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Recent reports suggest pain from surgical injury may influence the risks associated with exposure to opioids. In mice, hind-paw incision attenuates morphine-primed reinstatement due to kappa opioid receptor activation by dynorphin. In this focused group of studies, we examined the hypotheses that kappa-opioid receptor activation in the nucleus accumbens mediates attenuated drug- primed reinstatement after incisional surgery, and the G-protein biased mu-opioid agonist, oliceridine, leads to less priming of the dynorphin effect in comparison to morphine. To address these hypotheses, adult C57BL/6 male mice underwent intracranial cannulation for administration of the selective kappa-opioid antagonist norBNI directly into the nucleus accumbens. After recovery, they were conditioned with morphine or oliceridine after hind-paw incisional injury, then underwent extinction followed by opioid-primed reinstatement. Intra-accumbal administration of norBNI was carried out prior to testing. The nucleus accumbens and medial prefrontal cortex were extracted and analyzed for expression of prodynorphin. We observed that animals conditioned with morphine in the setting of incisional injury demonstrated blunted responses to opioid-primed reinstatement, and that the blunted responses were reversed with intra-accumbal norBNI administration. Persistently elevated levels of prodynorphin expression in the medial prefrontal cortex and nucleus accumbens were observed in the incised morphine-treated animals. However, both behavioral and molecular changes were absent in animals with incisional injury conditioned with oliceridine. These findings suggest a role for prodynorphin expression in the nucleus accumbens with exposure to morphine after surgery that may protect individuals from relapse not shared with biased mu- opioid receptor agonists.
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The aim of the present study was to investigate the effects of exercises with different durations and intensities on mitochondrial autophagy and FUNDC1 in rat skeletal muscles. Sixty male Sprague-Dawley rats were randomly divided into 2- and 4-week control groups (Con), moderate-intensity exercise groups (M-ex groups, treadmill exercise, 16 m/min, 1 h/d, 6 d/week), and high-intensity exercise groups (Hi-ex groups, treadmill exercise, 35 m/min, 20 min/d, 6 d/week). The bilateral soleus muscles were separated after the intervention, and paraffin sections were prepared for transmission electron microscopy. ELISA method was used to detect the content of citrate synthase (CS). The co-localizations of microtubule-associated protein 1 light chain 3 (LC3)/cytochrome c oxidase IV (COX-IV), FUNDC1/COX-IV and LC3/FUNDC1 were observed by immunofluorescent staining in frozen sections. The skeletal muscle mitochondria were extracted, and the expression of autophagy-related proteins, including AMPKα, p-AMPKα, Unc-51 like kinase 1 (ULK1), FUNDC1, LC3 and p62, were detected by Western blot. The results showed that exercise increased mitochondrial function, i.e. peroxisome proliferator-activated receptor γ co-activator-1α (PGC-1α), COX-I protein expression levels and CS content. There was no difference of mitochondrial function parameters between 2-week M-ex and 2-week Hi-ex groups, while mitochondrial function of 4-weeks Hi-ex group was significantly lower than that of 4-week M-ex group. Under the same exercise intensity, mitochondrial autophagy activation in skeletal muscle of 4-week exercise was higher than that in 2-week exercise group; Under the same duration of exercise, mitochondrial autophagy activation of Hi-ex group was higher than that in M-ex group. Both 2- and 4-week exercise intervention increased LC3/COX-IV, COX-IV/FUNDC1, and FUNDC1/LC3 co-localizations. Exercise increased LC3-II/LC3-I ratio, down-regulated p62 protein expression level, up-regulated FUNDC1, ULK1 protein expression levels and AMPKα phosphorylation, and the changes of these proteins in 4-week Hi-ex group were significantly greater than those in 4-week M-ex group. These results suggest exercise induces mitochondrial autophagy in skeletal muscles, and the activity of autophagy is related to the duration and intensity of exercise. The induction mechanism of exercise may involve the mediation of FUNDC1 expression through AMPK-ULK1 pathway.
