Cascadia Journal of Biomedical Research - Articles
Browse published articles from Cascadia Journal of Biomedical Research
Wang, W., Dong, Z., Hong, B., Guan, X., Wang, Y., Sun, Z., Miao, Q., Zhang, N.
Background Prostate cancer is among the most prevalent malignancies worldwide, and cardiovascular disease (CVD) is a major non‐cancer cause of death in affected patients. Androgen deprivation therapy (ADT), a mainstay treatment, has raised concerns about cardiotoxicity, yet the CVD risks of individual ADT agents remain unclear. Objectives To assess cardiovascular adverse events (AEs) associated with specific ADT drugs using data from the U.S. FDA Adverse Event Reporting System (FAERS). Methods AE reports related to ADT drugs were extracted from FAERS (Q1 2004–Q3 2024). Disproportionality analyses—including Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR)—were conducted to identify significant cardiovascular safety signals. Results Different ADT agents exhibited distinct cardiovascular AE profiles. Some drugs were linked to a broader range of CVD‐related AEs, while others had more limited associations. Conclusions ADT agents demonstrate heterogeneous cardiotoxicity profiles. These findings emphasize the need for individualized treatment strategies, particularly in patients with pre‐existing CVD risks, and may aid clinicians in balancing cancer control with cardiovascular safety.
Cardiovascular Safety Landscape of ADT in Prostate Cancer Treatment Based on Real‐World Analysis
Wang, W., Dong, Z., Hong, B., Guan, X., Wang, Y., Sun, Z., Miao, Q., Zhang, N.
Background Prostate cancer is among the most prevalent malignancies worldwide, and cardiovascular disease (CVD) is a major non‐cancer cause of death in affected patients. Androgen deprivation therapy (ADT), a mainstay treatment, has raised concerns about cardiotoxicity, yet the CVD risks of individual ADT agents remain unclear. Objectives To assess cardiovascular adverse events (AEs) associated with specific ADT drugs using data from the U.S. FDA Adverse Event Reporting System (FAERS). Methods AE reports related to ADT drugs were extracted from FAERS (Q1 2004–Q3 2024). Disproportionality analyses—including Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR)—were conducted to identify significant cardiovascular safety signals. Results Different ADT agents exhibited distinct cardiovascular AE profiles. Some drugs were linked to a broader range of CVD‐related AEs, while others had more limited associations. Conclusions ADT agents demonstrate heterogeneous cardiotoxicity profiles. These findings emphasize the need for individualized treatment strategies, particularly in patients with pre‐existing CVD risks, and may aid clinicians in balancing cancer control with cardiovascular safety.
Zhang, Y., Urquijo, M., Zitnay, R., Marks, K., Belote, R., Hansen, M., Ferita, M., Neuendorf, H., Liu, T., Smith, E., Mehrabad, E., Hejna, M., Moustafa, T., Lange, D., Hu, M., Vand-Rajabpour, F., Done, A., Becker, C., Lieberman, M., Chang, M., Lohman, B., Stubben, C., Reeves, M., Zhang, X., Weinberger, L., VanBrocklin, M., Deacon, D., Grossman, D., Spike, B., Lex, A., Boyle, G., Kulkarni, R., Zangle, T., Judson-Torres, R.
Metastatic spread and therapeutic resistance are the principal causes of cancer mortality. For melanoma, these processes rely on the capacity of cells to switch between transcriptional states. Although targeting transcriptional states pharmacologically is promising, the mechanisms by which melanoma cells switch between states—and how these processes differ from melanocytes—remain poorly understood. Here, we isolate distinct melanoma states with unique phenotypes: a MYC-driven state, essential for tumor initiation yet sensitive to BRAF inhibition, and a dedifferentiated, invasive BRN2-high state enriched in therapy-resistant cells but not directly tumorigenic. Transitions between phenotypes occur through intermediate, more differentiated states. Unexpectedly, the BRN2-high state is also present in melanocytes, whereas the MYC state is exclusive to melanoma. Melanoma cells also exhibit an increased frequency of transitions across states. These findings highlight that accelerated phenotypic switching, rather than mere state diversity, is a defining feature of melanoma progression.
