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Background: Systemic inflammation and glucose metabolism have been closely related to the survival of cancer patients. Therefore, we aimed to evaluate whether preoperative glucose-to-lymphocyte ratio (GLR) can be used to predict the survival of cancer patients. Methods: We retrospectively examined 2172 cancer patients who underwent surgery from January 1, 2014, to December 31, 2016. There were 240 patients with non-small cell lung cancer (NSCLC), 378 patients with colorectal cancer (CRC), 221 patients with breast cancer (BC), 335 patients with gastric cancer (GC), 270 patients with liver cancer, 233 patients with esophageal cancer (EC), 295 patients with renal cancer, and 200 patients with melanoma. The formula for preoperative GLR calculation was as follows: GLR=glucose/lymphocyte count. The overall survival (OS) was estimated using the Kaplan-Meier method. The predictive factors for OS were determined using multivariate analysis. Results: The Kaplan-Meier analysis showed that the median survival time in the high-GLR group was much shorter than that of those in the low-GLR group for different cancers. Cox multivariate regression analysis reveals that preoperative GLR was an independent factor for predicting overall survival in different tumor types. Conclusion: Elevated preoperative GLR was remarkably associated with a poorer prognosis in patients with NSCLC, CRC, breast cancer, gastric cancer, kidney cancer, liver cancer, esophageal cancer, and melanoma. Preoperative GLR promises to be an essential predictor of survival for cancer patients.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Esofágicas , Neoplasias Hepáticas , Neoplasias Pulmonares , Melanoma , Neoplasias Gástricas , Humanos , Glucose , Estudos Retrospectivos , Neoplasias Pulmonares/patologia , Linfócitos/patologia , Neoplasias Hepáticas/patologia , Neoplasias Esofágicas/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: The albumin-bilirubin (ALBI) score is a novel indicator of liver function. Some studies showed that the ALBI score was a predictive marker for the prognosis and efficacy of drug therapy in malignancies. We aimed to assess the predicted role of ALBI score in the sensitivity to therapy with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer (BC). The clinical data of 226 HER2-positive BC patients at the Harbin Medical University Cancer Hospital from January 2017 and December 2018 were retrospectively collected. The ALBI score was calculated with serum albumin and bilirubin before diagnosis. The associations between ALBI score and trastuzumab resistance were analyzed by logistic regression analyses. The patients with trastuzumab resistance had higher ALBI scores compared with the patients without trastuzumab resistance. Moreover, there were weak correlations between the ALBI score and lymph node status (P= 0.093). In addition, multivariate analysis revealed that the ALBI score was an independent prognostic factor for trastuzumab resistance in HER2-positive BC. High ALBI score is associated with trastuzumab resistance in HER2-positive BC. Future studies are needed.
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Neoplasias da Mama , Neoplasias Hepáticas , Feminino , Humanos , Bilirrubina , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias Hepáticas/patologia , Prognóstico , Estudos Retrospectivos , Albumina Sérica/análise , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Resistencia a Medicamentos AntineoplásicosRESUMO
BACKGROUND: Postoperative skeletal muscle loss (SM loss) was reported to be associated with a poor prognosis in early-stage non-small cell lung cancer (NSCLC). Small airway dysfunction (SAD) is a common but neglected respiratory abnormality. Little information is known about the association between preoperative SAD and postoperative SM loss in early-stage NSCLC. Therefore, this study aimed to investigate the correlation between preoperative SAD and SM loss after surgery in early-stage NSCLC patients. METHODS: There were 348 NSCLC patients with stages I-IIIA in this study from January 2017 to December 2020. All CT images were contrast-enhanced scans, and the skeletal muscle index (SMI) was measured using CT images. A 10.0% decrease in SMI over 12 months was determined as the cut-off value to define excessive SM loss. Logistic regression analyses were used to examine the relationship between SAD and SM loss. RESULTS: This study included 348 subjects who underwent pulmonary operation (159 males and 189 females; mean age: 57.5 ± 8.8 years). 