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Background and aim: Heart failure (HF) is a complex clinical syndrome that represents the end result of several pathophysiologic processes. Despite a dramatic evolution in diagnosis and management of HF, most patients eventually become resistant to therapy. Xin-Li Formula (XLF) is a Chinese medicine formula which shows great potential in the treatment of HF according to our previous studies. The present study was designed to investigate the effects of XLF on HF induced by a combination of hyperlipidemia and myocardial infarction (MI) in rats and reveal the underlying mechanism. Experimental procedure: A rat model of HF induced by hyperlipidemia and MI was established with intragastric administration of XLF and Perindopril. In vitro, CD4+ T cells from mouse spleen and LPS/ATP-stimulated THP-1 macrophages were employed. Results and conclusion: XLF was shown to have markedly protective effects on MI-induced HF with hyperlipidemia in rats, including improvement of left ventricular function, reduction of left ventricular fibrosis and infarct size. Moreover, XLF administration significantly increased the number of Foxp3+ Tregs, and inhibited mTOR phosphorylation and NLRP3 signaling pathway. In vitro, we found that XLF had induced Treg activation via the inhibition of mTOR phosphorylation in CD4+ T cells. Additionally, XLF inhibited NLRP3 inflammasome activation in LPS/ATP-stimulated THP-1 macrophages. Taken together, this study raises the exciting possibility that Xin-Li Formula may benefit HF patients due to its immunomodulatory and anti-inflammatory effects via Treg activation and NLRP3 inflammasome inhibition.
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BACKGROUND: Psoriasis is an immune-mediated chronic inflammatory skin disease characterized by well-defined erythema and white scales, which affects approximately 2% of the worldwide population and causes long-term distress to patients. Therefore, development of safe and effective therapeutic drugs is imminent. Autophagy, an evolutionarily conserved catabolic process, degrades intracellular constituents to maintain cellular energy homeostasis. Numerous studies have revealed that autophagy is closely related to immune function, such as removal of intracellular bacteria, inflammatory cytokine secretion, antigen presentation, and lymphocyte development. Phytochemicals derived from natural plants are often used to treat psoriasis due to their unique therapeutic properties and favorable safety. So far, a mass of phytochemicals have been proven to be able to activate autophagy and thus alleviate psoriasis. This review aimed to provide directions for finding phytochemicals that target autophagy to treat psoriasis. METHODS: The relevant literatures were collected from classical TCM books and a variety of databases (PubMed, Google Scholar, ScienceDirect, Springer Link, Web of Science and China National Knowledge Infrastructure) till December 2022. Search terms were "Phytochemical", "Psoriasis" and "Autophagy". The retrieved data followed PRISMA criteria (preferred reporting items for systematic review). RESULTS: Phytochemicals treat psoriasis mainly through regulating immune cell function, inhibiting excessive inflammatory response, and reducing oxidative stress. While the role and mechanism of autophagy in the pathogenesis of psoriasis have been confirmed in human trials, most of the evidence for phytochemicals that target autophagy to treat psoriasis comes from animal studies. The research focusing on the role of phytochemical-mediated autophagy in the prevention and treatment of psoriasis is limited, and the definite relationship between phytochemical-regulated autophagy and treatment of psoriasis still deserves further experimental confirmation. CONCLUSIONS: Phytochemicals with autophagic activities will provide new insights into the therapeutic intervention for psoriasis.
