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Abstract Background This study evaluated the impact of the tax increase in January 2019 on changes in intention to quit and the effect of cigarette prices on quit attempts and successful quitting among male cigarette smokers in Vietnam. Methods Data were derived from the ITC project in Vietnam, which included 1585 adult smokers at baseline (Wave 1, Aug-Oct 2018) followed up to waves 2 (Sep-Nov 2019) and 3 (Sep-Dec 2020). Generalized estimating equations regression was performed to estimate changes in the intention to quit. Multiple logistic regression analysis was used to evaluate the cigarette price of a cigarette pack in relation to quit attempts and successful quitting. Results The increase in cigarette tax in 2019 did not significantly increase the likelihood of the intention to quit. After the tax increase, 63.6% of participants who smoked made a quit attempt, and 27.6% successfully quit smoking in the follow-up waves. However, the price of a cigarette pack was not significantly associated with quit attempts and successful quitting. The study did not observe a significant impact of cigarette prices on quit attempts and successful quitting in all subgroups of household income. Factors associated with quit attempts included the number of cigarettes smoked and the intention to quit, while those associated with successful quitting included age, dual use of cigarettes and other tobacco products, and the intention to quit. Conclusion Current cigarette prices were not associated with cessation behaviors even within the lowest household income group. Therefore, a sharp rise in cigarette tax is required to incentivize smokers to quit smoking.

BackgroundSeeing portrayals of tobacco and alcohol in music videos (MVs) may reduce perceived risks, increase susceptibility, and lead to the initiation of tobacco and alcohol use among adolescents and young adults. Previous studies have predominantly concentrated on assessing tobacco and alcohol contents in English-language MVs within Western countries. However, many other countries have not only been influenced by the English music market but have also produced music in their native languages, and this content remains underexamined. ObjectiveThis study aims to investigate the prevalence of tobacco- and alcohol-related content in top Vietnamese MVs on YouTube from 2013 to 2021, to describe how tobacco and alcohol are portrayed in these MVs, and to examine associations between these portrayals and MV characteristics. MethodsA total of 410 Vietnamese MVs, including the top 40 or 50 most viewed released each year between 2013 and 2021, were analyzed. General information, such as the song name, its release date and ranking, age restriction, musical genre, and type of MV, was collected. We examined tobacco and alcohol content in the MVs, with specific details such as tobacco types, their brands, as well as the number, age, sex, and roles of individuals smoking or drinking. ResultsAmong the 410 MVs, 36 (8.8%) contained tobacco-related content and 136 (33.2%) featured alcohol-related content. Additionally, 28 (6.8%) out of 410 MVs included both tobacco and alcohol content. The prevalence of videos with tobacco and alcohol content fluctuated over the years. In MVs with tobacco-related content, a higher proportion of hip-hop or rap songs contained tobacco-related content (n=6, 30%) compared to other music genres. In MVs with tobacco-related content, cigarettes were the most frequently shown product (n=28, 77.8%), and smoking scenes were often depicted at parties (n=13, 36.1%) and during dancing and singing scenes (n=12, 33.3%). Among the 31 MVs portraying actual tobacco use, tobacco use was typically depicted with 1 person, often a young adult male, while 38.7% (n=12) showed singer(s) smoking. For MVs with alcohol-related content, there was a high proportion showing alcohol images at parties, bars, or pubs (n=96, 70.6%). Among 87 MVs containing drinking scenes, 60.9% (n=53) involved groups of young adults of both sexes, and 64% (n=56) depicted singers drinking. Additionally, only 2 (5.6%) MVs included health warnings about tobacco harm, and 2 MVs (1.5%) included warnings about drinking restricted to individuals 18 years and above. ConclusionsThe notable prevalence of tobacco and alcohol content in leading Vietnamese YouTube MVs raises concerns, especially as most of this content is portrayed without any warnings. The study underscores a regulatory gap in addressing such content on the internet, emphasizing the urgent need for stricter regulations and age restrictions on platforms such as YouTube.

