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2.
J Radiol Prot ; 41(4)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34673554

RESUMO

In 2021, the ICRP initiated the revision of the general recommendations of the system of radiation protection, and part of it will focus on dose quantities. The recently published ICRP Publication 147 and ICRU Report 95 have described the extent of the proposed modifications and paved the way for the strategy to be adopted. These revisions would seek to simplify, improve the accuracy and extend the field of use of dose quantities. While the Radiological Protection Working Group of the World Nuclear Association recognises the notable improvement in the estimation of the protection quantities and the usefulness of such changes for the medical and research sector, the benefits of the proposed new system seem very limited for the nuclear industry and industries involving naturally occurring radioactive materials. The complexity associated with changing a long-standing and robust system and the risk incurred by the human factor seem unjustified, bearing in mind the likely cost.


Assuntos
Proteção Radiológica , Humanos , Doses de Radiação
3.
Lett Appl Microbiol ; 68(6): 505-508, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30835838

RESUMO

We found that shochu slop, the residue generated during the production of distilled shochu liquor, which must be treated as industrial waste, can be used as an excellent medium for Escherichia coli culture. LB medium is generally used in laboratories for culturing E. coli. However, it is not the optimal medium for E. coli culture because the bacterial cells cannot grow to very high densities in LB medium. On the other hand, E. coli can grow to higher densities in Terrific broth and this medium is used when researchers want to grow E. coli to high density or to obtain a protein with high yield. In this study, we removed solid matter from shochu slop, adjusted the pH of the mixture to 7 and subsequently used the slop for E. coli culture. The ability of shochu slop to support E. coli growth was compared with those of LB Miller medium and Terrific broth. The results indicate that sweet potato shochu slop as culture medium for E. coli is comparable to Terrific broth and much better than LB Miller medium in terms of supporting cell proliferation, and plasmid and enzyme production. SIGNIFICANCE AND IMPACT OF THE STUDY: Shochu manufacturers incur a cost to dispose shochu slop, which is recognized as food manufactural residues. Escherichia coli has been used in laboratories and in industry. However, culture media used in the laboratories are expensive and those used in industry are expensive because of their large scale. We found that sweet potato shochu slop is an excellent culture medium for E. coli. This finding is not only useful for laboratories and industry, but also beneficial to the effective utilization of this renewable resource to create a sustainable society.


Assuntos
Bebidas Alcoólicas/microbiologia , Meios de Cultura/química , Escherichia coli K12/crescimento & desenvolvimento , Escherichia coli K12/metabolismo , Resíduos Industriais/análise , Escherichia coli K12/genética , Plasmídeos/genética
4.
Osteoarthritis Cartilage ; 27(6): 965-976, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30716534

