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BACKGROUND: Bone metastasis is frequently common in advanced lung cancer with the major issue of a pathological fracture. Previous studies suggested that Astragalus membranaceus (Qi) and Ampelopsis japonica (Lian), which are used as folk medicine in China, have potential effects on inhibiting tumor growth and protecting bones, respectively. In this study, an experiment on the inhibitory effect of the Qilian formula (AAF) in vivo was designed to examine tumor growth in bone and osteoclast formation. MATERIALS AND METHODS: The bone metastasis xenograft models were established by implanting NCI-H460-luc2 lung cancer cells into the right tibiae bones of mice. After confirming the model's viability through optical imaging 7 days post-implantation, 2 groups, namely the AAF group and the control group, were administered 0.3 mL of AAF extract (9 g/kg/day) or normal saline via intragastric delivery for a duration of 4 weeks. Throughout the study, we longitudinally assessed tumor burden, bone destruction, and weight-bearing capacity in vivo using reporter gene bioluminescence imaging (BLI), micro-CT, and dynamic weight-bearing (DWB) tests. Mechanistic insights were gained through Hematoxylin-eosin (H&E) staining, immunohistochemical (IHC) analysis, western blotting, and flow cytometry. RESULTS: Qilian formula produced significant inhibition to the progress of bone destruction and tumor burden in the right tibiae bone in the treatment group. It was further evidenced by molecular imaging in vivo via small animal micro-CT and BLI with parametric quantification, characterizing significantly lower uptake of BLI signal in the treated tumor lesions and improving the pathological changes in the microstructure of bone. Furthermore, DWB tests revealed that Qilian formula treatment significantly maintained the weight-bearing capacity. According to immunohistochemical analysis, the effect of the Qilian formula appeared to involve the suppression of osteoclast formation by lower expression of the tartrate-resistant acid phosphatase. Cell apoptosis and death induction were evidenced by a higher percentage of Bal2ãBAX and caspase 3 expressions of Qilian formula-treated tumor tissues. CONCLUSIONS: Our study demonstrated a significant inhibitory effect of the Qilian formula on the progression of osteolytic invasion in vivo by suppressing osteoclastogenesis and promoting apoptotic cell death.
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Neoplasias Ósseas , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Ósseas/tratamento farmacológico , Proliferação de Células , Osteoclastos/metabolismo , Osteoclastos/patologia , Ciclo Celular , Linhagem Celular TumoralRESUMO
Objective: To investigate the effects of systematic pregnancy management on labor and maternal and infant outcomes in gestational diabetes mellitus patients (GDM). Methods: From February 2020 to December 2021, 116 patients who were diagnosed with GDM at the first hospital of Hebei medical university were enrolled in this prospective study. According to the random number table, patients were divided into the control group (n = 58, routine nursing) and the intervention group (n = 58, systematic pregnancy management). Results: After treatment, the blood glucose levels of both groups decreased compared to that measured before treatment, and the blood glucose levels in the intervention group were lower than those in the control group (P < .05). After treatment, the lipid profile cholesterol levels of both groups decreased compared to those measured before treatment. However, the lipid profile cholesterol levels were lower in the intervention group than those in the control group (P < .05). The first, second, and third stages of labor and total labor time in the intervention group were lower than those in the control group (P < .05). The rate of natural delivery in the intervention group was higher than that in the control group, while the rate of cesarean section was lower than that in the control group (P < .05). Conclusion: Systematic pregnancy management can reduce the level of blood glucose and improve lipid metabolism in patients with GDM.
