M. Cvetaeva, Ultimi versi. 1938-1941, trad. di P. Napolitano, Voland, Roma 2021, pp. 149.

Viene proposta la recensione di un volumetto di poesie di Marina Cvetaeva tradotto e curato da Pina Napolitano. Pur evidenziando alcuni limiti filologici e talune scelte linguistiche che sembrano poco meditate (ad es. l'uso di calchi sintattici dal russo), si apprezza nell'insieme l'iniziativa editoriale e la resa generale della cifra cvetaeviana

Radiographic classification of coronal plane femoral deformities in polyostotic fibrous dysplasia

Fibrous dysplasia of bone is a skeletal dysplasia with a propensity to affect the femur in its polyostotic form, leading to deformity, fracture, and pain. The proximal femur is most commonly involved with a tendency to distal progression, thereby producing the typical shepherd's crook deformity. However, there are few data on the spectrum and progression of femoral deformities in polyostotic fibrous dysplasia

Dual tumor suppressing and promoting function of Notch1 signaling in human prostate cancer.

Adenocarcinomas of the prostate arise as multifocal heterogeneous lesions as the likely result of genetic and epigenetic alterations and deranged cell-cell communication. Notch signaling is an important form of intercellular communication with a role in growth/differentiation control and tumorigenesis. Contrasting reports exist in the literature on the role of this pathway in prostate cancer (PCa) development. We show here that i) compared to normal prostate tissue, Notch1 expression is significantly reduced in a substantial fraction of human PCas while it is unaffected or even increased in others; ii) acute Notch activation both inhibits and induces process networks associated with prostatic neoplasms; iii) down-modulation of Notch1 expression and activity in immortalized normal prostate epithelial cells increases their proliferation potential, while increased Notch1 activity in PCa cells suppresses growth and tumorigenicity through a Smad3-dependent mechanism involving p21WAF1/CIP1; iv) prostate cancer cells resistant to Notch growth inhibitory effects retain Notch1-induced upregulation of pro-oncogenic genes, like EPAS1 and CXCL6, also overexpressed in human PCas with high Notch1 levels. Taken together, these results reconcile conflicting data on the role of Notch1 in prostate cancer

Modular versus monoblock stem in revision total hip arthroplasty: a systematic review and meta-analysis

Background: Total hip arthroplasty (THA) is estimated to grow in the following decades with a consequent increase of THA revisions (rTHA). This systematic review and meta-analysis aims to compare modular and monoblock stem in rTHA surgery, focusing on clinical and radiological outcomes and complication rates. Methods: A literature search was performed using the following search strategy: ((Modular stem) OR (monolithic stem)) AND (hip review) on PubMed, Scopus, and Cochrane. Randomized controlled trials (RCTs) and observational studies (OS) compared clinical and radiological outcomes, and complication rates for monoblock and modular revision femoral stem were included. The risk of bias was assessed through the Methodological Index for Non-Randomized Studies (MINORS) score. The Review Manager (RevMan) software was used for the meta-analysis. The rate of complications was assessed using odds ratio (OR) with 95% confidence intervals (CIs). Results: The authors included 11 OS and one RCT with 3,671 participants (mean age: 68.4 years old). The mean follow-up was 46.9 months. There was no prevalence of subsidence for one type of stem. Mean subsidence was from 0.92 to 10 mm for modular stem and from 1 to 15 mm for monoblock stem. Postoperative Harris Hip Score (HHS) showed better results with modular stems without statistical significance [mean difference (MD) =1.32; 95% CI: −1.62 to 4.27; P=0.38]. No statistically significant difference was found for dislocations (OR =2.48; 95% CI: 0.67 to 9.14; P=0.17), infections (OR =1.07; 95% CI: 0.51 to 2.23; P=0.86), intraoperative fractures (OR =1.62; 95% CI: 0.42 to 6.21; P=0.48), and postoperative fractures (OR =1.60; 95% CI: 0.55 to 4.64; P=0.39). Conclusions: Modular and monoblock stems show comparable and satisfactory clinical and radiological outcomes for rTHA. Both stems are valid and effective options for managing femoral bone deficit in hip revision surgery. The main limitation of this study is the small number and low quality of enclosed studies that compared the two stems. Moreover, the modular stem is usually used for more complex cases with lower quality femoral bone stock

Nucleoporin 153 regulates estrogen-dependent nuclear translocation of endothelial nitric oxide synthase and estrogen receptor beta in prostate cancer.

Nucleoporin 153 (Nup153), key regulator of nuclear import/export, has been recently associated to oncogenic properties in pancreatic and breast tumour cells modulating either cell motility and migration or gene expression by chromatin association. In the present work, we have characterized the role of Nup153 in a cellular model of prostate cancer (PCa). The analysis of several immortalized cell lines derived from freshly explants of prostate cancer specimens showed that Nup153 protein was higher and present in multimeric complexes with eNOS and ER f as compared to normal/hyperplastic prostate epithelial cells. This phenomenon was enhanced in the presence of 17 f-estradiol (E2, 10-7M). Further experiments revealed that eNOS and ER f were present in a DNA binding complexes associated with Nup153 promoter as demonstrated by ChIPs. Notably, after Nup153 depletion (siNup153), a reduction of migration capacity and colony formation in primary tumor-derived and metastatic PCa cells was observed. In addition, eNOS and ER f nuclear localization was lost upon siNup153 regardless of E2 treatment, suggesting that Nup153 is a key regulator of prostate cancer cell function and of the nuclear translocation of these proteins in response to hormone stimulus. Taken altogether our findings indicate that in PCa cells: i. the expression and function of Nup153 is modulated by estrogen signaling; ii. Nup153 contributes to cell migration and proliferation; iii. Nup153 regulates the nuclear translocation of eNOS and ER f by forming a multimeric complex. Our findings unveil Nup153 as a novel component of the estrogen-dependent multimeric complex, thus representing a potential therapeutic candidate in prostate cancer

