RESUMO
We provide a detailed molecular and phylogenetic description of Bertiella studeri tapeworms infecting children in Sri Lanka. Our findings can be used to identify multiple species of Bertiella tapeworms that can infect human hosts in the Old World.
Assuntos
Cestoides , Animais , Criança , Análise por Conglomerados , Humanos , Filogenia , Sri Lanka/epidemiologiaRESUMO
Gartanin, a 4-prenylated xanthone, has been identified from the purple mangosteen fruit as a potent growth inhibitor of various cancer cell lines, including prostate cancer. However, much of Gartanin's anticancer mechanism remains unknown. We have discovered that Gartanin docked onto the regulatory subunit of the precursor cell-expressed developmentally downregulated 8 (NEDD8)-activating enzyme (NAE) complex and next to the NEDD8 binding complex, which leads to inhibit NEDD8 conjugations to both Cullin1 and Ubc12 in prostate cancer cell lines and Ubc12 NEDDylation in an in vitro assay. The S phase kinase-associated protein (Skp2) and F-box and WD-repeat domain-containing 2 (FBXW2), the NEDD8 family members of E3 ubiqutin ligases, were also downregulated and upregulated by Gartainin, respectively. Knock-down of NEDD8 expression by short harpin (Sh) RNAs blocked or attenuated these effects of Gartainin. Finally, Gartanin demonstrated its ability to inhibit growth of prostate cancer lines via autophagy initiation. Our data support that Gartanin is a naturally occurring NEDDylation inhibitor and deserves further investigation for prostate cancer prevention and treatment.
Assuntos
Autofagia/efeitos dos fármacos , Proteínas F-Box/metabolismo , Proteína NEDD8/antagonistas & inibidores , Neoplasias da Próstata/metabolismo , Proteínas Quinases Associadas a Fase S/metabolismo , Xantonas/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Proteínas F-Box/genética , Humanos , Masculino , Proteína NEDD8/metabolismo , Células PC-3 , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Interferência de RNARESUMO
The new compound Cu2(I)(TCNQF4(II-))(MeCN)2 (TCNQF4(2-) = dianion of 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane) has been synthesized by electrochemically directed synthesis involving reduction of TCNQF4 to TCNQF4(2-) in acetonitrile containing [Cu(MeCN)4](+)(MeCN) and 0.1 M Bu4NPF6. In one scenario, TCNQF4(2-) is quantitatively formed by reductive electrolysis of TCNQF4 followed by addition of [Cu(MeCN)4](+) to form the Cu2(I)(TCNQF4(II-))(MeCN)2 coordination polymer. In a second scenario, TCNQF4 is reduced in situ at the electrode surface to TCNQF4(2-), followed by reaction with the [Cu(MeCN)4](+) present in the solution, to electrocrystallize Cu2(I)(TCNQF4(II-))(MeCN)2. Two distinct phases of Cu2(I)(TCNQF4(II-))(MeCN)2 are formed in this scenario; the kinetically favored form being rapidly converted to the thermodynamically favored Cu2(I)(TCNQF4(II-))(MeCN)2. The postulated mechanism is supported by simulations. The known compound Cu(I)TCNQF4(I-) also has been isolated by one electron reduction of TCNQF4 and reaction with [Cu(MeCN)4](+). The solubility of both TCNQF4(2-)- and TCNQF4(â¢-)-derived solids indicates that the higher solubility of Cu(I)TCNQF4(I-) prevents its precipitation, and thus Cu2(I)(TCNQF4(II-))(MeCN)2 is formed. UV-visible and vibrational spectroscopies were used to characterize the materials. Cu2(I)(TCNQF4(II-))(MeCN)2 can be photochemically transformed to Cu(I)TCNQF4(I-) and Cu(0). Scanning electron microscopy images reveal that Cu(I)TCNQF4(I-) and Cu2(I)(TCNQF4(II-))(MeCN)2 are electrocrystallized with distinctly different morphologies. Thermogravimetric and elemental analysis data confirm the presence of CH3CN, and single-crystal X-ray diffraction data for the Cu2(I)(TCNQF4(II-))(EtCN)2 analogue shows that this compound is structurally related to Cu2(I)(TCNQF4(II-))(MeCN)2.
RESUMO
Intestinal dysbiosis has recently become known as an important driver of gastrointestinal and liver disease. It remains poorly understood, however, how gastrointestinal microbes bypass the intestinal mucosa and enter systemic circulation to enact an inflammatory immune response. In the context of chronic liver disease (CLD), insults that drive hepatic inflammation and fibrogenesis (alcohol, fat) can drastically increase intestinal permeability, hence flooding the liver with gut-derived microbiota. Consequently, this may result in exacerbated liver inflammation and fibrosis through activation of liver-resident Kupffer and stellate cells by bacterial, viral, and fungal antigens transported to the liver via the portal vein. This review summarizes the current understanding of microbial translocation in CLD, the cell-specific hepatic response to intestinal antigens, and how this drives the development and progression of hepatic inflammation and fibrosis. Further, we reviewed current and future therapies targeting intestinal permeability and the associated, potentially harmful anti-microbial immune response with respect to their potential in terms of limiting the development and progression of liver fibrosis and end-stage cirrhosis.
