RESUMEN

The synergistic effects on the 0.18 µm PPD CISs induced by neutron displacement damage and gamma ionization damage are investigated. The typical characterizations of the CISs induced by the neutron displacement damage and gamma ionization damage are presented separately. The CISs are irradiated by reactor neutron beams up to 1 × 1011 n/cm2 (1 MeV neutron equivalent fluence) and 60Co γ-rays up to the total ionizing dose level of 200 krad(Si) with different sequential order. The experimental results show that the mean dark signal increase in the CISs induced by reactor neutron radiation has not been influenced by previous 60Co γ-ray radiation. However, the mean dark signal increase in the CISs induced by 60Co γ-ray radiation has been remarkably influenced by previous reactor neutron radiation. The synergistic effects on the PPD CISs are discussed by combining the experimental results and the TCAD simulation results of radiation damage.

RESUMEN

Hexaploid triticale is an important genetic resource for genetic improvement of common wheat, which can broaden the genetic basis of wheat. In order to lay a foundation for the subsequent research and utilization of triticale germplasm materials, the chromosomal genetic characteristics of cross and backcross offspring of hexaploid triticale×hexaploid wheat were investigated in the process of transferring rye chromatin from hexaploid triticale to hexaploid wheat. Hybrid and backcross combinations were prepared with hexaploid triticale 16yin171 as the maternal parent and hexaploid wheat Chuanmai62 as the paternal parent. The chromosomes in root tip cells of F1, BC1F1 and BC1F2 plants were traced and identified non-denaturing florescence in situ hybridization (ND-FISH). The results indicated that the backcross setting rate of hybrid F1 was 2.61%. The transmission frequency of 2R chromosome was the highest in BC1F1 plants while the transmissibility of rye chromosome in BC1F2 plant was 6R>4R>2R, and the 5B-7B wheat translocation in BC1F2 plants showed severe segregation. A total of 24 structural variant chromosomes were observed both in BC1F1 and BC1F2 plants, including chromosome fragments, isochromosomes, translocations, and dicentric chromosomes. In addition, the seed length and 1000-grain weight of some BC1F2 plants were better than that of the hexaploid wheat parent Chuanmai 62. Therefore, multiple backcrosses should be adopted as far as possible to make the rapid recovery of group D chromosomes, ensuring the recovery of fertility in offspring, when hexaploid tritriale is used as a bridge to introduce rye genetic material into common wheat. At the same time, the potential application value of chromosomal structural variation materials should be also concerned.

Asunto(s)

Triticale , Triticum , Triticum/genética , Triticale/genética , Secale/genética , Cromosomas de las Plantas/genética , Hibridación in Situ , Translocación Genética

Asunto(s)

Mutación de Línea Germinal , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/genética , Proteína BRCA2/genética , Predisposición Genética a la Enfermedad

