Differential Expression of Kisspeptin System and Kisspeptin Receptor Trafficking during Spermatozoa Transit in the Epididymis

The hypothalamus–pituitary–testis axis controls the production of spermatozoa, and the kisspeptin system, comprising Kiss1 and Kiss1 receptor (Kiss1R), is the main central gatekeeper. The activity of the kisspeptin system also occurs in testis and spermatozoa, but currently the need of peripheral kisspeptin to produce gametes is not fully understood. Hence, we characterized kisspeptin system in rat spermatozoa and epididymis caput and cauda and analyzed the possible presence of Kiss1 in the epididymal fluid. The presence of Kiss1 and Kiss1R in spermatozoa collected from epididymis caput and cauda was evaluated by Western blot; significant high Kiss1 levels in the caput (p < 0.001 vs. cauda) and constant levels of Kiss1R proteins were observed. Immunofluorescence analysis revealed that the localization of Kiss1R in sperm head shifts from the posterior region in the epididymis caput to perforatorium in the epididymis cauda. In spermatozoa-free epididymis, Western blot revealed higher expression of Kiss1 and Kiss1R in caput (p < 0.05 vs. cauda). Moreover, immunohistochemistry revealed that Kiss1 and Kiss1R proteins were mainly localized in the secretory epithelial cell types and in contractile myoid cells, respectively. Finally, both dot blot and Elisa revealed the presence of Kiss1 in the epididymal fluid collected from epididymis cauda and caput, indicating that rat epididymis and spermatozoa possess a complete kisspeptin system. In conclusion, we reported for the first time in rodents Kiss1R trafficking in spermatozoa during the epididymis transit and Kiss1 measure in the epididymal fluid, thus suggesting a possible role for the system in spermatozoa maturation and storage within the epididymis

Adjuvant capecitabine in triple negative breast cancer patients with residual disease after neoadjuvant treatment: real-world evidence from CaRe, a multicentric, observational study

Background: In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized CREATE-X study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available. Methods: We carried out a multicenter, observational study, involving 44 oncologic centres. Triple negative breast cancer patients with residual disease, treated with adjuvant capecitabine from January 2017 through June 2021, were recruited. We primarily focused on treatment tolerability, with toxicity being reported as potential cause of treatment discontinuation. Secondarily, we assessed effectiveness in the overall study population and in a subset having a minimum follow-up of 2 years. Results: Overall, 270 patients were retrospectively identified. The 50.4% of the patients had residual node positive disease, 7.8% and 81.9% had large or G3 residual tumor, respectively, and 80.4% a Ki-67 >20%. Toxicity-related treatment discontinuation was observed only in 10.4% of the patients. In the whole population, at a median follow-up of 15 months, 2-year disease-free survival was 62%, 2 and 3-year overall survival 84.0% and 76.2%, respectively. In 129 patients with a median follow-up of 25 months, 2-year disease-free survival was 43.4%, 2 and 3-year overall survival 78.0% and 70.8%, respectively. Six or more cycles of capecitabine were associated with more favourable outcomes compared with less than six cycles. Conclusion: The CaRe study shows an unexpectedly good tolerance of adjuvant capecitabine in a real-world setting, although effectiveness appears to be lower than that observed in the CREATE-X study. Methodological differences between the two studies impose significant limits to comparability concerning effectiveness, and strongly invite further research

Biophysical Studies on the Effect of the 13 Position Substitution of the Anticancer Alkaloid Berberine on Its DNA Binding

The structural effects and thermodynamics of the DNA binding of six berberine analogues with alkyl chains of varying length and a terminal phenyl group at the C-13 position were investigated. All the analogues bound DNA noncooperatively in contrast to the cooperative binding of berberine. The binding affinity was higher and the effect of the chain length was only up to (CH₂)₃, after which the binding affinity decreased slightly. Intercalative binding with strong stabilization of the DNA helix was revealed. Binding resulted in the weakening of the base stacking with moderate conformational changes within the B-form. The binding was entropy driven in each case, the entropy contribution to the free energy increasing with the chain length up to the threshold (CH₂)₃. The complexation was dominated by nonpolyelectrolytic forces in each case; polyelectrolytic forces contributed only a quarter to the total free energy at 50 mM [Na⁺]. Overall, the phenylalkyl substitution at the C-13 position considerably enhanced the DNA binding and was highest for the analogue with (CH₂)₃. Structural and thermodynamic data on the DNA binding aspects of the substituted berberines are presented in comparison with berberine

Annali storici di Principato Citra, A. 1, n. 1.1 (2003)

