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This study aimed to investigate the interaction between miR-1278 and Caldesmon (CALD1) in gastric cancer (GC) and the regulatory mechanism. In both GC cells and tissues, the levels of CALD1, miR-1278, migration-related markers (E-cadherin, N-cadherin, and Snail), and MAPK signaling pathway-related proteins were clarified using quantitative real-time PCR and western blotting analyses. The effects of miR-1278 and CALD1 on GC cell viability and migration were analyzed using CCK-8 and Transwell assays, respectively. The targeting effect of miR-1278 on CALD1 was investigated using bioinformatics prediction and a dual luciferase reporter assay. The effect of miR-1278 on tumor growth was estimated in vivo using a tumor xenograft assay. In GC, miR-1278 expression decreased, whereas CALD1 was highly expressed. Transfecting an miR-1278 mimic into cells inhibited the viability as well as migration of GC cells, and suppressed Ras, phosphorylated (p)-P38, and p-ERK1/2 protein levels. Moreover, miR-1278 targeted and negatively regulated CALD1 expression. CALD1 overexpression promoted GC cell survival and migration and activated the MAPK pathway. Treatment with an miR-1278 mimic partially rescued the changes caused by CALD1 overexpression. Overall, our study revealed that miR-1278 suppresses the malignant behavior of GC cells by targeting CALD1 and regulating the MAPK pathway.
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Chinese doctors widely prescribed Platycodon grandiflorus A. DC. (PG) to treat lung carbuncles in ancient China. Modern clinical experiences have demonstrated that PG plays a crucial role in treating chronic pharyngitis, plum pneumonia, pneumoconiosis, acute and chronic laryngitis, and so forth. Additionally, PG is a food with a long history in China, Japan, and Korea. Furthermore, Platycodin D (PLD), an oleanane-type triterpenoid saponin, is one of the active substances in PG. PLD has been revealed to have anti-inflammatory, anti-viral, anti-oxidation, anti-obesity, anticoagulant, spermicidal, anti-tumor etc., activities. And the mechanism of the effects draws lots of attention, with various signaling pathways involved in these processes. Additionally, research on PLD's pharmacokinetics and extraction processes is under study. The bioavailability of PLD could be improved by being prescribed with Glycyrrhiza uralensis Fisch. or by creating a new dosage form. PLD has been recently considered to have the potential to be a solubilizer or an immunologic adjuvant. Meanwhile, PLD was discovered to have hemolytic activity correlated. PLD has broad application prospects and reveals practical pharmacological activities in pre-clinical research. The authors believe that these activities of PLD contribute to the efficacy of PG. What is apparent is that the clinical translation of PLD still has a long way to go. With the help of modern technology, the scope of clinical applications of PLD is probable to be expanded from traditional applications to new fields.
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Objectives: To evaluate the clinical effects of chemotherapy combined with immunotherapy in patients with advanced non-small-cell lung cancer (NSCLC) and the effect on their nutritional status and immune function. Methods: Total 120 patients with advanced NSCLC admitted to Affiliated Hospital of Hebei University from May 2019 to October 2021 were randomly divided into two groups (n= 60, respectively). Patients in the control group were treated by chemotherapy with cisplatin-paclitaxel (TP) alone: 120 mg/m2 paclitaxel was used on d1; and 25mg/m2 cisplatin (CDDP) was used for more than two hour, once every 14 days, for three consecutive three cycles. Patients in the study group were additionally given 200 mg sindilizumab by intravenous drip, once every three weeks. The contrastive analysis of clinical effects, the incidence of adverse reactions, improvement of the nutrient index and the changes in levels of CD3+, CD4+, CD8+, and CD4+/CD8+ in T-lymphocyte subsets was performed between the two groups. Result: The overall response rate (ORR) was 80% and 61% in the study group and the control group, respectively; and the difference was statistically significant (p=0.03); the contrast analysis of the incidence of post-treatment adverse drug reactions (ADRs) in patients in the two groups suggested that the incidence of adverse reactions was 33.3% and 45% in the study group and the control group, respectively; and the difference was not statistically significant (p=0.19). After the treatment, the improvement of hemoglobin, albumin, serum iron and ferritin levels in the study group was more significant than that in the control group; and the difference was statistically significant (p < 0.05). After the treatment, the levels of CD3+, CD4+ and CD4+/CD8+ in the study group were much higher than those in the control group; and the difference was statistically significant (p < 0.05). Conclusion: Chemotherapy combined with immunotherapy is effective in treating patients with advanced NSCLC without increasing the incidence of adverse reactions, and can significantly improve their nutritional status and T-lymphocyte function. This therapeutic regimen is of much higher clinical value than the chemotherapy-only regimen.
