Displaying publications 1 - 20 of 227 in total

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  1. Wu YS, Osman AI, Hosny M, Elgarahy AM, Eltaweil AS, Rooney DW, et al.
    ACS Omega, 2024 Feb 06;9(5):5100-5126.
    PMID: 38343989 DOI: 10.1021/acsomega.3c07047
    Mercury is a type of hazardous and toxic pollutant that can result in detrimental effects on the environment and human health. This review is aimed at discussing the state-of-the-art progress on the recent developments on the toxicity of mercury and its chemical compounds. More than 210 recent works of literature are covered in this review. It first delineates the types (covering elemental mercury, inorganic mercury compounds, organic mercury compounds), structures, and sources of mercury. It then discusses the pharmacokinetic profile of mercury, molecular mechanisms of mercury toxicity, and clinical manifestation of acute and chronic mercury toxicity to public health. It also elucidates the mercury toxicity to the environment and human health in detail, covering ecotoxicity, neurotoxicity diseases, neurological diseases, genotoxicity and gene regulation, immunogenicity, pregnancy and reproductive system damage, cancer promotion, cardiotoxicity, pulmonary diseases, and renal disease. In order to mitigate the adverse effects of mercury, strategies to overcome mercury toxicity are recommended. Finally, some future perspectives are provided in order to advance this field of research in the future.
  2. Dorison CA, Lerner JS, Heller BH, Rothman AJ, Kawachi II, Wang K, et al.
    Affect Sci, 2022 Sep;3(3):577-602.
    PMID: 36185503 DOI: 10.1007/s42761-022-00128-3
    The COVID-19 pandemic (and its aftermath) highlights a critical need to communicate health information effectively to the global public. Given that subtle differences in information framing can have meaningful effects on behavior, behavioral science research highlights a pressing question: Is it more effective to frame COVID-19 health messages in terms of potential losses (e.g., "If you do not practice these steps, you can endanger yourself and others") or potential gains (e.g., "If you practice these steps, you can protect yourself and others")? Collecting data in 48 languages from 15,929 participants in 84 countries, we experimentally tested the effects of message framing on COVID-19-related judgments, intentions, and feelings. Loss- (vs. gain-) framed messages increased self-reported anxiety among participants cross-nationally with little-to-no impact on policy attitudes, behavioral intentions, or information seeking relevant to pandemic risks. These results were consistent across 84 countries, three variations of the message framing wording, and 560 data processing and analytic choices. Thus, results provide an empirical answer to a global communication question and highlight the emotional toll of loss-framed messages. Critically, this work demonstrates the importance of considering unintended affective consequences when evaluating nudge-style interventions.
  3. Albert C, Zapf A, Haase M, Röver C, Pickering JW, Albert A, et al.
    Am J Kidney Dis, 2020 12;76(6):826-841.e1.
    PMID: 32679151 DOI: 10.1053/j.ajkd.2020.05.015
    RATIONALE & OBJECTIVE: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction.

    STUDY DESIGN: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines.

    SETTING & STUDY POPULATIONS: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms.

    SELECTION CRITERIA FOR STUDIES: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI.

    DATA EXTRACTION: Individual-study-data meta-analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis.

    ANALYTICAL APPROACH: Individual-study-data meta-analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses.

    RESULTS: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.79-0.81) and 0.86 (95% CI, 0.84-0.86). Cutoff concentrations at 95% specificity for urinary NGAL were>580ng/mL with 27% sensitivity for severe AKI and>589ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were>364ng/mL with 44% sensitivity and>546ng/mL with 26% sensitivity, respectively.

    LIMITATIONS: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies.

    CONCLUSIONS: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.

  4. Chen L, Xu YY, Lin JY, Ji ZP, Yang F, Tan S, et al.
    Asian J Psychiatr, 2024 Mar;93:103958.
    PMID: 38364597 DOI: 10.1016/j.ajp.2024.103958
    BACKGROUND AND AIM: Suicide is nearly always associated with underlying mental disorders. Risk factors for suicide attempts (SAs) in patients with bipolar disorder (BD) misdiagnosed with major depressive disorder (MDD) remain unelucidated. This study was to evaluate the prevalence and clinical risk factors of SAs in Chinese patients with BD misdiagnosed with MDD.

