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81.
Alessia DAloia Michela Ceriani Renata Tisi Simone Stucchi Elena Sacco Barbara Costa 《International journal of molecular sciences》2022,23(13)
Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has been discussed for its safety and efficacy in cancer treatments. For this reason, we have inquired into its use on triple-negative human breast cancer. Analyzing the biological effects of CBD on MDA-MB-231, we have demonstrated that both CBD dosage and serum concentrations in the culture medium influence its outcomes; furthermore, light scattering studies demonstrated that serum impacts the CBD aggregation state by acting as a surfactant agent. Pharmacological studies on CBD in combination with chemotherapeutic agents reveal that CBD possesses a protective action against the cytotoxic effect exerted by cisplatin on MDA-MB-231 grown in standard conditions. Furthermore, in a low serum condition (0.5%), starting from a threshold concentration (5 µM), CBD forms aggregates, exerts cytostatic antiproliferative outcomes, and promotes cell cycle arrest activating autophagy. At doses above the threshold, CBD exerts a highly cytotoxic effect inducing bubbling cell death. Finally, IGF-1 and EGF antagonize the antiproliferative effect of CBD protecting cells from harmful consequences of CBD aggregates. In conclusion, CBD effect is strongly associated with the physical state and concentration that reaches the treated cells, parameters not taken into account in most of the research papers. 相似文献
82.
Paola Tedeschi Manuela Nigro Alessia Travagli Martina Catani Alberto Cavazzini Stefania Merighi Stefania Gessi 《International journal of molecular sciences》2022,23(13)
Garlic, Allium sativum, has long been utilized for a number of medicinal purposes around the world, and its medical benefits have been well documented. The health benefits of garlic likely arise from a wide variety of components, possibly working synergistically. Garlic and garlic extracts, especially aged garlic extracts (AGEs), are rich in bioactive compounds, with potent anti-inflammatory, antioxidant and neuroprotective activities. In light of these effects, garlic and its components have been examined in experimental models of Alzheimer’s disease (AD), the most common form of dementia without therapy, and a growing health concern in aging societies. With the aim of offering an updated overview, this paper reviews the chemical composition, metabolism and bioavailability of garlic bioactive compounds. In addition, it provides an overview of signaling mechanisms triggered by garlic derivatives, with a focus on allicin and AGE, to improve learning and memory. 相似文献
83.
84.
This paper reports the results of experimental and theoretical research conducted on perforated brick masonry walls under in-plane loading. The walls?? structural behavior depends strongly on their specific features, e.g. geometry, mechanical properties of the masonry material, brick arrangement and loading conditions. The experimental program was designed to study the incidence of brick arrangement in the spandrels and piers, and of the acting vertical load on the failure mode and load-bearing capacity of the walls. Six specimens of brick masonry wall with a central opening were submitted to a constant vertical load and a monotonic horizontal force that was gradually increased until the kinematic mechanism condition was reached. The object of the theoretical research was to develop a simplified analytical model for describing the kinematic mechanism of the walls. The results of the experiments indicate that brick arrangement strongly influences the failure mode and load-bearing capacity of the walls. Proper a priori assessment of the failure mode of walls becomes fundamental to an accurate evaluation of their load-bearing capacity using the proposed model. 相似文献
85.
Matteo L. Zaffalon Ye Wu Francesca Cova Luca Gironi Xiaoming Li Valerio Pinchetti Yang Liu Muhammad Imran Alessia Cemmi Ilaria Di Sarcina Liberato Manna Haibo Zeng Sergio Brovelli 《Advanced functional materials》2023,33(48):2305564
The search for efficient, re-absorption-free scintillators has recently focused the attention on antimony-based halides, which exhibit largely Stokes shifted luminescence due to radiative recombination of excitons self-trapped (STE) in strongly Jahn–Teller distorted Sb3+ color centers. Here, the synthesis of a hybrid structure is reported with chemical formula (C13H14N3)3SbCl6 consisting of spatially isolated [SbCl6]3− octahedra separated by organic N,N'-diphenylguanidinium (Gua) molecules. The optical properties of this material are mainly determined by the inorganic component and are characterized by a pronounced Stokes shift of ≈1.3 eV and a room-temperature photoluminescence (PL) efficiency of up to 85%. Remarkably, highly efficient radioluminescence (RL) is observed with scintillation light yields of ≈2000 ph MeV−1 using both soft X-rays and a 124 keV gamma source. Temperature-dependent PL and RL measurements confirm the minor role of non-radiative channels, which are completely suppressed below 100 K. Thermally stimulated luminescence measurements suggest that the traps in Gua3SbCl6 crystals have a significantly large energy depth distribution below the absorbing state. 相似文献
86.
