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1.
Diabetes Obes Metab ; 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39161060

ABSTRACT

AIM: To assess the effects of a small-molecule nicotinamide N-methyltransferase (NNMT) inhibitor, 5A1MQ, on body composition, metabolic variables, fatty liver pathologies, and circulating biomarkers in diet-induced obese (DIO) mice, and characterize its plasma pharmacokinetics (PK) and tissue distribution in vivo. MATERIALS AND METHODS: DIO mice were administered vehicle or 5A1MQ once daily for 28 days. Longitudinal measures of body composition, blood glucose and plasma insulin levels, and terminal measures of liver histopathology and serum markers, were evaluated. Plasma and tissue PK were established in age- and strain-matched mice after intravenous, oral, and subcutaneous dosing of 5A1MQ. RESULTS: 5A1MQ treatment dose-dependently limited body weight and fat mass gains, improved oral glucose tolerance and insulin sensitivity, and suppressed hyperinsulinaemia in DIO mice. Liver histology from 5A1MQ-treated DIO mice showed attenuated hepatic steatosis and macrophage infiltration, and correspondingly reduced liver weight, size, and triglyceride levels. 5A1MQ treatment normalized circulating levels of alanine transaminase, aspartate transaminase, and ketone bodies, supporting an overall improvement in liver and metabolic functions. The pharmacodynamic effects of 5A1MQ were further corroborated by its high systemic exposure and effective distribution to metabolically active tissues, including adipose, muscle and liver, following subcutaneous dosing of mice. CONCLUSIONS: This work validates NNMT inhibition as a viable pharmacological approach to ameliorate metabolic imbalances and improve liver pathologies that develop with obesity.

2.
3 Biotech ; 14(9): 209, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39184913

ABSTRACT

Currently, numerous glycosides have been synthesized and used in clinical applications, neutraceuticals, cosmetics, and food processing. Structurally, a glycoside is composed of aglycone attaching to one or several sugar moieties so-called glycone. It is found that biochemical or biopharmaceutical properties of glycoside are mainly determined by its sugar part and thereby alternation of this glycone resulting in novel structure and characteristics as well. The use of traditional production methods of glycosides such as direct extraction and purification from plants, animals, or microorganisms is very challenging (laborious, time-consuming, technique, high price, low yield, etc.). Alternatively, the use of enzymatic methods for the biosynthesis of glycosides has become a highly promising tool. Particularly, the diverse structure of glycosides can be obtained using the promiscuous catalytic activity of glycosyltransferases (GT) mined from bioresources (plants, fungi, microorganisms, etc.). In addition, the exploration of GT catalytic promiscuity toward diverse aglycones, and glycones has indeed been interesting and played a key role in the production of novel glycosides. This review described the recent advances in glycosyltransferase-mediated glycodiversification of small molecules (flavonoids, steroids, terpenoids, etc.). Mostly, references were collected from 2014 to 2023.

3.
Allergy ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987868

ABSTRACT

INTRODUCTION: Evidence on the early life risk factors of adult CRS, and the history of asthma and allergies across the life course, is limited. AIM: To investigate relationships between respiratory infective/allergic conditions in childhood, and asthma and allergies across the life course and CRS in middle age. METHODS: Data were from the population-based Tasmanian Longitudinal Health Study (TAHS) cohort, first studied in 1968 when aged 6-7 years (n = 8583) and serially followed into middle age (n = 3609). Using a well-accepted epidemiological definition, participants were assigned a CRS-severity subtype at age 53: no sinusitis/CRS (reference); past doctor diagnosis only; current symptoms without doctor diagnosis; and doctor-diagnosed CRS with current symptoms. Relationships with infective/allergic respiratory illnesses at age 7, and previously published asthma-allergy trajectories from 7 to 53 years, were examined using multinominal regression. RESULTS: In middle age, 5.8% reported current CRS symptoms with 2.5% doctor-diagnosed. Childhood conditions associated with symptomatic doctor-diagnosed CRS included frequent head colds (multinomial odds ratio [mOR] = 2.04 (95% confidence interval [95% CI]: 1.24, 3.37)), frequent tonsillitis (mOR = 1.61 [95% CI: 1.00, 2.59]) and current childhood asthma (mOR = 2.23 [95% CI: 1.25, 3.98]). Life course trajectories that featured late-onset or persistent asthma and allergies were associated with all CRS subtypes in middle age; early-onset persistent asthma and allergies (mOR = 6.74, 95% CI: 2.76, 16.4); late-onset asthma allergies (mOR = 15.9, 95% CI: 8.06, 31.4), and late-onset hayfever (mOR = 3.02, 95% CI: 1.51, 6.06) were associated with symptomatic doctor-diagnosed CRS. CONCLUSION: Current asthma, frequent head colds and tonsillitis at age 7 could signal a susceptible child who is at higher risk for CRS in mid-adult life and who might benefit from closer monitoring and/or proactive management. Concurrent asthma and allergies were strongly associated and are potential treatable traits of adult CRS.

