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Context: Sanchi promotes wound healing by repressing fibroblast proliferation. Objective: This study examined the effect of Sanchi on keratinocytes (KCs) and microvascular endothelial cells (MECs) and rats with skin injury. Materials & methods: Hydrogels containing different concentrations of Sanchi extract were prepared to observe wound closure over 10 days. SD rats were divided into the control, Hydrogel, 5% Hydrogel, 10% Hydrogel, 10% Hydrogel + Ad5-NC, and 10% Hydrogel + Ad5-IL1B groups. KCs and MECs were induced with H2O2 for 24 h. Cell viability, apoptosis, and the levels of inflammation- and oxidative stress-related factors were examined. The effect of IL1B on wound healing was also evaluated. Results: Compared to the Control group (83% ± 7.4%) or Hydrogel without Sanchi extract (84% ± 8.5%), Hydrogel with 5% (95% closure ± 4.0%) or 10% Sanchi extract (98% ± 1.7%) accelerated wound healing in rats and attenuated inflammation and oxidative stress. Hydrogels containing Sanchi extract increased collagen deposition and CD31 expression in tissues. H2O2 (100 µM) induced injury in KCs and MECs, whereas Sanchi rescued the viability of KCs and MECs. Sanchi inhibited cell inflammation and oxidative stress and decreased apoptosis. As Sanchi blocked the NFκB pathway via IL1B, IL1B mitigated the therapeutic effect of Sanchi. Discussion and conclusion: Sanchi demonstrated therapeutic effects on wound healing in rats by promoting KCs and MECs activity. These findings provide valuable information for the clinical application of Sanchi, which needs to be validated in future clinical trials.
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Alzheimer's disease (AD) is a neurodegenerative disorder where oxidative stress, induced by ferroptosis, has been linked to neuronal damage and cognitive deficits. The objective of this study is to investigate if the potential therapeutic agent, Curculigoside (CUR), could ameliorate AD by inhibiting ferroptosis. The potential therapeutic targets, such as GPX4 and SLC7A11, were identified using weighted gene co-expression network analysis (WGCNA). Concurrently, CUR was also screened against these potential targets using various analytical methods. For the in vivo studies, intragastric administration of CUR significantly ameliorated cognitive impairment in AD model mice induced by scopolamine and okadaic acid (OA). In vitro, CUR protected neuronal cells by altering the levels of ferroptosis-related specific markers in OA and scopolamine-induced neurotoxicity. The administration of CUR through intragastric route significantly reduced the levels of AD-promoting factors (such as Aß1-42, p-tau) and ferroptosis-promoting factors in the hippocampus and cortex of AD mice. Furthermore, CUR up-regulated the expression of GPX4 and decreased the expression of SLC7A11 in the ferroptosis signaling pathway, thereby increasing the ratio of glutathione (GSH)/oxidized glutathione (GSSG) in vivo and vitro. In conclusion, the cumulative results suggest that the natural compound CUR may serve as a promising therapeutic agent to ameliorate AD by inhibiting ferroptosis.
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Doença de Alzheimer , Benzoatos , Modelos Animais de Doenças , Ferroptose , Glucosídeos , Lignanas , Estresse Oxidativo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Animais , Doença de Alzheimer/tratamento farmacológico , Ferroptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Glucosídeos/farmacologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Masculino , Lignanas/farmacologia , Sistema y+ de Transporte de Aminoácidos/metabolismo , Peptídeos beta-Amiloides/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Medicina Tradicional Chinesa , Camundongos Endogâmicos C57BL , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
Peptidyl arginine deiminase 4 (PAD4) is an important biocatalytic enzymes involved in the conversion of protein arginine to citrulline, its dysregulation has a great impact on many physiological processes. Recently, PAD4 has emerged as a potential therapeutic target for the treatment of various diseases including rheumatoid arthritis (RA). Traditional Chinese Medicines (TCMs), also known as herbal plants, have gained great attention by the scientific community due to their good therapeutic performance and far fewer side effects observed in the clinical treatment. However, limited researches have been reported to screen natural PAD4 inhibitors from herbal plants. The color developing reagent (COLDER) or fluorescence based methods have been widely used in PAD4 activity assay and inhibitor screening. However, both methods measure the overall absorbance or fluorescence in the reaction solution, which are easy to be affected by the background interference due to colorful extracts from herbal plants. In this study, a simple, and robust high-performance liquid chromatography ultraviolet-visible (HPLC-UV) based method was developed to determine PAD4 activity. The proposed strategy was established based on COLDER principle, while used hydrophilic l-arginine instead of hydrophobic N-benzoyl-l-arginine ethyl ester (BAEE) as a new substrate to determine PAD4 inhibition activity of herbal extracts. The herbal extracts and PAD4 generated hydrophobic l-citrulline were successfully separated by the HPLC, and the developed method was optimized and validated with a known PAD4 inhibitor (GSK484) in comparison with COLDER assay. The IC50 value of GSK484 measured by HPLC-UV method was 153 nM, and the detection limit of the citrulline was 0.5 nmol, respectively, with a linear range of 0.5 nmol to 20 nmol. The IC50 value of the HPLC-UV method was improved by nearly three times compared with COLDER assay (527 nM), and the results indicated the reliability of PAD4 inhibition via HPLC-UV method. The inhibitory effect against PAD4 were fast and accurately screened for the twenty-four extracts from eight herbs. Among them, Ephedra Herba extracts showed significant inhibitory activity against the PAD4 with the IC50 values of three extracts (ethanol, ethyl acetate and water) ranging from 29.11 µg/mL to 41.36 µg/mL, which may help researchers to discover novel natural compounds holding high PAD4 inhibition activity.
