Building a risk matrix for the safety assessment of wood derived biochars

Biochar is recognized as an efficient amendment and soil improver. However, environmental and quality assessments are needed to ensure the sustainability of its use in agriculture. This work considers the biochar's chemical-physical characterization and its potential phyto- and geno-toxicity, assessed with germination and Ames tests, obtaining valuable information for a safe field application. Three biochar types, obtained from gasification at different temperatures of green biomasses from the Tuscan-Emilian Apennines (in Italy), were compared through a broad chemical, physical and biological evaluation. The results obtained showed the relevance of temperature in determining the chemical and morphological properties of biochar, which was shown with several analytical techniques such as the elemental composition, water holding capacity, ash content, but also with FTIR and X-ray spectroscopies. These techniques showed the presence of different relevant surface aliphatic and aromatic groups. The procedures for evaluating the potential toxicity using seeds germination and Ames genotoxicity assay highlights that biochar does not cause detrimental effects when it enters in contact with soil, micro- and macro-organisms, and plants. The genotoxicity test provided a new highlight in evaluating biochar environmental safety

Deregulated PTEN/PI3K/AKT/mTOR signaling in prostate cancer: Still a potential druggable target?

Although the prognosis of patients with localized prostate cancer is good after surgery, with a favorable response to androgen deprivation therapy, about one third of them invariably relapse, and progress to castration-resistant prostate cancer. Overall, prostate cancer therapies remain scarcely effective, thus it is mandatory to devise alternative treatments enhancing the efficacy of surgical castration and hormone administration. Dysregulation of the phosphoinositide 3-kinase pathway has attracted growing attention in prostate cancer due to the highly frequent association of epigenetic and post-translational modifications as well as to genetic alterations of both phosphoinositide 3-kinase and PTEN to onset and/or progression of this malignancy, and to resistance to canonical androgen-deprivation therapy. Here we provide a summary of the biological functions of the major players of this cascade and their deregulation in prostate cancer, summarizing the results of preclinical and clinical studies with PI3K signaling inhibitors and the reasons of failure independent from genomic changes

Constitutive expression of the barley dehydrin gene aba2 enhances Arabidopsis germination in response to salt stress

Dehydrins (DHNs) are a sub-family of the late embryogenesis abundant proteins generally induced during development of desiccation tolerance in seeds and water deficit or salinity stress in plants. Nevertheless, a detailed understanding of the DHNs function is still lacking. In this work we investigated the possible protective role during salt stress of a Dhn from Hordeum vulgare (L.), aba2. The coding sequence of the aba2 gene was constitutively expressed in transgenic lines of Arabidopsis thaliana (L.). During salt stress conditions germination rate, cotyledon expansion and greening were greatly improved in the transgenic lines as compared to the wild type. Between 98 and 100% of the transgenic seeds germinated after two weeks in media containing up to 250 mM NaCl, and 90% after 22 days at 300 mM NaCl. In conditions of 200 mM NaCl 93% of the transgenic cotyledons had greened after two weeks, outperforming the wild type by 45%. Our study provides further evidence that DHNs have an important role in salt stress tolerance. The production of plants constitutively expressing DHNs could be an effective strategy to improve plant breeding programs

Standard surgical treatment for benign prostatic hyperplasia is safe for patients over 75 years: analysis of 100 cases from a high-volume urologic center

OBJECTIVES: In this study, we aimed to determine the complications of standard surgical treatments among patients over 75 years in a high-volume urologic center. METHODS: We analyzed 100 consecutive patients older than 75 years who had undergone transurethral prostatic resection of the prostate or open prostatectomy for treatment of benign prostatic hyperplasia from January 2008 to March 2010. We analyzed patient age, prostate volume, prostate-specific antigen level, international prostatic symptom score, quality of life score, urinary retention, co-morbidities, surgical technique and satisfaction with treatment. RESULTS: Median age was 79 years. Forty-eight patients had undergone transurethral prostatic resection of the prostate, and 52 had undergone open prostatectomy. The median International Prostatic Symptom Score was 20, the median prostate volume was 83 g, 51% were using an indwelling bladder catheter, and the median prostatespecific antigen level was 5.0 ng/ml. The most common comorbidities were hypertension, diabetes and coronary disease. After a median follow-up period of 17 months, most patients were satisfied. Complications were present in 20% of cases. The most common urological complication was urethral stenosis, followed by bladder neck sclerosis, urinary fistula, late macroscopic hematuria and persistent urinary incontinence. The most common clinical complication was myocardial infarction, followed by acute renal failure requiring dialysis. Incidental carcinoma of the prostate was present in 6% of cases. One case had urothelial bladder cancer. CONCLUSIONS: Standard surgical treatments for benign prostatic hyperplasia are safe and satisfactory among the elderly. Complications are infrequent, and urethral stenosis is the most common. No clinical variable is associated with the occurrence of complications

Mechanisms Predisposing Penile Fracture And Long-term Outcomes On Erectile And Voiding Functions