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Histone lysine-specific demethylase 1(LSD1) has become a promising molecular target for lung cancer therapy. Upon the screening platform for LSD1 activity, some Chinese herbal extracts were screened for LSD1 activity inhibition, and the underlying mechanism was preliminarily investigated at both molecular and cellular levels. The results of LSD1 inhibition showed that Puerariae Lobatae Radix extract can effectively reduce LSD1 expression to elevate the expression of H3 K4 me2 and H3 K9 me2 substrates in H1975 and H1299 cells. Furthermore, Puerariae Lobatae Radix was evaluated for its anti-lung cancer activity. It had a potent inhibitory ability against the proliferation and colony formation of both H1975 and H1299 cells. Flow cytometry and DAPI staining assays indicated that Puerariae Lobatae Radix can induce the apoptosis of lung cancer cells. In addition, it can significantly suppress the migration and reverse the epithelial-mesenchymal transition(EMT) process of lung cancer cells by activating E-cadherin and suppressing the expression of N-cadherin, slug and vimentin. To sum up, Puerariae Lobatae Radix displayed a robust inhibitory activity against lung cancer, and the mechanism may be related to the down-regulation of LSD1 expression to induce the cell apoptosis and suppress the cell migration and EMT process. These findings will provide new insights into the action of Puerariae Lobatae Radix as an anti-lung cancer agent and offer new ideas for the study on the anti-cancer action of Chinese medicine based on the epigenetic modification.
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Neoplasias , Pueraria , Pueraria/química , Histona Desmetilases/genética , Histona Desmetilases/análise , Raízes de Plantas/química , Transição Epitelial-MesenquimalRESUMO
Objectives: To investigate the short-term efficacy and radiotoxicity 3.543of chronoradiotherapy in patients with cervical cancer. We also examined the overall symptom score and quality of life (QOL) of patients who underwent morning radiotherapy and evening radiotherapy. Methods: We conducted a multicenter randomized controlled trial to compare the effects of morning radiotherapy (9:00-11:00 AM) with evening radiotherapy (7:00-9:00 PM) in cervical cancer patients receiving radiotherapy. From November 2021 to June 2022, 114 cervical cancer patients admitted to eight cancer center hospitals in Tianjin, Chongqing, Hubei, Shanxi, Shandong, Shaanxi, Hebei, and Cangzhou were randomly divided into the morning radiotherapy group (MG; N = 61) and the evening radiotherapy group (EG; N = 53). The short-term efficacy of radiotherapy on cervical cancer patients at different time points and the occurrence of radiotoxicity were explored after patients had undergone radiotherapy. Results: The total effective response (partial remission [PR] + complete remission [CR]) rate was similar across the two groups (93.5% vs. 96.3%, p > 0.05). However, the incidence of bone marrow suppression and intestinal reaction in the two groups were significantly different (p < 0.05). The patients in the MG had significantly higher Anderson symptom scores than patients in the EG (21.64 ± 7.916 vs. 18.53 ± 4.098, p < 0.05). In terms of physical activity, functional status, and overall QOL, the MG had significantly lower scores than the EG (p < 0.05). No other measures showed a significant difference between the groups. Conclusion: The radiotherapy effect of the MG was consistent with that of the EG. The incidence of radiation enteritis and radiation diarrhea in the MG was significantly higher than that in the EG; however, bone marrow suppression and blood toxicity in the EG were more serious than in the MG. Because of the small sample size of the study, we only examined the short-term efficacy of radiotherapy. Therefore, further clinical trials are needed to verify the efficacy and side effects of chronoradiotherapy. Clinical Trial Registration: http://www.chictr.org.cn/searchproj.aspx, Registration Number: ChiCTR2100047140.