Targeting acetylcholinesterase is one of the most important strategies for developing therapeutics against Alzheimer’s disease. In this work, we have employed a new approach that combines machine learning models, a multi-step similarity search of the PubChem library and molecular dynamics simulations to investigate potential inhibitors for acetylcholinesterase. Our search strategy has been shown to significantly enrich the set of compounds with strong predicted binding affinity to acetylcholinesterase. Both machine learning prediction and binding free energy calculation, based on linear interaction energy, suggest that the compound CID54414454 would bind strongly to acetylcholinesterase and hence is a promising inhibitor.

Abstract Background Several studies have focused on the use of triptan and the risk of acute vascular events but the existence of such association is still debated and has never been quantified in patients over 65 years. To assess whether triptan use among older is associated with an increased risk of hospitalization for acute vascular events. Methods A propensity score-matched cohort study was designed using the French national health insurance database linked to hospital stays. Patients aged ≥ 65 years, newly treated by triptans between 2011 and 2014, were included… The primary event was hospitalization for an acute ischemic vascular event within de 90 days following triptan initiation. Association with triptan exposure was investigated through cox regression model, considering exposure at inclusion, and with exposure as a time-varying variable A case-crossover (CCO) and a self-controlled case series (SCCS) analyses were also conducted to address potential residual confounding. Results The cohort included 24, 774 triptan users and 99 096 propensity matched controls (mean (SD) age: 71 years (5.9), 74% of women). Within 90 days after cohort entry, 163 events were observed in the triptan group, and 523 in the control group (0.66% vs. 0.53%, adjusted hazard ratio (aHR) exposed/not exposed 1.25 95%CI [1.05–1.49]; aHR time−varying 8.74 [5.21–14.66]). The association was significant (CCO) for all events (adjusted odds ratio (aOR1.63 [1.22–2.19]) with a more consistent association with cerebral events (aOR 2.14 [1.26–3.63]). The relative incidence (RI) for all events was 2.13 [1.76–2.58] in the SCCS, for cardiac (RI: 1.67 [1.23–2.27]) and for cerebral events (RI: 3.20, [2.30–4.45]). Conclusion The incidence of acute vascular events was low among triptan users. We found that triptan use among older may be associated with a low increased risk for acute vascular events, which may be more marked for cerebral events such as stroke, than for cardiac events.

Background: Alcohol drinking behaviors change temporally and can lead to changes in related cancer risks; previous studies have been unable to identify the association between the two using a single-measurement approach. Thus, this study aimed to investigate the association of drinking trajectories with the cancer risk in Korean men. Methods: A trajectory analysis using group-based trajectory modeling was performed on 2,839,332 men using data on alcohol drinking levels collected thrice during the Korean National Health Insurance Service’s general health screening program conducted between 2002 and 2007. Cox proportional hazards regression was performed to evaluate the associations between drinking trajectories and cancer incidence, after adjustments for age, income, body mass index, smoking status, physical activity, family history of cancer, and comorbidities. Results: During 10.5 years of follow-up, 189,617 cancer cases were recorded. Six trajectories were determined: non-drinking, light, moderate, decreasing-heavy, increasing-heavy, and steady-heavy. Light-to-heavy alcohol consumption increased the risk for all cancers combined in a dose-dependent manner (adjusted hazard ratio [aHR] 1.03; 95% confidence interval [CI], 1.02–1.05 for light drinking, aHR 1.06; 95% CI 1.05–1.08 for moderate drinking, aHR 1.19; 95% CI, 1.16–1.22 for decreasing-heavy drinking, aHR 1.23; 95% CI, 1.20–1.26 for increasing-heavy drinking, and aHR 1.33; 95% CI, 1.29–1.38 for steady-heavy drinking [P-trend