RESUMO

OBJECTIVE: The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that integrates nutrients to execute cell growth. We hypothesized that mTOR is influential in the intervertebral disc-largest avascular, low-nutrient organ. Our objective was to identify the optimal mTOR inhibitor for treating human degenerative disc disease. DESIGN: mTOR complex 1 (mTORC1) regulates p70/ribosomal S6 kinase (p70/S6K), negatively regulates autophagy, and is controlled by Akt. Akt is controlled by phosphatidylinositol 3-kinase (PI3K) and mTOR complex 2 (mTORC2). mTORC1 inhibitors-rapamycin, temsirolimus, everolimus, and curcumin, mTORC1&mTORC2 inhibitor-INK-128, PI3K&mTOR inhibitor-NVP-BEZ235, and Akt inhibitor-MK-2206-were applied to human disc nucleus pulposus (NP) cells. mTOR signaling, autophagy, apoptosis, senescence, and matrix metabolism were evaluated. RESULTS: mTORC1 inhibitors decreased p70/S6K but increased Akt phosphorylation, promoted autophagy with light chain 3 (LC3)-II increases and p62/sequestosome 1 (p62/SQSTM1) decreases, and suppressed pro-inflammatory interleukin-1 beta (IL-1ß)-induced apoptotic terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity (versus rapamycin, 95% confidence interval (CI) -0.431 to -0.194; temsirolimus, 95% CI -0.529 to -0.292; everolimus, 95% CI -0.477 to -0.241; curcumin, 95% CI -0.248 to -0.011) and poly (ADP-ribose) polymerase (PARP) and caspase-9 cleavage, senescent senescence-associated beta-galactosidase (SA-ß-gal) positivity (versus rapamycin, 95% CI -0.437 to -0.230; temsirolimus, 95% CI -0.534 to -0.327; everolimus, 95% CI -0.485 to -0.278; curcumin, 95% CI -0.210 to -0.003) and p16/INK4A expression, and catabolic matrix metalloproteinase (MMP) release and activation. Meanwhile, dual mTOR inhibitors decreased p70/S6K and Akt phosphorylation without enhanced autophagy and suppressed apoptosis, senescence, and matrix catabolism. MK-2206 counteracted protective effects of temsirolimus. Additional disc-tissue analysis found relevance of mTOR signaling to degeneration grades. CONCLUSION: mTORC1 inhibitors-notably temsirolimus with an improved water solubility-but not dual mTOR inhibitors protect against inflammation-induced apoptosis, senescence, and matrix catabolism in human disc cells, which depends on Akt and autophagy induction.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Núcleo Pulposo/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzoxazóis/farmacologia , Curcumina/farmacologia , Everolimo/farmacologia , Matriz Extracelular/metabolismo , Feminino , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Imidazóis/farmacologia , Inflamação , Masculino , Metaloproteinases da Matriz/efeitos dos fármacos , Metaloproteinases da Matriz/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Alvo Mecanístico do Complexo 2 de Rapamicina/antagonistas & inibidores , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Proteínas Associadas aos Microtúbulos/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Núcleo Pulposo/citologia , Núcleo Pulposo/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirimidinas/farmacologia , Quinolinas/farmacologia , Proteínas Quinases S6 Ribossômicas 70-kDa/efeitos dos fármacos , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Proteína Sequestossoma-1/efeitos dos fármacos , Proteína Sequestossoma-1/metabolismo , Sirolimo/análogos & derivados , Sirolimo/farmacologia , beta-Galactosidase/efeitos dos fármacos , beta-Galactosidase/metabolismo
5.
Bone Joint J ; 100-B(8): 1066-1073, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30062938

RESUMO

Aims: The aim of this study was to report the mid-term clinical outcome of cemented unlinked J-alumina ceramic elbow (JACE) arthroplasties when used in patients with rheumatoid arthritis (RA). Patients and Methods: We retrospectively reviewed 87 elbows, in 75 patients with RA, which was replaced using a cemented JACE total elbow arthroplasty (TEA) between August 2003 and December 2012, with a follow-up of 96%. There were 72 women and three men, with a mean age of 62 years (35 to 79). The mean follow-up was nine years (2 to 14). The clinical condition of each elbow before and after surgery was assessed using the Mayo Elbow Performance Index (MEPI, 0 to 100 points). Radiographic loosening was defined as a progressive radiolucent line of >1 mm that was completely circumferential around the prosthesis. Results: The mean MEPI scores significantly improved from 40 (10 to 75) points preoperatively to 95 (30 to 100) points at final follow-up (p < 0.0001). Complications were noted in ten elbows (ten patients; 11%). Two had an intraoperative humeral fracture which was treated by fixation and united. One had a postoperative fracture of the olecranon which united with conservative treatment and one had a radial neuropathy which resolved. Further surgery was required for one with a dislocation, three with an ulnar neuropathy and one with a postoperative humeral fracture. Revision with removal of the components was performed in one elbow due to deep infection. There was no radiographic evidence of loosening around the components. With any revision surgery or revision with implant removal as the endpoint, the rates of survival up to 14 years were 93% (95% confidence interval (CI), 83.9 to 96.6) and 99% (95% CI 91.9 to 99.8), respectively, as determined by Kaplan-Meier analysis. Conclusion: With the appropriate indications, the mid-term clinical performance of the cemented JACE TEA is reliable and comparable to other established TEAs in the management of the elbow in patients with RA. Cite this article: Bone Joint J 2018;100-B:1066-73.


