Publications by authors named "A Tan"

3,849 Publications

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The correlation between serum total alkaline phosphatase and bone mineral density in young adults.

BMC Musculoskelet Disord 2022 May 18;23(1):467. Epub 2022 May 18.

Department of Geriatrics, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650034, Yunnan, People's Republic of China.

Background: Elevated total alkaline phosphatase (T-ALP) levels are usually indicative of enhanced osteoblastic activity and bone conversion status and are thus considered as a key factor needed for fresh bone mineralization and synthesis. To date, there is no consistent conclusion on the association between the serum T-ALP levels and bone mineral density (BMD). Therefore, the present study focused on exploring the association of serum T-ALP with lumbar BMD among young adults.

Methods: The present cross-sectional study included 6,331 subjects included in the National Health and Nutrition Examination Survey (NHANES) during 2011-2016. The participants aged 20-40 years included 3,349 males and 2,982 females. Serum T-ALP was our main variable, lumbar BMD was our outcome variable, and additional variables were the possible impact modifiers. The relations were analysed by the trend study, weighted multiple linear regression models, smooth curve fitting, and stratified analyses.

Results: In a completely corrected multiple regression model, a negative association between serum T-ALP and lumbar BMD was discovered (β = -0.0007, 95% CI: -0.0009- -0.0005, P < 0.000001). After converting the continuous variable serum T-ALP into the categorical one, the significant negative association was still observed (P < 0.001), and in the subgroup and smooth curve fitting analyses, this negative correlation remained significant, too.

Conclusions: Our study results indicated that serum T-ALP was negatively associated with lumbar BMD among young adults. Serum T-ALP measurement in the near future might become an effective biomarker to diagnose and treat osteoporosis on time.
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http://dx.doi.org/10.1186/s12891-022-05438-yDOI Listing
May 2022

Native mitral valve endocarditis masquerading as ST-segment elevation myocardial infarction.

Clin Med (Lond) 2022 May;22(3):287-289

National Heart Centre Singapore, Singapore.

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http://dx.doi.org/10.7861/clinmed.2022-0067DOI Listing
May 2022

Chromatin Rewiring by Mismatch Repair Protein MSH2 Alters Cell Adhesion Pathways and Sensitivity to BET Inhibition in Gastric Cancer.

Cancer Res 2022 May 18. Epub 2022 May 18.

Duke NUS Graduate Medical School, Singapore, Singapore.

Mutations in the DNA mismatch repair gene MSH2 are causative of microsatellite instability (MSI) in multiple cancers. Here, we discovered that besides its well-established role in DNA repair, MSH2 exerts a novel epigenomic function in gastric cancer (GC). Unbiased CRISPR-based mass spectrometry combined with genome-wide CRISPR functional screening revealed that in early-stage GC MSH2 genomic binding is not randomly distributed but rather is associated specifically with tumor-associated super-enhancers controlling the expression of cell adhesion genes. At these loci, MSH2 genomic binding was required for chromatin rewiring, de novo enhancer-promoter interactions, maintenance of histone acetylation levels, and regulation of cell adhesion pathway expression. The chromatin function of MSH2 was independent of its DNA repair catalytic activity but required MSH6, another DNA repair gene, and recruitment to gene loci by the SWI/SNF chromatin remodeler SMARCA4/BRG1. Loss of MSH2 in advanced GCs was accompanied by deficient cell adhesion pathway expression, epithelial-mesenchymal transition, and enhanced tumorigenesis in vitro and in vivo. However, MSH2-deficient GCs also displayed addiction to BAZ1B, a bromodomain-containing family member, and consequent synthetic lethality to bromodomain and extra-terminal motif (BET) inhibition. Our results reveal a role for MSH2 in GC epigenomic regulation and identify BET inhibition as a potential therapy in MSH2-deficient gastric malignancies.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-2072DOI Listing
May 2022

Genotyping of respiratory syncytial virus among influenza-like illness and severe acute respiratory infection cases of children in the Philippines from 2006 to 2016.

Influenza Other Respir Viruses 2022 May 18. Epub 2022 May 18.

Department of Virology, Research Institute for Tropical Medicine, Muntinlupa, Philippines.

Objective: Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory infection, and therefore, a major threat to global health. This study determined the epidemiological and molecular characteristics of RSV among cases of influenza-like illness (ILI) and severe acute respiratory infection (SARI) among children in the Philippines.

Method: The study included archived nasopharyngeal swab and oropharyngeal swab samples collected from patients under the age of five who are presented with ILI or SARI for the period of 2006-2016. Swabs were examined for RSV subgroup by multiplex real-time qRT-PCR. Partial genome sequencing and phylogenetic analyses of the second hypervariable region (HVR) of the G gene were used to determine the genotype of RSV isolates.

Results: A total of 1036 representative samples from all sites were selected and tested. Of these samples, 122 were RSV-positive at 11.8% prevalence rate, and 58.2% (71/122) were classified as RSV-A. Six genotypes were identified, which include NA1 (27/122, 22.1%), ON1 (5/122, 4.1%), GA2 (1/122, 0.8%), and GA5 (1/122, 0.8%) for RSV-A; and BA2 (13/122, 10.7%) and BA9 (1/122, 0.8%) for RSV-B. Most RSV-related cases were significantly associated with clinical characteristics such as runny nose (88.1% RSV vs. 11.9% non-RSV: p value = 0.021), pneumonia (80.6% RSV vs. 19.4% non-RSV; p value = 0.015), and bronchitis (71.7% RSV vs. 28.3% non-RSV; p value < 0.001). Increased RSV-related cases were observed among children below 24 months old.

Conclusion: The RSV trend and genetic variability in the Philippines resembles a similar pattern of transmission globally.
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http://dx.doi.org/10.1111/irv.12986DOI Listing
May 2022

Deficiency of the splicing factor RBM10 limits EGFR inhibitor response in EGFR mutant lung cancer.

J Clin Invest 2022 May 17. Epub 2022 May 17.

UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, United States of America.

Molecularly targeted cancer therapy has improved outcomes for cancer patients with targetable oncoproteins, such as mutant epidermal growth factor receptor (EGFR) in lung cancer. Yet, long-term patient survival remains limited because treatment responses are typically incomplete. One potential explanation for the lack of complete and durable responses is that oncogene-driven cancers with activating mutations in the EGFR often harbor additional co-occurring genetic alterations. This hypothesis remains untested for most genetic alterations that co-occur with mutant EGFR. Here, we report the functional impact of inactivating genetic alteration of the mRNA splicing factor RBM10 that co-occur with mutant EGFR. RBM10 deficiency decreased EGFR inhibitor efficacy in patient-derived EGFR mutant tumor models. RBM10 modulated mRNA alternative splicing of the mitochondrial apoptotic regulator Bcl-x to regulate tumor cell apoptosis during treatment. Genetic inactivation of RBM10 diminished EGFR inhibitor-mediated apoptosis by decreasing the ratio of Bcl-xS-(pro-apoptotic)-to-Bcl-xL(anti-apoptotic) Bcl-x isoforms. RBM10 deficiency was a biomarker of poor response to EGFR inhibitor treatment in clinical samples. Co-inhibition of Bcl-xL and mutant EGFR overcame resistance induced by RBM10 deficiency. This study sheds light on the role of co-occurring genetic alterations, and on the impact of splicing factor deficiency in the modulation of sensitivity to targeted kinase inhibitor cancer therapy.
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http://dx.doi.org/10.1172/JCI145099DOI Listing
May 2022
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