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Indocyanine green (ICG) is the FDA-approved fluorescent dye used for in vivo medical imaging, diagnostics, and photothermal therapy. However, this dye is easily degradable in the human vascular system, and therefore its stabilization is preferable. In this work, ICG molecules were stabilized by their adsorption on the surface of the L-methionine-capped Ag and Au nanoparticles (Ag and Au @LM NPs) in aqueous colloidal dispersions. The result is the formation of hybrid metal core/ICG shell NPs in colloidal dispersions. Additionally, colloidal dispersions were stabilized, indicating a double effect of ICG adsorption. The obtained hybrid NPs were studied experimentally (UV-Vis spectrophotometry, HRTEM, DLS, FTIR) and theoretically (DFT calculations). HRTEM revealed that the interplanar spacing between adjacent planes of NPs decreases after the dye adsorption. The results obtained from the DFT study confirmed the formation of a covalent bond between the oxygen from ICG dye SO 3 - group and metal NPs. Considering the characteristics of both components of the NPs/ICG hybrid system, the authors assume that this hybrid system can exhibit the synergistic effect that could lead to more successful theranostic treatment of cancer in nanomedicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The synthesis of 24 hybrid molecules, consisting of naturally occurring sclareol (SCL) and synthetic 1,2,4-triazolo[1,5-a]pyrimidines (TPs), is described. New compounds were designed with the aim of improving the cytotoxic properties, activity, and selectivity of the parent compounds. Six analogs (12a-f) contained 4-benzylpiperazine linkage, while 4-benzyldiamine linkage was present in eighteen derivatives (12g-r and 13a-f). Hybrids 13a-f consist of two TP units. After purification, all hybrids (12a-r and 13a-f), as well as their precursors (9a-e and 11a-c), were tested on human glioblastoma U87 cells. More than half of the tested synthesized molecules, 16 out of 31, caused a significant reduction of U87 cell viability (more than 75% reduction) at 30 µM. The concentration-dependent cytotoxicity of these 16 compounds was also examined on U87 cells, corresponding multidrug-resistant (MDR) U87-TxR cells with increased P-glycoprotein (P-gp) expression and activity, and normal lung fibroblasts MRC-5. Importantly, 12l and 12r were active in the nanomolar range, while seven compounds (11b, 11c, 12i, 12l, 12n, 12q, and 12r) were more selective towards glioblastoma cells than SCL. All compounds except 12r evaded MDR, showing even better cytotoxicity in U87-TxR cells. In particular, 11c, 12a, 12g, 12j, 12k, 12m, 12n, and SCL showed collateral sensitivity. Hybrid compounds 12l, 12q, and 12r decreased P-gp activity to the same extent as a well-known P-gp inhibitor - tariquidar (TQ). Hybrid compound 12l and its precursor 11c affected different cellular processes including the cell cycle, cell death, and mitochondrial membrane potential, and changed the levels of reactive oxygen and nitrogen species (ROS/RNS) in glioblastoma cells. Collateral sensitivity towards MDR glioblastoma cells was caused by the modulation of oxidative stress accompanied by inhibition of mitochondria., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Thirteen undescribed 24-methylene lanostane triterpenoids, named polyporenic acids E-M and fomitosides L-O, as well as seventeen known analogues, were isolated from the fruiting bodies of the mushroom Fomitopsis betulina. Their structures were determined using 1D, 2D NMR, IR, and HRESIMS. Fomitoside L and fomitoside N exhibited cytotoxicity against HL60 leukemia cells (IC 50  = 15.8 and 23.7 μM, respectively). Among the known compounds, notable cytotoxicities against HL60 leukemia cells and selectivity with respect to MRC-5 healthy cells were noticed for dehydropachymic acid (IC 50  = 10.9 μM, SI 8.6), pachymic acid (IC 50  = 11.0 μM, SI 9.8), 3-epi-dehydrotumulosic acid (IC 50  = 19.9 μM, SI 5.8) and 12α-hydroxy-3α-(3'-hydroxy-4'-methoxycarbonyl-3'-methylbutyryloxy)-24-methyllanosta-8,24 (31)-dien-26-oic acid (IC 50  = 19.2 μM, SI 2.2)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Supervised exercise training (walking) is recommended in patients with intermittent claudication, both as a means to improve symptoms (walking distance and quality of life [QoL]) and as a means to improve general cardiovascular health (including vascular function and heart rate variability [HRV]). Our aim was to compare two types of supervised training (moderate-pain and pain-free walking) with comparable intensity based on heart rate, in terms of walking capacity, QoL, vascular function, biomarkers, and HRV in patients with intermittent claudication., Methods: Thirty-six adults with intermittent claudication were randomized to either moderate-pain or pain-free exercise training (36 sessions, two or three times a week) or usual care (no supervised exercise). Initial walking distance and absolute walking distance using treadmill testing, flow-mediated vasodilation and pulse wave velocity using ultrasound, N-terminal pro-B-type natriuretic peptide and fibrinogen levels, HRV, and QoL (36-Item Short Form Health Survey questionnaire) were determined at baseline and after the intervention period., Results: Twenty-nine patients (mean age, 64 ± 9 years; 72% male) completed the study. Both training programs similarly improved walking capacity. Initial walking distance and absolute walking distance significantly increased with either moderate-pain walking (median, 50 m to 107 m [P = .005] and 85 m to 194 m [P = .005], respectively) or pain-free walking (median, 53 m to 128 m [P = .003] and 92 m