Natural Products for the Management of Asthma and COPD.

Chronic airway inflammatory diseases like asthma, chronic obstructive pulmonary disease (COPD), and their associated exacerbations cause significant socioeconomic burden. There are still major obstacles to effective therapy for controlling severe asthma and COPD progression. Advances in understanding the pathogenesis of the two diseases at the cellular and molecular levels are essential for the development of novel therapies. In recent years, significant efforts have been made to identify natural products as potential drug leads for treatment of human diseases and to investigate their efficacy, safety, and underlying mechanisms of action. Many major active components from various natural products have been extracted, isolated, and evaluated for their pharmacological efficacy and safety. For the treatment of asthma and COPD, many promising natural products have been discovered and extensively investigated. In this chapter, we will review a range of natural compounds from different chemical classes, including terpenes, polyphenols, alkaloids, fatty acids, polyketides, and vitamin E, that have been demonstrated effective against asthma and/or COPD and their exacerbations in preclinical models and clinical trials. We will also elaborate in detail their underlying mechanisms of action unraveled by these studies and discuss new opportunities and potential challenges for these natural products in managing asthma and COPD.

Angiotensin II type-2 receptor activation in alveolar macrophages mediates protection against cigarette smoke-induced chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. Cumulative evidence has implicated renin-angiotensin system (RAS) in the pathogenesis of COPD. Alveolar macrophages (AMs) are the first line immune defense in the respiratory system and play a critical role in the lung homeostasis. This study aimed to investigate the role of AMs in contributing to the protective effects of angiotensin II type-2 receptor (AT2R) activation in cigarette smoke (CS)-induced COPD. The AM polarization, phagocytosis and metabolism, and the underlying biochemical mechanisms of compound 21 (C21), a selective and potent non-peptide small molecule AT2R agonist, were evaluated in a two-week CS-induced COPD mouse model. C21 restored AM phagocytosis ability, reversing CS-induced AM phagocytosis impairment. CS exposure polarized AMs towards M1 phenotype, whereas, C21 skewed the CS-exposed AMs towards M2 phenotype. C21 reprogrammed CS-exposed AM metabolism from a high glycolysis-driven process to support inflammation energy demand to a high mitochondrial respiration process to limit inflammation. Besides, C21 upregulated AT2R and Mas receptor levels in CS-exposed AMs, favoring the anti-inflammatory Ang II/AT2R axis and Ang 1-7/Mas axis in the RAS. C21 restored the normal levels of sirtuin 1 (SIRT1) and MAPK phosphatase 1 (MKP1) in CS-exposed AMs, leading to the reduction of phospho-p38, phospho-ERK and p65 subunit of NF-κB levels in CS-exposed AMs. We report here for the first time that AT2R agonist C21 acts by boosting the protective functions of AMs against CS-induced COPD, and our results support the development of AT2R agonist for the treatment of COPD.

Gender differences in psychosocial status of adolescents during COVID-19: a six-country cross-sectional survey in Asia Pacific.

BACKGROUND: School closures and family economic instability caused by the COVID-19 lockdown measures have threatened the mental health and academic progress of adolescents. Through secondary data analysis of World Vision Asia Pacific Region's COVID-19 response-assessments in May-June 2020, this study examined whether adolescents' study, physical, and leisure activities, psychosocial status, and sources of COVID-19 information differed by gender. METHODS: The assessments used cross-sectional surveys of adolescents in poor communities served by World Vision (n = 5552 males and n = 6680 females) aged 10-18 years old in six countries. The study households of adolescents were selected either by random sampling or non-probability convenience sampling and assessed using telephone or in-person interviews. Multivariate logistic regression analyses examined the relationship between gender and psychosocial status; daily activities (e.g., play, study); and sources of information about COVID-19. RESULTS: Participation in remote education was low (range: 0.5-20.7% across countries), with gender difference found only in Vietnam. Compared to males, female adolescents were less likely to play physically with a range of AOR: 0.36-0.55 (n = 5 countries) or play video games with a range of AOR: 0.55-0.72 (n = 2 countries). Female adolescents were more likely to feel isolated or stressed (India, AOR = 1.13, 95%CI:1.00, 1.26); feel unsafe (the Philippines, AOR = 2.22, 95%CI:1.14, 4.33; Vietnam, AOR = 1.31, 95%CI:1.03, 1.47); be concerned about education (India, AOR = 1.24, 95%CI:1.09, 1.41; Myanmar, AOR = 1.59, 95%CI:1.05, 2.40); or be concerned about household income (India, AOR = 1.13, 95%CI:1.00, 1.28; Vietnam, AOR = 1.31, 95%CI:1.09, 1.58). Female adolescents were also less likely to obtain COVID-19 related information through internet/social media (Bangladesh, AOR = 0.51, 95%CI:0.41, 0.64; India, AOR = 0.84, 95%CI:0.73, 0.96; and Myanmar, AOR = 0.65, 95%CI:0.43, 0.97) and mobile call or short message (India, AOR = 0.88, 95%CI:0.80, 0.98) but more likely to get the information from friends (Vietnam, AOR = 1.18, 95%CI:1.02, 1.36) and family (Bangladesh, AOR = 1.44, 95% CI:1.21, 1.70; India, AOR = 1.29, 95% CI:1.15, 1.45). CONCLUSIONS: An understanding of gender differences in the impacts of COVID-19 on adolescents' schooling, physical, and mental health can inform adolescent protection interventions. Psychosocial support during response and recovery phases needs to pay special attention to gender differences, since female adolescents' psychosocial status is at higher risk when facing the challenges of this pandemic.