Assuntos
Óxido de Alumínio/administração & dosagem , Artrite Reumatoide/cirurgia , Artroplastia de Substituição do Cotovelo/métodos , Cimentos Ósseos/efeitos adversos , Prótese de Cotovelo , Adulto , Idoso , Artrite Reumatoide/diagnóstico por imagem , Artroplastia de Substituição do Cotovelo/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Radiografia , Sucção/métodos , Técnicas de Sutura , Sinovectomia/métodos , Resultado do Tratamento
6.
Bone Joint Res ; 7(3): 252-262, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29922443

RESUMO

OBJECTIVES: This study aimed to examine the effects of SRT1720, a potent SIRT1 activator, on osteoarthritis (OA) progression using an experimental OA model. METHODS: Osteoarthritis was surgically induced by destabilization of the medial meniscus in eight-week-old C57BL/6 male mice. SRT1720 was administered intraperitoneally twice a week after surgery. Osteoarthritis progression was evaluated histologically using the Osteoarthritis Research Society International (OARSI) score at four, eight, 12 and 16 weeks. The expression of SIRT1, matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), cleaved caspase-3, PARP p85, and acetylated nuclear factor (NF)-κB p65 in cartilage was examined by immunohistochemistry. Synovitis was also evaluated histologically. Primary mouse epiphyseal chondrocytes were treated with SRT1720 in the presence or absence of interleukin 1 beta (IL-1ß), and gene expression changes were examined by real-time polymerase chain reaction (PCR). RESULTS: The OARSI score was significantly lower in mice treated with SRT1720 than in control mice at eight and 12 weeks associated with the decreased size of osteophytes at four and eight weeks. The delayed OA progression in the mice treated with SRT1720 was also associated with increased SIRT1-positive chondrocytes and decreased MMP-13-, ADAMTS-5-, cleaved caspase-3-, PARP p85-, and acetylated NF-κB p65-positive chondrocytes and decreased synovitis at four and eight weeks. SRT1720 treatment partially rescued the decreases in collagen type II alpha 1 (COL2A1) and aggrecan caused by IL-1ß, while also reducing the induction of MMP-13 by IL-1ß in vitro. CONCLUSION: The intraperitoneal injection of SRT1720 attenuated experimental OA progression in mice, indicating that SRT1720 could be a new therapeutic approach for OA.Cite this article: K. Nishida, T. Matsushita, K. Takayama, T. Tanaka, N. Miyaji, K. Ibaraki, D. Araki, N. Kanzaki, T. Matsumoto, R. Kuroda. Intraperitoneal injection of the SIRT1 activator SRT1720 attenuates the progression of experimental osteoarthritis in mice. Bone Joint Res 2018;7:252-262. DOI: 10.1302/2046-3758.73.BJR-2017-0227.R1.

7.
Bone Joint Res ; 7(2): 139-147, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29437637

RESUMO

OBJECTIVES: Diabetes mellitus (DM) is known to impair fracture healing. Increasing evidence suggests that some microRNA (miRNA) is involved in the pathophysiology of diabetes and its complications. We hypothesized that the functions of miRNA and changes to their patterns of expression may be implicated in the pathogenesis of impaired fracture healing in DM. METHODS: Closed transverse fractures were created in the femurs of 116 rats, with half assigned to the DM group and half assigned to the control group. Rats with DM were induced by a single intraperitoneal injection of streptozotocin. At post-fracture days five, seven, 11, 14, 21, and 28, miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was performed with miRNA samples from each group on post-fracture days five and 11. For further analysis, real-time polymerase chain reaction (PCR) analysis was performed at each timepoint. RESULTS: Microarray analysis showed that there were 14 miRNAs at day five and 17 miRNAs at day 11, with a greater than twofold change in the DM group compared with the control group. Among these types of miRNA, five were selected based on a comparative and extended literature review. Real-time PCR analysis revealed that five types of miRNA (miR-140-3p, miR-140-5p, miR-181a-1-3p, miR-210-3p, and miR-222-3p) were differentially expressed with changing patterns of expression during fracture healing in diabetic rats compared with controls. CONCLUSIONS: Our findings provide information to further understand the pathology of impaired fracture healing in a diabetic rat model. These results may allow the potential development of molecular therapy using miRNA for the treatment of impaired fracture healing in patients with DM.Cite this article: S. Takahara, S. Y. Lee, T. Iwakura, K. Oe, T. Fukui, E. Okumachi, T. Waki, M. Arakura, Y. Sakai, K. Nishida, R. Kuroda, T. Niikura. Altered expression of microRNA during fracture healing in diabetic rats. Bone Joint Res 2018;7:139-147. DOI: 10.1302/2046-3758.72.BJR-2017-0082.R1.