Myc and Omomyc functionally associate with the Protein Arginine Methyltransferase 5 (PRMT5) in glioblastoma cells

The c-Myc protein is dysregulated in many human cancers and its function has not been fully elucitated yet. The c-Myc inhibitor Omomyc displays potent anticancer properties in animal models. It perturbs the c-Myc protein network, impairs c-Myc binding to the E-boxes, retaining transrepressive properties and inducing histone deacetylation. Here we have employed Omomyc to further analyse c-Myc activity at the epigenetic level. We show that both Myc and Omomyc stimulate histone H4 symmetric dimethylation of arginine (R) 3 (H4R3me2s), in human glioblastoma and HEK293T cells. Consistently, both associated with protein Arginine Methyltransferase 5 (PRMT5)-the catalyst of the reaction-and its co-factor Methylosome Protein 50 (MEP50). Confocal experiments showed that Omomyc co-localized with c-Myc, PRMT5 and H4R3me2s-enriched chromatin domains. Finally, interfering with PRMT5 activity impaired target gene activation by Myc whereas it restrained Omomyc-dependent repression. The identification of a histone-modifying complex associated with Omomyc represents the first demonstration of an active role of this miniprotein in modifying chromatin structure and adds new information regarding its action on c-Myc targets. More importantly, the observation that c-Myc may recruit PRMT5-MEP50, inducing H4R3 symmetric di-methylation, suggests previously unpredictable roles for c-Myc in gene expression regulation and new potential targets for therapy

Somatic deletion in exon 10 of aryl hydrocarbon receptor gene in human GH-secreting pituitary tumors

Objective/Purpose: The aryl hydrocarbon receptor (AHR) pathway plays a critical role in the biology of Growth Hormone (GH)-secreting pituitary tumor (somatotropinoma). Germline rs2066853 AHR variant was found to be more frequent among acromegaly patients and associated with a more severe disease with larger invasive somatropinoma, and with resistance to somatostatin analogs treatment in patients living in polluted areas. However, no somatic changes in AHR gene have been reported so far in acromegaly patients. On that basis, the aim of the study was to assess at the somatic level the AHR gene status encompassing exon 10 region, also because of the high rate of variants found in this genomic region. Methods: A cohort of 13 patients aged 20\u201376 years with biochemical, clinical and histological diagnosis of somatotropinoma was studied. DNA and RNA from pituitary tumor histological samples have been extracted and analyzed by PCR and direct sequencing for AHR gene variants, and compared with corresponding patients\u2019 germline DNA as well as normal pituitary tissue as reference control. Results: A degenerated letter codes in the region corresponding to AHR exon 10 (c.1239-c.2056) was detected in somatotropinomas-derived DNA but not in that of matched germline and pituitary normal tissue. By multiple PCR and sequencing analysis, we observed amplification only before codon 1246 and after codon 1254, confirming the presence of a tumor-restricted somatic deletion in the 5\u2019 upstream region of AHR exon 10. Analysis of PCR-amplified cDNA revealed a wildtype sequence of exon 9 and 10 in normal pituitary tissue, and a wildtype sequence of exon 9 and 10 up to codon 1246 and no sequence after the deletion region (c.1246-c.1254) in 6 out of 9 tumor samples. Patients carrying the germline rs2066853 AHR variant showed no somatic LOH at the corresponding genetic locus. Conclusion: This is the first demonstration of a recurrent somatic deletion in the exon 10 of the AHR gene in somatotropinomas. The functional impact of this genetic finding needs to be clarifie

Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health.

The short-lived turquoise killifish Nothobranchius furzeri (Nfu) is a valid model for aging studies. Here, we investigated its age-associated cardiac function. We observed oxidative stress accumulation and an engagement of microRNAs (miRNAs) in the aging heart. MiRNA-sequencing of 5 week (young), 12-21 week (adult) and 28-40 week (old) Nfu hearts revealed 23 up-regulated and 18 down-regulated miRNAs with age. MiR-29 family turned out as one of the most up-regulated miRNAs during aging. MiR-29 family increase induces a decrease of known targets like collagens and DNA methyl transferases (DNMTs) paralleled by 5´methyl-cytosine (5mC) level decrease. To further investigate miR-29 family role in the fish heart we generated a transgenic zebrafish model where miR-29 was knocked-down. In this model we found significant morphological and functional cardiac alterations and an impairment of oxygen dependent pathways by transcriptome analysis leading to hypoxic marker up-regulation. To get insights the possible hypoxic regulation of miR-29 family, we exposed human cardiac fibroblasts to 1% O <sub>2</sub> levels. In hypoxic condition we found miR-29 down-modulation responsible for the accumulation of collagens and 5mC. Overall, our data suggest that miR-29 family up-regulation might represent an endogenous mechanism aimed at ameliorating the age-dependent cardiac damage leading to hypertrophy and fibrosis