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Autofagia , Mitocondrias , Animales , Terapia por Ejercicio , Humanos , Masculino , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/fisiología , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/fisiología , Músculo Esquelético/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Compared to the nitrogen-reaction based pH optical responsive compounds, oxygen-reaction related pH sensors have attracted less attention. In this paper, hemicyanine based pH probes are designed by establishing the equilibrium between phenolate and phenol, and their reversible absorption and emission responses towards pH are evaluated. The indolium-phenol based tetramethylene hemicyanine (1a) has colorimetric responses at 455 and 578 nm due to the protonating and deprotonating processes; its emission spectra shows ratiometric changes at 594 and 654 nm with large Stokes shifts under acidic (139 nm) and basic conditions (76 nm). The bromide substituent of the hemicyanine (1b) has a lower pKa value compared with unsubstituted hemicyanine (1a), which suggests that adjustable pKa can be achieved by the modification of electron withdrawing groups. The theoretical calculations based on the density functional theory (DFT) were also used to explain the optical properties. Moreover, the in cellulo fluorescence imaging shows that the hemicyanine (1a) can be used for the detection of intracellular pH levels.
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Carbocianinas/química , Colorimetría/métodos , Fenoles/química , Concentración de Iones de Hidrógeno , Sondas Moleculares/química , Estructura MolecularRESUMEN
As an important forestry pest, Coronaproctus castanopsis (Monophlebidae) has caused serious damage to the globally valuable Gutianshan ecosystem, China. In this study, we assembled the first chromosome-level genome of the female specimen of C. castanopsis by merging BGI reads, HiFi long reads and Hi-C data. The assembled genome size is 700.81 Mb, with a scaffold N50 size of 273.84 Mb and a contig N50 size of 12.37 Mb. Hi-C scaffolding assigned 98.32% (689.03 Mb) of C. Castanopsis genome to three chromosomes. The BUSCO analysis (n = 1,367) showed a completeness of 91.2%, comprising 89.2% of single-copy BUSCOs and 2.0% of multicopy BUSCOs. The mapping ratio of BGI, second-generation RNA, third-generation RNA and HiFi reads are 97.84%, 96.15%, 97.96%, and 99.33%, respectively. We also identified 64.97% (455.3 Mb) repetitive elements, 1,373 non-coding RNAs and 10,542 protein-coding genes. This study assembled a high-quality genome of C. castanopsis, which accumulated valuable molecular data for scale insects.
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Agricultura Forestal , Genoma de los Insectos , Hemípteros , Femenino , Cromosomas , Ecosistema , Filogenia , ARN , Hemípteros/genéticaRESUMEN
Soft ticks (Ixodida: Argasidae) are ectoparasites of terrestrial vertebrates with worldwide distributions. As one representative group of Argasidae, the genus Argas has an important vectorial role in transmitting zoonotic diseases. However, our knowledge of the subgenus Argas in China is still limited, as most literature only lists occurrence records or describes specific case reports without providing detailed morphological characteristics and further molecular data. This study aims to characterize Argas vulgaris through complete mitochondrial sequencing and morphological diagnostic techniques based on a batch of adult specimens collected from Ningxia Hui Autonomous Regions (NXHAR), North China. The morphology and microstructures of Ar. vulgaris and other lectotypes of argasid ticks in the subgenus Argas were also observed using a stereomicroscope. Following DNA extraction and sequencing, a complete mitochondrial sequence of Ar. vulgaris was assembled and analyzed within a phylogenetic context. The 14,479 bp mitogenome of Ar. vulgaris consists of 37 genes, including 13 genes for protein coding, two for ribosomal RNA, 22 for transfer RNA, and one for control region (D-loops). Phylogenetic analysis of Ar. vulgaris showed 98.27%-100% nucleotide identity with Ar. japonicus, indicating a close relationship between the two tick species. The morphological diagnostic features to differentiate Ar. vulgaris from other ticks within the subgenus Argas included the location of the anus and setae on the anterior lip of the female genital aperture. This study provided high-resolution scanning electron microscope images of female Ar. vulgaris and corresponding molecular data, representing valuable resources for future accurate species identification.