8.
J Appl Microbiol ; 123(6): 1561-1570, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28948675

RESUMO

AIMS: To confirm the stress-relieving effects of heat-inactivated, enteric-colonizing Lactobacillus gasseri CP2305 (paraprobiotic CP2305) in medical students taking a cadaver dissection course. METHODS AND RESULTS: Healthy students (21 males and 11 females) took paraprobiotic CP2305 daily for 5 weeks during a cadaver dissection course. The General Health Questionnaire and the Pittsburgh Sleep Quality Index were employed to assess stress-related somatic symptoms and sleep quality respectively. The aggravation of stress-associated somatic symptoms was observed in female students (P = 0·029). Sleep quality was improved in the paraprobiotic CP2305 group (P = 0·038), particularly in men (P = 0·004). Among men, paraprobiotic CP2305 shortened sleep latency (P = 0·035) and increased sleep duration (P = 0·048). Diarrhoea-like symptoms were also effectively controlled with CP2305 (P = 0·005) in men. Thus, we observed sex-related differences in the effects of paraprobiotic CP2305. In addition, CP2305 affected the growth of faecal Bacteroides vulgatus and Dorea longicatena, which are involved in intestinal inflammation. CONCLUSIONS: CP2305 is a potential paraprobiotic that regulates stress responses, and its beneficial effects may depend on specific cell component(s). SIGNIFICANCE AND IMPACT OF THE STUDY: This study characterizes the effects of a stress-relieving para-psychobiotic in humans.


Assuntos
Lactobacillus gasseri , Probióticos/uso terapêutico , Sono , Estresse Psicológico/tratamento farmacológico , Adulto , Fezes/microbiologia , Feminino , Humanos , Masculino , Fatores Sexuais , Estudantes de Medicina
9.
Osteoarthritis Cartilage ; 25(12): 2134-2146, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28888905

RESUMO

OBJECTIVE: The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that integrates nutrients to execute cell growth and protein synthesis. We hypothesized that mTOR is essential for the intervertebral disc, the largest avascular, low-nutrient organ. Our objective was to elucidate roles of mTOR signaling in human disc cells. DESIGN: The mTOR exists in two complexes: mTORC1 containing the regulatory-associated protein of mTOR (RAPTOR) and mTORC2 containing the rapamycin-insensitive companion of mTOR (RICTOR). To analyze their functions in human disc nucleus pulposus cells, RNA interference (RNAi) of mTOR targeting mTORC1 and mTORC2, RAPTOR targeting mTORC1, or RICTOR targeting mTORC2 or rapamycin, a pharmacological mTORC1 inhibitor, was applied. First, mTOR signaling including Akt, p70/ribosomal S6 kinase (p70/S6K), and autophagy were assessed. Then, apoptosis, senescence, and matrix metabolism were evaluated under pro-inflammatory interleukin-1 beta (IL-1ß) stimulation. RESULTS: Western blotting showed significant decreases in specific proteins by each RNAi (all P < 0.0001). In mTOR signaling, RNAi of mTOR and RICTOR decreased p70/S6K and Akt phosphorylation, whereas RAPTOR RNAi decreased p70/S6K but increased Akt phosphorylation. All RNAi treatments increased light chain 3 (LC3)-II and decreased p62/sequestosome 1 (p62/SQSTM1), indicating enhanced autophagy. In apoptosis, IL-1ß-induced terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells and poly (ADP-ribose) polymerase (PARP) and caspase-9 cleavage decreased by RAPTOR RNAi. In senescence, IL-1ß-induced senescence-associated beta-galactosidase (SA-ß-gal)-positive cells and p16/INK4A expression also decreased by RAPTOR RNAi. In matrix metabolism, RAPTOR RNAi reduced IL-1ß-induced catabolic matrix metalloproteinase (MMP) release and activation and up-regulated anabolic gene expression. These findings were all consistent with rapamycin administration. Additional disc-tissue analysis detected expression and phosphorylation of mTOR-signaling molecules in varying ages. CONCLUSION: Selective interference of mTORC1/RAPTOR protects against inflammation-induced apoptosis, senescence, and matrix catabolism possibly through Akt and autophagy induction in human disc cells.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Núcleo Pulposo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteína Regulatória Associada a mTOR/antagonistas & inibidores , Western Blotting , Matriz Extracelular/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Interleucina-1beta/farmacologia , Disco Intervertebral/citologia , Disco Intervertebral/efeitos dos fármacos , Disco Intervertebral/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 2 de Rapamicina , Proteínas Associadas aos Microtúbulos/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/metabolismo , Núcleo Pulposo/citologia , Núcleo Pulposo/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , Proteína Regulatória Associada a mTOR/genética , Proteínas Quinases S6 Ribossômicas 70-kDa , Proteína Sequestossoma-1/efeitos dos fármacos , Proteína Sequestossoma-1/metabolismo , Sirolimo/farmacologia
11.
Benef Microbes ; 8(2): 153-162, 2017 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-28443383

