RESUMO
Chemotherapy is a crucial treatment for colorectal tumors. However, its efficacy is restricted by chemoresistance. Recently, Golgi dispersal has been suggested to be a potential response to chemotherapy, particularly to drugs that induce DNA damage. However, the underlying mechanisms by which Golgi dispersal enhances the capacity to resist DNA-damaging agents remain unclear. Here, we demonstrated that DNA-damaging agents triggered Golgi dispersal in colorectal cancer (CRC), and cancer stem cells (CSCs) possessed a greater degree of Golgi dispersal compared with differentiated cancer cells (non-CSCs). We further revealed that Golgi dispersal conferred resistance against the lethal effects of DNA-damaging agents. Momentously, Golgi dispersal activated the Golgi stress response via the PKCα/GSK3α/TFE3 axis, resulting in enhanced protein and vesicle trafficking, which facilitated drug efflux through ABCG2. Identification of Golgi dispersal indicated an unexpected pathway regulating chemoresistance in CRC.
Assuntos
Neoplasias Colorretais , Resistencia a Medicamentos Antineoplásicos , Complexo de Golgi , Células-Tronco Neoplásicas , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Humanos , Complexo de Golgi/metabolismo , Complexo de Golgi/efeitos dos fármacos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Dano ao DNA , Camundongos , Camundongos Nus , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêuticoRESUMO
Abnormal nuclear enlargement is a diagnostic and physical hallmark of malignant tumors. Large nuclei are positively associated with an increased risk of developing metastasis; however, a large nucleus is inevitably more resistant to cell migration due to its size. The present study demonstrated that the nuclear size of primary colorectal cancer (CRC) cells at an advanced stage was larger than cells at an early stage. In addition, the nuclei of CRC liver metastases were larger than those of the corresponding primary CRC tissues. CRC cells were sorted into large-nucleated cells (LNCs) and small-nucleated cells (SNCs). Purified LNCs exhibited greater constricted migratory and metastatic capacity than SNCs in vitro and in vivo. Mechanistically, ErbB4 was highly expressed in LNCs, which phosphorylated lamin A/C at serine 22 via the ErbB4-Akt1 signaling pathway. Furthermore, the level of phosphorylated lamin A/C was a negative determinant of nuclear stiffness. Taken together, CRC LNCs possessed greater constricted migratory and metastatic potential than SNCs due to ErbB4-Akt1-mediated lamin A/C phosphorylation and nuclear softening. These results may provide a potential treatment strategy for tumor metastasis by targeting nuclear stiffness in patients with cancer, particularly CRC.
Assuntos
Núcleo Celular , Neoplasias Colorretais , Lamina Tipo A , Proteínas Proto-Oncogênicas c-akt , Receptor ErbB-4 , Transdução de Sinais , Animais , Feminino , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Movimento Celular , Núcleo Celular/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Lamina Tipo A/metabolismo , Camundongos Nus , Metástase Neoplásica , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-4/metabolismo , Receptor ErbB-4/genéticaRESUMO
In recent years, the accumulation ability of heavy metals in sediment has become a key indicator for sediment pollution prevention and control. The adsorption-desorption processes of typical heavy metal pollutants in sediments under different conditions were explored and relied in this article. In addition, different binary competitive adsorption systems were designed to study the competitive adsorption properties of heavy metal contaminants, The quasi-secondary kinetic model simulated the adsorption kinetic process. The sediment adsorption rates for heavy metals were (in descending order) Cu, Pb, Cd, Zn. The Elovich equation simulated the desorption kinetics process better, and the sediment desorption rates for heavy metals were (in descending order) Cd, Cu, Zn, Pb. The average free adsorption energy E of heavy metals was within the range of 8-16 kJâmol-1. After the removal of organic matter, the ability of the sediment to sequester heavy metals decreases, The binary competitive adsorption results showed that the presence of interfering ions had the greatest effect on Cd and the least effect on Pb. The adsorption and desorption of the four heavy metals by the sediments in the submerged zone increased with the increase of temperature, and the ratio of desorption to adsorption also increased therewith: the adsorptions of heavy metals by the sediments were all spontaneous processes (under heat absorption reactions). The presence of organic matter can increase the ability of the sediment to sequester Cd, Pb, Cu, and Zn. Additionally, heavy metals exhibited significant selective adsorption properties.