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Produtos Biológicos , Medicamentos de Ervas Chinesas , Inibidores Enzimáticos , Proteína-Arginina Desiminase do Tipo 4 , Cromatografia Líquida de Alta Pressão , Citrulina , Proteína-Arginina Desiminase do Tipo 4/antagonistas & inibidores , Reprodutibilidade dos Testes , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Medicamentos de Ervas Chinesas/químicaRESUMO
Sclerotinia sclerotiorum is a necrotrophic plant pathogenic fungus with broad distribution and host range. Bioactive compounds derived from plant extracts have been proven to be effective in controlling S. sclerotiorum. In this study, the mycelial growth of S. sclerotiorum was effectively inhibited by maleic acid, malonic acid, and their combination at a concentration of 2 mg/mL, with respective inhibition rates of 32.5%, 9.98%, and 67.6%. The treatment of detached leaves with the two acids resulted in a decrease in lesion diameters. Interestingly, maleic acid and malonic acid decreased the number of sclerotia while simultaneously increasing their weight. The two acids also disrupted the cell structure of sclerotia, leading to sheet-like electron-thin regions. On a molecular level, maleic acid reduced oxalic acid secretion, upregulated the expression of Ss-Odc2 and downregulated CWDE10, Ss-Bi1 and Ss-Ggt1. Differently, malonic acid downregulated CWDE2 and Ss-Odc1. These findings verified that maleic acid and malonic acid could effectively inhibit S. sclerotiorum, providing promising evidence for the development of an environmentally friendly biocontrol agent.
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BACKGROUND: α1-antitrypsin deficiency is most commonly caused by a mutation in exon-7 of SERPINA1 (SA1-ATZ), resulting in hepatocellular accumulation of a misfolded variant (ATZ). Human SA1-ATZ-transgenic (PiZ) mice exhibit hepatocellular ATZ accumulation and liver fibrosis. We hypothesized that disrupting the SA1-ATZ transgene in PiZ mice by in vivo genome editing would confer a proliferative advantage to the genome-edited hepatocytes, enabling them to repopulate the liver. METHODS: To create a targeted DNA break in exon-7 of the SA1-ATZ transgene, we generated 2 recombinant adeno-associated viruses (rAAV) expressing a zinc-finger nuclease pair (rAAV-ZFN), and another rAAV for gene correction by targeted insertion (rAAV-TI). PiZ mice were injected i.v. with rAAV-TI alone or the rAAV-ZFNs at a low (7.5×1010vg/mouse, LD) or a high dose (1.5×1011vg/mouse, HD), with or without rAAV-TI. Two weeks and 6 months after treatment, livers were harvested for molecular, histological, and biochemical analyses. RESULTS: Two weeks after treatment, deep sequencing of the hepatic SA1-ATZ transgene pool showed 6%±3% or 15%±4% nonhomologous end joining in mice receiving LD or HD rAAV-ZFN, respectively, which increased to 36%±12% and 36%±12%, respectively, 6 months after treatment. Two weeks postinjection of rAAV-TI with LD or HD of rAAV-ZFN, repair by targeted insertion occurred in 0.10%±0.09% and 0.25%±0.14% of SA1-ATZ transgenes, respectively, which increased to 5.2%±5.0% and 33%±13%, respectively, 6 months after treatment. Six months after rAAV-ZFN administration, there was a marked clearance of ATZ globules from hepatocytes, and resolution of liver fibrosis, along with reduction of hepatic TAZ/WWTR1, hedgehog ligands, Gli2, a TIMP, and collagen content. CONCLUSIONS: ZFN-mediated SA1-ATZ transgene disruption provides a proliferative advantage to ATZ-depleted hepatocytes, enabling them to repopulate the liver and reverse hepatic fibrosis.