RESUMO

The present study examined whether Lactobacillus casei strain Shirota (LcS) improves sleep quality under psychological stress. A double-blind, placebo-controlled trial was conducted in healthy 4th year medical students exposed to academic examination stress. The trial was repeated over two consecutive years in different groups of students, and the data were pooled. For 8 weeks prior to and 3 weeks after a national standardised examination, a total of 48 and 46 subjects received a daily dose of 100 ml of LcS-fermented milk or non-fermented placebo milk, respectively. Study measures included subjective anxiety, overnight single-channel electroencephalography (EEG) recordings, and the Oguri-Shirakawa-Azumi (OSA) sleep inventory scores of subjective sleep quality. Total OSA scores were significantly lower than baseline on the day before the exam and recovered after the exam, indicating a stress-induced decline in sleep quality. There was a significant positive effect of LcS treatment on OSA factors for sleepiness on rising and sleep length. Sleep latency measured by EEG lengthened as the exam approached in the placebo group but was significantly suppressed in the LcS group. The percentage of stage 3 non-REM (N3) sleep decreased in the placebo group as the exam approached, whereas it was maintained in the LcS group throughout the trial. Delta power during the first sleep cycle, measured as an index of sleep intensity, increased as the exam approached in the LcS group and was significantly higher than in the placebo group. These findings suggest that daily consumption of LcS may help to maintain sleep quality during a period of increasing stress. The observed retention of N3 sleep and increased delta power in the LcS group may have contributed to higher perceived sleep satisfaction.


Assuntos
Ansiedade/terapia , Lacticaseibacillus casei , Probióticos/uso terapêutico , Medicamentos Indutores do Sono/uso terapêutico , Transtornos do Sono-Vigília/terapia , Estresse Psicológico/terapia , Adulto , Ondas Encefálicas/efeitos dos fármacos , Suplementos Nutricionais/microbiologia , Método Duplo-Cego , Eletroencefalografia , Feminino , Humanos , Masculino , Transtornos do Sono-Vigília/psicologia , Estudantes de Medicina/psicologia , Inquéritos e Questionários , Adulto Jovem
12.
Andrologia ; 49(1)2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27136193

RESUMO

Male infertility is common at infertile clinics, and 10-20% of infertile males are azoospermic. Non-obstructive azoospermia is a complex multifactorial disease, and the process of spermatogenesis remains largely unknown. Ovol1 and Ovol2, a family of zinc finger transcription factors, are expressed in spermatocytes at the pachytene stage and are suggested to be critical regulators of pachytene progression in male germ cells. In this study, we examined the expression of human Ovol2 (hOvol2) in the seminiferous tubes of patients subjected to testicular sperm extraction. We first cloned hOvol1 and hOvol2 from the testis of one of the patients and found no alteration in these nucleotide sequences of this patient. While hOvol1 and hOvol2 were detected by RT-PCR in the testis of patients capable of spermatogenesis, they were not detected in those with Sertoli cell-only syndrome. We recently succeeded in preparing anti-Ovol2 antibody by immunising rats with recombinant mouse Ovol2 (mOvol2) and confirmed the specificity and cross-reactivity of this antibody with hOvol2 in cells transfected with hOvol1 or hOvol2 cDNA. hOvol2 expression was restricted to the XY body of spermatocytes at the pachytene stage. This study demonstrates that hOvol2 is expressed in germ cells and may be involved in spermatogenesis.