Increased apical sodium-dependent glucose transporter abundance in the ctenidium of the giant clam Tridacna squamosa upon illumination.

Giant clams contain phototrophic zooxanthellae, and live in nutrient-deficient tropical waters where light is available. We obtained the complete cDNA coding sequence of a homolog of mammalian sodium/glucose cotransporter 1 (SGLT1) - SGLT1-like - from the ctenidium of the fluted giant clam, Tridacna squamosaSGLT1-like had a host origin and was expressed predominantly in the ctenidium. Molecular characterizations reveal that SGLT1-like of T. squamosa could transport urea, in addition to glucose, as other SGLT1s do. It has an apical localization in the epithelium of ctenidial filaments and water channels, and the apical anti-SGLT1-like immunofluorescence was stronger in individuals exposed to light than to darkness. Furthermore, the protein abundance of SGLT1-like increased significantly in the ctenidium of individuals exposed to light for 12 h, although the SGLT1-like transcript level remained unchanged. As expected, T. squamosa could perform light-enhanced glucose absorption, which was impeded by exogenous urea. These results denote the close relationships between light-enhanced glucose absorption and light-enhanced SGLT1-like expression in the ctenidium of T. squamosa Although glucose absorption could be trivial compared with the donation of photosynthates from zooxanthellae in symbiotic adults, SGLT1-like might be essential for the survival of aposymbiotic larvae, leading to its retention in the symbiotic stage. A priori, glucose uptake through SGLT1-like might be augmented by the surface microbiome through nutrient cycling, and the absorbed glucose could partially fulfill the metabolic needs of the ctenidial cells. Additionally, SGLT1-like could partake in urea absorption, as T. squamosa is known to conduct light-enhanced urea uptake to benefit the nitrogen-deficient zooxanthellae.

Light exposure enhances urea absorption in the fluted giant clam, Tridacna squamosa, and up-regulates the protein abundance of a light-dependent urea active transporter, DUR3-like, in its ctenidium.

Giant clams live in nutrient-poor reef waters of the Indo-Pacific and rely on symbiotic dinoflagellates (Symbiodinium spp., also known as zooxanthellae) for nutrients. As the symbionts are nitrogen deficient, the host clam has to absorb exogenous nitrogen and supply it to them. This study aimed to demonstrate light-enhanced urea absorption in the fluted giant clam, Tridacna squamosa, and to clone and characterize the urea active transporter DUR3-like from its ctenidium (gill). The results indicate that T. squamosa absorbs exogenous urea, and the rate of urea uptake in the light was significantly higher than that in darkness. The DUR3-like coding sequence obtained from its ctenidium comprised 2346 bp, encoding a protein of 782 amino acids and 87.0 kDa. DUR3-like was expressed strongly in the ctenidium, outer mantle and kidney. Twelve hours of exposure to light had no significant effect on the transcript level of ctenidial DUR3-like However, between 3 and 12 h of light exposure, DUR3-like protein abundance increased progressively in the ctenidium, and became significantly greater than that in the control at 12 h. DUR3-like had an apical localization in the epithelia of the ctenidial filaments and tertiary water channels. Taken together, these results indicate that DUR3-like might participate in light-enhanced urea absorption in the ctenidium of T. squamosa When made available to the symbiotic zooxanthellae that are known to possess urease, the absorbed urea can be metabolized to NH3 and CO2 to support amino acid synthesis and photosynthesis, respectively, during insolation.

Differences in the early impact of COVID-19 on food security and livelihoods in rural and urban areas in the Asia Pacific Region.

Lockdowns due to COVID-19 in early 2020 had health, economic, and social consequences globally. Using survey data collected as part of a rapid assessment among non-governmental organization- (NGO) supported communities in six Asia Pacific countries (n = 13,522), this study examined if the early impacts of COVID-19 on job loss or reduced income, food expenditure, food availability at households and markets, and affordability of essential items, differed between rural and urban areas. Job loss or reduced income was higher in urban areas than in rural areas in India (91.2% vs. 82.5%), Myanmar (72.0% vs. 48.6%), and Vietnam (76.5% vs. 44.9%). While there was a significant decline in food expenditure in all six countries, there were significantly larger reductions in food expenditures in urban areas versus rural areas in India (35.2% vs. 24.0%), Myanmar (30.8% vs. 8.5%), and Vietnam (31.0% vs. 2.3%). Food stocks were less available in urban areas than in rural areas in Bangladesh (18.8% vs. 37.8%), India (91.5% vs.76.0%), and Myanmar (72.0% vs. 59.0%). Foods and essential items were largely available at markets, without significant differences between rural and urban areas, except in Vietnam. Full affordability was only 20%-30% for most items, with a trend of higher affordability of some items in urban areas than in rural areas. Recommendations to mitigate the impacts of COVID-19 include promoting urban agriculture with efficient food distribution and cash support and supporting small-holder farmers for procurement and adequate functioning of the supply chain system in the region.