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The continual emergence of tick-borne rickettsioses has garnered widespread global attention. Candidatus Rickettsia barbariae (Candidatus R. barbariae), which emerged in Italy in 2008, has been detected in humans from northwestern China. However, the lack of Candidatus R. barbariae genome and isolated strains limits the understanding of its biological characteristics and genomic features. Here, we isolated the Rickettsia for the first time from eggs of Rhipicephalus turanicus in northwestern China, and assembled its whole genome after next-generation sequencing, so we modified the proposed name to Rickettsia barbariae (R. barbariae) to conform to the International Code of Nomenclature of Prokaryotes. Phylogenetic analysis based on the whole genome revealed that it was most closely related to the pathogenic Rickettsia parkeri and Rickettsia africae. All virulence factors, present in the pathogenic spotted fever group rickettsiae, were identified in the R. barbariae isolate. These findings highlight the pathogenic potential of R. barbariae and the necessity for enhanced surveillance of the emerging Rickettsia in the human population.
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Genoma Bacteriano , Filogenia , Rickettsia , Rickettsia/genética , Rickettsia/aislamiento & purificación , Rickettsia/clasificación , Animales , China , Rhipicephalus/microbiología , Humanos , Infecciones por Rickettsia/microbiología , Factores de Virulencia/genética , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento , Secuenciación Completa del Genoma , Óvulo/microbiologíaRESUMEN
Ticks are important vectors of zoonotic pathogens, and represent an increasing threat for human and animal health. Considering the complex natural environments of Ningxia Hui Autonomous Region, China, we expect the diverse tick species in this region. Here, we conduct a field survey on parasitic and host-seeking ticks. A total of 10,419 ticks were collected, which belonged to nine species of four genera. There were significant differences in terms of vegetation index, altitude, and seven climatic factors among the four tick genera -Hyalomma, Dermacentor, Haemaphysalis, and Ixodes, except between Haemaphysalis and Ixodes, where no significant differences were observed in these factors. The ecological niche modelling revealed that the suitable habitats for Hyalomma asiaticum was in the northwest Ningxia, with annual ground surface temperature as the most important factor. The suitable area for Dermacentor nuttalli was in the southwest and eastern regions of Ningxia with elevation as the highest contribution. D. silvarum was best suited to the southern Ningxia also with elevation as the most important factor. The four tick species including Haemaphysalis longicornis, Hae. qinghaiensis, Hae. japonica, and Ixodes persulcatus were best suited to the southernmost Ningxia with annual precipitation as the main factors for Hae. longicornis and elevation for the other three ticks. The results of predicted potential distribution of different tick species provide a scientific basis for the prevention and control of ticks and tick-borne diseases in the region. Furthermore, the subsequent impacts of the Greening Program to regain forests and grasslands from former agricultural lands in Ningxia on tick population dynamics deserve further investigation.
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BACKGROUND: Haemaphysalis longicornis is drawing attentions for its geographic invasion, extending population, and emerging disease threat. However, there are still substantial gaps in our knowledge of viral composition in relation to genetic diversity of H. longicornis and ecological factors, which are important for us to understand interactions between virus and vector, as well as between vector and ecological elements. RESULTS: We conducted the meta-transcriptomic sequencing of 136 pools of H. longicornis and identified 508 RNA viruses of 48 viral species, 22 of which have never been reported. Phylogenetic analysis of mitochondrion sequences divided the ticks into two genetic clades, each of which was geographically clustered and significantly associated with ecological factors, including altitude, precipitation, and normalized difference vegetation index. The two clades showed significant difference in virome diversity and shared about one fifth number of viral species that might have evolved to "generalists." Notably, Bandavirus dabieense, the pathogen of severe fever with thrombocytopenia syndrome was only detected in ticks of clade 1, and half number of clade 2-specific viruses were aquatic-animal-associated. CONCLUSIONS: These findings highlight that the virome diversity is shaped by internal genetic evolution and external ecological landscape of H. longicornis and provide the new foundation for promoting the studies on virus-vector-ecology interaction and eventually for evaluating the risk of H. longicornis for transmitting the viruses to humans and animals. Video Abstract.
