Andresenmichaelsen1077

The minireview considers the current trends in the synthesis of some biologically active compounds based on 2-aminobenzothiazole. The presented information covers publications of the last five years.An azo coupling reaction of α-nitro ketones with 5-diazoazoles was used to obtain 4-alkyl-3-nitro-1,4-dihydroazolo[5,1-с][1,2,4]triazines, which were characterized with respect to their antiviral activity against influenza and Coxsackie B3 viruses.

The online version contains supplementary material available at 10.1007/s10593-021-02926-2.

The online version contains supplementary material available at 10.1007/s10593-021-02926-2.Isotope-labeled antiviral drug Triazavirin containing 2H, 13C, and 15N atoms in its structure has been synthesized. 13C2H3I and KS13CN served as donors of 13C isotopes. The use of 13С-MeI containing 2H atoms made it possible to additionally incorporate deuterium labels into the structure of the compound. The 15N atoms were incorporated using 15N-enriched sodium nitrite, aminoguanidine carbonate, and ethyl nitroacetate. The resulting 2H3,13C2,15N3-Triazavirin was characterized by NMR spectroscopy.

The online version contains supplementary material available at 10.1007/s10593-021-02927-1.

The online version contains supplementary material available at 10.1007/s10593-021-02927-1.A recent screening study highlighted a molecular compound, apilimod, for its efficacy against the SARS-CoV-2 virus, while another compound, tetrandrine, demonstrated a remarkable synergy with the benchmark antiviral drug, remdesivir. Here, we find that because of significantly reduced potential energy barriers, which also give rise to pronounced quantum effects, the rotational dynamics of the most dynamically active methyl groups in apilimod and tetrandrine are much faster than those in remdesivir. Because dynamics of methyl groups are essential for biochemical activity, screening studies based on the computed potential energy profiles may help identify promising candidates within a given class of drugs.

Coronavirus disease 19 (COVID-19) has many manifestations, including respiratory, thrombotic, neurologic, digestive, and cutaneous ones. Cutaneous manifestations have been classified into 5 clinical patterns acro-ischemic (pseudo-chilblain), vesicular, urticarial, maculopapular, and livedoid. Oral manifestations have also been reported, but much less frequently.

We performed a cross-sectional study in which we examined the oral mucosa of 666 patients with COVID-19 at the IFEMA field hospital in Madrid in April 2020.

Seventy-eight patients (11.7%) had changes involving the oral mucosa. The most common were transient anterior U-shaped lingual papillitis (11.5%) accompanied or not by tongue swelling (6.6%), aphthous stomatitis (6.9%), a burning sensation in the mouth (5.3%), mucositis (3.9%), glossitis with patchy depapillation (3.9%), white tongue (1.6%), and enanthema (0.5%). Most of the patients also reported taste disturbances.

COVID-19 also manifests in the oral cavity. The most common manifestations are transient U-shaped lingual papillitis, glossitis with patchy depapillation, and burning mouth syndrome. Mucositis with or without aphthous ulcers or enanthema may also be observed. Any these findings may be key clues to a diagnosis of COVID-19.