A. 1, n. 1.1 (2003): G. Guardia, Editoriale, P. 3 ; F. Sofia, Il “Bollettino Storico di Salerno e Principato Citra”: un bilancio (1983- 1999) e alcune riflessioni, P. 5 ; F. La Greca, Tredici anni di Annali Cilentani (1989-2001), P. 12 ; G. D’Ajello, Lo statista Matteo d’Ajello e la politica nazionale al tramonto della monarchia normanna in Sicilia, P. 17 ; A. D’Auria, A caccia di prebende: il clero di Principato Citra a Napoli, P. 67 ; S. Micera, Gli universitari a Napoli dalla restaurazione dei Borbone all’unita’, P. 106 ; R.M. Valisena, Briganti nel Vallo di Diano, P. 119 ; P. Zoccoli, Alcune considerazioni sulla commercializzazione dei prodotti tipici locali attraverso il web: il caso della ditta Palilia, P. 150 ; C. Cerone, Il mulino a vento di Montecorice: progetto di recupero funzionale, P. 161 ; L. Rossi, Augusto Placanica, P. 206 ; F. Sofia, Un ricordo personale di Augusto Placanica, P. 208 ; G. Guardia, Miro’, P. 213

T-Large Granular Lymphocytic Leukemia with Hepatosplenic T-Cell Lymphoma? A Rare Case of Simultaneous Neoplastic T-Cell Clones Highlighted by Flow Cytometry and Review of Literature

Lymphoproliferative diseases are a heterogeneous set of malignant clonal proliferations of lymphocytes. Despite well-established diagnostic criteria, the diagnosis remains difficult due to their variety in clinical presentation and immunophenotypic profile. Lymphoid T-cell disorders are less common than B-cell entities, and the lack of a clear immunophenotypic characteristic makes their identification hard. Flow cytometry turned out to be a useful tool in diagnosing T-cell disorders and to resolve complicated cases, especially if the number of analyzable neoplastic cells is small. We present a case of a 55-year-old man with simultaneous lymphoproliferative neoplastic T-cell clones, one αβ and the other γδ, identified and characterized by flow cytometry (FC), exploiting the variable expression intensity of specific markers. However, the patient’s rapid decline made it impossible to define a differential diagnosis in order to confirm the identity of the γδ clone, which remains uncertain. This case is added to the few other cases already documented in the literature, characterized by the co-existence of T-large granular lymphocytic leukemia (T-LGLL)-αβ and T-LGLL-γδ/Hepatosplenic T-cell lymphoma (HSTCL). Our case underlines the key role of sensitive diagnostic tools in the assessment of potential relationship between the diagnosis, prognosis, and treatment in the two pathologies

Unveiling the mechanism of action of acylated temporin L analogues against multidrug-resistant Candida albicans

AbstractThe increasing resistance of fungi to conventional antifungal drugs has prompted worldwide the search for new compounds. In this work, we investigated the antifungal properties of acylated Temporin L derivatives, Pent-1B and Dec-1B, against Candida albicans, including the multidrug-resistant strains. Acylated peptides resulted to be active both on reference and clinical strains with MIC values ranging from 6.5 to 26 µM, and they did not show cytotoxicity on human keratinocytes. In addition, we also observed a synergistic or additive effect with voriconazole for peptides Dec-1B and Pent-1B through the checkerboard assay on voriconazole-resistant Candida strains. Moreover, fluorescence-based assays, NMR spectroscopy, and confocal microscopy elucidated a potential membrane-active mechanism, consisting of an initial electrostatic interaction of acylated peptides with fungal membrane, followed by aggregation and insertion into the lipid bilayer and causing membrane perturbation probably through a carpeting effect

The interplay between kisspeptin and endocannabinoid systems modulates male hypothalamic and gonadic control of reproduction in vivo

Introduction: Male reproduction is under the control of the hypothalamus–pituitary–gonadal (HPG) axis. The endocannabinoid system (ECS) and the kisspeptin system (KS) are two major signaling systems in the central and peripheral control of reproduction, but their possible interaction has been poorly investigated in mammals. This manuscript analyzes their possible reciprocal modulation in the control of the HPG axis. Materials and methods: Adolescent male rats were treated with kisspeptin-10 (Kp10) and endocannabinoid anandamide (AEA), the latter alone or in combination with the type 1 cannabinoid receptor (CB1) antagonist rimonabant (SR141716A). The hypothalamic KS system and GnRH expression, circulating sex steroids and kisspeptin (Kiss1) levels, and intratesticular KS and ECS were evaluated by immunohistochemical and molecular methods. Non-coding RNAs (i.e., miR145-5p, miR-132-3p, let7a-5p, let7b-5p) were also considered. Results: Circulating hormonal values were not significantly affected by Kp10 or AEA; in the hypothalamus, Kp10 significantly increased GnRH mRNA and aromatase Cyp19, Kiss1, and Kiss1 receptor (Kiss1R) proteins. By contrast, AEA treatment affected the hypothalamic KS at the protein levels, with opposite effects on the ligand and receptor, and SR141716A was capable of attenuating the AEA effects. Among the considered non-coding RNA, only the expression of miR145-5p was positively affected by AEA but not by Kp10 treatment. Localization of Kiss1+/Kiss1R+ neurons in the arcuate nucleus revealed an increase of Kiss1R-expressing neurons in Kp10- and AEA-treated animals associated with enlargement of the lateral ventricles in Kp10-treated animals. In the brain and testis, the selected non-coding RNA was differently modulated by Kp10 or AEA. Lastly, in the testis, AEA treatment affected the KS at the protein levels, whereas Kp10 affected the intragonadal levels of CB1 and FAAH, the main modulator of the AEA tone. Changes in pubertal transition-related miRNAs and the intratesticular distribution of Kiss1, Kiss1R, CB1, and CB2 following KP and AEA treatment corroborate the KS-ECS crosstalk also showing that the CB1 receptor is involved in this interplay. Conclusion: For the first time in mammals, we report the modulation of the KS in both the hypothalamus and testis by AEA and revealed the KP-dependent modulation of CB1 and FAAH in the testis. KP involvement in the progression of spermatogenesis is also suggested