RESUMEN

Objective: To investigate the clinical value of observing perioperative changes of myeloperoxidase (MPO) and neutrophil elastase (NE) in coronary artery circulation in patients underwent valve replacement surgery. Methods: This perspective cohort study was performed in patients who underwent valvular surgery in Nanjing Drum Tower Hospital and Fuwai Hospital from June 2021 to June 2022. Patients were divided into perioperative myocardial injury group and age-, sex- and type of cardiac procedure-matched non-perioperative myocardial injury control group in the ratio of 1∶1. Perioperative myocardial injury was defined as cardiac troponin T (cTnT)>0.8 μg/L on the first postoperative day (POD), and the cTnT level on the second POD increased by more than 10% compared with the cTnT level on the first POD. During the operation, blood samples were collected from the coronary sinus before clamping ascending aorta, and within 5 minutes after de-clamping ascending aorta. Then, the levels of MPO and NE on coronary sinus were continuously measured. The death, severe ventricular arrhythmia, pneumonia, re-intubation, repeat cardiac surgery, extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP), continuous renal replacement therapy (CRRT), mechanical ventilation time and the duration of intensive care unit (ICU) were recorded. The levels of MPO and NE and the incidence of clinical outcomes were compared between the myocardial injury group and the control group. The independent risk factors of myocardial injury were analyzed by multivariate logistic regression. Results: A total of 130 patients were enrolled, aged (60.6±7.6) years old, with 59 males (45.4%). There were 65 patients in the myocardial injury group and 65 patients in the control group. During hospitalization, there was no death, ECMO, IABP and CRRT cases in both groups. Compared with the control group, the incidence of severe ventricular arrhythmia (13.8%(9/65) vs. 3.1%(2/65), P=0.03), pneumonia (20.0%(13/65) vs. 3.1%(2/65), P=0.03), re-intubation (6.2%(4/65) vs. 0, P=0.04) was significantly higher in myocardial injury group. The mechanical ventilation time (16.8(10.7, 101.7) h vs. 7.5(4.7, 15.1) h, P<0.01), and the duration of ICU (3.7(2.7, 18.9) vs. 2.7(1.8, 6.9)d, P<0.01) were significantly longer in myocardial injury group compared with the control group. There was no significant difference in the levels of MPO and NE in coronary sinus blood between the two groups before aortic clamping (all P>0.05). However, MPO ((551.3±124.2) μg/L vs. (447.2±135.9) μg/L, P<0.01) and NE ((417.0±83.1)μg/L vs. (341.0±68.3)μg/L, P<0.01) after 5 min aortic de-clamping were significantly higher in myocardial injury group than in the control group. Multivariate logistic regression analysis showed that the levels of NE (OR=1.02, 95%CI: 1.01-1.02, P<0.01), MPO (OR=1.00, 95%CI: 1.00-1.01, P=0.02) and mechanical ventilation time (OR=1.03, 95%CI: 1.01-1.06, P=0.02) were independent risk factors of myocardial injury in patients after surgical valvular replacement. Conclusion: Perioperative myocardial injury is related poor clinical outcomes, perioperative NE and MPO in coronary artery circulation are independent risk factors of perioperative myocardial injury in patients undergoing valve replacement surgery.

Asunto(s)

Anciano , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios de Cohortes , Circulación Coronaria , Elastasa de Leucocito , Peroxidasa , Pronóstico , Estudios Retrospectivos

RESUMEN

STUDY OBJECTIVE: The purpose of the present study was to evaluate the efficacy of levosimendan in patients with acute myocardial infarction related ventricular septal rupture (AMI-VSR) underwent cardiac surgery. DESIGN: Prospective observational cohort study with propensity score analysis. PATIENTS: There were 261 patients with AMI-VSR in our study. After 1:1 propensity matching, 106 patients (53 levosimendan and 53 control) were selected in the matched cohort. INTERVENTIONS: None. MEASUREMENTS: Patients who received levosimendan were assigned to the levosimendan group (n = 164). The patients who were not received were levosimendan assigned to the control group (n = 97). The levosimendan was initiated immediately after cardiopulmonary bypass. Then, it has been maintained during the postoperative 3 days. The poor outcomes were identified as follows: death and postoperative complications (postoperative stroke, low cardiac output syndromeneeded mechanical circulatory support after surgery, acute kidney injury (≥ stage III), postoperative infection or septic shock, new developed atrial fibrillation or ventricular arrhythmias). MAIN RESULTS: Before matching, the control group had more length of ICU stay (6.69 ± 3.90 d vs. 5.20 ± 2.24 d, p < 0.001) and longer mechanical ventilation time (23 h, IQR: 16-53 h vs. 16 h, IQR: 11-23 h, p < 0.001). Other postoperative outcomes have not shown significant differences between two groups. After matching, no significant difference was found between both groups for all postoperative outcomes. The Kaplan-Meier survivul estimate and log-rank test showed that the 90-day survival had no significant differences between two groups before and after matching. CONCLUSION: Our study found that a low-dose infusion of levosimendan in AMI-VSR patients underwent surgical repair did not associated with positively affect to postoperative outcomes.

