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1.
Nutrients ; 15(11)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37299424

RESUMO

With advancing age, women experience irreversible deterioration in the quality of their oocytes, resulting in reduced fertility. To gain a deeper understanding of the influence of ferroptosis-related genes on ovarian aging, we employed a comprehensive approach encompassing spatial transcriptomics, single-cell RNA sequencing, human ovarian pathology, and clinical biopsy. This investigation revealed the intricate interactions between ferroptosis and cellular energy metabolism in aging germ cells, shedding light on the underlying mechanisms. Our study involved 75 patients with ovarian senescence insufficiency, and we utilized multi-histological predictions of ferroptosis-related genes. Following a two-month supplementation period with DHEA, Ubiquinol CoQ10, and Cleo-20 T3, we examined the changes in hub genes. Our results showed that TFRC, NCOA4, and SLC3A2 were significantly reduced and GPX4 was increased in the supplement group, confirming our prediction based on multi-omic analysis. Our hypothesis is that supplementation would enhance the mitochondrial tricarboxylic acid cycle (TCA) or electron transport chain (ETC), resulting in increased levels of the antioxidant enzyme GPX4, reduced lipid peroxide accumulation, and reduced ferroptosis. Overall, our results suggest that supplementation interventions have a notable positive impact on in vitro fertilization (IVF) outcomes in aging cells by improving metal ion and energy metabolism, thereby enhancing oocyte quality in older women.


Assuntos
Ferroptose , Humanos , Feminino , Idoso , Ferroptose/genética , Ovário , Envelhecimento/genética , Oócitos/metabolismo , Senescência Celular
2.
Biomed Pharmacother ; 163: 114888, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37196543

RESUMO

The decline in oocyte quality with age is an irreversible process that results in low fertility. Reproductive aging causes an increase in oocyte aneuploidy leading to a decrease in embryo quality and an increase in the incidence of miscarriage and congenital defects. Here, we show that the dysfunction associated with aging is not limited to the oocyte, as oocyte granulosa cells also show a range of defects related to mitochondrial activity. The addition of Y-27632 and Vitamin C combination drugs to aging germ cells was effective in enhancing the quality of aging cells. We observed that supplement treatment significantly decreased the production of reactive oxygen species (ROS) and restored the balance of mitochondrial membrane potential. Supplementation treatment reduces excessive mitochondrial fragmentation in aging cells by upregulating mitochondrial fusion. Moreover, it regulated the energy metabolism within cells, favoring oxygen respiration and reducing anaerobic respiration, thereby increasing cellular ATP production. In an experiment with aged mice, supplement treatment improved the maturation of oocytes in vitro and prevented the buildup of ROS in aging oocytes in culture. Additionally, this treatment resulted in an increased concentration of anti-mullerian hormone (AMH) in the culture medium. By improving mitochondrial metabolism in aging females, supplement treatment has the potential to increase quality of oocytes during in vitro fertilization.


Assuntos
Envelhecimento , Oócitos , Feminino , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Oócitos/metabolismo , Senescência Celular , Mitocôndrias
3.
Taiwan J Obstet Gynecol ; 61(2): 223-229, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35361380

RESUMO

OBJECTIVE: Poor ovarian responder (POR) poses a significant challenge for in vitro fertilization (IVF). Previous studies have suggested that dehydroepiandrosterone (DHEA) may improve IVF outcomes in POR. The current study attempts to investigate the clinical benefits of DHEA in POR and the possible mechanism of DHEA on cumulus cells (CCs). MATERIALS AND METHODS: A total of 60 women who underwent IVF treatment participated, including 22 normal ovarian responders (NORs) and 38 PORs. PORs were assigned to receive DHEA supplementation (n = 18) or not (n = 20) before IVF cycles. For all patients, CCs were obtained after oocyte retrieval. In the CCs, mRNA expression of mitochondrial dynamics relataed genes were measured. RESULTS: Supplementation of DHEA in POR reduced mitochondrial fission in CCs and decreased the expression of PGAM5 in CCs. CONCLUSION: The benefit of DHEA supplementation on IVF outcomes in POR is significant, and this effect may be mediated in part through improved mitochondrial dynamics in CC.


Assuntos
Células do Cúmulo , Desidroepiandrosterona , Dinâmica Mitocondrial , Proteínas Mitocondriais , Indução da Ovulação , Fosfoproteínas Fosfatases , Células do Cúmulo/citologia , Células do Cúmulo/efeitos dos fármacos , Desidroepiandrosterona/farmacologia , Feminino , Fertilização in vitro , Humanos , Dinâmica Mitocondrial/efeitos dos fármacos , Proteínas Mitocondriais/genética , Ovário , Fosfoproteínas Fosfatases/genética
4.
Biosci Biotechnol Biochem ; 86(5): 646-654, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35218182