Purpose. To determine the mechanisms predisposing penile fracture as well as the rate of long-term penile deformity and erectile and voiding functions. Methods. All fractures were repaired on an emergency basis via subcoronal incision and absorbable suture with simultaneous repair of eventual urethral lesion. Patients' status before fracture and voiding and erectile functions at long term were assessed by periodic follow-up and phone call. Detailed history included cause, symptoms, and single-question self-report of erectile and voiding functions. Results. Among the 44 suspicious cases, 42 (95.4%) were confirmed, mean age was 34.5 years (range: 18-60), mean follow-up 59.3 months (range 9-155). Half presented the classical triad of audible crack, detumescence, and pain. Heterosexual intercourse was the most common cause (28 patients, 66.7%), followed by penile manipulation (6 patients, 14.3%), and homosexual intercourse (4 patients, 9.5%). "Woman on top" was the most common heterosexual position (n = 14, 50%), followed by "doggy style" (n = 8, 28.6%). Four patients (9.5%) maintained the cause unclear. Six (14.3%) patients had urethral injury and two (4.8%) had erectile dysfunction, treated by penile prosthesis and PDE-5i. No patient showed urethral fistula, voiding deterioration, penile nodule/curve or pain. Conclusions. "Woman on top" was the potentially riskiest sexual position (50%). Immediate surgical treatment warrants long-term very low morbidity. © 2014 Leonardo O. Reis et al.Kamdar, C., Mooppan, U.M.M., Kim, H., Gulmi, F.A., Penile fracture: Preoperative evaluation and surgical technique for optimal patient outcome (2008) BJU International, 102 (11), pp. 1640-1644. , 2-s2.0-56649083856 10.1111/j.1464-410X.2008.07902.xKramer, A.C., Penile fracture seems more likely during sex under stressful situations (2011) Journal of Sexual Medicine, 8 (12), pp. 3414-3417. , 2-s2.0-82955237445 10.1111/j.1743-6109.2011.02461.xSawh, S.L., O'Leary, M.P., Ferreira, M.D., Berry, A.M., Maharaj, D., Fractured penis: A review (2008) International Journal of Impotence Research, 20 (4), pp. 366-369. , 2-s2.0-48249147767 10.1038/ijir.2008.12Amit, A., Arun, K., Bharat, B., Navin, R., Sameer, T., Shankar, D.U., Penile fracture and associated urethral injury: Experience at a tertiary care hospital (2013) Canadian Urological Association Journal, 7, pp. E168-E170Moslemi, M.K., Evaluation of epidemiology, concomitant urethral disruption and seasonal variation of penile fracture: A report of 86 cases (2013) Canadian Urological Association Journal, 7, pp. E572-E575Hatzichristodoulou, G., Dorstewitz, A., Gschwend, J.E., Herkommer, K., Zantl, N., Surgical management of penile fracture and long-term outcome on erectile function and voiding (2013) The Journal of Sexual Medicine, 10, pp. 1424-1430Nomura, J.T., Sierzenski, P.R., Ultrasound diagnosis of penile fracture (2010) Journal of Emergency Medicine, 38 (3), pp. 362-365. , 2-s2.0-77949914168 10.1016/j.jemermed.2008.03.010Ash, A., Miller, J., Preston, D., Point-of-care ultrasound used to exclude penile fracture (2012) Critical Ultrasound Journal, 417Beysel, M., Tekin, A., Gürdal, M., Yücebaş, E., Dengör, F., Evaluation and treatment of penile fractures: Accuracy of clinical diagnosis and the value of corpus cavernosography (2002) Urology, 60 (3), pp. 492-496. , 2-s2.0-0036753673 10.1016/S0090-4295(02)01813-7Gamal, W.M., Osman, M.M., Hammady, A., Aldahshoury, M.Z., Hussein, M.M., Saleem, M., Penile fracture:;ong-term results of surgical and conservative management (2011) Journal of Trauma, 71 (2), pp. 491-493. , 2-s2.0-80051783736 10.1097/TA.0b013e318209311

Ankrd2/ARPP is a novel Akt2 specific substrate andregulates myogenic differentiation upon cellular exposure to H(2)O(2).

Activation of Akt-mediated signaling pathways is crucial for survival, differentiation, and regeneration of muscle cells. A proteomic-based search for novel substrates of Akt was therefore undertaken in C(2)C(12) murine muscle cells exploiting protein characterization databases in combination with an anti-phospho-Akt substrate antibody. A Scansite database search predicted Ankrd2 (Ankyrin repeat domain protein 2, also known as ARPP) as a novel substrate of Akt. In vitro and in vivo studies confirmed that Akt phosphorylates Ankrd2 at Ser-99. Moreover, by kinase assay with recombinant Akt1 and Akt2, as well as by single-isoform silencing, we demonstrated that Ankrd2 is a specific substrate of Akt2. Ankrd2 is typically found in skeletal muscle cells, where it mediates the transcriptional response to stress conditions. In an attempt to investigate the physiological implications of Ankrd2 phosphorylation by Akt2, we found that oxidative stress induced by H(2)O(2) triggers this phosphorylation. Moreover, the forced expression of a phosphorylation-defective mutant form of Ankrd2 in C(2)C(12) myoblasts promoted a faster differentiation program, implicating Akt-dependent phosphorylation at Ser-99 in the negative regulation of myogenesis in response to stress conditions

