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Calcaratarin D, a labdane diterpenoid, attenuates mouse asthma via modulating alveolar macrophage function

Abstract

Background and purpose: Alveolar macrophages (AMs) contribute to airway inflammation and remodelling in allergic asthma. Calcaratarin D (CalD), a labdane diterpenoid from rhizomes of the medicinal plant Alpinia calcarata, has recently been shown to possess anti-inflammatory properties. The present study evaluated protective effects of CalD in a house dust mite (HDM)-induced asthma mouse model.

Experimental approach: The effects of CalD on AMs in contributing to anti-inflammatory effects in asthma were investigated through in vivo, ex vivo, and in vitro experiments.

Key results: CalD reduced total bronchoalveolar lavage fluid and differential cell count, serum IgE levels, mucus hypersecretion, and airway hyperresponsiveness in HDM-challenged mice. Additionally, CalD affected a wide array of pro-inflammatory cytokines and chemokines and oxidative damage markers in isolated lung tissues. CalD suppressed the HDM-induced increase in Arg1 (M2 macrophage marker) in AMs from lung tissue and reduced lung polyamine levels. CalD weakened antigen presentation capability of AMs by reducing CD80 expression, reduced AM-derived CCL17 and CCL22 levels, and lessened Th2 cytokines from CD4+ T-cells from asthma lung digest. CalD blocked the HDM-induced FoxO1/IRF4 pathway and restored impaired the Nrf2/HO-1 antioxidant pathway in lung tissues. CalD inhibited IL-4/IL-13-stimulated JAK1/STAT6 pathway, FoxO1 protein expression, and chemokine production in primary AMs. Structure-activity relationship study revealed the α,β-unsaturated γ-butyrolactone in CalD is capable of forming covalent bonds with cellular protein targets essential for its action.

Conclusion and implications: Our results demonstrate for the first time that CalD is a novel anti-inflammatory natural compound for allergic asthma that modulates AM function.

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ACS Nano article by Prof. Dean HO and A/P Edward CHOW: IDentif.AI-Omicron

Nanomedicine-based and unmodified drug interventions to address COVID-19 have evolved over the course of the pandemic as more information is gleaned and virus variants continue to emerge. For example, some early therapies (e.g., antibodies) have experienced markedly decreased efficacy. Due to a growing concern of future drug resistant variants, current drug development strategies are seeking to find effective drug combinations. In this study, we used IDentif.AI, an artificial intelligence-derived platform, to investigate the drug–drug and drug–dose interaction space of six promising experimental or currently deployed therapies at various concentrations: EIDD-1931, YH-53, nirmatrelvir, AT-511, favipiravir, and auranofin.

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More than 30 NUS researchers placed among world’s most influential scientific minds

Congratulation to Dr Alan Prem Kumar and Prof. Guillermo C. Bazan (Joint Professor at Pharmacology) on being 2 of the 34 NUS researchers that have been placed among some of the world’s most highly cited researchers, according to the Highly Cited Researchers 2022. List published by data analytics firm Clarivate.

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Congratulations to Faculty Recognized Among Top 2% of Scientists Worldwide

The Department of Pharmacology congratulates 17 faculty members on being recognized among the top 2% of scientists worldwide in a study from Stanford University (Ioannidis, 2022).

Congratulations to faculty members Professor Wong Wai-Shiu, Fred, Professor Goh Boon Cher, Professor Ho, Dean, Associate Professor Gautam Sethi, Associate Professor Chen Li-Hsian, Christopher, Associate Professor Chow Kai-Hua, Edward, Dr Kumar, Alan Prem; joint faculty members Professor Bazan, Guillermo C., Professor Kini, R. Manjunatha, Professor Moore, Philip Keith; adjunct faculty members Associate Professor Manser, Edward J., Associate Professor Moochhala, Shabbir M.; retired faculty members Emeritus Professor Lee Jon Deoon, Edmund, Associate Professor Tan Kwon Huat, Benny; Associate Professor Sim Meng Kwoon; and visiting professors Professor Chun, Jerold, and Professor Foster, Paul S.

Ioannidis, John P.A. (2022), “September 2022 data-update for “Updated science-wide author databases of standardized citation indicators”, Mendeley Data, V4, doi: 10.17632/btchxktzyw.4

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Proteins in cell-based particles could lead to early diagnosis and treatment of breast cancer metastasis

One woman is diagnosed with breast cancer every fourteen seconds somewhere across the globe — based on data showing that an approximate 2.3 million women worldwide were newly diagnosed with breast cancer in 2020.

In Singapore, it is the most common cancer among women, and will likely affect one in thirteen women in their lifespan. Although advances in medicine today allow for treatments for early-stage and non-metastatic breast cancer, advanced stage and metastatic breast cancer is considered incurable with current treatment options, with very poor prognosis.

The early detection of breast cancer metastasis is therefore paramount in the treatment of the condition, and a team of researchers discovered a non-invasive biomarker that could aid with earlier diagnosis.

Led by Assistant Professor Minh Le from the Institute for Digital Medicine (WisDM) and Department of Pharmacology at the National University of Singapore’s Yong Loo Lin School of Medicine (NUS Medicine), and Associate Professor Andrew Grimson from the Department of Molecular Biology and Genetics at Cornell University, the researchers found that particles which are secreted by tumour cells, extracellular vesicles (EVs), displayed a high level of protein integrins αv and β1, in patients with locally advanced and metastatic breast cancer.

Asst Prof Le said, “Metastasis is the chief concern for breast cancer patients. The study highlights the potential of integrins αv and β1 as a promising prognostic and therapeutic target for patients with metastatic breast cancer. Our research has opened several doors, and we hope that future work will help develop new ways to assess, monitor and suppress this hallmark of cancer.”

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NUS study: Black cardamom effective against lung cancer cells

In Indian Ayurvedic medicine, black cardamom has been used in formulations to treat cancer and lung conditions. A team of researchers from the NUS Faculty of Science, NUS Yong Loo Lin School of Medicine, and NUS College of Design and Engineering studied the scientific basis behind this traditional medicinal practice and provided evidence of the cytotoxic effect of black cardamom on lung cancer cells. The research highlighted the spice as a source of potent bioactives, such as cardamonin and alpinetin, which could be used in the treatment or prevention of lung cancer. The study is the first to report the association of black cardamom extract with oxidative stress induction in lung cancer cells, and compare the spice’s effects on lung, breast and liver cancer cells.

“With black cardamom being commonly used as an important spice in cooking, further in-depth investigation about its impact on lung cancer progression in the pre-clinical models can provide strong evidence in support of the “food as medicine” philosophy of Hippocrates that has been neglected to great extent in the present day,” said Associate Professor Gautam Sethi from the Department of Pharmacology at the NUS Yong Loo Lin School of Medicine, who was a collaborator for the research.

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Winner of Graduate Mentor of the Year (GRAMAY) Award 2022

Congratulations to Dr. LE Thi Nguyet Minh for receiving the Graduate Mentor of the Year (GRAMAY) Award 2022. The GRAMAY Award is an annual award that honors and celebrates faculty staff for their excellence in mentorship and the professional development of graduate students in the Yong Loo Lin School of Medicine. The award is given to recognize the important key roles played by the Faculty staff in inspiring and nurturing future biomedical- and clinician-scientists. The award recipients should have shown excellence in graduate supervision, intellectual and professional development as well as career development of their graduate students.

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