152 (43.7%) patients were identified as having SAD before surgery, and 179 patients (51.4%) were identified as having SM loss after 1 year. Moreover, a higher incidence of SAD was found in the SM loss group compared with that in the non-SM loss group (52.0% vs. 34.9%, p = 0.001). The patients with SAD were older, had larger tumor size, and had lower albumin levels. Furthermore, there were significant correlations between the lung function parameters manifesting SAD and the percentage change in SMI (for the forced expiratory flow when 75% of forced vital capacity has been exhaled (FEF75%), Pearson r=-0.107, p = 0.046; for FEF50%, r = -0.142, p = 0.008; and for FEF25-75%, r=-0.124, p = 0.021; respectively). However, no significant correlations were found between SMI and the lung function parameters reflecting proximal airway obstruction (p > 0.05). Logistic regression analysis revealed that preoperative SAD (HR, 2.465; 95% CI, 1.256-4.838; p = 0.009) was independent risk factor for postoperative SM loss in early-stage NSCLC. In addition, multivariable analysis revealed that SAD (HR, 1.816; 95% CI, 1.025-3.216, P = 0.041) were associated with postoperative complications. CONCLUSION: Preoperative SAD is significantly associated with postoperative complications and SM loss in early NSCLC patients. Our results suggest that preoperative assessment of SAD may be useful for risk stratification of surgical candidates with potential for targeted interventions.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Prognóstico , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Complicações Pós-Operatórias/epidemiologia , Estudos RetrospectivosRESUMO
OBJECTIVE: To observe the effect of Nailifu Spray on the treatment of premature ejaculation. METHODS: A total of 90 patients were included in this study from January 1, 2022 to January 1, 2023. Nailifu spray was used to spray the surface of penile skin once a day, 2 sprays per session for 4 weeks.And the patients' premature ejaculation diagnostic tool (PEDT) scores, intravaginal ejaculation latency time (IELT), and international index of erectile function-5 (IIEF-5) scores were collected before and after treatment, respectively. RESUTS: The median (P25,P75) PEDT scores was 16.0(15.0,18.0) scores before treatment and 10.0(10.0,10.0) scores after treatment. The median (P25,P75) of IELT was 20.0 (10.0,30.0) s before treatment and 240.0 (180.0,300.0) s after treatment. The median (P25,P75) of IIEF-5 scores was 21.0 (21.0,22.0) scores before treatment and 21.0 (21.0,21.0) scores after treatment. Compared with baseline levels, IELT was significantly longer and PEDT scores were significantly lower, with statistically significant differences. No significant changes in IIEF-5 scores were seen. CONCLUSION: Nailifu spray treatment of premature ejaculation is accurate and effective, worthy of clinical promotion.
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Ejaculação Precoce , Masculino , Humanos , Ejaculação Precoce/tratamento farmacológico , Ejaculação , Pelve , PênisRESUMO
BACKGROUND: As a transmembrane protein, C-type lectin-like receptor 2 (CLEC-2) is mainly expressed on platelets and released into plasma after platelet activation. Activated platelets participate in the regulation of innate immune cells. Patients with different microsatellite statuses have distinct immune profiles. This study aimed to investigate the association of plasma CLEC-2 levels with microsatellite status among colorectal cancer (CRC) patients. METHODS: A cross-sectional analysis of 430 CRC patients from Harbin Medical University Cancer Hospital was conducted. CLEC-2 levels were measured with fasting venous blood samples drawn from each participant before any treatment. The microsatellite status was evaluated with DNA obtained from fresh frozen tumor tissue samples. The other clinical data were collected and recorded based on the medical system records. RESULTS: CLEC-2 levels were significantly higher among patients with high microsatellite instability phenotype than the stable microsatellite group, adjusting for other confounding variables. CONCLUSIONS: The increased CLEC-2 is associated with the high microsatellite instability subtype of CRC.