    METHODS: A total of 1487 patients with MDD from 13 mental health institutions in China were enrolled. Mini International Neuropsychiatric Interview (MINI) was used to identify patients with BD who are misdiagnosed as MDD. The general sociodemographic and clinical data of the patients were collected and MINI suicide module was used to identify patients with SAs in these misdiagnosed patients.

    RESULTS: In China, 20.6% of patients with BD were incorrectly diagnosed as having MDD. Among these misdiagnosed patients, 26.5% had attempted suicide. These patients tended to be older, had a higher number of hospitalizations, and were more likely to experience frequent and seasonal depressive episodes with atypical features, psychotic symptoms, and suicidal thoughts. Frequent depressive episodes and suicidal thoughts during depression were identified as independent risk factors for SAs. Additionally, significant sociodemographic and clinical differences were found between individuals misdiagnosed with MDD in BD and patients with MDD who have attempted suicide.

    CONCLUSIONS: This study highlights the importance of accurate diagnosis in individuals with BD and provide valuable insights for the targeted identification and intervention of individuals with BD misdiagnosed as having MDD and those with genuine MDD, particularly in relation to suicidal behavior.

  5. Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.
    Autophagy, 2021 Jan;17(1):1-382.
    PMID: 33634751 DOI: 10.1080/15548627.2020.1797280
    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
  6. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
  7. Chen Z, Song J, Tang L
    BMC Oral Health, 2023 Nov 02;23(1):827.
    PMID: 37919698 DOI: 10.1186/s12903-023-03575-x
    OBJECTIVE: Several research has considered the potential correlation between periodontitis and serum lipids. However, serum lipid profiles correlation with periodontitis remains largely unknown. The investigation objective was to examine periodontitis correlation with serum lipid levels using a bidirectional Mendelian randomization (MR) analysis.

    METHODS: The study employed a bidirectional MR analysis with two samples, utilizing a freely accessible genome-wide association study (GWAS). Furthermore, the primary analysis employed the inverse variance weighted (IVW) method. To determine whether the lipid profiles were associated with periodontitis, a variety of sensitivity analyses (including MR-Egger regression, MR-PRESSO, and weighted median), as well as multivariable MR, were employed.

    RESULTS: MR analysis performed by IVW did not reveal any relationship between periodontitis and low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), or total cholesterol (TC). It was also found that LDL, HDL, TG, and TC were not associated to periodontitis. Furthermore, the MR estimations exhibited consistency with other MR sensitivity and multivariate MR (MVMR) analyses. These results show that the correlation between serum lipid levels and periodontitis could not be established.

    CONCLUSION: The finding indicates a negligible link between periodontitis and serum lipid levels were identified, despite previous observational studies reporting a link between periodontitis and serum lipid levels.

  8. Vermunt J, Bragg F, Halsey J, Yang L, Chen Y, Guo Y, et al.
    PMID: 34728472 DOI: 10.1136/bmjdrc-2021-002495
    INTRODUCTION: We examined the associations between long-term usual random plasma glucose (RPG) levels and cause-specific mortality risks among adults without known diabetes in China.

    RESEARCH DESIGN AND METHODS: The China Kadoorie Biobank recruited 512,891 adults (59% women) aged 30-79 from 10 regions of China during 2004-2008. At baseline survey, and subsequent resurveys of a random subset of survivors, participants were interviewed and measurements collected, including on-site RPG testing. Cause of death was ascertained via linkage to local mortality registries. Cox regression yielded adjusted HR for all-cause and cause-specific mortality associated with usual levels of RPG.

    RESULTS: During median 11 years' follow-up, 37,214 deaths occurred among 452,993 participants without prior diagnosed diabetes or other chronic diseases. There were positive log-linear relationships between RPG and all-cause, cardiovascular disease (CVD) (n=14,209) and chronic kidney disease (CKD) (n=432) mortality down to usual RPG levels of at least 5.1 mmol/L. At RPG <11.1 mmol/L, each 1.0 mmol/L higher usual RPG was associated with adjusted HRs of 1.14 (95% CI 1.12 to 1.16), 1.16 (1.12 to 1.19) and 1.44 (1.22 to 1.70) for all-cause, CVD and CKD mortality, respectively. Usual RPG was positively associated with chronic liver disease (n=547; 1.45 (1.26 to 1.66)) and cancer (n=12,680; 1.12 (1.09 to 1.16)) mortality, but with comparably lower risks at baseline RPG ≥11.1 mmol/L. These associations persisted after excluding participants who developed diabetes during follow-up.

