Developing theragnostics for Alzheimer's disease: Insights from cancer treatment.

The prevalence of Alzheimer's disease (AD) and its associated economic and societal burdens are on the rise, but there are no curative treatments for AD. Interestingly, this neurodegenerative disease shares several biological and pathophysiological features with cancer, including cell-cycle dysregulation, angiogenesis, mitochondrial dysfunction, protein misfolding, and DNA damage. However, the genetic factors contributing to the overlap in biological processes between cancer and AD have not been actively studied. In this review, we discuss the shared biological features of cancer and AD, the molecular targets of anticancer drugs, and therapeutic approaches. First, we outline the common biological features of cancer and AD. Second, we describe several anticancer drugs, their molecular targets, and their effects on AD pathology. Finally, we discuss how protein-protein interactions (PPIs), receptor inhibition, immunotherapy, and gene therapy can be exploited for the cure and management of both cancer and AD. Collectively, this review provides insights for the development of AD theragnostics based on cancer drugs and molecular targets.

Trends in Research on Patients With COVID-19 in Korean Medical Journals.

OBJECTIVES: This study was conducted to systematically summarize trends in research concerning patients with coronavirus disease 2019 (COVID-19) as reported in Korean medical journals. METHODS: We performed a literature search of KoreaMed from January 2020 to September 2022. We included only primary studies of patients with COVID-19. Two reviewers screened titles and abstracts, then performed full-text screening, both independently and in duplicate. We first identified the 5 journals with the greatest numbers of eligible publications, then extracted data pertaining to the general characteristics, study population attributes, and research features of papers published in these journals. RESULTS: Our analysis encompassed 142 primary studies. Of these, approximately 41.0% reported a funding source, while 3.5% disclosed a conflict of interest. In 2020, 42.9% of studies included fewer than 10 participants; however, by 2022, the proportion of studies with over 200 participants had increased to 40.6%. The most common design was the cohort study (48.6%), followed by case reports/series (35.2%). Only 3 randomized controlled trials were identified. Studies most frequently focused on prognosis (58.5%), followed by therapy/intervention (20.4%). Regarding the type of intervention/exposure, therapeutic clinical interventions comprised 26.1%, while studies of morbidity accounted for 13.4%. As for the outcomes measured, 50.7% of studies assessed symptoms/clinical status/improvement, and 14.1% evaluated mortality. CONCLUSIONS: Employing a systematic approach, we examined the characteristics of research involving patients with COVID-19 that was published in Korean medical journals from 2020 onward. Subsequent research should assess not only publication trends over a longer timeframe but also the quality of evidence provided.

Design of a Novel Sericite-Phosphoric Acid Framework for Enhancement of Pb(II) Adsorption.

In this study, phosphoric acid was used to attach anions to the weak interlayer structure of sericite, one of the clay minerals composed of a tetrahedral structure of silicate, to increase the adsorption capacity of cations. Natural sericite beads (NSB) and activated sericite beads with phosphoric acid (PSB) were prepared as beads in order to increase reusability and facilitate the separation of adsorbates and adsorbents. Using this, lead (Pb(II)) removal efficiency from an aqueous solution was comparatively analyzed. The pHpzc was 6.43 in NSB but lowered to 3.96 in PSB, confirming that more acidic functional groups were attached to the PSB surface. According to FT-IR analysis, P=O, P-O-C, P=OOH and P-O-P bonds appeared on the surface of the PSB adsorbent, and the peaks of carboxyl groups and OH-groups were large and broad. The maximum adsorption capacity of Langmuir was 52.08 mg/g for NSB and 163.93 mg/g for PSB. The adsorption process was close to physical adsorption for NSB and chemical adsorption for PSB, and both adsorbents were endothermic reactions in nature in that the higher the temperature, the higher the adsorption efficiency. The adsorption mechanism of Pb(II) to PSB was achieved by ion exchange, electrostatic interaction, hydrogen bonding, and complexation. The adsorption of Pb(II) using PSB was not significantly affected by the adsorption of competing ions and showed a high adsorption efficiency of 94% in reuse up to 6 times. This confirms the favorable feasibility of removing Pb(II) from industrial wastewater using PSB.

