Advances in pathogenesis and therapeutic strategies for osteoporosis

Pharmacology & Therapeutics, Journal Year: 2022, Volume and Issue: 237, P. 108168 - 108168

Published: March 10, 2022

Language: Английский

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The Effect of Oxidative Stress-Induced Autophagy by Cadmium Exposure in Kidney, Liver, and Bone Damage, and Neurotoxicity

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(21), P. 13491 - 13491

Published: Nov. 4, 2022

Environmental and occupational exposure to cadmium has been shown induce kidney damage, liver injury, neurodegenerative disease, osteoporosis. However, the mechanism by which induces autophagy in these diseases remains unclear. Studies have that is an effective inducer of oxidative stress, DNA ER autophagy, are thought be adaptive stress responses allow cells exposed survive adverse environment. excessive will cause tissue damage inducing apoptosis, pyroptosis, ferroptosis. Evidently, stress-induced plays different roles low- or high-dose exposure-induced cell either causing ferroptosis survival. Meanwhile, types sensitivities cadmium, ultimately determines fate cell. In this review, we provided a detailed survey current literature on cadmium-induced damage. A better understanding complex regulation death might contribute development novel preventive therapeutic strategies treat acute chronic toxicity.

Language: Английский

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Cell death regulation: A new way for natural products to treat osteoporosis

Pharmacological Research, Journal Year: 2022, Volume and Issue: 187, P. 106635 - 106635

Published: Dec. 26, 2022

Osteoporosis is a common metabolic bone disease that results from the imbalance of homeostasis within bone. Intra-bone dependent on precise dynamic balance between resorption by osteoclasts and formation mesenchymal lineage osteoblasts, which comprises series complex highly standardized steps. Programmed cell death (PCD) (e.g., apoptosis, autophagy, ferroptosis, pyroptosis, necroptosis) process involves cascade gene expression events with tight structures. These play certain role in regulating metabolism determining fate cells. Moreover, existing research has suggested natural products derived wide variety dietary components medicinal plants modulate PCDs based different mechanisms, show great potential for prevention treatment osteoporosis, thus revealing emergence more acceptable complementary alternative drugs lower costs, fewer side effects long-term application. Accordingly, this review summarizes types field osteoporosis. perspective targeting PCDs, also discussed roles currently reported osteoporosis involved mechanisms. Based this, provides insights into new molecular mechanisms reference developing anti-osteoporosis future.

Language: Английский

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Antioxidant, Anti-Inflammatory, Anti-Menopausal, and Anti-Cancer Effects of Lignans and Their Metabolites

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(24), P. 15482 - 15482

Published: Dec. 7, 2022

Since chronic inflammation can be seen in severe, long-lasting diseases such as cancer, there is a high demand for effective methods to modulate inflammatory responses. Among many therapeutic candidates, lignans, absorbed from various plant sources, represent type of phytoestrogen classified into secoisolariciresionol (Seco), pinoresinol (Pino), matairesinol (Mat), medioresinol (Med), sesamin (Ses), syringaresinol (Syr), and lariciresinol (Lari). Lignans consumed by humans further modified END or ENL the activities gut microbiota. are known exert antioxidant anti-inflammatory activities, together with activity estrogen receptor-dependent pathways. may have potential postmenopausal symptoms, including cardiovascular disease, osteoporosis, psychological disorders. Moreover, antitumor efficacy lignans has been demonstrated cancer cell lines, hormone-dependent breast prostate well colorectal cancer. Interestingly, molecular mechanisms these involve inhibition signals, nuclear factor (NF)-κB pathway. Therefore, we summarize recent vitro vivo studies evaluating biological effects focusing on their values agents.

Language: Английский

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

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 94, P. 102196 - 102196

Published: Jan. 12, 2024

Language: Английский

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Luteolin rescues postmenopausal osteoporosis elicited by OVX through alleviating osteoblast pyroptosis via activating PI3K-AKT signaling

Phytomedicine, Journal Year: 2024, Volume and Issue: 128, P. 155516 - 155516

Published: March 16, 2024

Recently, osteoblast pyroptosis has been proposed as a potential pathogenic mechanism underlying osteoporosis, although this remains to be confirmed. Luteolin (Lut), flavonoid phytochemical, plays critical role in the anti-osteoporosis effects of many traditional Chinese medicine prescriptions. However, its protective impact on osteoblasts postmenopausal osteoporosis (PMOP) not elucidated. This research aimed determine effect Lut ameliorating PMOP by alleviating and sustaining osteogenesis. was designed investigate novel both cell animal models. Ovariectomy-induced models were established mice with/without daily gavaged 10 or 20 mg/kg body weight Lut. The bone microstructure, metabolism oxidative stress evaluated with 0.104 Estradiol Valerate Tablets positive control. Network pharmacological analysis molecular docking employed mechanisms treatment. Subsequently, impacts PI3K/AKT axis, stress, mitochondria, assessed. In vitro, cultured (MC3T3-E1(14) cells exposed H2O2 examine signaling pathway, osteogenic differentiation, mitochondrial function, pyroptosis. Our findings demonstrated that Lut, similar control drug, effectively reduced systemic loss enhanced induced ovariectomy. indicated axis target, response nuclear membrane function being key mechanisms. Consequently, investigated. vivo data revealed deactivated following ovariectomy, restored phosphorylation proteins, thereby reactivating axis. Additionally, alleviated abnormalities intervention mitigated inhibition osteogenesis, well H2O2-induced Furthermore, attenuated ROS accumulation dysfunction. including osteogenesis restoration, anti-pyroptosis, maintenance, all reversed LY294002 (a pathway inhibitor). summary, could improve dysfunction, alleviate GSDME-mediated maintain via activating PI3K/Akt offering new therapeutic strategy for PMOP.