5.
Chemosphere ; 361: 142452, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38810804

ABSTRACT

CuCoFe-LDO/BCD was successfully synthesized from CuCoFe-LDH and biochar derived from durian shell (BCD). Ciprofloxacin (CFX) degraded more than 95% mainly by O2•- and 1O2 in CuCoFe-LDO/BCD(2/1)/PMS system within 10 min with a rate constant of 0.255 min-1, which was 14.35 and 2.66 times higher than those in BCD/PMS and CuCoFe-LDO/PMS systems, respectively. The catalytic system exhibited good performance over a wide pH range (3-9) and high degradation efficiency of other antibiotics. Built-in electric field (BIEF) driven by large difference in the work function/Fermi level ratio between CuCoFe-LDO and BCD accelerated continuous electron transfer from CuCoFe-LDO to BCD to result in two different microenvironments with opposite charges at the interface, which enhanced PMS adsorption and activation via different directions. As a non-radical, 1O2 was mainly generated via PMS activation by C=O in BCD. The presence of C=O in BCD resulted in an increase in atomic charge of C in C=O and redistributed the charge density of other C atoms. As a result, strong adsorption of PMS at C atom in C=O and other C with a high positive charge was favorable for 1O2 generation, whereas an enhanced adsorption of PMS at negatively charged C accounted for the generation of •OH and SO4•-. After adsorption, electrons in C of BCD became deficient and were fulfilled with those transferred from CuCoFe-LDO driven by BIEF, which ensured the high catalytic activity of CuCoFe-LDO/BCD. O2•-, on the other hand, was generated via several pathways that involved in the transformation of •OH and SO4•- originated from PMS activation by the transition of metal species in CuCoFe-LDO and negatively charged C in BCD. This study proposed a new idea of fabricating a low-cost metal-LDH and biomass-derived catalyst with a strong synergistic effect induced by BIEF for enhancing PMS activation and antibiotic degradation.


Subject(s)
Anti-Bacterial Agents , Charcoal , Peroxides , Charcoal/chemistry , Anti-Bacterial Agents/chemistry , Catalysis , Peroxides/chemistry , Ciprofloxacin/chemistry , Oxides/chemistry , Copper/chemistry , Adsorption , Water Pollutants, Chemical/chemistry
6.
Lancet ; 403(10435): 1494-1503, 2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38490231

ABSTRACT

Lung development starts in utero and continues during childhood through to adolescence, reaching its peak in early adulthood. This growth is followed by gradual decline due to physiological lung ageing. Lung-function development can be altered by several host and environmental factors during the life course. As a result, a range of lung-function trajectories exist in the population. Below average trajectories are associated with respiratory, cardiovascular, metabolic, and mental health comorbidities, as well as with premature death. This Review presents progressive research into lung-function trajectories and assists the implementation of this knowledge in clinical practice as an innovative approach to detect poor lung health early, monitor respiratory disease progression, and promote lung health. Specifically, we propose that, similar to paediatric height and weight charts used globally to monitor children's growth, lung-function charts could be used for both children and adults to monitor lung health status across the life course. To achieve this proposal, we introduce our free online Lung Function Tracker tool. Finally, we discuss challenges and opportunities for effective implementation of the trajectory concept at population level and outline an agenda for crucial research needed to support such implementation.


