Wei Tse Li

Although there is a well-established connection between the gut microbiome and obesity, the specific mechanisms by which microbes regulate cell signalling, inflammation and adipocyte growth to influence disease severity in obese patients remain largely unclear. Subsequently, while obesity itself is a well-established risk factor for various cancers, the exact mechanisms by which it drives disease progression are not yet definitively known. In this study, we explored the link between obesity-associated microbiome alterations and cancer progression by analysing microbial abundance in tissue samples from obese and cancer patients, and we identified specific microbes correlated with body mass index (BMI) that are associated with key cancer-related pathways. Notably, BMI-associated microbial species such as Pseudomonas fluorescens and Lactobacillus sakei were linked with both pro-tumour and anti-tumour progression in cancer patients. Additionally, microbes found to be abundant in cancer and obese tissue, such as Pseudomonas baetica, were significantly associated with the upregulation of certain oncogenic signalling pathways. BMI-associated microbes were also correlated with chemokine signalling and TFR2/NFkB-related genes. Both of these have well-established roles in inflammatory activity and inflammasome expression, a critical step in obesity-related cancer progression. Therefore, these microbes were found to be associated with variations in disease prognosis and patient survival. This study provides new insights into how obesity-related microbiome dysbiosis may be associated with cancer development and aims to introduce novel potential avenues for precision medicine approaches in cancer treatment.

Although there is a well-established connection between the gut microbiome and obesity, the specific mechanisms by which microbes regulate cell signaling, inflammation, and adipocyte growth to influence disease severity in obese patients remains largely unclear. Subsequently, while obesity itself is a well-established risk factor for various cancers, the exact mechanisms by which it drives disease progression are not yet definitively known. In this study, we explored the link between obesity-associated microbiome alterations and cancer progression by analyzing microbial abundance in tissue samples from obese and cancer patients, and we identified specific microbes correlated with Body Mass Index (BMI) that are associated with key cancer-related pathways. Notably, BMI-associated microbial species as Pseudomonas fluorescens and Lactobacillus sakei, were linked with both pro-tumor and anti-tumor progression in cancer patients. Additionally, microbes found to be abundant in cancer and obese tissue, such as Pseudomonas baetica, were significantly associated with the upregulation of certain oncogenic signaling pathways. BMI-associated microbes were also correlated with chemokine signaling and TFR2/NFkB-related genes. Both of these have well established roles in inflammatory activity and inflammasome expression, a critical step in obesity related cancer progression. Therefore, these microbes were found to be associated with variations in disease prognosis and patient survival. This study provides new insights into how obesity-related microbiome dysbiosis may be associated with cancer development, and aims to introduce novel potential avenues for precision medicine approaches in cancer treatment.

Although there is a well-established connection between the gut microbiome and obesity, the specific mechanisms by which microbes regulate cell signaling, inflammation, and adipocyte growth to influence disease severity in obese patients remains largely unclear. Subsequently, while obesity itself is a well-established risk factor for various cancers, the exact mechanisms by which it drives disease progression are not yet definitively known. In this study, we explored the link between obesity-associated microbiome alterations and cancer progression by analyzing microbial abundance in tissue samples from obese and cancer patients, and we identified specific microbes correlated with Body Mass Index (BMI) that are associated with key cancer-related pathways. Notably, BMI-associated microbial species as Pseudomonas fluorescens and Lactobacillus sakei, were linked with both pro-tumor and anti-tumor progression in cancer patients. Additionally, microbes found to be abundant in cancer and obese tissue, such as Pseudomonas baetica, were significantly associated with the upregulation of certain oncogenic signaling pathways. BMI-associated microbes were also correlated with chemokine signaling and TFR2/NFkB-related genes. Both of these have well established roles in inflammatory activity and inflammasome expression, a critical step in obesity related cancer progression. Therefore, these microbes were found to be associated with variations in disease prognosis and patient survival. This study provides new insights into how obesity-related microbiome dysbiosis may be associated with cancer development, and aims to introduce novel potential avenues for precision medicine approaches in cancer treatment.

Background/Objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative condition whose growing prevalence has become an increasingly important public health concern as the population ages. The lack of a definitive cure elevates the importance of identifying risk factors that are crucial for prevention efforts. Hypertension (HTN) and obesity have emerged as two highly widespread, interrelated conditions that have independently been associated with AD risk. Despite extensive research into AD pathology, the impact of obesity in a hypertensive population is not well explored. This study aims to investigate how obesity and blood pressure control within a hypertensive population may interact with genomic risk and environmental factors to influence AD incidence. Methods: A retrospective cohort of matched AD and normal patients diagnosed with HTN and taking anti-HTN drugs (n = 1862) from the All of Us database was analyzed. In this hypertensive cohort, obesity was significantly associated with increased AD risk. Genome-wide association studies (GWASs) were conducted on hypertensive AD individuals (n = 1030) and identified six single nucleotide variants (SNVs) that were associated with AD development in this population. Results: Obesity and Area Deprivation Index, a measure of socioeconomic status, were significantly associated with elevated AD risk within the hypertensive cohort. GWAS analysis identified six SNVs significantly associated with AD development among the hypertensive cohort. Conclusions: Our findings suggest that among hypertensive individuals, comorbid obesity and the Area Deprivation Index confer greater AD risk. These results highlight the critical need for obesity prevention and management strategies as part of Alzheimer’s risk reduction efforts.

