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It is established that high rates of morbidity and mortality caused by fungal infections are related to the current limited number of antifungal drugs and the toxicity of these agents. Imidazolium salts as azole derivatives can be successfully used in the treatment of fungal infections in humans. Steroid-functionalized imidazolium salts were synthesized using a new, more efficient method. As a result, 20 salts were obtained with high yields, 12 of which were synthesized and characterized for the first time. They were derivatives of lithocholic acid and 3-oxo-23,24-dinorchol-4-ene-22-al and were fully characterized by 1H and 13C nuclear magnetic resonance (NMR), infrared spectroscopy (IR), and high resolution mass spectrometry (HRMS). Due to the excellent activity against bacteria and Candida albicans, new research was extended to include tests on five species of pathogenic fungi and molds: Aspergillus niger ATCC 16888, Aspergillus fumigatus ATCC 204305, Trichophyton mentagrophytes ATCC 9533, Cryptococcus neoformans ATCC 14116, and Microsporum canis ATCC 11621. The results showed that the new salts are almost universal antifungal agents and have a broad spectrum of activity against other human pathogens. To initially assess the safety of the synthesized salts, hemocompatibility with host cells and cytotoxicity were also examined. No toxicity was observed at the concentration at which the compounds were active against pathogens.

Dilated cardiomyopathy (DCM) is clinically characterised by dilated ventricular cavities and reduced ejection fraction, leading to heart failure and increased thromboembolic risk. Mutations in thin filament regulatory proteins can cause DCM and have been shown in vitro to reduce contractility and myofilament Ca2+-affinity. In this work we have studied the functional consequences of mutations in cardiac troponin T (R131W), cardiac troponin I (K36Q) and α-tropomyosin (E40K) using adenovirally transduced isolated guinea pig left ventricular cardiomyocytes. We find significantly reduced fractional shortening with reduced systolic Ca2+. We also observe slowed contraction and Ca2+-reuptake times, which contrast with some findings in murine models of myofilament Ca2+-desensitisation. We also observe increased sarco-endoplasmic reticulum (SR) Ca2+ load and smaller fractional SR Ca2+ release. This corresponds to a reduction in SR Ca2+-ATPase activity and increase in Sodium-Calcium Exchanger activity. The disequilibrium of Ca2+ handling promotes dephosphorylation and nuclear translocation of the Nuclear-Factor-of-Activated T-cells (NFAT), with concordant RAC-alpha serine/threonine-protein kinase (AKT) phosphorylation but no change to Extracellular‐Signal‐Regulated Kinase activation in chronically paced cardiomyocytes expressing DCM mutations. These changes in Ca2+-handling and signalling are common to all three mutations, indicating a common pathway of disease pathogenesis in thin filament sarcomeric DCM. Previous work has shown changes to myofilament Ca2+ sensitivity caused by DCM mutations are qualitatively opposite those resulting from hypertrophic cardiomyopathy (HCM) mutations. However, we find several common pathways such as increased relaxation times and NFAT activation that are also hallmarks of HCM. This suggests more complex intracellular signalling underpinning DCM, driven by the primary mutation.

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In recent years, there has been a significant surge in reports on the health-promoting benefits of winter cherry (Withania somnifera), also known as Ashwagandha. Its current research covers many aspects of human health, including neuroprotective, sedative and adaptogenic effects and effects on sleep. There are also reports of anti-inflammatory, antimicrobial, cardioprotective and anti-diabetic properties. Furthermore, there are reports of reproductive outcomes and tarcicidal hormone action. This growing body of research on Ashwagandha highlights its potential as a valuable natural remedy for many health concerns. This narrative review delves into the most recent findings and provides a comprehensive overview of the current understanding of ashwagandha’s potential uses and any known safety concerns and contraindications.

New indenylidene-type second generation catalysts bearing modified unsymmetrically substituted Nheterocyclic carbene ligands were synthesized. The complexes contain an N-mesityl and N 0 -nitrobenzyl substituted NHC ligand. The precursors of free carbenes-imidazolinium salts-were obtained in an easy and environmentfriendly way (under aqueous or neat conditions). The new catalysts were prepared by reaction of in situ generated carbenes with a 1st generation indenylidene catalyst, containing pyridine ligands instead of tricyclohexylphosphine. The complexes were tested in RCM, CM, and ene-yne metathesis model reactions in commercial-grade solvents in air. Their activities were compared with that of commercially available indenylidene catalyst. The structures of complexes and their stability were investigated using static DFT calculations with mixed basis set.

Liver abscesses are focal necroinflammatory lesions of bacterial, fungal, or amoebic origin. Pharmacological treatment is rarely sufficient if negative blood cultures are present. The report presents the case of a 62-year-old man with hypertension and type 2 diabetes, diagnosed with liver abscesses. The patient received two-stage empirical antibiotic therapy. Firstly in the hospital setting-cefuroxym, gentamicin, and metronidazole. After a 10-fold reduction in C-reactive protein and clinical improvement the patient was discharged home. In the second stage-ceftibutyn, metronidazole, and fluconasol were used in the outpatient setting. During rehospitalisation, a significant reduction in the size of abscesses was noted. The patient was twice consulted bacteriologically (treatment was accepted) and his computed tomography (CT) scans were sent for surgical consultation, which confirmed the effectiveness of the drug treatment and did not qualify for surgical treatment. In the 8-month follow-up there was no relapse and CT scans showed only scarring of the liver. Streszczenie Ropnie wątroby są zmianami ogniskowymi miąższu wątroby o etiologii bakteryjnej, amebowej lub grzybiczej. Rzadko udaje się je wyleczyć jedynie metodą farmakologiczną przy ujemnych wynikach posiewów krwi. W pracy przedstawiono przypadek 62-letniego mężczyzny leczącego się z powodu nadciśnienia tętniczego i cukrzycy typu 2, u którego rozpoznano ropnie wątroby. U chorego zastosowano dwuetapową antybiotykoterapię empiryczną. W pierwszym etapie (złożona antybiotykoterapia) w warunkach szpitalnych podawano cefuroksym, gentamycynę i metronidazol. Po 10-krotnej redukcji wartości stężenia białka C-reaktywnego oraz uzyskaniu poprawy klinicznej pacjenta wypisano do domu. W drugim etapie leczenia (ambulatoryjnym) stosowano ceftibutyn, metronidazol i flukonazol. Przy ponownej hospitalizacji stwierdzono znaczne zmniejszenie wymiaru ropni wątroby. Przypadek konsultowano 2 razy bakteriologicznie (zaakceptowano leczenie), a wyniki badań obrazowych przesłano na konsylium chirurgiczne, gdzie potwierdzono skuteczność leczenia farmakologicznego i nie zakwalifikowano chorego do leczenia operacyjnego. W obserwacji 8-miesięcznej nie stwierdzono nawrotu choroby, a w obrazie tomografii komputerowej jamy brzusznej opisano jedynie zmiany bliznowate w wątrobie.