A BRN2:MYC transcriptional axis regulates interconversion between therapy-resistant and tumorigenic phenotypes in melanoma
Zhang, Y., Urquijo, M., Zitnay, R., Marks, K., Belote, R., Hansen, M., Ferita, M., Neuendorf, H., Liu, T., Smith, E., Mehrabad, E., Hejna, M., Moustafa, T., Lange, D., Hu, M., Vand-Rajabpour, F., Done, A., Becker, C., Lieberman, M., Chang, M., Lohman, B., Stubben, C., Reeves, M., Zhang, X., Weinberger, L., VanBrocklin, M., Deacon, D., Grossman, D., Spike, B., Lex, A., Boyle, G., Kulkarni, R., Zangle, T., Judson-Torres, R.
Metastatic spread and therapeutic resistance are the principal causes of cancer mortality. For melanoma, these processes rely on the capacity of cells to switch between transcriptional states. Although targeting transcriptional states pharmacologically is promising, the mechanisms by which melanoma cells switch between states—and how these processes differ from melanocytes—remain poorly understood. Here, we isolate distinct melanoma states with unique phenotypes: a MYC-driven state, essential for tumor initiation yet sensitive to BRAF inhibition, and a dedifferentiated, invasive BRN2-high state enriched in therapy-resistant cells but not directly tumorigenic. Transitions between phenotypes occur through intermediate, more differentiated states. Unexpectedly, the BRN2-high state is also present in melanocytes, whereas the MYC state is exclusive to melanoma. Melanoma cells also exhibit an increased frequency of transitions across states. These findings highlight that accelerated phenotypic switching, rather than mere state diversity, is a defining feature of melanoma progression.
Johnson, L., Jamieson, L., Kubjane, M., Meyer-Rath, G.
Background High incidence rates of HIV, sexually transmitted infections (STIs), and teenage pregnancy are major challenges facing South Africa. The role of socio-economic factors in driving these incidence rates is complex, with high socio-economic status protecting against some risk behaviours (condomless sex, early sexual debut, and casual/transactional sex in females) but increasing other risk behaviours (e.g., male engagement in casual and commercial sex). We aimed to model the effect of socio-economic status, and associated economic strengthening interventions, in South Africa. Methods and findings We extended a previously-developed agent-based model of HIV, STIs, and fertility in South Africa to assess effects of education, employment, and per capita household income on sexual behaviours. We estimated these effects from literature and from calibration of the model to African randomized controlled trials of economic strengthening interventions. Population attributable fractions (PAFs) were calculated. We considered three intervention types, all targeting households with log per capita income below the national average: school support to reduce school dropout; vocational training for unemployed adults; and unconditional cash transfers. We estimate that low socio-economic status accounted for 13% of new HIV infections, 7% of incident STIs (gonorrhoea, chlamydia, and trichomoniasis) and 31% of teenage births in South Africa, over 2000−2020. However, because of uncertainties regarding effect sizes, confidence intervals around these PAFs are wide (1,50% for HIV; −1,19% for STIs; and 10,76% for teenage births). Over 2025−2040, none of the interventions are estimated to reduce HIV, STIs, or teenage births significantly, due to limited impact on secondary economic outcomes. The greatest impact would be that of school support on teenage births (a 5% reduction, 95% CI: −1,12%). Key limitations include the assumption of uniform STI treatment access across socio-economic strata, and the exclusion of possible socio-economic effects at a community level. Conclusions Although poverty is likely to be a significant driver of HIV, STIs, and teenage pregnancy in South Africa, precise quantification is challenging. Recently trialled economic strengthening interventions have insufficient impact on socio-economic status to reduce HIV and STIs significantly at a population level.
Evaluation of economic strengthening in South Africa and its impact on HIV, sexually transmitted infections, and teenage births: A modelling study (JOS DOCX counterpart)
Johnson, L., Jamieson, L., Kubjane, M., Meyer-Rath, G.