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Psoríase , Animais , Humanos , Psoríase/tratamento farmacológico , Autofagia , Pele , China , Bases de Dados FactuaisRESUMO
Psoriasis is a chronic inflammatory skin disorder characterized by abnormal keratinocytes proliferation and multiple immune cells infiltration in the dermis and epidermis. Although most psoriasis-related researches have been concentrated on the interleukin-23 (IL-23)/interleukin-17 (IL-17) axis, new data suggest that keratinocytes also play a pivotal role in psoriasis. Previously, we found that punicalagin (PUN), a bioactive ellagitannin extracted from Pericarpium Granati (the pericarpium of Punica granatum L.), exerts a therapeutic effect on psoriasis. However, the underlying mechanism, especially its potential modulatory effect on keratinocytes, remains obscure. Our study aims to reveal the potential regulatory effect and its underlying cellular mechanism of PUN on the hyperproliferation of keratinocytes. We used tumor necrosis factor α (TNF-α), IL-17A and interleukin-6 (IL-6) to induce abnormal proliferation of HaCaT cells (Human Keratinocytes Cells) in vitro. Then, we evaluated the effects of PUN through MTT assay, EdU staining and cell cycle detection. Finally, we explored the underlying cellular mechanisms of PUN via RNA-sequencing, WB in vitro and in vivo. Here, we found that PUN can directly and dose-dependently decrease TNF-α, IL-17A and IL-6-induced abnormal proliferation of HaCaT cells in vitro. Mechanically, PUN suppresses the hyperproliferation of keratinocytes through repressing S-phase kinase-associated protein 2 (SKP2) expression in vitro and in vivo. Moreover, overexpression of SKP2 can partly abolish PUN-mediated inhibition of aberrantly proliferative keratinocytes. These results illustrate that PUN can reduce the severity of psoriasis through directly repressing SKP2-mediated abnormal proliferation of keratinocytes, which gives new insight into the therapeutic mechanism of PUN on psoriasis. Moreover, these findings imply that PUN might be a promising drug candidate for the treatment of psoriasis.
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Taninos Hidrolisáveis , Psoríase , Humanos , Taninos Hidrolisáveis/farmacologia , Taninos Hidrolisáveis/uso terapêutico , Interleucina-17/metabolismo , Interleucina-17/farmacologia , Interleucina-17/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Proteínas Quinases Associadas a Fase S/metabolismo , Queratinócitos , Psoríase/tratamento farmacológico , Psoríase/patologia , Proliferação de CélulasRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Qidan Tiaozhi capsule (QD), a traditional Chinese medicine, has been used to treat metabolic syndrome for over a decade. However, the mechanism of QD in the treatment of metabolic syndrome is still unknown. AIM OF THE STUDY: Growing studies demonstrate that impaired mitophagy is one of the important causes of metabolic syndrome. Thus, this research aims to investigate the mechanism of mitophagy in the QD treatment of metabolic syndrome. MATERIALS AND METHODS: Network pharmacology and molecular docking were used to probe the mechanism of QD treatment of metabolic syndrome. In an oleic acid-induced cell model, glucose consumption and uptake capacity, triglyceride (TG), total cholesterol (TC), malonaldehyde (MDA), superoxide dismutase (SOD) and ROS levels, and mitochondrial membrane potential (MMP) were examined. mRFP-GFP-LC3 adenovirus and GFP-LC3 lentivirus were used to examine the effect of QD on mitophagy. The IRS2-PI3K and AMPK/PINK1-Parkin signal pathways were also determined. What's more, the PINK1 gene was silenced to verify the above findings. In a high-fat diet-fed mouse model, body weight, organ indexes, OGTT, ITT, HOMA-IR, insulin sensitivity, serum MDA, SOD, TC, TG, LDL-C and HDL-C, hepatic TC, TG, LDL-C and HDL-C levels, hepatic steatosis, and IRS2-PI3K and AMPK/PINK1-Parkin signal pathways were investigated. RESULTS: Results from network pharmacology and molecular docking suggested that QD might suppress oxidative stress to improve metabolic syndrome. In an oleic acid-induced cell model, compared with the model group, enhanced glucose consumption and uptake ability, inhibited intracellular lipid accumulation, TC, TG, MDA and ROS levels, and increased SOD level and MMP were found in QD groups. And mitophagy levels, IRS2-PI3K and AMPK/PINK1-Parkin signal pathways were promoted. Interestingly, PINK1 silencing reversed the therapeutic action of QD on oleic acid-induced cells. In high-fat diet-fed mice, inhibited body weight, abdominal fat indexes, liver indexes, HOMA-IR, serum and hepatic TC, TG and LDL-C, serum MDA and hepatic steatosis, and increased insulin sensitivity, serum and hepatic HDL-C, serum SOD, and activated IRS2-PI3K and AMPK/PINK1-Parkin signal pathways were found in QD groups. CONCLUSION: QD activates AMPK/PINK1-Parkin-mediated mitophagy to suppress oxidative stress to treat metabolic syndrome.