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Edição de Genes , Nucleases de Dedos de Zinco , Humanos , Animais , Camundongos , Cirrose Hepática/genética , Cirrose Hepática/terapia , Hepatócitos , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
Longdan Xiegan (LDXG) decoction, an ancient Chinese herbal formula, has been widely used in treating herpes zoster. This meta-analysis aimed to evaluate whether LDXG formula as adjuvant therapy had additional benefits in acute herpes zoster patients. Two authors independently searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journal Database, and Wanfang database from their inception to July 31, 2021. Relevant randomized controlled trials (RCTs) that investigated the add-on effects of LDXG formula (decoction, capsule, or pill) in the management of acute herpes zoster were included. Nine RCTs with 821 patients were identified. A random effect model meta-analyses showed that LDXG formula plus conventional therapy significantly reduced the time to blister resolution (weighted mean difference [WMD] -1.31 days; 95% confidence intervals [CI] -1.56 to -1.06), time to crust formation (WMD -1.91 days; 95% CI -2.31 to -1.50), time to pain resolution (WMD -2.13 days; 95% CI -2.65 to -1.60), pain intensity assessed by visual analogue scale (WMD -1.13; 95% CI -2.03 to -0.24), and incidence of persistent pain (risk ratio [RR] 0.28; 95% CI 0.15-0.50) compared with the conventional therapy alone. However, the overall certainty of evidence was very low to moderate. LDXG formula as adjuvant therapy may achieve additional benefits in terms of accelerating skin healing process, relieving pain symptoms, and preventing persistent pain in acute herpes zoster patients. However, interpretation of these findings should be considered the presence of statistical heterogeneity and/or unclear risk of bias.
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Herpes Zoster , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Herpes Zoster/tratamento farmacológico , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3 , Terapia Combinada , DorRESUMO
Ganoderma, a fungal genus, is a traditional medicine with immuno-modulating effects. Asthma is an inflammatory disease of airways, and the main trigger of asthma is allergic inflammation. In this study, the effects of Ganoderma (an anti-inflammatory agent) given via oral administration (G/O) or intraperitoneal injection (G/IP) on asthma was evaluated. Forty BALB/c mice were divided into four groups, including the control, OVA-challenge, OVA-challenge + G/O, and OVA-challenge + G/IP. To determine AHR, the MCh challenge test was done. The levels of IL-1ß, -4, -5, -6, -8, -10, -12, -13, -17, -25, -33, -38, Cys-LT, LTB4, and hydroxyproline were measured. Finally, lung histopathology was evaluated to determine eosinophilic inflammation, goblet cell hyperplasia, and mucus hyper-secretion. Treatment with G/O and G/IP could significantly reduce the levels of IL-1ß, -5, -6, -8, -17, -25, -33, and -38; the levels of IL-4 and IL-13 had no significant changes, but the levels of IL-10 and IL-12 were enhanced. The mice treated with G/O and G/IP showed decreased levels of Cys-LT, LTB4, peribronchial and perivascular inflammation, but no significant changes were observed in AHR, hydroxyproline level, goblet cell hyperplasia, and mucus hyper-secretion. Ganoderma can be applied as an immunomodulatory and anti-inflammatory agent for managing asthma.
