Acció dels andrògens en el testicle: un paper per a la meiosi

La funció que duen a terme els andrògens en l'espermatogènesi és, encara en certa mesura, enigmàtica: mentre que llur implicació és absolutament vital en la iniciació i en el manteniment del procés espermatogènic normal, la seva funció específica encara no està definida de manera precisa. Els andrògens, com les altres hormones esteroïdals, actuen a través del seu corresponent receptor anomenat receptor d'andrògens (AR). Fins avui, no hi ha gaire evidència que recolzi l'existència de diverses isoformes de l'AR com en el cas del sistema estrògensreceptor d'estrògens. Per tant, la pregunta de com els andrògens duen a terme la seva acció en l'espermatogènesi s'ha d'abordar definint dos processos: en primer lloc, s'han d'identifi- car amb total certesa els tipus cell. ulars testiculars capaços de respondre directament a l'estimulació androgènica. De manera específica, la qüestió per resoldre és quins són els tipus cellulars que expressen l'AR en el testicle. En segon lloc, sabent també que el complex del lligand unit a l'AR actua com a factor de transcripció, caldrà determinar quins són els gens que estaran activats o reprimits en les cèll. ules que tenen AR en resposta a l'estimulació androgènica. Fins que aquestes dues preguntes no estiguin contestades amb tota certesa, el mecanisme pel qual els andrògens regulen l'espermatogènesi serà, en el millor dels casos, especulatiu. En aquesta revisió presentem evidència que els andrògens actuen únicament a les cèll. ules somàtiques del testicle, com són les cèll. ules de Sertoli, les de Leydig, les mioides peritubulars i les cèll. ules del múscul llis que envolten els vasos sanguinis. A més a més, també discutim la possibilitat que els andrògens siguin indispensables per a l'inici de la meiosi, encara que continua essent desconegut el mecanisme pel qual els andrògens actuen en aquest procés.The role that androgens play in spermatogenesis still remains enigmatic: whereas their involvement is absolutely vital to the initiation and maintenance of the normal spermatogenic process, their specific role is yet to be defined. Androgens, like other steroid hormones, act via their corresponding receptor termed the androgen receptor (AR). To date, there is little evidence to support the notion that there are multiple forms of AR as is the case for the estrogen-estrogen receptor system. Thus, the question of how androgens manifest their action on spermatogenesis becomes one of defining two processes: First, the cell types within the testis that are capable of responding directly to androgen stimulation must be identified with absolute certainty. Specifically, this question can be stated as what cell types in the testis express AR. Second, given that the ligand-bound AR serves as a transcription factor, the question then becomes what are the genes turned on or off in AR positive cells in response to androgen stimulation? Until these two questions are unequivocally answered, the mechanism of how androgens regulate spermatogenesis will remain speculative at best. In this review we present evidence that androgens act solely at the level of the somatic cells of the testis, including Sertoli cells, Leydig cells, peritubular myoid cells and smooth muscle cells surrounding blood vessels. In addition, we discuss the likely possibility that androgens are indispensable for the onset of meiosis, albeit how they accomplish this remains a mystery

SIRT3-mediated inhibition of FOS through histone H3 deacetylation prevents cardiac fibrosis and inflammation.

Sirtuin 3 (SIRT3) is a deacetylase that modulates proteins that control metabolism and protects against oxidative stress. Modulation of SIRT3 activity has been proposed as a promising therapeutic target for ameliorating metabolic diseases and associated cardiac disturbances. In this study, we investigated the role of SIRT3 in inflammation and fibrosis in the heart using male mice with constitutive and systemic deletion of SIRT3 and human cardiac AC16 cells. SIRT3 knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of AP-1. Consistent with this, SIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-alpha. Notably, these effects were associated with a decrease in the mRNA and protein levels of FOS and the DNA-binding activity of AP-1. Finally, we demonstrated that SIRT3 inhibits FOS transcription through specific histone H3 lysine K27 deacetylation at its promoter. These findings highlight an important function of SIRT3 in mediating the often intricate profibrotic and proinflammatory responses of cardiac cells through the modulation of the FOS/AP-1 pathway. Since fibrosis and inflammation are crucial in the progression of cardiac hypertrophy, heart failure, and diabetic cardiomyopathy, our results point to SIRT3 as a potential target for treating these diseases