Asunto(s)

Procedimientos Quirúrgicos Cardíacos , Infarto del Miocardio , Piridazinas , Rotura Septal Ventricular , Enfermedad Aguda , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Cardiotónicos , Femenino , Humanos , Hidrazonas/uso terapéutico , Masculino , Infarto del Miocardio/complicaciones , Infarto del Miocardio/tratamiento farmacológico , Complicaciones Posoperatorias , Puntaje de Propensión , Estudios Prospectivos , Piridazinas/uso terapéutico , Simendán , Rotura Septal Ventricular/tratamiento farmacológico

RESUMEN

Triploid is considered a reproductive barrier and also a bridge in the formation of polyploids. However, few reports are available in Cymbidium. In this study, diploid 'Xiaofeng', sexual triploid 'Yuchan' and 'Huanghe' of Cymbidium were used to evaluate hybridization compatibility of the triploids. Results showed that the sexual triploids were fertile whether they were used as male or female parents. 'Yuchan' produced male gametes of 1x, 1x~2x, 2x, 2x~3x, and 3x at frequencies of 8.89%, 77.78%, 6.67%, 3.33%, and 3.33%, respectively; while 'Huanghe' produced 3.33% 1x, 80.00% 1x~2x, 8.89% 2x, 5.56% 2x~3x, and 2.22% 3x male gametes. The cross of 'Xiaofeng' with 'Yuchan' produced progenies with a wide range of ploidy levels, including one diploid, 34 2×~3× aneuploids, 12 triploids, and one tetraploid, indicating that male gametes produced by sexual triploid were fertile and could be transmitted and fused with egg cells. On the other hand, 10 progenies obtained from the cross of 'Yuchan' × 'Xiaofeng' were all aneuploids. The cross of 'Yuchan' with 'Huanghe' produced 40 progenies including three 2×~3× aneuploids, nine 3×~4× aneuploids, 21 tetraploids, six 4×~5× aneuploids, and one pentaploid, suggesting that 2x gametes, instead of the unreduced ones played a more important role in the formation of tetraploids. The survival rates of the hybrids were all above 80.00%, with the tetraploids at 96.67%. Cytological analysis revealed that during meiosis of sexual polyploids, two chromosome sets of the 2n gamete were inclined to enter into the same daughter cell, resulting in the production of 2x gametes. Our results indicate that the triploid cymbidiums are not reproductive barrier but serve as a bridge in the formation of polyploid plants.

RESUMEN

Tumour-associated macrophages (TAMs) represent an attractive cell target for anticancer therapy. However, selective and efficient targeting of TAMs remains difficult. Here, we constructed a novel dually functionalised nanoparticle platform (s-Tpep-NPs) by surface co-modification of nanoparticles (NPs) with tuftsin (Tpep) and legumain protease-sheddable polyethylene glycol 5k (PEG5k) to achieve selective targeted delivery to TAMs. The fluorescence resonance energy transfer experiment and in vitro cellular uptake assay confirmed that s-Tpep-NPs can responsively shed PEG5k and transform into active Tpep-NPs upon the cleavage of legumain that is overexpressed on TAM surfaces, which then promotes TAM phagocytosis through Fc receptor-mediated pathways. Owing to the shielding effect by legumain-sheddable PEG5k, s-Tpep-NPs can effectively decrease the Tpep-induced non-specific accumulation in mononuclear phagocyte system (MPS) organs during systemic circulation. Moreover, s-Tpep-NPs can significantly enhance the tumoural accumulation and improve the specificity and efficiency of targeting to TAMs, as compared with both controls of Tpep-NPs and non-sheddable ns-Tpep-NPs. Overall, this study provides a robust nanoplatform with a novel avenue for improved selectivity of targeted delivery to TAMs.

Asunto(s)

Nanopartículas , Tuftsina , Cisteína Endopeptidasas , Péptido Hidrolasas , Polietilenglicoles , Macrófagos Asociados a Tumores