EGFR is a potential dual molecular target for cancer and Alzheimer's disease.

Many researchers are attempting to identify drugs that can be repurposed as effective therapies for Alzheimer's disease (AD). Several recent studies have highlighted epidermal growth factor receptor (EGFR) inhibitors approved for use as anti-cancer drugs as potential candidates for repurposing as AD therapeutics. In cancer, EGFR inhibitors target cell proliferation and angiogenesis, and studies in AD mouse models have shown that EGFR inhibitors can attenuate amyloid-beta (Aß) pathology and improve cognitive function. In this review, we discuss the different functions of EGFR in cancer and AD and the potential of EGFR as a dual molecular target for AD diseases. In addition, we describe the effects of anti-cancer EGFR tyrosine kinase inhibitors (TKIs) on AD pathology and their prospects as therapeutic interventions for AD. By summarizing the physiological functions of EGFR in cancer and AD, this review emphasizes the significance of EGFR as an important molecular target for these diseases.

Assessment of sludge reduction and biogas production in two-step anaerobic co-digestion using sesame oil cake and sewage sludge.

The aim of this study was to investigate the sewage sludge reduction and biogas production using two-stage anaerobic co-digestion of sesame oil cake and sewage sludge. In the first stage (acidogenic fermentation), sesame oil cake (SOC) was acidogenic fermented to produce fermented sesame oil cake (FSOC). In the second step (anaerobic co-digestion), sewage sludge and FSOC were mixed in various ratios of (100:0 (R1), 70:30 (R2), 50:50 (R3), and 30:70 (R4)) and observed for 30 days at a mesophilization temperature of 35±2 °C. In the anaerobic co-digestion using FSOC as a co-feedstock, the volatile solids (VS) and total solids (TS) removal were in the range of 53.7-64.9 and 42.6-53.2% for R2 and R3, respectively. The highest cumulative biogas production (389.67 mL/g·VSin) and methane production (0.56 m3·CH4/kg·VS) was achieved with the R3. In addition, R3 had the shortest reaction delay time (λ), and stabilization of the process was the fastest of all samples. The co-digestion performance index (CPI) was determined to be 1.29, 1.39, and 1.10 for R2, R3, and R4, respectively. The highest value for R3 confirmed the highest synergistic effect. This suggests the possibility of biogas production using sesame oil cake.

Donepezil ameliorates Aß pathology but not tau pathology in 5xFAD mice.

The cholinesterase inhibitor donepezil is used to improve Aß pathology and cognitive function in patients with Alzheimer's disease (AD). However, the impact of donepezil on tau pathology is unclear. Thus, we examined the effects of donepezil on Aß and tau pathology in 5xFAD mice (a model of AD) in this study. We found that intraperitoneal injection of donepezil (1 mg/kg, i.p.) exhibited significant reductions in Aß plaque number in the cortex and hippocampal DG region. In addition, donepezil treatment (1 mg/kg, i.p.) reduced Aß-mediated microglial and, to a lesser extent, astrocytic activation in 5xFAD mice. However, neither intraperitoneal/oral injection of donepezil nor oral injection of rivastigmine altered tau phosphorylation at Thr212/Ser214 (AT100), Thr396, and Thr231 in 5xFAD mice. Surprisingly, we observed that intraperitoneal/oral injection of donepezil treatment significantly increased tau phosphorylation at Thr212 in 5xFAD mice. Taken together, these data suggest that intraperitoneal injection of donepezil suppresses Aß pathology but not tau pathology in 5xFAD mice.

Identification of a Novel Class of Anti-Melanogenic Compounds, (Z)-5-(Substituted benzylidene)-3-phenyl-2-thioxothiazolidin-4-one Derivatives, and Their Reactive Oxygen Species Scavenging Activities.