Background High incidence rates of HIV, sexually transmitted infections (STIs), and teenage pregnancy are major challenges facing South Africa. The role of socio-economic factors in driving these incidence rates is complex, with high socio-economic status protecting against some risk behaviours (condomless sex, early sexual debut, and casual/transactional sex in females) but increasing other risk behaviours (e.g., male engagement in casual and commercial sex). We aimed to model the effect of socio-economic status, and associated economic strengthening interventions, in South Africa. Methods and findings We extended a previously-developed agent-based model of HIV, STIs, and fertility in South Africa to assess effects of education, employment, and per capita household income on sexual behaviours. We estimated these effects from literature and from calibration of the model to African randomized controlled trials of economic strengthening interventions. Population attributable fractions (PAFs) were calculated. We considered three intervention types, all targeting households with log per capita income below the national average: school support to reduce school dropout; vocational training for unemployed adults; and unconditional cash transfers. We estimate that low socio-economic status accounted for 13% of new HIV infections, 7% of incident STIs (gonorrhoea, chlamydia, and trichomoniasis) and 31% of teenage births in South Africa, over 2000−2020. However, because of uncertainties regarding effect sizes, confidence intervals around these PAFs are wide (1,50% for HIV; −1,19% for STIs; and 10,76% for teenage births). Over 2025−2040, none of the interventions are estimated to reduce HIV, STIs, or teenage births significantly, due to limited impact on secondary economic outcomes. The greatest impact would be that of school support on teenage births (a 5% reduction, 95% CI: −1,12%). Key limitations include the assumption of uniform STI treatment access across socio-economic strata, and the exclusion of possible socio-economic effects at a community level. Conclusions Although poverty is likely to be a significant driver of HIV, STIs, and teenage pregnancy in South Africa, precise quantification is challenging. Recently trialled economic strengthening interventions have insufficient impact on socio-economic status to reduce HIV and STIs significantly at a population level.
Johnson, L., Jamieson, L., Kubjane, M., Meyer-Rath, G.
Background High incidence rates of HIV, sexually transmitted infections (STIs), and teenage pregnancy are major challenges facing South Africa. The role of socio-economic factors in driving these incidence rates is complex, with high socio-economic status protecting against some risk behaviours (condomless sex, early sexual debut, and casual/transactional sex in females) but increasing other risk behaviours (e.g., male engagement in casual and commercial sex). We aimed to model the effect of socio-economic status, and associated economic strengthening interventions, in South Africa. Methods and findings We extended a previously-developed agent-based model of HIV, STIs, and fertility in South Africa to assess effects of education, employment, and per capita household income on sexual behaviours. We estimated these effects from literature and from calibration of the model to African randomized controlled trials of economic strengthening interventions. Population attributable fractions (PAFs) were calculated. We considered three intervention types, all targeting households with log per capita income below the national average: school support to reduce school dropout; vocational training for unemployed adults; and unconditional cash transfers. We estimate that low socio-economic status accounted for 13% of new HIV infections, 7% of incident STIs (gonorrhoea, chlamydia, and trichomoniasis) and 31% of teenage births in South Africa, over 2000−2020. However, because of uncertainties regarding effect sizes, confidence intervals around these PAFs are wide (1,50% for HIV; −1,19% for STIs; and 10,76% for teenage births). Over 2025−2040, none of the interventions are estimated to reduce HIV, STIs, or teenage births significantly, due to limited impact on secondary economic outcomes. The greatest impact would be that of school support on teenage births (a 5% reduction, 95% CI: −1,12%). Key limitations include the assumption of uniform STI treatment access across socio-economic strata, and the exclusion of possible socio-economic effects at a community level. Conclusions Although poverty is likely to be a significant driver of HIV, STIs, and teenage pregnancy in South Africa, precise quantification is challenging. Recently trialled economic strengthening interventions have insufficient impact on socio-economic status to reduce HIV and STIs significantly at a population level.
Evaluation of economic strengthening in South Africa and its impact on HIV, sexually transmitted infections, and teenage births: A modelling study (PMC XML)
Johnson, L., Jamieson, L., Kubjane, M., Meyer-Rath, G.
Background High incidence rates of HIV, sexually transmitted infections (STIs), and teenage pregnancy are major challenges facing South Africa. The role of socio-economic factors in driving these incidence rates is complex, with high socio-economic status protecting against some risk behaviours (condomless sex, early sexual debut, and casual/transactional sex in females) but increasing other risk behaviours (e.g., male engagement in casual and commercial sex). We aimed to model the effect of socio-economic status, and associated economic strengthening interventions, in South Africa. Methods and findings We extended a previously-developed agent-based model of HIV, STIs, and fertility in South Africa to assess effects of education, employment, and per capita household income on sexual behaviours. We estimated these effects from literature and from calibration of the model to African randomized controlled trials of economic strengthening interventions. Population attributable fractions (PAFs) were calculated. We considered three intervention types, all targeting households with log per capita income below the national average: school support to reduce school dropout; vocational training for unemployed adults; and unconditional cash transfers. We estimate that low socio-economic status accounted for 13% of new HIV infections, 7% of incident STIs (gonorrhoea, chlamydia, and trichomoniasis) and 31% of teenage births in South Africa, over 2000−2020. However, because of uncertainties regarding effect sizes, confidence intervals around these PAFs are wide (1,50% for HIV; −1,19% for STIs; and 10,76% for teenage births). Over 2025−2040, none of the interventions are estimated to reduce HIV, STIs, or teenage births significantly, due to limited impact on secondary economic outcomes. The greatest impact would be that of school support on teenage births (a 5% reduction, 95% CI: −1,12%). Key limitations include the assumption of uniform STI treatment access across socio-economic strata, and the exclusion of possible socio-economic effects at a community level. Conclusions Although poverty is likely to be a significant driver of HIV, STIs, and teenage pregnancy in South Africa, precise quantification is challenging. Recently trialled economic strengthening interventions have insufficient impact on socio-economic status to reduce HIV and STIs significantly at a population level.
