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The progressive accumulation of senescent cells in tissues in response to damage importantly contributes to pathophysiological conditions such as fibrosis, diabetes, cancer, Alzheimer's and ageing. Consistent with this, eliminating senescent cells prolongs the lifespan and healthspan in animals and ameliorates certain diseases. Detecting and clearing senescent cells from human tissues could therefore have a significant diagnostic and prognostic impact. However, identifying senescent cells in vivo has proven to be complex. To address this, we characterized and validated a panel of novel membrane markers of senescence. Here, we show the application of molecularly imprinted nanoparticles (nanoMIPs) against an extracellular epitope of one of these markers, B2M, to detect senescent cells in vitro and in vivo. We show that nanoMIPs do not elicit toxic responses in the cells or in mice and successfully recognize old animals, which have a higher proportion of senescent cells in their organs. Importantly, nanoMIPs loaded with drugs can specifically kill senescent cells. Our results provide a proof-of-principle assessment of specific and safe nanotechnology-based approaches for senescent cell detection and clearance with potential clinical relevance.

One of the hallmarks of aging is the progressive accumulation of senescent cells in organisms, which has been proposed to be a contributing factor to age‐dependent organ dysfunction. We recently reported that Bruton's tyrosine kinase (BTK) is an upstream component of the p53 responses to DNA damage. BTK binds to and phosphorylates p53 and MDM2, which results in increased p53 activity. Consistent with this, blocking BTK impairs p53‐induced senescence. This suggests that sustained BTK inhibition could have an effect on organismal aging by reducing the presence of senescent cells in tissues. Here, we show that ibrutinib, a clinically approved covalent inhibitor of BTK, prolonged the maximum lifespan of a Zmpste24−/− progeroid mice, which also showed a reduction in general age‐related fitness loss. Importantly, we found that certain brain functions were preserved, as seen by reduced anxiety‐like behaviour and better long‐term spatial memory. This was concomitant to a decrease in the expression of specific markers of senescence in the brain, which confirms a lower accumulation of senescent cells after BTK inhibition. Our data show that blocking BTK has a modest increase in lifespan in Zmpste24−/− mice and protects them from a decline in brain performance. This suggests that specific inhibitors could be used in humans to treat progeroid syndromes and prevent the age‐related degeneration of organs such as the brain., We showed that blocking Bruton's tyrosine kinase (BTK) dampens p53 activity and the induction of senescence in vitro. Here, we show that BTK inhibitors increase maximum lifespan and healthspan of progeroid mice. Moreover, they prevent the deterioration of certain cognitive functions and reduce the accumulation of senescent cells in the brain. This suggests that clinically available BTK inhibitors could ameliorate some features of ageing in susceptible patients.

Background: Quinine (QU) has been identified as a testicular toxicant that leads to infertility. However some plant extracts have demonstrated protective effects on the testes.Objective: To determine the effect of Mucuna pruriens (MP) seed extract on the testes and its protective role on QU-induced testicular damage.Methods: Twenty male rats weighing between 120-150 g were used for the study. They were divided into four groups of five rats each. Group I (control) administered distilled water for 8 weeks. Group II received 10 mg/kg of QU only for 8 weeks. Group III rats were treated with QU and MP seed extract at 10 and 75 mg/kg concurrently for 8 weeks. Group IV received 75 mg/kg of MP seed extract only for 8 weeks. At the end of the experimental durations animals were sacrificed by cervical dislocation. Testes harvested, processed for testicular: glutathione (GSH), catalase activity (CAT), superoxide dismutase (SOD) activity, testicular malondialdehyde (MDA) and microscopic studies. Blood samples collected for testosterone assay.Results: There were significant increases in serum testosterone and testicular antioxidants (GSH, CAT and SOD) levels and a decrease in MDA levels in rats treated with MP only and parallel doses of QU and MP for 8 weeks when compared to control and animals treated with QU alone. The histology showed corresponding improvement compared to control and QU treated rats.Conclusion: MP increases testosterone levels and testicular antioxidant enzymes as well as protecting the testis against QU induced testicular damage.Keywords: Mucuna pruriens, Testis, Quinine, Infertility