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Ixodidae , Phlebovirus , Garrapatas , Animales , Humanos , Ixodidae/genética , Haemaphysalis longicornis , Viroma/genética , Filogenia , Phlebovirus/genéticaRESUMEN
Theileria, a tick-borne intracellular protozoan, can cause infections of various livestock and wildlife around the world, posing a threat to veterinary health. Although more and more Theileria species have been identified, genomes have been available only from four Theileria species to date. Here, we assembled a whole genome of Theileria luwenshuni, an emerging Theileria, through next-generation sequencing of purified erythrocytes from the blood of a naturally infected goat. We designated it T. luwenshuni str. Cheeloo because its genome was assembled by the researchers at Cheeloo College of Medicine, Shandong University, China. The genome of T. lunwenshuni str. Cheeloo was the smallest in comparison with the other four Theileria species. T. luwenshuni str. Cheeloo possessed the fewest gene gains and gene family expansion. The protein count of each category was always comparable between T. luwenshuni str. Cheeloo and T. orientalis str. Shintoku in the Eukaryote Orthologs annotation, though there were remarkable differences in genome size. T. luwenshuni str. Cheeloo had lower counts than the other four Theileria species in most categories at level 3 of Gene Ontology annotation. Kyoto Encyclopedia of Genes and Genomes annotation revealed a loss of the c-Myb in T. luwenshuni str. Cheeloo. The infection rate of T. luwenshuni str. Cheeloo was up to 81.5% in a total of 54 goats from three flocks. The phylogenetic analyses based on both 18S rRNA and cox1 genes indicated that T. luwenshuni had relatively low diversity. The first characterization of the T. luwenshuni genome will promote better understanding of the emerging Theileria. IMPORTANCE Theileria has led to substantial economic losses in animal husbandry. Whole-genome sequencing data of the genus Theileria are currently limited, which has prohibited us from further understanding their molecular features. This work depicted whole-genome sequences of T. luwenshuni str. Cheeloo, an emerging Theileria species, and reported a high prevalence of T. luwenshuni str. Cheeloo infection in goats. The first assembly and characterization of T. luwenshuni genome will benefit exploring the infective and pathogenic mechanisms of the emerging Theileria to provide scientific basis for future control strategies of theileriosis.
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Theileria , Theileriosis , Animales , Bovinos , Theileria/genética , Filogenia , Cabras , GenómicaRESUMEN
A new type of handshape tuina-cupping instrument is developed to overcome the shortcomings of traditional cupping therapy, such as indentation and pain, and simulates the tuina manipulation, so as to realize the combination of cupping therapy and tuina manipulation. The handshape tuina-cupping instrument has a trumpet-shaped, silica gel edge. At the same time, the finger-belly shape is added at the cupping edge to simulate the shape of fingers during tuina. Under the action of air suction and deflation of pulsating airflow, the purpose of simulating tuina manipulation is achieved, and the indentation and pain caused by the handshape tuina-cupping instrument is significantly less than that of the traditional cupping instrument.
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Masaje , Medicina Tradicional China , Humanos , Dolor , TecnologíaRESUMEN
Bisphenol A (BPA) is one of the most prevalent chemicals in many products used on a daily basis, making human exposure to it incredibly pervasive and raising concerns about its health consequences. One area of research focus has been the role of BPA exposure in promoting the development of ovarian cancer; however, the doses used in most of previous studies are relatively high and most likely exceed physiologically relevant levels. At the same time, few studies have described potential mechanisms underlying the link between BPA and increased cancer risk. To address these concerns we investigated the mechanism(s) by which low concentrations of BPA promote proliferation and energy metabolism in the human ovarian cancer cell line OVCAR-3. We found that even sub-toxic BPA concentrations not only drove increased OVCAR-3 cell proliferation but also promoted glycolysis-based metabolism, as evidenced by elevated cell viability, accelerated cell proliferation, increased levels of intracellular ATP, lactate, and pyruvic acid. Importantly, all of these effects were estrogen receptor α (ERα) dependent, as siRNA-mediated ERα silencing decreased BPA-induced proliferation, pinpointing the crucial role of ERα-conducted signaling in BPA-induced biological effects. Together, our findings revealed a new mechanism through which BPA promoted cell proliferation by reinforcing glycolysis-based energy production dependent on ER signaling. This study would thus open a new path to understand BPA-induced biological effects on tumor cells.