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Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airflow limitation, and is associated with abnormal inflammatory responses in the lungs to cigarette smoke and toxic and harmful gases. Due to the existence of common risk factors, COPD is prone to multiple complications, among which cardiovascular disease (CVD) is the most common. It is currently established that cardiovascular comorbidities increase the risk of exacerbations and mortality from COPD. COPD is also an independent risk factor for CVD, and its specific mechanism is still unclear, which may be related to chronic systemic inflammation, oxidative stress, and vascular dysfunction. There is evidence that chronic inflammation of the airways can lead to destruction of the lung parenchyma and decreased lung function. Inflammatory cells in the airways also generate reactive oxygen species in the lungs, and reactive oxygen species further promote lung inflammation through signal transduction and other pathways. Inflammatory mediators circulate from the lungs to the whole body, causing intravascular dysfunction, promoting the formation and rupture of atherosclerotic plaques, and ultimately leading to the occurrence and development of CVD. This article reviews the pathophysiological mechanisms of COPD complicated by CVD and the effects of common cardiovascular drugs on COPD.
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Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC50 value (0.09 µM < IC50 < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC50 = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC50 = 0.73 µM and 0.14 µM respectively), and A549 cells (IC50 = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC50 = 3.1 ± 0.5 µM) than colchicine (IC50 = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network.
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Antineoplásicos , Moduladores de Tubulina , Compostos de Anilina/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células , Colchicina/química , Colchicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Piridinas/farmacologia , Relação Estrutura-Atividade , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacologiaRESUMO
BACKGROUND AND OBJECTIVES: Although the association between dietary protein intake and inflammatory bowel disease (IBD) risk has been investigated, the results are inconsistent. Therefore, we conducted a meta-analysis to reassess the relationship between dietary protein intake and IBD risk. METHODS AND STUDY DESIGN: The PubMed, Web of Knowledge, and Wanfang databases were searched for pertinent studies through January 31, 2020. Relative risks (RRs) with 95% confidence intervals (CIs) were derived using a random-effect model. Subgroup analyses according to disease type, geographic location, and sex; sensitivity analysis; and publication bias analysis were performed. RESULTS: The current report includes 8 articles consisting of 12 studies with 1069 cases and 330,676 participants. The pooled RR (95% CI) of the highest vs. the lowest categories of dietary protein intake for the IBD risk was 1.561 (0.384-6.347) in cohort studies and 1.060 (0.663-1.694) in case-control studies. Evidence of heterogeneity was found both in cohort studies (I2=86.4%, p=0.007) and in case-control studies (I2=49.0%, p=0.039). However, the association was significant among Asian populations (RR=1.675, 95% CI=1.096-2.559) but not in other populations. We did not find any relationship of dietary protein intake with the risk of either Crohn's disease or ulcerative colitis. CONCLUSIONS: Based on limited information, the highest dietary protein intakes among Asians may increase the risk of IBD, undifferentiated for ulcerative colitis or Crohn's disease. This may reflect dietary patterns for which protein is a marker rather than implicate protein itself.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Proteínas Alimentares , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , RiscoRESUMO
Maintaining proteostasis in the endoplasmic reticulum (ER) is critical for cell viability and plant survival under adverse conditions. The unfolded protein response (UPR) pathways interact with reactive oxygen species (ROS) to precisely trigger adaptive outputs or cell death under ER stress with varying degrees. However, little information is known about the relationship between UPR signalling and ROS regulation. Here, Arabidopsis GOLGI ANTI-APOPTOTIC PROTEIN1 (GAAP1)-GAAP4 were found to play redundant positive roles under ER stress. Genetic analysis showed that GAAP4 played a role in INOSITOL-REQUIRING ENZYME (IRE1)-dependent and -independent pathways. In addition, GAAPs played negative roles to activate the adaptive UPR under conditions of stress. Quantitative biochemical analysis showed that mutations in GAAP genes decreased the oxidised glutathione content and altered the pattern of ROS and glutathione in early ER stress. When plants were challenged with unmitigated ER stress, mutations in GAAP advanced ROS accumulation, which was associated with a decline in adaptive UPR. These data indicated that GAAPs resist cell death by regulating glutathione content to inhibit ROS accumulation and maintain UPR during ER stress. They provide a basis for further analysis of the regulation of cell fate decision under ER stress.