    CONCLUSIONS: Among Chinese adults without diabetes, higher RPG levels were associated with higher mortality risks from several major diseases, with no evidence of apparent thresholds below the cut-points for diabetes diagnosis.

  9. Chen Y, Chen Y, Shi W, Hu S, Huang Q, Liu GS, et al.
    Biosens Bioelectron, 2022 Feb 15;198:113787.
    PMID: 34864241 DOI: 10.1016/j.bios.2021.113787
    High sensitivity and capturing ratio are strongly demanded for surface plasmon resonance (SPR) sensors when applied in detection of small molecules. Herein, an SPR sensor is combined with a novel smart material, namely, MoS2 nanoflowers (MNFs), to demonstrate programmable adsorption/desorption of small bipolar molecules, i.e., amino acids. The MNFs overcoated on the plasmonic gold layer increase the sensitivity by 25% compared to an unmodified SPR sensor, because of the electric field enhancement at the gold surface. Furthermore, as the MNFs have rich edge sites and negatively charged surfaces, the MNF-SPR sensors exhibit not only much higher bipolar-molecule adsorption capability, but also efficient desorption of these molecules. It is demonstrated that the MNF-SPR sensors enable controllable detection of amino acids by adjusting solution pH according to their isoelectric points. In addition, the MNFs decorated on the plasmonic interface can be as nanostructure frameworks and modified with antibody, which allows for specific detection of proteins. This novel SPR sensor provides a new simple strategy for pre-screening of amino acid disorders in blood plasma and a universal high-sensitive platform for immunoassay.
  10. Li Z, Lee SHR, Chin WHN, Lu Y, Jiang N, Lim EH, et al.
    Blood Adv, 2021 12 14;5(23):5226-5238.
    PMID: 34547766 DOI: 10.1182/bloodadvances.2021004895
    Among the recently described subtypes in childhood B-lymphoblastic leukemia (B-ALL) were DUX4- and PAX5-altered (PAX5alt). By using whole transcriptome RNA sequencing in 377 children with B-ALL from the Malaysia-Singapore ALL 2003 (MS2003) and Malaysia-Singapore ALL 2010 (MS2010) studies, we found that, after hyperdiploid and ETV6-RUNX1, the third and fourth most common subtypes were DUX4 (n = 51; 14%) and PAX5alt (n = 36; 10%). DUX4 also formed the largest genetic subtype among patients with poor day-33 minimal residual disease (MRD; n = 12 of 44). But despite the poor MRD, outcome of DUX4 B-ALL was excellent (5-year cumulative risk of relapse [CIR], 8.9%; 95% confidence interval [CI], 2.8%-19.5% and 5-year overall survival, 97.8%; 95% CI, 85.3%-99.7%). In MS2003, 21% of patients with DUX4 B-ALL had poor peripheral blood response to prednisolone at day 8, higher than other subtypes (8%; P = .03). In MS2010, with vincristine at day 1, no day-8 poor peripheral blood response was observed in the DUX4 subtype (P = .03). The PAX5alt group had an intermediate risk of relapse (5-year CIR, 18.1%) but when IKZF1 was not deleted, outcome was excellent with no relapse among 23 patients. Compared with MS2003, outcome of PAX5alt B-ALL with IKZF1 codeletion was improved by treatment intensification in MS2010 (5-year CIR, 80.0% vs 0%; P = .05). In conclusion, despite its poor initial response, DUX4 B-ALL had a favorable overall outcome, and the prognosis of PAX5alt was strongly dependent on IKZF1 codeletion.
  11. Wang W, Zhou F, Chang Y, Cui J, He D, Du J, et al.
    Bull Environ Contam Toxicol, 2020 Mar;104(3):380-385.
    PMID: 31932904 DOI: 10.1007/s00128-020-02786-0
    In this study, three soil amendments (inorganic, liming, or organic-inorganic materials) were used in a Cd-contaminated purple field soil to investigate their impacts on soil Cd availability, enzyme (urease, catalase, sucrase, and acid phosphatase) activities, microbial biomass (carbon/nitrogen) and type (bacteria, fungi, and actinomycetes) in mustard and corn trials. Results showed that soil amendments generally decreased soil exchangeable Cd, fungi and bacterial populations while increasing the activities of all the four soil enzymes tested, microbial biomass carbon and populations of actinomycetes (p  0.05) whereas stronger effects appeared in soil organic matter and available nutrients (nitrogen, phosphorous and potassium; p 
  12. Chung HC, Kang YK, Chen Z, Bai Y, Wan Ishak WZ, Shim BY, et al.
    Cancer, 2022 Mar 01;128(5):995-1003.
    PMID: 34878659 DOI: 10.1002/cncr.34019
    BACKGROUND: KEYNOTE-063 (NCT03019588) investigated pembrolizumab versus paclitaxel as second-line therapy in Asian patients with advanced programmed death ligand 1 (PD-L1)-positive (combined positive score ≥1) gastric/gastroesophageal junction (GEJ) cancer.