Fontaine, M., Oyelaran, T.
Genome size varies widely, even among closely related species, yet much less is known about chromosome size variation. Here we use the fourth chromosome of Drosophila , also known as the “Muller F element” or “dot chromosome”, as a model to investigate chromosome-specific size expansion. The F element of most Drosophila species is small (∼1.3 Mb) and almost entirely heterochromatic, yet harbors approximately 80 protein-coding genes. Here, we study D. kikkawai , D. takahashii , D. ananassae , and D. bipectinata , whose F elements are 2- to 15-fold larger in size compared to D. melanogaster . Through manual gene curation and comparative genomic analysis, we find that their F elements have expanded primarily via accumulation of transposable elements (TEs) in introns and intergenic regions. Natural selection appears less efficient on these expanded F elements: they have smaller effective population sizes and their genes exhibit reduced usage of optimal codons, compared to D. melanogaster . We propose that F element size variation is driven by differences in F element recombination rates. The ultra-long (∼20 Mb) F elements of D. ananassae and D. bipectinata display high rates of rearrangement and sequence evolution and exhibit independent TE-driven expansions. Our results suggest that F elements of most Drosophila species likely recombine enough to prevent size expansion, while F element recombination in D. ananassae and D. bipectinata is either absent or rare enough to allow TEs and other deleterious mutations to accumulate via Muller's ratchet; thus, these chromosomes evolve more like a Y chromosome than a typical Drosophila F element. Updated in version 2 to clarify the scope of the analysis.
Recombination Suppression Drives Expansion of the Drosophila Dot Chromosome: methods and sensitivity checks
Fontaine, M., Oyelaran, T.
Genome size varies widely, even among closely related species, yet much less is known about chromosome size variation. Here we use the fourth chromosome of Drosophila , also known as the “Muller F element” or “dot chromosome”, as a model to investigate chromosome-specific size expansion. The F element of most Drosophila species is small (∼1.3 Mb) and almost entirely heterochromatic, yet harbors approximately 80 protein-coding genes. Here, we study D. kikkawai , D. takahashii , D. ananassae , and D. bipectinata , whose F elements are 2- to 15-fold larger in size compared to D. melanogaster . Through manual gene curation and comparative genomic analysis, we find that their F elements have expanded primarily via accumulation of transposable elements (TEs) in introns and intergenic regions. Natural selection appears less efficient on these expanded F elements: they have smaller effective population sizes and their genes exhibit reduced usage of optimal codons, compared to D. melanogaster . We propose that F element size variation is driven by differences in F element recombination rates. The ultra-long (∼20 Mb) F elements of D. ananassae and D. bipectinata display high rates of rearrangement and sequence evolution and exhibit independent TE-driven expansions. Our results suggest that F elements of most Drosophila species likely recombine enough to prevent size expansion, while F element recombination in D. ananassae and D. bipectinata is either absent or rare enough to allow TEs and other deleterious mutations to accumulate via Muller's ratchet; thus, these chromosomes evolve more like a Y chromosome than a typical Drosophila F element. Updated in version 2 to clarify the scope of the analysis.
Dvořák, D., Zhang, K., Silva, S., Hayashi, J., Hansen, H., Abdi, O., Marchetti, G., Sharma, V., Kim, K., Dvořák, V., Watanabe, M., Jovanović, A., Larsen, D., Delacroix, L., Hakimi, O., Bergström, D., Engel, H., Santoro, R., Okonkwo, T., Lemaire, M., Sandberg, S., Moreau, M., Lindgren, H., Holmberg, M., Tembo, A., Abdi, R., Khalil, I., Müller, C., Iyer, N., Lindgren, D., Castellanos, I.