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Medicamentos de Ervas Chinesas , Fígado Gorduroso , Resistência à Insulina , Síndrome Metabólica , Mitofagia , Animais , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , LDL-Colesterol , Síndrome Metabólica/tratamento farmacológico , Mitofagia/efeitos dos fármacos , Simulação de Acoplamento Molecular , Ácido Oleico/farmacologia , Fosfatidilinositol 3-Quinases , Espécies Reativas de Oxigênio/metabolismo , Triglicerídeos , Ubiquitina-Proteína Ligases/metabolismo , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
INTRODUCTION: Cytopathology is an important part of pathology that is used to diagnose disease on the cellular level. The application of the cell block (CB) technique plays a vital role in cytological diagnosis, as blocks and slides can be further used for special stains, immunohistochemistry (IHC), and molecular pathological analysis. Several methods for making CBs have been reported, but their procedures and cellular yield are still deemed unsatisfactory. In this article, we used gellan gum (GG) as an adjuvant for CBs, which resulted in higher cellular yield with simpler procedures. METHODS: CBs were prepared by using GG, copper sulfate, plasma/thrombin, or pregelatinized starch methods. The procedures of each of these four methods were then compared. CB sections were stained with hematoxylin and eosin (H&E), and the background and morphological features seen by H&E staining were compared. A preliminary IHC and fluorescence in situ hybridization (FISH) study was performed using cytology specimens from eleven and five cases, respectively. The expression of immunocomplex by IHC and the molecular signals detected by FISH were compared in CB sections made by the four methods and a section derived from the biopsy specimen block from the same patient. Feulgen staining, Alcian blue staining, and Masson trichrome staining were performed on the CB sections from 3 cases of pleural fluid. The cellular yield of CB sections from 83 cases according to the four methods was compared using NDP analysis software. RESULTS: The results demonstrated that sections derived from CBs made with GG had a clear background and good morphological features by H&E staining. The expression of immunocomplex by IHC and the molecular signals of FISH detection in the sections from CBs made by GG were accurately located just as those in biopsy sections from the same patient. The DNA, acidic mucus, and fibrin could be clearly identified through special stains in the CB sections. The procedures involved in the GG method were easily controllable and the coagulated gel increased the ease by which the CB was embedded and sectioned. Specifically, sections from CBs made by the GG method contained higher cellular yield because cells could be concentrated on the bottom of the gel after centrifugation. CONCLUSION: This novel method for making CBs is a practical, simple method that can result in higher cellular yield. This method is therefore worth promoting in clinical applications.
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Citodiagnóstico , Humanos , Citodiagnóstico/métodos , Hibridização in Situ Fluorescente , Imuno-Histoquímica , BiópsiaRESUMO
Background: Metabolic syndrome is characterized by central obesity, hyperglycemia and hyperlipidemia. Insulin resistance is the leading risk factor for metabolic syndrome. Kun-Dan decoction (KD), a traditional Chinese medicine, has been applied to treat patients with metabolic syndrome for over ten years. It is increasingly recognized that autophagy deficiency is the key cause of metabolic syndrome. Therefore, we aimed to explore whether KD can activate autophagy to improve metabolic syndrome. Methods: Network pharmacology was used to explore the underlying mechanism of KD in the treatment of metabolic syndrome. The high-fat diet-fed rats and oleic acid-induced LO2 cells were employed in our study. Oral glucose tolerance test and insulin tolerance test, obesity and histological examination, serum cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity in high-fat diet-fed rats were analyzed. Furthermore, the protein expressions of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), phospho-AMPK, mammalian target of rapamycin (mTOR), phospho-mTOR, p62, autophagy related protein (Atg) 5, Atg7, Atg12, Atg13, Atg16L1 and microtubule-associated protein 1A/1B-light chain 3 (LC3)-â ¡/â were examined in rats and LO2 cells. Moreover, autophagy activator rapamycin and inhibitor 3-methyladenine, and small interfering RNA against Atg7 were utilized to verify the role of autophagy in the treatment of metabolic syndrome by KD in oleic acid-induced LO2 cells. Results: Results from network pharmacology indicated that targeted insulin resistance might be the critical mechanism of KD in the treatment of metabolic syndrome. We found that KD significantly suppressed obesity, serum cholesterol, triglyceride and LDL-C levels and increased serum HDL-C level in high-fat diet-fed rats. Furthermore, KD enhanced insulin sensitivity and attenuated HOMA-IR in high-fat diet-fed rats. Western blot showed that KD could enhance autophagy to increase the insulin sensitivity of high-fat diet-fed rats and oleic acid-induced LO2 cells. Furthermore, 3-methyladenine and small interfering RNA against Atg7 could reverse the protective effect of KD on LO2 cells. However, rapamycin could cooperate with KD to enhance autophagic activation to increase insulin sensitivity in LO2 cells. Conclusion: The induction of autophagy may be the major mechanism for KD to improve insulin resistance and metabolic syndrome.