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Neoplasias Colorretais , Lectinas Tipo C , Neoplasias Colorretais/genética , Estudos Transversais , Humanos , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Glicoproteínas de Membrana , Instabilidade de Microssatélites , Ativação PlaquetáriaRESUMO
Background: Breast cancer is one of the most commonly diagnosed cancers, and the fourth leading cause of cancer deaths in females worldwide. Sarcopenia is related to adverse clinical outcomes in patients with malignancies. Muscle index is a key parameter in evaluating sarcopenia. However, there is no data investigating the association between muscle index and distant metastasis in breast cancer. The aim of this study was to explore whether muscle index can effectively predict distant metastasis and death outcomes in breast cancer patients. Study Design: The clinical data of 493 breast cancer patients at the Harbin Medical University Cancer Hospital between January 2014 and December 2015 were retrospectively analyzed. Quantitative measurements of pectoralis muscle area and skeletal muscle area were performed at the level of the fourth thoracic vertebra (T4) and the eleventh thoracic vertebra (T11) of the chest computed tomography image, respectively. The pectoralis muscle index (PMI) and skeletal muscle index (SMI) were assessed by the normalized muscle area (area/the square of height). Survival analysis was performed using the log-rank test and Cox proportional hazards regression analysis. Result: The patients with metastases had lower PMI at T4 level (PMI/T4) and SMI at T11 level (SMI/T11) compared with the patients without metastases. Moreover, there were significant correlations between PMI/T4 and lymphovascular invasion, Ki67 expression, multifocal disease, and molecular subtype. In addition, multivariate analysis revealed that PMI/T4, not SMI/T11, was an independent prognostic factor for distant metastasis-free survival (DMFS) and overall survival (OS) in breast cancer patients. Conclusions: Low PMI/T4 is associated with worse DMFS and OS in breast cancer patients. Future prospective studies are needed.
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The roles played by several inflammatory factors in screening for prostate cancer (PCa) among gray area patients, namely those with serum prostate-specific antigen (PSA) levels between 4 and 10 ng/ml, have not been completely identified, and few effective diagnostic nomograms have been developed exclusively for these patients. We aimed to investigate new independent predictors of positive biopsy (PB) results and develop a novel diagnostic nomogram for this group of patients. The independent predictors of PB results were identified, and a nomogram was constructed using multivariate logistic regression analysis based on a cohort comprising 401 Gy area patients diagnosed at Xijing Hospital (Xi'an, China) between January 2016 and December 2019. The predictive accuracy of the nomogram was assessed using the receiver operating characteristic curve, and the nomogram was calibrated by comparing the prediction with the observation. The performance of the nomogram was further validated using an independent cohort. Finally, lymphocyte-to-monocyte ratio (LMR) > 4.11 and red blood cell distribution width (RDW)-standard deviation (SD) > 42.9 fl were identified as independent protective predictors of PB results, whereas PSA density (PSAD) > 0.141 was identified as an independent risk predictor. The nomogram established using PSAD, LMR, and RDW-SD was perfectly calibrated, and its predictive accuracy was superior to that of PSAD in both internal and external validations (0.827 vs 0.769 and 0.765 vs 0.713, respectively). This study is the first to report the importance of LMR and RDW-SD in screening for PCa among gray area patients and to construct an exclusive nomogram to predict the individual risk of positive 13-core biopsy results in this group of patients. With superior performance over PSAD, our nomogram will help increase the accuracy of PCa screening, thereby avoiding unnecessary biopsy.
Assuntos
Nomogramas , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Idoso , Biópsia , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangueRESUMO
BACKGROUND: Phyllanthus emblica L (PEL), a well-known medical plant, has been used in Asian countries for a long time. Increasing evidence suggests that it can prevent the tumorigenesis of cancer associated with nonresolving inflammation. However, the possible anti-inflammatory mechanism responsible for preventing tumorigenesis of precancerous lung lesions is not well elucidated. MATERIALS AND METHODS: Male A/J mice were randomly divided into 5 groups with 10 mice in each group: (1) blank group (saline), (2) benzo(a)pyrene [B(a)P] group, (3) and (4) B(a)P + PEL (5 g/kg/d, 10 g/kg/d, administered by gavage), (5) B(a)P + celecoxib (30 mg/kg/d, administered by gavage). Nodes on the lung surface were observed and calculated. The levels of macrophage inflammatory protein (MIP-2), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß were detected by enzyme-linked immunosorbent assay (ELISA) kits. Cyclo-oxygenase-2 (COX-2), hypoxia-inducible factor-1 (HIF-α), IL-1ß, miR-101, and Lin28B protein levels were evaluated by immunohistochemistry and Western blotting. RESULTS: PEL extract treatment significantly reduced the number of nodes on the lung surface and attenuated B(a)P-induced levels of proinflammatory cytokines MIP-2, TNF-α, IL-6, and IL-1ß in lung tissue. The protein expressions of COX-2 and HIF-α were significantly decreased by the treatment of PEL. In addition, both PEL extract and celecoxib markedly upregulate the expression of miR-101 while downregulating IL-1ß and Lin28B levels. CONCLUSION: Our study indicated that treatment with PEL extract can not only protect the lung from inflammatory injury but effectively prevent precancerous lung lesions through regulating the IL-1ß/miR-i101/Lin28B signaling pathway.