The rate-determining role of tyrosinase makes it a critical component in the mechanism that is responsible for melanogenesis. Thirteen (Z)-5-(substituted benzylidene)-3-phenyl-2-thioxothiazolidin-4-one ((Z)-BPTT) analogs were designed based on the structural features of two potent tyrosinase inhibitors, viz. (Z)-5-(3-hydroxy-4-methoxybenzylidene)-2-thioxothiazolidin-4-one (5-HMT) and (Z)-2-(2,4-dihydroxybenzylidene)benzo[4,5]imidazo[2,1-b]thiazol-3(2H)-one (compound I). The trisubstituted double bond geometry of the (Z)-BPTT analogs that were generated by Knoevenagel condensation was determined using vicinal 1H and 13C coupling constants in 13C NMR spectra. Four analogs, numbers 1-3 and 6, inhibited mushroom tyrosinase 9 to 29 times more potently than kojic acid did. Kinetic study results indicated that these four analogs inhibited mushroom tyrosinase competitively and this was supported by docking simulation. Also, docking results using human tyrosinase suggested that analogs 2 and 3 might be potent human tyrosinase inhibitors. In vitro studies using B16F10 cells (a melanoma cell line) showed that analogs 1, 2, 3, and 6 inhibited cellular tyrosinase and melanin production more than kojic acid did, without perceptible cytotoxicity. In particular, analog 2, which possesses a catechol group, exerted an extremely potent anti-melanogenic effect. In addition, analog 2 showed strong scavenging activity against DPPH and ABTS radicals. Furthermore, analog 2 not only reduced ROS levels, which induce melanogenesis, but it also suppressed tyrosinase and MITF (microphthalamia-associated transcription factor) protein levels and the expressions of melanogenesis-related genes. These results suggest that analog 2 is an efficient tyrosinase inhibitor that alleviates melanogenesis by dual mechanisms of (i) the inhibition of melanogenesis-related proteins and genes and (ii) the direct inhibition of tyrosinase activity.

Identification of (Z)-2-benzylidene-dihydroimidazothiazolone derivatives as tyrosinase inhibitors: Anti-melanogenic effects and in silico studies.

As part of our continuous search for novel tyrosinase inhibitors, we designed 5,6-dihydroimindazo[2,1-b]thiazol-3(2H)-one (DHIT) derivatives based on the structure of MHY773; a potent tyrosinase inhibitor with a 2-iminothiazolidin-4-one template. Of the 11 DHIT derivatives synthesized using a Knoevenagel condensation, three DHIT derivatives 1a (IC50 = 36.14 ± 3.90 µM), 1b (IC50 = 0.88 ± 0.91 µM), and 1f (IC50 = 17.10 ± 1.01 µM) inhibited mushroom tyrosinase more than kojic acid (IC50 = 84.41 ± 2.87 µM). Notably, compound 1b inhibited mushroom tyrosinase around 100- and 3.3-fold more potently than kojic acid and MHY773, respectively. Lineweaver-Burk plots demonstrated that compounds 1b and 1f competitively inhibited mushroom tyrosinase, and in silico docking results supported our kinetic results and indicated that these two compounds bind more strongly to the active site of tyrosinase than kojic acid. Docking simulation results using a human tyrosinase homology model confirmed the abilities of 1b and 1f to strongly inhibit human tyrosinase. B16F10 murine melanoma cells were used to investigate whether these two compounds display tyrosinase inhibitory activities and anti-melanogenesis effects in cells. Both compounds were found to significantly and dose-dependently inhibit cellular tyrosinase activity and intracellular and extracellular melanin production more potently than kojic acid. The similarities observed between the cellular tyrosinase and melanogenesis inhibitory effects of 1b and 1f suggest their observed anti-melanogenic effects were due to tyrosinase inhibition. These results indicate that compounds 1b and 1f, which possess the DHIT template, are promising candidates as anti-browning agents and therapeutic agents for hyperpigmentation disorders.

Optimization of the extraction conditions of Nypa fruticans Wurmb. using response surface methodology and artificial neural network.