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Diabetes Gestacional , Gravidez , Humanos , Lactente , Feminino , Diabetes Gestacional/terapia , Diabetes Gestacional/diagnóstico , Resultado da Gravidez , Glicemia/metabolismo , Cesárea , Estudos Prospectivos , Lipídeos , ColesterolRESUMO
BACKGROUND: Oxidative stress and chronic non-infectious inflammation caused vascular endothelial dysfunction (VED) is a critical and initiating factor in Type 2 diabetes induced vascular complications, while macrophage polarization plays a regulatory role in VED. Astragalus polysaccharide (APS) has been widely used for treating diabetic vascular diseases, but its mechanisms of action have not been fully elucidated. PURPOSE: This study aimed to investigate the modulatory effects of APS on macrophage polarization and to reveal the potential mechanisms of APS in LPS and HG stimulated macrophages and diabetic model rats. METHODS: In vitro and in vivo studies were used to explore the mechanism of APS. The macrophage polarization and reactive oxygen species (ROS) release was monitored by flow cytometry and the associated inflammatory factors were detected by ELISA. For oxidative stress regulatory pathway detection, protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme oxygenase-1 (HO-1) was measured by Western blotting. The vascular endothelial functions were measured by transwell, tube formation assay, scratch assay, adhesion assay. The thoracic aorta pathological changes were evaluated by Haematoxylin-eosin and immunohistochemistry. RESULTS: In vitro, APS inhibited the LPS/HG-stimulated THP-1 macrophage differentiated into macrophage M1, coupling with reduction in the ROS production and pro-inflammatory factors (TNF-α, IL-6, IL-12) release. Furthermore, endothelial cells proliferation and apoptosis were ameliorated after APS treatment. Meanwhile, APS-treated THP-1/macrophage occurred a differentiation into M2 polarization and anti-inflammatory factors (IL-4, IL-10, and Arg-1) release via enhancing Nrf2/HO-1 signaling pathway, which could be disturbed by using siNrf2. APS promoted the migration and angiogenesis of endothelial cells in co-cultured of HUVECs and macrophages under high glucose. Finally, similar results were observed in vivo, APS alleviated thoracic aorta complications of diabetic rats accompanied by a remarkable reduction in inflammation and an increased in the number of anti-inflammatory macrophage polarization. CONCLUSION: Our results demonstrated that APS ameliorated vascular endothelial dysfunction in diabetes by stimulating macrophage polarization to M2 via enhancing the Nrf2/HO-1 pathway.
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Astrágalo , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Ratos , Animais , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Lipopolissacarídeos/farmacologia , Células Endoteliais/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Transdução de Sinais , Polissacarídeos/farmacologia , Inflamação/metabolismo , Macrófagos/metabolismo , Anti-Inflamatórios/farmacologiaRESUMO
The high demand and extensive exploitation of uranium resources resulted in the ubiquity and high detection levels of uranium mineral-related substances in various environment media in China. The potential adverse effects of uranium mineral-related substances on environment and human health have received extensive attention. Therefore, we reviewed the occurrence and spatial distribution of uranium mineral-related substances in various basins and environmental media in China to obtain an overall understanding. We collected information from over 70 papers reporting the occurrence and distribution of uranium mineral-related substances in multiple environments and 183 articles on the genesis of uranium deposits in China from 2001 to 2021. Then the occurrence of uranium mineral-related substances and corresponding correlation in different basins, environmental media and depth ranges were compared in detail. And this review assessed the uranium mineral-related pollution in China based on various environmental quality standards of China, EPA and WHO, and proposed the priority uranium mineral-related heavy metals and radioactive substances based on cluster analysis. This review showed that there were obvious differences in the occurrence characteristics of various uranium mineral-related substances in different environmental media, especially in the surrounding environment of sandstone type and hard rock type uranium deposits. These results will guide us to tackle the challenge of uranium mineral-related pollution in China. The correlation analysis of uranium mineral-related pollutants in different environmental media and the identification of priority pollutants will also provide instructions for us to control uranium mineral-related pollution. Finally, we put forward a series of urgent and practical suggestions on risk management and control of uranium mining according to the current situation of uranium mining environment in China, which is of guiding significance for the realization of "green uranium mining".