RESUMO

Atopic dermatitis (AD) is a chronic inflammatory and pruritic disease; it can be treated by inhibiting inflammation. Sarcodia suiae sp. is an edible, artificially cultivable red algae with multiple bioactivities. We assessed the anti-inflammatory activity of the ethyl acetate fraction of S. suiae sp. ethanol extract (PD1) on 1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD-like lesions. Results show that PD1 alleviated symptoms and significantly decreased clinical dermatitis score. PD1 inhibited serum immunoglobulin E expression and alleviated swelling in the spleen and subiliac lymph nodes. In skin tissues, PD1 alleviated aberrant hyperplasia, decreased epidermal thickness, and decreased the accumulation of mast cells. PD1 mediated the recovery of skin barrier-related proteins, such as claudin-1 and filaggrin. Our study demonstrated that PD1 has anti-inflammatory effects, alleviates AD symptoms, inhibits inflammatory responses in skin tissues, and restores barrier function in DNCB-induced AD mice. These findings reveal that S. suiae sp. extract provides an alternative protective option against AD.


Assuntos
Dermatite Atópica , Rodófitas , Acetatos , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Citocinas/metabolismo , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/metabolismo , Dinitroclorobenzeno/metabolismo , Dinitroclorobenzeno/farmacologia , Dinitroclorobenzeno/uso terapêutico , Etanol/metabolismo , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/metabolismo , Rodófitas/metabolismo , Pele
5.
Phytother Res ; 35(7): 3954-3967, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33825221

RESUMO

Microalgae extracts have shown antitumor activities. However, the antitumor mechanism of them is not yet completely clear, especially the effect on cancer stem cells (CSCs). This study aimed to elucidate the antitumor activity and mechanism of microalgal extract from thermotolerant Coelastrella sp. F50 (F50) in hepatocellular carcinoma (HCC). Oncogenic behaviors were analyzed using cell proliferation, colony formation, invasion, sphere formation, and side population cells (SPCs) assays in HCC cells after F50 treatment. The molecular mechanism was further studied by quantitative real-time PCR, immunoblot, and immunofluorescence analyses. The chemopreventive efficacy of F50 was evaluated in rat orthotopic hepatoma, and the hepatic pathologies were investigated by immunohistochemical, immunoblot, and immunofluorescence analyses. F50 specifically suppressed hepatic CSCs (tumor spheres, drug efflux, CD133/ABCG2 CSCs markers) with no cytotoxicity in vitro. In the animal experiments, prophylactic F50 administration significantly attenuated tumor progression and improved liver function in HCC-bearing rats. In the mechanistic analysis, F50 potentially inhibited cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2 ) axis in HCC cells and rat hepatoma, and exogenous PGE2 restored CSCs properties in F50-treated HCC cells. In summary, F50 extract inhibits hepatic CSCs by COX-2/PGE2 downregulation and may facilitate a novel phytotherapy for HCC prevention.


Assuntos
Carcinoma Hepatocelular , Clorofíceas/química , Neoplasias Hepáticas , Células-Tronco Neoplásicas/efeitos dos fármacos , Extratos Vegetais , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Hepáticas/tratamento farmacológico , Microalgas/química , Extratos Vegetais/farmacologia , Ratos
6.
Cryobiology ; 98: 80-86, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33386123

RESUMO

Coral reefs worldwide are receding because of detrimental human activities, and cryopreservation of coral larvae would ensure that their genetic biodiversity is not irremediably lost. In recent years, the vitrification and laser warming of coral propagules has demonstrated promising results. During cryopreservation, cellular membranes undergo substantial reconfigurations that may affect survival. Fat enrichment may alter the physical proprieties of cell membranes and improve resistance to low temperatures. Therefore, the aim of this study was to determine whether supplementation of exogenous lipids using liposomes would improve cryosurvival and further development of the vitrified and laser-warmed coral larvae of Seriatopora caliendrum and Pocillopora verrucosa. A vitrification solution (VS) composed of 2 M ethylene glycol (EG), 1 M propylene glycol (PG), 40% (w/v) Ficoll, and 10% gold nanoparticles (at a final concentration of 1.2 × 1018 particles/m3 and an optimised emission wavelength of 535 nm) was chosen. Coral larvae were subjected to vitrification with VS incorporating one of four lipid classes: phosphatidylcholine (PC), phosphatidylethanolamine (PE), erucic acid (EA), and linoleic acid (LA). Warming was achieved using a single laser pulse (300 V, 10 ms pulse width, 2 mm laser beam diameter). A significantly higher vitality rate was observed in S. caliendrum larvae subjected to vitrification and laser warming with EA-incorporated VS, and P. verrucosa larvae vitrified and laser warmed using PE-incorporated VS achieved a significantly higher settlement rate. Our study demonstrated that supplementation of exogenous lipids with liposomes enhances coral larvae cryotolerance and improves cryopreservation outcomes. Lipid enrichment may play a key role in cryobanking coral propagules, and in propagule development after thawing.