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Asma , Ganoderma , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Asma/patologia , Líquido da Lavagem Broncoalveolar , Citocinas , Modelos Animais de Doenças , Hidroxiprolina/uso terapêutico , Hiperplasia/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Leucotrieno B4/uso terapêutico , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , OvalbuminaRESUMO
BACKGROUND/PURPOSE: Prosthetic implants are the primary treatment for patients with edentulism. This study aims to explore and compare the biological characteristics of mucosal thickness and tensile strength of the paranasal sinuses (maxillary and frontal sinuses) in goats, thereby providing a theoretical basis and guidance for mucosa-related problems involved in maxillary sinus lifting. MATERIALS AND METHODS: The paranasal sinus mucosa (maxillary sinus crest, maxillary sinus floor and frontal sinus mucosa) was obtained from the goats for use in maxillary sinus lifting. The mucosa was made into tissue section specimens and evaluated by a computer with built-in screenshot software and an optical microscope with a graduated eyepiece. A total of 3 readings were randomly selected and recorded. The mucosa was clamped with a laboratory-made clamp device. After connecting the push-pull meter, the mucosa exposed by the inner ring of the clamp device was pressed vertically and uniformly until it ruptured. The strength value was read and recorded. The left and right ends of the mucosa were connected with the clamp device; horizontal tension was applied evenly to the mucosa until the mucosa ruptured. The strength value was read and recorded. The normality test, analysis of variance, LSD pairwise comparison and linear regression were performed for each group of data. RESULTS: The thicknesses of the maxillary sinus crest mucosa, floor mucosa and frontal sinus mucosa in goats were 410.03 ± 65.97 um, 461.33 ± 91.37 um and 216.90 ± 46.47 um, respectively. There were significant differences between the maxillary sinus crest and frontal sinus and the maxillary sinus floor and frontal sinus (P < .05). The range of tensile strength of the maxillary sinus crest mucosa, floor mucosa and frontal sinus mucosa in goats was 0.48 ± 0.10 kg, 0.54 ± 0.11kg and 0.20 ± 0.05kg, respectively. There were significant differences between the maxillary sinus crest and frontal sinus and the maxillary sinus floor and frontal sinus (P < .05). Tensile strength was positively correlated with the thickness of the mucosa of the maxillary and frontal sinuses (P < .05). CONCLUSION: The mucosal thickness and tensile strength of the maxillary sinus crest and floor were greater than those of the frontal sinus mucosa. There was a positive correlation between the tensile strength and the thickness of the mucosa.
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Levantamento do Assoalho do Seio Maxilar , Animais , Face , Cabras , Humanos , Seio Maxilar , MucosaRESUMO
Selenium (Se) is a component of many enzymes and indispensable for human health due to its characteristics of reducing oxidative stress and enhancing immunity. Human beings take Se mainly from Se-containing crops. Taking measures to biofortify crops with Se may lead to improved public health. Se accumulation in plants mainly depends on the content and bioavailability of Se in soil. Beneficial microbes may change the chemical form and bioavailability of Se. This review highlights the potential role of microbes in promoting Se uptake and accumulation in crops and the related mechanisms. The potential approaches of microbial enhancement of Se biofortification can be summarized in the following four aspects: (1) microbes alter soil properties and impact the redox chemistry of Se to improve the bioavailability of Se in soil; (2) beneficial microbes regulate root morphology and stimulate the development of plants through the release of certain secretions, facilitating Se uptake in plants; (3) microbes upregulate the expression of certain genes and proteins that are related to Se metabolism in plants; and (4) the inoculation of microbes give rise to the generation of certain metabolites in plants contributing to Se absorption. Considering the ecological safety and economic feasibility, microbial enhancement is a potential tool for Se biofortification. For further study, the recombination and establishment of synthesis microbes is of potential benefit in Se-enrichment agriculture.
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Biofortificação , Produtos Agrícolas/metabolismo , Selênio/metabolismo , Microbiologia do Solo , Solo , Disponibilidade BiológicaRESUMO
The functions and mechanisms of GPR40 receptor to ameliorating the Alzheimer's disease (AD) by external treatment of encephalopathy remain unknown. In present study, the typical Aß1-42 induced mice model was applied to explore the functions and mechanisms of GPR40 receptor by external treatment of encephalopathy in AD. GPR40 agonist GW9508 and antagonist GW1100 were given by i.g injection to activate/inhibit the GPR40 receptor respectively in the gut of AD mouse which illustrated the function and mechanism of GPR40 receptor in ameliorating AD symptoms by external treatment of encephalopathy. A series of behavioral experiments were used to investigate the cognitive function and memory ability of mice, while molecular biology experiments such as Western blot, ELISA, flow cytometry were used to detect the corresponding changes of signaling pathways. The results revealed that intragastric administrated GW9508 could significantly ameliorate cognitive deficits of AD mouse, up-regulate the expression levels of gut-brain peptides both in blood circulation and hypothalamus thus up-regulate the expression levels of α-MSH in hypothalamus, while the negative autophagy-related proteins and inflammation-related proteins were down-regulated correspondingly. Meanwhile, GW9508 could also inhibit the pathological process of neuroinflammation in microglia. GW1100 reversed the effects of GW9508 significantly. These results suggested that GPR40 was an underlying therapeutic target for the external treatment of encephalopathy related to AD and GPR40 agonist could be explored as the emerging AD therapeutic drug.