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Poluentes Radioativos do Solo , Urânio , China , Monitoramento Ambiental/métodos , Humanos , Minerais/análise , Mineração , Urânio/toxicidadeRESUMO
BACKGROUND: Macrophages infiltration and activation play multiple roles in maintaining intestinal homeostasis and participate in the occurrence and development of UC. Thus, the restoration of immune balance can be achieved by targeting macrophage polarization. Previous studies have reported that TXYF could effectively ameliorate DSS-induced colitis. However, the underlying mechanisms of TXYF for DSS-induced colitis are still ill-defined. METHODOLOGY: This study was designed to explore the therapeutic effect of TXYF and its regulation in macrophages polarization during DSS-induced mice. In C75BL/6 mice, dextran sulfate sodium (DSS) was used to induce colitis and concomitantly TXYF was taken orally to evaluate its curative effect. In vitro experiment was implemented on BMDMs by lipopolysaccharide, IFN- and ATP. RESULTS: Here, we found that TXYF ameliorated clinical features in DSS-induced mice, decreased macrophages M1 polarization but remarkably increased M2 polarization. Mechanically, TXYF treatment effectively inhibited the activities of nuclear transcription factor NF-κB, which further contributed to the decrease of the inflammasome genes of NLRP3, limiting the activation of NLRP3 inflammasome in vivo and in vitro. CONCLUSION: Our findings demonstrated administration of TXYF can interfere with macrophage infiltration and polarization to improve the symptoms of acute colitis, by repressing NF-κB/NLRP3 signaling pathway activation. This enriches the mechanism and provides new prospect for TXYF in the treatment of colitis.
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Colite , NF-kappa B , Trifosfato de Adenosina/metabolismo , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana/efeitos adversos , Medicamentos de Ervas Chinesas , Inflamassomos , Lipopolissacarídeos/farmacologia , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de SinaisRESUMO
Objective: This research paper is based on a retrospective case-control study for exploring the effects of medical nursing integration and the continuous 4C nursing model to improve the clinical treatment and nursing quality of patients with acute stroke. Method: For this purpose, a total of 313 patients with acute stroke, treated in our hospital from February 2020 to April 2021, were enrolled. They were divided into control and study groups with an even number of patients. The control group received integrated medical care number (N = 156), while the study group received integrated medical care and a continuous 4C nursing model (N = 157). In integrated medical care, the general data, self-nursing ability, degree of neurological impairment, Fugl-Meyer Assessment (FMA) score, Barthel index score, and quality of life score were compared between the two groups. Result: The self-nursing concept, self-nursing responsibility, self-nursing skills, health knowledge, and total score of the patients in the study group were higher than those in the control group (P < 0.05). The neurological function scores of the study group were lower than those of the control group at 1, 3, and 6 months after discharge (P < 0.05). The scores of the study group were higher than those of the control group at 1, 3, and 6 months after discharge (P < 0.05). The Barthel index score of the study group was higher than that of the control group at 1, 3, and 6 months after discharge. The scores of physical function, psychological function, social function, and health self-cognition in the study group were lower than those in the control group (P < 0.05). Conclusion: The application of integrated medical care and the continuous 4C nursing model for patients with acute stroke is beneficial to enhance the degree of neurological impairment of stroke patients, improve activities of daily life and motor function, and facilitate patients' quality of life. It is helpful to strengthen the attitude and feeling of cooperation between doctors and nurses, promote cooperation between doctors and nurses, reduce the defects of nursing work, heighten the quality of nursing, and achieve the requirement and goal of effectively promoting high-quality nursing.
