A Novel Dipterocarpol Derivative That Targets Alpha-Glucosidase and NLRP3 Inflammasome Activity for Treatment of Diabetes Mellitus.

Type 2 diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia, chronic inflammation, impaired insulin secretion, and/or peripheral insulin resistance. Current α-glucosidase inhibitors approved for clinical use exhibit limited efficacy compared to other glucose-lowering agents. In this study, a series of mono- and bis-benzylidene derivatives were synthesized via aldol condensation of 3-oxo-dammarane triterpenoids with terephthalic aldehyde.

Intraoperative assessment of resection margins by Raman spectroscopy to guide oral cancer surgery.

Patients with oral cavity cancer are almost always treated with surgery. The goal is to remove the tumor with a margin of more than 5 mm of surrounding healthy tissue. Unfortunately, this is only achieved in about 15% to 26% of cases.

New Organometallic Ru(II) Compounds with Lonidamine Motif as Antitumor Agents.

The combination of one molecule of organic and metal-based fragments that exhibit antitumor activity is a modern approach in the search for new promising drugs. In this work, biologically active ligands based on lonidamine (a selective inhibitor of aerobic glycolysis used in clinical practice) were introduced into the structure of an antitumor organometallic ruthenium scaffold. Resistant to ligand exchange reactions, compounds were prepared by replacing labile ligands with stable ones.

3-Arylidene-2-oxindoles as Potent NRH:Quinone Oxidoreductase 2 Inhibitors.

The enzyme NRH:quinone oxidoreductase 2 (NQO2) plays an important role in the pathogenesis of various diseases such as neurodegenerative disorders, malaria, glaucoma, COVID-19 and cancer. NQO2 expression is known to be increased in some cancer cell lines. Since 3-arylidene-2-oxindoles are widely used in the design of new anticancer drugs, such as kinase inhibitors, it was interesting to study whether such structures have additional activity towards NQO2.

Amino Derivatives of Diaryl Pyrimidines and Azolopyrimidines as Protective Agents against LPS-Induced Acute Lung Injury.

The problem of lung damage originating from excessive inflammation and cytokine release during various types of infections remains relevant and stimulates the search for highly effective and safe drugs. The biological activity of the latter may be associated with the regulation of hyperactivation of certain immune cells and enzymes. Here, we propose the design and synthesis of amino derivatives of 4,6- and 5,7-diaryl substituted pyrimidines and [1,2,4]triazolo[1,5-]pyrimidines as promising double-acting pharmacophores inhibiting IL-6 and NO.

6-(Tetrazol-5-yl)-7-aminoazolo[1,5-]pyrimidines as Novel Potent CK2 Inhibitors.

In this work, we describe the design, synthesis, and structure-activity relationship of 6-(tetrazol-5-yl)-7-aminoazolo[1,5-a]pyrimidines as inhibitors of Casein kinase 2 (CK2). At first, we optimized the reaction conditions for the azide-nitrile cycloaddition in the series of 6-cyano-7-aminoazolopyridimines and sodium azide. The regioselectivity of this process has been shown, as the cyano group of the pyrimidine cycle was converted to tetrazole while the nitrile of the azole fragment did not react.

Guanidine Derivatives of Quinazoline-2,4(1,3)-Dione as NHE-1 Inhibitors and Anti-Inflammatory Agents.

Quinazolines are a rich source of bioactive compounds. Previously, we showed NHE-1 inhibitory, anti-inflammatory, antiplatelet, intraocular pressure lowering, and antiglycating activity for a series of quinazoline-2,4(1,3)-diones and quinazoline-4(3)-one guanidine derivatives. In the present work, novel N1,N3-bis-substituted quinazoline-2,4(1,3)-dione derivatives bearing two guanidine moieties were synthesized and pharmacologically profiled.

Intracranial rheumatoid nodule causing recurrent transient neurological deficits.

A 67-year-old man with rheumatoid arthritis developed recurrent acute onset of stereotyped focal neurological abnormalities. Cerebral imaging showed a mass lesion in the left parieto-occipital lobe. Imaging did not show the time evolution expected in stroke and so he underwent an extensive workup, which was inconclusive.

Anti-Inflammatory Activity of Soluble Epoxide Hydrolase Inhibitors Based on Selenoureas Bearing an Adamantane Moiety.

The inhibitory potency of the series of inhibitors of the soluble epoxide hydrolase (sEH) based on the selenourea moiety and containing adamantane and aromatic lipophilic groups ranges from 34.3 nM to 1.2 μM.

Discovery of Nitro-azolo[1,5-]pyrimidines with Anti-Inflammatory and Protective Activity against LPS-Induced Acute Lung Injury.

Acute lung injury remains a challenging clinical condition, necessitating the development of novel, safe and efficient treatments. The prevention of macrophage M1-polarization is a viable venue to tackle excessive inflammation. We performed a phenotypic screening campaign to identify azolopyrimidine compounds that effectively inhibit LPS-induced NO synthesis and interleukin 6 (IL-6) secretion.

miRNA Decoy Screen Reveals miR-124a as a Suppressor of Melanoma Metastasis.

Melanoma is a highly prevalent cancer with an increasing incidence worldwide and high metastatic potential. Brain metastasis is a major complication of the disease, as more than 50% of metastatic melanoma patients eventually develop intracranial disease. MicroRNAs (miRNAs) have been found to play an important role in the tumorigenicity of different cancers and have potential as markers of disease outcome.

Takotsubo Cardiomyopathy: A COVID-19 Complication.