Mechanisms involved in the promoting activity of fibroblasts in HTLV-1-mediated lymphomagenesis: Insights into the plasticity of lymphomatous cells

Among the mechanisms leading to progression to Adult T-cell Leukaemia/Lymphoma in Human T-cell Leukaemia Virus type 1 (HTLV-1)-infected subjects, the contribution of stromal components remains poorly understood. To dissect the role of fibroblasts in HTLV-1-mediated lymphomagenesis, transcriptome studies, cytofluorimetric and qRT-PCR analyses of surface and intracellular markers linked to plasticity and stemness in coculture, and in vivo experiments were performed. A transcriptomic comparison between a more lymphomagenic (C91/III) and the parental (C91/PL) cell line evidenced hyperactivation of the PI3K/Akt pathway, confirmed by phospho-ELISA and 2-DE and WB analyses. C91/III cells also showed higher expression of mesenchymal and stemness genes. Short-term coculture with human foreskin fibroblasts (HFF) induced these features in C91/PL cells, and significantly increased not only the cancer stem cells (CSCs)-supporting CD10+GPR77+ HFF subpopulation, but also the percentage of ALDH1bright C91/PL cells. A non-cytotoxic acetylsalicylic acid treatment decreased HFF-induced ALDH1bright C91/PL cells, downregulated mesenchymal and stemness genes in cocultured cells, and delayed lymphoma growth in immunosuppressed mice, thus hindering the supportive activity of HFF on CSCs. These data suggest that crosstalk with HFF significantly intensifies the aggressiveness and plasticity of C91/PL cells, leading to the enrichment in lymphoma-initiating cells. Additional research is needed to better characterize these preliminary findings

Neurofilament light chain: a specific serum biomarker of axonal damage severity in rat models of Chemotherapy-Induced Peripheral Neurotoxicity

Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) is a severe and long-lasting side effect of anticancer therapy, which can severely impair patients’ quality of life. It is a sensory and length-dependent neuropathy, which predominantly affects large myelinated fibers. Easy and reliable monitoring of CIPN in patients is still an unmet clinical need. Since increasing clinical evidence supports the potential use of neurofilament light chain (NfL) as a biomarker of axonal injury, in this study we measured serum NfL levels in animals chronically treated with cisplatin (CDDP) and paclitaxel (PTX), two antineoplastic drugs with different neuronal targets. Wistar rats were treated with CDDP (2 mg/kg i.p. twice/week for 4 weeks) or PTX (10 mg/kg i.v. once/week for 4 weeks). Repeated serum NfL quantification was obtained using the Single Molecule Array (Simoa) technology. The onset and progression of peripheral neurotoxicity were evaluated through neurophysiology, morphological assessments and intraepidermal nerve fibers density quantification. Our results showed that serum NfL measurements correlated with the severity of axonal damage. In fact, both treatments induced serum NfL increase, but higher levels were evidenced in PTX-treated animals, compared with CDDP-treated rats, affected by a milder neurotoxicity. Notably, also the timing of the NfL level increase was associated with the severity of morphological and functional alterations of axonal structure. Therefore, NfL could be a useful biomarker for axonal damage in order to follow the onset and severity of axonal degeneration and possibly limit the occurrence of serious PNS disease

Nuclear phospholipase C β1 signaling, epigenetics and treatments in MDS.

Myelodysplastic syndromes (MDS), clonal hematopoietic stem-cell disorders mainly affecting older adult patients, show ineffective hematopoiesis in one or more of the lineages of the bone marrow. Most MDS are characterized by anemia, and a number of cases progresses to acute myeloid leukemia (AML). Indeed, the molecular mechanisms underlying the MDS evolution to AML are still unclear, even though the nuclear signaling elicited by PI-PLCβ1 has been demonstrated to play an important role in the control of the balance between cell cycle progression and apoptosis in MDS cells. Here we review both the role of epigenetic therapy on PI-PLCβ1 promoter and the changes in PI-PLCβ1 expression in MDS patients treated for anemia.Myelodysplastic syndromes (MDS), clonal hematopoietic stem-cell disorders mainly affecting older adult patients, show ineffective hematopoiesis in one or more of the lineages of the bone marrow. Most MDS are characterized by anemia, and a number of cases progresses to acute myeloid leukemia (AML). Indeed, the molecular mechanisms underlying the MDS evolution to AML are still unclear, even though the nuclear signaling elicited by PI-PLCβ1 has been demonstrated to play an important role in the control of the balance between cell cycle progression and apoptosis in MDS cells. Here we review both the role of epigenetic therapy on PI-PLCβ1 promoter and the changes in PI-PLCβ1 expression in MDS patients treated for anemia. © 2012 Elsevier Ltd