PEGylated chitosan-coated nanophotosensitizers for effective cancer treatment by photothermal-photodynamic therapy combined with glutathione depletion.

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has emerged as a promising strategy for cancer treatment. However, the poor photostability and photothermal conversion efficiency (PCE) of organic small-molecule photosensitizers, and the intracellular glutathione (GSH)-mediated singlet oxygen scavenging largely decline the antitumor efficacy of PTT and PDT. Herein, a versatile nanophotosensitizer (NPS) system is developed by ingenious incorporation of indocyanine green (ICG) into the PEGylated chitosan (PEG-CS)-coated polydopamine (PDA) nanoparticles via multiple π-π stacking, hydrophobic and electrostatic interactions. The PEG-CS-covered NPS showed prominent colloidal and photothermal stability as well as high PCE (ca 62.8 %). Meanwhile, the Michael addition between NPS and GSH can consume GSH, thus reducing the GSH-induced singlet oxygen scavenging. After being internalized by CT26 cells, the NPS under near-infrared laser irradiation produced massive singlet oxygen with the aid of thermo-enhanced intracellular GSH depletion to elicit mitochondrial damage and lipid peroxide formation, thus leading to ferroptosis and apoptosis. Importantly, the combined PTT and PDT delivered by NPS effectively inhibited CT26 tumor growth in vivo by light-activated intense hyperthermia and redox homeostasis disturbance. Overall, this work presents a new tactic of boosting antitumor potency of ICG-mediated phototherapy by PEG-CS-covered NPS.

Secular Trends in Incidence of Esophageal Cancer in Taiwan from 1985 to 2019: An Age-Period-Cohort Analysis.

In Taiwan, the age-standardized incidence of EC, especially esophageal squamous cell carcinoma (ESCC), has increased substantially during the past thirty years. We described the incidence trends of EC from 1985−2019 by an average annual percentage change (AAPC) and age-period-cohort model by using Taiwan Cancer Registry data. Age-period-cohort modeling was used to estimate the period and cohort effects of ESCC and esophageal adenocarcinoma (EAC). The Spearman's correlation coefficient was used to analyze the correlation between age-adjusted incidence rates of EC and the prevalence of risk factors from national surveys. The results showed the incidence rate of ESCC in men (AAPC = 4.2, 95% CI = 3.1−5.4, p < 0.001) increased prominently from 1985−1989 to 2015−2019 while that of EAC in men (AAPC = 1.2, 95% CI = 0.9−1.5, p < 0.001) and ESCC in women (AAPC = 1.7, 95% CI = 1.4−2.1, p < 0.001) increased to a lesser degree. Increased period effects were observed in ESCC in men, ESCC in women, and EAC in men. High correlations were found between the risk factors and the increased birth-cohort effects of ESCC (p < 0.05). To conclude, the incidence of ESCC in both sex and EAC in men increased with statistical significance in recent decades. The increased prevalence of risk factors from approximately 1970−1995 could explain the increased cohort effects of ESCC.

Synthesis of benzofused cyclobutaoxepanones via intramolecular annulation of o-cinnamyl chalcones.

Intramolecular stereoselective annulation of o-cinnamyloxy chalcones provides two kinds of tricyclic benzofused cyclobutaoxepanones via the synthesized routes of DABCO/NBS (1,4-diazabicyclo[2.2.2]octane/N-bromosuccinimide)-mediated Baylis-Hillman type cyclization or low-pressure mercury (LP Hg) lamp-promoted photocontrolled [2 + 2] cycloaddition. Diversified reaction conditions have been investigated for one-pot facile, high-yield transformation.

A novel one-pot synthesis of flavones.

In this paper, a one-pot facile route for the BiCl3/RuCl3-mediated synthesis of functionalized flavones is described, including: (i) intermolecular ortho-acylation of substituted phenols with cinnamoyl chlorides, and (ii) intramolecular cyclodehydrogenation of the resulting o-hydroxychalcones. The reaction conditions are discussed herein.

Construction of Sulfonyl Dihydrobenzo[c]xanthen-7-ones Core via NH4OAc/PdCl2/CuCl2-Mediated Double Cyclocondensation of α-Sulfonyl o-Hydroxyacetophenones with 2-Allylbenzaldehydes.

NH4OAc/PdCl2/CuCl2 mediated domino double cyclocondensation of α-sulfonyl o-hydroxyacetophenones and 2-allylbenzaldehydes provides tetracyclic sulfonyl dihydrobenzo[c]xanthen-7-one core with good to excellent yields in MeOH. The intermediates contain a 3-sulfonyl flavanone motif. Only water is generated as a byproduct. The use of various catalysts and reaction conditions is studied for the facile-operational conversion.

Neuroprotective Effects of Betulin in Pharmacological and Transgenic Caenorhabditis elegans Models of Parkinson's Disease.

Parkinson's disease (PD) is the second most common degenerative disorder of the central nervous system in the elderly. It is characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta, as well as by motor dysfunction. Although the causes of PD are not well understood, aggregation of α-synuclein (α-syn) in neurons contributes to this disease. Current therapeutics for PD provides satisfactory symptom relief but not a cure. Treatment strategies include attempts to identify new drugs that will prevent or arrest the progressive course of PD by correcting disease-specific pathogenic process. Betulin is derived from the bark of birch trees and possesses anticancer, antimicrobial, and anti-inflammatory properties. The aim of the present study was to evaluate the potential for betulin to ameliorate PD features in Caenorhabditis elegans ( C. elegans) models. We demonstrated that betulin diminished α-syn accumulation in the transgenic C. elegans model. Betulin also reduced 6-hydroxydopamine-induced dopaminergic neuron degeneration, reduced food-sensing behavioral abnormalities, and reversed life-span decreases in a pharmacological C. elegans model. Moreover, we found that the enhancement of proteasomes activity by promoting rpn1 expression and downregulation of the apoptosis pathway gene, egl-1, may be the molecular mechanism for betulin-mediated protection against PD pathology. Together, these findings support betulin as a possible treatment for PD and encourage further investigations of betulin as an antineurodegenerative agent.

Irisflorentin improves α-synuclein accumulation and attenuates 6-OHDA-induced dopaminergic neuron degeneration, implication for Parkinson's disease therapy.

Parkinson's disease (PD) is a degenerative disorder of the central nervous system that is characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta as well as motor impairment. Aggregation of α-synuclein in neuronal cells plays a key role in this disease. At present, therapeutics for PD provides moderate symptomatic benefits, but it is not able to delay the development of the disease. Current efforts toward the treatment of PD are to identify new drugs that slow or arrest the progressive course of PD by interfering with a disease-specific pathogenetic process in PD patients. Irisflorentin derived from the roots of Belamcanda chinensis (L.) DC. is an herb which has been used for the treatment of inflammatory disorders in traditional Chinese medicine. The purpose of the present study was to assess the potential for irisflorentin to ameliorate PD in Caenorhabditis elegans models. Our data reveal that irisflorentin prevents α-synuclein accumulation in the transgenic Caenorhabditis elegans model and also improves dopaminergic neuron degeneration, food-sensing behavior, and life-span in a 6-hydroxydopamine-induced Caenorhabditis elegans model, thus indicating its potential as a anti-parkinsonian drug candidate. Irisflorentin may exert its effects by promoting rpn-3 expression to enhance the activity of proteasomes and down-regulating egl-1 expression to block apoptosis pathways. These findings encourage further investigation on irisflorentin as a possible potent agent for PD treatment.