    METHODS: This randomized, open-label, phase 3 study was conducted at 36 medical centers in China (mainland), Malaysia, South Korea, and Taiwan. Patients were randomly assigned 1:1 to 200 mg of pembrolizumab intravenously every 3 weeks for ≤2 years or 80 mg/m2 of paclitaxel intravenously every week. Primary end points were overall survival (OS) and progression-free survival (PFS). Secondary end points were objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 and safety.

    RESULTS: Between February 16, 2017, and March 12, 2018, 94 patients were randomly assigned (47 pembrolizumab/47 paclitaxel) after screening; enrollment was stopped on March 12, 2018, based on the results of the global KEYNOTE-061 study, and patients were followed until the last patient's last visit. Median OS was 8 months (95% confidence interval [CI], 4-10 months) with pembrolizumab versus 8 months (95% CI, 5-11 months) with paclitaxel (hazard ratio [HR], 0.99; 95% CI, 0.63-1.54). Median PFS was 2 months (95% CI, 1-3 months) with pembrolizumab versus 4 months (95% CI, 3-6 months) with paclitaxel (HR, 1.62; 95% CI, 1.04-2.52). ORR was 13% for pembrolizumab versus 19% for paclitaxel. Any-grade treatment-related adverse events occurred in 28 pembrolizumab-treated patients (60%) and 42 paclitaxel-treated patients (96%); grades 3 to 5 events occurred in 5 patients (11%) and 28 patients (64%), respectively.

    CONCLUSIONS: Definitive conclusions about the efficacy of second-line pembrolizumab in Asian patients with advanced PD-L1-positive gastric/GEJ cancer are limited because of insufficient power, but pembrolizumab was well tolerated in this patient population. Efficacy followed a trend similar to that observed in the phase 3 KEYNOTE-061 trial.

  13. Glubb DM, Thompson DJ, Aben KKH, Alsulimani A, Amant F, Annibali D, et al.
    Cancer Epidemiol Biomarkers Prev, 2021 Jan;30(1):217-228.
    PMID: 33144283 DOI: 10.1158/1055-9965.EPI-20-0739
    BACKGROUND: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers.

    METHODS: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data.

    RESULTS: Genetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10-5). We found seven loci associated with risk for both cancers (P Bonferroni < 2.4 × 10-9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P < 5 × 10-7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation.

    CONCLUSIONS: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis.

    IMPACT: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.

  14. Kar SP, Tyrer JP, Li Q, Lawrenson K, Aben KK, Anton-Culver H, et al.
    Cancer Epidemiol Biomarkers Prev, 2015 Oct;24(10):1574-84.
    PMID: 26209509 DOI: 10.1158/1055-9965.EPI-14-1270
    BACKGROUND: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations.

    METHODS: We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls).

    RESULTS: Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network.

    CONCLUSION: We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development.

    IMPACT: Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization.

