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Fulltext Curculin exhibits sweet-tasting and taste-modifying activities through its distinct molecular surfaces

Kurimoto E, Suzuki M, Amemiya E, Yamaguchi Y, Nirasawa S, Shimba N, et al.

J Biol Chem, 2007 Nov 16;282(46):33252-33256.
PMID: 17895249 DOI: 10.1074/jbc.C700174200

Curculin isolated from Curculigo latifolia, a plant grown in Malaysia, has an intriguing property of modifying sour taste into sweet taste. In addition to this taste-modifying activity, curculin itself elicits a sweet taste. Although these activities have been attributed to the heterodimeric isoform and not homodimers of curculin, the underlying mechanisms for the dual action of this protein have been largely unknown. To identify critical sites for these activities, we performed a mutational and structural study of recombinant curculin. Based on the comparison of crystal structures of curculin homo- and heterodimers, a series of mutants was designed and subjected to tasting assays. Mapping of amino acid residues on the three-dimensional structure according to their mutational effects revealed that the curculin heterodimer exhibits sweet-tasting and taste-modifying activities through its partially overlapping but distinct molecular surfaces. These findings suggest that the two activities of the curculin heterodimer are expressed through its two different modes of interactions with the T1R2-T1R3 heterodimeric sweet taste receptor.
Interactive impacts of photoaged micro(nano)plastics and co-occurring chemicals in the environment

Junaid M, Hamid N, Liu S, Abbas Z, Imran M, Haider MR, et al.

Sci Total Environ, 2024 Jun 01;927:172213.
PMID: 38580116 DOI: 10.1016/j.scitotenv.2024.172213

In the environment, sunlight or ultraviolet (UV) radiation is considered to be the primary cause of plastic aging, leading to their fragmentation into particles, including micro(nano)plastics (MNPs). Photoaged MNPs possess diverse interactive properties and ecotoxicological implications substantially different from those of pristine plastic particles. This review aims to highlight the mechanisms and implications of UV-induced photoaging of MNPs, with an emphasis on various UV sources and their interactions with co-occurring organic and inorganic chemicals, as well as the associated ecological and health impacts and factors affecting those interactions. Compared to UV-B, UV-A and UV-C were more widely used in laboratory studies for MNP degradation. Photoaged MNPs act as vectors for the transportation of organic pollutants, organic matter, and inorganic chemicals in the environment. Literature showed that photoaged MNPs exhibit a higher sorption capacity for PPCPs, PAHs, PBDEs, pesticides, humic acid, fulvic acid, heavy metals, and metallic nanoparticles than pristine MNPs, potentially causing significant changes in associated ecological and health impacts. Combined exposure to photoaged MNPs and organic and inorganic pollutants significantly altered mortality rate, decreased growth rate, histological alterations, neurological impairments, reproductive toxicity, induced oxidative stress, thyroid disruption, hepatotoxicity, and genotoxicity in vivo, both in aquatic and terrestrial organisms. Limited studies were reported in vitro and found decreased cellular growth and survival, induced oxidative stress, and compromised the permeability and integrity of the cell membrane. In addition, several environmental factors (temperature, organic matter, ionic strength, time, and pH), MNP properties (polymer types, sizes, surface area, shapes, colour, and concentration), and chemical properties (pollutant type, concentration, and physiochemical properties) can influence the photoaging of MNPs and associated impacts. Lastly, the research gaps and prospects of MNP photoaging and associated implications were also summarized. Future research should focus on the photoaging of MNPs under environmentally relevant conditions, exploiting the polydisperse characteristics of environmental plastics, to make this process more realistic for mitigating plastic pollution.
Adverse metabolic consequences of androgen deprivation therapy (ADT) on Asian patients with prostate cancer: Primary results from the real-life experience of ADT in Asia (READT) study

Wong CHM, Xu N, Lim J, Feng KK, Chan WKW, Chan MTY, et al.

Prostate, 2023 Jun;83(8):801-808.
PMID: 36938957 DOI: 10.1002/pros.24519

BACKGROUND: Androgen deprivation therapy (ADT) use in prostate cancer (PCa) has seen a rising trend. We investigated the relationship between ADT and adverse changes in metabolic parameters in an Asian population.
METHODS: This is an international prospective multicenter single-arm cohort yielded from the real-life experience of ADT in Asia (READT) registry. Consecutive ADT-naïve patients diagnosed of PCa and started on ADT were prospectively recruited from 2016 and analyzed. Baseline patient characteristics, PCa disease status, and metabolic parameters were documented. Patients were followed up at 6-month interval for up to 5 years. Metabolic parameters including body weight, lipid profiles, and glycemic profiles were recorded and analyzed.
RESULTS: 589 patients were eligible for analysis. ADT was associated with adverse glycemic profiles, being notable at 6 months upon ADT initiation and persisted beyond 1 year. Comparing to baseline, fasting glucose level and hemoglobin A1c level increased by 4.8% (p
Fulltext Health-Related Quality of Life Assessment in Prostate Cancer Patient Undergoing Androgen Deprivation Therapy: Real-World Experience in the READT Study

Lim J, Ng CF, Wei Y, Ong TA, Chu PS, Chan WKW, et al.

World J Mens Health, 2024 Apr;42(2):449-459.
PMID: 37853536 DOI: 10.5534/wjmh.230042

PURPOSE: To investigate the effect of androgen deprivation therapy (ADT) on health-related quality of life (HRQOL) in Asian men with all stages of prostate cancer.
MATERIALS AND METHODS: READT (real-life evaluation of the effect of ADT in prostate cancer patients in Asia) was a multi-center, prospective observational study involving six sites across four Asian populations. We enrolled eligible prostate cancer patients, who opted for ADT alone or in combination without prior neoadjuvant or adjuvant ADT within 12 months. The EuroQoL-5 dimensions, 5 level scale (EQ-5D-5L) utility index scores and visual analog scale (VAS) were evaluated at baseline, month 6 and month 12.
RESULTS: A total of 504 patients were recruited into READT between September 2016 and May 2020 with 52.9% diagnosed with metastatic prostate cancer. The EQ-5D-5L was evaluable in 442/504 (87.7%) of patients. Overall baseline EQ-5D-5L utility index score was 0.924 (interquartile range [IQR] 0.876-1.000). We observed a statistically significant difference in baseline EQ-5D-5L utility index score among different populations with a median EQ-5D-5L utility index score of 1 for Taiwan & Hong Kong, 0.897 for China and 0.838 for Malaysia. Similar trend was observed throughout multiple treatment time-points. Stage IV prostate cancer were significantly associated with a lower baseline EQ-5D-5L utility index score compared to stage I-III prostate cancer, producing a median disutility value of -0.080. Participants had a high median VAS (80, IQR 70-90), indicating good overall health on average during ADT initiation.
CONCLUSIONS: The study highlights the differences in health state utility index scores among various Asian prostate cancer patients receiving ADT at real-world setting. Our findings will be informative and useful in cost-effectiveness evaluation and policy decision making.