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Compuestos de Bencidrilo/farmacología , Proliferación Celular/efectos de los fármacos , Receptor alfa de Estrógeno/metabolismo , Glucólisis/efectos de los fármacos , Neoplasias Ováricas/patología , Fenoles/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Estrógenos no Esteroides/farmacología , Femenino , Humanos , Neoplasias Ováricas/metabolismo , Receptores de Estrógenos/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Objective The ideal agents for conscious sedation during ambulatory inguinal hernia repair are still unclear. We aimed to compare the analgesic, sedative, haemodynamic, and side effects of dexmedetomidine with those of propofol in combination with fentanyl for conscious sedation in patients undergoing inguinal hernia repair. Methods Eighty patients undergoing unilateral inguinal hernia repair were prospectively randomized to receive either dexmedetomidine (n = 40) or propofol (n = 40). Dexmedetomidine and propofol dosages were adjusted to maintain the targeted level of sedation. Results After administration of sedative drugs, patients who received dexmedetomidine had a significantly lower heart rate. The intraoperative requirement of fentanyl was significantly lower in patients who received dexmedetomidine compared with patients who received propofol. Administration of dexmedetomidine was associated with a reduced postoperative pain score, longer time for onset of sedation, and a slightly longer recovery time. No serious adverse events occurred in either group. The patients' overall satisfaction score was comparable between the two groups. Conclusion Dexmedetomidine is an effective adjuvant when co-administered with fentanyl for conscious sedation in patients who undergo inguinal hernia repair. Administration of dexmedetomidine decreases the requirement of fentanyl and the pain score, but slightly prolongs the time to sedation and recovery.
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Analgésicos no Narcóticos , Anestésicos Intravenosos , Sedación Consciente/métodos , Dexmedetomidina , Hernia Inguinal/cirugía , Dolor Postoperatorio/prevención & control , Propofol , Anciano , Anciano de 80 o más Años , Combinación de Medicamentos , Femenino , Fentanilo , Frecuencia Cardíaca/efectos de los fármacos , Hernia Inguinal/patología , Humanos , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/fisiopatología , Satisfacción del Paciente/estadística & datos numéricos , Estudios ProspectivosRESUMEN
PURPOSE: To identify the characteristics and function of the truncated cadherin cDNA which encodes a soluble molecule containing the sequence of VE-cadherin extracellular domain repeats from repeat 1 to 4 (designated as CED1-4) and a secreting signal peptide at N terminal. METHODS: A pMSCV/CED1-4 vector was constructed. Recombinant retrovirus ReCED1-4 and ReEmpty were produced by 293 package cells and transfected into MDA-MB435 human breast cancer cells. The expression of CED1-4 in transfectants and their supernatant was analyzed by RT-PCR and Western blot, respectively. MDA-MB435 cell proliferation assays were performed in vitro and in vivo. CED-14-induced apoptosis was demonstrated using Annexin V binding, TUNEL and caspase 3 assays. The expression of integrin beta1 and c-fos mRNA was detected by RT-PCR. RESULTS: The constructed soluble CED1-4 encoded 484 amino acids and a secreting signal peptide (27 amino acids). CED1-4 was expressed by MDA-MB435/CED1-4 cells, and detected in the supernatant of CED1-4 tranfectants. CED1-4 transfection significantly inhibited the growth of MDA-MB435 cells in vitro and in vivo. About 22-fold increase in the early apoptotic cells in MDA-MB435/CED1-4 cells was observed as compared with MDA-MB435/empty cells. Increased activity of caspase 3 in MDA-MB435/CED1-4 cells was more than two times as compared with that of the control cells. Interestingly, integrin beta1 transcriptional level in MDA-MB435/CED1-4 cells was down-regulated as compared with control cells. The resistance of fibronectin to CED1-4 apoptotic inducibility was confirmed by detection of caspase 3. The blockage of c-fos transcriptional expression was detected in MDA-MB435/CED1-4 cells. CONCLUSIONS: The soluble truncated cadherin may be considered an apoptotic inducer and growth inhibitor in the MDA-MB435 breast carcinoma cell line. Down-regulation of integrin beta1 and blockage of c-fos expression may be related to CED1-4-induced apoptosis and growth inhibition.
