Biological effects of Cannabidiol on normal human healthy cell populations: Systematic review of the literature.

A systematic review was performed to evaluate the biological effects of Cannabidiol (CBD), one of the major components of Cannabis Sativa, on normal human healthy cell populations in terms of cell viability, proliferation, migration, apoptosis and inflammation. Inclusion criteria were: studies on cell lines and primary cell culture from healthy donors, CBD exposure as variable, no CBD exposure as control and published in English language. Quality assessment was based on ToxR tool, with a score of reliability ranging from 15 to 18.Following the PRISMA statement, three independent reviewers performed both a manual and an electronic search using MEDLINE via PubMed, Scopus, Web of Science and Cochrane. From a total of 9437eligible articles, 29 studies have been selected. The average quality assessment score was 16.48.Theresults showed heterogeneous CBD concentration exposure (0.01-50 μM or 0.1 nmol/mL-15 mg/mL). The definition of a threshold limit would allow the identification of specific effects on expected outcomes. From the data obtained CBD resulted to inhibit cell viability in a dose-dependent manner above 2 μM, while in oral cell populations the inhibitory concentration is higher than 10 μM. Moreover, it was observed a significantly inhibition of cell migration and proliferation. On the contrary, it was highlighted a stimulation of apoptosis only at high doses (from 10 μM).Finally, CBD produced an anti-inflammatory effect, with a reduction of the pro-inflammatory cytokine gene expression and secretion. CBD down-regulated ROS production, although at high concentrations (16 μM) increased ROS-related genes expression. The diffusion of CBD for therapeutic and recreational uses require a precise definition of its potential biological effects. A thorough knowledge of these aspects would allow a safe use of this substance without any possible side effects

Pb effects on an experimental model of porcine prepubertal Sertoli cells

The environmental pollution is one of the main factors implicated in the world’s fertility decline. Lead (Pb) is one of the major heavy metal contaminants that impairs several organs but preferentially accumulates in male reproductive organs and alters in vivo and in vitro sperm quality [1]. Nowadays, the underlying mechanisms remain unclear. Sertoli cells (SC) provides structural and metabolic support to the spermatogenic cells within the seminiferous tubules, therefore, metabolic and structural changes in SC affect the developing germ cells and consequently alter spermatogenesis. This study aimed to assess whether exposure to subtoxic doses of Pb would adversely affect superior mammalian SC function. Highly purified and functional porcine pre-pubertal SC were isolated [2] and treated with three different Pb acetate concentrations. Parameters of SC functionality, such as inhibin B and anti-Müllerian hormone (AMH) mRNAs and proteins were decreased by Pb exposure respect to the control, such as the FSH-r integrity in terms of 17-β-estradiol production, under FSH stimulation. In addition, we observed an increase of AKT and mTOR mRNAs, p38 phosphorylation ratio and Akt phosphorylation ratio in all experimental conditions, respect to the control. In conclusion, the Pb-related toxicity on SC, even at low concentrations, is expected to alter spermatogenesis

The X-ray Polarization Probe mission concept

The X-ray Polarization Probe (XPP) is a second generation X-ray polarimeter following up on the Imaging X-ray Polarimetry Explorer (IXPE). The XPP will offer true broadband polarimetery over the wide 0.2-60 keV bandpass in addition to imaging polarimetry from 2-8 keV. The extended energy bandpass and improvements in sensitivity will enable the simultaneous measurement of the polarization of several emission components. These measurements will give qualitatively new information about how compact objects work, and will probe fundamental physics, i.e. strong-field quantum electrodynamics and strong gravity.Comment: submitted to Astrophysics Decadal Survey as a State of the Profession white pape

Diazepam effects on non-syndromic cleft lip with or without palate: Epidemiological studies, clinical findings, genes and extracellular matrix

Importance of the field: This review analyses international studies investigating the combined genetic and environmental causes of cleft lip with or without cleft palate (CL/P) and describes successes and limitations in identifying underlying genetic and environmental factors. CL/P, the most common congenital facial malformation, is a major public health burden in terms of medical costs and emotional stress to patients and families. Because genetic and environmental factors determine risk of occurrence, CL/P has a complex, multifactor aetiology. Areas covered in this review: English language reports from 1980 to 2010 were searched for in Medline, PubMed, Science Citation Index, textbooks and review articles on drugs and pregnancy. Key words were diazepam or benzodiazepine(s) combined with cleft lip, cleft palate, oral malformations, prenatal exposure, GABA, gene expression and extracellular matrix. What the reader will gain: This review presents an updated assessment of the mutagenic and genotoxic effects of diazepam (DZ), one of the most commonly used benzodiazepines, on CL/P occurrence. Take home message: Data are divergent; more studies are needed for an in-depth picture of the effects of DZ during gestation on the child's development, particularly on orofacial clefts

Molecular basis of primary hyperoxaluria: clues to innovative treatments

Primary hyperoxalurias (PHs) are rare inherited disorders of liver glyoxylate metabolism, characterized by the abnormal production of endogenous oxalate, a metabolic end-product that is eliminated by urine. The main symptoms are related to the precipitation of calcium oxalate crystals in the urinary tract with progressive renal damage and, in the most severe form named Primary Hyperoxaluria Type I (PH1), to systemic oxalosis. The therapies currently available for PH are either poorly effective, because they address the symptoms and not the causes of the disease, or highly invasive. In the last years, advances in our understanding of the molecular bases of PH have paved the way for the development of new therapeutic strategies. They include (i) substrate-reduction therapies based on small-molecule inhibitors or the RNA interference technology, (ii) gene therapy, (iii) enzyme administration approaches, (iv) colonization with oxalate-degrading intestinal microorganisms, and, in PH1, (v) design of pharmacological chaperones. This paper reviews the basic principles of these new therapeutic strategies and what is currently known about their application to PH