p53 is a tumour suppressor that is activated in response to various types of stress. It is regulated by a complex pattern of over 50 different post-translational modifications, including ubiquitination by the E3 ligase MDM2, which leads to its proteasomal degradation. We have previously reported that expression of Bruton's Tyrosine Kinase (BTK) induces phosphorylation of p53 at the N-terminus, including Serine 15, and increases its protein levels and activity. The mechanisms involved in this process are not completely understood. Here, we show that BTK also increases MDM2 and is necessary for MDM2 upregulation after DNA damage, consistent with what we have shown for other p53 target genes. Moreover, we found that BTK binds to MDM2 on its PH domain and induces its phosphorylation. This suggested a negative regulation of MDM2 functions by BTK, supported by the fact BTK expression rescued the inhibitory effects of MDM2 on p53 transcriptional activity. Indeed, we observed that BTK mediated the loss of the ubiquitination activity of MDM2, a process that was dependent on the phosphorylation functions of BTK. Our data together shows that the kinase activity of BTK plays an important role in disrupting the MDM2-p53 negative feedback loop by acting at different levels, including binding to and inactivation of MDM2. This study provides a potential mechanism to explain how BTK modulates p53 functions.

Aim: This study was carried out to determine the effects of Cissus populnea and Panax ginseng on flutamide-induced testicular toxicities in pre-pubertal rats. Place and Duration of Study: Department of Anatomy, College of Medicine of the University of Lagos, Lagos – Nigeria, between May and December 2010. Methodology: 20 male immature (25 days old) Wistar rats were used. They were randomly divided into 4 groups; 1 control and 3 treatment groups. Group A served as control, group B was administered flutamide and Cissus populnea, group C was administered flutamide and Panax ginseng and group D was administered flutamide alone. Body weight and testicular weights were measured. Hormonal assay for testosterone, FSH and LH were done using Enzyme-Linked Immunosorbent Assay (ELISA). Histopathology of the testis was also investigated. Result: There were no statistically significant differences in serum testosterone levels in all three treatment groups when compared with the control group. There was a significant increase in the serum LH level in group D when compared with the control group (p

A three- year- old Doberman was presented with complaint of lethargy and weight- loss. Physical examination revealed a mass in the right abdomen. Laboratory abnormalities included anaemia, azotaemia and metabolic acidosis. Sonogram of the mass was an anaechoic area surrounded by hypoechoic tissue. The mass was located between the right kidney and ovary and showed papillary and tubular pattern of cystadenocarcinoma. Nephroureterectomy and ovariohysterectomy was performed; however bitch was euthanized owing to poor improvement, while necropsy of the left kidney revealed an end-stage kidney. It was concluded that the cystadenocarcinoma must have arisen secondary to a primary ovarian adenocarcinoma through stromal invasion. Se presentó una perra doberman de tres años de edad aquejada de letargo y pérdida de peso. El examen físico reveló una masa en el abdomen derecho. El examen de laboratorio mostró anormalidades que incluyeron anemia, azotemia y acidosis metabólica. La ecografía de la masa mostró un área anecoica rodeada por tejido hipoecoico. La masa se localizó entre el riñón derecho y ovario y mostró el patrón papilar y tubular del cistoadenocarcinoma. Se realizó la nefroureterectomía y ovariohisterectomía, sin embargo la perra fue sacrificada debido a la falta de mejoría, donde la autopsia del riñón izquierdo reveló un riñón en etapa terminal. Se concluyó que el cistoadenocarcinoma debió haber surgido secundario a un adenocarcinoma primario de ovario a través de la invasión del estroma.