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Doença de Alzheimer/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Metilaminas/administração & dosagem , Doenças Neuroinflamatórias/tratamento farmacológico , Propionatos/administração & dosagem , Receptores Acoplados a Proteínas G/agonistas , Administração Oral , Doença de Alzheimer/complicações , Doença de Alzheimer/imunologia , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/administração & dosagem , Peptídeos beta-Amiloides/toxicidade , Animais , Técnicas de Observação do Comportamento , Barreira Hematoencefálica/metabolismo , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/imunologia , Disfunção Cognitiva/patologia , Regulação para Baixo/efeitos dos fármacos , Humanos , Hipotálamo/efeitos dos fármacos , Hipotálamo/imunologia , Hipotálamo/patologia , Masculino , Metilaminas/farmacocinética , Camundongos , Microglia/efeitos dos fármacos , Microglia/imunologia , Microglia/patologia , Doenças Neuroinflamatórias/diagnóstico , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/patologia , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/toxicidade , Propionatos/farmacocinética , Receptores Acoplados a Proteínas G/metabolismo , Distribuição TecidualRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Semen Cuscutae and Fructus Lycii (SC-FL) is a commonly used herbal pair for male infertility treatment. Studies have found that the mechanism of SC-FL treatment may be related to repairing the blood-testis barrier (BTB). The application of network pharmacology can be used to explore the correlation between medicines and diseases and predict the potential pharmacological mechanisms of SC-FL. AIM OF THE STUDY: This study aimed to explore the specific effects and mechanisms of SC-FL in repairing the BTB and initially revealed the mechanism of Chinese medicine treating male infertility through network pharmacology and animal experiments. MATERIALS AND METHODS: We searched databases using the network pharmacology method and performed mass spectrometry analysis. We analyzed and predicted the active ingredients, targets and key pathways of SC-FL in male infertility treatment. Then, we designed animal experiments to verify the results. Thirty-six Sprague-Dawley rats were randomly divided into the normal control group (NC group), spermatogenic dysfunction group (SD group) and SC-FL treatment group (SCFL group). Glucosides of Tripterygium wilfordii Hook. F (GTW) (40 mg/kg/d) was administered for 4 weeks to generate a spermatogenic dysfunction model. The rats in the SCFL group were given the SC-FL suspension (6 g/kg/d) daily. After 4 weeks of treatment, we detected the sperm quality of each group of rats and observed the cell morphology. Western blotting and qRT-PCR were used to detect the expression of BTB-related proteins in testicular tissues. RESULTS: 213 chemical ingredients of SC and FL were retrieved from the TCMSP database, and 54 effective chemical ingredients were obtained. Mass spectrometry analysis showed the above results were credible. Then, we identified 44 potential targets for the treatment of male infertility, and we plotted a network diagram of the interaction network between the core targets and a diagram of herbal medicine-active ingredient-target-disease interactions. The target genes were enriched according to biological functions, and 22 biological processes, 49 cellular components, 1487 molecular functions, and 122 signaling pathways were obtained. The results of the animal experiments showed that the sperm concentration and motility of the SCFL group were significantly improved compared with those of the SD group. Compared with those in the SD group, the structure and morphology of the Sertoli cells and seminiferous tubules of rats in the SCFL group improved, and the number of spermatogenic cells increased significantly. Western blotting and qRT-PCR results showed that compared with that in the SD group, the expression of p38 MAPK decreased significantly, and the expression of c-Jun, Occludin, ZO-1 and connexin 43 increased significantly in the SCFL group. CONCLUSION: We predicted that the active ingredients of SC-FL can treat male infertility by interacting with the core targets JUN, IL6, MAPK1, TP53, MYC, CCND1, AR, EGF, FOS, and MAPK8, and the possible mechanism is related to the MAPK signaling pathway. SC-FL can regulate the MAPK pathway and affect the expression of Occludin, ZO-1 and connexin 43 to repair damaged BTB and improve spermatogenic dysfunction induced by GTW, which may be one of the possible mechanisms.