Abstract Background Nearly one-in-two Vietnamese men smoke cigarettes placing them among the highest tobacco consumers in the world. Despite the need for smoking cessation to curb the burden of tobacco-related diseases in Vietnam, this rate remains at less than 30%. Therefore, this study examines individual-, social- and policy factors associated with smoking cessation among adult male smokers in Vietnam. Methods We established a longitudinal International Tobacco Control study of male smokers in Hanoi, Vietnam, in September 2018. This paper analyses 1525 men who participated in baseline and one-year follow-up. We applied a weighted multivariable logistic regression to examine the association between smoking cessation and individual-, social- and policy predictors. Results At follow-up, 14.8% of participants had quit smoking for at least 30 consecutive days during the last year. Among the persistent smokers, 56.6% expressed intention to quit smoking. Factors associated with smoking cessation included a lower number of cigarettes smoked per day (aOR = 0.96, 95% CI: 0.94, 0.99) and having several attempts to quit smoking (aOR = 2.16, 95% CI 1.13, 4.12). Intention to quit smoking was associated with multiple quit attempts, a chronic condition diagnosis, more tobacco-related knowledge, greater self-efficacy, and more worries about their future health. The perceived impact of smoke-free policy and health warning labels were positively associated with intention to quit at any stage. Conclusions Interventions aimed at increasing smoking cessation should focus on all aspects of individual, social, and policy factors. Persistent smokers are more motivated to quit if they have made multiple quit attempts, more self-efficacy of quitting and worried about their future health, indicating that increasing smokers’ beliefs and knowledge may be important for behavioural change. Health warning labels and tobacco taxation policies should be maintained and promoted as they are perceived to be particularly useful for persistent smokers’ intention to quit.

Abstract Combinations of lifestyle behaviors may lead to different cancer risks. This study aimed to identify the latent classes based on lifestyle behavior trajectories and to investigate the association between these latent classes and cancer risk. Participants in the 2002–2003 National Health Insurance Service general health examination were included. Data on smoking, alcohol drinking, body mass index (BMI), and physical activity measured four times between 2002 and 2009 were analyzed. Incident cancer cases were tracked from 2010 to 2018. Patterns of alcohol drinking, smoking, BMI, and physical activity and latent classes based on trajectories of smoking, alcohol drinking, BMI, and physical activity were identified. Among 2,735,110 adults (1,787,486 men and 947,624 women), 111,218 (69,089 men and 42,129 women) developed incident cancer. Six latent classes of lifestyle behavior were identified, with Class 1 (healthy class) involving only 0.2% of men and 0.5% of women. The highest risk class in males tended to be steady light drinkers and steady moderate smokers, have steady low frequency of physical activity, and be obese. This class showed a 1.47 times higher (95% CI = 1.29–1.69) risk of all cancers than did the healthy class. Among women, there was only an association between the highest risk class (tendency to be non-drinkers, light smokers) and colorectal cancer (HR = 1.70, 95% CI = 1.02–2.83). Only a small percentage of participants maintained a long-term healthy lifestyle. Identifying classes of behavior combinations and their links to cancer development is therefore critical for cancer prevention.

Introduction Previous research on post-diagnosis smoking among cancer survivors mainly relied on smoking status, which may not fully reflect the impact of changes in smoking levels. This study aimed to evaluate mortality risk according to smoking trajectories among Korean male cancer survivors, using a trajectory approach to comprehensively capture smoking patterns. Methods The study included 110555 men diagnosed with cancer between 2002 and 2018 from the Korean National Health Information Database. Group-based trajectory modelling was used to identify post-diagnosis smoking trajectories among pre-diagnosis current smokers (n=45331). Cox hazards models were fitted to evaluate mortality risk according to smoking trajectories for pooled cancers, pooled smoking-related cancers, smoking-unrelated cancers, and gastric, colorectal, liver, and lung cancers. Results Smoking trajectories included light-smoking quitters, heavy-smoking quitters, consistent moderate smokers, and decreasing heavy smokers. Smoking significantly increased all-cause and cancer mortality risks in cancer patients for pooled cancers, pooled smoking-related cancers, and pooled smoking-unrelated cancers. Compared to non-smokers, all-cause mortality risk for pooled cancers significantly increased according to smoking trajectories: (AHR=1.33; 95% CI: 1.27–1.40), (AHR=1.39; 95% CI: 1.34–1.44), (AHR=1.44; 95% CI: 1.34–1.54), and (AHR=1.47; 95% CI: 1.36–1.60), respectively. Smoking increased all-cause and cancer mortality risks in gastric and colorectal cancer patients and cancer-specific mortality in lung cancer patients. The significant associations of smoking trajectories with all-cause and cancer mortality risks were primarily observed in 5-year survivors but not in short-term survivors. Among heavy smokers, smoking cessation significantly reduced all-cause mortality risk in the long-term. Conclusions The post-diagnosis smoking trajectory independently predicts cancer prognosis among male cancer patients. Proactive cessation support should be strengthened, particularly for those who smoke heavily.