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Qualidade de Vida , Acidente Vascular Cerebral , Estudos de Casos e Controles , Humanos , Modelos de Enfermagem , Estudos Retrospectivos , Acidente Vascular Cerebral/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Atopic dermatitis (AD), a common inflammatory skin disorder, severely affects the life quality of patients and renders heavy financial burden on patient's family. The Chinese medicine Viola yedoensis Makino formula (VYAC) has been widely used for treating various skin disorders. Previous studies have reported that VYAC is effective in relieving DNCB-induced AD and inflammation. However, the anti-inflammatory mechanism of VYAC is still ill-defined and poorly understood. This study aims to investigate the therapeutic effects of VYAC on DNCB-induced AD and to elucidate the underlying anti-inflammatory mechanisms. METHODOLOGY: VYAC were extracted with 70% ethanol and lyophilized for use. AD mice were established by DNCB. The therapeutic effects of VYAC were evaluated by oral administration VYAC (150, 300 and 600 mg/kg) daily in vivo. The histopathological and immunohistochemistry were used to analyze skin lesion and macrophages infiltration, RT-qPCR and Elisa were used to analyze the inflammatory factors in skin tissues and serum. To explore the underlying mechanism of VYAC against AD in vitro. RAW264.7 cells and bone-marrow-derived macrophages (BMDMs) were employed for macrophage polarization analysis. Flow cytometer, immunofluorescence and western blot were used to analyze M2 macrophages markers. STAT3 siRNA were transfected into both cells to validate the effects of VYAC-induced macrophages M2 polarization via JAK2/STAT3 signaling pathway. RESULTS: VYAC ameliorated skin lesion of DNCB-induced AD mice by decreased clinical scores and epidermal thickness, decreased the level of pro-inflammatory factors (IL-1ß, TNF-α and IL-18) and enhanced IL-10 anti-inflammatory factor level, inhibited macrophages infiltration and promoted M2 macrophages polarization in vivo. VYAC significantly promoted M2 macrophages polarization in vitro. It is observed that VYAC not only inhibited the phosphorylation of JAK2 and STAT3 in RAW264.7 cells and BMDMs, but also accelerated the translocation to the nucleus. What's more, VYAC reduced the polarization of M2 macrophage by activating JAK2/STAT3 signaling pathway was observed in both cells. CONCLUSIONS: Our findings demonstrate that VYAC significantly ameliorates skin lesion of DNCB-induced AD mice and reduces the levels of inflammatory factors by activating JAK2/STAT3 signaling pathway and promoting M2 macrophages polarization.
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Dermatite Atópica , Medicamentos de Ervas Chinesas , Janus Quinase 2 , Macrófagos , Fator de Transcrição STAT3 , Viola , Animais , Anti-Inflamatórios/uso terapêutico , Polaridade Celular , Citocinas/metabolismo , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/metabolismo , Dinitroclorobenzeno , Medicamentos de Ervas Chinesas/farmacologia , Janus Quinase 2/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/farmacologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Viola/químicaRESUMO
BACKGROUND: Scutellaria barbata D.Don (SBD) is derived from the dried whole plant of Labiate which has been widely used to treat patients with multiple cancer. It was previously reported that the ethanol extract of SBD is able to promote apoptosis, and inhibit cell proliferation and angiogenesis in cancer. MATERIALS AND METHODS: CCK8, Edu assays and colony formation assay were performed to assess the effect of SBD on PCa cell growth. Effect of SBD on apoptosis and cell cycle was detected by flow cytometry. Transwell and wounding healing assay were conducted to detect the invasion and migration activities of PCa cells. Western blot was employed to detect the protein expression. 2RRV1 mouse xenograft model was established to detect the effect of SBD on prostate cancer. Angiogenesis was analysed by coculturing PCa cell lines and HUVECs. RESULTS: The results showed that SBD induced a significant decrease in cell viability and clonogenic growth in a dose-dependent manner. SBD induced cell apoptosis and cell cycle G2/M phase arrest by inactivating PI3K/AKT signalling pathway. Treatment with SBD also significantly decreased the cell migration and invasion via phenotypic inversion of EMT that was characterized by the increased expression of E-cadherin and Vimentin, and decreased expression of N-cadherin, which could be partially attributed to inhibiting PI3K/AKT signalling pathway. Subsequently, using AKT inhibitor MK2206, we concluded that PI3K/AKT are also involved in cell apoptosis and metastasis of PCa cells stimulated by SBD. Apart from its direct effects on PCa cells, SBD also exhibited anti-angiogenic properties. SBD alone or conditioned media from SBD-treated PCa cells reduced HUVEC tube formation on Matrigel without affecting HUVEC viability. Furthermore, 22RV1 xenograft C57BL/6 mice treated with SBD in vivo showed a significant inhibitory in tumour size and tumour weight without toxicity. In addition, administration with medium- or high-dose of SBD significantly inhibited the cell proliferation and enhanced the damage to tumour tissues. CONCLUSIONS: Collectively, our in vitro and in vivo findings suggest that SBD has the potential to develop into a safe and potent alternative therapy for PCa patients.
