Targeting the gut microbiota-related metabolites for osteoporosis: The inextricable connection of gut-bone axis

Ageing Research Reviews, Год журнала: 2024, Номер 94, С. 102196 - 102196

Опубликована: Янв. 12, 2024

Язык: Английский

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Pueraria lobata-derived exosome-like nanovesicles alleviate osteoporosis by enhacning autophagy

Journal of Controlled Release, Год журнала: 2023, Номер 364, С. 644 - 653

Опубликована: Ноя. 16, 2023

Osteoporosis (OP) is the most common bone disorder worldwide, especially in postmenopausal women. However, many OP drugs are not suitable for long term use due to major adverse effects. Therefore, there an urgent need identify more effective and safe therapeutic drugs. Pueraria lobata has been reported promote osteoblast growth regeneration, but exact mechanisms still further exploration. The current study found that lobata-derived exosome-like nanovesicles (PELNs) promoting primary human mesenchymal stem cells (hBMSCs) differentiation mineralization both vitro ovariectomized (OVX)-induced osteoporotic rats. Interestingly, relative abundance of harmful strains significantly decreased intestine osteoporosis SD rat model administrated PELNs via regulation trimethylamine-N-oxide (TMAO), a metabolite gut microbiota. Moreover, RNA sequencing revealed osteogenic activity autophagy signaling. In vivo experiments also showed treatment with promoted function hBMSCs by elevating degradation TMAO. Collectively, demonstrate promise as approach OP, TMAO emerging potential target treatment.

Язык: Английский

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Gut microbially produced tryptophan metabolite melatonin ameliorates osteoporosis via modulating SCFA and TMAO metabolism

Journal of Pineal Research, Год журнала: 2024, Номер 76(3)

Опубликована: Апрель 1, 2024

Abstract Osteoporosis (OP) is a severe global health issue that has significant implications for productivity and human lifespan. Gut microbiota dysbiosis been demonstrated to be closely associated with OP progression. Melatonin (MLT) an important endogenous hormone modulates bone metabolism, maintains homeostasis, improves Multiple studies indicated MLT participates in the regulation of intestinal gut barrier function. However, promising effects microbiota‐derived remain unclear. Here, we found resulted tryptophan disorder decreased production MLT, while administration could mitigate OP‐related clinical symptoms reverse dysbiosis, including diversity microbiota, relative abundance many probiotics such as Allobaculum Parasutterella , metabolic function flora amino acid nucleotide energy metabolism. Notably, significantly increased short‐chain fatty acids trimethylamine N‐oxide‐related metabolites. Importantly, modulate dynamic balance M1/M2 macrophages, reduce serum levels pro‐inflammatory cytokines, restore gut‐barrier Taken together, our results highlighted roles microbially derived progression via “gut‐bone” axis SCFA which may provide novel insight into development drug treating OP.

Язык: Английский

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Gold nanoparticles exhibit anti-osteoarthritic effects via modulating interaction of the “microbiota-gut-joint” axis

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Апрель 8, 2024

Abstract Osteoarthritis (OA) is a common degenerative joint disease that can cause severe pain, motor dysfunction, and even disability. A growing body of research indicates gut microbiota their associated metabolites are key players in maintaining bone health the progression OA. Short-chain fatty acids (SCFAs) series active widely participate homeostasis. Gold nanoparticles (GNPs) with outstanding anti-bacterial anti-inflammatory properties, have been demonstrated to ameliorate excessive loss during osteoporosis (OP) rheumatoid arthritis (RA). However, protective effects GNPs on OA not clear. Here, we observed significantly alleviated anterior cruciate ligament transection (ACLT)-induced microbiota-dependent manner. 16S rDNA gene sequencing showed changed microbial diversity structure, which manifested as an increase abundance Akkermansia Lactobacillus . Additionally, increased levels SCFAs (such butyric acid), could improved destruction by reducing inflammatory response. Notably, modulated dynamic balance M1/M2 macrophages, serum cytokines such IL-10. To sum up, our study indicated exhibited anti-osteoarthritis via modulating interaction “microbiota-gut-joint” axis, might provide promising therapeutic strategies for

Язык: Английский

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Association of serum trimethylamine N-oxide levels and bone mineral density in type 2 diabetes mellitus

Endocrine, Год журнала: 2024, Номер 84(3), С. 958 - 968

Опубликована: Янв. 29, 2024

Язык: Английский

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PCSK9 and APOA4: The Dynamic Duo in TMAO-induced Cholesterol Metabolism and Cholelithiasis

Journal of Clinical and Translational Hepatology, Год журнала: 2025, Номер 000(000), С. 000 - 000

Опубликована: Фев. 11, 2025

Background and AimsCholesterol synthesis gallstone formation are promoted by trimethylamine-N-oxide (TMAO), a derivative of trimethylamine, which is metabolite gut microbiota. However, the underlying mechanisms TMAO-induced lithogenesis remain incompletely understood. This study aimed to explore specific molecular through TMAO promotes formation.

