An efficient and facile green synthesis of spirooxindole derivatives bearing pyrano[2,3-c]pyrazole moiety has been achieved via a [Formula: see text]-NPs catalyzed four-component reaction in water. The protocol offers an environmentally benign and effective approach to highly functionalized and biologically interesting spiro[indoline-3,4[Formula: see text]-pyrano[2,3-c]pyrazole] derivatives. The synthesized compounds exhibit potent antioxidant and antibacterial activities.

We hypothesized that photodynamic therapy (PDT) with Chlorin e6 (Ce6) enhances antitumor abscopal effects via inhibition of the programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint. By using syngeneic melanoma and pancreatic tumor mouse models, we studied the Ce6-PDT-induced immune responses in local and distant tumor microenvironments. In addition, the Ce6-PDT's target in the PD-1/PD-L1 interaction was analyzed in MC38-hPD-L1 colon cancer and PD-1 expressing Jurkat T cell coculture. The tumors in the irradiated and non-irradiated sites in the abscopal effective (Abseff) group of both mouse models were regressed, proving the abscopal effect. The immunogenic effect in the Abseff group was associated with an expansion of T cell and other immune cells infiltration without changes in the CD39+ population in either the right or left tumors compared to control group. Furthermore, the abscopal ineffective (Absineff) group demonstrated lesser increase of T cells, decreased immune cell infiltration, and increased CD39-expressing Treg cells without suppression of tumor growth. In the coculture with PD-1-expressing Jurkat T cell, Ce6-PDT efficiently suppressed the PD-1/PD-L1 interactions by increasing the proliferation and cytotoxic activity of CD8+ T cells while decreasing CD39-expressing Treg cells in a dose-dependent manner. Likewise, the inhibition of PD-1/PD-L1 interactions was also correlated with the increased production of IL-2 and Granzyme B. Our findings imply that Ce6-PDT is a promising immunotherapy with the potential to improve the abscopal effect.

An efficientp rotocolf or the direct sulfanylation of various 4-hydroxycoumarins and4 -hydroxyquinolinones in good yield with arylsulfonylhydrazides as sulfanylating agents was developed via copper(I) bromide·dimethyl sulfide-catalyzed S-O, S-N bond cleavage and C-S cross-coupling reactions.Ahighly selective fluorescence turning-on sensing of cadmium(II) ions in water using the synthesized 3-sulfanyl-4-hydroxycoumarin derivative was also investigated.

Photodynamic therapy and photoacoustic (PA) imaging are emerging therapeutic modalities for the diagnosis and treatment of various types of cancer or other diseases. In this study, the second-generation photosensitizer Chlorin e6 was prepared on a pilot scale by using the rapid, simple, and green synthetic method as compared to a conventional protocol. In the modified method, the extraction/reaction time and volume of solvents were significantly reduced. The dark and photodynamic cytotoxicity of Ce6 was measured against B16F10 melanoma cell line. Ce6 did not affect cancer cells in the dark up to 192 µM, ensuring their safety in the absence of light. After PDT, it displayed significant cytotoxicity at lower concentrations (IC50: 18.9 µM). For in vivo study, B16F10 allograft mice were treated with Ce6 at 2.5 mg/kg and then exposed to red light (660 nm) after 3 h. The Ce6-PDT caused the inhibition of tumor growth. Furthermore, Ce6 was also used as a photoacoustic imaging agent in ICR mice to visualize the internal organs. Therefore, this study provides valuable information about Ce6-PDT as a promising strategy for anti-cancer therapy as well as visualization of internal organs without surgery or X-rays.

In the current study, the therapeutic and preventive effects of Euonymus alatus (EA) twig extract were investigated in a mouse model of cognitive deficit and B35 cells. Twig extract 1 was extracted with 70% ethanol and later twig extract 2 was extracted through liquid-liquid extraction with 70% ethanol and hexane. EA twig 2 (300 mg/kg) along with the standard drug donepezil (5 mg/kg) were orally administered to the mice for 34 days. Scopolamine was given intraperitoneally for 7 days. Administration of EA twig extract 2 significantly improved the passive avoidance test (PAT) in mice. EA twigs extract also restored the scopolamine-reduced brain-derived neurotrophic factor (BDNF)/extracellular regulated kinase (ERK)/cyclic AMP responsive element binding protein (CREB) signaling in B35 cells and the mouse hippocampus. In addition, EA twig extract significantly inhibited the acetylcholine esterase (AChE) activity in B35 cells in a dose-dependent manner. Chromatography and ESI MS analysis of EA twig extract revealed the presence of flavonoids; epicatechin, taxifolin, aromadendrin, and naringenin with catechin being the most abundant. These flavonoids exerted protective effects alone and had the possibility of synergistic effects in combination. Our work unmasks the ameliorating effect of EA twig extract 2 on scopolamine-associated cognitive impairments through the restoration of cholinergic systems and the BDNF/ERK/CREB pathway.