In this study, we conducted response surface methodology (RSM) and artificial neural network (ANN) to predict and estimate the optimized extraction condition of Nypa fruticans Wurmb. (NF). The effect of ethanol concentration (X1; 0-100%), extraction time (X2; 6-24 h), and extraction temperature (X3; 40-60 °C) on the antioxidant potential was confirmed. The optimal conditions (57.6% ethanol, 19.0 h extraction time, and 51.3 °C extraction temperature) of 2,2-diphenyl-1-1picrylhydrazyl (DPPH) scavenging activity, cupric reducing antioxidant capacity (CUPRAC) and ferric reducing antioxidant power (FRAP), total phenolic content (TPC), and total flavonoid contents (TFC) resulted in a maximum value of 62.5%, 41.95 and 48.39 µM, 143.6 mg GAE/g, and 166.8 CAE/g, respectively. High-resolution mass spectroscopic technique was performed to profile phenolic and flavonoid compounds. Upon analyzing, total 48 compounds were identified in NF. Altogether, our findings can provide a practical approach for utilizing NF in various bioindustries.

Antipathogenic Compounds That Are Effective at Very Low Concentrations and Have Both Antibiofilm and Antivirulence Effects against Pseudomonas aeruginosa.

Pseudomonas aeruginosa, a human pathogen, causes both acute and chronic infections that are mediated by virulence factor production and biofilm formation. Since both characteristics of P. aeruginosa are regulated by quorum sensing (QS), we screened 126 synthetic chemicals for anti-QS activity and finally selected the compounds that have both antivirulence and antibiofilm activities. To efficiently screen the chemical library, the following reporter-based bioassay systems were used: the QS- or biofilm-specific promoter-lacZ fusions (lasIp- or PA1897p-lacZ for the QS activity and cdrAp-lacZ for measuring the intracellular c-di-GMP levels). We also measured the production of virulence factors and biofilm formation in P. aeruginosa. A small-animal infection model using mealworms was also used for virulence analysis. From this screening, MHY1383 and MHY1387 were found to have both antivirulence and antibiofilm activities in P. aeruginosa. Most importantly, MHY1383 and MHY1387 exhibited these activities at very low concentrations, showing a significant anti-QS effect at 100 pM and an antibiofilm effect at 1 to 10 pM. By treating P. aeruginosa with these compounds, the virulence factor production and biofilm formation of P. aeruginosa were significantly reduced. These compounds can be developed as promising antipathogenic and antibiofilm drugs that can be applied in situations where such compounds must be used in an extremely low concentration. Our findings also offer a significant advantage for developing therapeutic agents with few adverse side effects. IMPORTANCE Many antibiotics are increasingly losing their efficacy due to antibiotic resistance mediated by biofilm formation. In this study, we screened a synthetic chemical library and discovered several compounds that have both antivirulence and antibiofilm effects against Pseudomonas aeruginosa, a notorious human pathogen. Two of them had these effects at extremely low concentrations and are expected not to develop resistance, unlike conventional antibiotics, because they have no effect on the growth of bacteria. Our results strongly suggest that these compounds act on the target in a noncompetitive manner, indicating that they are distinct from other previously known quorum sensing inhibitors or biofilm inhibitors. Our findings offer a significant advantage for developing therapeutic agents with few adverse side effects.

New Benzimidazothiazolone Derivatives as Tyrosinase Inhibitors with Potential Anti-Melanogenesis and Reactive Oxygen Species Scavenging Activities.