to 163 m [P = .003], respectively). QoL also similarly improved with both training modalities, whereas only moderate-pain walking was also associated with a statistically significant improvement in the vascular parameters flow-mediated vasodilation (4.4% to 8.0%; P = .002) and pulse wave velocity (6.6 m/s to 6.1 m/s; P = .013). Neither training program was associated with changes in biomarker levels and HRV., Conclusions: Both moderate-pain and pain-free training modalities were safe and similarly improved walking capacity and health-related QoL. Conversely, vascular function improvements were associated with only moderate-pain walking., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Adults with repaired tetralogy of Fallot (ToF) have impaired exercise capacity, vascular and cardiac autonomic function, and quality of life (QoL). Specific effects of high-intensity interval or moderate continuous exercise training on these parameters in adults with repaired ToF remain unknown., Methods and Results: Thirty adults with repaired ToF were randomized to either high-intensity interval, moderate intensity continuous training (36 sessions, 2-3 times a week) or usual care (no supervised exercise). Exercise capacity, flow-mediated vasodilation, pulse wave velocity, NT-proBNP and fibrinogen levels, heart rate variability and recovery, and QoL (SF-36 questionnaire) were determined at baseline and after the intervention period. Twenty-seven patients (mean age 39±9years, 63% females, 9 from each group) completed this pilot study. Both training groups improved in at least some parameters of cardiovascular health compared to no exercise. Interval-but not continuous-training improved VO2peak (21.2 to 22.9ml/kg/min, p=0.004), flow-mediated vasodilation (8.4 to 12.9%, p=0.019), pulse wave velocity (5.4 to 4.8m/s, p=0.028), NT-proBNP (202 to 190ng/L, p=0.032) and fibrinogen levels (2.67 to 2.46g/L, p=0.018). Conversely, continuous-but not interval-training improved heart rate variability (low-frequency domain, 0.32 to 0.22, p=0.039), heart rate recovery after 2min post-exercise (40 to 47 beats, p=0.023) and mental domain of SF-36 (87 to 95, p=0.028)., Conclusion: Both interval and continuous exercise training modalities were safe. Interval training seems more efficacious in improving exercise capacity, vascular function, NT-proBNP and fibrinogen levels, while continuous training seems more efficacious in improving cardiac autonomic function and QoL. (Clinicaltrials.gov, NCT02643810)., (Copyright © 2018 Elsevier Ireland Ltd. All rights reserved.)

Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 3' and 3″-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 3' and 3″-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Medicinal plants are recognized from ancient times as a source of diverse therapeutic agents and many of them are used as dietary supplements. Comprehensive approaches are needed that would identify bioactive components with evident activity against specific indications and provide a better link between science (ethno-botany, chemistry, biology and pharmacology) and market. Recently, the bark of black alder (Alnus glutinosa) appeared at market in the form of food supplement for treatment of different skin conditions. This study aimed to evaluate protective effects of two diarylheptanoids isolated from the bark of black alder: platyphylloside, 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-β-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-β-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2) towards doxorubicin damaging activity. To that end, we employed HaCaT cells, non-cancerous human keratinocytes commonly used for skin regenerative studies. Diarylheptanoids significantly antagonized the effects of doxorubicin by lowering the sensitivity of HaCaT cells to this drug. Compound 2 prevented doxorubicin-induced cell death by activating autophagy. Both 1 and 2 protected HaCaT cells against doxorubicin-induced DNA damage. They significantly promoted migration and affected F-actin distribution. These results indicate that chemo-protective effects of diarylheptanoids may occur at multiple subcellular levels. Therefore, diarylheptanoids 1 and 2 could be considered as protective agents for non-cancerous dividing cells during chemotherapy., (Copyright © 2015 Elsevier B.V. All rights reserved.)

An extended study of minor diarylheptanoids from the bark of black alder has resulted in the isolation of twenty diarylheptanoids, ten of which have not previously been reported (14-18, 20-24). The structures and configurations of all compounds were elucidated by NMR, HRESIMS, UV, IR, and CD. The anti-cancer potency of twenty diarylheptanoids and four previously isolated compounds (7, 10, 12, 13) was investigated in human non-small cell lung carcinoma cell lines (sensitive and multi-drug resistant variants) as well as in normal human keratinocytes. Diarylheptanoids with a p-coumaroyl group, 14 and 18, platyphylloside (1), platyphyllonol-5-O-β-D-xylopyranoside (2), alnuside B (4) and hirsutenone (9) exhibited strong anti-cancer activity, considerably higher than diarylheptanoid curcumin, which served as a positive control. Compounds 4, 9, 14, and 18 displayed significant selectivity towards the cancer cells. Structure/activity analysis of twenty-four closely related diarylheptanoids revealed a high dependence of cytotoxic action on the presence of a carbonyl group at C-3. Substitution of a heptane chain on C-5 and a number of hydroxyl groups in the aromatic rings also emerged as a significant structural feature that influenced their cytotoxic potential., (Copyright © 2013 Elsevier Ltd. All rights reserved.)