Assuntos
Poluentes Ambientais , Metais Pesados , Poluentes Químicos da Água , Adsorção , Cádmio , Chumbo , Sedimentos Geológicos , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Metais Pesados/análise , China , Medição de RiscoRESUMO
BACKGROUND: Anastomotic leakage (AL) is a fatal complication in patients with rectal cancer after undergoing anterior resection. However, the role of abdominal composition in the development of AL has not been studied. AIM: To investigate the relationship between abdominal composition and AL in rectal cancer patients after undergoing anterior resection. METHODS: A retrospective case-matched cohort study was conducted. Complete data for 78 patients with AL were acquired and this cohort was defined as the AL group. The controls were matched for the same sex and body mass index (± 1 kg/m2). Parameters related to abdominal composition including visceral fat area (VFA), subcutaneous fat area (SFA), subcutaneous fat thickness (SFT), skeletal muscle area (SMA), skeletal muscle index (SMI), abdominal circumference (AC), anterior to posterior diameter of abdominal cavity (APD), and transverse diameter of abdominal cavity (TD) were evaluated based on computed tomography (CT) images using the following Hounsfield Unit (HU) thresholds: SFA: -190 to -30, SMA: -29 to 150, and VFA: -150 to -20. The significance of abdominal composition-related parameters was quantified using feature importance analysis; an artificial intelligence method was used to evaluate the contribution of each included variable. RESULTS: Two thousand two hundred and thirty-eight rectal cancer patients who underwent anterior resection from 2010 to 2020 in a large academic hospital were investigated. Finally, 156 cases were enrolled in the study. Patients in the AL group showed longer operative time (225.03 ± 55.29 vs 207.17 ± 40.80, P = 0.023), lower levels of preoperative hemoglobin (123.32 ± 21.17 vs 132.60 ±1 6.31, P = 0.003) and albumin (38.34 ± 4.01 vs 40.52 ± 3.97, P = 0.001), larger tumor size (4.07 ± 1.36 vs 2.76 ± 1.28, P < 0.001), and later cancer stage (P < 0.001) compared to the controls. Patients who developed AL exhibited a larger VFA (125.68 ± 73.59 vs 97.03 ± 57.66, P = 0.008) and a smaller APD (77.30 ± 23.23 vs 92.09 ± 26.40, P < 0.001) and TD (22.90 ± 2.23 vs 24.21 ± 2.90, P = 0.002) compared to their matched controls. Feature importance analysis revealed that TD, APD, and VFA were the three most important abdominal composition-related features. CONCLUSION: AL patients have a higher visceral fat content and a narrower abdominal structure compared to matched controls.
RESUMO
In this study, four new species of Russula subg. Brevipedum collected from China are described based on morphological characteristics and molecular evidence. Russula brevispora has a white body whose whole parts often stain brownish-orange or grayish-orange, extremely crowded lamellae with the presence of lamellulae, basidiospores with low warts and an inamyloid suprahilar spot, and clavate or lageniform hymenial cystidia often with a papillary or submoniliform appendage. Russula flavescens is characterized by a white pileus often turning yellowish brown when touched, white lamellae turning brown or light orange, basidiospores with an inamyloid suprahilar spot, and fusiform hymenial cystidia often with an appendage. Russula longicollis is morphologically characterized by a white pileus, turning grayish orange when bruised, white lamellae turning pale yellow when bruised, basidiospores with isolated warts and an amyloid suprahilar spot, and fusiform hymenial cystidia usually with a long appendage. Russula pseudojaponica has a yellowish-brown pileus center, yellowish lamellae unchanging when bruised, basidiospores with low warts and an inamyloid suprahilar spot, clavate hymenial cystidia often with a papillary appendage, and clavate pileocystidia with granulose contents. Phylogenetic analyses showed that R. flavescens, R. brevispora, and R. pseudojaponica are members of the subsect. Pallidosporinae, whereas R. longicollis belongs to subsect. Lactarioideae, and is somewhat related to R. leucocarpa.
RESUMO
Fungi associated with black point were isolated from three highly susceptible wheat genotypes in the North China Plain. The 21 isolates represented 11 fungal genera. The most prevalent genera were Alternaria (isolation frequency of 56.7%), Bipolaris (16.1%), and Fusarium (6.0%). The other eight genera were Curvularia, Aspergillus, Cladosporium, Exserohilum, Epicoccum, Nigrospora, Penicillium, and Ulocladium; their isolation frequencies ranged from 0.8 to 4.8%. The pathogenicity of the isolates was individually assessed in the greenhouse by inoculating wheat plants with spore suspensions. Ten of the 21 isolates caused significantly higher incidences of black point than that the controls. These isolates belonged to eight fungal species (A. alternata, B. sorokiniana, B. crotonis, B. cynodontis, C. spicifera, F. equiseti, E. rostratum, and E. sorghinum) based on morphological traits and phylogenetic analysis. The average incidences of black point in the eight fungal species were 32.4, 54.3, 43.0, 41.9, 37.2, 38.8, 50.1, and 34.1%, respectively. B. sorokiniana and A. alternata were determined to be the most important pathogens in the North China Plain based on fungal prevalence and symptom severity. This study is the first to identify E. rostratum as a major pathogen causing black point in wheat.