Thirteen (Z)-2-(substituted benzylidene)benzimidazothiazolone analogs were synthesized and evaluated for their inhibitory activity against mushroom tyrosinase. Among the compounds synthesized, compounds 1-3 showed greater inhibitory activity than kojic acid (IC50 = 18.27 ± 0.89 µM); IC50 = 3.70 ± 0.51 µM for 1; IC50 = 3.05 ± 0.95 µM for 2; and IC50 = 5.00 ± 0.38 µM for 3, and found to be competitive tyrosinase inhibitors. In silico molecular docking simulations demonstrated that compounds 1-3 could bind to the catalytic sites of tyrosinase. Compounds 1-3 inhibited melanin production and cellular tyrosinase activity in a concentration-dependent manner. Notably, compound 2 dose-dependently scavenged ROS in B16F10 cells. Furthermore, compound 2 downregulated the protein kinase A (PKA)/cAMP response element-binding protein (CREB) and mitogen-activated protein kinase (MAPK) signaling pathways, which led to a reduction in microphthalmia-associated transcription factor (MITF) expression, and decreased tyrosinase, tyrosinase related protein 1 (TRP1), and TRP2 expression, resulting in anti-melanogenesis activity. Hence, compound 2 may serve as an anti-melanogenic agent against hyperpigmentation diseases.

Novel Anti-Melanogenic Compounds, (Z)-5-(Substituted Benzylidene)-4-thioxothiazolidin-2-one Derivatives: In Vitro and In Silico Insights.

To confirm that the ß-phenyl-α,ß-unsaturated thiocarbonyl (PUSTC) scaffold, similar to the ß-phenyl-α,ß-unsaturated carbonyl (PUSC) scaffold, acts as a core inhibitory structure for tyrosinase, twelve (Z)-5-(substituted benzylidene)-4-thioxothiazolidin-2-one ((Z)-BTTZ) derivatives were designed and synthesized. Seven of the twelve derivatives showed stronger inhibitory activity than kojic acid against mushroom tyrosinase. Compound 2b (IC50 = 0.47 ± 0.97 µM) exerted a 141-fold higher inhibitory potency than kojic acid. Kinetic studies' results confirmed that compounds 2b and 2f are competitive tyrosinase inhibitors, which was supported by high binding affinities with the active site of tyrosinase by docking simulation. Docking results using a human tyrosinase homology model indicated that 2b and 2f might potently inhibit human tyrosinase. In vitro assays of 2b and 2f were conducted using B16F10 melanoma cells. Compounds 2b and 2f significantly and concentration-dependently inhibited intracellular melanin contents, and the anti-melanogenic effects of 2b at 10 µM and 2f at 25 µM were considerably greater than the inhibitory effect of kojic acid at 25 µM. Compounds 2b and 2f similarly inhibited cellular tyrosinase activity and melanin contents, indicating that the anti-melanogenic effects of both were due to tyrosinase inhibition. A strong binding affinity with the active site of tyrosinase and potent inhibitions of mushroom tyrosinase, cellular tyrosinase activity, and melanin generation in B16F10 cells indicates the PUSTC scaffold offers an attractive platform for the development of novel tyrosinase inhibitors.

High Resolution Mass Spectroscopy-Based Secondary Metabolite Profiling of Nymphaea nouchali (Burm. f) Stem Attenuates Oxidative Stress via Regulation of MAPK/Nrf2/HO-1/ROS Pathway.

The secondary metabolites profiling of Nymphaea nouchali stem (NNSE) extract was carried out using a high-resolution mass spectroscopic technique. The antioxidant effects of NNSE, as well as the underlying mechanisms, were also investigated in tert-butyl hydroperoxide (t-BHP)-stimulated oxidative stress in RAW264.7 cells. Tandem mass spectroscopy with (-) negative mode tentatively revealed the presence of 54 secondary metabolites in NNSE. Among them, phenolic acids and flavonoids were predominant. Phenolic acids (brevifolincarboxylic acid, p-coumaroyltartaric acid, niazinin B, lalioside, 3-feruloylquinic acid, and gallic acid-O-rutinoside), flavonoids (elephantorrhizol, apigenin-6-C-galactoside 8-C-arabinoside, and vicenin-2), sialic acid (2-deoxy-2,3-dehydro-N-acetylneuraminic acid), and terpenoid (α-γ-onoceradienedione) were identified in NNSE for the first time. Unbridled reactive oxygen species/nitrogen species (ROS/RNS) and redox imbalances participate in the induction and development of many oxidative stress-linked diseases. The NNSE exhibited significant free radical scavenging capabilities and was also able to reduce t-BHP-induced cellular generation in RAW264.7 cells. The NNSE prevented oxidative stress by inducing the endogenous antioxidant system and the levels of heme oxygenase-1 (HO-1) by upregulating Nrf2 through the modulation of mitogen-activated protein kinases (MAPK), such as phosphorylated p38 and c-Jun N terminal kinase. Collectively, these results indicate that the NNSE exhibits potent effects in preventing oxidative stress-stimulated diseases and disorders through the modulation of the MAPK/Nrf2/HO-1 signaling pathway. Our findings provide new insights into the cytoprotective effects and mechanisms of Nymphaea nouchali stem extract against oxidative stress, which may be a useful remedy for oxidative stress-induced disorders.