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Cisplatin-based chemotherapeutic regimens are the most frequently used adjuvant treatments for many types of cancer. However, the development of chemoresistance to cisplatin results in treatment failure. Despite the significant developments in understanding the mechanisms of cisplatin resistance, effective strategies to enhance the chemosensitivity of cisplatin are lacking. Phytochemicals are naturally occurring plant-based compounds that can augment the anti-cancer activity of cisplatin, with minimal side effects. Notably, some novel phytochemicals, such as curcumin, not only increase the efficacy of cisplatin but also decrease toxicity induced by cisplatin. However, the exact mechanisms underlying this process remain unclear. In this review, we discussed the progress made in utilizing phytochemicals to enhance the anti-cancer efficacy of cisplatin. We also presented some ideal phytochemicals as novel agents for counteracting cisplatin-induced organ damage.
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Antineoplásicos Fitogênicos/uso terapêutico , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Animais , Antineoplásicos Fitogênicos/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Cisplatino/metabolismo , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Humanos , Neoplasias/metabolismo , Compostos Fitoquímicos/metabolismo , Compostos Fitoquímicos/farmacologiaRESUMO
OBJECTIVE: To explore the preventive and therapeutic effects of Resveratrol combined with total flavones of hawthorn, compatibility of traditional Chinese medicines, on the endothelial cells injury after artery bypass graft surgery. METHODS: The animal model of coronary artery bypass grafting (CABG) was prepared by transplanting a segment of autologous jugular vein onto the transected common carotid artery in rabbits. After CABG surgery, the rabbits were administrated with saline (model group), aspirin (Aspirin group), resveratrol (Res group), total flavones of hawthorn (Haw group) and resveratrol combined with total flavones of hawthorn (Res+Haw group) once a day for eight weeks, respectively. Eight weeks later, the grafting arteries from all group were obtained for the pathomorphism observation, peripheral blood was collected to detect circulating endothelial cells (CECs) by flow cytometry. And the concentration of albumen and mRNA of ICAM-1 in the serum were measured by western blot and quantitative real-time polymerase chain reaction, respectively. RESULTS: Compared with the model group, the level of CECs density and the expressions of albumen and mRNA of ICAM-1 were significantly decreased in the aspirin,resveratrol,total flavones of hawthorn and resveratrol combined with total flavones of hawthorn groups (Pâ¯<â¯.05). Of note, above all parameters were lower in Res group than aspirin group. CONCLUSION: The Resveratrol combined with total flavones of hawthorn could protect the endothelial cells after coronary artery bypass graft.
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Ponte de Artéria Coronária/efeitos adversos , Crataegus/química , Endotélio Vascular/patologia , Flavonas/farmacologia , Estilbenos/farmacologia , Animais , Aspirina/farmacologia , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/cirurgia , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão Intercelular/genética , Coelhos , ResveratrolRESUMO
The discovery of new therapeutic drugs with the efficacious and safe ability to prevent epidermal hyperplasia is extremely urgent for psoriasis. Cryptotanshinone (CTS), an active component isolated from the root of Salvia miltiorrhiza Bunge, has been reported to have antibacterial and antitumor effects. However, its effects on psoriasis have not been reported. Here, we investigated the therapeutic effects of CTS on imiquimod (IMQ)-induced psoriatic-like skin model and explored the underlying mechanisms. Our results revealed that CTS effectively alleviates IMQ-induced epidermal hyperplasia. In vitro studies also indicated that CTS potently inhibits the growth of keratinocytes. We further found that STAT3, a transcription factor for the cell growth, is the key mediator of CTS on the proliferation of keratinocytes. Taken together, our findings indicated that the curative effects of CTS on psoriasis are accomplished mainly through modulating STAT3, which providing evidences to develop CTS as a potential therapeutic agent for patients with psoriasis.