A three- year- old Doberman was presented with complaint of lethargy and weight- loss. Physical examination revealed a mass in the right abdomen. Laboratory abnormalities included anaemia, azotaemia and metabolic acidosis. Sonogram of the mass was an anaechoic area surrounded by hypoechoic tissue. The mass was located between the right kidney and ovary and showed papillary and tubular pattern of cystadenocarcinoma. Nephroureterectomy and ovariohysterectomy was performed; however bitch was euthanized owing to poor improvement, while necropsy of the left kidney revealed an end-stage kidney. It was concluded that the cystadenocarcinoma must have arisen secondary to a primary ovarian adenocarcinoma through stromal invasion.

The histology of the middle cerebral artery (MCA) in Nigerian Africans has not been previously studied. One hundred MCAs obtained at autopsy from fifty adult Nigerians were studied. The vessels were processed and stained with Ehrlich's haematoxylin and eosin, elastic Van Gieson and Masson's trichrome stains. Early branches were given off before the perforators in two middle cerebral arteries, and there was one accessory MCA, making an incidence of anomalies of 3%. No aneurysm was observed in any of the cases. The internal elastic laminas were well developed but the external elastic laminas of the vessels were poorly developed. Cióse to the bif urcations the túnica media tapered gradually and at the bif urcations, the túnica media was completely deficient being replaced by the túnica adventitia (Forbus raphé). The túnica adventitia was thicker at the bifurcations (0.21mm) compared to other sites of the vessel. The average thickness of the MCA túnica media atits origin was 0.12mm while thatof the túnica adventitia was O.lOmm. Theseresults are similar to what has been described in the literature for Caucasians. It buttresses the assertion that anatomical anomalies of the MCA are rare. The seemingly low frequency of MCA aneurysms in Nigerian Africans is not due to its anomalies or histology.

The histology of the middle cerebral artery (MCA) in Nigerian Africans has not been previously studied. One hundred MCAs obtained at autopsy from fifty adult Nigerians were studied. The vessels were processed and stained with Ehrlich's haematoxylin and eosin, elastic Van Gieson and Masson's trichrome stains. Early branches were given off before the perforators in two middle cerebral arteries, and there was one accessory MCA, making an incidence of anomalies of 3%. No aneurysm was observed in any of the cases. The internal elastic laminas were well developed but the external elastic laminas of the vessels were poorly developed. Cióse to the bif urcations the túnica media tapered gradually and at the bif urcations, the túnica media was completely deficient being replaced by the túnica adventitia (Forbus raphé). The túnica adventitia was thicker at the bifurcations (0.21mm) compared to other sites of the vessel. The average thickness of the MCA túnica media atits origin was 0.12mm while thatof the túnica adventitia was O.lOmm. Theseresults are similar to what has been described in the literature for Caucasians. It buttresses the assertion that anatomical anomalies of the MCA are rare. The seemingly low frequency of MCA aneurysms in Nigerian Africans is not due to its anomalies or histology. La histología de la arteria cerebral media (ACM) de los africanos de Nigeria no ha sido previamente estudiada. Fueron examinadas 100 ACM, obtenidas en autopsias de 50 individuos nigerianos adultos. Las arterias fueron procesadas y teñidas con hematoxilina y eosina de Ehrlich, Van Gieson para fibras elásticas y tricrómico de Masson. Ramas proximales se originan antes de la división en dos arterias cerebrales medias, y había una ACM accesoria, constituyendo una incidencia de anomalías del 3%. No se observó aneurisma en ninguno de los casos. La lámina elástica interna estaba bien desarrollada, pero la lámina elástica externa de los vasos estaba pobremente desarrollada. Cerca de la bifurcación la túnica media es gradualmente cónica, la túnica media es totalmente deficiente siendo sustituida por la túnica adventicia (Forbus raphé). La túnica adventicia es más gruesa en las bifurcaciones (0.21mm) en comparación con otros lugares del buque. El grosor medio de la túnica media de ACM en su origen fue 0.12mm mientras que el de la túnica adventicia de O.lOmm. Estos resultados son similares a los que han sido descritos en la literatura para Caucásicos. Es importante la afirmación que las anomalías anatómicas de la ACM son raras. La aparentemente baja frecuencia de los aneurismas de ACM en nigerianos africanos no es debido a sus anomalías o a la histología.