Prostate cancer is among the most prevalent malignancies worldwide, and cardiovascular disease (CVD) is a major non‐cancer cause of death in affected patients. Androgen deprivation therapy (ADT), a mainstay treatment, has raised concerns about cardiotoxicity, yet the CVD risks of individual ADT agents remain unclear. To assess cardiovascular adverse events (AEs) associated with specific ADT drugs using data from the U.S. FDA Adverse Event Reporting System (FAERS).
Further evidence: Cardiovascular Safety Landscape of ADT in Prostate Cancer Treatment Based on Real‐World Analysis
Dvořák, D., Zhang, K., Silva, S., Hayashi, J., Hansen, H., Abdi, O., Marchetti, G., Sharma, V., Kim, K., Dvořák, V., Watanabe, M., Jovanović, A., Larsen, D., Delacroix, L., Hakimi, O., Bergström, D., Engel, H., Santoro, R., Okonkwo, T., Lemaire, M., Sandberg, S., Moreau, M., Lindgren, H., Holmberg, M., Tembo, A., Abdi, R., Khalil, I., Müller, C., Iyer, N., Lindgren, D., Castellanos, I.
Prostate cancer is among the most prevalent malignancies worldwide, and cardiovascular disease (CVD) is a major non‐cancer cause of death in affected patients. Androgen deprivation therapy (ADT), a mainstay treatment, has raised concerns about cardiotoxicity, yet the CVD risks of individual ADT agents remain unclear. To assess cardiovascular adverse events (AEs) associated with specific ADT drugs using data from the U.S. FDA Adverse Event Reporting System (FAERS).
Ivanova, K., Laurent, M., Gunnarsson, H., Tanaka, H., Moreau, A.
Further evidence: UCHL1 regulated by Sp1 ameliorates cochlear hair cell senescence and oxidative damage
Ivanova, K., Laurent, M., Gunnarsson, H., Tanaka, H., Moreau, A.
Wu, Z., Pang, S., Mei, Y., Qin, C., Jin, Y., Lin, R.
Background: As a populous country in the world, China ranks among the top in terms of new cancer cases and deaths worldwide. This study aims to provide a detailed evaluation of the cancer burden in China, considering the evolving social, economic, and environmental factors that may have influenced cancer incidence and mortality rates. Methods: The cancer incidence, mortality, and the contributions of risk factors were estimated using data from the Global Burden of Disease Study (GBD) 2021. The number of new cases and deaths with their 95% uncertainty intervals (UIs) were analyzed. The trends of cancer age-standardized incidence rates (ASIR) from 1990 to 2021 and age-standardized death rates (ASDR) from 1980 to 2021 were estimated. Besides, risk factor contributions were also assessed. Results: In 2021, the total burden of cancer in China comprised 13.66 million new cases (95% UI: 11.79 to 15.85 million) and 2.82 million deaths (95% UI: 2.35 to 3.36 million). In 2021, ASIR and ASDR of cancers were 790.2 (95% UI: 676.8–926.3) per 100,000 population and 137.5 (95% UI: 115.1–163.4) per 100,000 population, respectively. In 2021, tracheal, bronchus, and lung cancer showed the highest ASIR of 44.0 (95% UI: 35.4–53.3) per 100,000 population among site-specific tumors, followed by non-melanoma skin cancer (37.5 [95% UI: 32.4–42.7] per 100,000 population), colon and rectum cancer (31.4 [95% UI: 25.5–38.0] per 100,000 population), stomach cancer (29.1 [95% UI: 22.4–36.2] per 100,000 population), breast cancer (19.4 [95% UI: 15.0–24.3] per 100,000 population), esophageal cancer (15.0 [95% UI: 12–18.4] per 100,000 population), and liver cancer (9.5 [95% UI: 7.7–11.8] per 100,000 population). Besides, the ASDR of cancers decreased about 29.78% in males and 42.00% in females in the past forty years in China. Tracheal, bronchus, and lung cancer showed the highest ASIR (62.63 per 100,000 population) and ASDR (56.45 per 100,000 population) in males. Of note, 31.73% of all cancer deaths in China were digestive cancers in 2021. For level 1 risks in 2021, behavioral risks were linked to 73.57% of cancer deaths. Conclusions: The disease burden of cancers remains a major public health concern in China. The ASIR increased from 1990 to 2021 and the ASDR decreased from 1980 to 2021 in cancers. Tracheal, bronchus, and lung cancer remain the most common types of cancer in China.