Urolithin and Reduced Urolithin Derivatives as Potent Inhibitors of Tyrosinase and Melanogenesis: Importance of the 4-Substituted Resorcinol Moiety.

We previously reported (E)-ß-phenyl-α,ß-unsaturated carbonyl scaffold ((E)-PUSC) played an important role in showing high tyrosinase inhibitory activity and that derivatives with a 4-substituted resorcinol moiety as the ß-phenyl group of the scaffold resulted in the greatest tyrosinase inhibitory activity. To examine whether the 4-substituted resorcinol moiety could impart tyrosinase inhibitory activity in the absence of the α,ß-unsaturated carbonyl moiety of the (E)-PUSC scaffold, 10 urolithin derivatives were synthesized. To obtain more candidate samples, the lactone ring in synthesized urolithins was reduced to produce nine reduced urolithins. Compounds 1c (IC50 = 18.09 ± 0.25 µM), 1h (IC50 = 4.14 ± 0.10 µM), and 2a (IC50 = 15.69 ± 0.40 µM) had greater mushroom tyrosinase-inhibitory activities than kojic acid (KA) (IC50 = 48.62 ± 3.38 µM). The SAR results suggest that the 4-substituted resorcinol motif makes an important contribution to tyrosinase inhibition. To investigate whether these compounds bind to human tyrosinase, a human tyrosinase homology model was developed. Docking simulations with mushroom and human tyrosinases showed that 1c, 1h, and 2a bind to the active site of both tyrosinases with higher binding affinities than KA. Pharmacophore analyses showed that two hydroxyl groups of the 4-substituted resorcinol entity act as hydrogen bond donors in both mushroom and human tyrosinases. Kinetic analyses indicated that these compounds were all competitive inhibitors. Compound 2a inhibited cellular tyrosinase activity and melanogenesis in α-MSH plus IBMX-stimulated B16F10 melanoma cells more strongly than KA. These results suggest that 2a is a promising candidate for the treatment of skin pigment disorders, and show the 4-substituted resorcinol entity importantly contributes to tyrosinase inhibition.

Prunus mume Seed Exhibits Inhibitory Effect on Skin Senescence via SIRT1 and MMP-1 Regulation.

The Prunus mume seed is a by-product of the food industry, and we studied its potential as a food biomaterial, particularly for nutraceutical and inner beauty products. Alternative animal tests showed that an extract of P. mume ripened seed (PmRS) was not toxic on the skin. PmRS exhibited protective effects against ultraviolet- (UV-) induced skin aging in mice, confirmed by phenotypic indications, including increased collagen levels and decreased skin thickness. Compared with the UV-saline group, the UV-PmRS group showed increased levels of silent mating type information regulation 2 homolog 1 (SIRT1) and collagen and decreased matrix metalloproteinase- (MMP-) 1 expression. The protective effect of PmRS treatment against UVB-mediated cell viability was observed in vitro without any cytotoxicity, and PmRS prevented UVB-induced reactive oxygen species generation in HaCaT cells. PmRS downregulated MMP-1 and MMP-13 compared with the UVB-irradiated group. However, mRNA expressions of tissue inhibitor of metalloproteinase-1 and SIRT1 were upregulated by PmRS treatment. MMP-1 and SIRT1 treated with PmRS were decreased and increased, respectively, at the protein level. Moreover, PmRS treatment reduced c-Jun N-terminal kinase and p38 phosphorylation compared with the UVB-treated group. We postulate that P. mume seed could be a useful ingredient in nutraceuticals and inner beauty-purpose foods.