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Arabidopsis , Estresse do Retículo Endoplasmático , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Arabidopsis/metabolismo , Morte Celular , Estresse do Retículo Endoplasmático/fisiologia , Glutationa/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Resposta a Proteínas não DobradasRESUMO
To discover PDE4/tubulin dual inhibitors with novel skeleton structures, 7-trimethoxyphenylbenzo[d]oxazoles 4a-u and 4-trimethoxyphenylbenzo[d]oxazoles 5a-h were designed and synthesized by migrating the trimethoxyphenyl group of TH03 to the benzo[d]oxazole moiety. Among these compounds, approximately half of them displayed good antiproliferative activities against glioma (U251) and lung cancer (A549 and H460) cell lines. The structure-activity relationships of trimethoxyphenylbenzo[d]oxazoles led to the identification of 4r bearing indol-5-yl side-chain as a novel dual PDE4/tubulin inhibitor, which exhibited satisfactory antiproliferative activities against glioma (IC50 = 300 ± 50 nM) and lung cancer (average IC50 = 39.5 nM) cells. Further investigations revealed that 4r induced apoptosis at G2/M phase arrest and disrupted the microtubule network. The preliminary mechanism of action showed that 4r down-regulated the expression of cyclin B1 and its upstream regulator gene cdc25C in A549.
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Apoptose/efeitos dos fármacos , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Descoberta de Drogas , Glioma/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Oxazóis/farmacologia , Inibidores da Fosfodiesterase 4/farmacologia , Moduladores de Tubulina/farmacologia , Tubulina (Proteína)/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glioma/metabolismo , Glioma/patologia , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Estrutura Molecular , Oxazóis/síntese química , Oxazóis/química , Inibidores da Fosfodiesterase 4/síntese química , Inibidores da Fosfodiesterase 4/química , Relação Estrutura-Atividade , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/química , Células Tumorais CultivadasRESUMO
To screen the sensitive cell lines of active fraction from clove(AFC) on human colon cancer cells, investigate the effects of AFC on the cells proliferation and apoptosis as well as PI3 K/Akt/mTOR(phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin) signaling pathways involved, and reveal the mechanism of AFC for inducing apoptosis of human colorectal carcinoma cells. Cell counting kit-8(CCK-8) assay was used to detect the cytotoxic effect of different concentrations of AFC. AFC-induced apoptosis was detected by Hoechst 33258 fluorescence staining and Annexin V-FITC/PI double staining. HCT116 cells were treated with AFC with or without pretreatment with insulin-like growth factor-â (IGF-â ), and then the protein expression levels of caspase-3, caspase-9, poly ADP-ribose polymerase(PARP), PI3 K, p-PI3 K, Akt, p-Akt, mTOR and p-mTOR in PI3 K/Akt/mTOR signaling pathway were detected by Western blot. RESULTS:: showed that the most obvious inhibitory effect of AFC was on human colon cancer HCT116 cells, and the optimal AFC treatment time was 48 hours. After AFC treatment, typical apoptotic features such as nuclear chromatin concentration, nuclear fragmentation and apoptotic bodies appeared in a dose-dependent manner. Annexin V-FITC/PI double staining showed that as compared with the control group, 50 and 100 µg·mL~(-1) AFC groups increased the apoptosis rate of HCT116 cells significantly(P<0.001); AFC activated caspase-9, cleaved caspase-3 and cleaved PARP in a concentration-dependent manner. The protein expression levels of cleaved caspase-3/procaspase-3, cleaved PARP/PARP and caspase-9/ß-actin after treatment of AFC(100 µg·mL~(-1)) were significantly different from those in the control group(P<0.001). The relative protein expression of p-PI3 K, p-Akt and p-mTOR decreased in a concentration dependent manner, while Akt and mTOR showed no significant differences among groups. The ratios of p-PI3 K/PI3 K, p-Akt/Akt and p-mTOR/mTOR in the AFC groups(50 and 100 µg·mL~(-1)) were significantly lower than those in the control group(P<0.01). Its combination with IGF-â weakened the effect of AFC in inhibiting PI3 K/Akt/mTOR signaling pathway. The ratios of p-Akt/Akt and p-mTOR/mTOR in the AFC+IGF-â group were significantly enhanced as compared with the AFC group(P<0.05). Apoptosis-related protein expression levels(cleaved caspase-3 and cleaved PARP) in HCT116 cells treated with AFC+IGF-â were also down regulated. As compared with the AFC group, the ratios of cleaved caspase-3/procaspase-3 and cleaved PARP/PARP in the AFC+IGF-â group were significantly decreased(P<0.01). In summary, AFC activated caspase-mediated cascades and induced HCT116 cells apoptosis in a dose-dependent manner, which may be associated with the inhibition of the PI3 K/Akt/mTOR signaling pathway.