Subject(s)
Lung , Respiratory Tract Diseases , Adult , Adolescent , Child , Humans , Mental Health , Health Status
7.
Environ Sci Pollut Res Int ; 31(18): 26773-26789, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38456975

ABSTRACT

In this study, CoCr layered double hydroxide material (CoCr-LDH) was prepared and used as an effective catalyst for peroxymonosulfate (PMS) activation to degrade organics in water. The prepared CoCr-LDH material had a crystalline structure and relatively porous structure, as determined by various surface analyses. In Rhodamine B (RhB) removal, the most outstanding PMS activation ability belongs to the material with a Co:Cr molar ratio of 2:1. The removal of RhB follows pseudo-first-order kinetics (R2 > 0.99) with an activation energy of 38.23 kJ/mol and efficiency of 98% after 7 min of treatment, and the total organic carbon of the solution reduced 47.2% after 10 min. The activation and oxidation mechanisms were proposed and the RhB degradation pathways were suggested with the key contribution of O2•- and 1O2. Notably, CoCr-LDH can activate PMS over a wide pH range of 4 - 9, and apply to a wide range of organic pollutants and aqueous environments. The material has high stability and good recovery, which can be reused for 5 cycles with a stable efficiency of above 88%, suggesting a high potential for practical recalcitrant water treatment via PMS activation by heterogeneous catalysts.


Subject(s)
Peroxides , Water Pollutants, Chemical , Water Purification , Water Pollutants, Chemical/chemistry , Peroxides/chemistry , Water Purification/methods , Rhodamines/chemistry , Kinetics , Oxidation-Reduction , Catalysis
8.
Int J Mol Sci ; 25(5)2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38473971

ABSTRACT

UDP-glycosyltransferases (UGTs) form a large enzyme family that is found in a wide range of organisms. These enzymes are known for accepting a wide variety of substrates, and they derivatize xenobiotics and metabolites for detoxification. However, most UGT homologs have not been well characterized, and their potential for biomedical and environmental applications is underexplored. In this work, we have used a fluorescent assay for screening substrates of a plant UGT homolog by monitoring the formation of UDP. We optimized the assay such that it could be used for high-throughput screening of substrates of the Medicago truncatula UGT enzyme, UGT71G1, and our results show that 34 of the 159 screened compound samples are potential substrates. With an LC-MS/MS method, we confirmed that three of these candidates indeed were glycosylated by UGT71G1, which includes bisphenol A (BPA) and 7-Ethyl-10-hydroxycamptothecin (SN-38); derivatization of these toxic compounds can lead to new environmental and medical applications. This work suggests that UGT homologs may recognize a substrate profile that is much broader than previously anticipated. Additionally, it demonstrates that this screening method provides a new means to study UDP-glycosyltransferases, facilitating the use of these enzymes to tackle a wide range of problems.


Subject(s)
Glycosyltransferases , Tandem Mass Spectrometry , Glycosyltransferases/metabolism , Chromatography, Liquid , Plants/metabolism , Uridine Diphosphate
9.
Thorax ; 79(7): 615-623, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38388490