Abstract Aim To estimate the risk of cancer incidence and mortality among patients with alcoholic liver disease in South Korea. Methods A matched cohort study was conducted, including 1,042,185 men (alcoholic liver disease cases: 208,437; controls: 833,748) and 100,400 women (alcoholic liver disease cases: 20,080; controls: 80,320), matched for sex, age, smoking, alcohol consumption, and body mass index at a 1:4 ratio. The risk of cancer incidence and mortality in the alcoholic liver disease group was assessed using Cox proportional hazards regression models. Results Both men and women with alcoholic liver disease had an elevated risk of all‐cancer and liver cancer incidence and mortality in comparison with the control group. In men, alcoholic liver disease was associated with a significantly higher risk of development of 10 cancer types, including lip, oral cavity, and pharynx; esophagus; liver; gallbladder and biliary tract; pancreas; larynx; lung; kidney; thyroid gland; and leukemia. Subgroup analysis by hepatitis B and C infection showed increased hazard ratios of all cancer incidences and mortality in the alcoholic liver disease group, regardless of hepatitis B or C infection status. In both sexes, a higher number and more years of hospital or clinic visits for alcoholic liver disease were associated with an increased risk of incidence and mortality from all cancers and liver cancer. A more profound dose–response relationship between alcoholic liver disease and alcohol consumption was observed in women than in men. Conclusions Our findings emphasize the need for a clinical surveillance program and the early detection of cancer in patients with alcoholic liver disease.

Abstract Background Physical activity (PA) changes throughout an individual’s life, but the association between such changes and cancer risk seems to be overlooked in the literature. Thus, this study aimed to examine the association between the trajectories of PA frequency and cancer incidence among middle-aged Korean adults. Methods A total of 1,476,335 eligible participants (992,151 men and 484,184 women) aged ≥40 years from the National Health Insurance Service cohort (2002–2018) were included. Assessment of PA frequency was a self-reported measure, based on the question: “How many times per week do you perform exercise that makes you sweat?”. PA frequency trajectories (i.e., trajectory classes of change in PA frequency) from 2002 to 2008 were identified using group-based trajectory modeling. Cox proportional hazards regression was used to assess the associations between the PA trajectories and cancer incidence. Results Five PA frequency trajectories over 7 years were identified: persistently low (men:73.5%; women:74.7%), persistently moderate (men:16.2%; women:14.6%), high-to-low (men:3.9%; women:3.7%), low-to-high (men:3.5%; women:3.8%), and persistently high (men:2.9%; women:3.3%). Compared with persistently low frequency, maintaining a high PA frequency was associated with a lower risk of all cancers (Hazard ratio (HR) = 0.92, 95%CI = 0.87–0.98) and breast cancer (HR = 0.82, 95%CI = 0.70–0.96) among women. There was a lower risk for thyroid cancer among men in the high-to-low (HR = 0.83, 95%CI = 0.71–0.98), low-to-high (HR = 0.80, 95%CI = 0.67–0.96), and high PA trajectories (HR = 0.82, 95%CI = 0.68–0.99). There was a significant association between moderate trajectory and lung cancer in men (HR = 0.88, 95%CI = 0.80–0.95), in both smoking and non-smoking men. Conclusion Long-term persistent high frequency of PA as part of the daily routine should be widely promoted and encouraged to reduce the risk for all cancer development in women.