Assuntos
Anti-Inflamatórios/farmacologia , Proteínas de Ligação a DNA/metabolismo , Interleucina-1beta/metabolismo , Pulmão/efeitos dos fármacos , MicroRNAs/metabolismo , Phyllanthus emblica/química , Lesões Pré-Cancerosas/tratamento farmacológico , Animais , Benzopirenos/farmacologia , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-6/metabolismo , Pulmão/metabolismo , Masculino , Camundongos , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/metabolismo , Proteínas de Ligação a RNA , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Tauroursodeoxycholic acid (TUDCA), one of the main ingredients from bear gall which hold "Clearing heat and detoxification, Removing liver fire for improving eyesight" functions, is formed by the conjugation of ursodeoxycholic acid (UDCA) with taurine. However, the limited information of TUDCA on protecting diabetic retinopathy (DR) has been known. The present study was conducted to evaluate the protection of TUDCA on high glucose-induced human retinal microvascular endothelial cells (HRMECs) dysfunction and streptozotocin (STZ)-induced diabetic retinopathy (DR) rats and the possible mechanism underlying was also explored. MATERIALS AND METHODS: The proliferation of high glucose-induced HRMECs was determined by MTT assay. DR rats' model was established by an administration of high-glucose-fat diet and an intraperitoneal injection of STZ (30mg/kg). The cell supernatant and rats' serum were collected for the assays of NO content by ELISA kits. Retinas were stained with hematoxylin and eosin (HE) to observe pathological changes. Immunohistochemical assay was applied to examine the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF in rat retinas. Furthermore, western blot analysis was carried out to examine the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF in high glucose-induced HRMECs. RESULTS: After treating with TUDCA, high glucose-induced HRMECs proliferation could be significantly inhibited. TUDCA (5.0µM, 25.0µM and 125.0µM) could decrease NO content in high glucose-induced HRMECs. Furthermore, TUDCA (500mg/kg/d and 250mg/kg/d) also decrease NO content in serum of DR rats. Additionally, both immunocytochemistry analysis and western blot analysis showed that the over-expression of ICAM-1, NOS, NF-κB p65 and VEGF were significantly decreased by TUDCA. CONCLUSION: The data indicated that TUDCA could ameliorate DR by decreasing NO content and down-regulating the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF. Thus, our experimental results suggested that TUDCA might be a potential drug for the prevention and treatment of DR.
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Diabetes Mellitus Experimental/complicações , Retinopatia Diabética/prevenção & controle , Células Endoteliais/efeitos dos fármacos , Glucose/toxicidade , Vasos Retinianos/citologia , Ácido Tauroquenodesoxicólico/farmacologia , Animais , Regulação Enzimológica da Expressão Gênica , Humanos , Molécula 1 de Adesão Intercelular , Masculino , Camundongos , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismoRESUMO
Mol Med Rep 12:[Related article:] 79928002, 2015; DOI: 10.3892/mmr.2015.4449 Following the publication of this article, an interested reader drew to our attention an anomaly associated with the presentation of Fig. 2; essentially, an image had been inadvertently selected from the same original photomicrograph to represent Fig. 2D, the centre panel [+80 nM phorbol-12-myristate-13-acetate (TPA), + 20 µM calycosin (Cal)] and Fig. 2F, the second panel from the right (+ 80 nM TPA, + 30 µM Cal). After having re-examined our original data, the panel originally featured in Fig. 2F was identified as having been selected incorrectly for the Figure. A corrected version of Fig. 2 is presented on next page, which features the proper data for Fig. 2F. Fig. 2D and F showed the effect of different concentrations of Cal on the migration and invasive ability of the TPA-treated A549 cells, respectively; Cal was demonstrated to inhibit the migration, and to suppress the invasive ability, of the A549 cells induced by TPA. Therefore, this error did not affect the overall conclusions reported in the present study. We sincerely apologize for this mistake, and thank the reader of our article who drew this matter to our attention. Furthermore, we regret any inconvenience this mistake has caused.