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Apoptosis/genética , Neoplasias de la Mama/metabolismo , Cadherinas/genética , Carcinoma/metabolismo , Proteínas Recombinantes/genética , Proteínas Adaptadoras Transductoras de Señales , Animales , Western Blotting , Neoplasias de la Mama/genética , Cadherinas/biosíntesis , Carcinoma/genética , Caspasa 3/efectos de los fármacos , Caspasa 3/metabolismo , Línea Celular Tumoral , Proliferación Celular , Clonación Molecular , Regulación hacia Abajo/efectos de los fármacos , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/genética , Técnicas de Transferencia de Gen , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas de la Membrana/genética , Ratones , Ratones Desnudos , Proteínas Proto-Oncogénicas c-fos/genética , ARN Mensajero/genética , Proteínas Recombinantes/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Solubilidad , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Reduced expression levels of caveolin1 (Cav1) in tumor stromal fibroblasts influences the occurrence and progression of tumors, particularly in breast cancer, but the relevant molecular mechanism is unclear. The present study aimed to clarify the potential mechanism underlying the promotion of tumor growth by reduced Cav1 expression levels, by investigating Cav1targeted molecules in fibroblasts and breast cancer cells. The expression of growth factors in the ESF fibroblast cell line transfected with Cav1 small interfering RNA (siRNA) was examined. The expression of apoptotic regulators in the BT474 breast cancer cell line that was cocultured with the fibroblasts, was also investigated. The transfection of Cav1targeting siRNA in ESF cells resulted in efficient and specific inhibition of Cav1 expression. The downregulation of Cav1 increased the expression and secretion of stromal cellderived factor1 (SDF1), epidermal growth factor (EGF) and fibroblastspecific protein1 (FSP1) in ESF cells. This resulted in the accelerated proliferation of the breast cancer cells. Tumor protein 53induced glycolysis and apoptosis regulator (TIGAR) was upregulated in the BT474 cells under the condition of coculture with Cav1 siRNA fibroblasts, while levels of reactive oxygen species (ROS) were decreased, resulting in apoptosis inhibition in the breast cancer cells. These results demonstrated that the downregulation of Cav1 promoted the growth of breast cancer cells through increasing SDF1, EGF and FSP1 in tumor stromal fibroblasts, and TIGAR levels in breast cancer cells. To the best of our knowledge, the present study supports the hypothesis that Cav1 possesses tumorsuppressor properties, with the mechanism of Cav1dependent signaling involving the regulation of SDF1, EGF, FSP1 and TIGAR.
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Caveolina 1/metabolismo , Regulación hacia Abajo , Fibroblastos/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Regulación hacia Arriba , Apoptosis , Proteínas Reguladoras de la Apoptosis , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Línea Celular Tumoral , Proliferación Celular , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Técnicas de Cocultivo , Factor de Crecimiento Epidérmico/genética , Factor de Crecimiento Epidérmico/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Monoéster Fosfórico Hidrolasas , Interferencia de ARN , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/metabolismo , Proteína de Unión al Calcio S100A4RESUMEN
Interleukin-13 (IL-13), a Th2 cytokine, plays an important role in fibrosis, inflammation, tissue hyperresponsiveness and tumor development. Although studies have demonstrated that IL-13 exerts its roles through signal transducer and activator of transcription 6 (STAT6) signaling pathway, recent studies have revealed that I kappa B kinase (IKK)/nuclear factor kappa B (NFκB) pathway may also be involved in. The aim of this study was to investigate whether IL-13 delivers signals to IKKß/NFκBp65 and whether autophagy genes are IL-13-induced the activation of NFκBp65 transcriptional targets in fibroblasts of breast tumor stroma. We examined the phosphorylation of IKKß, the activation of NFκBp65 and NFκBp65-targeted autophagy genes in fibroblasts co-cultured with breast cancer cells under the condition of IL-13 stimulation. Results of this study showed that IL-13 induced IKKß phosphorylation in the fibroblast line ESF co-cultured with breast cancer cell line BT474, and subsequently NFκBp65 was activated and aimed at beclin 1 and microtubule-associated protein 1 light chain 3 B (MAP1LC3B or LC3B) in these ESF cells. BMS345541, an inhibitor of IKK/NFκB pathway, significantly inhibited the IL-13-induced the activation of NFκB and also inhibited NFκB-targeted beclin 1 and LC3B expression. Our results suggest that IL-13 regulates beclin 1 and LC3B expression through IKKß/NFκBp65 in fibroblasts co-cultured with breast cancer cells, and IL-13 plays role in activating IKKß/NFκBp65.
