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Fulltext Asia Cohort Consortium: challenges for collaborative research

Song M, Rolland B, Potter JD, Kang D

J Epidemiol, 2012;22(4):287-90.
PMID: 22672913 DOI: 10.2188/jea.je20120024

In this era of chronic diseases, large studies are essential in investigating genes, environment, and gene-environment interactions as disease causes, particularly when associations are important but not strong. Moreover, to allow expansion and generalization of the results, studies should be conducted in populations outside Western countries. Here, we briefly describe the Asia Cohort Consortium (ACC), a collaborative cancer cohort research project that was first proposed in 2004 and now involves more than 1 million healthy individuals across Asia. There are approximately 50 active members from Bangladesh, China, India, Japan, Korea, Malaysia, Singapore, Taiwan, Thailand, the United States, and elsewhere. To date, the work of the ACC includes 3 articles published in 2011 on the roles of body mass index, tobacco smoking, and alcohol consumption in mortality, diabetes, and cancer of the small intestine. Many challenges remain, including data harmonization, resolution of ethical and legal issues, establishment of protocols for biologic samples and transfer agreements, and funding procurement.
Technology transfer for green investments: exploring how technology transfer through foreign direct investments can contribute to sustainable practices and reduced environmental impact in OIC economies

Song M, Anees A, Rahman SU, Ali MSE

Environ Sci Pollut Res Int, 2024 Feb;31(6):8812-8827.
PMID: 38180671 DOI: 10.1007/s11356-023-31553-x

Estimating the asymmetrical influence of foreign direct investment is the primary goal of the current study. In addition, further controlled variables affect environmental degradation in OIC nations. Due to this, current research employs the asymmetric (NPARDL) approach and the data period from 1980 to 2021 to estimate about viability of the EKC (environmental Kuznets curve) theory. The study utilized greenhouse gas (GHG) including emissions of carbon dioxide (CO2), nitrous oxide (N2O), methane (CH4), and ecological footprint as substantial parameters of environmental quality. A nonlinear link between foreign direct investments, trade openness, economic growth, urbanization, energy consumption, and environmental pollution with CO2, N2O, CH4, and ecological footprint in the OIC nations is confirmed by the study's outcomes, which however reveals inconsistent results. Furthermore, the results also show that wrong conclusions might result from disregarding intrinsic nonlinearities. The study's conclusions provide the most important recommendations for decision-makers.
Fulltext An all-silk-derived bilayer hydrogel for osteochondral tissue engineering

Jiang W, Xiang X, Song M, Shen J, Shi Z, Huang W, et al.

Mater Today Bio, 2022 Dec 15;17:100485.
PMID: 36388458 DOI: 10.1016/j.mtbio.2022.100485

Osteochondral repair remains a challenge in clinical practice nowadays despite extensive advances in tissue engineering. The insufficient recruitment of endogenous cells in the early stage and incomplete cell differentiation in the later stage constitute the major difficulty of osteochondral repair. Here, a novel all-silk-derived multifunctional biomaterial platform for osteochondral engineering is reported. The bilayer methacrylated silk fibroin (SilMA) hydrogel was fabricated through stratified photocuring as the basic provisional matrix for tissue regeneration. Platelet-rich plasma (PRP) incorporation promoted the migration and pre-differentiation of the bone marrow mesenchymal stem cells (BMSCs) in the early stage of implantation. The long-term regulation of BMSCs chondrogenesis and osteogenesis was realized by the stratified anchoring of the silk fibroin (SF) microspheres respectively loaded with Kartogenin (KGN) and berberine (BBR) in the hydrogel. The composite hydrogels were further demonstrated to promote BMSCs chondrogenic and osteogenic differentiation under an inflammatory microenvironment and to achieve satisfying cartilage and subchondral bone regeneration with great biocompatibility after 8 weeks of implantation. Since all the components used are readily available and biocompatible and can be efficiently integrated via a simple process, this composite hydrogel scaffold has tremendous potential for clinical use in osteochondral regeneration.
Levels of Ancylostoma infections and phylogenetic analysis of cox 1 gene of A. ceylanicum in stray cat faecal samples from Guangzhou, China

Hu W, Yu XG, Wu S, Tan LP, Song MR, Abdulahi AY, et al.