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Barreira Hematotesticular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Infertilidade Masculina/tratamento farmacológico , Espermatogênese/efeitos dos fármacos , Testículo , Tripterygium/química , Animais , Caderinas/genética , Caderinas/metabolismo , Simulação por Computador , Conexina 43/genética , Conexina 43/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Genes jun/efeitos dos fármacos , Glucosídeos/toxicidade , Técnicas In Vitro , Infertilidade Masculina/induzido quimicamente , Masculino , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Ocludina/genética , Ocludina/metabolismo , Mapas de Interação de Proteínas/efeitos dos fármacos , Ratos Sprague-Dawley , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia , Testículo/ultraestrutura , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
INTRODUCTION: Erectile dysfunction refers to the continued inability of the penis to reach and maintain sufficient erections to achieve a satisfactory sex life and last at least 6 months. As part of traditional Chinese medicine, acupuncture has been widely used in clinical practice. In order to evaluate, the exact effect of acupuncture on the clinical efficacy of patients with Post-stroke Erectile dysfunction (PSED), this experiment uses randomized controlled experiments. METHODS/DESIGN: This pragmatic randomized controlled trial will recruit 103 patients who are diagnosed with PSED. Simple randomization to conventional treatment with a 1:1 allocation ratio will be used. Ten 30-min acupuncture sessions will be provided to patients assigned to the Intervention group. All participants will continue to receive conventional treatment. The selection of outcomes will be evaluated by International Erectile Function Index-5 (IIEF-5) score at week 8. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of acupuncture for patients with PSED. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000030231, Registered on February 25, 2020.
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Terapia por Acupuntura/métodos , Disfunção Erétil/terapia , Acidente Vascular Cerebral/fisiopatologia , Terapia por Acupuntura/economia , Adulto , Análise Custo-Benefício , Disfunção Erétil/diagnóstico , Disfunção Erétil/etiologia , Humanos , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Resultado do TratamentoRESUMO
BACKGROUND: Ureteral calculi generally refer to the temporary obstruction of the human body after the ureteral stenosis. When the ureteral stones are not discharged in time, they can grow in the original site, causing the patient to have corresponding clinical manifestations, such as: renal colic, hematuria, etc, when severe, can cause renal obstruction and hydronephrosis, seriously endangering the patient's health. Ureteral calculi usually occur in young and middle-aged people. The peak age of the disease is between 20 and 50 years old. It also occurs in the young and middle-aged labor force. The men incidence rate is 2 to 3 times that of women. Ureteral calculi is one of the current refractory diseases, and the effect after treatment with integrated Chinese and Western medicine is remarkable. METHODS AND ANALYSIS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to November 2018. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of ureteral. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of Traditional Chinese medicine for ureteral. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process Trial.Registration number: PROSPERO CRD42019137095.
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Medicina Tradicional Chinesa , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Cálculos Ureterais/terapia , HumanosRESUMO
BACKGROUND: Among male sterility factors, oligoasthenozoospermia is the most common. As people's lifestyle changes and the population ages, the incidence of oligoasthenozoospermia continues to increase. The studies have shown that about 15% of married couples in the world are affected by infertility, among which infertility caused by male factors alone accounts for about 50%. Many clinical trials have proven that Wuzi Yanzong Pill has a significant effect in the treatment of oligoasthenozoospermia. In this systematic review, we aim to evaluate the effectiveness and safety of Wuzi Yanzong Pill for oligoasthenozoospermia. METHODS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online, and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to April 2019. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of oligoasthenozoospermia. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of Wuzi Yanzong Pill for treating oligoasthenozoospermia. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process Trial. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019119170.
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Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Oligospermia , Humanos , Masculino , China , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/uso terapêutico , Infertilidade Masculina/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Oligospermia/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Metanálise como Assunto , Revisões Sistemáticas como AssuntoRESUMO
WNT4 (wingless-type MMTV integration site family, member 4) plays a key role in the ovarian differentiation and development in mammals. However, the possible roles of Wnt4 during gonadal differentiation and development need further clarification in teleosts. In this study, we cloned and characterized the full-length cDNA of Qi river crucian carp (Carassius auratus) wnt4a gene (CA-wnt4a). The cDNA of CA-wnt4a is 2337â¯bp, including the ORF of 1059â¯bp, encoding a putative protein with a transmembrane domain and a WNT family domain. Sequence and phylogenetic analyses revealed that the CA-Wnt4a identified is a genuine Wnt4a. Tissue distribution analysis showed that CA-wnt4a is expressed in all the tissues examined, including ovary. CA-wnt4a undergoes a stepwise increase in the embryonic stages, suggesting that CA-wnt4a might be involved in the early developmental stage. Ontogenic analysis demonstrated that CA-wnt4a expression is upregulated in the ovaries at 30-50â¯days after hatching (dah), the critical period of sex determination/differentiation in Qi river crucian carp. From 90 dah, the expression of CA-wnt4a was gradually downregulated in the developing ovaries. Immunohistochemistry demonstrated that CA-Wnt4a was expressed in the somatic and germ cells of the ovary by 30 dah, thereafter, positive signals of Wnt4a were detected in the somatic cells, oogonia and primary growth oocytes from 60 dah. In the sex-reversed testis induced by letrozole treatment, the expression level of CA-wnt4a was significantly downregulated. When CA-wnt4a expression was inhibited by injection of FH535 (an inhibitor of canonical Wnt/ß-catenin signal pathway) in the ovaries, levels of cyp19a1a, foxl2 mRNA were significantly downregulated, while sox9b and cyp11c1 were upregulated, which suggested that together with Foxl2-leading estrogen pathway, CA-wnt4a signaling pathway might be involved in ovarian differentiation and repression of the male pathway gene expression in Qi river crucian carp.