RESUMEN

To analyze the performance of the Prostate Health Index (phi) and its derivatives for predicting Gleason score (GS) upgrading between prostate biopsy and radical prostatectomy (RP) in the Chinese population, an observational, prospective RP cohort consisting of 351 patients from two medical centers was established from January 2017 to September 2020. Pathological reclassification was determined by the Gleason Grade Group (GG). The area under the receiver operating characteristic curve (AUC) and logistic regression (LR) models were used to evaluate the predictive performance of predictors. In clinically low-risk patients with biopsy GG ≤2, phi (odds ratio [OR] = 1.80, 95% confidence interval [95% CI]: 1.14-2.82, P = 0.01) and its derivative phi density (PHID; OR = 2.34, 95% CI: 1.30-4.20, P = 0.005) were significantly associated with upgrading to GG ≥3 after RP, and the results were confirmed by multivariable analysis. Similar results were observed in patients with biopsy GG of 1 for the prediction of upgrading to RP GG≥2. Compared to the base model (AUC = 0.59), addition of the phi or PHID could provide additional predictive value for GS upgrading in low-risk patients (AUC = 0.69 and 0.71, respectively, both P < 0.05). In conclusion, phi and PHID could predict GS upgrading after RP in clinically low-risk patients.

Asunto(s)

Próstata , Neoplasias de la Próstata , Biopsia , Humanos , Masculino , Clasificación del Tumor , Estudios Prospectivos , Próstata/patología , Próstata/cirugía , Antígeno Prostático Específico , Prostatectomía/métodos , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Circulating tumor cells (CTCs) play an important role in tumor metastasis and may be a target for metastasis prevention. The traditional Chinese medicine Jinfukang functions to improve immunity, prevent metastasis, and prolong lung cancer patient survival periods. Yet, whether Jinfukang prevents metastasis by regulating immune cells to clearance CTCs is still unknown. AIM OF THE STUDY: To explore the anti-metastasis mechanism of Jinfukang from the perspective of regulating NK cells to clear CTCs. MATERIALS AND METHODS: CTC-TJH-01 cell was treated with Jinfukang. Cytokine chip was used to detect cytokines in cell culture supernatant. Lymphocyte recruitment assay was detected by Transwell and flow cytometry. Protein expression was analysis by Western blot. LDH kit was used to detect cytotoxicity. NOD-SCID mice used for tail vein injection to study lung metastasis. RESULTS: Jinfukang could promote the expression and secretion of the chemokine CX3CL1 by CTCs. In addition, Jinfukang could promote the recruitment of natural killer (NK) cells by CTCs and significantly increase the cytotoxic effect of NK cells on CTCs. Moreover, Jinfukang could upregulate the expression of FasL and promote the secretion of TNF-α by NK cells and that NK cells could induce the apoptosis of CTCs through the Fas/FasL signaling pathway. Finally, we confirmed that Jinfukang could promote NK cells to kill CTCs and then inhibit lung cancer metastasis in vivo. The above effects of Jinfukang could be partially reversed by an anti-CX3CL1 mAb. CONCLUSIONS: These results suggest that Jinfukang may prevent lung cancer metastasis by enhancing the clearance of CTCs in the peripheral blood by NK cells, providing evidence for the anti-metastasis effect of Jinfukang.

Asunto(s)

Antineoplásicos/farmacología , Quimiocina CX3CL1/genética , Medicamentos Herbarios Chinos/farmacología , Células Asesinas Naturales/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Metástasis de la Neoplasia/prevención & control , Células Neoplásicas Circulantes/efectos de los fármacos , Animales , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Quimiocina CX3CL1/antagonistas & inhibidores , Quimiocina CX3CL1/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/uso terapéutico , Proteínas Ligadas a GPI/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Células Asesinas Naturales/inmunología , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Masculino , Ratones Endogámicos NOD , Ratones SCID , Metástasis de la Neoplasia/inmunología , Células Neoplásicas Circulantes/inmunología , Células Neoplásicas Circulantes/patología , Receptores de Muerte Celular/metabolismo , Transducción de Señal/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Receptor fas/metabolismo