ABSTRACT

BACKGROUND: There is growing interest in the joint effects of hazardous trace elements (HTEs) on lung function deficits, but the data are limited. This is a critical research gap given increased global industrialisation. METHODS: A national cross-sectional study including spirometry was performed among 2112 adults across 11 provinces in China between 2020 and 2021. A total of 27 HTEs were quantified from urine samples. Generalised linear models and quantile-based g-computation were used to explore the individual and joint effects of urinary HTEs on lung function, respectively. RESULTS: Overall, there were negative associations between forced expiratory volume in 1 s (FEV1) and urinary arsenic (As) (z-score coefficient, -0.150; 95% CI, -0.262 to -0.038 per 1 ln-unit increase), barium (Ba) (-0.148, 95% CI: -0.258 to -0.039), cadmium (Cd) (-0.132, 95% CI: -0.236 to -0.028), thallium (Tl) (-0.137, 95% CI: -0.257 to -0.018), strontium (Sr) (-0.147, 95% CI: -0.273 to -0.022) and lead (Pb) (-0.121, 95% CI: -0.219 to -0.023). Similar results were observed for forced vital capacity (FVC) with urinary As, Ba and Pb and FEV1/FVC with titanium (Ti), As, Sr, Cd, Tl and Pb. We found borderline associations between the ln-quartile of joint HTEs and decreased FEV1 (-20 mL, 95% CI: -48 to +8) and FVC (-14 mL, 95% CI: -49 to+2). Ba and Ti were assigned the largest negative weights for FEV1 and FVC within the model, respectively. CONCLUSION: Our study investigating a wide range of HTEs in a highly polluted setting suggests that higher urinary HTE concentrations are associated with lower lung function, especially for emerging Ti and Ba, which need to be monitored or regulated to improve lung health.


Subject(s)
Environmental Exposure , Trace Elements , Humans , Cross-Sectional Studies , Male , Female , Middle Aged , Environmental Exposure/adverse effects , Environmental Exposure/analysis , China/epidemiology , Trace Elements/urine , Adult , Forced Expiratory Volume , Spirometry , Vital Capacity , Lung/physiopathology , Aged
10.
Phys Chem Chem Phys ; 26(9): 7611-7617, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38363118

ABSTRACT

The recently uncovered two-dimensional materials serve as versatile building blocks for electronic devices. In this study, we methodically investigate the impact of substrate-induced strain and exchange field effects on the electronic density of states (EDOS) and electronic heat capacity (EHC) of single-layer ß12-borophene. Utilizing the Green's function approach, we compute these functions. The van Hove singularities in EDOS are observed to shift with strain, and depending on the direction and strength of the exchange field, the number of singularities increases. All these responses can be attributed to the renormalization of the velocity of electronic bands. Additionally, the inherent Schottky anomaly (an unusual peak at low temperatures) in the EHC undergoes a notable shift to higher and lower temperatures and variations in the intensity of the EHC due to substrate effects.

11.
Am J Respir Crit Care Med ; 210(6): 766-778, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38422471

ABSTRACT

Rationale: Chronic obstructive pulmonary disease (COPD) results from gene-environment interactions over the lifetime. These interactions are captured by epigenetic changes, such as DNA methylation. Objectives: To systematically review the evidence form epigenome-wide association studies related to COPD and lung function. Methods: A systematic literature search performed on PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases identified 1,947 articles that investigated epigenetic changes associated with COPD and/or lung function; 17 of them met our eligibility criteria, from which data were manually extracted. Differentially methylated positions (DMPs) and/or annotated genes were considered replicated if identified by two or more studies with a P < 1 × 10-4. Measurements and Main Results: Ten studies profiled DNA methylation changes in blood and seven in respiratory samples, including surgically resected lung tissue (n = 3), small airway epithelial brushings (n = 2), BAL (n = 1), and sputum (n = 1). Main results showed: 1) high variability in study design, covariates, and effect sizes, which prevented a formal meta-analysis; 2) in blood samples, 51 DMPs were replicated in relation to lung function and 12 related to COPD; 3) in respiratory samples, 42 DMPs were replicated in relation to COPD but none in relation to lung function; and 4) in COPD versus control studies, 123 genes (2.6% of total) were shared between one or more blood and one or more respiratory samples and associated with chronic inflammation, ion transport, and coagulation. Conclusions: There is high heterogeneity across published COPD and/or lung function epigenome-wide association studies. A few genes (n = 123; 2.6%) were replicated in blood and respiratory samples, suggesting that blood can recapitulate some changes in respiratory tissues. These findings have implications for future research. Systematic Review [protocol] registered with Open Science Framework (OSF).