Assuntos
Azoospermia/metabolismo , Espermatócitos/metabolismo , Fatores de Transcrição/metabolismo , Azoospermia/genética , Azoospermia/patologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Células HEK293 , Humanos , Masculino , Túbulos Seminíferos/metabolismo , Espermatogênese/genética , Fatores de Transcrição/genética
14.
J Appl Microbiol ; 122(1): 212-224, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27761980

RESUMO

AIMS: To clarify the effects of Lactobacillus gasseri CP2305 (CP2305) on quality of life and clinical symptoms and its functional mechanisms in patients with irritable bowel syndrome (IBS). METHODS AND RESULTS: After the patients were administered CP2305 daily for 4 weeks, the IBS-severity index score was significantly improved compared with that of the placebo group, and this improvement was accompanied by a reduction in health-related worry and changes in intestinal microbiota. The gene expression profiling of the peripheral blood leucocytes showed that CP2305 treatment significantly up-regulated genes related to eukaryotic initiation factor 2 (EIF2) signalling. Eighty-two genes were down-regulated in IBS patients compared with healthy controls. The expression of 23 of these genes exhibited a CP2305-dependent increase associated with an improvement in IBS severity. The majority of the restored genes were related to EIF2 signalling. CONCLUSIONS: CP2305 administration is a potential candidate therapeutic option for patients with IBS. SIGNIFICANCE AND IMPACT OF THE STUDY: Although probiotics have been proposed to benefit IBS patients, objective clinical evidence and elucidation of the functional mechanism remain insufficient. Our study demonstrated that CP2305 administration beneficially influences IBS patients in both subjective and objective evaluations, and gene expression profiling provided insights into the functional mechanism.


Assuntos
Síndrome do Intestino Irritável/tratamento farmacológico , Lactobacillus gasseri/fisiologia , Probióticos/administração & dosagem , Adulto , Feminino , Humanos , Síndrome do Intestino Irritável/genética , Síndrome do Intestino Irritável/metabolismo , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Resultado do Tratamento
15.
Int Cancer Conf J ; 6(2): 50-54, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31149470

RESUMO

A patient who underwent fertility-sparing surgery for Stage IA clear cell carcinoma may have developed de novo clear cell carcinoma in the contralateral ovary 9 years later. She underwent fertility-sparing surgery and postoperative adjuvant chemotherapy for right ovarian carcinoma at 33 years of age (when endometriosis was observed in the contralateral ovary). At the age of 41 years, a tumor was discovered in the left ovary. This was diagnosed pathologically as clear cell carcinoma with clear cell adenofibroma, which may have developed de novo. A consensus is currently taking shape that although fertility-sparing surgery is a therapeutic option for patients with Stage IA clear cell carcinoma, long-term outpatient monitoring is advised to watch for its recurrence or de novo development in the contralateral ovary.

16.
Andrology ; 4(5): 964-71, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27230983

RESUMO

Androgen deprivation therapy (ADT) is the standard medical approach to the management of prostate cancer. Patients switched from a GnRH antagonist to a GnRH agonist, did not experience a testosterone surge in spite of the occurrence of luteinizing hormone (LH) surge in our protocol of clinical study. To clarify this observation, male mice pre-treated with two different doses of the GnRH antagonist degarelix for 28 days were further administered the GnRH agonist leuprolide or chorionic gonadotropin, and testosterone production of the mice was studied. Serum LH and testosterone levels, the size of Leydig cells, and expression level of steroidogenesis-related genes in the testis were analyzed. Treatment of mice with a high dose of degarelix (0.1 µg/mouse; HDG), but not a low dose (0.05 µg/mouse; LDG), for 28 days reproduced declined steroidogenesis observed in prostate cancer patients during ADT switched from a GnRH antagonist to a GnRH agonist. The size of the Leydig cells in the HDG mice was not significantly different from that in naive mice. Although expression levels of StAR, P450scc, and 17ß HSD increased significantly in the LDH testis, those in the HDG testis did not change. Treatment of mice with a high dose of degarelix for 28 days reproduced the decline in steroidogenesis observed in prostate cancer patients during ADT. In this animal model, we demonstrated that initial ADT may inhibit the ability of Leydig cells to produce testosterone by suppressing the expression of genes involved in steroidogenesis, such as StAR, P450scc, and 17ßHSD.