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Neoplasias do Colo , Syzygium , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/tratamento farmacológico , Células HCT116 , Humanos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
Human umbilical vein endothelial cells (HUVECs) serve a critical role in maintaining normal vascular function. Lipopolysaccharide (LPS), which is released from pathogenic bacteria in the blood, induces HUVEC apoptosis and injury to cause vascular dysfunction and infectious vascular diseases. Procyanidin B2 (PB2) possesses numerous functions, including antioxidant, antitumor, antiinflammatory and antiapoptosis effects, but the molecular mechanism is not completely understood. The present study investigated the effects of PB2 on LPSinduced cytotoxicity and apoptosis in HUVECs, as well as the underlying mechanisms. The effects of PB2 on LPSmediated alterations to cytotoxicity, mitochondrial membrane potential, apoptosis were assessed by performing Cell Counting Kit8, JC1 fluorescence, Hoechst 33258 staining assays, respectively. IL1ß, IL6 and TNFα mRNA expression and protein levels were measured by performing reverse transcriptionquantitative PCR and ELISAs, respectively. Bcl2, Bax, cleaved caspase3, cleaved caspase7, cleaved caspase9, phosphorylated (p)IκBα, pIκBß, pNFκBp65 and total NFκB p65 protein expression levels were determined via western blotting. NFκB p65 nuclear translocation was assessed via immunofluorescence. PB2 pretreatment markedly attenuated LPSinduced cytotoxicity and apoptosis in HUVECs. PB2 also significantly downregulated the expression levels of IL1ß, IL6, TNFα, Bax, cleaved caspase3, cleaved caspase7, cleaved caspase9 and pNFκBp65, but upregulated the expression levels of Bcl2, pIκBα and pIκBß in LPSinduced HUVECs. Moreover, PB2 markedly inhibited LPSinduced NFκB p65 nuclear translocation in HUVECs. The results suggested that the potential molecular mechanism underlying PB2 was associated with the Bax/Bcl2 and NFκB signalling pathways. Therefore, PB2 may serve as a useful therapeutic for infectious vascular diseases.
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Apoptose/efeitos dos fármacos , Biflavonoides/farmacologia , Catequina/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Proantocianidinas/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Modelos Biológicos , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Hepatic cavernous hemangioma is the most common type of benign liver tumor. Although ruptures and hemorrhages of hepatic hemangioma are rare complications, they are associated with high mortality. Most practitioners only pay more attention to abdominal hemorrhages caused by the rupture of hepatic hemangiomas. However, spontaneous intracapsular hemorrhages can often be neglected and poorly understood. CASE PRESENTATION: A 65-year-old man was referred to our institution with right upper quadrant pain, which had occurred suddenly and without a history of recent trauma. The blood test results were normal. Magnetic resonance imaging (MRI) of the abdomen showed a cystic mass in the right liver lobe. Considering the possibility of hepatic cystadenoma with hemorrhage, the patient underwent a right hepatic lobectomy. The pathological findings unexpectedly revealed intratumoral hemorrhage of hepatic hemangioma. The patient recovered well and was discharged eight days after surgery. CONCLUSIONS: Intracapsular hemorrhage of hepatic cavernous hemangioma is challenging to diagnose and has a high potential risk of rupture. MRI is beneficial for diagnosing subacute internal hemorrhage cases, and it is recommended to undergo surgery for patients with a definitive diagnosis.
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Hemangioma Cavernoso , Hemangioma , Neoplasias Hepáticas , Idoso , Hemangioma Cavernoso/complicações , Hemangioma Cavernoso/diagnóstico por imagem , Hemangioma Cavernoso/cirurgia , Hemorragia/etiologia , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgiaRESUMO
Talaromyces purpurogenus strain Q2 is a kind of beneficial microbe originally separated from the rhizosphere of healthy cucumber. In this study, we evaluated the biocontrol potential of strain Q2 against four soil-borne diseases by plate confrontation culture, potting in the greenhouse. We further estimated the control efficacy of strain Q2 combined metam-sodium fumigation against Fusarium wilt of bitter gourd in the field. The mechanism of strain Q2 controlling bitter gourd wilt and regulating soil microbial community was examined by plate dilution culture, high throughput sequencing and quantitative PCR. The results showed that strain Q2 could efficiently reduce disease incidence of Fusarium wilt of bitter gourd, potato stem canker, black shank of tobacco and black root rot of tobacco in the green house. Its biocontrol efficacy on black shank of tobacco and bitter gourd wilt was 75.3% and 63.4%, respectively. Biocontrol efficacy of strain Q2 on bitter gourd wilt was 51.0% in the artificial disease nursery inoculated pathogen of bitter gourd wilt, while the control efficacy of strain Q2 combined with soil fumigation technology was more than 80% in the same experiment condition. Strain Q2 application and soil fumigation altered soil microbial community composition and recovery trend. Metam-sodium fumigation significantly reduced the abundances of Fusarium oxysporum and causal agent of bitter gourd wilt. Strain Q2 further suppressed the efficient recovery trend of the pathogen. After application of strain Q2, Penicillium was enriched in soil, as well as the beneficial microbes involved in the suppression of F. oxysporum, such as Bacillus and Gaiella. Overall, after soil fumigation, biocontrol efficacy of strain Q2 on soil-borne diseases such as Fusarium wilt could attribute to the formation of beneficial microbial communities in soil and inhibition of strain Q2 on growth and development of F. oxysporum.