On the Hake population dynamics from Galicia (NW Spain) with a preliminary assessment

In the present work, first we have computed the fishing mortalities vectors exerted on the hake (Merluccius merluccius L.), that inhabit in the Galician shelf. To do that we have used the Jone's cohort analisys, with which we also obtain a estimation of the recruitement. This fishing mortality vector was subdivided by gears. From these F Acutal vectors obtained on this way, we have done some simulations about mesh size and fishing effort's changes to know the potential effects of these fishing strategy changes, in the yields. To do that we have used the Jone's model changes in mesh size and effort, and multi-gears Ricker modelDans le présent travail, on fait en premier lieu un calcul des vecteurs de mortalité par pêche à Ia quelle est soumise le merlu (Merluccius merluccius L.) qui vit sur la plataforme continentale galicienne. Pour cela, nous avons utilisé le modèle d'analyse de cohortes sur une distributions de tailles avec lequel nous obtenons aussi une estimation du recrutement, ce vecteur de mortalité par pêche s'est subdivisé par engines de pêche. On second lieu, et à partir de ces vecteurs F actuels ainsi obtenus, nous avons réalisé des simulations de changements de maille et effort de pêche pour connaitre les effets qui causereient ces posssibles changements de la stratégie de pêche, dans les rendements à la longue terme échéance qui seraient obtenus. Pour cela, nous evons utilisé le modèle de changement de mille et effort de Jones et la modèle multi-engines de Ricker

Prevalence and characterization of breakthrough pain in patients with cancer in Spain: the CARPE-DIO study.

We aimed to evaluate the prevalence, characteristics and impact of breakthrough pain (BTP) in patients with cancer attending the main specialties involved in the diagnosis and management of BTP in Spain using a multicenter, observational, cross-sectional, multidisciplinary study. Investigators had to record all patients seen at the clinic during 1 month, determine whether the patients had cancer pain, and apply the Davies algorithm to ascertain whether the patients were suffering from BTP. Of the 3,765 patients with cancer, 1,117 (30%) had cancer-related pain, and of these patients, 539 had BTP (48%, 95%CI:45-51). The highest prevalence was found in patients from palliative care (61%, 95%CI:54-68), and the lowest was found in those from hematology (25%, 95%CI:20-31). Prevalence varied also according to sex and type of tumor. According to the Alberta Breakthrough Pain Assessment Tool duration, timing, frequency, location, severity, quality, causes, and predictability of the BTP varied greatly among these patients. BTP was moderate (Brief Pain Inventory [BPI]-severity median score = 5.3), and pain interference was moderate (BPI-interference median score = 6.1) with a greater interference with normal work, general activity, and enjoyment of life. Patients with BTP showed a mean ± standard deviation score of 28.5 ± 8.0 and 36.9 ± 9.5 in the physical and mental component, respectively, of the SF-12 questionnaire. In conclusion, prevalence of BTP among patients exhibiting cancer-related pain is high. Clinical presentation is heterogeneous, and therefore, BTP cannot be considered as a single entity. However, uniformly BTP has an important impact on a patient's functionality, which supports the need for early detection and treatment