Abstract Background Perception of harm plays an important role in predicting intention to quit—an integral part of the cessation process. Perception on harm from bamboo waterpipe tobacco was unknown, even the predominant of this type of tobacco use. This study investigated the effects of perceived harm from cigarette and bamboo waterpipe tobacco on intention to quit among adult male Vietnamese tobacco users. Methods From the nationally-representative 2015 Global Adult Tobacco Survey, we included 1,351 adult males (≥ 18 years old) who used cigarettes, bamboo waterpipes, or both. Demographic characteristics, tobacco use behaviors, perceived harm from tobacco use, and regulation/policy exposure were measured. Effects of perceived harm from cigarette and bamboo waterpipe tobacco on intention to quit were assessed by logistic regression. Results Intention to quit prevalence was 59.0%, 55.0%, and 58.4% for cigarette, waterpipe, and dual users, respectively. Tobacco users who perceived that “using cigarettes and/or waterpipe could cause severe illness” and “waterpipe use is less harmful than cigarette smoking”, had tobacco use bans at home, or were exposed to anti-smoking campaigns or encouragement to quit information were more likely to intend to quit. When analyzed by tobacco users, intention to quit was more likely for those users who perceived their tobacco product as more harmful than the other product type, although statistical significance was only observed for cigarette users. Conclusions Misperceptions regarding harm from tobacco use could negatively affect intention to quit. Dissemination of accurate information on the risks from all forms of tobacco use and enforcement of tobacco control policies are important for encouraging intention to quit.

Abstract This study aimed to examine the association between chronic pancreatitis (CP) and cancer incidence and mortality among the Korean population. Based on a cancer-free cohort of 8,317,616 individuals between 2002 and 2010, a matched cohort study was conducted, including 10,899 patients with CP, matched for sex and age with 32,697 individuals without CP. The case and control groups were followed up until the date of onset of cancer or death or the end of follow-up date (December 31, 2018). Cox proportional hazards regression was performed to assess the risk of cancer incidence and mortality. Compared to the control group, patients with CP had a higher risk of all cancers with a hazard ratio (HR) of 1.2 [95% confidence interval (CI) 1.1–1.3]. CP was associated with an increased risk of esophageal cancer (HR 3.9, 95% CI 1.8–8.5) and pancreatic cancer (HR 3.9, 95% CI 2.7–5.5) and a decreased risk of colorectal cancer (HR 0.7, 95% CI 0.5–0.9). Regarding cancer mortality, patients with CP had a 1.2-fold risk of all cancer mortality (95% CI 1.1–1.4), compared with the control group. Patients with CP had a higher risk of death from esophageal cancer (HR 3.5, 95% CI 1.5–8.0) and pancreatic cancer (HR 3.3, 95% CI 2.3–4.7) but had a lower risk of death due to stomach cancer (HR 0.4, 95% CI 0.2–0.8). Patients with CP had a higher risk for both incidence and mortality of all cancer types, especially pancreatic and esophageal cancers, compared with the sex- and age-matched control group.

Abstract Small extracellular vesicles (sEVs) play a pivotal role in tumor progression by mediating intercellular communication in the tumor microenvironment (TME). Syntenin-1 induces malignant tumor progression in various types of human cancers, including human lung cancer and regulates biogenesis of sEVs. However, the function of syntenin-1-regulated sEVs and miRNAs in sEVs remains to be elucidated. In the present study, we aimed to demonstrate the role of oncogenic Ras/syntenin-1 axis in the release of sEVs and elucidate the function of syntenin-1-mediated miRNAs in sEVs in lung cancer progression. The results revealed that oncogenic Ras promoted the release of sEVs by inducing syntenin-1 expression; disruption of syntenin-1 expression impaired the release of sEVs as well as sEV-mediated cancer cell migration and angiogenesis. Moreover, we identified three miRNAs, namely miR-181a, miR-425-5p, and miR-494-3p, as onco-miRNAs loaded into syntenin-1-dependent sEVs. Remarkably, miR-494-3p was highly abundant in sEVs and its release was triggered by syntenin-1 expression and oncogenic Ras. Ectopic expression of the miR-494-3p mimic enhanced the migration and proliferation of lung cancer cells as well as tube formation in endothelial cells; however, the miR-494-3p inhibitor blocked sEV-mediated effects by targeting tyrosine-protein phosphatase nonreceptor type 12 (PTPN12), a tumor suppressor. sEVs promoted tumor growth and angiogenesis by downregulating PTPN12 expression; however, the miR-494-3p inhibitor significantly suppressed these effects in vivo, confirming that miR-494-3p acts as a major onco-miRNA loaded into lung cancer cell-derived sEVs. Eventually, the oncogenic Ras/syntenin-1 axis may induce cancer progression by increasing miR-494-3p loading into sEVs in lung cancer cells in the TME.