Assuntos
Antozoários , Nanopartículas Metálicas , Animais , Criopreservação/métodos , Suplementos Nutricionais , Ouro , Larva , Lasers , Lipídeos , Lipossomos , Vitrificação
7.
Zhongguo Zhen Jiu ; 40(7): 721-5, 2020 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-32648395

RESUMO

OBJECTIVE: To observe the therapeutic effect of herb-separated moxibustion combined with budesonide nasal spray (rhinocort) on moderate to severe persistent allergic rhinitis (AR) of kidney-yang deficiency type, and to explore the correlation between nasal temperature and condition of allergic rhinitis. METHODS: A total of 70 patients with moderate to severe persistent AR were randomized into an observation group (35 cases) and a control group (35 cases, 3 cases dropped off). Both groups were treated with rhinocort, one spray on each side of the nostril (approximately 64 µg each spray), once in the morning and once in the evening, for 4 weeks. On the basis of the above treatment, the observation group was treated with herb-separated moxibustion at Shenshu (BL 23), Feishu (BL 13), Zhiyang (GV 9), Dazhui (GV 14), 3 moxibustions per acupoint, a single treatment lasting about 30 min. This treatment was given once every other day, 3 times every week, and totally continuous 4 weeks. The changes of AR symptom visual analogue scale (VAS) scores were observed before and after treatment and at 3 months follow-up after treatment. The heat variation (temperature, range) on projection areas of the nose, lungs, large intestine and kidneys of the two groups' patients before and after treatment were detected by the infrared thermal imaging diagnostic system, and the correlation between the VAS scores and nasal temperature before and after treatment was analyzed. The clinical effects of both groups were evaluated according to the VAS score. RESULTS: The total effective rate in the observation group after treatment was 85.7% (30/35), which was higher than 71.9% in the control group (23/32, P<0.05). After treatment and at follow-up, the VAS scores of both groups were lower than those before treatment (P<0.05), and the VAS score of the observation group was lower than that of the control group at follow-up (P<0.05). After treatment, the nasal temperature, pulmonary range, large intestinal range and renal range of the observation group were all lower than those before treatment (P<0.05), the nasal temperature and nasal range of the control group were lower than before treatment (P<0.05), and the reduction of nasal temperature, nasal range and renal range in the observation group was greater than that of the control group (P<0.05). Before and after treatment, there was a correlation between VAS score and nasal temperature (P<0.05). CONCLUSION: The herb-separated moxibustion combining western medication has a better effect and long-term effect than western medication alone for moderate to severe persistent AR, which can improve heat variation on projected areas of the nose, lung, large intestine and kidney of patients. In addition, nasal temperature can reflect the severity of the symptoms of patients with moderate to severe persistent AR, or it can be used as a secondary indicator to evaluate condition of AR.


Assuntos
Terapia por Acupuntura , Moxibustão , Rinite Alérgica/terapia , Pontos de Acupuntura , Budesonida/uso terapêutico , Humanos , Deficiência da Energia Yang
8.
Zhen Ci Yan Jiu ; 45(1): 46-50, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-32144908

RESUMO

OBJECTIVE: To observe the clinical effect of herbal cake-partitioned moxibustion combined with Rhinocort spray in the treatment of symptoms, sleep quality and daily life quality of patients with moderate-severe allergic rhinitis(AR).. METHODS: A total of 67 patients with persistent moderate-severe AR were recruited in the present study and randomized into a treatment group (n=35) and a control group (n=32). The patients in the treatment group were treated by herbal cake-partitioned moxibustion (applied to Dazhui [GV14], and bilateral Feishu [BL13], Shenshu [BL23] and Zhiyang [GV9], 3 moxa-cones/time, once every other day) plus Rhinocort spray (once in the morning and evening separately, 256 µg/d), and patients in the control group treated by Rhinocort spray alone (the same to that mentioned above). All the treatments were given for 4 weeks. The therapeutic effect was evaluated with reference to the "Principles and Recommended Schemes for Diagnosis and Treatment of AR" formulated by Otolaryngology Branch of Chinese Medical Association before and after the treatment. The severity of symptoms of AR was assessed by using visual analogue scale (VAS), the life quality of nasal conjunctivitis assessed using "Rhino-conjunctivitis Quality of Life Questionnaire (RQLQ)", and the sleep quality assessed using "Pittsburgh Sleep Quality Index (PSQI)" before and after the treatment, followed by 3 months' follow-up survey. RESULTS: After the treatment, the VAS and RQLQ scores in both groups and PSQI of the treatment group were significantly decreased in comparison with their own base-line levels of pre-treatment in each group (P<0.05). The RQLQ and PSQI in the treatment group were substantially lower than those in the control group (P<0.05). No marked difference was found between the two groups in VAS(P>0.05). Follow-up survey showed that the VAS and RQLQ scores in both groups and PSQI of the treatment group were still significantly lower than those of pre-treatment in each group(P<0.05), and the VAS, RQLQ and PSQI scores of the treatment group were significantly lower than those of the control group(P<0.05). After 4 weeks' treatment, of the 32 and 35 AR patients in the control and treatment groups, 7 and 16 experienced marked improvement, 16 and 14 were effective, and 9 and 5 failed, with the effective rate being 71.9% and 85.7%, respectively. The effective rate of the treatment group was significantly superior to that of the control group (P<0.05). CONCLUSION: Herbal cake-partitioned moxibustion combined with Rhinocort spray has a good therapeutic effect in improving symptoms, sleep and quality of life in patients with persistent moderate-severe AR, which is obviously superior to that of Rhinocort spray alone in improving sleep and quality of life.