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Metastasis is the main cause of death in lung cancer patients. Circulating tumor cells (CTCs) may be an important target of metastasis intervention. Previous studies have shown that Jinfukang could prevent the recurrence and metastasis of lung cancer, and we have established a circulating lung tumor cell line CTC-TJH-01. However, whether Jinfukang inhibition of lung cancer metastasis is related to CTCs is still unknown. AIM OF THE STUDY: To further explore the mechanism of Jinfukang in anti-metastasis of lung cancer from the perspective of intervention of CTCs. MATERIALS AND METHODS: CTC-TJH-01 and H1975 cells were treated with Jinfukang. Cell viability was detected by CCK8, and the cell apoptosis was detected by flow cytometry. Transwell was used to detected cell migration and invasion. Cell anoikis was detected by anoikis detection kit. Protein expression was analysis by Western blot. RESULTS: Jinfukang could inhibit the proliferation, migration and invasion of CTC-TJH-01 and H1975 cells. Besides, Jinfukang could also induce anoikis in CTC-TJH-01 and H1975 cells. Analysis of the mRNA expression profile showed ECM-receptor interaction and focal adhesion were regulated by Jinfukang. Moreover, it was also find that Jinfukang significantly inhibited integrin/Src pathway in CTC-TJH-01 and H1975 cells. When suppress the expression of integrin with ATN-161, it could promote Jinfukang to inhibit migration and induce anoikis in CTC-TJH-01 and H1975 cells. CONCLUSIONS: Our results indicate that the migration and invasion of CTCs are inhibited by Jinfukang, and the mechanism may involve the suppression of integrin/Src axis to induce anoikis. These data suggest that Jinfukang exerts anti-metastatic effects in lung cancer may through anoikis.

Asunto(s)

Anoicis/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Movimiento Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Integrinas/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Células Neoplásicas Circulantes/efectos de los fármacos , Familia-src Quinasas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/patología , Invasividad Neoplásica , Metástasis de la Neoplasia , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Transducción de Señal

RESUMEN

Objective:To investigate the taxonomic structure and diversity of endophytic fungi from <italic>Datura metel </italic>and screen the strains with anti-dermatophyte activities， so as to provide resources for the development of new lead compounds against dermatomycosis. Method:Endophytic fungi were isolated from the roots， stems and leaves of <italic>D. metel</italic> after tissue block incubation and then identified by morphological analysis and rDNA-internal transcribed spacer（ITS） sequencing. Their anti-dermatophyte activities were detected by agar diffusion assay. Result:A total of 292 strains of endophytic fungi were isolated from <italic>D. metel</italic>， belonging to 34 genera， with<italic> Fusarium</italic> （72.97%） in roots， <italic>Fusarium </italic>（37.25%） and <italic>Plectosphaerella </italic>（28.43%） in stems， and <italic>Colletotrichum </italic>（39.66%） in leaves as the dominant species. The isolation rate （89.23%）， colonization rate （84.62%）， and diversity index （1.82） of endophytic fungi in leaves were significantly higher than those in roots （70.48%， 70.48% and 1.23） and stems （69.39%，68.03% and 1.64）. The determination of anti-dermatophyte activities of 35 endophytic fungal fermented filtrates showed that the strains exhibiting inhibitory activities against <italic>Microsporum canis</italic>， <italic>Trichosporon mucoides</italic>， <italic>Trichophyton rubrum</italic> and <italic>Candida albicans </italic>accounted for 97.14%， 71.43%， 45.71%， and 25.71%， respectively. Among them， six strains （17.14%）， namely <italic>Fusarium </italic>sp. R1， <italic>Penicillium </italic>sp. R5， <italic>Aspergillus </italic>sp. R7， <italic>Metarhizium </italic>sp.<italic> </italic>S18， <italic>Diaporthe </italic>sp. S19， and <italic>Glomerella </italic>sp.<italic> </italic>L57， all inhibited the four types of cutaneous fungal pathogens. Conclusion:The endophytic fungi in <italic>D. metel</italic> are diverse， and the proportion of endophytic fungi possessing anti-dermatophyte activities is high， allowing them to serve as potential resources for the development of new anti-dermatophyte agents.