J Helminthol, 2016 Jul;90(4):392-7.
PMID: 26123649 DOI: 10.1017/S0022149X15000413

Ancylostoma ceylanicum is a common zoonotic nematode. Cats act as natural reservoirs of the hookworm and are involved in transmitting infection to humans, thus posing a potential risk to public health. The prevalence of feline A. ceylanicum in Guangzhou (South China) was surveyed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In total, 112 faecal samples were examined; 34.8% (39/112) and 43.8% (49/112) samples were positive with hookworms by microscopy and PCR method, respectively. Among them, 40.8% of samples harboured A. ceylanicum. Twelve positive A. ceylanicum samples were selected randomly and used for cox 1 sequence analysis. Sequencing results revealed that they had 97-99% similarity with A. ceylanicum cox 1 gene sequences deposited in GenBank. A phylogenetic tree showed that A. ceylanicum isolates were divided into two groups: one comprising four isolates from Guangzhou (South China), and the other comprising those from Malaysia, Cambodia and Guangzhou. In the latter group, all A. ceylanicum isolates from Guangzhou were clustered into a minor group again. The results indicate that the high prevalence of A. ceylanicum in stray cats in South China poses a potential risk of hookworm transmission from pet cats to humans, and that A. ceylanicum may be a species complex worldwide.
Clinical features and treatment of nonalcoholic fatty liver disease across the Asia Pacific region-the GO ASIA initiative

Chan WK, Treeprasertsuk S, Imajo K, Nakajima A, Seki Y, Kasama K, et al.

Aliment Pharmacol Ther, 2018 Mar;47(6):816-825.
PMID: 29333610 DOI: 10.1111/apt.14506

BACKGROUND: The Gut and Obesity Asia (GO ASIA) workgroup was formed to study the relationships between obesity and gastrointestinal diseases in the Asia Pacific region.
AIM: To study factors associated with nonalcoholic steatohepatitis (NASH) and advanced fibrosis, and medical treatment of biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients.
METHODS: Retrospective study of biopsy-proven NAFLD patients from centres in the GO ASIA Workgroup. Independent factors associated with NASH and with advanced fibrosis on binary logistic regression analyses in a training cohort were used for the development of their corresponding risk score, which were validated in a validation cohort.
RESULTS: We included 1008 patients from nine centres across eight countries (NASH 62.9%, advanced fibrosis 17.2%). Independent predictors of NASH were body mass index ≥30 kg/m2 , diabetes mellitus, dyslipidaemia, alanine aminotransferase ≥88 U/L and aspartate aminotransferase ≥38 U/L, constituting the Asia Pacific NASH risk score. A high score has a positive predictive value of 80%-83% for NASH. Independent predictors of advanced fibrosis were age ≥55 years, diabetes mellitus and platelet count <150 × 109 /L, constituting the Asia-Pacific NAFLD advanced fibrosis risk score. A low score has a negative predictive value of 95%-96% for advanced fibrosis. Only 1.7% of patients were referred for structured lifestyle program, 4.2% were on vitamin E, and 2.4% were on pioglitazone.
CONCLUSIONS: More severe liver disease can be suspected or ruled out based on factors identified in this study. Utilisation of structured lifestyle program, vitamin E and pioglitazone was limited despite this being a cohort of biopsy-proven NAFLD patients with majority of patients having NASH.
NEDD4L contributes to ferroptosis and cell growth inhibition in esophageal squamous cell carcinoma by facilitating xCT ubiquitination

Chen Z, Wang W, Hou J, Gao C, Song M, Zhao Z, et al.

Cell Death Discov, 2024 Nov 18;10(1):473.
PMID: 39557844 DOI: 10.1038/s41420-024-02243-5

The oncogene xCT plays an indispensable role in tumor growth by protecting cancer cells from oxidative stress and ferroptosis. Emerging evidence indicated xCT function is tightly controlled by posttranslational modifications, especially ubiquitination. However, it still remains unclear what specific regulatory mechanism of xCT by ubiquitin ligases in human cancers. Here, we reported that NEDD4L, an E3 ubiquitin ligases, inhibited esophageal squamous cell carcinoma (ESCC) tumor growth and facilitated ferroptosis by ubiquitination of xCT. NEDD4L expression was declined in ESCC and was associated with tumor invasion, lymph node metastasis and distant metastasis. Silencing NEDD4L triggered ESCC tumor growth. Meanwhile, knock down of NEDD4L prevented the accumulation of ROS, elevated the level of GSH, reduced the content of MDA in ESCC cells, thereby inhibiting ferroptosis. Mechanistically, NEDD4L directly bound to the ∆CT domain of xCT through its WW and HECT domain. More importantly, NEDD4L promoted xCT degradation by facilitating its polyubiquitination in ESCC cells. Collectively, these findings suggest that NEDD4L is crucial in governing the stability of xCT and mediating ferroptosis in ESCC.
Fulltext Association of Circulating Vitamin D With Colorectal Cancer Depends on Vitamin D-Binding Protein Isoforms: A Pooled, Nested, Case-Control Study