Cancer burden and the contributions of risk factors in China: A systematic analysis for the Global Burden of Disease Study 2021
Wu, Z., Pang, S., Mei, Y., Qin, C., Jin, Y., Lin, R.
Background: As a populous country in the world, China ranks among the top in terms of new cancer cases and deaths worldwide. This study aims to provide a detailed evaluation of the cancer burden in China, considering the evolving social, economic, and environmental factors that may have influenced cancer incidence and mortality rates. Methods: The cancer incidence, mortality, and the contributions of risk factors were estimated using data from the Global Burden of Disease Study (GBD) 2021. The number of new cases and deaths with their 95% uncertainty intervals (UIs) were analyzed. The trends of cancer age-standardized incidence rates (ASIR) from 1990 to 2021 and age-standardized death rates (ASDR) from 1980 to 2021 were estimated. Besides, risk factor contributions were also assessed. Results: In 2021, the total burden of cancer in China comprised 13.66 million new cases (95% UI: 11.79 to 15.85 million) and 2.82 million deaths (95% UI: 2.35 to 3.36 million). In 2021, ASIR and ASDR of cancers were 790.2 (95% UI: 676.8–926.3) per 100,000 population and 137.5 (95% UI: 115.1–163.4) per 100,000 population, respectively. In 2021, tracheal, bronchus, and lung cancer showed the highest ASIR of 44.0 (95% UI: 35.4–53.3) per 100,000 population among site-specific tumors, followed by non-melanoma skin cancer (37.5 [95% UI: 32.4–42.7] per 100,000 population), colon and rectum cancer (31.4 [95% UI: 25.5–38.0] per 100,000 population), stomach cancer (29.1 [95% UI: 22.4–36.2] per 100,000 population), breast cancer (19.4 [95% UI: 15.0–24.3] per 100,000 population), esophageal cancer (15.0 [95% UI: 12–18.4] per 100,000 population), and liver cancer (9.5 [95% UI: 7.7–11.8] per 100,000 population). Besides, the ASDR of cancers decreased about 29.78% in males and 42.00% in females in the past forty years in China. Tracheal, bronchus, and lung cancer showed the highest ASIR (62.63 per 100,000 population) and ASDR (56.45 per 100,000 population) in males. Of note, 31.73% of all cancer deaths in China were digestive cancers in 2021. For level 1 risks in 2021, behavioral risks were linked to 73.57% of cancer deaths. Conclusions: The disease burden of cancers remains a major public health concern in China. The ASIR increased from 1990 to 2021 and the ASDR decreased from 1980 to 2021 in cancers. Tracheal, bronchus, and lung cancer remain the most common types of cancer in China.
Liu, M., Gong, J., Liu, Y., Yu, J., Hu, Z., Liu, Z.
The gut-bone axis plays a pivotal role in skeletal health, yet the integration of multi-omics approaches to elucidate circadian metabolite-bone interactions remains limited. This review synthesizes evidence from metagenomics, metabolomics, and germ-free models to uncover how microbiota-derived metabolites—including short-chain fatty acids (SCFAs), bile acids, tryptophan derivatives, and gaseous molecules—orchestrate bone remodeling in osteoporosis, osteoarthritis, and bone malignancies. Many studies demonstrate that SCFAs inhibit osteoclastogenesis via GPR43/HDAC signaling and promote osteoblast metabolic reprogramming, while bile acids enhance osteogenesis through FXR/Wnt/β-catenin activation. Tryptophan metabolites repair intestinal barrier integrity and modulate osteoimmunity via the AhR pathway. Single-cell omics reveal circadian oscillations of metabolite receptors (e.g., GPR43, FXR) in bone stromal cells, linking microbial diurnal rhythms to epigenetic regulation of bone turnover. We propose a novel “metabolite-immune-bone triad” model, highlighting microbiome-driven immunometabolic reprogramming as a central regulator of skeletal homeostasis. These insights advance precision microbial therapeutics and chrono-nutritional strategies, bridging multi-omics discoveries with clinical applications for bone disorders.
Multi-omics reveals circadian regulation of bone homeostasis by gut microbiota metabolites: mechanisms and chronotherapeutic implications
Liu, M., Gong, J., Liu, Y., Yu, J., Hu, Z., Liu, Z.
The gut-bone axis plays a pivotal role in skeletal health, yet the integration of multi-omics approaches to elucidate circadian metabolite-bone interactions remains limited. This review synthesizes evidence from metagenomics, metabolomics, and germ-free models to uncover how microbiota-derived metabolites—including short-chain fatty acids (SCFAs), bile acids, tryptophan derivatives, and gaseous molecules—orchestrate bone remodeling in osteoporosis, osteoarthritis, and bone malignancies. Many studies demonstrate that SCFAs inhibit osteoclastogenesis via GPR43/HDAC signaling and promote osteoblast metabolic reprogramming, while bile acids enhance osteogenesis through FXR/Wnt/β-catenin activation. Tryptophan metabolites repair intestinal barrier integrity and modulate osteoimmunity via the AhR pathway. Single-cell omics reveal circadian oscillations of metabolite receptors (e.g., GPR43, FXR) in bone stromal cells, linking microbial diurnal rhythms to epigenetic regulation of bone turnover. We propose a novel “metabolite-immune-bone triad” model, highlighting microbiome-driven immunometabolic reprogramming as a central regulator of skeletal homeostasis. These insights advance precision microbial therapeutics and chrono-nutritional strategies, bridging multi-omics discoveries with clinical applications for bone disorders.
Shiu, S., DeLuca, M., Chui, W., Zhang, P., Mo, X., Siu, R., Dong, E., Qu, S., Cheung, C., Kinghorn, A., Whitehouse, W., Cui, J., He, W., Wang, X., Li, J., Khan, A., von Torklus, S., Yu, T., Al-Jamal, K., Tse, E., Arya, G., Fang, N., Zhou, K., Tanner, J.
Assembly of DNA nanostructures to sub-millimetre scales is expected to have significant potential for applications in materials science and medicine. One approach to control nanostructure growth is through using acoustic waves to create pressure nodes for clustering. Here, we report a facet-based underlying DNA nanostructure architecture with structural and stability characteristics ideal for acoustic patterning. The architecture comprises only 16 canonical DNA oligonucleotides which self-assemble to form a nested cube, inspired by the four-dimensional hypercube known as a “tesseract.” Cryogenic electron microscopy (Cryo-EM) and atomic force microscopy (AFM) analysis revealed a fully formed tesseract structure with exceptional stiffness and a melting temperature of 84°C, significantly higher than other unmodified DNA nanostructures. The DNA tesseract nanostructures could be acoustically shaped into wires spanning over 500 µm, observed after deposition onto an interdigitated electrode (IDE). The wires were shown to be electrically conductive, highlighting unique prospects for application. Simplified bottom-up assembly of a small number of oligonucleotides into a relatively complex and structurally stable DNA nanostructure with characteristics ideal for modular assembly holds promise for applications across bioelectronics and other fields.
Acoustically seeded fabrication of a DNA tesseract into a conductive wire
Shiu, S., DeLuca, M., Chui, W., Zhang, P., Mo, X., Siu, R., Dong, E., Qu, S., Cheung, C., Kinghorn, A., Whitehouse, W., Cui, J., He, W., Wang, X., Li, J., Khan, A., von Torklus, S., Yu, T., Al-Jamal, K., Tse, E., Arya, G., Fang, N., Zhou, K., Tanner, J.
Assembly of DNA nanostructures to sub-millimetre scales is expected to have significant potential for applications in materials science and medicine. One approach to control nanostructure growth is through using acoustic waves to create pressure nodes for clustering. Here, we report a facet-based underlying DNA nanostructure architecture with structural and stability characteristics ideal for acoustic patterning. The architecture comprises only 16 canonical DNA oligonucleotides which self-assemble to form a nested cube, inspired by the four-dimensional hypercube known as a “tesseract.” Cryogenic electron microscopy (Cryo-EM) and atomic force microscopy (AFM) analysis revealed a fully formed tesseract structure with exceptional stiffness and a melting temperature of 84°C, significantly higher than other unmodified DNA nanostructures. The DNA tesseract nanostructures could be acoustically shaped into wires spanning over 500 µm, observed after deposition onto an interdigitated electrode (IDE). The wires were shown to be electrically conductive, highlighting unique prospects for application. Simplified bottom-up assembly of a small number of oligonucleotides into a relatively complex and structurally stable DNA nanostructure with characteristics ideal for modular assembly holds promise for applications across bioelectronics and other fields.