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Proliferação de Células/efeitos dos fármacos , Epiderme/patologia , Fenantrenos/uso terapêutico , Psoríase/tratamento farmacológico , Fator de Transcrição STAT3/antagonistas & inibidores , Animais , Linhagem Celular , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Hiperplasia/induzido quimicamente , Hiperplasia/tratamento farmacológico , Hiperplasia/patologia , Imiquimode , Queratinócitos , Masculino , Camundongos Endogâmicos C57BL , Fenantrenos/farmacologia , Psoríase/induzido quimicamente , Psoríase/patologiaRESUMO
Hepatocellular carcinoma (HCC) is one of the most common and fatal cancers in the world. Tumor metastasis is an important factor of poor prognosis in patients with HCC. Tumor hypoxia can promote tumor cell metastasis in HCC. Epigenetic modification is closely related to tumor hypoxia and metastasis. In our previous research, we found that basil polysaccharide suppressed migration and invasion of HCC cell by inhibiting hypoxia induced histone methylation in vitro. In the present study, we investigated the effect of basil polysaccharide on the walker 256 carcinoma cell metastasis in rat. We established an intratumoral hypoxic model in rat by hepatic artery ligation (HAL). Then rats were treated with basil polysaccharide (75, 150 and 300mg/kg). The results showed that HAL could promote tumor metastasis by aggravating tumor hypoxia. However, basil polysaccharide could inhibit tumor metastasis in intratumoral hypoxia. Further, we demonstrated that basil polysaccharide could down-regulate the expression of HIF-1α, G9a, LSD1, JMJD1A, JMJD2B, JARID1B and H3K9me2. Synchronously, basil polysaccharide could increase E-cadherin and VMP1 expression, and decrease N-cadherin, vimentin and ß-catenin expression. The results indicated that histone modifying enzymes might be a new therapeutic target of basil polysaccharide on hepatocellular carcinoma metastasis.
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Carcinoma Hepatocelular/tratamento farmacológico , Artéria Hepática/patologia , Histonas/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Ocimum basilicum/química , Polissacarídeos/uso terapêutico , Animais , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Hipóxia Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Ligadura , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Metilação , Metástase Neoplásica , Proteínas de Neoplasias/metabolismo , Polissacarídeos/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos WistarRESUMO
OBJECTIVES: Chromosomal rearrangements of ALK and ROS1 genes in non-small cell lung carcinoma (NSCLC) define a molecular subgroup of lung adenocarcinoma (ADC) that is amenable to targeted therapy with tyrosine kinase inhibitors (TKIs) crizotinib. Emerging clinical studies have demonstrated that patients with RET-rearranged NSCLC may also benefit from existing RET TKIs, including cabozantinib and vandetanib. However, the reported cases of lung squamous cell carcinomas (SCC) harboring gene rearrangements have been detected via fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) from materials such as biopsy or resection. Fusion events identified in lung SCC raise the question of whether this histologic subtype should also be evaluated for merit molecular testing. This work was undertaken to study the prevalence of lung SCC harboring ALK, ROS1, and RET translocations. MATERIALS AND METHODS: Squamous cell carcinomas were confirmed using both histological examination by pathologists and immunohistochemistry analysis with positive staining of P63 and CK5/6 combined with negative CK7 and TTF-1 staining. 214 samples from surgically resected patient tissues were used to search for ALK, ROS1, and RET rearrangements by a NanoString analysis method. Fusion events were detected in a single-tube, multiplex assay system that relied on a complementary strategy of interrogation of 3' gene overexpression and detection of specific fusion transcript variants. RESULTS AND CONCLUSION: ALK, ROS1 or RET gene rearrangements appeared 0 times out of 214 cases of lung SCC. Our data revealed that these fusions may be very rare in lung squamous cancer. The molecular screening strategy should therefore be focused on lung adenocarcinoma as the current National Comprehensive Cancer Network (NCCN) guideline recommends.