COVID-19 also manifests in the oral cavity. The most common manifestations are transient U-shaped lingual papillitis, glossitis with patchy depapillation, and burning mouth syndrome. Mucositis with or without aphthous ulcers or enanthema may also be observed. Any these findings may be key clues to a diagnosis of COVID-19.Obesity is a major health problem whose well-known association with psoriasis has been amply described. The importance of obesity as a risk factor for poor prognosis in the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 infection has recently been demonstrated. This review examines a possible relationship between obesity, psoriasis, and COVID-19, analyzing the pathophysiological links and their practical implications. On the one hand, a higher body mass index increases the risk of psoriasis and is also a factor in metabolic syndrome, which is common in patients with psoriasis and has been implicated in reducing the effectiveness of psoriasis treatments. On the other hand, obesity is a risk factor for severe COVID-19 and mortality. Obesity also promotes a proinflammatory state in the lung, where it compromises respiratory mechanics.CK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found to enhance CK2 activity and to induce the phosphorylation of several CK2 substrates (either viral and host proteins). CK2 is also considered an emerging target for neurological diseases, inflammation and autoimmune disorders, diverse ophthalmic pathologies, diabetes, and obesity. In addition, CK2 activity has been associated with cardiovascular diseases, as cardiac ischemia-reperfusion injury, atherosclerosis, and cardiac hypertrophy. The hypothesis of considering CK2 inhibition for cystic fibrosis therapies has been also entertained for many years. Moreover, psychiatric disorders and syndromes due to CK2 mutations have been recently identified. On these bases, CK2 is emerging as an increasingly attractive target in various fields of human medicine, with the advantage that several very specific and effective inhibitors are already available. Here, we review the literature on CK2 implication in different human pathologies and evaluate its potential as a pharmacological target in the light of the most recent findings.A major challenge in three-dimensional (3D) microscopy is to obtain accurate spatial information while simultaneously keeping the microscopic samples in their native states. In conventional 3D microscopy, axial resolution is inferior to spatial resolution due to the inaccessibility to side scattering signals. In this study, we demonstrate the isotropic microtomography of free-floating samples by optically rotating a sample. Contrary to previous approaches using optical tweezers with multiple foci which are only applicable to simple shapes, we exploited 3D structured light traps that can stably rotate freestanding complex-shaped microscopic specimens, and side scattering information is measured at various sample orientations to achieve isotropic resolution. EX 527 The proposed method yields an isotropic resolution of 230 nm and captures structural details of colloidal multimers and live red blood cells, which are inaccessible using conventional tomographic microscopy. We envision that the proposed approach can be deployed for solving diverse imaging problems that are beyond the examples shown here.The tumor microenvironment is deeply involved in the process of tumor growth and development. In this study, we focused on cancer-associated fibroblasts (CAFs) and their derived exosomes on the lymphoma microenvironment to uncover their clinical significance. CAFs were established from primary lymphoma samples, and exosomes secreted from CAFs were obtained by standard procedures. We then investigated the roles of CAFs and their derived exosomes in the survival and drug resistance of lymphoma cells. CAFs supported the survival of lymphoma cells through increased glycolysis, and the extent differed among CAFs. Exosomes were identified as a major component of the extracellular vesicles from CAFs, and they also supported the survival of lymphoma cells. The suppression of RAB27B, which is involved in the secretion of exosomes, using a specific siRNA resulted in reduced exosome secretion and decreased survival of lymphoma cells. Moreover, anti-pyrimidine drug resistance was induced in the presence of exosomes through the suppression of the pyrimidine transporter, equilibrative nucleoside transporter 2 (ENT2), and the suppression of ENT2 was significant in in vivo experiments and clinical samples. RNA sequencing analysis of miRNAs in exosomes identified miR-4717-5p as one of the most abundant miRNAs in the exosome, which suppressed the expression of ENT2 and induced anti-pyrimidine drug resistance in vitro. Our results suggest that exosomes including miR-4717-5p secreted from CAFs play a pivotal role in the lymphoma microenvironment, indicating that they are a promising therapeutic target.

Excess visceral obesity and ectopic organ fat is associated with increased risk of cardiometabolic disease. However, circulating markers for early detection of ectopic fat, particularly pancreas and liver, are lacking.

Lipid storage in pancreas, liver, abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from 68 healthy or pre-diabetic Caucasian and Chinese women enroled in the TOFI_Asia study was assessed by magnetic resonance imaging/spectroscopy (MRI/S). Plasma metabolites were measured with untargeted liquid chromatography-mass spectroscopy (LC-MS). Multivariate partial least squares (PLS) regression identified metabolites predictive of VAT/SAT and ectopic fat; univariate linear regression adjusting for potential covariates identified individual metabolites associated with VAT/SAT and ectopic fat; linear regression adjusted for ethnicity identified clinical and anthropometric correlates for each fat depot.

PLS identified 56, 64 and 31 metabolites which jointly predicted pancdent of adiposity-related parameters, but not age.

Untargeted metabolomics identified candidate markers of visceral and ectopic fat that improved fat level prediction over clinical markers. Several plasma metabolites were associated with level of liver fat and VAT/SAT ratio independent of age, total and visceral adiposity, whereas pancreatic fat deposition was only associated with increased sulfolithocholic acid independent of adiposity-related parameters, but not age.Direct-acting antiviral (DAA) therapy carries a potential risk of inducing hepatitis B virus (HBV) reactivation. However, the HBV kinetics during and after DAA therapy in patients co-infected with hepatitis C virus (HCV) and HBV remain unknown. We retrospectively evaluated the HBV kinetics during and after sofosbuvir/ribavirin therapy in four HBV inactive carriers co-infected with HCV. HCV was eradicated in all patients. Changes in HBV-DNA levels during treatment differed among patients. The hepatitis B surface antigen (HBsAg) levels uniformly decreased (mean -0.530 logIU/mL) by the end of treatment and returned to near the baseline in all patients. Sofosbuvir/ribavirin therapy thus demonstrated a suppressive effect on HBsAg.We herein report a fatal case of coronavirus disease 2019 (COVID-19) pneumonia with rapid progression of respiratory failure and lymphopenia. Excessive recruitment and sequestration of lymphocytes in the lung were suggested as the pathophysiology underlying COVID-19-associated lymphopenia. Interestingly, the autopsy in this case revealed lymphocytic infiltration in the lungs even at sites that appeared normal on autopsy imaging. These findings suggest that in COVID-19 cases with risk factors of severe exacerbation, early glucocorticoid administration should be considered, especially if lymphopenia is present, even if the imaging findings show only mild abnormalities.