Health problems associated with the amount of air pollutants are increasing worldwide. Pollution damages not only the lungs; it also has an impact on skin health and is co-responsible for the development of skin diseases.Anti-pollution products are on the rise in the cosmetic market but so far, there is no established method to directly assess the impact of pollution on the skin and to test the efficacy of anti-pollution products.To address this problem, two different chambers were developed for the reproducible exposure to realistic air pollutant concentrations. One chamber for the exclusive use of excised skin and hair samples, the second chamber for ex vivo and in vivo measurements. Measurements of nicotine next to the investigated skin area allow conclusions to be drawn on the particle concentration to which the skin is exposed. Electron paramagnetic resonance spectroscopy, which enables the detection of free radicals in different systems, was applied to assess the hazard potential of pollution in the skin. A direct proof of the formation of free radicals in the skin by the model pollutant cigarette smoke could be demonstrated. An additional application of UV irradiation even increased the formation of free radicals in the skin seven-fold (sum parameter). Depending on the question of interest, the use of different spin probes allows various assessments of the radical formation in skin: the amount of radicals but also the antioxidant status of the microenvironment can be estimated.Using two exposure chambers, the direct formation of oxidative stress by cigarette smoke on ex vivo skin, with and without additional UV exposure, could be reproducibly examined. This measurement method is promising for the assessment of anti-pollution products and could allow a direct causal connection between pollutant, effect on the skin and the protective function of skin care products.

As a result of the increase in global climate change and the development of social networks, the study of ecotourism and the impact of social networks has been getting greater attention. Nonetheless, research examining the impact of social networks on ecotourism has been limited. This study investigates the relationship between ease of use, perceived usefulness, wordof-mouth (WOM), perceived trust, and tourist attitude towards ecotourism, and examines the moderating role of perceived risk on these relationships in the context of Vietnam. The regression analysis was conducted with data from answers of 231 respondents. The results show that perceived trust has the largest impact on tourist attitude towards ecotourism, which is followed by perceived usefulness. WOM communication has the least impact. The study also highlights the role of perceived risk in moderating the relationship between social networks and tourist attitudes.

Air pollution is increasing worldwide and skin is exposed to high levels of pollution daily, causing oxidative stress and other negative consequences. The methods used to determine oxidative stress in the skin are invasive and non-invasive label-free in vivo methods, which are severely limited. Here, a non-invasive and label-free method to determine the effect of cigarette smoke (CS) exposure on skin ex vivo (porcine) and in vivo (human) was established. The method is based on the measurement of significant CS-exposure-induced enhancement in red- and near-infrared (NIR)-excited autofluorescence (AF) intensities in the skin. To understand the origin of red- and NIR-excited skin AF, the skin was exposed to several doses of CS in a smoking chamber. UVA irradiation was used as a positive control of oxidative stress in the skin. The skin was measured with confocal Raman microspectroscopy before CS exposure, immediately after CS exposure, and after skin cleaning. CS exposure significantly increased the intensity of red- and NIR-excited skin AF in a dose-dependent manner in the epidermis, as confirmed by laser scanning microscopy AF imaging and fluorescence spectroscopy measurements. UVA irradiation enhanced the intensity of AF, but to a lower extent than CS exposure. We concluded that the increase in red- and NIR-excited AF intensities of the skin after CS exposure could clearly be related to the induction of oxidative stress in skin, where skin surface lipids are mainly oxidized.