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Carcinoma de Células Escamosas/genética , Rearranjo Gênico , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Carcinoma de Células Escamosas/diagnóstico , Estudos de Coortes , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas de Fusão Oncogênica , Transcrição Gênica , Translocação GenéticaRESUMO
Connexin 26 (cx26) plays an important role in the intercellular signaling and is related to K(+) metabolism in stria vascularis (SV). Reactive oxygen species (ROS) are negative regulators of cx26, reducing intercellular coupling in cochlea. ROS plays an important role in acoustic trauma. Radix astragali is a natural antioxidant that decreases impulse noise-induced hearing loss through its ability to inhibit ROS. The purpose of this study was to investigate if radix astragali has the potential to reduce the change of cx26 in SV from impulse noise. Guinea pigs in the experimental group were administered radix astragali intraperitoneally. Auditory thresholds were assessed by sound-evoked auditory brainstem response (ABR) at click and tone bursts of 8, 16 and 32 kHz, 24 h before and 72 h after exposure to impulse noise. 4-Hydroxynonenal, cx26 and KCNQ1 were determined immunohistochemically in SV. SV was analyzed by transmission electron microscopy. Radix astragali significantly reduced the ABR deficits and the SV damage, and decreased the shifts of the expression of cx26 and KCNQ1 in the SV. These results suggest that the beneficial effect of radix astragali on impulse noise-induced hearing loss may be also due to its ability to reduce the change of cx26 in SV.
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Conexinas/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Perda Auditiva Provocada por Ruído/tratamento farmacológico , Perda Auditiva Provocada por Ruído/metabolismo , Estria Vascular/metabolismo , Aldeídos/metabolismo , Animais , Astragalus propinquus , Limiar Auditivo , Conexina 26 , Modelos Animais de Doenças , Regulação para Baixo , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Cobaias , Perda Auditiva Provocada por Ruído/etiologiaRESUMO
OBJECTIVE: To observe the effect of detoxifying and blood circulation activating Chinese herb extraction of polygonum cuspidatum and hawthorn on carotid intima-media thickness (IMT), plaque integral and plaque stability related serum indexes of patients with carotid atherosclerosis. METHOD: Sixty and four cases of carotid artery atherosclerosis patients were assigned randomly to 2 groups: detoxifying and blood circulation activating treatment group (treatment group, 32 cases) and control group (32 cases). Patients in treatment group were treated with capsules of extraction of polygonum cuspidatum and hawthorn, 1 pill po, bid (dosage of administration: polygonum cuspidatum extraction 5.33 mg x kg(-1) x d(-1), hawthorn extraction 5.0 mg x kg(-1) x d(-1)); patients in control group were treated with lovastatin 20 mg po, qd (dosage of administration: 0.33 mg x kg(-1) x d(-1)). The course of treatment was six months. To observe changes of IMT, plaque integral, and detect the level of plaque stability related serum indexes such as Hs-CRP, MMP-1 and TIMP-1. RESULT: After 6 months of treatment, in control group one patient quit the clinical trial because of liver dysfunction and one patient was rejected because of having not followed the therapeutic regimen. 32 cases in treatment group and 30 cases in control group were analyzed. The results showed that IMT and plaque integral of treatment group decreased significantly after the treatment (P < 0.05, P < 0.01), and there was no significant difference compared with control grope. Serum Hs-CRP, MMP-1 and MMP-1/TIMP-1 decreased after the treatment (P < 0.05, P < 0.01), and the treatment group was superior to control group in decreasing serum Hs-CRP (P < 0.05). CONCLUSION: Detoxifying and blood circulation activating Chinese herb extraction of polygonum cuspidatum and hawthorn has good effect of anti-atherosclerosis and promoting plaque stability. Its mechanism might be related with anti-inflammation and inhibiting degradation of extracellular matrix, and deserves further studies.
