Novel anticancer drug 5h-pyro[3,2-a] phenoxazin-5-one (PPH) regulates lncRNA HOTAIR and HOXC genes in human MCF-7 cells

Breast cancer in women is the second most commonly cancer, after skin cancer. The percentage of mortality risk for breast cancer is 1 in 37 women (2.7%), which makes breast cancer represent the second cause of cancer death in women. Recently, new research based on previously published work in systemic chemotherapy and endocrine therapy field, have improved the incidence rates. The quinonic nucleus is common to many natural and synthetic products associated with anticancer and antibacterial activities, these compounds are typically DNA-intercalating agents. The Class I Homeobox genes (HOX in human and hox in mouse) control embryonic development and specific determination of positional identity anteroposterior axis of the human body. The HOX genes, are 39 transcription factors related to morphological, physiological disease. It has been demonstrated that any deregulation into the network is able to induce neoplastic transformation. Particularly, HOXC locus collaborating with lncRNA HOTAIR play a key role in breast cancer. In this study, our group evaluated the chemical and metabolic stability of new anticancer molecule 5H-pyro[3,2-a] phenoxazin-5-one (PPH). In a recent paper, we have already demonstrated that a new and potent anticancer synthetic iminoquinone, the 5H-pyrido[3,2-a]phenoxazin-5-one (PPH), is able to inhibit a large number of lymphoblastoid and solid-tumor-derived cells at submicromolar concentrations. Based on our previous research, we decided to analyze the cytotoxic effect and capability of PPH to control the lncRNA HOTAIR and HOXC locus gene expression in human breast cancer cells MCF-7, in order to demonstrate its role like potential new breast cancer antitumor drug

Chemistry meets Industry and Society A creative showcase conference

Buffalo milk contributes to 13% of the world milk production and is abundantly produced in Southern Italy regions. Buffalo milk is appreciated for its nutritive properties and is highly suitable for the manufacturing of wide range of dairy products. Several studies showed many bioactive peptides in different dairy species such as bovine, ovine and caprine milk, but few studies have been conducted on the buffalo dairy products (1). The present work is focused on the identification of bioactive peptides released after in vitro simulated gastrointestinal digestion of protein fraction isolated from buffalo-milk dairy products by ultra- and nanofiltration pilot plant. The gastrointestinal digests of protein fractions were monitored by RP-UHPLC-DAD, while, the peptide identification was carried out by UHPLC-Orbitrap-based tandem mass spectrometry. 165 peptides were identified in Yoghurt, 152 in Scamorza, 146 in Mozzarella, 136 in Grana and Ricotta and 120 in Ice Cream samples (1). The peptides belong to both buffalo caseins (αs1-, β-, k-CN) and whey proteins (α-LA, β-LG). Six G.I. digests of dairy products were tested in a model of oxidative stress using IEC-6 cells. Among them, buffalo ricotta cheese was the most active. UHPLC-PDA-MS/MS analysis revealed the presence of two abundant β-lactoglobulin peptides (BRP: YVEELKPTPEGDL, f:60-72 and BRP2: SFNPTQL, f:168-174). To confirm the hypothesized chemical structures and study their specific biological activity, the peptides were synthesized by conventional solid-phase peptide synthesis methods. The antioxidant potential of the identified peptides was then evaluated in a model of hydrogen peroxide induced oxidative stress in IEC-6 cell line. The peptides reduce ROS release and increase nuclear factor (erythroid-derived 2)-like 2 activation and the expression of antioxidant cytoprotective factors such as heme oxygenase 1, NAD(P)H: quinone oxidoreductase 1 and superoxide dismutase (2). The bioavailability of β-lactoglobulin peptides was evaluated in intestinal transport studies through Caco-2 cell monolayer. Only BRP2 showed equal bi-directional transport and linear permeability, suggesting that it was mainly absorbed through passive diffusion. In addition to its local effects, administration of BPR2 on mice mesenteric arteries counteracts the Angiotensin II-induced vasoconstriction by Nrf2 nuclear translocation, reduction of active form of Ras-related C3 botulinum toxin substrate 1 (Rac1) and NADPH oxidase activity. The analysis at molecular level of treated vessels showed an induction of Nrf2 translocation to nucleus associated with increased expression of MnSOD and Rac1 deactivation. The data indicate how protein fraction of buffalo ricotta cheese could be an important source of antioxidant compounds, as well as YVEELKPTPEGDL and SFNPTQL peptides could be considered as an “ingredient” for nutraceuticals formulations and functional and personalized foods, in order to prevent the onset of some gastrointestinal pathologies and cardiovascular diseases

Novel Anticancer Drug 5H-pyro[3,2-a] Phenoxazin-5-one (PPH) Regulates lncRNA HOTAIR and HOXC genes in Human MCF-7 Cells