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A flavonoid fraction of Herba Epimedii, including eight flavonoid glycoside compounds, epimedoside A, ikarisoside F, baohuoside II, sagittatoside A, sagittatoside B, 7-O-rhamnosyl icariside II, 2"-O-rhamnosyl icariside II, and baohuoside I, was isolated and prepared from the leaves of Herba Epimedii. This study was conducted to assess the potential effect of the flavonoid fraction of Herba Epimedii on osteoporosis in ovariectomized rats. Rats received repeated administration of a vehicle (ovariectomized), the flavonoid fraction of Herba Epimedii (7.5, 15, 30 mg/kg/d), and ipriflavone (200 mg/kg/d) once a day for 8 weeks, beginning 4 weeks after ovariectomization. Then, the bone turnover markers, bone biomechanical properties, trabecular architecture, and related protein expressions were evaluated by biochemical assay kits, mechanical testing, microcomputed tomography, immunohistochemical evaluation, and Western blot analysis. Treatment with the flavonoid fraction of Herba Epimedii (15, 30 mg/kg/d) and ipriflavone (200 mg/kg/d) significantly increased bone strength while dramatically inhibiting the serum alkaline phosphatase and tartrate-resistant acid phosphatase levels in ovariectomized rats. Furthermore, the flavonoid fraction of Herba Epimedii also increased osteoprotegerin protein expression and reduced the receptor activator of nuclear factor-κB ligand protein expression compared with ovariectomized rats. In addition, the microcomputed tomography results showed that the flavonoid fraction of Herba Epimedii treatment significantly improved trabecular bone mineral density and restored the bone microarchitecture in ovariectomized rats. Therefore, our results indicated that the flavonoid fraction of Herba Epimedii might be beneficial for improving postmenopausal osteoporosis and should be considered as a promising candidate for treating postmenopausal osteoporosis.
Assuntos
Osso e Ossos/metabolismo , Epimedium/química , Flavonoides/uso terapêutico , Osteoporose/tratamento farmacológico , Animais , Biomarcadores/metabolismo , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Feminino , Ovariectomia , Ratos , Ratos Sprague-DawleyRESUMO
In this study, bovine serum albumin (BSA)/methylglyoxal (MGO) non-enzymatic glycosylation reaction system was used for the evaluation of the inhibitory effects of Moutan Cortex extracts on the formation of AGEs. The HPLC-LC-ESI-MS/MS technology was adopted to test and indentify active components in Moutan Cortex against AGEs formation. The different concentrations of extracts (crude herb concentration 50, 100, 150, 200, 250 gâ¢L⻹) from Moutan Cortexwas determined by fluorospectrophotometry, indicating an activity against AGEs formation in different concentrations of extracts, the inhibition ratio were (36.2±5.3)%, (43.5±6.2)%, (55.4±7.8)%, (68.6±6.7)%, (70.4±8.2)%, respectively after 6-day reaction in a dose dependent manner. Besides, the forming speed of AGEs tended to be steady after 24 h reaction. The HPLC technology was used to analyze chromatograms before and after the incubation of Moutan Cortex and methylglyoxal, identify changes in five chromatographic peaks and show decrease or increase in chromatographic peaks. These substances were trigalloyl glucose, tetragalloyl glucose, galloylpaeoniflorin, hexagalloyl glucose and benzoylpaeoniflorin after LC-ESI-MS/MS identification. Extracts from Moutan Cortex showed the remarkable inhibitory effects against formation of AGEs in BSA/glucose system. Furthermore, these potential active components might be associated with the efficacy of Moutan Cortex on treatment of diabetic nephropathy, which enriches basic studies for Moutan Cortex and provides ideas and reference basis for subsequent studies.