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Doenças das Artérias Carótidas/tratamento farmacológico , Crataegus/química , Medicamentos de Ervas Chinesas/farmacologia , Fallopia japonica/química , Proteína C-Reativa/metabolismo , Doenças das Artérias Carótidas/sangue , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Masculino , Metaloproteinase 1 da Matriz/sangue , Pessoa de Meia-Idade , Segurança , Inibidor Tecidual de Metaloproteinase-1/sangueRESUMO
In the present study, a polysaccharide extract was obtained from Ocimum basilicum (basil polysaccharide, BPS) and the effects of curcumin and BPS on the invasion activity of the SKOV3 ovarian cancer cells and human monocyte-derived dendritic cells (DCs) were investigated. SKOV3 cells and immature or mature DCs were treated with 50 µM curcumin or 100 µg/ml BPS. A transwell invasion assay demonstrated that curcumin and BPS differentially regulate the invasion of SKOV3 cells and DCs. Curcumin significantly decreased the invasion of SKOV3 cells and immature and mature DCs, while BPS only decreased SKOV3 cell invasion. Osteopontin (OPN) mRNA and protein expression were significantly reduced in curcumin and BPS-treated SKOV3 cells and curcumin-treated DCs. Furthermore, flow cytometry showed that curcumin significantly inhibited the surface expression of CD44 in SKOV3 cells and DCs, while BPS had a minimal effect on CD44 expression. Matrix metallopeptidase-9 (MMP-9) mRNA and protein expression were also reduced in all curcumin-treated cells and BPS-treated SKOV3 cells. The results indicated that curcumin and BPS regulated invasion of SKOV3 cells and DCs by distinctly downregulating OPN, CD44 and MMP-9 expression. Therefore, Curcumin and BPS may be suitable candidates for DC-based vaccines for ovarian cancer immunotherapy.
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Curcumina/farmacologia , Células Dendríticas/citologia , Monócitos/citologia , Ocimum basilicum/química , Neoplasias Ovarianas/patologia , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Animais , Western Blotting , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Invasividade Neoplásica , Osteopontina/genética , Osteopontina/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: To observe the effect of Huxin Formula on expressions of the chief reverse cholesterol transport (RCT) associated genes, caveolin-1 and scavenger receptor-BI (SR-BI) in ApoE-gene knockout [ApoE (-/-)] mice. METHODS: Thirty ApoE (-/-) mice of 4-6 weeks old were randomly divided into three groups (A-C). After being fed with high-fat diet for 16 weeks, they were treated with HXF (1 mL/100 g), pravachol (0.3 mg/100 g), and saline in equal volume respectively for 16 weeks successively; in addition, a blank group was set up with 10 C57BL/6J mice of 6-week old received 16-week high-fat feeding and saline treatment. Animals were sacrificed at the termination of the experiment, their paraffin sections of aortic tissue were used to measure the size of plaque, expressions of cavolin-1 and SR-BI were detected by immunological histochemical method. RESULTS: As compared with the blank group, levels of caveolin-1 and SR-BI were increased in Groups A and B (P<0.01); but the increase in Group A was more significant than that in Group B (P<0.05). The plaque/aorta area ratio decreased significantly in Groups A and B, but showed insignificant difference between the two groups. CONCLUSION: HXF could obviously increase the expressions of RCT associated genes, caveolin-1 and SR-BI, promote the RCT process, so as to reduce the formation of aorta atherosclerotic plaque in ApoE (-/-) mice.
Assuntos
Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Colesterol/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Aterosclerose/patologia , Transporte Biológico/efeitos dos fármacos , Caveolina 1/metabolismo , Feminino , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Placa Aterosclerótica/patologia , Receptores Depuradores/metabolismoRESUMO
OBJECTIVE: To observe the regulatory effect of Chinese herbal compound for detoxifying and activating blood circulation on expression of nuclear factor-kappaB (NF-kappaB) and matrix metalloproteinase-9 (MMP-9) in aorta of apolipoprotein E gene knocked-out (ApoE (-/-)) mice. METHODS: ApoE (-/-) mice of 13-week old were divided into two groups and fed with normal diet (Group A) and hyperlipidemic diet (Group B) respectively, the latter was subdivided into 7 groups as Group B1 - 7. Besides, a normal control group was set up with C57BL/6J mice. The drugs used for intervention were polydatin (PD, with 26.6 mg/kg as one dose) for detoxifying and Xiongshao Capsule (XC, with 110 mg/kg as one dose) for activating blood circulation respectively. The intervention was started 19 weeks later by treated Group B1 with PD one dose daily, Group B2 with XC one dose daily, Group B3 with PD and XC each 2 doses daily, Group B4 with PD and XC each one dose daily, Group B5 with PD and XC each half dose daily, Group B6 with lovastatin. To the Group B 7 (as a hyperlipidemia model group) as well as Group A and the normal control group, normal saline was given. After 17 weeks of intervention, the expressions of NF-kappaB and MMP-9 in aorta of mice were determined with immunohistochemical assay. RESULTS: Expressions of NF-kappaB and MMP-9 in aorta and sclerotic plaque were higher in group B7 than those in the normal control group, which were lowered in group B1 - 6 (P < 0.01), and the optimal effect was shown in group B3 (P <0.01). CONCLUSION: Combined use of Chinese herbal medicine for detoxifying and activating blood circulation could reduce expression of NF-kappaB and MMP-9 in aorta of ApoE (-/-) mice, and the effect of the combination of the two was superior to that of use either of them.