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Antineoplásicos , Neoplasias da Próstata , Scutellaria , Animais , Antineoplásicos/uso terapêutico , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Scutellaria/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Cucurbitacin B (CuB), extracted from muskmelon pedicel, is a widely available triterpenoid molecule that exerts influence on various biological activities. Modern pharmacological studies have found that cucurbitacin B has many kinds of pharmacological anti-tumor and anti-metastasis functions. AIM OF THE STUDY: To explore the mechanism of anti-tumor and anti-metastasis effect of cucurbitacin B. MATERIALS AND METHODS: The effect of cucurbitacin B on the growth of HCT116 and CT-26 was detected by CCK8; apoptosis was determined by flow cytometry and colony formation; the expression of apoptosis-related protein Bax, Bcl-2 and Cleaved-caspase-3 were examined by western Blot. To explore the underlying mechanism of cucurbitacin B against tumor, the Western blot, Immunofluorescence staining, Microscale Thermophoresis assays were used. Multiple molecular biology experiments were applied to validate the effect of polarization of cucurbitacin B-induced macrophages. The supernatant of Cucurbitacin B-induced macrophages and colon cells were co-cultured in vitro, and then transwell and wound healing assay were employed to the related phenotypes. C57BL/6 and BALB/c murine colon cancer model were also used to study the drug effects in vivo. RESULTS: Cucurbitacin B distinctly induced the apoptosis of CRC cells. It was observed that cucurbitacin B not only inhibited the phosphorylation of JAK2 and STAT3, but also the translocation from the cytosol to the nucleus. Meanwhile, we observed that cucurbitacin B is bound to STAT3. Further experimentation demonstrated that cucurbitacin B reduced the polarization of M2 macrophage by down-regulating JAK2/STAT3 signaling pathway. Cucurbitacin B-induced M2-like macrophages were found to diminish the migration of CRC cells. In vitro study suggested that cucurbitacin inhibited the CRC cells proliferation via JAK2/STAT3 and suppressed the cell migration by suppressing M2-like macrophages polarization. Consistent with in vitro results, the cucurbitacin B therapy significantly inhibited tumor growth and metastasis in mice. Moreover, in vivo the treatment with cucurbitacin B enhanced anti-tumor immunity by regulating M2-like macrophages and promoted the expression of CD4 and CD8 in tumor microenvironment. CONCLUSION: Our results proved that cucurbitacin B might be a potential candidate agent for adjuvant therapy in the process of CRC growth and metastasis.