  15. Ochieng J, Nangami GN, Ogunkua O, Miousse IR, Koturbash I, Odero-Marah V, et al.
    Carcinogenesis, 2015 Jun;36 Suppl 1:S128-59.
    PMID: 26106135 DOI: 10.1093/carcin/bgv034
    The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of low-dose environmental mixtures and carcinogens in the promotion of invasion and metastasis in specific tumors such as breast and prostate, the overarching theme is the role of low-dose carcinogens in the progression of cancer stem cells. It is becoming clearer that cancer stem cells in a tumor are the ones that assume invasive properties and colonize distant organs. Therefore, low-dose contaminants that trigger epithelial-mesenchymal transition, for example, in these cells are of particular interest in this review. This we hope will lead to the collaboration between scientists who have dedicated their professional life to the study of carcinogens and those whose interests are exclusively in the arena of tissue invasion and metastasis.
  16. Goodson WH, Lowe L, Carpenter DO, Gilbertson M, Manaf Ali A, Lopez de Cerain Salsamendi A, et al.
    Carcinogenesis, 2015 Jun;36 Suppl 1:S254-96.
    PMID: 26106142 DOI: 10.1093/carcin/bgv039
    Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.
  17. Lawrenson K, Iversen ES, Tyrer J, Weber RP, Concannon P, Hazelett DJ, et al.
    Carcinogenesis, 2015 Nov;36(11):1341-53.
    PMID: 26424751 DOI: 10.1093/carcin/bgv138
    Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1×10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72×10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.
  18. Chen Z, Wang W, Abdul Razak SR, Han T, Ahmad NH, Li X
    Cell Death Dis, 2023 Jul 24;14(7):460.
    PMID: 37488128 DOI: 10.1038/s41419-023-05930-w
    Ferroptosis is a recently discovered essential type of cell death that is mainly characterized by iron overload and lipid peroxidation. Emerging evidence suggests that ferroptosis is a double-edged sword in human cancer. However, the precise underlying molecular mechanisms and their differential roles in tumorigenesis are unclear. Therefore, in this review, we summarize and briefly present the key pathways of ferroptosis, paying special attention to the regulation of ferroptosis as well as its dual role as an oncogenic and as a tumor suppressor event in various human cancers. Moreover, multiple pharmacological ferroptosis activators are summarized, and the prospect of targeting ferroptosis in cancer therapy is further elucidated.
  19. Sargsian S, Chen Z, Lee SC, Robertson A, Thur RS, Sproch J, et al.
    Cell Rep, 2022 Nov 29;41(9):111725.
    PMID: 36450245 DOI: 10.1016/j.celrep.2022.111725
    Soil-transmitted intestinal worms known as helminths colonize over 1.5 billion people worldwide. Although helminth colonization has been associated with altered composition of the gut microbiota, such as increases in Clostridia, individual species have not been isolated and characterized. Here, we isolate and sequence the genome of 13 Clostridia from the Orang Asli, an indigenous population in Malaysia with a high prevalence of helminth infections. Metagenomic analysis of 650 fecal samples from urban and rural Malaysians confirm the prevalence of species corresponding to these isolates and reveal a specific association between Peptostreptococcaceae family members and helminth colonization. Remarkably, Peptostreptococcaceae isolated from the Orang Asli display superior capacity to promote the life cycle of whipworm species, including hatching of eggs from Trichuris muris and Trichuris trichiura. These findings support a model in which helminths select for gut colonization of microbes that support their life cycle.
  20. Sun Y, Tang H, Du S, Chen Y, Ou Z, Zhang M, et al.
    Eco Environ Health, 2023 Dec;2(4):208-218.
    PMID: 38435359 DOI: 10.1016/j.eehl.2023.08.001
    Indoor microorganisms impact asthma and allergic rhinitis (AR), but the associated microbial taxa often vary extensively due to climate and geographical variations. To provide more consistent environmental assessments, new perspectives on microbial exposure for asthma and AR are needed. Home dust from 97 cases (32 asthma alone, 37 AR alone, 28 comorbidity) and 52 age- and gender-matched controls in Shanghai, China, were analyzed using high-throughput shotgun metagenomic sequencing and liquid chromatography-mass spectrometry. Homes of healthy children were enriched with environmental microbes, including Paracoccus, Pseudomonas, and Psychrobacter, and metabolites like keto acids, indoles, pyridines, and flavonoids (astragalin, hesperidin) (False Discovery Rate 
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