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Medicamentos de Ervas Chinesas/química , Produtos Finais de Glicação Avançada/química , Paeonia/química , Cromatografia Líquida de Alta Pressão , Aldeído Pirúvico/química , Soroalbumina Bovina/química , Espectrometria de Massas em TandemRESUMO
To analyze and compare the chemical compositions of Moutan Cortex, Paeoniae Rubra Radix and Paeoniae Alba Radix based on "component structure" theory. Thirteen batches of Moutan Cortex, 14 batches of Paeoniae Rubra Radix from different origins and 10 batches of Paeoniae Alba Radix from different origins were analyzed by HPLC-DAD method. Hierarchical cluster analysis and principal component analysis were used for analysis. The significant differences of principal component from Moutan Cortex, Paeoniae Rubra Radix and Paeoniae Alba Radix were investigated by using F test. HPLC fingerprints were established for 13 batches of Moutan Cortex, 14 batches of Paeoniae Rubra Radix and 10 batches of Paeoniae Alba Radix, and 7 glycosides and phenolic acids components were identified. Comparative study of Moutan Coetex, Paeoniae Rubra Radix and Paeoniae Alba Radix was conducted according to the results of hierarchical cluster analysis, principal component analysis and "component structure" theory. Moutan Cortex, Paeoniae Rubra Radix and Paeoniae Alba Radix have significant differences in mass fraction of major chemical components and their ratios, leading to different curative effects.
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Medicamentos de Ervas Chinesas/química , Paeonia/química , Cromatografia Líquida de Alta Pressão , Análise de Componente PrincipalRESUMO
To observe the effect of Epimedii Herba alcohol extract (HE) on tumor growth of lung cancer by establishing the model of Lewis tumor-bearing mice, ELISA method was used to detect the levels of TNF-α, IL-10, IL-17, IL-2 in serum. Ki67 and P53 protein expression was detected in lung cancer tissues by using Western blot assay method and immunohistochemical assay method. The experimental results showed that HE has certain inhibitory effect on Lewis lung cancer tumor growth, and it can reduce the levels of TNF-α, IL-10 and IL-17 in serum, improve the level of IL-2,significantly decrease the expression of Ki67, and significantly increase P53 expression. HE has obvious inhibitory effect against lung cancer, and has the ability to improve immune regulating effect. This study reveals the anti-lung cancer effect of HE may be related to its ability of improving immunity, thus provides the basis for further research on anti-lung cancer effect of HE.
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Carcinoma Pulmonar de Lewis/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Epimedium/química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Animais , Carcinoma Pulmonar de Lewis/genética , Carcinoma Pulmonar de Lewis/imunologia , Carcinoma Pulmonar de Lewis/fisiopatologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Feminino , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Neoplasias Pulmonares/genética , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
The migration and invasion of lung cancer cells into the extracellular matrix contributes to the high mortality rates of lung cancer. The protein kinase C (PKC) and downstream signaling pathways are important in the invasion and migration of lung cancer cells. Calycosin (Cal), an effector chemical from Astragalus has been reported to affect the recurrence and metastasis of cancer cells via the regulation of the protein expression of matrix metalloproteinases (MMPs). The inhibition of Cal on the migration and invasion of A549 cells was investigated in the present study. Cell viability and apoptosis assays were performed using MTT and flow cytometric analyses. A wound healing assay and Transwell invasion assay were performed to evaluate the effect of Cal on A549 cell migration and invasion. Invasionassociated proteins, including MMP2, MMP9, Ecadherin (Ecad), integrin ß1, PKCα and extracellular signalregulated kinase 1/2 (ERK1/2) were detected using western blotting. In addition, PKCα inhibitor, AEB071, and ERK1/2 inhibitor, PD98059, were used to determine the association between the suppression of PKCα /ERK1/2 and invasion, MMP2, MMP9, Ecad and integrin ß1. Cal was observed to suppress cell proliferation and induce apoptosis. There were significant differences between the phorbol12myristate13acetate (TPA)induced A549 cells treated with Cal and the untreated cells in the rates of migration and invasion. The levels of MMP2, MMP9, Ecad and integrin ß1 in the TPAinduced A549 cells changed markedly, compared with the untreated cells. In addition, the suppression of Cal was affected by the PKC inhibitor, AEB071, an ERK1/2 inhibitor, PD98059. The results of the present study indicated that Cal inhibited the proliferation, adhesion, migration and invasion of the TPAinduced A549 cells. The Calinduced repression of PKCα/ERK1/2, increased the expression of ECad and inhibited the expression levels of MMP2, MMP9 and integrin ß1, which possibly demonstrates the mechanism underlying the biological anticancer effects of Cal.