Assuntos
Moxibustão , Rinite Alérgica , Pontos de Acupuntura , Budesonida , Humanos , Qualidade de Vida , Rinite Alérgica/terapia
9.
Artigo em Inglês | MEDLINE | ID: mdl-31803144

RESUMO

Background: Dehydroepiandrosterone (DHEA) supplementation has been reported to have beneficial effects on the in vitro fertilization (IVF) outcomes of patients with poor ovarian response or diminished ovarian reserve. The Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) stratification is a set of newly established criteria for low prognosis patients. The aim of this study was to examine the potential effects of DHEA supplementation on the IVF outcomes of patients who fulfill the POSEIDON group 4 criteria. Methods: This retrospective cohort study investigated 297 cycles that fulfilled the POSEIDON group 4 criteria and underwent IVF treatment using the gonadotropin-releasing hormone antagonist protocol. The study group contained 159 cycles that received DHEA (30 mg three times per day) daily for 12 weeks before their IVF cycles. The control group included 138 cycles that underwent IVF cycles but did not receive DHEA. The baseline characteristics and cycle parameters as well as the IVF outcomes of both groups were compared. Results: In terms of baseline characteristics, more previous IVF attempts and lower AMH levels were found in the study group than in the control group. Regarding IVF outcomes, patients in the study group had significantly higher follicular oocyte index and higher numbers of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day 3 embryos and top-quality day 3 embryos than those in the control group. Besides, a higher cumulative pregnancy rate and lower cancellation rate were observed in the study group than in the control group although clinical pregnancy rate, live birth rate, and cumulative live birth rate did not differ between the two groups. Whether patients are aged ≤ 40 years or aged > 40, higher numbers of oocytes and embryos were observed in the study group than in the control group. In patients aged > 40, cumulative pregnancy rate was significantly higher in the study group than in the control group. Conclusions: Our data suggest that DHEA supplementation might increase both oocyte and embryo yields, as well as cumulative pregnancy rates, in patients fulfilling the POSEIDON group 4 criteria.

10.
Sci Rep ; 9(1): 12633, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477754

RESUMO

Lung injury is one of the pathological hallmarks of most respiratory tract diseases including asthma, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). It involves progressive pulmonary tissue damages which are usually irreversible and incurable. Therefore, strategies to facilitate drug development against lung injury are needed. Here, we characterized the zebrafish folate-deficiency (FD) transgenic line that lacks a fully-developed swim bladder. Whole-mount in-situ hybridization revealed comparable distribution patterns of swim bladder tissue markers between wild-type and FD larvae, suggesting a proper development of swim bladder in early embryonic stages. Unexpectedly, neutrophils infiltration was not observed in the defective swim bladder. Microarray analysis revealed a significant increase and decrease of the transcripts for cathepsin L and a cystatin B (CSTB)-like (zCSTB-like) proteins, respectively, in FD larvae. The distribution of cathepsin L and the zCSTB-like transcripts was spatio-temporally specific in developing wild-type embryos and, in appropriate measure, correlated with their potential roles in maintaining swim bladder integrity. Supplementing with 5-formyltetrahydrofolate successfully prevented the swim bladder anomaly and the imbalanced expression of cathepsin L and the zCSTB-like protein induced by folate deficiency. Injecting the purified recombinant zebrafish zCSTB-like protein alleviated FD-induced swim bladder anomaly. We concluded that the imbalanced expression of cathepsin L and the zCSTB-like protein contributed to the swim bladder malformation induced by FD and suggested the potential application of this transgenic line to model the lung injury and ECM remodeling associated with protease/protease inhibitor imbalance.


