XRD/DFT, Hirshfeld surface analysis and molecular modelling simulations for unfolding reactivity of newly synthesized vanillin derivatives: excellent optical, NLO and protein binding efficiency.

New vanillin derivatives, namely, ethyl (4-formyl-2-methoxyphenoxy)acetate (2a) and 2-(4-formyl-2-methoxyphenoxy)-N-phenylacetamide (2b), respectively, were synthesized and characterized by NMR (1H and 13C), IR, mass spectra and confirmed by single-crystal X-ray analysis. Hirshfeld surface (HS) analysis was performed to probe intra- and intermolecular interactions and surface reactivity. 2D fingerprint plots (FP) were used to study the nature and percentage contribution of intermolecular interactions leading to the formation of the crystal unit. Density functional theory (DFT) simulations were used to obtain the electronic structure and reactivity of the new molecules. Natural population analysis (NPA) and frontier molecular orbital (FMO) calculations reveal significant charge transfer and a reduced HOMO-LUMO gap up to 4.34 eV for 2b. Bader's quantum theory of atoms in molecules (QTAIM) study is utilized to understand the surface topological and bonding nature of 2a and 2b. The performed molecular electrostatic potential (MESP) and density of states (DOS) study further suggest sites likely to be attractive to incoming reagents. At the same time, hyperpolarizability (ßo) is used to characterize the nonlinear optical properties, and TD-DFT study shows the excitation energy and absorption behavior. In silico studies were performed, including docking, binding free energies (MMBGSA) and molecular dynamics simulations. Compounds 2a and 2b were docked with RdRp of SARS-Cov-2, and the MMBGSA for 2a and 2b were -30.70 and -28.47 kcal/mol, respectively, while MD simulation showed the stability of protein-ligand complexes.Communicated by Ramaswamy H. Sarma.

Ketorolac-fluconazole: A New Combination Reverting Resistance in Candida albicans from Acute Myeloid Leukemia Patients on Induction Chemotherapy: In vitro Study.

BACKGROUND AND OBJECTIVES: Candida albicans is a significant source of morbidity and mortality for patients with acute myeloid leukemia (AML). Prolonged use of fluconazole as empirical antifungal prophylaxis in AML patients leads to overexpression of efflux pump genes that resulted in the emergence of azole-resistant species. Consequently, the introduction of a new strategy to improve the management of C. albicans infections is an urgent need. Nonsteroidal anti-inflammatory drug (NSAID) ketorolac is associated with a reduction in cancer relapses. The present study was performed to investigate the use of ketorolac-fluconazole combination to reverse fluconazole resistance in C. albicans isolated from AML patients on induction chemotherapy. PATIENTS AND METHODS: One hundred and seventy AML patients were evaluated. Fifty C. albicans were isolated and subjected to disc diffusion assay and broth microdilution for fluconazole alone and combined with different concentrations of ketorolac. Efflux pump gene (CDR1, CDR2, and MDR1) expressions were quantified by real-time PCR. RESULTS: The tested ketorolac acted synergistically with fluconazole against resistant C. albicans with the minimum inhibitory concentration (MIC) of fluconazole decreased from >160 µg/mL to 0.3-1.25 µg/mL in (93.8%) of resistant isolates with fractional inhibitory concentration index (FICI) value of 0.25. The majority of the resistant isolates overexpressed CDR1 (71.1%) and MDR1 (60%). CONCLUSION: Ketorolac-fluconazole in vitro combination would be a promising strategy for further clinical in vivo trials to overcome fluconazole resistance in AML patients on induction chemotherapy.

Tissue-based long non-coding RNAs "PVT1, TUG1 and MEG3" signature predicts Cisplatin resistance in ovarian Cancer.

OBJECTIVES: The current study aimed to investigate the potentiality of three lncRNAs "Plasmacytoma variant translocation 1(lnc-PVT1), Taurine upregulated gene type 1(lnc-TUG1) and Maternally expressed gene 3 (lnc-MEG-3)", to predict Cisplatin resistance in ovarian cancer (OC), in addition, to access their prognostic significance. METHODS: The expression level of lncRNAs were measured in 100 formalin-fixed paraffin-embedded tissue (FFET) samples of OC patients who were treated by Cisplatin-based chemotherapy using qPCR. RESULTS: The results showed that lnc_PVT1 was significantly upregulated by 2.3 folds in Cisplatin resistant tissues, while, lnc-TUG1 and lnc-MEG3 were downregulated by 1.2 and 3 folds, respectively. In addition, the three lncRNAs exhibited high sensitivity and specificity in predicting chemo-resistance and they were negatively associated with OS and progression-free survival (p < 0.001). CONCLUSION: The lnc-PVT1, lnc-TUG1, and lnc-MEG3 transcriptome signatures could be used for predicting resistance to Cisplatin in OC patients.

Pfeifferinella sp. (Pfeifferinellidae, Apicomplexa) infecting the fresh water snail Pirenella conica light and electron microscope studies.

Coccidian oocysts were proved to be found in 70 of 100 collected Pirenella conica snails, with a natural infection of 70%. It was observed that, Pfeifferinella sp. was transferred between hepatopancreas and small intestine of snail. The prepatent period of Pfeifferinella sp. infecting P. conica snails ranged from 14-18 days and the patent period was reached 50 days (P.I.). Merogony stages were the early stages observed in this study. These stages were observed in the hepatopancreas and in a large clear parasiteophorous vacuole (PV). In snails killed 4 days P.I. immature meronts were measured 12 x 10 µm containing 8 nuclei. Meanwhile, mature meronts with about 6 differentiated merozoites were detected as early as 6 days P.I., and measured 3.1 x 1.4 µm. The earliest gametogonic stages were seen in the intestine of Pirenella conica snails killed 12 days P.I. Microgamonts contained about 4 nuclei and measured 7.9 x6.7 µm. The macrogamonts measured 7.3 x 5.6 µm. Macrogametes were characterized by the presence of the vaginal tube, this tube measured 4.3 x 1.1 µm. Fertilization was occurred in the intestine of the infected snails at 12 days P.I. Zygotes developed into young oocysts after fertilization. Sporogony occurred in the intestine. In the earliest stage, the nucleus of young oocyst was occupied the central position that were observed through the examination of the intestine of infected Pirenella snails at 14 day P.I. These oocysts were found to be colorless and ellipsoid or spherical in shape measured 9.5 x 8.5 µm. The oocyst wall consists of two layers, micropyle and micropyle cap were not observed in these oocysts, and wall forming bodies were arranged at the periphery of oocyst directly under the developed oocyst wall. Sporulated oocyst contains 8 sporozoites filling the entire cavity of the oocyst without sporocyst formation. Fully sporulated oocysts were excreted in the faces of infected snails from 14-18 day P.I., these oocysts measured 9.5 x 8.5 µm, Micropyle was absent and while a residual body was observed.