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Antineoplásicos Fitogênicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Triterpenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/patologia , Células HCT116 , Humanos , Janus Quinase 2/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células THP-1 , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: A Traditional Chinese Medicine (TCM) formula (VYAC) consists of three herbs including Viola yedoensis Makino, herb (Violaceae, Viola), Sophora flavescens Aiton, root (Fabaceae, Sophora) and Dictamnus dasycarpus Turcz, root and rhizome (Rutaceae, Dictamnus), has been traditionally prescribed to treat various skin diseases in clinic. AIM OF THE STUDY: This study aims to investigate the therapeutic effects of VYAC on the 2,4-dinitrobenzene (DNCB) induced atopic dermatitis (AD)-like mice and to explore the underlying mechanisms. MATERIALS AND METHODS: VYAC was extracted with 70 % aqueous ethanol and lyophilized powder was used. AD-like mice were challenged by DNCB, VYAC (150 and 300 mg/kg) were oral administration daily from day 7 to day 28. At the end of experiment, the clinical scores were recorded, serum and skin in the dorsal were isolated to evaluate the therapeutic effects of VYAC. RBL-2H3 cells were stimulated with C48/80 for degranulation and plasmids expressing constitutively active form of Syk (Silence or overexpression) were transfected into RBL-2H3 cells to explore the underlying mechanisms in vitro. RESULTS: VYAC significantly ameliorated the cardinal symptoms in the DNCB-induced AD-like mice by repairing the skin barrier function, inhibiting mast cells infiltration, restraining the serum IgE and histamine release and decreasing TNF-α, IL-4 as well as Syk mRNA level in dorsal skin and alleviating inflammation. Besides, VYAC significantly blocked RBL-2H3 cells degranulation, reduced ß-hexosaminidase and histamine release, and suppressed NF-κB pathway. What's more, the degranulation of RBL-2H3 was reduced after Syk silence and increased after Syk overexpression. CONCLUSION: Our findings clearly suggested that VYAC treat AD through inhibiting the inflammatory mediator productions and blocking mast cell degranulation via suppressing Syk mediated NF-κB pathway.
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Dermatite Atópica/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Mastócitos/efeitos dos fármacos , NF-kappa B/metabolismo , Animais , Degranulação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Dermatite Atópica/patologia , Dinitroclorobenzeno , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Inativação Gênica , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Quinase Syk/genéticaRESUMO
Bufalin (Buf), an active ingredient of the traditional Chinese medicine Chansu, is known to have anticancer effects for breast cancer. However, its poor solubility, high toxicity, and extensive side effects limit its use. Metal-organic frameworks (MOFs) are a class of promising drug delivery systems known for their high porosity. Here, we designed and constructed pH-sensitive and redox-responsive folic acid-modified MOFs as drug carriers of Buf (FA-MOF/Buf). Moreover, the anticancer activity of nanomedicines was also explored in vitro and in vivo. Compared to free Buf, the FA-MOF/Buf nanoparticles demonstrated improved water solubility and stability, higher intracellular uptake, and enhanced cytotoxicity in breast cancer cells in vitro. Furthermore, it displayed improved accumulation in the tumor site, enhanced anticancer activity, and reduced side effects in vivo. Our results demonstrated that FA-MOF could be developed as a potential delivery system for Buf to improve its antitumor activity for breast cancer treatment.
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In worldwide, lung cancer has a major socio-economic impact and is one of the most common causes of cancer-related deaths. Current therapies for lung cancer are still quite unsatisfactory, urging for alternative new treatments. Traditional Chinese Medicine (TCM) is currently increasingly popular and exhibits a complicated intervention in cancers therapy. In this study, we evaluated the anti-tumor effect and explored the mechanisms of a TCM formula Yangyinwenyang (YYWY) in non-small cell lung cancer (NSCLC) models. YYWY induced the apoptosis of lung cancer cells in vitro. In Lewis NSCLC-bearing mice model, YYWY significantly inhibited the tumor growth. Further, RNA-seq analysis and immunostaining of the tumor tissue implied the critical role of YYWY in the regulation of immune response, especially the dendritic cells (DCs) in the effect of YYWY. Therefore, we focused on DCs, which were the initiator and modulator of the immune response. YYWY facilitated the maturation of DCs through MAPK and NF-κB signaling pathways and promoted the release of the cytokines IFN-γ, interleukin (IL)-1ß, IL-2, IL-12, and tumor necrosis factor (TNF)-α by DCs. Moreover, the YYWY-matured DCs enhanced the proliferation of T cells and promoted the differentiation of T cells into T helper Th1 and cytotoxic T cell (CTL). In addition, YYWY increased the ratio of Th1/Th2 (IFN-γ/IL-4 radio). Collectively, our findings clearly suggested that YYWY exerted an anti-tumor effect on NSCLC, at least partially through facilitating the mature DCs to activate the proliferation and differentiation of T cells.