Breast cancer in women is the second most commonly cancer, after skin cancer. The percentage of mortalityrisk for breast cancer is 1 in 37 women (2.7%), which makes breast cancer represent the second cause of cancerdeath in women. Recently, new research based on previously published work in systemic chemotherapy andendocrine therapy field, have improved the incidence rates. The quinonic nucleus is common to many naturaland synthetic products associated with anticancer and antibacterial activities, these compounds are typicallyDNA-intercalating agents. The Class I Homeobox genes (HOX in human and hox in mouse) control embryonicdevelopment and specific determination of positional identity anteroposterior axis of the human body. The HOXgenes, are 39 transcription factors related to morphological, physiological disease. It has been demonstratedthat any deregulation into the network is able to induce neoplastic transformation. Particularly, HOXC locuscollaborating with lncRNA HOTAIR play a key role in breast cancer. In this study, our group evaluated the chemical and metabolic stability of new anticancer molecule 5H-pyro[3,2-a] phenoxazin-5-one (PPH). In a recent paper, we have already demonstrated that a new and potent anticancersynthetic iminoquinone, the 5H-pyrido[3,2-a]phenoxazin-5-one (PPH), is able to inhibit a large number oflymphoblastoid and solid-tumor-derived cells at submicromolar concentrations. Based on our previous research, we decided to analyze the cytotoxic effect and capability of PPH to control thelncRNA HOTAIR and HOXC locus gene expression in human breast cancer cells MCF-7, in order to demonstrateits role like potential new breast cancer antitumor drug

New insights in pediatrics in 2021: choices in allergy and immunology, critical care, endocrinology, gastroenterology, genetics, haematology, infectious diseases, neonatology, neurology, nutrition, palliative care, respiratory tract illnesses and telemedicine

In this review, we report the developments across pediatric subspecialties that have been published in the Italian Journal of Pediatrics in 2021. We highlight advances in allergy and immunology, critical care, endocrinology, gastroenterology, genetics, hematology, infectious diseases, neonatology, neurology, nutrition, palliative care, respiratory tract illnesses and telemedicine

The Utility of Capsicum annuum L. in Internal Medicine and In Dentistry: A Comprehensive Review

Capsaicin is a chili peppers extract, genus Capsicum, commonly used as a food spice. Since ancient times, Capsaicin has been used as a "homeopathic remedy" for treating a wild range of pathological conditions but without any scientific knowledge about its action. Several studies have demonstrated its potentiality in cardiovascular, nephrological, nutritional, and other medical fields. Capsaicin exerts its actions thanks to the bond with transient receptor potential vanilloid subtype 1 (TRPV1). TRPV1 is a nociceptive receptor, and its activation starts with a neurosensitive impulse, responsible for a burning pain sensation. However, constant local application of Capsaicin desensitized neuronal cells and leads to relief from neuropathic pain. In this review, we analyze the potential adjuvant role of Capsaicin in the treatment of different pathological conditions either in internal medicine or dentistry. Moreover, we present our experience in five patients affected by oro-facial pain consequent to post-traumatic trigeminal neuropathy, not responsive to any remedy, and successfully treated with topical application of Capsaicin. The topical application of Capsaicin is safe, effective, and quite tolerated by patients. For these reasons, in addition to the already-proven beneficial actions in the internal field, it represents a promising method for the treatment of neuropathic oral diseases

Nobiletin and xanthohumol sensitize colorectal cancer stem cells to standard chemotherapy

Colorectal cancer (CRC) mortality is mainly caused by patient refractoriness to common anti-cancer therapies and consequent metastasis formation. Besides, the notorious toxic side effects of chemotherapy are a concurrent obstacle to be tackled. Thus, new treatment approaches are needed to effectively improve patient outcomes. Compelling evidence demonstrated that cancer stem cells (CSCs) are responsible for treatment failure and relapse. New natural treatment approaches showed capabilities to selectively target the CSC subpopulation by rendering them targetable by standard cytotoxic compounds. Herein we show the anti-cancer properties of the polymethoxyflavones and prenylflavonoids extracted from Citrus sinensis and Humulus lupulus, respectively. The natural biofunctional fractions, singularly and in combination, reduced the cell viability of CRC stem cells (CR-CSCs) and synergized with 5-fluorouracil and oxaliplatin (FOX) chemotherapy. These phenomena were accompanied by a reduced S and G2/M phase of the cell cycle and upregulation of cell death-related genes. Notably, both phytoextracts in combination with FOX thwarted stemness features in CR-CSCs as demonstrated by the impaired clonogenic potential and decreased Wnt pathway activation. Extracts lowered the expression of CD44v6 and affected the expansion of metastatic CR-CSCs in patients refractory to chemotherapy. Together, this study highlights the importance of polymethoxyflavones and prenylflavonoids as natural remedies to aid oncological therapies

The GAPS Programme at TNG : LV. Multiple molecular species in the atmosphere of HAT-P-11 b and review of the HAT-P-11 planetary system