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Fusarium , Microbiota , Doenças das Plantas , Solo , Microbiologia do Solo , TalaromycesRESUMO
Fusarium oxysporum f. sp. momordica was used as the target pathogenic fungus to screen actinomycetes that were isolated from rhizosphere soil of Momordica charantia by confrontation culture and antifungal tests of fermentation filtrate. The candidate strain 0250 had broad antifungal activity. According to cultural characteristics, physiological and biochemical properties, as well as average nucleotide identity analysis of the strains with similar homology, the strain 0250 was identified as Streptomyces rhizosphaericus. Its effects on growth promotion and control of bitter gourd wilt were evaluated in both greenhouse and field. The results showed that the plate inhibition percentage of S. rhizosphaericus strain 0250 against F. oxysporum f. sp. momordica was 69.2%, while the plate inhibition percentage against 17 plant pathogenic fungi reached 64.3%-85.6%. The suspension treatment of the strain could promote the growth and development of roots and stems and improve production of bitter gourd in pots and field. The control efficacy of Fusarium wilt of bitter gourd was 66.9% and 61.5%, respectively. When soils were treated with the strain 0250 suspension in advance and inoculated with the fungal pathogen, the inhibition percentage on the soil F. oxysporum reached 62.1%. The activity of phenylalanine ammonia-lyase, peroxidase and ß-1,3-glucanase as well as root activity were significantly improved in bitter gourd seedlings. In summary, strain 0250 is an actinomycetes resource with biocontrol potential to Fusarium wilt of bitter gourd.
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Actinobacteria , Fusarium , Momordica charantia , Actinomyces , Programas de Rastreamento , Doenças das Plantas/prevenção & controle , StreptomycesRESUMO
Scutellaria baicalensis Georgi. (SB) is a common heat-clearing medicine in traditional Chinese medicine (TCM). It has been used for thousands of years in China and its neighboring countries. Clinically, it is mostly used to treat diseases such as cold and cough. SB has different harvesting periods and processed products for different clinical symptoms. Botanical researches proved that SB included in the Chinese Pharmacopoeia (1st, 2020) was consistent with the medicinal SB described in ancient books. Modern phytochemical analysis had found that SB contains hundreds of active ingredients, of which flavonoids are its major components. These chemical components are the material basis for SB to exert pharmacological effects. Pharmacological studies had shown that SB has a wide range of pharmacological activities such as antiinflammatory, antibacterial, antiviral, anticancer, liver protection, etc. The active ingredients of SB were mostly distributed in liver and kidney, and couldn't be absorbed into brain via oral absorption. SB's toxicity was mostly manifested in liver fibrosis and allergic reactions, mainly caused by baicalin. The non-medicinal application prospects of SB were broad, such as antibacterial plastics, UV-resistant silk, animal feed, etc. In response to the Coronavirus Disease In 2019 (COVID-19), based on the network pharmacology research, SB's active ingredients may have potential therapeutic effects, such as baicalin and baicalein. Therefore, the exact therapeutic effects are still need to be determined in clinical trials. SB has been reviewed in the past 2 years, but the content of these articles were not comprehensive and accurate. In view of the above, we made a comprehensive overview of the research progress of SB, and expect to provide ideas for the follow-up study of SB.