Язык: Английский

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Maintaining gut microbiota micro-environment homeostasis via silver-nanocubes for ameliorating estrogen deficiency-induced osteoporosis

Nano Today, Год журнала: 2025, Номер 62, С. 102671 - 102671

Опубликована: Фев. 17, 2025

Язык: Английский

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Ångstrom-scale gold particles loaded with alendronate via alpha-lipoic acid alleviate bone loss in osteoporotic mice

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Апрель 30, 2024

Osteoporosis is a highly prevalent metabolic disease characterized by low systemic bone mass and deterioration of microarchitecture, resulting in reduced strength increased fracture risk. Current treatment options for osteoporosis are limited factors such as efficacy, cost, availability, side effects, acceptability to patients. Gold nanoparticles show promise an emerging therapy due their osteogenic effects ability allow therapeutic delivery but have inherent constraints, specificity the potential heavy metal accumulation body. This study reports synthesis ultrasmall gold particles almost reaching Ångstrom (Ång) dimension. The antioxidant alpha-lipoic acid (LA) used dispersant stabilizer coat Ångstrom-scale (AuÅPs). Alendronate (AL), amino-bisphosphonate commonly drug osteoporosis, conjugated through LA surface AuÅPs, allowing targeted enhancing antiresorptive effects. In this study, alendronate-loaded (AuÅPs-AL) were first time promote osteogenesis alleviate loss regulation WNT signaling pathway, shown vitro tests. vivo AuÅPs-AL demonstrated established mouse model. results Micro-computed Tomography, histology, tartrate-resistant phosphatase staining indicated that significantly improved density prevented loss, with no evidence nanoparticle-associated toxicity. These findings suggest possible future application point developing new approaches treating diseases using particles.

Язык: Английский

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Krüppel‐like factors family in health and disease

MedComm, Год журнала: 2024, Номер 5(9)

Опубликована: Сен. 1, 2024

Abstract Krüppel‐like factors (KLFs) are a family of basic transcription with three conserved Cys2/His2 zinc finger domains located in their C‐terminal regions. It is acknowledged that KLFs exert complicated effects on cell proliferation, differentiation, survival, and responses to stimuli. Dysregulation associated range diseases including cardiovascular disorders, metabolic diseases, autoimmune conditions, cancer, neurodegenerative diseases. Their multidimensional roles modulating critical pathways underscore the significance both physiological pathological contexts. Recent research also emphasizes crucial involvement complex interplay skeletal system. Despite substantial progress understanding various cellular processes, several gaps remain. Here, we elucidated multifaceted capabilities body health via compliable signaling pathways. The associations between energy metabolism epigenetic modification during bone reconstruction have been summarized. This review helps us better understand coupling pivotal functions multiple systems detailed mechanisms remodeling develop potential therapeutic strategies for clinical treatment by targeting KLF family.

Язык: Английский

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Innovative Nanomedicine Delivery: Targeting Tumor Microenvironment to Defeat Drug Resistance

Pharmaceutics, Год журнала: 2024, Номер 16(12), С. 1549 - 1549

Опубликована: Дек. 3, 2024

Nanodrug delivery systems have revolutionized tumor therapy like never before. By overcoming the complexity of microenvironment (TME) and bypassing drug resistance mechanisms, nanotechnology has shown great potential to improve efficacy reduce toxic side effects. This review examines impact TME on recent advances in nanomedicine overcome this challenge. Characteristics such as hypoxia, acidity, high interstitial pressure significantly effectiveness chemotherapy radiotherapy, leading increased cells. Then, summarizes innovative nanocarrier designs for these microenvironmental features, including hypoxia-sensitive nanoparticles, pH-responsive carriers, multifunctional nanosystems that enable targeted release improved penetration accumulation tumors. combining with therapeutic strategies, offers a novel perspective by focusing design nanocarriers interact TME, dimension often overlooked similar reviews. We highlight dual role modulation, emphasize their resistance, look at future research directions.

Язык: Английский

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