Subject(s)
DNA Methylation , Epigenome , Genome-Wide Association Study , Pulmonary Disease, Chronic Obstructive , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Disease, Chronic Obstructive/physiopathology , Humans , DNA Methylation/genetics , Epigenome/genetics , Epigenesis, Genetic , Female , Male , Lung/physiopathology , Respiratory Function Tests , Middle Aged , Gene-Environment Interaction , Aged
12.
Am J Respir Crit Care Med ; 209(12): 1431-1440, 2024 06 15.
Article in English | MEDLINE | ID: mdl-38236192

ABSTRACT

Rationale: The term "pre-chronic obstructive pulmonary disease" ("pre-COPD") refers to individuals at high risk of developing COPD who do not meet conventional spirometric criteria for airflow obstruction. New approaches to identifying these individuals are needed, particularly in younger populations. Objectives: To determine whether lung function thresholds and respiratory symptoms can be used to identify individuals at risk of developing COPD. Methods: The Tasmanian Longitudinal Health Study comprises a population-based cohort first studied in 1968 (at age 7 yr). Respiratory symptoms, pre- and post-bronchodilator (BD) spirometry, diffusing capacity, and static lung volumes were measured in a subgroup at age 45, and the incidence of COPD was assessed at age 53. For each lung function measure, z-scores were calculated using Global Lung Function Initiative references. The optimal threshold for best discrimination of COPD incidence was determined by the unweighted Youden index. Measurements and Main Results: Among 801 participants who did not have COPD at age 45, the optimal threshold for COPD incidence by age 53 was pre-BD FEV1/FVC z-score less than -1.264, corresponding to the lowest 10th percentile. Those below this threshold had a 36-fold increased risk of developing COPD over an 8-year follow-up period (risk ratio, 35.8; 95% confidence interval, 8.88 to 144), corresponding to a risk difference of 16.4% (95% confidence interval, 3.7 to 67.4). The sensitivity was 88%, and the specificity was 87%. Positive and negative likelihood ratios were 6.79 and 0.14, respectively. Respiratory symptoms, post-BD spirometry, diffusing capacity, and static lung volumes did not improve on the classification achieved by pre-BD FEV1/FVC alone. Conclusions: This is the first study, to our knowledge, to evaluate the discriminatory accuracy of spirometry, diffusing capacity, and static lung volume thresholds for COPD incidence in middle-aged adults. Our findings support the inclusion of pre-BD spirometry in the physiological definition of pre-COPD and indicate that pre-BD FEV1/FVC at the 10th percentile accurately identifies individuals at high risk of developing COPD in community-based settings.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Spirometry , Humans , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Male , Female , Middle Aged , Prospective Studies , Spirometry/methods , Tasmania/epidemiology , Incidence , Longitudinal Studies , Cohort Studies , Respiratory Function Tests/methods , Forced Expiratory Volume , Vital Capacity , Adult
13.
Respirology ; 29(1): 63-70, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37733623

ABSTRACT

BACKGROUND AND OBJECTIVE: Early-life risk factors for obstructive sleep apnoea (OSA) are poorly described, yet this knowledge may be critical to inform preventive strategies. We conducted the first study to investigate the association between early-life risk factors and OSA in middle-aged adults. METHODS: Data were from population-based Tasmanian Longitudinal Health Study cohort (n = 3550) followed from 1st to 6th decades of life. Potentially relevant childhood exposures were available from a parent-completed survey at age 7-years, along with previously characterized risk factor profiles. Information on the primary outcome, probable OSA (based on a STOP-Bang questionnaire cut-off ≥5), were collected when participants were 53 years old. Associations were examined using logistic regression adjusting for potential confounders. Analyses were repeated using the Berlin questionnaire. RESULTS: Maternal asthma (OR = 1.5; 95% CI 1.1-2.0), maternal smoking (OR = 1.2; 1.05, 1.5), childhood pleurisy/pneumonia (OR = 1.3; 1.04, 1.7) and frequent bronchitis (OR = 1.2; 1.01, 1.5) were associated with probable OSA. The risk-factor profiles of 'parental smoking' and 'frequent asthma and bronchitis' were also associated with probable OSA (OR = 1.3; 1.01, 1.6 and OR = 1.3; 1.01-1.9, respectively). Similar associations were found for Berlin questionnaire-defined OSA. CONCLUSIONS: We found novel temporal associations of maternal asthma, parental smoking and frequent lower respiratory tract infections before the age of 7 years with adult OSA. While determination of their pathophysiological and any causal pathways require further research, these may be useful to flag the risk of OSA within clinical practice and create awareness and vigilance among at-risk groups.