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Mimicking different pharmacophoric units into one scaffold is a promising structural modification tool to design new drugs with enhanced biological properties. To continue our research on the tubulin inhibitors, the synthesis and biological evaluation of arylpyridine derivatives (9-29) are described herein. Among these compounds, 6-arylpyridines (13-23) bearing benzo[d]imidazole side chains at the 2-position of pyridine ring displayed selective antiproliferative activities against HT-29 cells. More interestingly, 2-trimethoxyphenylpyridines 25, 27, and 29 bearing benzo[d]imidazole and benzo[d]oxazole side chains displayed more broad-spectrum antitumor activities against all tested cancer cell lines. 29 bearing a 6-methoxybenzo[d]oxazole group exhibited comparable activities against A549 and U251 cells to combretastatin A-4 (CA-4) and lower cytotoxicities than CA-4 and 5-Fu. Further investigations revealed 29 displays strong tubulin polymerization inhibitory activity (IC50 = 2.1 µM) and effectively binds at the colchicine binding site and arrests the cell cycle of A549 in the G2/M phase by disrupting the microtubules network.
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In this study, we evaluated the diagnostic value and molecular characteristics of plasma extracellular vesicles (EVs)-derived miRNAs for patients with solitary pulmonary nodules (SPNs), particularly ground-glass nodules (GGNs). This study was registered at www.clinicaltrials.gov under registration number NCT03230019. Small RNA sequencing was performed to assess plasma EVs miRNAs in 59 patients, including 12 patients with benign nodules (2017, training set). MiRNA profiles of 40 an additional individuals were sequenced (2018, validation set). Overall, 16 pure GGNs, 21 mixed GGNs, and 42 solid nodules were included, with paired post-operative plasma samples available for 20 patients. The target miRNA/reference miRNA ratio was used to construct a support vector machine (SVM) model. The SVM model with the best specificity showed 100% specificity in both the training and validation sets independently. The model with the best sensitivity showed 100% and 96.9% sensitivity in the training and validation sets, respectively. Principal component analysis revealed that pure GGN distributions were distinct from those of solid nodules, and mixed GGNs had a diffuse distribution. Among differentially expressed miRNAs, miR-500a-3p, miR-501-3p, and miR-502-3p were upregulated in tumor tissues and enhanced overall survival. The SVM classifier accurately distinguished malignant GGNs and benign nodules. The distinct profile characteristics of miRNAs provided insights into the feasibility of EVs miRNAs as prognostic factors in lung cancer.
RESUMO
DNA alkylation and oxidation are two most common forms of cytotoxic damage with the characteristics of mutagenic and carcinogenic. Human alkyladenine DNA glycosylase (hAAG) is the only glycosylase known to repair a wide variety of alkylative and oxidative DNA lesions. However, few approaches are capable of real-time monitoring hAAG activity. Methods: Herein, we develop a facile fluorescent strategy for homogeneous and sensitive sensing of hAAG activity based on the controllable autocatalytic cleavage-mediated fluorescence recovery. The presence of hAAG enables the cleavage of hairpin probe 1 (HP1) at the damaged 2'-deoxyinosine site by AP endonuclease 1 (APE1), forming a DNA duplex. The trigger 1 built in the resultant DNA duplex may hybridize with hairpin probe 2 (HP2) to induce the T7 exonuclease (T7 exo)-catalyzed recycling cleavage of HP2 (Cycle I) to release trigger 2. The trigger 2 can further hybridize with the signal probe (a fluorophore (FAM) and a quencher (BHQ1) modified at its 5' and 3' ends) to induce the subsequent recycling cleavage of signal probes (Cycle II) to liberate FAM molecules. Through two-recycling autocatalytic cleavage processes, large amounts of fluorophore molecules (i.e., FAM) are liberated from the FAM-BHQ1 fluorescence resonance energy transfer (FRET) pair, leading to the amplified fluorescence recovery. Results: Taking advantage of the high accuracy of in vivo DNA repair mechanism, the high specificity of T7 exo-catalyzed mononucleotides hydrolysis, and the high efficiency of autocatalytic recycling amplification, this strategy exhibits high sensitivity with a detection limit of 4.9 × 10-6 U/µL and a large dynamic range of 4 orders of magnitude from 1 × 10-5 to 0.1 U/µL, and it can further accurately evaluate the enzyme kinetic parameters, screen the potential inhibitors, and even quantify the hAAG activity from 1 cancer cell. Conclusion: The proposed strategy can provide a facile and universal platform for the monitoring of DNA damage-related repair enzymes, holding great potential for DNA repair-related biochemical research, clinical diagnosis, drug discovery, and cancer therapy.