Notes

Account activation of the M3AChR and also Notch1/HSF1 Signaling Process by Choline Reduces Angiotensin II-Induced Cardiomyocyte Apoptosis.
In addition, our study validates the ability of plant cells to metabolize VH into madagascine anthrone, anthraquinones and unexpected metabolites. These results pave the way for new hypotheses on anthranoid metabolism in plants.The growing demand for metabolism-specific imaging techniques has rekindled interest in Deuterium (2H) Metabolic Imaging (DMI), a robust method based on administration of a substrate (glucose, acetate, fumarate, etc.) labeled with the stable isotope of hydrogen and the observation of its metabolic fate in three-dimensions. This technique allows the investigation of multiple metabolic processes in both healthy and diseased states. Despite its low natural abundance, the short relaxation time of deuterium allows for rapid radiofrequency (RF) pulses without saturation and efficient image acquisition. In this review, we provide a comprehensive picture of the evolution of DMI over the course of recent decades, with a special focus on its potential clinical applications.Pantothenic acid (vitamin B5) is an essential trace nutrient required for the synthesis of coenzyme A (CoA). It has previously been shown that pantothenic acid is significantly decreased in multiple brain regions in both Alzheimer's disease (ADD) and Huntington's disease (HD). The current investigation aimed to determine whether similar changes are also present in cases of Parkinson's disease dementia (PDD), another age-related neurodegenerative condition, and whether such perturbations might occur in similar regions in these apparently different diseases. Brain tissue was obtained from nine confirmed cases of PDD and nine controls with a post-mortem delay of 26 h or less. Tissues were acquired from nine regions that show high, moderate, or low levels of neurodegeneration in PDD the cerebellum, motor cortex, primary visual cortex, hippocampus, substantia nigra, middle temporal gyrus, medulla oblongata, cingulate gyrus, and pons. A targeted ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) approach was used to quantify pantothenic acid in these tissues. ALK inhibitor Pantothenic acid was significantly decreased in the cerebellum (p = 0.008), substantia nigra (p = 0.02), and medulla (p = 0.008) of PDD cases. These findings mirror the significant decreases in the cerebellum of both ADD and HD cases, as well as the substantia nigra, putamen, middle frontal gyrus, and entorhinal cortex of HD cases, and motor cortex, primary visual cortex, hippocampus, middle temporal gyrus, cingulate gyrus, and entorhinal cortex of ADD cases. Taken together, these observations indicate a common but regionally selective disruption of pantothenic acid levels across PDD, ADD, and HD.Asthma is a highly heterogeneous disease, but the pathogenesis of asthma is still unclear. It is well known that the airway inflammatory immune response is the pathological basis of asthma. Metabolomics is a systems biology method to analyze the difference of low molecular weight metabolites ( less then 1.5 kDa) and explore the relationship between metabolic small molecules and pathophysiological changes of the organisms. The functional interdependence between immune response and metabolic regulation is one of the cores of the body's steady-state regulation, and its dysfunction will lead to a series of metabolic disorders. The signal transduction effect of specific metabolites may affect the occurrence of the airway inflammatory immune response, which may be closely related to the pathogenesis of asthma. Emerging metabolomic analysis may provide insights into the pathogenesis and diagnosis of asthma. The review aims to analyze the changes of metabolites in blood/serum/plasma, urine, lung tissue, and exhaled breath condensate (EBC) samples, and further reveals the potential pathogenesis of asthma according to the disordered metabolic pathways.Glycans play a fundamental role in several biological processes, such as cell-cell adhesion, signaling, and recognition. Similarly, abnormal glycosylation is involved in many pathological processes, among which include tumor growth and progression. Several highly glycosylated proteins found in blood are currently used in clinical practice as cancer biomarkers (e.g., CA125, PSA, and CA19-9). The development of novel non-invasive diagnostic procedures would greatly simplify the screening and discovery of pathologies at an early stage, thus also allowing for simpler treatment and a higher success rate. In this observational study carried out on 68 subjects diagnosed with either breast or lung cancer and 34 healthy volunteers, we hydrolyzed the glycoproteins in saliva and quantified the obtained free sugars (fucose, mannose, galactose, glucosamine, and galactosamine) by using high-performance anion-exchange chromatography with pulsed-amperometric detection (HPAEC-PAD). The glycosidic profiles were compared by using multivariate statistical analysis, showing differential glycosylation patterns among the three categories. Furthermore, Receiver Operating Characteristics (ROC) analysis allowed obtaining a reliable and minimally invasive protocol able to discriminate between healthy and pathological subjects.We report an observational study performed between March and May 2020 in a Spanish university hospital during the SARS-CoV-2 pandemic. The main objective was to analyse the association between the levels of micronutrients in severe COVID-19 patients and their outcome. Adult patients with a positive polymerase-chain-reaction (PCR) for SARS-CoV-2 in the nasopharyngeal swab or in tracheal aspirate culture in the case of intubation were included. Micronutrient data were obtained from plasma analysis of a standard nutritional assessment