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Arginine kinase plays an important role in cellular energy metabolism and is closely related to the environmental stress response in marine invertebrates. We studied the Cu(2+)-mediated inhibition and aggregation of Sepia pharaonis arginine kinase (SPAK) and found that Cu(2+) markedly inhibited the SPAK activity along with mixed-type inhibition against the arginine substrate and noncompetitive inhibition against the ATP cofactor. Spectrofluorimetry results showed that Cu(2+) induced a tertiary structure change in SPAK, resulting in exposure of the hydrophobic surface and increased aggregation. Cu(2+)-mediated SPAK aggregation followed first-order kinetics consistent with monophasic and a biphasic processes. Addition of osmolytes, including glycine and proline, effectively blocked SPAK aggregation and restored SPAK activity. Our results demonstrated the effects of Cu(2+) on SPAK catalytic function, conformation, and aggregation, as well as the protective effects of osmolytes on SPAK folding. This study provided important insights into the role of Cu(2+) as a negative effector of the S. pharaonis metabolic enzyme AK and the possible responses of cephalopods to unfavorable environmental conditions.
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Arginina Quinasa/química , Arginina Quinasa/metabolismo , Agregado de Proteínas/efectos de los fármacos , Sepia/enzimología , Adenosina Trifosfato/farmacología , Animales , Arginina Quinasa/antagonistas & inhibidores , Dicroismo Circular , Activación Enzimática/efectos de los fármacos , Glicina/farmacología , Cinética , Prolina/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Espectrometría de FluorescenciaRESUMEN
BACKGROUND: There are still no absolute parameters predicting progression of adenoma into cancer. The present study aimed to characterize functional differences on the multistep carcinogenetic process from the adenoma-carcinoma sequence. METHODS: All samples were collected and mRNA expression profiling was performed by using Agilent Microarray high-throughput gene-chip technology. Then, the characteristics of mRNA expression profiles of adenoma-carcinoma sequence were described with bioinformatics software, and we analyzed the relationship between gene expression profiles of adenoma-adenocarcinoma sequence and clinical prognosis of colorectal cancer. RESULTS: The mRNA expressions of adenoma-carcinoma sequence were significantly different between high-grade intraepithelial neoplasia group and adenocarcinoma group. The biological process of gene ontology function enrichment analysis on differentially expressed genes between high-grade intraepithelial neoplasia group and adenocarcinoma group showed that genes enriched in the extracellular structure organization, skeletal system development, biological adhesion and itself regulated growth regulation, with the P value after FDR correction of less than 0.05. In addition, IPR-related protein mainly focused on the insulin-like growth factor binding proteins. CONCLUSION: The variable trends of gene expression profiles for adenoma-carcinoma sequence were mainly concentrated in high-grade intraepithelial neoplasia and adenocarcinoma. The differentially expressed genes are significantly correlated between high-grade intraepithelial neoplasia group and adenocarcinoma group. Bioinformatics analysis is an effective way to study the gene expression profiles in the adenoma-carcinoma sequence, and may provide an effective tool to involve colorectal cancer research strategy into colorectal adenoma or advanced adenoma.