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Proliferação de Células/efeitos dos fármacos , Isoflavonas/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteína Quinase C-alfa/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caderinas/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Flavonoides/farmacologia , Humanos , Integrina beta1/metabolismo , Isoflavonas/química , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Ésteres de Forbol/farmacologia , Proteína Quinase C-alfa/antagonistas & inibidores , Pirróis/farmacologia , Quinazolinas/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Development of the disease is the result of several factors involved in biological network changes. The nature of drug intervention is to regulate these pathological changes to the normal range. Advantages of traditional Chinese medicine (TCM) are to integrally and systematically regulate this biological networks and systematic pathology through multi-targets, multi-levels, multi-channels. Structural components TCM provides the controlled and precise basis "substance" for this regulation and also to clarify the "truth" of the nature of the regulation by the network pharmacology. Network pharmacology provides new strategy for the research on mechanism of structural components TCM. This study not only reflects the overall characteristics of the development of the disease, but also fully embodies the essence of TCM for preventing and treating diseases through changing traditional model on "one drug, one gene, one disease". This paper explores systematically the integration essence, features and research strategies of structural components TCM and the network pharmacology, understand the interaction of structural components TCM and body from the perspective of the overall concept of improving or restoring the balance of.biological networks. It is effective measure to reveal the structure of a multi-component for regulating biological networks mechanisms, and also provide new ideas and methods for further scientific research and innovation of structural component TCM.
Assuntos
Tratamento Farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Interações Medicamentosas , Medicamentos de Ervas Chinesas/química , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Medicina Tradicional ChinesaRESUMO
Immunomodulatory effect has been found to be an important therapeutic measure for immune responses against cancer. In this study, we evaluated the inhibition of Scutellaria barbata D. Don (SB), an anti-inflammatory and an antitumor Chinese herb, including flavonoids and scutebarbatines on tumor growth and its immunomodulatory effects in vivo. HPLC and LC/MS/MS methods were conducted for the analysis of flavonoids and scutebarbatines in SB. Lewis-bearing C57BL/6 mice model was established and tumor volume was evaluated by high frequency color ultrasound experiment. ELISA and western blot analysis were performed for the determination of immunomodulatory factors. SB treatment at the dose of 10, 6.67, and 3.33 g crude drug/kg/d significantly inhibited tumor growth of Lewis-bearing C57BL/6 mice with the inhibition rates of 44.41 ± 5.44%, 33.56 ± 4.85%, and 27.57 ± 4.96%, respectively. More importantly, the spleen and thymus indexes were increased remarkably by SB treatment. SB could decrease IL-17, IL-10, FOXP3, TGF-ß1, RORγt, and IL-6 levels whereas it could increase remarkably IL-2 and IFN-γ levels. Our results demonstrated that SB could inhibit tumor growth in vivo through regulating immune function in tumor-bearing mice and suggested that the immunomodulatory function of SB had a potential therapeutic effect in lung cancer.
RESUMO
Alisma orientalis is a traditional herb medicine commonly used in clinical. With the increasing report of its toxicity in clinical, the renal toxicity of Alisma orientalis has got gradually attention. This paper systematically reviews the research on the chemical material basis of Alisma orientalis including its chemical composition and toxicity of ingredients; and also declares its toxic ingredients and targets according to Network toxicology. Based on the controversy on renal toxicity of Alisma orientalis, we analyzed the possible reasons that may be associated with renal toxicity. It might be associated with the differences of the material basis composition and regulatory toxicology network, differences in employed processing technology, the metabolic function leading to accumulation of compounds, dosage and duration of the experiment and compatibility. The review provides possible reference and ideas for the quality control and rational use of Alisma orientalis.