Assuntos
Sacos Aéreos/patologia , Catepsina L/metabolismo , Cistatina B/metabolismo , Endopeptidases/metabolismo , Deficiência de Ácido Fólico/complicações , Lesão Pulmonar/etiologia , Inibidores de Proteases/metabolismo , Peixe-Zebra/fisiologia , Sacos Aéreos/metabolismo , Sequência de Aminoácidos , Animais , Biomarcadores/metabolismo , Catepsina L/genética , Cistatina B/química , Cistatina B/genética , Modelos Animais de Doenças , Embrião não Mamífero/patologia , Desenvolvimento Embrionário , Larva/metabolismo , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes/metabolismo , Relação Estrutura-Atividade , Peixe-Zebra/embriologia , Proteínas de Peixe-Zebra/metabolismo
11.
Ecotoxicol Environ Saf ; 182: 109380, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31279279

RESUMO

Ultraviolet (UV) is an omnipresent environmental carcinogen transmitted by sunlight. Excessive UV irradiation has been correlated to an increased risk of skin cancers. UVB, the most mutagenic component among the three UV constituents, causes damage mainly through inducing DNA damage and oxidative stress. Therefore, strategies or nutrients that strengthen an individual's resistance to UV-inflicted harmful effects shall be beneficial. Folate is a water-soluble B vitamin essential for nucleotides biosynthesis, and also a strong biological antioxidant, hence a micronutrient with potential of modulating individual's vulnerability to UV exposure. In this study, we investigated the impact of folate status on UV sensitivity and the protective activity of folate supplementation using a zebrafish model. Elevated reactive oxygen species (ROS) level and morphological injury were observed in the larvae exposed to UVB, which were readily rescued by supplementing with folic acid, 5-formyltetrahydrofolate (5-CHO-THF) and N-acetyl-L-cysteine (NAC). The UVB-inflicted abnormalities and mortality were worsened in Tg(hsp:EGFP-γGH) larvae displaying folate deficiency. Intriguingly, only supplementation with 5-CHO-THF, as opposed to folic acid, offered significant and consistent protection against UVB-inflicted oxidative damage in the folate-deficient larvae. We concluded that the intrinsic folate status correlates with the vulnerability to UVB-induced damage in zebrafish larvae. In addition, 5-CHO-THF surpassed both folic acid and NAC in preventing UVB-inflicted oxidative stress and injury in our current experimental zebrafish model.


Assuntos
Deficiência de Ácido Fólico/prevenção & controle , Leucovorina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Complexo Vitamínico B/farmacologia , Peixe-Zebra/metabolismo , Acetilcisteína/farmacologia , Animais , Antioxidantes/farmacologia , Suplementos Nutricionais , Deficiência de Ácido Fólico/metabolismo , Larva/efeitos dos fármacos , Larva/metabolismo , Estresse Oxidativo/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo
12.
Trials ; 20(1): 372, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221225

RESUMO

BACKGROUND: Patients with moderate and severe persistent allergic rhinitis (AR) have long-term physical and mental stress, leading to dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis, which results in recurrence of AR. Previous research has proved acupuncture can regulate the function of the neuron-endocrine-immune system and contribute to improving the quality of life of patients with AR. This research aims to investigate the mechanism of acupuncture on the HPA axis in patients with moderate or severe persistent AR. METHODS/DESIGN: This randomized controlled trial aims to study the impact of acupuncture on the HPA axis of patients with moderate and severe AR. This research also aims to compare the curative effects of different treatments in three groups of patients: those receiving western medicine, western medicine and conventional acupuncture, or western medicine and mind-regulating acupuncture. We will study the therapeutic effect of acupuncture and the correlation between the changes of therapeutic indexes and experimental indexes after the treatments. Therapeutic indexes include the Visual Analog Scale (VAS) of nasal symptoms and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) for AR patients; experimental indexes include corticotropin releasing hormone (CRH), adreno-corticotropic hormone (ACTH), cortisol (CORT), interleukin 4 (IL-4), and interferon-γ (IFN-γ). DISCUSSION: The results of this trial will provide evidence for the influence of chronic, long-term, repeated stimulation in patients with moderate and severe persistent AR and the impact of acupuncture on the HPA axis of these patients. TRIAL REGISTRATION: Acupuncture-Moxibustion Clinical Trial Registry, AMCTR-IOR-16000009 . Registered on 22 August 2016.


Assuntos
Terapia por Acupuntura , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rinite Alérgica/terapia , Terapia por Acupuntura/efeitos adversos , Adolescente , Hormônio Adrenocorticotrópico/sangue , Adulto , Humanos , Interferon gama/sangue , Pessoa de Meia-Idade , Qualidade de Vida , Projetos de Pesquisa , Rinite Alérgica/psicologia , Adulto Jovem
13.
Mar Drugs ; 17(3)2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30818790

RESUMO

Gingival recession (GR) potentially leads to the exposure of tooth root to the oral cavity microenvironment and increases susceptibility to dental caries, dentin hypersensitivity, and other dental diseases. Even though many etiological factors were reported, the specific mechanism of GR is yet to be elucidated. Given the species richness concerning marine biodiversity, it could be a treasure trove for drug discovery. In this study, we demonstrate the effects of a marine compound, (+)-rhodoptilometrin from crinoid, on gingival cell migration, wound healing, and oxidative phosphorylation (OXPHOS). Experimental results showed that (+)-rhodoptilometrin can significantly increase wound healing, migration, and proliferation of human gingival fibroblast cells, and it does not have effects on oral mucosa fibroblast cells. In addition, (+)-rhodoptilometrin increases the gene and protein expression levels of focal adhesion kinase (FAK), fibronectin, and type I collagen, changes the intracellular distribution of FAK and F-actin, and increases OXPHOS and the expression levels of complexes I~V in the mitochondria. Based on our results, we believe that (+)-rhodoptilometrin might increase FAK expression and promote mitochondrial function to affect cell migration and promote gingival regeneration. Therefore, (+)-rhodoptilometrin may be a promising therapeutic agent for GR.