Subject(s)
Asthma , Bronchitis , Sleep Apnea, Obstructive , Adult , Middle Aged , Humans , Child , Risk Factors , Smoking , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/epidemiology , Surveys and Questionnaires
14.
Lancet Respir Med ; 12(2): 129-140, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38109918

ABSTRACT

BACKGROUND: Cough is a common yet heterogeneous condition. Little is known about the characteristics and course of cough in general populations. We aimed to investigate cough subclasses, their characteristics from childhood across six decades of life, and potential treatable traits in a community-based cohort. METHODS: For our analysis of the Tasmanian Longitudinal Health Study (TAHS), a prospective, community-based cohort study that began on Feb 23, 1968, and has so far followed up participants in Tasmania, Australia, at intervals of 10 years from a mean age of 7 years to a mean age of 53 years, we used data collected as part of the TAHS to distinguish cough subclasses among current coughers at age 53 years. For this analysis, participants who answered Yes to at least one cough-related question via self-report questionnaire were defined as current coughers and included in a latent class analysis of cough symptoms; participants who answered No to all nine cough-related questions were defined as non-coughers and excluded from this analysis. Two groups of longitudinal features were assessed from age 7 years to age 53 years: previously established longitudinal trajectories of FEV1, forced vital capacity [FVC], FEV1/FVC ratio, asthma, and allergies-identified via group-based trajectory analysis or latent class analysis-and symptoms at different timepoints, including asthma, current productive cough, ever chronic productive cough, current smoking, and second-hand smoking. FINDINGS: Of 8583 participants included at baseline in the TAHS, 6128 (71·4%) were traced and invited to participate in a follow-up between Sept 3, 2012, and Nov 8, 2016; 3609 (58·9%) of these 6128 returned the cough questionnaire. The mean age of participants in this analysis was 53 years (SD 1·0). 2213 (61·3%) of 3609 participants were defined as current coughers and 1396 (38·7%) were categorised as non-coughers and excluded from the latent class analysis. 1148 (51·9%) of 2213 participants in this analysis were female and 1065 (48·1%) were male. Six distinct cough subclasses were identified: 206 (9·3%) of 2213 participants had minimal cough, 1189 (53·7%) had cough with colds only, 305 (13·8%) had cough with allergies, 213 (9·6%) had intermittent productive cough, 147 (6·6%) had chronic dry cough, and 153 (6·9%) had chronic productive cough. Compared with people with minimal cough, and in contrast to other cough subclasses, people in the chronic productive cough and intermittent productive cough subclasses had worse lung function trajectories (FEV1 persistent low trajectory 2·9%, 6·4%, and 16·1%; p=0·0011, p<0·0001; FEV1/FVC early low-rapid decline trajectory 2·9%, 12·1%, and 13·0%; p=0·012, p=0·0007) and a higher prevalence of cough (age 53 years 0·0%, 32·4% [26·1-38·7], and 50·3% [42·5-58·2]) and asthma (age 53 years 6·3% [3·7-10·6], 26·9% [21·3-33·3], and 41·7% [24·1-49·7]) from age 7 years to age 53 years. INTERPRETATION: We identified potential treatable traits for six cough subclasses (eg, asthma, allergies, and active and passive smoking for productive cough). The required management of productive cough in primary care (eg, routine spirometry) might differ from that of dry cough if our findings are supported by other studies. Future population-based studies could apply our framework to address the heterogeneity and complexity of cough in the community. FUNDING: The National Health and Medical Research Council of Australia, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, Victorian Asthma Foundation, Queensland Asthma Foundation, Tasmanian Asthma Foundation, The Royal Hobart Hospital Research Foundation, the Helen MacPherson Smith Trust, GlaxoSmithKline, and the China Scholarship Council.