In vitro anti-melanogenic effects of chimeric compounds, 2-(substituted benzylidene)-1,3-indanedione derivatives with a ß-phenyl-α, ß -unsaturated dicarbonyl scaffold.

Tyrosinase is considered a key contributor to melanogenesis, and safe, potent tyrosinase inhibitors are needed for medical and cosmetic purposes to treat skin hyperpigmentation and prevent fruit and vegetable browning. According to our accumulated SAR data on tyrosinase inhibitors, the ß-phenyl-α,ß-unsaturated carbonyl scaffold in either E or Z configurations, can confer potent tyrosinase inhibitory activity. In this study, twelve indanedione derivatives were synthesized as chimeric compounds with a ß-phenyl-α,ß-unsaturated dicarbonyl scaffold. Two of these derivatives, that is, compounds 2 and 3 (85% and 96% inhibition, respectively), at 50 µM inhibited mushroom tyrosinase markedly more potently than kojic acid (49% inhibition). Docking studies predicted that compounds 2 and 3 both inhibited tyrosinase competitively, and these findings were supported by Lineweaver-Burk plots. In addition, both compounds inhibited tyrosinase activity and reduced melanin contents in B16F10 cells more than kojic acid without perceptible cytotoxicity. These results support the notion that chimeric compounds with the ß-phenyl-α,ß-unsaturated dicarbonyl scaffold represent promising starting points for the development of potent tyrosinase inhibitors.

Giving or receiving spouse care and marital satisfaction among older Korean individuals.

Health challenges are expected in later life, but they may place older married adults in Korea at greater risk than in the past due to increasing risks of extended morbidity associated with a longer lifespan, and limited availability of traditional long-term care provided by children in an extended family context. As spouse care has become more prevalent among older adults, the present study examined whether provision or receipt of spouse care might be differentially associated with marital quality for men and women, and whether availability of care from adult children (i.e., sons, daughters, or children-in-law) might moderate the association between receipt of spouse care and marital satisfaction. The analytic sample was drawn from five waves of the Korean Longitudinal Study of Ageing (2006-2014), consisting of married individuals, with both age 60 years or older at Wave 1. For analyses, multilevel models were estimated using SAS PROC MIXED. Findings showed that first, for men, becoming a caregiver for their wife was associated with a small increase in marital satisfaction; the transition to spouse caregiving was associated with a decline in marital satisfaction for women. Secondly, transitioning to receiving spouse care was associated with a decline in marital satisfaction among men, but an increase in marital satisfaction for women. Third, new care from daughters in the form of (I)ADL assistance was associated with a benefit to marital satisfaction among men and women who began to receive care from their spouses. Overall, findings highlighted Korean families in transition. Marriage might fare better in a more recent form of family care-husbands providing care for their wives. In addition, daughters might play a bigger role in family care now compared to daughters-in-law, the designated provider of family care under the Confucian patriarchal system.

In silico and in vitro insights into tyrosinase inhibitors with a 2-thioxooxazoline-4-one template.