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There is limited information regarding the molecular epidemiology and antifungal susceptibilities of Candida isolates using the Neo-Sensitabs method in patients with vulvovaginal candidiasis (VVC). From August 2012 to March 2013, 301 non-pregnant patients aged 18-50 years with suspected VVC were prospectively screened at a teaching hospital in southern China. The vaginal isolates were identified by DNA sequencing of internal transcribed spacer and the D1/D2 domain. Antifungal susceptibility testing of seven antifungal agents was performed using the Neo-Sensitabs tablet diffusion method. Candida species were isolated from 186 cases (61.79â%). The most common pathogen was Candida albicans (91.4â%), followed by Candida glabrata (4.3â%), Candida tropicalis (3.2â%) and Candida parapsilosis (1.1â%). The susceptibility rates to C. albicans were higher for caspofungin, voriconazole and fluconazole than those for itraconazole, miconazole, ketoconazole and terbinafine (P<0.01). The resistance rates to C. albicans were 4.7, 6.5, 7.1, 7.6, 12.3, 27.7 and 74.7â% for caspofungin, miconazole, itraconazole, voriconazole, fluconazole, ketoconazole and terbinafine, respectively. No drugs tested apart from fluconazole exhibited differences in resistance between C. albicans and non-albicans Candida isolates. The results demonstrate that, using DNA sequencing, C. albicans is the most common isolate from Chinese patients with VVC. Caspofungin, voriconazole and fluconazole may be preferable to other azoles and terbinafine in the treatment of VVC.
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Antifúngicos/farmacología , Candida/clasificación , Candida/efectos de los fármacos , Candidiasis Vulvovaginal/microbiología , Técnicas Microbiológicas/métodos , Técnicas de Diagnóstico Molecular/métodos , Adolescente , Adulto , Candida/genética , Candida/aislamiento & purificación , China , ADN de Hongos/química , ADN de Hongos/genética , ADN Ribosómico/química , ADN Ribosómico/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Farmacorresistencia Fúngica , Femenino , Humanos , Persona de Mediana Edad , Datos de Secuencia Molecular , ARN Ribosómico/genética , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
Bisphenol A (BPA), a carbon-based synthetic compound, exhibits hormone-like properties and is present ubiquitously in the environment and in human tissues due to its widespread use and biological accumulation. BPA can mimic estrogen to interact with estrogen receptors α and ß, leading to changes in cell proliferation, apoptosis, or migration and thereby, contributing to cancer development and progression. At the genetic level, BPA has been shown to be involved in multiple oncogenic signaling pathways, such as the STAT3, MAPK, and PI3K/AKT pathways. Moreover, BPA may also interact with other steroid receptors (such as androgen receptor) and plays a role in prostate cancer development. This review summarizes the current literature regarding human exposure to BPA, the endocrine-disrupting effects of BPA, and the role of BPA in hormone-associated cancers of the breast, ovary, and prostate.
Asunto(s)
Compuestos de Bencidrilo/toxicidad , Neoplasias de la Mama/inducido químicamente , Disruptores Endocrinos/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Neoplasias Ováricas/inducido químicamente , Fenoles/toxicidad , Neoplasias de la Próstata/inducido químicamente , Femenino , Humanos , MasculinoRESUMEN
AIM: To elucidate the clinical and laboratory features of localized gastric amyloidosis via a rare report along with a review of related literatures. METHODS: The clinical manifestations, laboratory results and surgical treatment of a female patient with localized gastric amyloidosis in our hospital were summarized. The relevant literatures were reviewed on the etiology, clinical features, diagnosis, treatment and prognosis of this disease. RESULTS: The patient was lack of specific clinical manifestations and positive laboratory results. Prior to the treatment, she was suspected to be of malignization from gastric ulcer by both gastroscopy and endoscopic ultrasonography, which was denied by the gastric biopsy. The patient was treated with subtotal gastrectomy and clearance of perigastric lymph nodes. The postoperative pathological diagnosis determined the lesion to be the deposition of amyloid materials in the gastric mucosa, submucosa and blood vessel walls with intestinal metaplasia and atrophy of the gastric glands, in which no malignant tumor was found. Congo red staining with prior potassium permanganate incubation confirmed the AA type of amyloid in this case. Multiple biopsies from esophagus, remnant stomach, duodenum, colon and bone marrow in the follow-up survey showed no amyloidal deposition in these tissues and organs. Up to the present, no signs of recurrence have been found in this patient. CONCLUSION: Localized gastric amyloidosis, being rare in incidence, should be considered in the differentiation of gastric tumors, in which biopsy is the only means to confirm the diagnosis. Currently, surgical resection of pathological tissue and circumambient lymph nodes may be a preferable therapeutic strategy for the localized amyloidosis to prevent possible complications. Although with a benign prognosis, gastric amyloidosis possesses a recurrent tendency as suggested by the literatures.