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BACKGROUND: Percutaneous coronary intervention (PCI) could develop periprocedural myocardial infarction and inflammatory response and statins can modify inflammatory responses property. The aim of this study was to evaluate whether short-term high-dose atorvastatin therapy can reduce inflammatory response and myocardial ischemic injury elicited by PCI. METHODS: From March 2012 to May 2014, one hundred and sixty-five statin-naive patients with unstable angina referred for PCI at Department of Cardiology of the 306th Hospital, were enrolled and randomized to 7-day pretreatment with atorvastatin 80 mg/d as high dose group (HD group, n = 56) or 20 mg/d as normal dose group (ND group, n = 57) or an additional single high loading dose (80 mg) followed 6-day atorvastatin 20 mg/d as loading dose group (LD group, n = 52). Plasma C-reactive protein (CRP) and interleukin-6 (IL-6) levels were determined before intervention and at 5 minutes, 24 hours, 48 hours, 72 hours, and 7 days after intervention. Creatine kinase-myocardial isoenzyme (CK-MB) and cardiac troponin I (cTnI) were measured at baseline and then 24 hours following PCI. RESULTS: Plasma CRP and IL-6 levels increased from baseline after PCI in all groups. CRP reached a maximum at 48 hours and IL-6 level reached a maximum at 24 hours after PCI. Plasma CRP levels at 24 hours after PCI were significantly lower in the HD group ((9.14±3.02) mg/L) than in the LD group ((11.06±3.06) mg/L) and ND group ((12.36±3.08) mg/L, P < 0.01); this effect persisted for 72 hours. IL-6 levels at 24 hours and 48 hours showed a statistically significant decrease in the HD group ((16.19±5.39) ng/L and (14.26±4.12) ng/L, respectively)) than in the LD group ((19.26±6.34) ng/L and (16.03±4.08) ng/L, respectively, both P < 0.05) and ND group ((22.24±6.98) ng/L and (17.24±4.84) ng/L, respectively). IL-6 levels at 72 hours and 7 days showed no statistically significant difference among the study groups. Although PCI caused a significant increase in CK-MB and cTnI at 24 hours after the procedure in all groups, the elevated CK-MB and cTnI values were lower in the HD group ((4.71±4.34) ng/ml and (0.086±0.081) ng/ml, respectively) than in the ND group ((7.24±6.03) ng/ml and (0.138±0.103) ng/ml, respectively, both P < 0.01) and LD group ((6.80±5.53) ng/ml and (0.126±0.101) ng/ml, respectively, both P < 0.01). CONCLUSION: Short-term high-dose atorvastatin treatment before PCI significantly reduced systemic inflammatory response and myocardial ischemic injury elicited by PCI.