The ß-phenyl-α,ß-unsaturated carbonyl (PUSC) scaffold confers tyrosinase inhibitory activity, and in the present study, 16 (Z)-5-(substituted benzylidene)-3-phenyl-2-thioxooxazolidin-4-one analogues containing this scaffold were synthesized. Mushroom tyrosinase inhibitory activities were examined. Compound 1c (IC50 = 4.70 ± 0.40 µM) and compound 1j (IC50 = 11.18 ± 0.54 µM) inhibited tyrosinase by 4.9 and 2.1-fold, respectively, and did so more potently than kojic acid (IC50 = 23.18 ± 0.11 µM). Kinetic analysis of tyrosinase inhibition revealed that 1c and 1j inhibited tyrosinase competitively. Results of docking simulation with mushroom tyrosinase using four docking programs suggested that 1c and 1j bind more strongly than kojic acid to the active site of tyrosinase and supported kinetic findings that both compounds are competitive inhibitors. The docking results of human tyrosinase homology model indicated that 1c and 1j can also strongly inhibit human tyrosinase. EZ-cytox assays revealed 1c and 1j were not cytotoxic to B16F10 melanoma cells. The effects of 1c and 1j on cellular tyrosinase activity and melanin production were also investigated in α-MSH- and IBMX-co-stimulated these cells. Both compounds significantly and dose-dependently reduced tyrosinase activity, and at 10 µM were more potent than kojic acid at 20 µM. Compounds 1c and 1j also inhibited melanogenesis, which suggested that the inhibitory effects of these compounds on melanin production were mainly attributable to their inhibitions of tyrosinase. These results indicate that compounds 1c and 1j with the PUSC scaffold have potential use as whitening agents for the treatment of hyperpigmentation-associated diseases.

Lablab Purpureus Protects HaCaT Cells from Oxidative Stress-Induced Cell Death through Nrf2-Mediated Heme Oxygenase-1 Expression via the Activation of p38 and ERK1/2.

Ultraviolet B (UV-B) radiation induces the extreme production of either reactive oxygen species (ROS) or inflammatory mediators. The aim of this study was to evaluate the antioxidant activities of 70% ethanolic extract of Lablab purpureus (LPE) and the underlying mechanisms using HaCaT cells exposed to UV-B. High-performance liquid chromatography (HPLC) confirmed the presence of gallic acid, catechin, and epicatechin in LPE. LPE was shown to have a very potent capacity to scavenge free radicals. The results showed that LPE prevented DNA damage and inhibited the generation of ROS in HaCaT cells without causing any toxicity. LPE increased the expression of endogenous antioxidant enzymes such as superoxide dismutase-1 and catalase. Furthermore, LPE treatment facilitates the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf-2), boosting the phase II detoxifying enzyme heme oxygenase-1 (HO-1) leading to the combatting of oxidative stress. However, pretreatment of LPE also caused the phosphorylation of mitogen-activated protein kinases (MAPK kinase) (p38 kinase) and extracellular signal-regulated kinase (ERK), whereas treatment with p38 and ERK inhibitors substantially suppressed LPE-induced Nrf2 and heme oxygenase (HO)-1 expression. These findings suggest that LPE exhibits antioxidant activity via Nrf-2-mediated HO-1 signaling through the activation of p38 and ERK, indicating that LPE can potentially be used as a remedy to combat oxidative stress-induced disorder.

Phytochemical Characterization of Dillenia indica L. Bark by Paper Spray Ionization-Mass Spectrometry and Evaluation of Its Antioxidant Potential Against t-BHP-Induced Oxidative Stress in RAW 264.7 Cells.

The antioxidant effects of the ethyl acetate fraction of Dillenia indica bark (DIBEt) and the underlying mechanisms were investigated in tert-butyl hydroperoxide (t-BHP)-stimulated oxidative stress in RAW 264.7 cells. Paper spray ionization-mass spectroscopy with positive-ion mode tentatively revealed 27 secondary metabolites in D. indica bark extract; predominant among them were alkaloids, phenolic acids, and flavonoids. A new triterpenoid (nutriacholic acid) was confirmed in DIBEt for the first time. DIBEt had strong free radical-scavenging capabilities and was also able to reduce t-BHP-induced cellular reactive oxygen species (ROS) generation in RAW 264.7 cells. DIBEt was found to prevent oxidative stress by boosting the levels of heme oxygenase-1 (HO-1) through the up-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) via the regulation of extracellular signal-regulated kinase (ERK) phosphorylation in RAW 264.7 cells. These results support the potential of DIBEt for defense against oxidative stress-stimulated diseases.