Context. The atmospheric characterisation of hot and warm Neptune-size exoplanets is challenging mainly due to their relatively small radius and atmospheric scale height, which reduce the amplitude of atmospheric spectral features. The warm-Neptune HAT-P-11 b is a remarkable target for atmospheric characterisation because of the large brightness of its host star (V = 9.46 mag; H = 7.13 mag). Aims: The aims of this work are to review the main physical and architectural properties of the HAT-P-11 planetary system, and to probe the presence of eight molecular species in the atmosphere of HAT-P-11 b through near-infrared (NIR) high-resolution transmission spectroscopy. Methods: We reviewed the physical and architectural properties of the HAT-P-11 planetary system by analysing transits and occultations of HAT-P-11 b from the Kepler data set as well as HIRES at Keck archival radial-velocity data. We modelled the latter with Gaussian-process regression and a combined quasi-periodic and squared-exponential kernel to account for stellar variations on both (short-term) rotation and (long-term) activity-cycle timescales. In order to probe the atmospheric composition of HAT-P-11 b, we observed four transits of this target with the NIR GIANO-B at TNG spectrograph and cross-correlated the data with template atmospheric transmission spectra. Results: We find that the long-period radial-velocity signal previously attributed to the HAT-P-11 c planet (P ~ 9.3 yr; Mp sin i ~ 1.6 MJ; e ~ 0.6) is more likely due to the stellar magnetic activity cycle. Nonetheless, the HIPPARCOS-Gaia difference in the proper-motion anomaly suggests that an outer-bound companion might still exist. For HAT-P-11 b, we measure a radius of Rp = 0.4466 ± 0.0059 RJ, a mass of Mp = 0.0787 ± 0.0048 MJ, a bulk density of ρp = 1.172 ± 0.085 g cm−3, and an orbital eccentricity of e = 0.2577−0.0025+0.0033. These values are compatible with those from the literature. Probing its atmosphere, we detect the presence of two molecular species, H2O and NH3, with a S/N of 5.1 and 5.3, and a significance of 3.4 σ and 5.0 σ, respectively. We also tentatively detect the presence of CO2 and CH4, with a S/N of 3.0 and 4.8, and a significance of 3.2 σ and 2.6 σ, respectively. Conclusions: We revisit the HAT-P-11 planetary system, confirm the presence of H2O, and report the detection of NH3 in the atmosphere of HAT-P-11 b, also finding hints for the presence of CO2 and CH4 that need to be confirmed by further observations

The GAPS Programme at TNG XXXVI. Measurement of the Rossiter-McLaughlin effect and revising the physical and orbital parameters of the HAT-P-15, HAT-P-17, HAT-P-21, HAT-P-26, HAT-P-29 eccentric planetary systems

Context. The measurement of the spin-orbit alignment of hot Jupiters, including a range of orbital and physical properties, can provide information about the evolution of the orbits of this special class of giant planets.Aims. We aim to refine the orbital and physical parameters and determine the sky-projected planet orbital obliquity ? of five eccentric (e ? 0.1–0.3) transiting planetary systems: HAT-P-15, HAT-P-17, HAT-P-21, HAT-P-26, and HAT-P-29, whose parent stars have an effective temperature between 5100 K < Teff < 6200 K. Each of the systems hosts a hot Jupiter, except for HAT-P-26, which hosts a Neptune-mass planet.Methods. We observed transit events of these planets with the HARPS-N spectrograph, obtaining high-precision radial velocity measurements that allow us to measure the Rossiter–McLaughlin effect for each of the target systems. We used these new HARPS-N spectra and archival data, including those from Gaia, to better characterise the stellar atmospheric parameters. The photometric parameters for four of the hot Jupiters were recalculated using 17 new transit light curves, obtained with an array of medium-class telescopes, and data from the TESS space telescope. HATNet time-series photometric data were checked for the signatures of rotation periods of the target stars and their spin axis inclination.Results. From the analysis of the Rossiter-McLaughlin effect, we derived a sky-projected obliquity of ? = 13° ± 6°, ? = -26.3° ± 6.7°, ? = -0.7° ± 12.5°, ? = -26° ± 16°, for HAT-P-15 b, HAT-P-17 b, HAT-P-21 b, and HAT-P-29 b, respectively. Based on theoretical considerations, these small values of ? should be of primordial origin, with the possible exception of HAT-P-21. Due to the quality of the data, we were not able to fully constrain ? for HAT-P-26 b, although a prograde orbit is favoured (? = 18° ± 49°). The stellar activity of HAT-P-21 indicates a rotation period of 15.88 ± 0.02 days, which allowed us to determine its true misalignment angle ? = 25° ± 16°. Our new analysis of the physical parameters of the five exoplanetary systems returned values compatible with those existing in the literature. Using TESS and the available transit light curves, we reviewed the orbital ephemeris for the five systems and confirmed that the HAT-P-26 system shows transit timing variations, which may tentatively be attributed to the presence of a third body