Subject(s)
Asthma , Hypersensitivity , Tobacco Smoke Pollution , Adult , Male , Humans , Female , Child , Middle Aged , Cohort Studies , Prospective Studies , Asthma/diagnosis , Cough/epidemiology , Cough/etiology , Australia/epidemiology , Vital Capacity , Spirometry , Chronic Cough , Lung , Forced Expiratory Volume
15.
Front Immunol ; 14: 1196434, 2023.
Article in English | MEDLINE | ID: mdl-38077406

ABSTRACT

The herb Prunella vulgaris has shown significant immune-stimulatory and anti-inflammatory effects in mouse models. Here, the effects of a novel Prunella vulgaris-containing herbal mixture, PV-1, were examined in several mouse models for cancer, including chemically induced models of lung and oral cancers as well as syngraft models for lung cancer and melanoma. PV-1, consisting of extracts from Prunella vulgaris, Polygonum bistorta, Sonchus brachyotus and Dictamnus dasycarpus, exhibited no toxicity in a dose escalation study in A/J mice. PV-1 significantly inhibited mouse lung tumor development induced by the lung carcinogens vinyl carbamate and benzo[a]pyrene. PV-1 also hindered the induction of oral squamous cell carcinomas in C57BL/6 mice caused by 4-nitroquinoline-1-oxide. Flow cytometry analysis showed that PV-1 increased the numbers of CD8+ tumor-infiltrating lymphocytes (TILs) and increased the production of granzyme B, TNF-α, and IFN-γ by CD8+ TILs. PV-1 also suppressed granulocytic myeloid-derived suppressor cell numbers (g-MDSCs) and improved the anti-cancer activity of anti-PD-1 immunotherapy. These results indicate that PV-1 remodels the tumor immune microenvironment by selectively inhibiting g-MDSCs and increasing CD8+ TILs within tumors, resulting in decreased immune suppression and enhanced cancer chemopreventive efficacy.


Subject(s)
Head and Neck Neoplasms , Lung Neoplasms , Mouth Neoplasms , Prunella , Mice , Animals , Mice, Inbred C57BL , Lung Neoplasms/drug therapy , Mouth Neoplasms/drug therapy , Head and Neck Neoplasms/drug therapy , Chemoprevention , Tumor Microenvironment
16.
Occup Environ Med ; 80(10): 564-571, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37797979

ABSTRACT

OBJECTIVES: There is a scarcity of evidence on occupational exposures that may increase eczema in adults. We aimed to investigate potential associations between occupational exposures and eczema in middle-aged adults. METHODS: A lifetime work history calendar was collected from the Tasmanian Longitudinal Health Study participants when they were at age 53. Their work history was collated with the occupational asthma-specific job exposure matrix to define ever-exposure and cumulative exposure unit-years since no eczema job exposure matrix is available. Eczema was determined using the report of flexural rash that was coming and going for at least 6 months in the last 12 months. Skin prick tests were used to further subgroup eczema and atopic eczema (AE) or non-AE (NAE). Logistic and multinomial regression models were used to investigate the associations. RESULTS: Eczema prevalence was 9.1%. Current occupational exposure to animals (adjusted OR, aOR=3.06 (95% CI 1.43 to 6.58)), storage mites (aOR=2.96 (95% CI 1.38 to 6.34)) and endotoxin (aOR=1.95 (95% CI 1.04 to 3.64)) were associated with increased risk of current eczema. Furthermore, increased odds of NAE were associated with current exposure to animals (aOR=5.60 (95% CI 1.45 to 21.7)) and storage mites (aOR=5.63 (95% CI 1.45 to 21.9)). Current exposures to isocyanates (aOR=5.27 (95% CI 1.17 to 23.7)) and acrylates (aOR=8.41 (95% CI 1.60 to 44.3)) were associated with AE. There was no evidence of associations between cumulative exposures and eczema prevalence. Cumulative exposure to metalworking fluids (aOR=1.10 (95% CI 1.01 to 1.22)) was associated with NAE and acrylates (aOR=1.24 (95% CI 1.04 to 1.46)) with AE. CONCLUSIONS: In this exploratory assessment, multiple occupational exposures were associated with current eczema in middle-aged adults. Raising awareness and limiting these exposures during an individual's productive working life will likely have various health benefits, including reducing eczema prevalence.