Gabriele La Monica Antonino Lauria Alessia Bono Annamaria Martorana 《International journal of molecular sciences》2021,22(11)
The approval of the first HIV-1 protease inhibitors (HIV-1 PRIs) marked a fundamental step in the control of AIDS, and this class of agents still represents the mainstay therapy for this illness. Despite the undisputed benefits, the necessary lifelong treatment led to numerous severe side-effects (metabolic syndrome, hepatotoxicity, diabetes, etc.). The HIV-1 PRIs are capable of interacting with “secondary” targets (off-targets) characterized by different biological activities from that of HIV-1 protease. In this scenario, the in-silico techniques undoubtedly contributed to the design of new small molecules with well-fitting selectivity against the main target, analyzing possible undesirable interactions that are already in the early stages of the research process. The present work is focused on a new mixed-hierarchical, ligand-structure-based protocol, which is centered on an on/off-target approach, to identify the new selective inhibitors of HIV-1 PR. The use of the well-established, ligand-based tools available in the DRUDIT web platform, in combination with a conventional, structure-based molecular docking process, permitted to fast screen a large database of active molecules and to select a set of structure with optimal on/off-target profiles. Therefore, the method exposed herein, could represent a reliable help in the research of new selective targeted small molecules, permitting to design new agents without undesirable interactions. 相似文献
87.
Giuseppe Schepisi Caterina Gianni Sara Bleve Silvia De Padova Cecilia Menna Cristian Lolli Alessia Filograna Vincenza Conteduca Milena Urbini Valentina Gall Chiara Casadei Giovanni Rosti Ugo De Giorgi 《International journal of molecular sciences》2021,22(10)
Testicular cancer (TC) is the most frequent tumor in young males. In the vast majority of cases, it is a curable disease; therefore, very often patients experience a long survival, also due to their young age at diagnosis. In the last decades, the role of the vitamin D deficiency related to orchiectomy has become an increasingly debated topic. Indeed, vitamin D is essential in bone metabolism and many other metabolic pathways, so its deficiency could lead to various metabolic disorders especially in long-term TC survivors. In our article, we report data from studies that evaluated the incidence of hypovitaminosis D in TC survivors compared with cohorts of healthy peers and we discuss molecular mechanisms and clinical implications. 相似文献
88.
Alessia Mongelli Veronica Barbi Michela Gottardi Zamperla Sandra Atlante Luana Forleo Marialisa Nesta Massimo Massetti Alfredo Pontecorvi Simona Nanni Antonella Farsetti Oronzo Catalano Maurizio Bussotti Laura Adelaide Dalla Vecchia Tiziana Bachetti Fabio Martelli Maria Teresa La Rovere Carlo Gaetano 《International journal of molecular sciences》2021,22(11)
The SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis, inflammatory cytokine release, and immunosuppression. This condition has led to the death of about 2.15% of the total infected world population so far. Among survivors, the presence of the so-called persistent post-COVID-19 syndrome (PPCS) is a common finding. In COVID-19 survivors, PPCS presents one or more symptoms: fatigue, dyspnea, memory loss, sleep disorders, and difficulty concentrating. In this study, a cohort of 117 COVID-19 survivors (post-COVID-19) and 144 non-infected volunteers (COVID-19-free) was analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. The results show a consistent biological age increase in the post-COVID-19 population, determining a DeltaAge acceleration of 10.45 ± 7.29 years (+5.25 years above the range of normality) compared with 3.68 ± 8.17 years for the COVID-19-free population (p < 0.0001). A significant telomere shortening parallels this finding in the post-COVID-19 cohort compared with COVID-19-free subjects (p < 0.0001). Additionally, ACE2 expression was decreased in post-COVID-19 patients, compared with the COVID-19-free population, while DPP-4 did not change. In light of these observations, we hypothesize that some epigenetic alterations are associated with the post-COVID-19 condition, particularly in younger patients (< 60 years). 相似文献
89.