Assuntos
Antraquinonas/farmacologia , Equinodermos/química , Fibroblastos/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Fibroblastos/citologia , Fibroblastos/fisiologia , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Gengiva/citologia , Gengiva/efeitos dos fármacos , Gengiva/fisiologia , Retração Gengival/tratamento farmacológico , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mucosa Bucal/citologia , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/fisiologia , Fosforilação Oxidativa/efeitos dos fármacos
14.
Reprod Biol Endocrinol ; 16(1): 90, 2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-30223902

RESUMO

BACKGROUND: Dehydroepiandrosterone (DHEA) is now widely used as an adjuvant for in vitro fertilization (IVF) cycles in poor ovarian responders (PORs). Several studies showed that DHEA supplementation could improve IVF outcomes of PORs. However, most of the PORs do not respond to DHEA clinically. Therefore, the aim of this study is to confirm the beneficial effects of DHEA on IVF outcomes of PORs and to investigate which subgroups of PORs can best benefit from DHEA supplementation. METHODS: This retrospective cohort study was performed between January 2015 and December 2017. A total of 151 PORs who fulfilled the Bologna criteria and underwent IVF cycles with the gonadotropin-releasing hormone antagonist protocol were identified. The study group (n = 67) received 90 mg of DHEA daily for an average of 3 months before the IVF cycles. The control group (n = 84) underwent the IVF cycles without DHEA pretreatment. The basic and cycle characteristics and IVF outcomes between the two groups were compared using independent t-tests, Chi-Square tests and binary logistic regression. RESULTS: The study and control groups did not show significant differences in terms of basic characteristics. The study group demonstrated a significantly greater number of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day 3 embryos and top-quality embryos at day 3 and a higher clinical pregnancy rate, ongoing pregnancy rate and live birth rate than those measures in the control group. The multivariate analysis revealed that DHEA supplementation was positively associated with clinical pregnancy rate (OR = 4.93, 95% CI 1.68-14.43, p = 0.004). Additionally, in the study group, the multivariate analysis showed that serum dehydroepiandrosterone-sulfate (DHEA-S) levels < 180 µg/dl were significantly associated with a rate of retrieved oocytes > 3 (OR = 5.92, 95% CI 1.48-23.26, p = 0.012). CONCLUSIONS: DHEA supplementation improves IVF outcomes of PORs. In PORs with DHEA pretreatment, women with lower DHEA-S level may have greater possibility of attaining more than 3 oocytes.


Assuntos
Desidroepiandrosterona/uso terapêutico , Fertilização in vitro , Adulto , Feminino , Humanos , Modelos Logísticos , Análise Multivariada , Recuperação de Oócitos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
15.
J Clin Med ; 7(10)2018 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-30241351

RESUMO

Mitochondrial dysfunction is related to reproductive decline in humans, with consequences for in vitro fertilization (IVF). We assessed whether dehydroepiandrosterone (DHEA) could regulate mitochondrial homeostasis and mitophagy of cumulus cells (CCs) in poor ovarian responders (PORs). A total of 66 women who underwent IVF treatment at the Reproductive Medicine Center of Kaohsiung Veterans General Hospital were included in this study. Twenty-eight normal ovarian responders (NOR) and 38 PORs were enrolled. PORs were assigned to receive DHEA supplementation (n = 19) or not (n = 19) before IVF cycles. DHEA prevents mitochondrial dysfunction by decreasing the activation of DNM1L and MFF, and increasing MFN1 expression. Downregulation of PINK1 and PRKN occurred after DHEA treatment, along with increased lysosome formation. DHEA not only promoted mitochondrial mass but also improved mitochondrial homeostasis and dynamics in the CCs of POR. We also observed effects of alterations in mRNAs known to regulate mitochondrial dynamics and mitophagy in the CCs of POR. DHEA may prevent mitochondrial dysfunction through regulating mitochondrial homeostasis and mitophagy.