Gibbs DC, Song M, McCullough ML, Um CY, Bostick RM, Wu K, et al.

JNCI Cancer Spectr, 2020 Feb;4(1):pkz083.
PMID: 32337495 DOI: 10.1093/jncics/pkz083

BACKGROUND: Higher circulating 25-hydroxyvitamin-D [25(OH)D] concentrations are consistently inversely associated with colorectal cancer (CRC) risk in observational studies. However, it is unknown whether this association depends on the functional GC-rs4588*A (Thr436Lys) variant encoding the vitamin D-binding protein-2 (DBP2) isoform, which may affect vitamin D status and bioavailability.
METHODS: We analyzed data from 1710 incident CRC cases and 1649 incidence-density-matched controls nested within three prospective cohorts of mostly Caucasians. Study-specific incidence rate ratios (RRs) for associations of prediagnostic, season-standardized 25(OH)D concentrations according to DBP2 isoform with CRC were estimated using multivariable unconditional logistic regression and were pooled using fixed-effects models. All statistical significance tests were two-sided.
RESULTS: The odds of having 25(OH)D concentrations less than 50 nmol/L (considered insufficient by the Institute of Medicine) were 43% higher for each DBP2-encoding variant (rs4588*A) inherited (per DBP2 odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.27 to 1.62, P trend = 1.2 × 10-8). The association of 25(OH)D concentrations with CRC risk differed by DBP2: 25(OH)D concentrations considered sufficient (≥ 50 nmol/L), relative to deficient (
Fulltext Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer: a Mendelian Randomization analysis using data from three large cohort studies

Nimptsch K, Song M, Aleksandrova K, Katsoulis M, Freisling H, Jenab M, et al.

Eur J Epidemiol, 2017 May;32(5):419-430.
PMID: 28550647 DOI: 10.1007/s10654-017-0262-y

Higher levels of circulating adiponectin have been related to lower risk of colorectal cancer in several prospective cohort studies, but it remains unclear whether this association may be causal. We aimed to improve causal inference in a Mendelian Randomization meta-analysis using nested case-control studies of the European Prospective Investigation into Cancer and Nutrition (EPIC, 623 cases, 623 matched controls), the Health Professionals Follow-up Study (HPFS, 231 cases, 230 controls) and the Nurses' Health Study (NHS, 399 cases, 774 controls) with available data on pre-diagnostic adiponectin concentrations and selected single nucleotide polymorphisms in the ADIPOQ gene. We created an ADIPOQ allele score that explained approximately 3% of the interindividual variation in adiponectin concentrations. The ADIPOQ allele score was not associated with risk of colorectal cancer in logistic regression analyses (pooled OR per score-unit unit 0.97, 95% CI 0.91, 1.04). Genetically determined twofold higher adiponectin was not significantly associated with risk of colorectal cancer using the ADIPOQ allele score as instrumental variable (pooled OR 0.73, 95% CI 0.40, 1.34). In a summary instrumental variable analysis (based on previously published data) with higher statistical power, no association between genetically determined twofold higher adiponectin and risk of colorectal cancer was observed (0.99, 95% CI 0.93, 1.06 in women and 0.94, 95% CI 0.88, 1.01 in men). Thus, our study does not support a causal effect of circulating adiponectin on colorectal cancer risk. Due to the limited genetic determination of adiponectin, larger Mendelian Randomization studies are necessary to clarify whether adiponectin is causally related to lower risk of colorectal cancer.
Fulltext Physical activity and risks of breast and colorectal cancer: a Mendelian randomisation analysis

Papadimitriou N, Dimou N, Tsilidis KK, Banbury B, Martin RM, Lewis SJ, et al.

Nat Commun, 2020 01 30;11(1):597.
PMID: 32001714 DOI: 10.1038/s41467-020-14389-8

Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers.