chinese patent medicine for rectal administration. It was included in the Guidelines for diagnosis and treatment of common gynecological diseases of traditional Chinese medicine published by the Chinese Academy of Traditional Chinese Medicine in 2012,the Pelvic inflammatory diseases diagnosis and treatment guidelines issued by the Infectious Diseases Collaborative Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association in 2014,and the group standard of Single use of traditional Chinese medicine/combined antibiot guidelines for clinical practice-pelvic inflammatory diseases of the Chinese Academy of Traditional Chinese Medicine in 2017. To further enhance clinicians' understanding of the drug and better guide its rational clinical use,experts from the field of gynecology of traditional Chinese and Western medicine were invited to develop and compile this expert consensus. This consensus takes full account of clinical evidences and expert clinical experience,and form recommendations for clinical problems based on evidences and consensus recommendations for clinical problems without evidence by nominal grouping method. The expert consensus is mainly formed in the consideration of six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on clinical research evidences and expert experience,this consensus provides a preliminary reference for the clinical use of the drug in a concise and clear format. However,evidence-based support is still required in a large number of high-quality studies,and this consensus will be revised in the future according to new clinical problems and the update of evidence-based evidence in practical application.


Subject(s)
Consensus , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Pelvic Inflammatory Disease/drug therapy , Female , Humans , Nonprescription Drugs , Suppositories
10.
BMJ Open ; 9(5): e027498, 2019 05 28.
Article in English | MEDLINE | ID: mdl-31142530

ABSTRACT

INTRODUCTION: Approximately 5%-20% of reproductive women suffer from polycystic ovary syndrome (PCOS). Auricular points acupressure (AA) may serve as alternative management for PCOS for its benefits in both physical and psychological well-being. However, the effects of AA for insulin resistance (IR) in overweight/obese PCOS women have not been confirmed. METHODS AND ANALYSIS: The present study is designed as a randomised, placebo-controlled pilot trial to evaluate the effectiveness and safety of AA in treating IR in women with PCOS. A total of 60 eligible PCOS subjects will be randomised into an intervention group (AA group) and a control group (sham AA group) in a ratio of 1:1. Magnetic beads will be taped to the auricular points by the same senior acupuncture specialist from the First Affiliated Hospital, Heilongjiang University of Chinese Medicine. The treatment will last for 12 weeks. Primary outcome measure will be changes in homeostasis model assessment of IR between baseline and after 3 months of AA/sham AA treatment. Secondary outcomes include hormonal profile, weight, waist/hip circumference, body mass index, blood pressure, Ferriman-Gallwey score, acne and the assessment of health-related quality of life. Outcome measures are collected at baseline and the end of treatment visit. ETHICS AND DISSEMINATION: The protocol has been approved by the ethics committee of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine (HZYLLKY201800301). Written informed consent will be obtained from all participants. The results will be disseminated through peer-reviewed journals for publications. TRIAL REGISTRATION NUMBER: NCT03546595; Pre-results.


Subject(s)
Acupressure/methods , Ear , Insulin Resistance , Obesity/complications , Overweight/complications , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/therapy , Research Design , Adolescent , Adult , Female , Follow-Up Studies , Humans , Pilot Projects , Treatment Outcome , Young Adult
11.
Trials ; 19(1): 512, 2018 Sep 20.
Article in English | MEDLINE | ID: mdl-30236149

ABSTRACT

BACKGROUND: Tai Chi is a moderately intense exercise that dates back to ancient China. It has been reported that Tai Chi not only has beneficial effects on metabolic disorders, such as diabetes, cardiovascular diseases and obesity, but also has favorable effects on psychological well-being. Since these conditions are quite closely associated with polycystic ovary syndrome (PCOS), we hypothesis that Tai Chi could be a potential treatment option for PCOS patients. We aim to determine the feasibility and effectiveness of Tai Chi on overweight/obese adolescent and young women with PCOS. METHODS: A total of 50 patients will be randomized into two arms: (1) Tai Chi or (2) self-monitored exercise. Both groups will exercise for 3 months. The primary hypothesis is that Tai Chi results in a significantly lower Body Mass Index (BMI) than self-monitored exercise. The study was approved by the Ethics Committee of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine. DISCUSSION: This is the first study to determine the feasibility and effectiveness of Tai Chi in treating overweight/obese adolescent and young women with PCOS. The trial will provide evidence to assess the feasibility of a future multicenter, randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02608554 . Registered on 17 November 2015.


Subject(s)
Pediatric Obesity/therapy , Polycystic Ovary Syndrome/therapy , Tai Ji , Adolescent , Adult , Age Factors , Body Mass Index , China , Feasibility Studies , Female , Humans , Pediatric Obesity/diagnosis , Pediatric Obesity/physiopathology , Pilot Projects , Polycystic Ovary Syndrome/diagnosis , Polycystic Ovary Syndrome/physiopathology , Randomized Controlled Trials as Topic , Single-Blind Method , Time Factors , Treatment Outcome , Weight Loss , Young Adult
12.
JAMA ; 317(24): 2502-2514, 2017 06 27.
Article in English | MEDLINE | ID: mdl-28655015

ABSTRACT

Importance: Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence. Objective: To assess whether active acupuncture, either alone or combined with clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome. Design, Setting, and Participants: A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups. Interventions: Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity. Main Outcomes and Measures: The primary outcome was live birth. Secondary outcomes included adverse events. Results: Among the 1000 randomized women (mean [SD] age, 27.9 [3.3] years; mean [SD] body mass index, 24.2 [4.3]), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene (P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 [28.7%] vs 70 of 455 [15.4%], respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 [21.8%] vs 105 of 468 [22.4%], respectively; difference, -0.6%; 95% CI, -5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 [5.0%] vs 8 of 500 [1.6%], respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 [7.4%] vs 9 of 500 [1.8%], respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%). Conclusions and Relevance: Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women. Trial Registration: clinicaltrials.gov Identifier: NCT01573858.


Subject(s)
Acupuncture Therapy , Clomiphene/therapeutic use , Fertility Agents, Female/therapeutic use , Infertility, Female/therapy , Live Birth/epidemiology , Polycystic Ovary Syndrome/therapy , Acupuncture Therapy/adverse effects , Acupuncture Therapy/statistics & numerical data , Adult , Body Mass Index , Clomiphene/adverse effects , Combined Modality Therapy/methods , Contusions/etiology , Diarrhea/etiology , Double-Blind Method , Drug Administration Schedule , Female , Fertility Agents, Female/adverse effects , Humans , Infertility, Female/drug therapy , Infertility, Female/etiology , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/drug therapy , Pregnancy , Single-Blind Method , Time Factors
13.
J Pharm Biomed Anal ; 120: 127-33, 2016 Feb 20.
Article in English | MEDLINE | ID: mdl-26730509

ABSTRACT

Polycystic ovary syndrome (PCOS) is a most common, heterogeneous, complex endocrinopathy disease. Traditional Chinese medicine (TCM) has been used in the treatment of PCOS for many years. However, the mechanism underlying TCM remains obscure and challenging. In this study, 30 PCOS subjects were separated into normoinsulinemic group (NI=13) and hyperinsulinemic group (HI=17), and treated for three menstrual cycles with TCM Formula, Bushen Huatan Formula (BHF). A metabolomics approach based on ultra-high-performance liquid chromatography (UPLC) coupled with linear ion trap Orbi-trap mass spectrometer (LTQ Orbi-trap MS) is used to investigate serum metabolic changes of TCM intervention to PCOS. After BHF intervention for three menstrual cycles, the serum levels of glycerophosphorylethanolamine (GPEA), creatine, creatinine decreased in both NI and HI groups. Furthermore, in NI group, the main manifestation was the changes of phospholipid metabolism. While in HI group, lysine, phenol sulfate, phe-phe etc. decreased, and ornithine, proline, betaine, acetylcholine etc. increased. Combined with clinical biochemical data, BHF was proved effective to PCOS by reducing the inflammatory reaction and oxidative stress. This study also illustrates that the LC-MS based metabolomic approach is a helpful tool to evaluate curative effect and to understand the mechanisms of TCM.


Subject(s)
Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/metabolism , Serum/metabolism , Adolescent , Adult , Chemistry, Pharmaceutical/methods , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/therapeutic use , Female , Humans , Inflammation/blood , Lipid Metabolism/drug effects , Mass Spectrometry/methods , Medicine, Chinese Traditional/methods , Metabolomics/methods , Oxidative Stress/drug effects , Phospholipids/metabolism , Polycystic Ovary Syndrome/drug therapy , Young Adult
14.
Se Pu ; 32(5): 464-71, 2014 May.
Article in Chinese | MEDLINE | ID: mdl-25185305

ABSTRACT

Polycystic ovary syndrome (PCOS) is a complex, heterogeneous disorder, which seriously impacts the health of reproductive age women. Thus reasonable individual-based treatment is important. In this study, the serum samples of 15 overweight PCOS patients before and after treatment with berberine for three months were collected for clinic biochemical test and metabolomic research. Metabolomic profiling based on ultra high performance liquid chromatography (UHPLC) coupled with quadrupole time-of-flight mass spectrometry (q-TOF MS) was used to investigate metabolic changes of PCOS. Compared with before treatment, the patients after berberine treatment can be separated into distinct clusters as displayed by the orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) score plot with model parameter: R2Y = 0.892, Q2 (cum) = 0.577, which indicated changes in metabolites after berberine treatment. The differential metabolites related to berberine treatment were selected when their variable importance values were more than 1, and p < 0.05 with nonparametric test. These differential metabolites were all involved in lipids metabolism, including phosphatidylcholines, sphingomyelin, stearic acid and erucamide. The pharmacological results and metabolomic data revealed that berberine can strengthen the sensitivity of insulin and rectify the dyslipidemia of overweight PCOS patients. This study also illustrates that the LC-MS based metabolomic method is helpful for evaluating the treatment of traditional Chinese medicines.


Subject(s)
Berberine/therapeutic use , Metabolomics , Polycystic Ovary Syndrome/drug therapy , Chromatography, High Pressure Liquid , Discriminant Analysis , Female , Humans , Least-Squares Analysis , Mass Spectrometry , Medicine, Chinese Traditional , Overweight/physiopathology , Polycystic Ovary Syndrome/metabolism
15.
J Proteome Res ; 13(2): 1101-11, 2014 Feb 07.
Article in English | MEDLINE | ID: mdl-24428203

ABSTRACT

Polycystic ovary syndrome (PCOS) is a complex, heterogeneous disorder, which produces in 5-10% reproductive age women. In this study, a nontargeted metabolomics approach based on ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry is used to investigate serum metabolic characteristics of PCOS. PCOS women and healthy control can be clustered into two distinct groups based on multivariate statistical analysis. Significant increase in the levels of unsaturated free fatty acids, fatty acid amides, sulfated steroids, glycated amino acid and the decrease in levels of lysophosphatidylcholines, lysophosphatidylethanolamines, etc., were found. These metabolites showed abnormalities of lipid- and androgen-metabolism, increase of stearoyl-CoA desaturase (SCD) activity and accumulation of advanced glycation end-products in PCOS patients. On the basis of the binary logistic regression model, free fatty acid (FFA) 18:1/FFA 18:0, FFA 20:3, dihydrotestosterone sulfate, glycated phenylalanine, and uridine were combined as a diagnostic biomarker. The area under the curve (AUC) of combinational biomarker was 0.839 in 131 discovery phase samples and 0.874 in 109 validation phase samples. The findings of our study offer a new insight to understand the pathogenesis mechanism, and the discriminating metabolites may provide a prospect for PCOS diagnosis.


Subject(s)
Chromatography, Liquid/methods , Mass Spectrometry/methods , Metabolomics , Polycystic Ovary Syndrome/blood , Adult , Female , Humans , Young Adult
16.
BMJ Open ; 3(11): e003934, 2013 Nov 25.
Article in English | MEDLINE | ID: mdl-24282248

ABSTRACT

INTRODUCTION: Letrozole is being used as an alternative to clomiphene citrate in women with polycystic ovary syndrome (PCOS) requiring ovulation induction. Berberine, a major active component of Chinese herbal medicine rhizoma coptidis, has been used to improve insulin resistance to facilitate ovulation induction in women with PCOS but there is no study reporting the live birth or its potential as a complementary treatment to letrozole. We aim to determine the efficacy of letrozole with or without berberine in achieving live births among 660 infertile women with PCOS in Mainland China. METHODS AND ANALYSIS: This study is a multicentre randomised, double-blind trial. The randomisation scheme is coordinated through the central mechanism and stratified by the participating site. Participants are randomised into one of the three treatment arms: (1) letrozole and berberine, (2) letrozole and berberine placebo, or (3) letrozole placebo and berberine. Berberine is administered three times a day (1.5 g/day) for up to 24 weeks, starting on day 1 after a spontaneous period or a withdrawal bleeding. Either letrozole or letrozole placebo 2.5 mg is given daily from day 3 to day 7 of the first three cycles and the dose is increased to 5 mg/day in the last three cycles, if not pregnant. The primary hypothesis is that the combination of berberine and letrozole results in a significantly higher live birth rate than letrozole or berberine alone. ETHICS AND DISSEMINATION: The study was approved by the ethics committee of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine. Study findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01116167.

17.
Article in English | MEDLINE | ID: mdl-24023577

ABSTRACT

Acupuncture is an alternative therapy to induce ovulation in women with polycystic ovary syndrome (PCOS), but there is no study reporting the live birth rate following ovulation induction by acupuncture or its potential as an adjuvant treatment to clomiphene citrate (CC). We assess the efficacy of acupuncture with or without CC in achieving live births among 1000 PCOS women in Mainland China. This paper reports the methodology of an ongoing multicenter randomized controlled trial. The randomization scheme is coordinated through the central mechanism and stratified by the participating sites. Participants will be randomized into one of the four treatment arms: (A) true acupuncture and CC, (B) control acupuncture and CC, (C) true acupuncture and placebo CC, and (D) control acupuncture and placebo CC. To ensure the quality and integrity of the trial we have developed a unique multinational team of investigators and Data and Safety Monitoring Board. Up to the end of April 2013, 326 subjects were recruited. In conclusion, the success of this trial will allow us to evaluate the additional benefit of acupuncture beyond the first line medicine for fertility treatment in PCOS women in an unbiased manner.

18.
Methods Mol Biol ; 1045: 145-71, 2013.
Article in English | MEDLINE | ID: mdl-23913146

ABSTRACT

Currently, the principal chemistries for the preparation of antibody-drug conjugates (ADC) target either lysines or cysteines for coupling cytotoxic drugs for delivery to target cells expressing tumor-specific antigens. All of these chemistries generate populations of molecules which differ in critical properties which are known to affect efficacy, pharmacokinetics, and the therapeutic window. Of key interest are methods to minimize this heterogeneity to achieve reproducible product profiles and efficacy. A current trend in the development of ADC is the evaluation of suitable targets, antibodies, and payloads, occurring well before process development to produce conjugates of clinical quality. This creates a need for an ability to generate comparably high-quality products early in development and at sufficient scale for evaluating in vitro potency and in vivo efficacy, as well as the early identification of any deficiencies in critical quality attributes including solubility and stability. Here we elaborate detailed protocols using maleimide-based chemistry for the conjugation to reduce hinge disulfides in antibodies by several cytotoxic drugs. We present a method for the initial characterization of the reduction/alkylation reaction using polyethylene-glycol (PEG) as a drug surrogate, a 5 mg scale drug conjugation to provide material for initial characterization including cell proliferation assays and a 150 mg scale process for performing efficacy studies in small animals. These methods yield well-defined predictable product profiles at high yield and with low impurities. These procedures include details relevant to the execution of these methods in a safe and contained manner within a typical laboratory environment.


Subject(s)
Antineoplastic Agents/chemistry , Immunoconjugates/chemistry , Maleimides/chemistry , Molecular Targeted Therapy , Neoplasms/drug therapy , Sulfhydryl Compounds/chemistry , Antineoplastic Agents/therapeutic use , Immunoconjugates/therapeutic use , Phosphines/chemistry , Pilot Projects , Polyethylene Glycols/chemistry , Reducing Agents/chemistry
19.
Trials ; 14: 226, 2013 Jul 18.
Article in English | MEDLINE | ID: mdl-23866924

ABSTRACT

BACKGROUND: Insulin resistance and hyperinsulinemia play a key role in the pathogenesis of polycystic ovary syndrome (PCOS), which is characterized by hyperandrogenism, ovulatory dysfunction, and presence of polycystic ovaries on pelvic scanning. Insulin resistance is significantly associated with the long-term risks of metabolic syndrome and cardiovascular disease. Berberine has effects on insulin resistance but its use in women with PCOS has not been fully investigated. In this paper, we present a research design evaluating the effects of berberine on insulin resistance in women with PCOS. METHODS/DESIGN: This is a multicenter, randomized, placebo-controlled and double-blind trial. A total of 120 patients will be enrolled in this study and will be randomized into two groups. Berberine or placebo will be taken orally for 12 weeks. The primary outcome is the whole body insulin action assessed with the hyperinsulinemic-euglycemic clamp. DISCUSSION: We postulate that women with PCOS will have improved insulin resistance following berberine administration. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov, NCT01138930.


Subject(s)
Berberine/therapeutic use , Blood Glucose/drug effects , Hypoglycemic Agents/therapeutic use , Insulin Resistance , Insulin/blood , Polycystic Ovary Syndrome/drug therapy , Research Design , Administration, Oral , Adolescent , Adult , Berberine/administration & dosage , Berberine/adverse effects , Biomarkers/blood , Blood Glucose/metabolism , China , Clinical Protocols , Double-Blind Method , Female , Glucose Clamp Technique , Glucose Tolerance Test , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/diagnosis , Polycystic Ovary Syndrome/physiopathology , Predictive Value of Tests , Treatment Outcome , Young Adult
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