Assuntos
Gonadotropina Coriônica/farmacologia , Antagonistas de Hormônios/farmacologia , Leuprolida/farmacologia , Oligopeptídeos/farmacologia , Neoplasias da Próstata/metabolismo , Testículo/efeitos dos fármacos , Testosterona/metabolismo , 17-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Antineoplásicos Hormonais/farmacologia , Tamanho Celular/efeitos dos fármacos , Modelos Animais de Doenças , Células Intersticiais do Testículo/citologia , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Hormônio Luteinizante/sangue , Masculino , Camundongos , Fosfoproteínas/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Testículo/citologia , Testículo/metabolismo , Testosterona/sangue
17.
Oncogenesis ; 5: e213, 2016 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-27043659

RESUMO

Ultraconserved regions (UCRs) are >200 bp genomic segments with perfect human-to-rodent sequence identity. Transcribed UCRs constitute a new category of noncoding RNAs whose functions remain poorly understood. The human transformer 2ß (TRA2B) gene contains a 419-bp UCR spanning the 276-bp exon 2 and its neighboring introns. TRA2B exon 2 has premature stop codons, whereas an exon 2-containing splice variant (TRA2ß4) was expressed preferentially in the nuclei of human colon cancer cells. TRA2ß4 knockdown p53-independently stimulated CDKN1A transcription and increased p21, resulting in the appearance of senescent cells. Biotin pull-down and RNA immunoprecipitation assays revealed that TRA2ß4 interacted with Sp1 through a Sp1-binding sequence (485-GGGG-488) in a stem-loop structure of exon 2. Mutation of this sequence (485-AAGG-488) disrupted the stem-loop structure, blocked the interaction with Sp1 and increased CDKN1A transcription. Overexpression of TRA2ß4 significantly decreased CDKN1A mRNA levels and accelerated cell growth, but the introduction of the mutation in the Sp1-binding sequence completely canceled these effects. Taken together, TRA2ß4 may sequester Sp1 from occupying promoters of target genes including CDKN1A, promoting cell growth by interrupting the senescence-related gene expression program. This novel function of TRA2ß4 may uncover an oncogenic function of transcribed UCRs.

18.
Rev Sci Instrum ; 87(2): 02B108, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26931990

RESUMO

To understand the Electron Energy Distribution Function (EEDF) in the Radio Frequency Inductively Coupled Plasmas (RF-ICPs) in hydrogen negative ion sources, the detailed analysis of the EEDFs using numerical simulation and the theoretical approach based on Boltzmann equation has been performed. It is shown that the EEDF of RF-ICPs consists of two parts, one is the low energy part which obeys Maxwellian distribution and the other is high energy part deviated from Maxwellian distribution. These simulation results have been confirmed to be reasonable by the analytical approach. The results suggest that it is possible to enhance the dissociation of molecules and the resultant H(-) negative ion production by reducing the gas pressure.

19.
Rev Sci Instrum ; 87(2): 02B128, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26932010

RESUMO

A numerical model of plasma transport and electromagnetic field in the J-PARC (Japan Proton Accelerator Research Complex) radio frequency ion source has been developed to understand the relation between antenna coil heat loadings and plasma production/transport processes. From the calculation, the local plasma density increase is observed in the region close to the antenna coil. Electrons are magnetized by the magnetic field line with absolute magnetic flux density 30-120 Gauss which leads to high local ionization rate. The results suggest that modification of magnetic configuration can be made to reduce plasma heat flux onto the antenna.

20.
Rev Sci Instrum ; 87(2): 02B139, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26932021

RESUMO

CERN's 160 MeV H(-) linear accelerator (Linac4) is a key constituent of the injector chain upgrade of the Large Hadron Collider that is being installed and commissioned. A cesiated surface ion source prototype is being tested and has delivered a beam intensity of 45 mA within an emittance of 0.3 π ⋅ mm ⋅ mrad. The optimum ratio of the co-extracted electron- to ion-current is below 1 and the best production efficiency, defined as the ratio of the beam current to the 2 MHz RF-power transmitted to the plasma, reached 1.1 mA/kW. The H(-) source prototype and the first tests of the new ion source optics, electron-dump, and front end developed to minimize the beam emittance are presented. A temperature regulated magnetron H(-) source developed by the Brookhaven National Laboratory was built at CERN. The first tests of the magnetron operated at 0.8 Hz repetition rate are described.

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