Acció dels andrògens en el testicle: un paper per a la meiosi

La funció que duen a terme els andrògens en l'espermatogènesi és, encara en certa mesura, enigmàtica: mentre que llur implicació és absolutament vital en la iniciació i en el manteniment del procés espermatogènic normal, la seva funció específica encara no està definida de manera precisa. Els andrògens, com les altres hormones esteroïdals, actuen a través del seu corresponent receptor anomenat receptor d'andrògens (AR). Fins avui, no hi ha gaire evidència que recolzi l'existència de diverses isoformes de l'AR com en el cas del sistema estrògensreceptor d'estrògens. Per tant, la pregunta de com els andrògens duen a terme la seva acció en l'espermatogènesi s'ha d'abordar definint dos processos: en primer lloc, s'han d'identifi- car amb total certesa els tipus cell. ulars testiculars capaços de respondre directament a l'estimulació androgènica. De manera específica, la qüestió per resoldre és quins són els tipus cellulars que expressen l'AR en el testicle. En segon lloc, sabent també que el complex del lligand unit a l'AR actua com a factor de transcripció, caldrà determinar quins són els gens que estaran activats o reprimits en les cèll. ules que tenen AR en resposta a l'estimulació androgènica. Fins que aquestes dues preguntes no estiguin contestades amb tota certesa, el mecanisme pel qual els andrògens regulen l'espermatogènesi serà, en el millor dels casos, especulatiu. En aquesta revisió presentem evidència que els andrògens actuen únicament a les cèll. ules somàtiques del testicle, com són les cèll. ules de Sertoli, les de Leydig, les mioides peritubulars i les cèll. ules del múscul llis que envolten els vasos sanguinis. A més a més, també discutim la possibilitat que els andrògens siguin indispensables per a l'inici de la meiosi, encara que continua essent desconegut el mecanisme pel qual els andrògens actuen en aquest procés.The role that androgens play in spermatogenesis still remains enigmatic: whereas their involvement is absolutely vital to the initiation and maintenance of the normal spermatogenic process, their specific role is yet to be defined. Androgens, like other steroid hormones, act via their corresponding receptor termed the androgen receptor (AR). To date, there is little evidence to support the notion that there are multiple forms of AR as is the case for the estrogen-estrogen receptor system. Thus, the question of how androgens manifest their action on spermatogenesis becomes one of defining two processes: First, the cell types within the testis that are capable of responding directly to androgen stimulation must be identified with absolute certainty. Specifically, this question can be stated as what cell types in the testis express AR. Second, given that the ligand-bound AR serves as a transcription factor, the question then becomes what are the genes turned on or off in AR positive cells in response to androgen stimulation? Until these two questions are unequivocally answered, the mechanism of how androgens regulate spermatogenesis will remain speculative at best. In this review we present evidence that androgens act solely at the level of the somatic cells of the testis, including Sertoli cells, Leydig cells, peritubular myoid cells and smooth muscle cells surrounding blood vessels. In addition, we discuss the likely possibility that androgens are indispensable for the onset of meiosis, albeit how they accomplish this remains a mystery

Repurposing the yellow fever vaccine for intratumoral immunotherapy

Live 17D is widely used as a prophylactic vaccine strain for yellow fever virus that induces potent neutralizing humoral and cellular immunity against the wild-type pathogen. 17D replicates and kills mouse and human tumor cell lines but not non-transformed human cells. Intratumoral injections with viable 17D markedly delay transplanted tumor progression in a CD8 T-cell-dependent manner. In mice bearing bilateral tumors in which only one is intratumorally injected, contralateral therapeutic effects are observed consistent with more prominent CD8 T-cell infiltrates and a treatment-related reduction of Tregs. Additive efficacy effects were observed upon co-treatment with intratumoral 17D and systemic anti-CD137 and anti-PD-1 immunostimulatory monoclonal antibodies. Importantly, when mice were preimmunized with 17D, intratumoral 17D treatment achieved better local and distant antitumor immunity. Such beneficial effects of prevaccination are in part explained by the potentiation of CD4 and CD8 T-cell infiltration in the treated tumor. The repurposed use of a GMP-grade vaccine to be given via the intratumoral route in prevaccinated patients constitutes a clinically feasible and safe immunotherapy approach

Repurposing the yellow fever vaccine for intratumoral immunotherapy

Live 17D is widely used as a prophylactic vaccine strain for yellow fever virus that induces potent neutralizing humoral and cellular immunity against the wild-type pathogen. 17D replicates and kills mouse and human tumor cell lines but not non-transformed human cells. Intratumoral injections with viable 17D markedly delay transplanted tumor progression in a CD8 T-cell-dependent manner. In mice bearing bilateral tumors in which only one is intratumorally injected, contralateral therapeutic effects are observed consistent with more prominent CD8 T-cell infiltrates and a treatment-related reduction of Tregs. Additive efficacy effects were observed upon co-treatment with intratumoral 17D and systemic anti-CD137 and anti-PD-1 immunostimulatory monoclonal antibodies. Importantly, when mice were preimmunized with 17D, intratumoral 17D treatment achieved better local and distant antitumor immunity. Such beneficial effects of prevaccination are in part explained by the potentiation of CD4 and CD8 T-cell infiltration in the treated tumor. The repurposed use of a GMP-grade vaccine to be given via the intratumoral route in prevaccinated patients constitutes a clinically feasible and safe immunotherapy approach