performed within the first 24 h of hospital admission. Vitamins A, B6, C and E were analysed with HPLC methods; 25-OH-vitamin D by immunoassay and zinc by colorimetric measurements. One hundred and twenty patients were included. We found that 74.2% patients had low levels of zinc (normal levels >84 µg/dL) with a mean value of 63.5 (SD 13.5); 71.7% patients had low levels of vitamin A (normal levels >0.3 mg/L) with a mean value of 0.17 (SD 0.06); 42.5% patients had low levels of vitssion to the ICU and orotracheal intubation. Patients older than 65 years had higher mortality. Randomized clinical trials are needed to examine whether micronutrient supplementation could be beneficial as an adjunctive treatment in COVID-19.Familial hypobetalipoproteinemia (FHBL) is a codominant genetic disorder characterized by reduced plasma levels of low-density lipoprotein cholesterol and apolipoprotein B. To our knowledge, no study on FHBL in Lebanon and the Middle East region has been reported. Therefore, we conducted genetic studies in unrelated families and probands of Lebanese origin presenting with FHBL, in order to identify the causes of this disease. We found that 71% of the recruited probands and their affected relatives were heterozygous for the p.(Arg490Trp) variant in the APOB gene. Haplotype analysis showed that these patients presented the same mutant haplotype. Moreover, there was a decrease in plasma levels of PCSK9 in affected individuals compared to the non-affected and a significant positive correlation between circulating PCSK9 and ApoB levels in all studied probands and their family members. Some of the p.(Arg490Trp) carriers suffered from diabetes, hepatic steatosis or neurological problems. In conclusion, the p.(Arg490Trp) pathogenic variant seems a cause of FHBL in patients from Lebanese origin, accounting for approximately 70% of the probands with FHBL presumably as a result of a founder mutation in Lebanon. This study is crucial to guide the early diagnosis, management and prevention of the associated complications of this disease.The incidence of respiratory disease is increasing. In relation to this, in addition to infection, factors associated with working with chemical insecticides are a cause for concern. Some of the chemicals involved have been shown to affect the respiratory system, and consequentially workers are at increased risk of conditions such as asthma. However, medical opinion around this area is still controversial; therefore, the objective of this study is to investigate the association between exposure to insecticides and asthma by means of a systematic review of the relevant literature. Relevant literature was identified, and a systematic review was conducted to investigate the association between exposure to insecticides and asthma. A total of five studies (three cross sectional and two cohort) including 45,435 subjects were identified as relevant. The summary odds ratios related to the impact of exposure to specific insecticides on asthma were organophosphates 1.31 (95%CI = 1.17-1.48, I2 = 27%, p = 0.172), carbamates 1.44 (95%CI 1.08-1.92, I2 = 56.7%, p = 0.031) and organochlorines 1.31 (95%CI 1.19-1.64, I2 = 37.3%, p = 0.131). Farmers exposed to certain insecticides may have an increased risk of asthma and asthmatic symptoms, but further research on that issue is urgently needed.Exposure to air pollutants in wildfire smoke and indoor pollution causes lung diseases. Short-term exposure to wood smoke (WS) is partially known to alter the expression of human matrix metalloproteinases (MMPs), inflammatory cytokines, and tissue inhibitors of metalloproteinases (TIMPs). Accordingly, we investigated the effect of exposing guinea pigs to WS for two and four three-hour periods on different days. The daily content of particles reported by indoor pollution was produced by 60 g of pinewood. We analyzed the cell profile and collagen content in bronchoalveolar lavages (BAL). The mRNA expression of pro-inflammatory cytokines, MMPs, and TIMPs was studied in lung tissue. Cytokines and gelatinolytic activity were analyzed in BAL and serum. The results showed that total cells, macrophages, neutrophils, and collagen increased in BAL, whereas neutrophils and lymphocytes decreased. TGF-β1, TNF-α, IFN-γ, IL-1β, IL-6, IL-8, MMP-2, MMP-9, TIMP-1, and TIMP-2 were upregulated in lungs, downregulating IL-12. TNF-α, IFN-γ, TGF-β1, IL-1β, IL-6, and IL-8 were increased in BAL and serum, decreasing IL-12. Gelatinase activity was increased in serum. Thus, guinea pigs exposed to short-term domestic doses of WS overexpressed pro-inflammatory cytokines, MMPs, and TIMPs. These results are similar to ECM remodeling and pulmonary and systemic inflammation reported in humans.Malignant melanoma represents the deadliest type of skin cancer with narrow treatment options in advanced stages. Herbal constituents possessing anticancer properties occupy a particular spot in melanoma research as potential chemotherapeutics. Rutin (RUT) is a natural compound exerting antioxidant, antimicrobial, anti-inflammatory, UV-filtering, and SPF-enhancing activities that are beneficial to the skin; however, its effect as an anti-melanoma agent is less investigated. The current study is focused on assessing the cytotoxic potential of RUT against two different human melanoma cell lines RPMI-7951 and SK-MEL-28 by evaluating its impact in terms of cell viability, cells' morphology, and nuclear aspect assessment, and senescence-inducing properties. The results indicate a dose-dependent decrease in the viability of both cell lines, with calculated IC50 values of 64.49 ± 13.27 µM for RPMI-7951 cells and 47.44 ± 2.41 µM for SK-MEL-28, respectively, accompanied by a visible reduction in the cell confluency and apoptotic features within the cell nuclei.
Website: https://www.selleckchem.com/ALK.html