The winged-helix domain of the methyl methanesulfonate and ultraviolet-sensitive 81 (wMUS81) is a potential cancer drug target. In this context, marine fungi compounds were indicated to be able to prevent wMUS81 structure via atomistic simulations. Eight compounds such as D197 (Tryptoquivaline U), D220 (Epiremisporine B), D67 (Aspergiolide A), D153 (Preussomerin G), D547 (12,13-dihydroxyfumitremorgin C), D152 (Preussomerin K), D20 (Marinopyrrole B) and D559 (Fumuquinazoline K) were indicated that they are able to prevent the conformation of wMUS81 via forming a strong binding affinity to the enzyme via perturbation approach. The electrostatic interaction is the dominant factor in the binding process of ligands to wMUS81. The residues Trp55, Arg59, Leu62, His63 and Arg69 were found to frequently form non-bonded contacts and hydrogen bonds to inhibitors. Moreover, the influence of the ligand D197, which formed the lowest binding free energy to wMUS81, on the structural change of enzyme was investigated using replica exchange molecular dynamics simulations. The obtained results indicated that D197, which forms a strong binding affinity, can modify the structure of wMUS81. Overall, the marine compounds probably inhibit wMUS81 due to forming a strong binding affinity to the enzyme as well as altering the enzymic conformation.

In our search for novel small molecules activating procaspase-3, we have designed and synthesised a series of novel acetohydrazides incorporating quinazolin-4(3H)-ones (5, 6, 7). Biological evaluation revealed eight compounds with significant cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). The most potent compound 5t displayed cytotoxicity up to 5-fold more potent than 5-FU. Analysis of structure-activity relationships showed that the introduction of different substituents at C-6 position on the quinazolin-4(3H)-4-one moiety, such as 6-chloro or 6-methoxy potentially increased the cytotoxicity of the compounds. In term of caspase activation activity, several compounds were found to exhibit potent effects, (e.g. compounds 7 b, 5n, and 5l). Especially, compound 7 b activated caspases activity by almost 200% in comparison to that of PAC-1. Further docking simulation also revealed that this compound potentially is a potent allosteric inhibitor of procaspase-3.

Cleistocalyx operculatus flower buds are used as a main ingredient in various beverages and herbal tea in tropical areas. The present study was conducted to investigate anti-osteoclastogenic effects of ethanol extract of C. operculatus flower buds (ECB) and to identify anti-osteoclastogenic compounds in these buds. ECB significantly inhibited RANKL-induced osteoclast differentiation and decreased RANKL-induced the activation of NFATc1. We isolated nineteen compounds from C. operculatus flower buds and found that eight compounds, including maslinic acid (6) and its two coumaroyl analogs (7 and 8), significantly inhibited RANKL-induced osteoclast formation. Among these, 3-O-trans-p-coumaroyl maslinic acid (8) showed the most potent inhibitory effect on RANKL-induced osteoclastogenesis via impairment of c-Fos and NF-κB activation, and subsequently, NFATc1 activation. These results suggested that identification of the anti-osteoclastogenic compounds from C. operculatus flower buds may extend our understanding of molecular mechanisms underlying biological activities of C. operculatus flower buds for osteoclast-related diseases.