Assuntos
Microbioma Gastrointestinal/imunologia , Cirrose Hepática/imunologia , Progressão da Doença , Disbiose/complicações , Microbioma Gastrointestinal/fisiologia , Células Estreladas do Fígado/metabolismo , Humanos , Imunidade Inata , Mucosa Intestinal/imunologia , Intestinos , Células de Kupffer/metabolismo , Fígado/imunologia , Fígado/patologia , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica , PermeabilidadeRESUMO
Paragonimus heterotremus Chen and Hsia (1964), and paragonimiasis caused by this species is a newly detected disease in Vietnam. Twelve samples of Paragonimus (Platyhelminthes: Trematoda: Digenea: Paragonimidae) from different life-stages (eggs, miracidia, metacercariae, adults from natural and experimental hosts) and host species (crab, dog, cat and human) were collected in different geographical locations in Vietnam. DNA sequences were obtained from each for partial mitochondrial cytochrome c oxidase subunit 1 (cox1) (387 bp) and the entire second ribosomal internal transcribed spacer (ITS-2) (361 bp). The ITS-2 sequences were identical among all specimens, including those previously reported in GenBank. For cox1, there were sequence differences between specimens from Vietnam (four provinces, different locations) and those from Guangxi (China) and Saraburi (Thailand). Phylogenetic trees inferred from cox1 and ITS-2 sequences using sequence data for 15 P. heterotremus and for other Paragonimus spp. revealed that all P. heterotremus originating from Vietnam, Thailand and China form a distinct group. This information also confirms the identity of the Vietnamese specimens as P. heterotremus.
Assuntos
Paragonimíase/epidemiologia , Paragonimíase/parasitologia , Paragonimus/genética , Paragonimus/isolamento & purificação , Animais , Sequência de Bases , Braquiúros/parasitologia , Gatos , Cães , Variação Genética , Interações Hospedeiro-Parasita , Humanos , Dados de Sequência Molecular , Óvulo , Filogenia , Vietnã/epidemiologiaRESUMO
Complete or near-complete mitochondrial genomes are now available for 11 species or strains of parasitic flatworms belonging to the Trematoda and the Cestoda. The organization of these genomes is not strikingly different from those of other eumetazoans, although one gene (atp8) commonly found in other phyla is absent from flatworms. The gene order in most flatworms has similarities to those seen in higher protostomes such as annelids. However, the gene order has been drastically altered in Schistosoma mansoni, which obscures this possible relationship. Among the sequenced taxa, base composition varies considerably, creating potential difficulties for phylogeny reconstruction. Long non-coding regions are present in all taxa, but these vary in length from only a few hundred to approximately 10000 nucleotides. Among Schistosoma spp., the long non-coding regions are rich in repeats and length variation among individuals is known. Data from mitochondrial genomes are valuable for studies on species identification, phylogenies and biogeography.
Assuntos
Infecções por Cestoides/parasitologia , DNA de Helmintos/genética , DNA Mitocondrial/genética , Platelmintos/genética , Schistosoma/genética , Esquistossomose/parasitologia , Animais , Sequência de Bases , Humanos , Filogenia , Platelmintos/classificação , Schistosoma/classificaçãoRESUMO
The hydrogen bonding-protonation equilibrium for retinyl Schiff base/propionic acid or 3-chloropropionic acid systems was examined by Fourier transform infrared spectroscopy in non polar solutions at temperatures ranging from 25 degrees C to about -150 degrees C. The spectra give evidence for the gradual increase in the degree of protonation as temperature is lowered. The bearing of this on applying low temperature spectroscopic results to physiological conditions in rhodopsin research is discussed.
Assuntos
Pigmentos da Retina , Retinoides , Análise de Fourier , Congelamento , Modelos Teóricos , Bases de Schiff , Soluções , Espectrofotometria Infravermelho/métodosRESUMO
Technical radiotherapy progress drive the practices towards increasingly more precise irradiations. The recent developments of the various imaging methods and specialized software made more controls possible. The fields of investigations relate to the quality assurance of the irradiation, the reproducibility of positioning, the movements evaluations and real time dosimetry. Radiotherapy finds, in the images exploitation, a strong potential in improving quality treatments, however it is conditioned by the implementation of ambitious programs, time consuming, but essential to grant the precision of virtual simulations and the daily practice. If all the existing technical devices and software offer higher tools than the current practices, the recommendations can be limited to the insurance of a sufficient precision and reproducibility of the whole treatments. It is thus fundamental to be able to filter the errors, the systematic deviations and to control the statistics of positioning and movements. Each radiotherapy department must apply an adapted program to each site and exploit the imaging chain to maintain its results.