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Angina Instável/terapia , Atorvastatina/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Intervenção Coronária Percutânea , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Idoso , Atorvastatina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Resultado do TratamentoRESUMO
Coptidis Rhizoma and Aconiti Kusnezoffii Radix represent hot Chinese medicine and cold Chinese medicine respectively. The purpose of this study is to observe the differentiation effect of Coptidis Rhizoma and Aconiti Kusnezoffii Radix on lewis lung cancer and compare effect of hot Chinese medicine and cold Chinese medicine on tumor progression. In this study, the rat serum containing Coptidis Rhizoma or Aconiti Kusnezoffii Radix was prepared to treat lewis lung cancer cells in vitro, and effects of the serum containing Coptidis Rhizoma or Aconiti Kusnezoffii Radix on cell differentiation, proliferation, adhesion, succinic dehydrogenase (SDH) activity and gap-junction intercellular communication (GJIC) were investigated. In vivo, the subcutaneous implant model and pulmonary metastasis model of lewis lung cancer were established. Tumor bearing mice were taken water decoction of coptis chinensis or aconite by intragastric administration bid for four weeks, and the influences of coptis chinensis and aconite on tumor progression were evaluated by body temperature, blood oxygen saturation, red cell ATPase, blood rheology, intratumor hypoxia, capillary permeability and GJIC. The results showed that the serum containing aconite could induce cell differentiation, inhibit cell proliferation and migration, promote SDH activity and GJIC in lewis lung cancer cells. The serum containing Coptidis Rhizoma increased cell adhesion and decreased SDH activity and GJIC without cell differentiation although it also suppressed cell proliferation. Aconiti Kusnezoffii Radix water decoction could keep body temperature, blood oxygen saturation, red cell ATPase and blood rheology, and improve intratumor hypoxia, capillary permeability and GJIC in tumor bearing mice, which led to slower tumor growth and less metastasis. Coptidis Rhizoma water decoction decreased body temperature, blood oxygen saturation, red cell ATPase, blood rheology and GJIC, and promoted intratumor hypoxia and capillary permeability, which resulted to more tumor metastasis although it also prevented tumor growth. These results suggested that the hot Chinese medicine could induce tumor cell differentiation and prevent tumor poison invagination, which is better for tumor treatment than cold Chinese medicine.
Assuntos
Aconitum/química , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Lewis/patologia , Diferenciação Celular/efeitos dos fármacos , Curcuma/química , Medicamentos de Ervas Chinesas/farmacologia , Animais , Linhagem Celular Tumoral , Camundongos , Metástase Neoplásica , Ratos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To observe the effect of alcohol extracts from Pharbitidis Semen on the proliferation and metastasis of Lewis lung cancer, and study its anti-tumor mechanism. METHOD: In vitro, MTT assay and scratch assay were adopted to detect the effect of alcohol extracts from Pharbitidis Semen on the proliferation and metastasis of Lewis lung cancer cells. The cell autophagy was detected by the acridine orange staining. The gap-junction intercellular communication (GJIC) was investigated by the fluorescent yellow transfer. The expression of aquaporin 1 (AQP1) was analyzed by the Western blotting. In vivo, the subcutaneous implant model and the experimental pulmonary metastasis model of Lewis lung cancer in mice were established to evaluate the anti-tumor and anti-metastasis effects of alcohol extract from Pharbitidis Semen. The serum carcinoembryonic antigen (CEA) and beta2 microglobulin (beta2-MG) of mice bearing Lewis lung cancer were detected by the electrochemiluminesence immunoassay. The expressions of lung AQP1 and Connexin 43 (Cx43) were examined by the immunohistochemical method. RESULT: In vitro, alcohol extracts from Pharbitidis Semen inhibited the cell proliferation in a dose-dependent matter, significantly prevented the cell migration, down-regulated AQP1 proteins of cells, promoted GJIC, and decreased the serum-free autophagy of tumor cells. In vivo, compared with untreated model mice, alcohol extracts from Pharbitidis Semen inhibited the tumor growth in a dose-dependent matter, prevented the tumor metastasis and prolonged the life span of mice bearing Lewis lung cancer, while decreasing serum CEA and beta2-MG of mice bearing Lewis lung cancer, enhancing the immumohistochemical staining intensity of Cx43 and weakening aquaporins AQP1 positive intensity. CONCLUSION: Alcohol extracts from Pharbitidis Semen could prevent the proliferation and metastasis in Lewis lung cancer cells. Its mechanism may be related to the promotion of GJIC and the down-regulation of AQP1.