Olean-12-en-27-oic acids possess a variety of pharmacological effects. However, their effects and underlying mechanisms on osteoclastogenesis remain unclear. This study aimed to investigate the anti-osteoclastogenic effects of five olean-12-en-27-oic acid derivatives including 3α,23-isopropylidenedioxyolean-12-en-27-oic acid (AR-1), 3-oxoolean-12-en-27-oic acid (AR-2), 3α-hydroxyolean-12-en-27-oic acid (AR-3), 23-hydroxy-3-oxoolean-12-en-27-oic acid (AR-4), and aceriphyllic acid A (AR-5). Among the five olean-12-en-27-oic acid derivatives, 3-hydroxyolean-12-en-27-oic acid derivatives, AR-3 and AR-5, significantly inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced mature osteoclast formation by reducing the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, F–actin ring formation, and mineral resorption activity. AR-3 and AR-5 decreased RANKL-induced expression levels of osteoclast-specific marker genes such as c-Src, TRAP, and cathepsin K (CtsK) as well as c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1). Mice treated with either AR-3 or AR-5 showed significant protection of the mice from lipopolysaccharide (LPS)-induced bone destruction and osteoclast formation. In particular, AR-5 suppressed RANKL-induced phosphorylation of JNK and ERK mitogen-activated protein kinases (MAPKs). The results suggest that AR-3 and AR-5 attenuate osteoclast formation in vitro and in vivo by suppressing RANKL-mediated MAPKs and NFATc1 signaling pathways and could potentially be lead compounds for the prevention or treatment of osteolytic bone diseases.

Objective: Magnolia coriacea is a rare species of Magnoliaceae and categorized as critically endangered, yet known for its valuable pharmaceutical properties. Phytochemical study of the plant was carried out, and the isolated compounds were subjected to different computational platforms to predict their chemical, inhibitory, physicochemical, and pharmacological properties. Methods: M coriacea dried twig or leaf powder was partially extracted with n -hexane, ethyl acetate, and 90% methanol to produce the corresponding extracts, which were subjected to column chromatography. The isolated compounds were identified by nuclear magnetic resonance (NMR) spectroscopic and electrospray ionization mass spectrometry (ESI-MS) methods. Results: Eight known aporphine alkaloids were isolated, (+)-glaucine N -oxide (1), N -methyl glaucine acetate (2), (+)-(S)-glaucine (3), magnoflorine (4), pontevedrine (5), O -methylatheroline (6), 7-hydroxydehydroglaucine (7), and mangochinine acetate (8). Quantum-based calculations found no abnormal structural constraints and suggested 2, 4, and 8 as the most promising inhibitors of protein structures in general with intensive nucleophilic reactive sites at their nitrogen atoms. Classical-based docking simulation agrees with this with respect to 3W37 (docking score [DS] < −12 kcal·mol−1) and PTP1B (DS ca −13 kcal·mol−1) structures. The biocompatibility and pharmacokinetics of the three candidates given by quantitative structure–activity relationship (QSAR) and absorption, distribution, metabolism, excretion, and toxicity (ADMET) regressions justify their potential for medicinal development. The results encourage further experimental studies of the promising M coriacea -extracted aporphine alkaloids for drug-developing purposes, especially mangochinine acetate (8). Conclusions: Isolation and molecular docking simulation of 8 aporphine alkaloids were accomplished. QSAR and ADMET regressions suggested that three compounds (2, 4, and 8) were the most suitable for medicinal applications given both biocompatibility and pharmacokinetics based on specific prediction toward 3W37 (α-glucosidase) and PTP1B (tyrosine phosphatase 1B) structures. [ABSTRACT FROM AUTHOR]

2′,4′-Dihydroxy-6’-methoxy-3′,5′-dimethylchalcone (DMC), a principal natural chalcone of Cleistocalyx operculatus buds, suppresses the growth of many types of cancer cells. However, the effects of this compound on pancreatic cancer cells have not been evaluated. In our experiments, we explored the effects of this chalcone on two human pancreatic cancer cell lines. A cell proliferation assay revealed that DMC exhibited concentration-dependent cytotoxicity against PANC-1 and MIA PACA2 cells, with IC50 values of 10.5 ± 0.8 and 12.2 ± 0.9 µM, respectively. Treatment of DMC led to the apoptosis of PANC-1 by caspase-3 activation as revealed by annexin-V/propidium iodide double-staining. Western blotting indicated that DMC induced proteolytic activation of caspase-3 and -9, degradation of caspase-3 substrate proteins (including poly[ADP-ribose] polymerase [PARP]), augmented bak protein level, while attenuating the expression of bcl-2 in PANC-1 cells. Taken together, our results provide experimental evidence to support that DMC may serve as a useful chemotherapeutic agent for control of human pancreatic cancer cells.