Assuntos
Garantia da Qualidade dos Cuidados de Saúde , Radioterapia (Especialidade)/normas , Planejamento da Radioterapia Assistida por Computador/instrumentação , Radioterapia Assistida por Computador , Humanos , Processamento de Imagem Assistida por Computador , Radioterapia (Especialidade)/instrumentação , SoftwareRESUMO
A CT acquisition during a free breathing examination generates images of poor quality. It creates an uncertainty on the reconstructed gross tumour volume and dose distribution. The aim of this study is to test the feasibility of a breath hold method applied in all preparation and treatment days. Five patients received a thoracic radiotherapy with the benefit of this procedure. The breathing of the patient was measured with a spirometer. The patient was coached to reproduce a constant level of breath-hold in a deep inspiration. Video glasses helped the patients to fix the breath-hold at the reference level. The patients followed the coaching during preparation and treatment, without any difficulty. The better quality of the CT reconstructed images resulted in an easier contouring. No movements of the gross tumour volume lead to a better coverage. The deep breath hold decreased the volume of irradiated lung. This method improves the reproducibility of the thoracic irradiation. The decrease of irradiated lung volume offers prospects in dose escalation and intensity modulation radiotherapy.
Assuntos
Neoplasias Pulmonares/radioterapia , Respiração , Espirometria , Idoso , Humanos , Medidas de Volume Pulmonar , Pessoa de Meia-Idade , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodosRESUMO
PURPOSE: To reduce errors in the positioning of patients treated with external conformal radiotherapy for prostate cancer, we evaluated both the use of an immobilization device and new fiducial markers. MATERIALS AND METHODS: The immobilization device consisted of an individual mold made of polyurethan foam. Two sets of skin markers located on the anterior tibial surfaces were used to identify the pelvic isocenter. The patient's position was evaluated by orthogonal port films which were then compared with the original simulation film. RESULTS: Results are presented with respect to orthogonal axes. Comparison with classic procedures without immobilization showed that use of the mold and new fiducial markers led to a decrease in set-up errors which were less than 5 mm. CONCLUSION: With the use of an immobilization device and optimized techniques for patients' positioning, conformal radiotherapy of prostate cancer is more accurate.
Assuntos
Imobilização , Neoplasias da Próstata/radioterapia , Planejamento da Radioterapia Assistida por Computador , Simulação por Computador , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Radioterapia de Alta Energia , Resultado do TratamentoRESUMO
Conformal radiotherapy results from several technical and data processing advances. The treatment planning and the daily treatments have benefited from a significant improvement of the quality control. However, all the steps of the process contain various limitations of varying effects. It appear important to identify, describe and exploit those limits to better drive the procedures and optimise the quality. Identifying the limits of the conformal radiotherapy should be an important help to implement intensity modulation radiotherapy.
Assuntos
Radioterapia Conformacional/métodos , Antropometria , Fracionamento da Dose de Radiação , Humanos , Neoplasias/radioterapia , Radiometria , Radioterapia Conformacional/instrumentaçãoRESUMO
Accuracy of conformal treatment planning for prostatic radiotherapy is based on the contours of target volumes (prostate +/- seminal vesicles) and normal tissues (rectum and bladder), drawn on CT (computed tomography) images by radiation oncologists. The interpretation of a given CT image can be different from one radiation oncologist to another, and may change in time with the state of filling of the bladder and of the rectum during the treatment. In order to quantify these variations, 12 patients treated with conformal radiotherapy for prostate carcinoma (pelvis 40 Gy/20 sessions + prostate 30 Gy/15 sessions) had two series of CT at one month intervals. Contouring of prostate, rectum and bladder were performed independently on each CT by two radiation oncologists. The first CT scan (planning CT) and the first series of contours (planning contours) were used for treatment planning. The contours of the second scan were compared to the planning contours after image fusion based on manual superimposition of bony anatomy of the two sets of CT images. Coherence ratio were defined to measure discrepancies in prostate volumes between radiation oncologists (RCE) and between scans (RCT). The mean RCE was 38 +/- 7% (1 standard deviation). Those discrepancies were primarily located at the prostate apex and at the interface between bladder and prostate and between rectum and prostate. The mean RCT was 42 +/- 8% (1 sigma). Those discrepancies were due to the prostate motion related to the state of filling of the rectum and bladder. For bladder and rectal walls, less important differences were observed between the two radiation oncologists for the same CT (4.5% for rectal volume receiving 65 Gy or more, 3% for bladder volume receiving 65 Gy or more). However, important differences in bladder and rectal volumes receiving 65 Gy or more (16% and 7% respectively) were noted for the same patient from a CT to another due to the variation in bladder or rectal filling. New techniques for planning CT acquisition are needed to decrease the discrepancies due to contouring. The treatment must, as far as possible, be delivered with an empty bladder and rectum in order to ensure a good reproduction of the initially planned treatment.