Mabrouk Horchani Gerardo Della Sala Alessia Caso Federica DAria Germana Esposito Ilaria Laurenzana Concetta Giancola Valeria Costantino Hichem Ben Jannet Anis Romdhane 《International journal of molecular sciences》2021,22(5)
Chemotherapy represents the most applied approach to cancer treatment. Owing to the frequent onset of chemoresistance and tumor relapses, there is an urgent need to discover novel and more effective anticancer drugs. In the search for therapeutic alternatives to treat the cancer disease, a series of hybrid pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered with hydrazide-hydrazones, 5a–h, was synthesized from condensation reaction of pyrazolopyrimidinone-hydrazide 4 with a series of arylaldehydes in ethanol, in acid catalysis. In vitro assessment of antiproliferative effects against MCF-7 breast cancer cells, unveiled that 5a, 5e, 5g, and 5h were the most effective compounds of the series and exerted their cytotoxic activity through apoptosis induction and G0/G1 phase cell-cycle arrest. To explore their mechanism at a molecular level, 5a, 5e, 5g, and 5h were evaluated for their binding interactions with two well-known anticancer targets, namely the epidermal growth factor receptor (EGFR) and the G-quadruplex DNA structures. Molecular docking simulations highlighted high binding affinity of 5a, 5e, 5g, and 5h towards EGFR. Circular dichroism (CD) experiments suggested 5a as a stabilizer agent of the G-quadruplex from the Kirsten ras (KRAS) oncogene promoter. In the light of these findings, we propose the pyrazolo-pyrimidinone scaffold bearing a hydrazide-hydrazone moiety as a lead skeleton for designing novel anticancer compounds. 相似文献
90.
Matteo Rosellini Matteo Santoni Veronica Mollica Alessandro Rizzo Alessia Cimadamore Marina Scarpelli Nadia Storti Nicola Battelli Rodolfo Montironi Francesco Massari 《International journal of molecular sciences》2021,22(4)
Prostate cancer is the most frequent malignancy in the worldwide male population; it is also one of the most common among all the leading cancer-related death causes. In the last two decades, the therapeutic scenario of metastatic castration-resistant prostate cancer has been enriched by the use of chemotherapy and androgen receptor signaling inhibitors (ARSI) and, more recently, by immunotherapy and poly(ADP–ribose) polymerase (PARP) inhibitors. At the same time, several trials have shown the survival benefits related to the administration of novel ARSIs among patients with non-castration-resistant metastatic disease along with nonmetastatic castration-resistant cancer too. Consequently, the therapeutic course of this malignancy has been radically expanded, ensuring survival benefits never seen before. Among the more recently emerging agents, the so-called “antibody–drug conjugates” (ADCs) are noteworthy because of their clinical practice changing outcomes obtained in the management of other malignancies (including breast cancer). The ADCs are novel compounds consisting of cytotoxic agents (also known as the payload) linked to specific antibodies able to recognize antigens expressed over cancer cells’ surfaces. As for prostate cancer, researchers are focusing on STEAP1, TROP2, PSMA, CD46 and B7-H3 as optimal antigens which may be targeted by ADCs. In this paper, we review the pivotal trials that have currently changed the therapeutic approach to prostate cancer, both in the nonmetastatic castration-resistant and metastatic settings. Therefore, we focus on recently published and ongoing trials designed to investigate the clinical activity of ADCs against prostate malignancy, characterizing these agents. Lastly, we briefly discuss some ADCs-related issues with corresponding strategies to overwhelm them, along with future perspectives for these promising novel compounds. 相似文献