Drenagem anômala de veia pulmonar inferior direita em veia cava inferior associada a apêndice hepático intracardíaco Anomalous drainage of the right inferior pulmonary vein into the inferior vena cava associated to intrathoracic hepatic appendix

Descreve-se o caso de uma paciente de 61 anos de idade, com drenagem anômala de veia pulmonar inferior direita em veia cava inferior, associada a apêndice hepático intratorácico, herniado através de fenda no diafragma. A correção cirúrgica foi realizada por anastomose direta da veia anômala com o átrio esquerdo, pela redução do apêndice hepático para a cavidade abdominal e, finalmente, pelo fechamento do defeito diafragmático. O pós-operatório decorreu sem qualquer complicação. Os autores chamam a atenção para a raridade do caso.<br>The authors present a case of a 61-year-old woman with anomalous drainage of the right inferior pulmonary vein into the inferior vena cava associated to an intrathoracic hepatic appendix herniated through a diaphragmatic defect. Surgical correction was obtained by direct anastomosis of the anomalous vein to the left atrium, reduction of the hepatic appendix to the abdominal cavity and closure of the diphragmatic defect. The postoperative course was unevenftul. The rarity of this condition is stressed

Mechanical properties of 3D-printed prosthetic materials compared with milled and conventional processing: A systematic review and meta-analysis of in vitro studies

Statement of problem Three-dimensional (3D) additive manufacturing (AM) is an evolving technology in dentistry, proposed as an alternative to subtractive milling manufacture (MM) or conventional processing. However, a systematic review of the use of AM technology instead of milling or conventional processing is lacking. Purpose The purpose of this systematic review and meta-analysis was to evaluate the mechanical properties of 3D-printed prosthetic materials compared with MM and conventional techniques. Material and methods An electronic search of the literature was conducted on the MEDLINE (via PubMed), Scopus, and Web of Science databases. The inclusion criteria were in vitro studies published in the last 5 years, in English or Italian, and with 3D AM printed dental prosthetic materials. Data extraction was focused on dental prosthetic materials (ceramics, polymers, and metals) and their mechanical properties: flexural strength, fracture load, hardness, roughness, removable partial denture (RPD) fit accuracy, trueness, marginal discrepancy, and internal fit. Data considered homogenous were subjected to meta-analysis using the Stata17 statistical software program (95% confidence interval [CI]; α=.05). Since all variables were continuous, the Hedge g measure was calculated. A fixed-effects model was used for I=0%, while the statistical analysis was conducted using a random-effects model with I2>0%. Results From a total of 3624 articles, 2855 studies were selected, and 76 studies included after full-text reading. The roughness of AM-printed ceramics generally increased compared with that of conventional processing while the marginal discrepancy was comparable both for ceramics and polymers. The flexural strength, hardness, and fracture load of AM-printed polymers were statistically lower than those of the conventional group (P.05). Milling techniques showed significantly higher values of flexural strength (Hedge g=-3.88; 95% CI, -7.20 to -0.58; P=.02), also after aging (Hedge g=-3.29; 95% CI, -6.41 to -0.17; P=.04), compared with AM printing. Conclusions AM is comparable with MM in terms of mechanical properties, in particular with polymeric materials. The flexural strength of AM-printed prostheses is lower than with conventional and MM techniques, as are the parameters of hardness and fracture load, while the marginal discrepancy is similar to that of MM and conventional techniques. AM prostheses are commonly used for interim crowns and fixed partial dentures, as their rigidity and fracture resistance cannot support mastication forces for extended periods. More comparative studies are needed

Effects of sub-toxic cadmium concentrations of bone gene expression program: results of an in vitro study

Since occupational and environmental exposure to the heavy metal Cadmium (Cd) affects human health this study investigated the effects of exposure to a single, or multiple, sub-toxic Cd concentrations on sub-confluent and confluent human osteoblast growth and expression of specific bone differentiation markers. RT-PCR quantified gene expression of type I collagen, metalloprotease (MMP13), runt-related transcription factor-2 (RUNX2), osterix, osteocalcin, osteonectin, alkaline phosphatase, integrins and bone sialoprotein (BSP). Expression of fibroblast growth factors 1 and 2 (FGF1, FGF2), transforming growth factor-beta(3) (TGFbeta(3)) and bone morphogenetic protein-2 (BMP2) were also evaluated to determine whether Cd-related effects were mediated by an imbalance in expression. Depending on osteoblast concentration and maturation stages, Cd inhibited or stimulated cell growth, decreased type I collagen, increased MMP13, FGF1 and BMP2 gene expression and stimulated the mineralization process only in continuously exposed cultures. These results suggest that in vivo, acute or chronic exposure to sub-toxic Cd concentrations may affect bone formation differently and support the hypothesis that Cd-induced bone disorders may involve downstream changes in growth factor expression. The results are of interest in forensic and occupational medicine in establishing preventive measures to reduce professional exposure risks