Notes

Self-assembled mRNA vaccinations.
The 2018 West Nile Virus (WNV) season in Europe was characterized by an extremely high infection rate and an exceptionally higher burden when compared to previous seasons. Overall, there was a 10.9-fold increase in incidence in Italy, with 577 human cases, 230 WNV neuroinvasive diseases (WNNV) and 42 WNV-attributed deaths. Methods in this paper we retrospectively reported the neurological presentation of 7 patients admitted to University Hospital of Udine with a diagnosis of WNNV, especially focusing on two patients who presented with atypical severe brain stem involvement. Conclusions the atypical features of some of these forms highlight the necessity to stay vigilant and suspect the diagnosis when confronted with neurological symptoms. We strongly encourage clinicians to consider WNNV in patients presenting with unexplained neurological symptoms in mild climate-areas at risk.Osteoarthritis (OA) is a degenerative disease of the joints which is associated with an impaired production of the cartilage matrix by the chondrocytes. Here, we investigated the role of Lysine-Specific Demethylase-1 (LSD1), a chromatin remodeling enzyme whose role in articular chondrocytes was previously associated with a catabolic activity and which is potentially involved during OA. Following a loss of function strategy and RNA sequencing analysis, we detail the genes which are targeted by LSD1 in human articular chondrocytes and identify COL9A1, a gene encoding the α1 chain of the cartilage-specific type IX collagen, as negatively regulated by LSD1. We show that LSD1 interacts with the transcription factor SOX9 and is recruited to the promoter of COL9A1. Interestingly, we observe that OA cartilage displays stronger LSD1 immunostaining compared with normal, and we demonstrate that the depletion of LSD1 in OA chondrocytes prevents the decrease in COL9A1 following Il-1β treatment. These results suggest LSD1 is a new regulator of the anabolic activity of articular chondrocytes potentially destabilizing the cartilage matrix, since it negatively regulates COL9A1, a gene encoding a crucial anchoring collagen molecule. This newly identified role played by LSD1 may thus participate in the alteration of the cartilage matrix during OA.We had discussed earlier that, after most of the primary author's multiple sclerosis (MS) symptoms were lessened by prior neuroimmune therapies, use of dimethyl fumarate (DMF) gradually subdued his asthma and urticaria symptoms, as well as his MS-related intercostal cramping; and bupropion supplemented with S-adenosylmethionine (SAMe) and vitamin D3 (vit-D3) helped remit major depression (MD). Furthermore, the same cocktail (bupropion plus supplements), along with previously discussed routines (yoga, meditation, physical exercises, and timely use of medications for other illnesses), continued to subdue MD during new difficulties with craniopharyngioma, which caused bitemporal vision loss; sphenoid sinus infections, which caused cranial nerve-VI (CN6) palsy and diplopia; and through their treatments. Impressed by the benefit the four compounds provided, in this manuscript, we focus on explaining current neuroimmune literature proposals on how (1) DMF impedes inflammation, oxidative stress, and cell death in CNS and peripheral tissues; (2) Bupropion curbs anxiety, MD, and enhances alertness, libido, and moods; (3) SAMe silences oxidative stress and depression by multiple mechanisms; and (4) Vit-D3 helps brain development and functioning and subdues inflammation. we realize that herein we have reviewed proposed mechanisms of remedies we discovered by literature searches and physician assisted auto-experimentation; and our methods might not work with other patients. We present our experiences so readers are heartened to reflect upon their own observations in peer-reviewed forums and make available a wide body of information for the chronically ill and their physicians to benefit from.Recently, the interest in plant-derived antimicrobial agents has increased. However, there are no sufficient studies dealing with their modes of action. Herein, we investigate an in-house library of common plant-based phenolic compounds for their potential antibacterial effects against the methicillin-resistant Staphylococcus aureus (MRSA), a widespread life-threatening superbug. Flavonoids, which are considered major constituents in the plant kingdom, were found to be a promising class of compounds against MRSA, particularly the non-glycosylated ones. On the other hand, the glycosylated derivatives, along with the flavonolignan silibinin A, were able to restore the inhibitory activity of ampicillin against MRSA. To explore the mode of action of this class, they were subjected to an extensive inverse virtual screening (IVS), which suggested penicillin-binding protein 2a (PBP2a) as a possible target that mediates both the antibacterial and the antibiotic-synergistic effects of this class of compounds. Further molecular docking and molecular dynamic simulation experiments were conducted to support the primary IVS and the in vitro results and to study their binding modes with PBP2a. Our findings shed a light on plant-derived natural products, notably flavonoids, as a promising and readily available source for future adjuvant antimicrobial therapy against resistant strains.Hangover resistance may be linked to an increased risk of continuing harmful drinking behaviours as well as involvement in potentially dangerous daily activities such as driving while hungover, mainly due to the absence of negative consequences (i.e., hangover symptoms) the day after alcohol consumption. The aim of this study was to examine the occurrence of claimed alcohol hangover resistance relative to estimated blood alcohol concentration (eBAC). A total of 1198 