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Carpas/genética , Rios , Triploidia , Proteína Wnt4/genética , Animais , Carpas/embriologia , Clonagem Molecular , DNA Complementar/genética , Regulação para Baixo/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Desenvolvimento Embrionário/genética , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Gônadas/efeitos dos fármacos , Gônadas/metabolismo , Letrozol/farmacologia , Masculino , Filogenia , Análise de Sequência de DNA , Sulfonamidas/farmacologia , Fatores de Tempo , Regulação para Cima/efeitos dos fármacosRESUMO
Invariant natural killer T (iNKT) cells develop from CD4+CD8+ double-positive (DP) thymocytes and express an invariant Vα14-Jα18 T-cell receptor (TCR) α-chain. Generation of these cells requires the prolonged survival of DP thymocytes to allow for Vα14-Jα18 gene rearrangements and strong TCR signaling to induce the expression of the iNKT lineage-specific transcription factor PLZF. Here, we report that the transcription factor Yin Yang 1 (YY1) is essential for iNKT cell formation. Thymocytes lacking YY1 displayed a block in iNKT cell development at the earliest progenitor stage. YY1-deficient thymocytes underwent normal Vα14-Jα18 gene rearrangements, but exhibited impaired cell survival. Deletion of the apoptotic protein BIM failed to rescue the defect in iNKT cell generation. Chromatin immunoprecipitation and deep-sequencing experiments demonstrated that YY1 directly binds and activates the promoter of the Plzf gene. Thus, YY1 plays essential roles in iNKT cell development by coordinately regulating cell survival and PLZF expression.
Assuntos
Células T Matadoras Naturais/imunologia , Proteína com Dedos de Zinco da Leucemia Promielocítica/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Timócitos/imunologia , Fator de Transcrição YY1/metabolismo , Animais , Diferenciação Celular , Linhagem da Célula , Sobrevivência Celular , Células Cultivadas , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína com Dedos de Zinco da Leucemia Promielocítica/genética , Receptores de Antígenos de Linfócitos T/genética , Transdução de Sinais , Fator de Transcrição YY1/genéticaRESUMO
This study aimed to evaluate the efficacy of electroacupuncture (EA) on Ciliao (BL 32) and Zhongliao (BL 33) acupoints at different depths for the treatment of benign prostatic hyperplasia (BPH) through a single-blind randomized controlled trial. All 120 patients diagnosed with BPH were randomly allocated to an experimental group (deep insertion group, DI group, n = 60) and control group (shallow insertion group, SI group, n = 60) 3 times a week for 4 weeks. The observed results included the International Prostate Symptom Score (IPSS), Quality of Life score (QOL), maximum urine flow rate (Qmax), and postvoid residual urine volume (PVR). After treatment, at both depths, the BPH symptoms of patients were improved by EA. There were significant differences between the IPSS, QOL, and the effective rate of the experimental group and the control group (P < 0.05). Although the observed PVR and Qmax were better than those before treatment, there was no statistical significance between two groups (P > 0.05). Thus, EA with deep insertion can effectively improve the patients' urinary symptoms and quality of life, and it will be suitable for clinical application.