Subject(s)
Asthma, Occupational , Dermatitis, Atopic , Eczema , Occupational Exposure , Middle Aged , Animals , Humans , Adult , Dermatitis, Atopic/complications , Eczema/epidemiology , Eczema/etiology , Occupational Exposure/adverse effects , Allergens , Prevalence , Asthma, Occupational/epidemiology , Asthma, Occupational/etiology , Acrylates , Risk Factors
19.
Int J Obes (Lond) ; 47(8): 661-668, 2023 08.
Article in English | MEDLINE | ID: mdl-37161067

ABSTRACT

BACKGROUND/OBJECTIVE: Obesity is a risk factor for multimorbidity, including depression and possibly anxiety. However, it is currently unclear how patterns of change in BMI over the life course differentially influence the magnitude in risk of depression and anxiety in mid-adulthood. We aimed to examine associations between BMI trajectories from childhood to adulthood and the risk of depression and anxiety in middle age. METHODS: In the Tasmanian Longitudinal Health Study (n = 2416), five distinct BMI trajectories were previously defined from age 5 to 45 years using group-based modelling. At age 53, current depression and anxiety were assessed using the Patient Health Questionnaire and the Generalized Anxiety Disorder scale, respectively. Logistic regression models adjusted for potential confounders estimated associations between BMI trajectories and these outcomes. RESULTS: Those belonging to the child average-increasing (OR = 2.24; 95%CI: 1.24, 4.06) and persistently high (OR = 2.64; 1.26, 5.52) trajectories were more likely to have depression in middle age, compared to the persistently average trajectory. However, the odds of experiencing greater severity of depressive symptoms was highest in the child average-increasing group (OR = 2.36; 1.59, 3.49). Despite finding no evidence of association between BMI trajectories and current anxiety, we observed less severe symptoms in the child high-decreasing trajectory (OR = 0.68; 0.51, 0.91). CONCLUSION: We found an increased risk of depression in middle age among individuals with a persistently high BMI from childhood to mid-adulthood and individuals with an average BMI in childhood which then increased consistently throughout adulthood. Encouragingly, resolving childhood adiposity by adulthood was associated with lesser anxiety symptoms. Taken together, these findings highlight the need to target mental health screening and treatment towards high-risk BMI trajectory groups and the importance of early interventions to prevent and resolve excess weight.


Subject(s)
Depression , Pediatric Obesity , Child , Humans , Middle Aged , Adolescent , Young Adult , Child, Preschool , Adult , Body Mass Index , Depression/epidemiology , Depression/psychology , Life Change Events , Longitudinal Studies , Pediatric Obesity/epidemiology , Anxiety/epidemiology
20.
Article in English | MEDLINE | ID: mdl-37239533

ABSTRACT

There is current interest in the role of ambient pollen in the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 or COVID-19) infection risk. The aim of this review is to summarise studies published up until January 2023 investigating the relationship between airborne pollen and the risk of COVID-19 infection. We found conflicting evidence, with some studies showing that pollen may increase the risk of COVID-19 infection by acting as a carrier, while others showed that pollen may reduce the risk by acting as an inhibiting factor. A few studies reported no evidence of an association between pollen and the risk of infection. A major limiting factor of this research is not being able to determine whether pollen contributed to the susceptibility to infection or just the expression of symptoms. Hence, more research is needed to better understand this highly complex relationship. Future investigations should consider individual and sociodemographic factors as potential effect modifiers when investigating these associations. This knowledge will help to identify targeted interventions.


Subject(s)
COVID-19 , Humans , SARS-CoV-2
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