16.
Zhen Ci Yan Jiu ; 43(7): 450-5, 2018 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-30094983

RESUMO

OBJECTIVE: To evaluate the clinical effect of herbal cake-partitioned moxibustion combined with medication in the treatment of moderate and severe persistent allergic rhinitis (PAR) patients of spleen deficiency pattern. METHODS: Sixty patients with moderate and severe PAR of spleen deficiency pattern were randomized into medication (Rhinocort) group and herbal cake-partitioned moxibustion combined with medication group (combination group, n=30 cases in each). Medicinal cake-partitioned moxibustion was applied to Yintang (GV 29, for about 20 min), Shenque(CV 8, about 50 min), bilateral Zusanli (ST 36, about 40 min)and Hegu(LI 4, about 40 min)once every other day for successive 8 weeks. All the patients received treatment with Rhinocort nasal spray, 2 jets/day for each nostril (64 µg/jet) for 8 weeks. The patients' conditions (symptoms of nasal sufferings, sleeping, sniffle, eye, emotion, etc.) were assessed by visual analogue scale (VAS) and rhino conjunctivitis quality of life questionnaire (RQLQ, 24 items of 7 aspects, 0-6 points/item), respectively. The spleen deficiency syndrome score was determined according to "Guiding Principles for Clinical Research of New Drugs of Chinese Materia Medica" (2002). The therapeutic effect was assessed by referring to "the Diagnostic and Therapeutic Principles and Recommended Schemes for Allergic Rhinitis" (2004). RESULTS: Following the treatment, the scores of VAS, RQLQ, spleen deficiency syndrome were significantly decreased on the 4thand the 8th week of treatment in both groups in comparison with those of their own individual pre-treatment (P<0.05, P<0.01). Four weeks' follow-up survey showed that the VAS score and RQLQ score of the combination group were obviously lower than those of the medication groups (P<0.05), suggesting a better post-effect of moxibustion. Of the two 30 cases in the medication and combination groups, 9 and 9 experienced marked improvement in their symptoms, 16 and 17 were effective, and 5 and 4 ineffective, with the effective rate being 83.3% and 86.7%, respectively. No significant differences were found between the two groups in the VAS and RQLQ scores on the 4th and 8th week during treatment and in the effective rate (P>0.05). CONCLUSION: Herbal cake-partitioned moxibustion combined with hormone (Rhinocort) nasal spray is effective in relieving symptoms of moderate and severe PAR patients of spleen deficiency syndrome, and has a better post-effect.


Assuntos
Moxibustão , Rinite Alérgica , Pontos de Acupuntura , Budesonida , Humanos , Sprays Nasais , Qualidade de Vida , Rinite Alérgica/terapia , Baço
17.
Cancer Med ; 7(6): 2567-2580, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29683262

RESUMO

Epirubicin is a chemotherapy agent for hepatocellular carcinoma (HCC). However, the outcome of HCC patients receiving epirubicin remains unsatisfactory. Moreover, our previous study indicated that celecoxib suppresses HCC progression and liver cancer stemness. This study evaluated the potential of celecoxib to serve as a complementary therapy during epirubicin treatment. Cell proliferation, apoptosis, invasiveness, and anchorage-independent growth were analyzed in hepatoma cells. Therapeutic efficacy was validated in rat orthotopic Novikoff hepatoma. After animal sacrifice, the antitumor mechanism of celecoxib and epirubicin combined therapy was investigated by histological analysis. Celecoxib enhanced the cytotoxic activity of epirubicin in HCC cells by promoting apoptosis. Besides, celecoxib potentiated the antineoplastic function of epirubicin in inhibiting the invasiveness and anchorage-independent growth of HCC cells. Ultrasound monitoring showed that combined therapy was more potent than either therapy alone in perturbing HCC progression. Consistently, the size and weight of dissected HCC tissues from rats receiving combined therapy were smallest among all groups. HCC treated with combined therapy exhibited the highest prevalence of apoptotic cells, which was accompanied by reduced proliferating and angiogenic activities in tumor tissues. Moreover, the expression levels of cancer stemness markers (CD44 and CD133) and drug transporter MDR-1 were significantly diminished in rats receiving combined therapy. Besides, celecoxib treatment increased the infiltration of cytotoxic T lymphocytes (CTLs) and reduced the number of regulatory T cells (Tregs), tumor-associated macrophages (TAMs), and the expression of immune checkpoint PD-L1 in HCC tissues during epirubicin therapy. Celecoxib augmented the therapeutic efficacy while modulated cancer stemness and antitumor immunity. Thus, celecoxib may serve as complementary therapy to improve the outcome of patients with advanced HCC during epirubicin treatment.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Celecoxib/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Epirubicina/farmacologia , Inibidores da Topoisomerase II/farmacologia , Animais , Apoptose/efeitos dos fármacos , Biomarcadores , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Humanos , Imunomodulação/efeitos dos fármacos , Neoplasias Hepáticas Experimentais , Ratos , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Int J Mol Sci ; 18(11)2017 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-29149031