RESUMEN

M2 tumor-associated macrophages (TAMs) play a pivotal role in cancer progression and therapy resistance. Inhibition of TAMs is of great significance to reshape the protumor environment to benefit therapeutic outcomes. In this work, we developed a novel TAMs and tumor cells dual-targeting nanoparticle (ATpep-NPs) system for cancer chemotherapy by integrating a docetaxel (DTX)-loaded nanocarrier and a multi-function peptide ATpep, which is composed of a phagocytosis-stimulating peptide-tuftsin (Tpep) fused with a substrate peptide-alanine-alanine-asparagine (AAN) of endoprotease legumain. In vitro protelytic and cellular uptake assays confirmed ATpep-NPs can be responsively activated into Tpep-NPs by cleavage of legumain that is overexpressed in both tumor cells and TAMs, which then promoted tumor cells internalization and TAMs phagocytosis through neuropilin-1/Fc receptor pathways. Due to AAN deactivation effect, ATpep-NPs can effectively decrease the Tpep-induced non-specific uptake by M1-polarized and normal macrophage during systemic circulation. Our results of in vivo experiments demonstrated ATpep-NPs outperformed Tpep-NPs in tumor and TAMs dual-targeting delivery efficiency with markedly enhanced efficacy against both tumor growth inhibition and TAMs depletion. Overall, this study offers a novel approach for development of multitargeted delivery vehicle for improved cancer chemotherapy.

Asunto(s)

Antineoplásicos , Nanopartículas , Neoplasias , Tuftsina , Antineoplásicos/farmacología , Línea Celular Tumoral , Cisteína Endopeptidasas , Péptido Hidrolasas

RESUMEN

BACKGROUND: Ginkgolide B (GKB) is a major active component of the extracts of Ginkgo biloba leaves, and it has been used as an anti-cancer agent. However, it is unknown whether GKB has the therapeutic effects on lung cancer. Here, we studied the effects of GKB on lung cancer cells. METHODS: The effects of GKB on lung cancer cell proliferation and invasion were analyzed by cell counting kit (CCK-8) and cell invasion assays, respectively. Apoptosis was detected by flow cytometry. Western blot analysis was used to confirm the expression of autophagy-associated proteins in GKB-treated cells. Immunofluorescence analysis was used to analyze the level of light chain 3B (LC3B). RESULTS: Treatment with GKB time-dependently inhibited the proliferation and decreased the invasive capacity of A549 and H1975 cells. GKB induced apoptosis of these cells, but there was no significant effect on apoptosis compared to the control treatment. GKB-induced inhibition of cell proliferation and GKB-induced cell death were due to autophagy rather than apoptosis. GKB-induced autophagy of lung cancer cells was dependent on beclin-1, and autophagy-induced inhibition of the NLRP3 inflammasome contributed to the anti-tumor effect of GKB. CONCLUSIONS: GKB-mediated autophagy of lung cancer cells is beclin-1-dependent and results in inhibition of the NLRP3 inflammasome. Therefore, GKB might be a potential therapeutic candidate for the treatment of lung cancer.

Asunto(s)

Antineoplásicos Fitogénicos/farmacología , Autofagia/efectos de los fármacos , Beclina-1/metabolismo , Ginkgólidos/farmacología , Lactonas/farmacología , Neoplasias Pulmonares/patología , Células A549 , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Estructura Molecular , Hojas de la Planta/química

RESUMEN

A Gram-stain-negative, stalked, oval-shaped and budding bacterial strain, designated E7T, was isolated from a deep-sea water sample collected from the Northwest Indian Ocean. The novel strain was strictly aerobic, and catalase- and oxidase-positive. It grew at 6-40 °C (optimum 30 °C) and pH 5.5-8.0 (optimum pH 7.0-7.5). The strain required 0.5-9.0 % (w/v) NaCl (optimum 3.0-5.0 %) for growth. Aesculin, starch, pectin and Tween 20 were hydrolysed. Based on 16S rRNA gene sequence analysis, strain E7T showed the highest similarity with Gimesia maris DSM 8797T (97.5 %). The average nucleotide identity and in silico DNA-DNA hybridization values between strain E7T and G. maris DSM 8797T were 78.0 and 19.3 %, respectively. The predominant cellular fatty acids of strain E7T were C16 : 0 and summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c). The major respiratory quinone was menaquinone-6 (MK-6) and the major polar lipids were phosphatidylethanolamine (PE), phosphatidylmonomethylethanolamine (PMME), phosphatidyldimethylethanolamine (PDME), phosphatidylcholine (PC) and diphosphatidylglycerol (DPG). The genomic DNA G+C content of strain E7T was 52.8 mol%. On the basis of phylogenetic inference and phenotypic characteristics, it is proposed that strain E7T represents a novel species of the genus Gimesia, for which the name Gimesia benthica sp. nov. is proposed. The type strain is E7T (=CGMCC 1.16119T=KCTC 72737T).