RESUMO
Qianlie Tongqiao Capsule (QTC) is clinically confirmed to be efficacious and safe in treating lower urinary tract syndromes and bladder dysfunction that are induced by benign prostatic hyperplasia (BPH). However, the functional mechanisms of QTC remain unclear. We aim to investigate the effects of QTC on both bladder weight and several growth factors in the bladder tissue of rats with testosterone-induced BPH. BPH in the rats was established through bilateral orchiectomy and subcutaneous administration of testosterone propionate (5 mg/kg) dissolved in corn oil. At the end of the study, all bladder tissues were collected and weighed, and a histological examination was conducted using H&E staining. Immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were applied to detect the expression of nerve growth factor (NGF), basic fibroblast growth factor (bFGF), and transformation growth factor-ß1 (TGF-ß1) in the bladder tissue. The expression of Bcl-2 and Bax in the bladder tissue was tested by Western Blot and qRT-PCR. We found that QTC, especially when administered in high-dosages, had a significant inhibitory effect on bladder weight gain and overexpression of NGF, bFGF, and TGF-ß1 in rats with BPH. In addition, QTC downregulated and upregulated protein and mRNA expression of Bcl-2 and Bax in the bladder after prostatic obstruction, respectively. Furthermore, QTC balanced the Bcl-2/Bax ratio. Overall, these results reveal possible functional mechanisms of QTC in treating BPH-caused bladder dysfunction, and further studies are needed.
RESUMO
BACKGROUND: We systematically reviewed randomized controlled trials (RCTs) of complementary and alternative interventions for fatigue after traumatic brain injury (TBI). METHODS: We searched multiple online sources including ClinicalTrials.gov, the Cochrane Library database, MEDLINE, CINAHL, Embase, the Web of Science, AMED, PsychINFO, Toxline, ProQuest Digital Dissertations, PEDro, PsycBite, and the World Health Organization (WHO) trial registry, in addition to hand searching of grey literature. The methodological quality of each included study was assessed using the Jadad scale, and the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. A descriptive review was performed. RESULTS: Ten RCTs of interventions for post-TBI fatigue (PTBIF) that included 10 types of complementary and alternative interventions were assessed in our study. There were four types of physical interventions including aquatic physical activity, fitness-center-based exercise, Tai Chi, and aerobic training. The three types of cognitive and behavioral interventions (CBIs) were cognitive behavioral therapy (CBT), mindfulness-based stress reduction (MBSR), and computerized working-memory training. The Flexyx Neurotherapy System (FNS) and cranial electrotherapy were the two types of biofeedback therapy, and finally, one type of light therapy was included. Although the four types of intervention included aquatic physical activity, MBSR, computerized working-memory training and blue-light therapy showed unequivocally effective results, the quality of evidence was low/very low according to the GRADE system. CONCLUSIONS: The present systematic review of existing RCTs suggests that aquatic physical activity, MBSR, computerized working-memory training, and blue-light therapy may be beneficial treatments for PTBIF. Due to the many flaws and limitations in these studies, further controlled trials using these interventions for PTBIF are necessary.
RESUMO
OBJECTIVE: To evaluate the effect and safety of Yimusake Tablets combined with dapoxetine hydrochloride and either of them used alone in the treatment of premature ejaculation (PE). METHODS: We randomly assigned 180 PE patients to oral medication of Yimusake Tablets at 1.5 g per night (group A), dapoxetine hydrochloride at 30 mg at 1ï¼3 hours before anticipated sexual activity (group B), the Yimusake Tablets plus dapoxetine hydrochloride simultaneously (group C), all for 8 weeks. After 4 and 8 weeks of medication, we recorded and compared the changes in the intravaginal ejaculation latency time (IELT), measures of the PE profile (PEP), and adverse events among the three groups of patients. RESULTS: The treatment was accomplished and complete data obtained from 154 of the patients, 56 in group A, 52 in group B, and 46 in group C. After 4 and 8 weeks of medication, the mean IELT was dramatically prolonged in all the three groups as compared with the baseline (P<0.01), most significantly at 8 weeks in group C (ï¼»2.08±0.68ï¼½ min), followed by B (ï¼»1.76±0.52ï¼½ min) and A (ï¼»1.47±0.44ï¼½ min), with statistically significant differences among the three groups (P<0.01). The PEP measures were remarkably improved in group A at 8 weeks (P<0.05), and both in B and C at 4 and 8 weeks (P<0.05), most significantly at 8 weeks in group C (P<0.05), in which the patients scored 1.96±0.77 in perception of control over ejaculation, 2.62±0.98 in satisfaction with sexual intercourse, 3.04±0.62 in PE-related distress, and 3.57±0.80 in PE-induced difficult relationship with their partners, all markedly improved as compared with groups A and B (P<0.05). Adverse reactions were observed in 2 cases (3.6%) in group A, 6 cases (9.6%) in B, and 5 cases (10.9%) in C. No severe adverse events occurred in any of the patients during the study. CONCLUSIONS: Combined medication of Yimusake Tablets and dapoxetine hydrochloride, with its advantages of effectiveness and safety, deserves to be recommended for the treatment of PE.