Rivista di studi salernitani. A.2, n.4 (1969)

A.2, n.4 (1969): Mario d’Addio, Il problema della politica in Bodin e in Vico, P.3 ; Gabriele De Rosa, Il Sinodo di Policastro del 1784 e la censura napoletana, P. 101 ; Giuseppe Passaro, Ferentinum, civitas dell’Irpinia, P. 127 ; Pasquale Lopez, Le Confraternite laicali in Italia e la Riforma cattolica , P. 133 ; Antonio Cestaro, Il VI Congresso cattolico italiano nei rapporti del Procuratore generale e del Questore di Napoli, P. 239 ; Lucio Avagliano, Alessandro Rossi e le origini dell’Italia industriale , P. 271 ; Francesco Malgeri, Aspetti politici, diplomatici e militari nella preparazione della guerra libica, P. 337 ; Ferdinando Cordova, Il colpo di stato del 3 marzo 1922 a Fiume, P. 393 ; Giuseppe Cacciatore, Il « momento della prassi » nello storicismo di Dilthey , P. 423 ; Luigi Torraca, Le epistole greche di Bruto tradotte in latino da Niccolò Angelio, P. 463 ; Giovanni Viansino, La tecnica didascalica nell’ars amatoria di Ovidio, P. 487 ; Luciano Osbat, Contributo per un esame socio-statistico della popolazione universitaria del Magistero di Salerno nell’anno accademico 1967-1968, P. 503 ; Francesco Lazzari, Il «filosofo» Camus tra religione e irreligione 319 Giuseppe Zarone, A proposito di un nuovo libro di storia del pensiero politico, P. 527 ; Elio D’Auria, Considerazioni sulla politica estera dell’Italia fascista 337 Maria Rosaria Lombardi, La caduta della parola , P. 551 ; Recensioni su A. Gambasin (R. Vergani), F. Malgeri (P. Borzomati), E. Faldella e L Capello (M. Mazzetti), S. Moravia (E. del Gaudio), R. Bortot (V. Dini), G. J. Di Renzo (F. C. Ghilardi), G. E. Rusconi (V. Dini), C. Webb (A. Corrado) , P. 55

PLASTAMINATION: Outcomes on the Central Nervous System and Reproduction

Background: Environmental exposures to non-biodegradable and biodegradable plastics are unavoidable. Microplastics (MPs) and nanoplastics (NPs) from the manufacturing of plastics (primary sources) and the degradation of plastic waste (secondary sources) can enter the food chain directly or indirectly and, passing biological barriers, could target both the brain and the gonads. Hence, the worldwide diffusion of environmental plastic contamination (PLASTAMINATION) in daily life may represent a possible and potentially serious risk to human health. Objective: This review provides an overview of the effects of non-biodegradable and the more recently introduced biodegradable MPs and NPs on the brain and brain-dependent reproductive functions, summarizing the molecular mechanisms and outcomes on nervous and reproductive organs. Data from in vitro, ex vivo, non-mammalian and mammalian animal models and epidemiological studies have been reviewed and discussed. Results: MPs and NPs from non-biodegradable plastics affect organs, tissues and cells from sensitive systems such as the brain and reproductive organs. Both MPs and NPs induce oxidative stress, chronic inflammation, energy metabolism disorders, mitochondrial dysfunction and cytotoxicity, which in turn are responsible for neuroinflammation, dysregulation of synaptic functions, metabolic dysbiosis, poor gamete quality, and neuronal and reproductive toxicity. In spite of this mechanistic knowledge gained from studies of non-biodegradable plastics, relatively little is known about the adverse effects or molecular mechanisms of MPs and NPs from biodegradable plastics. Conclusion: The neurological and reproductive health risks of MPs/NPs exposure warrant serious consideration, and further studies on biodegradable plastics are recommended