Alzheimer’s disease (AD) is a leading cause of dementia worldwide. As current diagnostic approaches remain limited in sensitivity and accessibility, there is a critical need for novel, non-invasive biomarkers aiding early detection. Non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), PIWI-interacting RNAs (piRNAs), and small nucleolar RNAs (snoRNAs), have emerged as promising candidates due to their regulatory roles in gene expression and association with diseases. In this study, we systematically profiled ncRNA expression from RNA sequencing data of 48 AD and 22 control blood tissue samples, aiming to evaluate their utility as biomarkers for AD classification. Differential expression analysis revealed widespread dysregulation of lncRNAs and piRNAs, with over 5000 lncRNAs and nearly 1000 piRNAs significantly upregulated in AD. Weighted gene co-expression network analysis (WGCNA) identified multiple ncRNA modules associated with the AD phenotype. Using supervised machine learning approaches, we evaluated the diagnostic potential of ncRNA expression profiles, including single-gene, multi-gene, and module-level models. Random Forest models trained on individual genes identified 121 ncRNAs with AUROC > 0.8. Feature importance analysis emphasized ncRNAs such as lnc-MYEF2-3, lnc-PRKACB2, and HBII-115 as major contributors to diagnostic accuracy. These findings support the potential of ncRNA signatures as reliable and non-invasive biomarkers for AD diagnosis.

Although there is a well-established connection between the gut microbiome and obesity, the specific mechanisms by which microbes regulate cell signaling, inflammation, and adipocyte growth to influence disease severity in obese patients remains largely unclear. Subsequently, while obesity itself is a well-established risk factor for various cancers, the exact mechanisms by which it drives disease progression are not definitively known. In this study, we explored the link between obesity-associated microbiome alterations and cancer progression by analyzing microbial abundance in tissue samples from obese and cancer patients, and we identified specific microbes correlated with Body Mass Index (BMI) that are associated with key cancer-related pathways. Notably, BMI-associated microbial species as Pseudomonas fluorescens and Lactobacillus sakei, were linked with both pro-tumor and anti-tumor progression in cancer patients. Additionally, microbes found to be abundant in cancer and obese tissue, such as Pseudomonas baetica, were significantly associated with the upregulation of certain oncogenic signaling pathways. BMI-associated microbes were also correlated with chemokine signaling and TFR2/NFkB-related genes. Both of these have well established roles in inflammatory activity and inflammasome expression, a critical step in obesity related cancer progression. Therefore, these microbes likely have an influence on both disease prognosis as well as patient survival. This study provides new insights into how obesity-related microbiome dysbiosis may contribute to cancer development, and aims to introduce novel potential avenues for precision medicine approaches in cancer treatment.

Transfer-RNA-derived fragments (tRFs) are a novel class of small non-coding RNAs that have been implicated in oncogenesis. tRFs may act as post-transcriptional regulators by recruiting AGO proteins and binding to highly complementary regions of mRNA at seed regions, resulting in the knockdown of the transcript. Therefore, tRFs may be critical to tumorigenesis and warrant investigation as potential biomarkers. Meanwhile, the incidence of papillary thyroid carcinoma (PTC) has increased in recent decades and current diagnostic technology stands to benefit from new detection methods. Although small non-coding RNAs have been studied for their role in oncogenesis, there is currently no standard for their use as PTC biomarkers, and tRFs are especially underexplored. Accordingly, we aim to identify dysregulated tRFs in PTC that may serve as biomarker candidates. We identified dysregulated tRFs and driver genes between PTC primary tumor samples (n = 511) and adjacent normal tissue samples (n = 59). Expression data were obtained from MINTbase v2.0 and The Cancer Genome Atlas. Dysregulated tRFs and genes were analyzed in tandem to find pairs with anticorrelated expression. Significantly anticorrelated tRF-gene pairs were then tested for potential binding affinity using RNA22—if a heteroduplex can form via complementary binding, this would support the hypothesized RNA silencing mechanism. Four tRFs were significantly dysregulated in PTC tissue (p < 0.05), with only AsnGTT 3′-tRF being upregulated. Binding affinity analysis revealed that tRF-30-RY73W0K5KKOV (AsnGTT 3′-tRF) exhibits sufficient complementarity to potentially bind to and regulate transcripts of SLC26A4, SLC5A8, DIO2, and TPO, which were all found to be downregulated in PTC tissue. In the present study, we identified dysregulated tRFs in PTC and found that AsnGTT 3′-tRF is a potential post-transcriptional regulator and biomarker.