Asunto(s)

Filogenia , Planctomycetales/clasificación , Agua de Mar/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Océano Índico , Hibridación de Ácido Nucleico , Fosfolípidos/química , Planctomycetales/aislamiento & purificación , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/química

RESUMEN

A novel Gram-stain-negative, aerobic, motile by peritrichous flagella, oval to rod-shaped bacterium, designated strain 2CG4T, was isolated from a deep-sea water sample collected from the Northwest Indian Ocean. The results of phylogenetic analysis of both 16S rRNA gene and RpoC protein sequences indicated that this strain was affiliated with the genus Halovulum in the Amaricoccus clade of the family Rhodobacteraceae of the class Alphaproteobacteria, sharing 95.3 % similarity at the 16S rRNA gene sequence level with the type strain of Halovulum dunhuangense YYQ-30T, the only species in the genus Halovulum. The predominant fatty acids (>10 %) of 2CG4T were summed feature 8 (C18 : 1ω7c and/ or C18 : 1ω6c; 61.1 %) and cyclo-C19 : 0ω8c (15.6 %). The polar lipids of 2CG4T were phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine and sulfoquinovosyldiacylglycerol. The only isoprenoid quinone of 2CG4T was ubiquinone-10. The DNA G+C content of 2CG4T was determined to be 69.4 %. The central gene pufLM for the photosynthetic reaction was not detected. No growth occurred for 2CG4T in the absence of NaCl. On the basis of these data, it is concluded that the 2CG4T represents a novel species of the genus Halovulum, for which the name Halovulum marinum sp. nov. is proposed. The type strain is 2CG4T (=CGMCC 1.16468T=JCM 32611T).

Asunto(s)

Filogenia , Rhodobacteraceae/clasificación , Agua de Mar/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Genes Bacterianos , Océano Índico , Fosfolípidos/química , ARN Ribosómico 16S/genética , Rhodobacteraceae/aislamiento & purificación , Análisis de Secuencia de ADN , Ubiquinona/análogos & derivados , Ubiquinona/química

RESUMEN

Lung adenocarcinoma is one of the most common types of lung cancer, and patients with epidermal growth factor receptor (EGFR) mutation-positive can be intervened with EGFR-TKI therapy to achieve longer survival. AURA3 study showed that patients resistant with the first generation of EGFR-TKI and with T790M mutation still received longer progression-free survival (PFS) after treatment with the third generation of EGFR-TKI osimertinib, and osimertinib also had a good effect on brain metastasis. Moreover, the FLAURA study published by the European Society of Medical Oncology (ESMO) in 2019 showed that the first line use of osimertinib could achieve a PFS of 18.9 months. In recent years, researches on lung cancer seem like blooming flowers. The new treatment mode for lung cancer treatment such as anti-angiogenic drugs, immunotherapy programs has satisfactory efficacy either alone or in combination. Notably, patients with lung adenocarcinoma often have single or multiple bone metastasis, which brings great suffering to patients, especially when metastases occurred in the weight-bearing bone. However, there is no solid evidence to prove that chemotherapy, targeted therapy, anti-angiogenic drugs, or immunotherapy have long-term efficacy in bone metastasis of lung adenocarcinoma. The present strategies for bone metastasis of lung cancer include of: palliative care, analgesia, improvement of bone metabolism, local radiotherapy, and radionuclide therapy. However, by far, no medical treatment has a significant advantage in inhibiting the course of bone metastasis in lung cancer at the source. In this case, patient with advanced lung adenocarcinoma and EGFR mutation was resistant with the first generation of EGFR-TKI treatment, and after detection of T790M mutation, we switched to osimertinib for primary disease control, bone metastasis was still obvious, and there was still no obvious effect after pain relief, bone metabolism improvement and local radiotherapy. This case is reported to suggest that further efforts in anti-tumor and palliative treatment in bone metastasis of lung adenocarcinoma are urgently needed.