Assuntos
Aorta/efeitos dos fármacos , Apolipoproteínas E/genética , Medicamentos de Ervas Chinesas/farmacologia , Metaloproteinase 9 da Matriz/biossíntese , NF-kappa B/biossíntese , Animais , Anticolesterolemiantes/farmacologia , Aorta/metabolismo , Aorta/fisiologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Cápsulas , Feminino , Imuno-Histoquímica , Lovastatina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/irrigação sanguínea , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismoRESUMO
OBJECTIVE: To observe the effect of Maixinkang Capsule (MXK) on Ca2t concentration and mitochondrial membrane potential in liver cells of ApoE(-/-) mice. METHODS: Liver cells from ApoE(-/-) mice were separated using collagenase digestive method. After the primary cells were cultured for 8 days in vitro, the concentration of 10% MXK contained rat's serum was added into the culture fluid. The Ca2+ concentration and mitochondrial membrane potential in liver cells after 48-hr culture were measured by confocal laser scanning microscopy with Flou-3 and Jc-1 as probes. RESULTS: MXK could decrease Ca2+ concentration in liver cells, which was significantly different to that in the control group (P < 0.01). Meanwhile, MXK could significantly improve mitochondrial membrane potential in liver cells (P < 0.01). There was no obvious dose-effect relationship shown in both effects of MXK. CONCLUSION: MXK can decrease Ca2+ concentration and improve the mitochondrial membrane potential in liver cells of ApoE(-/-) mice so as to regulate the lipids and prevent the occurrence and development of hyperlipemia and atherosclerosis.
Assuntos
Apolipoproteínas E/genética , Canais de Cálcio/efeitos dos fármacos , Hepatócitos/fisiologia , Membranas Mitocondriais/fisiologia , Animais , Animais Recém-Nascidos , Potenciais da Membrana , Camundongos , Camundongos KnockoutRESUMO
OBJECTIVE: To explore antitumor and synergy effect of "Bushen Huayu Jiedu Formula" (BSHYJDF) on hepatocarcinoma H22. METHODS: Transplanted hepatocarcinoma H22 mice were used, the inhibitory rates of H22 were observed respectively to BSHYJDF and BSHYJDF combined with cisplatin (DDP). RESULTS: BSHYJDF could significantly inhibit hepatocarcinoma H22 in transplanted mice (P < 0.05). CONCLUSION: BSHYJDF had inhibitive effect and synergy with chemotherapy to a certain extent in transplanted hepatocarcinoma mice.
Assuntos
Cisplatino/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/farmacologia , Sinergismo Farmacológico , Neoplasias Hepáticas Experimentais/patologia , CamundongosRESUMO
To explore Rh123 ion concentration effect of "Bushen huayu jiedu fang" (BSHYJD) on drug-resistance lung cancer cells, tumor-bearing animal drug-serum pharmacology and flow cytometry method were utilitied. In contrast with normal animal drug serum, BSHYJD drug-serum of tumor-bearing animal would markedly increase Rh123 concentration in drug-resistance lung cancer cells(P < 0.05), but which hasn't marked discrepancy in contrast with normal animal drug-serum(P > 0.05), that indicated BSHYJD drug-serum has increased drug concentration in drug-resistance lung cancer cells.