Assuntos
Alisma/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/toxicidade , Alisma/toxicidade , Animais , Humanos , Estrutura MolecularRESUMO
OBJECTIVE: To study the effect of different composition structures of total paeony glycoside (TPG) component and total phenolic acid of Ligusticum chuanxiong ( TLPA) on sodium dithionite (Na2S2O4) -induced human umbilical vein endothelial cells (HUVEC) hypoxic injury. The baseline geometric proportion was used to design different components structure. And then the best structure of components by cell injury model were optimized. METHOD: A HUVEC hypoxic injury model was established by being induced of Na2S2O4. Cell viability was measured by MTI colorimetric method, intracellular superoxide dismutase (SOD) activity, malondialdehyde (MDA), lactate dehydrogenase( LDH) levels, nitric oxide (NO) contents were measured by kits. At last, Western blot analysis was used to detect the expression of two proteins, Bcl-2 and Bax. RESULT: Compared with the model group, TPG component, TLPA component at different composition structures can significantly increase SOD activity and decrease MDA, LDH, NO levels (P < 0.01, P < 0.05). Paeoniae Radix Rubra and Chuanxiong Rhizoma components can downregulate the expression of Bax protein and upregulate the expression of Bcl-2 protein. The ratio of Bcl-2 and Bax was significantly increased (P < 0 01, P < 0 05), it means that cell apoptosis was inhibited. The results indicate that among all the component composition structures, TPG and TLPA component at the proportion of 8: 2 had the best protection on hypoxic injury of endothelial cells. CONCLUSION: TPG component and TLPA component can resist HUVEC hypoxia injury, the protective effect was the most evident under the structure of 8: 2, which may be due to the inhibition of intracellular lipid peroxidation and cell apoptosis.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Hipóxia/metabolismo , Paeonia/química , Rizoma/química , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/análise , Glicosídeos/análise , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Hidroxibenzoatos/análise , Hipóxia/tratamento farmacológico , Hipóxia/genética , Hipóxia/fisiopatologia , Malondialdeído/metabolismo , Oxigênio/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Fresh Portulaca oleracea L. (family: Portulacaceae; POL) has been used as a folk medicine for the treatment of diabetes mellitus for a long time. More bioactive components with higher activity could be retained in fresh medicinal herbs compared to the dried ones. The present study was conducted to compare different antidiabetic activity between fresh and dried POL, including hypoglycemic and antioxidant activities both in vivo and in vitro. Furthermore, in order to explore which components were responsible for the antidiabetic activity, the difference on chemical components between fresh and dried POL was analyzed and compared. MATERIALS AND METHODS: Insulin-resistant HepG2 cells induced by insulin were used to evaluate the promoting effect of the fresh and dried POL on glucose utilization in vitro. Streptozotocin (STZ)-induced C57BL/6J diabetic mice were used to compare the differences on hypoglycemic and antioxidant activities of fresh and dried POL, including the fasting blood glucose, glucose tolerance, serum insulin level, malondialdehyde (MDA) level and superoxide dismutase (SOD) activity in vivo. UPLC/Q-TOF-MS method was performed to analyze the difference of antidiabetic components between fresh and dried POL. RESULTS: Compared with the dried POL extract, the fresh POL extract significantly increased the consumption of extracellular glucose in insulin-resistant HepG2 cells (P<0.05). In STZ-induced C57BL/6J diabetic mice, both fresh and dried extracts decreased markedly the fasting blood glucose (FBG) levels, and improved significantly oral glucose tolerance test (OGTT), as well as enhanced significantly insulin secretion and antioxidative activities (P<0.05; P<0.01). Furthermore, the fresh extract showed stronger antidiabetic activity (P<0.05). The UPLC/Q-TOF-MS analysis results also revealed that the relative contents of polyphenols and alkaloids in the fresh herbs were more abundant than those in the dried POL. CONCLUSION: Our results indicated that both fresh and dried POL possessed antidiabetic activities, besides stronger activity was observed in the fresh herb. These findings provided evidence for the application and development of fresh POL in the treatment of diabetes mellitus.