RESUMO

Research so far has only shown that edible red macroalgae, Sarcodia ceylanica has the ability to eliminate free radicals and anti-diabetic, anti-bacterial properties. This study was conducted both in vitro and in vivo on the ethyl acetate extract (PD1) of farmed red macroalgae in order to explore its anti-inflammatory properties. In order to study the in vitro anti-inflammatory effects of PD1, we used lipopolysaccharide (LPS) to induce inflammatory responses in murine macrophages. For evaluating the potential in vivo anti-inflammatory and antinociceptive effects of PD1, we used carrageenan-induced rat paw edema to produce inflammatory pain. The in vitro results indicated that PD1 inhibited the LPS-induced pro-inflammatory protein, inducible nitric oxide synthase (iNOS) in macrophages. Oral PD1 can reduce carrageenan-induced paw edema and inflammatory nociception. PD1 can significantly inhibit carrageenan-induced leukocyte infiltration, as well as the protein expression of inflammatory mediators (iNOS, interleukin-1ß, and myeloperoxidase) in inflammatory tissue. The above results indicated that PD1 has great potential to be turned into a functional food or used in the development of new anti-inflammatory and antinociceptive agents. The results from this study are expected to help scientists in the continued development of Sarcodia ceylanica for other biomedical applications.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Extratos Vegetais/farmacologia , Alga Marinha/química , Acetatos/química , Animais , Biomarcadores/metabolismo , Carragenina/efeitos adversos , Fracionamento Químico , Modelos Animais de Doenças , Edema/patologia , Edema/terapia , Macrófagos/efeitos dos fármacos , Camundongos , Células RAW 264.7 , Ratos , Ratos Wistar
19.
Int J Med Sci ; 14(6): 585-594, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28638275

RESUMO

Poor ovarian responders (PORs) pose a great challenge for in vitro fertilization (IVF). Previous studies have suggested that dehydroepiandrosterone (DHEA) may improve IVF outcomes in PORs. The current study attempted to investigate the clinical benefits of DHEA in PORs and the possible mechanisms of DHEA on cumulus cells (CCs). This was a prospective study performed at one tertiary center from January 2015 to March 2016. A total of 131 women who underwent IVF treatment participated, including 59 normal ovarian responders (NORs) and 72 PORs. PORs were assigned to receive DHEA supplementation or not before the IVF cycle. For all patients, CCs were obtained after oocyte retrieval. In the CCs, mRNA expression of apoptosis-related genes and mitochondrial transcription factor A (TFAM) gene, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, mitochondrial dehydrogenase activity and mitochondrial mass were measured. The results indicated that PORs with DHEA supplementation produces a great number of top-quality embryos at day 3 and increased the number of transferred embryos and fertilization rate compared with those without DHEA supplementation. Additionally, supplementation with DHEA in PORs decreased DNA damage and apoptosis in CCs while enhancing the mitochondrial mass, mitochondrial dehydrogenase activity and TFAM expression in CCs. In conclusion, our results showed that the benefits of DHEA supplementation on IVF outcomes in PORs were significant, and the effects may be partially mediated by improving mitochondrial function and reducing apoptosis in CCs.


Assuntos
Células do Cúmulo/efeitos dos fármacos , Desidroepiandrosterona/administração & dosagem , Ovário/efeitos dos fármacos , Indução da Ovulação , Adulto , Apoptose/efeitos dos fármacos , Feminino , Fertilização in vitro , Humanos , Mitocôndrias/efeitos dos fármacos , Ovário/crescimento & desenvolvimento
20.
Gynecol Endocrinol ; 33(2): 100-104, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27684542

RESUMO

BACKGROUND: Growing studies have demonstrated that dehydroepiandrosterone (DHEA) may improve fertility outcomes in poor ovarian responders (PORs). The aim of this study was to compare clinical outcomes and cumulus cell (CC) expression before and after DHEA treatment in PORs undergoing in vitro fertilization (IVF) cycles. METHODS: Six patients with poor ovarian response were enrolled in the study according to Bologna criteria. DHEA was supplied at least 2 months before patients entered into the next IVF cycle. Expression of apoptosis-related genes in CCs was determined by quantitative real-time PCR. Mitochondrial dehydrogenase activity of CCs was assessed by cell counting kit-8 assay. RESULTS: Metaphase II oocytes, maturation rate, embryos at Day 3, and fertilization rate significantly increased following DHEA treatment. Expression of cytochrome c, caspase 9, and caspase 3 genes in CCs were significantly reduced after DHEA therapy. Additionally, increased mitochondrial activity of CCs was observed following DHEA supplementation. CONCLUSIONS: DHEA supplementation may protect CCs via improved mitochondrial activity and decreased apoptosis, leading to better clinical outcomes in PORs.


Assuntos
Células do Cúmulo/metabolismo , Desidroepiandrosterona/farmacologia , Fármacos para a Fertilidade Feminina/farmacologia , Fertilização in vitro/métodos , Fertilização/efeitos dos fármacos , Mitocôndrias/enzimologia , Avaliação de Resultados em Cuidados de Saúde , Adulto , Células do Cúmulo/efeitos dos fármacos , Desidroepiandrosterona/administração & dosagem , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Humanos , Mitocôndrias/efeitos dos fármacos , Gravidez
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