COVID-19 started as an unknown viral illness and has been a challenging pandemic to overcome. The virus has been associated with multiple organ involvement, including the heart. Takotsubo cardiomyopathy (TSCM), a stress cardiomyopathy, is an uncommon complication in patients diagnosed with COVID-19.

The histone demethylase PHF8 regulates TGFβ signaling and promotes melanoma metastasis.

The contribution of epigenetic dysregulation to metastasis remains understudied. Through a meta-analysis of gene expression datasets followed by a mini-screen, we identified Plant Homeodomain Finger protein 8 (PHF8), a histone demethylase of the Jumonji C protein family, as a previously unidentified prometastatic gene in melanoma. Loss- and gain-of-function approaches demonstrate that PHF8 promotes cell invasion without affecting proliferation in vitro and increases dissemination but not subcutaneous tumor growth in vivo, thus supporting its specific contribution to the acquisition of metastatic potential.

Ru(III) Complexes with Lonidamine-Modified Ligands.

A series of bifunctional Ru(III) complexes with lonidamine-modified ligands (lonidamine is a selective inhibitor of aerobic glycolysis in cancer cells) was described. Redox properties of Ru(III) complexes were characterized by cyclic voltammetry. An easy reduction suggested a perspective for these agents as their whole mechanism of action seems to be based on activation by metal atom reduction.

Diversity of Strains Isolated from Food Products in the Central European Part of Russia in 2000-2005 and 2019-2020.

Totally, 45 strains isolated from meat, poultry, dairy, and fish products in the Central European part of Russia in 2001-2005 and 2019-2020 were typed using a combined MLST and internalin profile (IP) scheme. Strains belonged to 14 clonal complexes (CCs) of the phylogenetic lineages I and II. Almost half of the strains (20 of 45) belonged to six CCs previously recognized as epidemic clones (ECs).

Antimicrobial Resistance of Strains Isolated from Humans, Animals, and Food Products in Russia in 1950-1980, 2000-2005, and 2018-2021.

Susceptibility of 117 strains isolated during three time periods (1950-1980; 2000-2005, and 2018-2021) to 23 antibiotics was tested by the disk diffusion method. All strains were sensitive to aminoglycosides (gentamicin, kanamycin, neomycin, streptomycin), glycopeptides (vancomycin and teicoplanin), clarithromycin, levofloxacin, amoxicillin/clavulanic acid, and trimethoprim/sulfamethoxazole. Resistance to clindamycin was observed in 35.

Evaluation of Cytotoxicity and α-Glucosidase Inhibitory Activity of Amide and Polyamino-Derivatives of Lupane Triterpenoids.

A series of two new and twenty earlier synthesized branched extra-amino-triterpenoids obtained by the direct coupling of betulinic/betulonic acids with polymethylenpolyamines, or by the cyanoethylation of lupane type alcohols, oximes, amines, and amides with the following reduction were evaluated for cytotoxicity toward the NCI-60 cancer cell line panel, α-glucosidase inhibitory, and antimicrobial activities. Lupane carboxamides, conjugates with diaminopropane, triethylenetetramine, and branched C3-cyanoethylated polyamine methyl betulonate showed high cytotoxic activity against most of the tested cancer cell lines with GI that ranged from 1.09 to 54.

Extraordinary structural complexity of ilmajokite: a multilevel hierarchical framework structure of natural origin.

The crystal structure of ilmajokite, a rare Na-K-Ba-Ce-titanosilicate from the Khibiny mountains, Kola peninsula, Russia, has been solved using single-crystal X-ray diffraction data. The crystal structure is based on a 3D titanosilicate framework consisting of trigonal prismatic titanosilicate (TPTS) clusters centered by Ce in [9]-coordination. Four adjacent TPTS clusters are linked into four-membered rings within the (010) plane and connected ribbons parallel to 101.

Desmicola lamdongensis sp. n. (Oxyuridomorpha: Thelastomatidae) from Vietnamese wood-burrowing cockroaches (Panesthiinae).

A new thelastomatid species, Desmicola lamdongensis sp. n. from the hindgut of Panesthiinae cockroaches collected in Bi Doup-Nui Ba National Park, Vietnam is described and illustrated.

Retrospective Study of Isolated in the Territory of Inner Eurasia from 1947 to 1999.

Listeriosis is one of the most significant humans and animals foodborne infectious diseases. Here, we characterized 48 strains isolated in the territory of inner Eurasia during the second half of the 20th century. A total of 23 strains (52.

Towards multi-target antidiabetic agents: Discovery of biphenyl-benzimidazole conjugates as AMPK activators.

Type 2 diabetes mellitus is a complex metabolic disorder requiring polypharmacology approaches for effective treatment. Combinatorial library of fifteen new tricyclic benzimidazole derivatives have been designed and synthesized to combine fragments commonly found in allosteric AMPK activators and AT receptor antagonists. It was found that 2'-cyanobiphenyl serves as the pharmacophore of AMPK-activating activity, which also increases with the expansion of the external hydrogenated cycle.

Automated multimodal spectral histopathology for quantitative diagnosis of residual tumour during basal cell carcinoma surgery.

Multimodal spectral histopathology (MSH), an optical technique combining tissue auto-fluorescence (AF) imaging and Raman micro-spectroscopy (RMS), was previously proposed for detection of residual basal cell carcinoma (BCC) at the surface of surgically-resected skin tissue. Here we report the development of a fully-automated prototype instrument based on MSH designed to be used in the clinic and operated by a non-specialist spectroscopy user. The algorithms for the AF image processing and Raman spectroscopy classification had been first optimised on a manually-operated laboratory instrument and then validated on the automated prototype using skin samples from independent patients.