RESUMEN

Solanum nigrum L. (Longkui) is one the most widely used anticancer herbs in traditional Chinese medicine. α­Solanine is an important ingredient of S. nigrum L. and has demonstrated anticancer properties in various types of cancer. However, the effects of α­solanine on colorectal cancer remain elusive. The aim of the present study was to assess the effects of α­solanine on human colorectal cancer cells. The results demonstrated that α­solanine inhibited the proliferation of RKO cells in a dose­ and time­dependent manner. In addition, α­solanine arrested the cell cycle at the G0/G1 phase and suppressed the expression levels of cyclin D1 and cyclin­dependent kinase 2 in RKO cells. α­Solanine induced apoptosis of RKO cells, as indicated by morphological changes and positive Annexin­FITC/propidium iodide staining. Additionally, α­solanine activated caspase­3, ­8 and ­9 in RKO cells, which contributed to α­solanine­induced apoptosis. α­Solanine also increased the generation of reactive oxygen species, which contributed to caspase activation and induction of apoptosis. α­Solanine inhibited the migration, invasion and adhesion of RKO cells, as well as the expression levels and activity of matrix metalloproteinase (MMP)­2 and MMP­9. In addition, α­solanine inhibited cell proliferation, activated caspase­3, ­8 and ­9, induced apoptosis, and inhibited the migration and invasion of HCT­116 cells. Furthermore, α­solanine inhibited tumor growth and induced apoptosis in vivo. These findings demonstrated that α­solanine effectively suppressed the growth and metastatic potential of human colorectal cancer.

Asunto(s)

Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Ciclina D1/metabolismo , Quinasa 2 Dependiente de la Ciclina/metabolismo , Solanina/administración & dosificación , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/metabolismo , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Humanos , Masculino , Ratones , Metástasis de la Neoplasia , Solanina/química , Solanina/farmacología , Factores de Tiempo , Ensayos Antitumor por Modelo de Xenoinjerto

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Jinfukang has long been used for the clinical treatment of lung cancer. Previous studies have shown that Jinfukang can induce the apoptosis of circulating tumor cells by intervening ROS-mediated DNA damage pathway. However, whether Jinfukang can inhibit the metastasis of circulating tumor cells and its mechanism are still unclear. AIM OF THE STUDY: To further investigate the mechanism of Jinfukang in anti-metastasis of lung cancer from the perspective of intervention of tumor exosomes. MATERIALS AND METHODS: The invadopodia formation was determined with immunofluorescence. Invasion and migration were detected using the Transwell assay. Ultracentrifugation was used to isolate exosomes. Exosomes were characterized by electron microscopy, nanoparticle tracking analysis and immunoblotting, and the protein profile was evaluated by proteomic analysis. The molecular functions, biological processes and signaling pathway enrichment analysis were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Key differentially expressed proteins were verified by Western blot. RESULTS: Jinfukang can inhibit the expression of MMP14, cortactin, Tks5 and the formation of invadopodia of CTC-TJH-01 cells. Furthermore, Jinfukang can significantly inhibit the invasion and migration of CTC-TJH-01 cells. The diameter of exosomes extracted from the CTC-TJH-01 cells treated by Jinfukang was 30-100 nm, and the exosomal markers CD63, CD81 and TSG101 were expressed. We identified 680 deferentially expressed proteins. Gene oncology analysis indicated that exosomes were mostly derived from plasma membrane and mainly involved in protein localization and intracellular signaling. The ingenuity pathway analysis showed that the EGF pathway was significantly inhibited, whereas the GP6 signaling pathway was significantly activated. We also confirmed that Jinfukang inhibited the expression of EGF pathway-related proteins in CTC-TJH-01 cells. Besides, when EGF was used to activate EGF signaling pathway, the inhibition of Jinfukang on CTC cell metastasis was reversed. CONCLUSION: Jinfukang inhibits the metastasis of CTC-TJH-01 cells through the EGF pathway.

Asunto(s)

Medicamentos Herbarios Chinos/farmacología , Exosomas/efectos de los fármacos , Exosomas/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Células Neoplásicas Circulantes/efectos de los fármacos , Células Neoplásicas Circulantes/metabolismo , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , MicroARNs/metabolismo , Proteómica/métodos , Transducción de Señal/efectos de los fármacos