participants completed an online survey by answering questions regarding their demographics, alcohol consumption and occurrence of hangover. Two methods were used to calculate eBAC, one based on the modified Widmark Equation (N = 955) and the other from an equation averaging the total body water (TBW) estimates of Forrest, Watson, Seidl, Widmark and Ulrich (males only) (N = 942). The percentage of participants who claimed to be hangover resistant decreased rapidly with increasing eBAC and only a small number of hangover resistant drinkers remained at higher eBACs. Comparisons of the eBACs calculated by the two methods revealed significantly higher BACs when using the modified Widmark equation. These findings suggest that additional research for eBAC calculations is needed to improve accuracy and comprehensiveness of these equations for future alcohol hangover research.In patients with liver cirrhosis the contribution of inherited and acquired prothrombotic disorders in the development of non-malignant portal vein thrombosis (PVT) is inconclusive. The purpose of this retrospective study was to examine the prevalence of thrombophilia in this setting at our center from January 2012 to November 2019. Tests included gene mutational analysis for Factor V Leiden, prothrombin G20210A, JAK2 (V617F), Calreticulin (CARL), in addition to activated protein C resistance, antithrombin III, protein C and S levels, and antiphospholipid antibodies. We included 77 patients, six of whom (7.8%) had a thrombophilic disorder antiphospholipid syndrome in four patients, prothrombin gene mutation in one and factor V Leiden mutation in one. This latter patient had also been diagnosed with polycythemia vera years before PVT development. Complete thrombosis of the main portal vein and re-thrombosis after stopping anticoagulation were more frequent in patients with thrombophilia, but the rates of recanalization under anticoagulant therapy were similar among groups. No other difference was accounted between groups. The low prevalence of acquired and inherited thrombophilia found in patients with cirrhosis and PVT support testing for these disorders on an individual basis and avoiding universal screening to reduce costs and unwarranted testing.Autophagy is a conserved recycling system required for cellular homeostasis. Identifications of diverse selective receptors/adaptors that recruit appropriate autophagic cargoes have revealed critical roles of selective autophagy in different biological processes in plants. In this review, we summarize the emerging roles of selective autophagy in both biotic and abiotic stress tolerance and highlight the new features of selective receptors/adaptors and their interactions with both the cargoes and Autophagy-related gene 8s (ATG8s). In addition, we review how the two major degradation systems, namely the ubiquitin-proteasome system (UPS) and selective autophagy, are coordinated to cope with stress in plants. We especially emphasize how plants develop the selective autophagy as a weapon to fight against pathogens and how adapted pathogens have evolved the strategies to counter and/or subvert the immunity mediated by selective autophagy.The study aimed to test the hypothesis that monomethyl branched-chain fatty acids (BCFAs) and a lipid extract of Conidiobolus heterosporus (CHLE), rich in monomethyl BCFAs, are able to activate the nuclear transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha). Rat Fao cells were incubated with the monomethyl BCFAs 12-methyltridecanoic acid (MTriA), 12-methyltetradecanoic acid (MTA), isopalmitic acid (IPA) and 14-methylhexadecanoic acid (MHD), and the direct activation of PPARalpha was evaluated by reporter gene assay using a PPARalpha responsive reporter gene. Furthermore, Fao cells were incubated with different concentrations of the CHLE and PPARalpha activation was also evaluated by using the reporter gene assay, and by determining the mRNA concentrations of selected PPARalpha target genes by real-time RT-PCR. The reporter gene assay revealed that IPA and the CHLE, but not MTriA, MHD and MTA, activate the PPARalpha responsive reporter gene. CHLE dose-dependently increased mRNA concentrations of the PPARalpha target genes acyl-CoA oxidase (ACOX1), cytochrome P450 4A1 (CYP4A1), carnitine palmitoyltransferase 1A (CPT1A) and solute carrier family 22 (organic cation/carnitine transporter), member 5 (SLC22A5). In conclusion, the monomethyl BCFA IPA is a potent PPARalpha activator. CHLE activates PPARalpha-dependent gene expression in Fao cells, an effect that is possibly mediated by IPA.AT-rich interactive domain 1A (ARID1A) is one of the most frequently mutated genes in hepatocellular carcinoma (HCC), but its clinical significance is not clarified. We aimed to evaluate the clinical significance of low ARID1A expression in HCC. By analyzing the gene expression data of liver from Arid1a-knockout mice, hepatic Arid1a-specific gene expression signature was identified (p less then 0.05 and 0.5-fold difference). From this signature, a prediction model was developed to identify tissues lacking Arid1a activity and was applied to gene expression data from three independent cohorts of HCC patients to stratify patients according to ARID1A activity. The molecular features associated with loss of ARID1A were analyzed using The Cancer Genome Atlas (TCGA) multi-platform data, and Ingenuity Pathway Analysis (IPA) was done to uncover potential signaling pathways associated with ARID1A loss. ARID1A inactivation was clinically associated with poor prognosis in all three independent cohorts and was consistently related to poor prognosis subtypes of previously reported gene signatures (highly proliferative, hepatic stem cell, silence of Hippo pathway, and high recurrence signatures).
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