Language: Английский

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Ginsenosides from Panax ginseng as Key Modulators of NF-κB Signaling Are Powerful Anti-Inflammatory and Anticancer Agents

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6119 - 6119

Published: March 24, 2023

Nuclear factor kappa B (NF-κB) signaling pathways progress inflammation and immune cell differentiation in the host response; however, uncontrollable stimulation of NF-κB is responsible for several inflammatory illnesses regardless whether conditions are acute or chronic. Innate cells, such as macrophages, microglia, Kupffer secrete pro-inflammatory cytokines, TNF-α, IL-6, IL-1β, via activation subunits, which may lead to damage normal including neurons, cardiomyocytes, hepatocytes, alveolar cells. This results occurrence neurodegenerative disorders, cardiac infarction, liver injury, eventually systemic cancer. Recently, ginsenosides from

Language: Английский

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CXCR4-BTK axis mediate pyroptosis and lipid peroxidation in early brain injury after subarachnoid hemorrhage via NLRP3 inflammasome and NF-κB pathway

Redox Biology, Journal Year: 2023, Volume and Issue: 68, P. 102960 - 102960

Published: Nov. 10, 2023

C-X-C chemokine receptor type 4 (CXCR4) is critical for homeostasis of the adaptive and innate immune system in some CNS diseases. Bruton's tyrosine kinase (BTK) an essential that regulates inflammation cells through multiple signaling pathways. This study aims to explore effect CXCR4 BTK on neuroinflammation pathogenesis early brain injury (EBI) after subarachnoid hemorrhage (SAH). Our results showed expression p-BTK increased significantly at 24 h SAH vivo vitro. Ibrutinib improved neurological impairment, BBB disruption, cerebral edema, lipid peroxidation, neuronal death SAH. Inhibition phosphorylation promoted vitro transition hemin-treated proinflammatory microglia anti-inflammatory state, inhibited p-P65 microglial pyroptosis. NLRP3 deficiency can reduce pyroptosis mice. Moreover, inhibition suppress NLRP3-mediated pyroptosis, NF-κB activation NOX2 vitro, ibrutinib abolish CXCR4-aggravated damage EBI The levels CSF patients increased, it positively correlated with GSDMD IL-1β levels, have a moderate diagnostic value outcome 6-month follow-up. findings revealed P-BTK peroxidation potential role patients. CXCR4-BTK axis attenuate by regulating

Language: Английский

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Exposure to Di-(2-Ethylhexyl) phthalate drives ovarian dysfunction by inducing granulosa cell pyroptosis via the SLC39A5/NF-κB/NLRP3 axis

Ecotoxicology and Environmental Safety, Journal Year: 2023, Volume and Issue: 252, P. 114625 - 114625

Published: Feb. 10, 2023

Endocrine-disrupting chemicals (EDCs) have been reported to affect populations by disrupting the human endocrine system. Di-(2-ethylhexyl) phthalate (DEHP) is an EDC that present in various consumer products. Exposure DEHP could contribute reproductive system dysfunction, with subsequent adverse female outcomes. Granulosa cells (GCs) play essential roles ovarian function and fertility. To further reveal underlying mechanism which impairs fertility affects normal of GCs, vivo vitro experiments were performed. Transcript sequencing was used identify genes differentially expressed GCs after treatment. SLC39A5 shown be overexpressed group compared control group. treatment overexpression activated NF-κB-related factors, followed increase transcript expression level NLRP3. NLRP3 inflammasomes crucial pyroptosis acting as sensors. Pyroptosis a type inflammation-related cell death associated diseases, including cancer polycystic ovary syndrome. Activation NF-κB contributed upregulation while factors downregulated inhibition JSH-23. The same phenomenon also observed mouse model DEHP-treated mice had higher levels markers GCs. Moreover, this partially reversed inhibitor disrupted function-related inhibited proliferation Reproductive impairment exposed DEHP. lower body weight, smaller organs, fewer healthy follicles, diminished reserve. Thus, contributes dysfunction inducing via SLC39A5/NF-κB/NLRP3 axis

Language: Английский

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Urolithin A Alleviates Colitis in Mice by Improving Gut Microbiota Dysbiosis, Modulating Microbial Tryptophan Metabolism, and Triggering AhR Activation

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(20), P. 7710 - 7722

Published: May 11, 2023

Urolithin A (UroA) is a microbial metabolite derived from ellagitannins and ellagic acid with good bioavailability. In this study, we explored the anticolitis activity of UroA clarified mechanism by 16S rDNA sequencing metabonomics. alleviated dextran sulfate sodium (DSS)-induced colitis in mice, characterized decreased disease index, increased colon length, improved colonic histopathological lesions, along inhibited phosphorylation mitogen-activated protein kinase signaling pathway. addition, gut microbiota dysbiosis modulated metabolome. Furthermore, targeted metabolomics focused on tryptophan catabolites showed that significantly production indole-3-aldehyde (IAld) subsequently led to expression aryl hydrocarbon receptor (AhR) promoted serum content IL-22 mice colitis. Collectively, our data identified novel improving dysbiosis, modulating metabolism, promoting IAld production, triggering AhR/IL-22 axis activation. However, limitation noted study these beneficial effects were found at 50 μM vitro 20 mg/kg vivo, which nonphysiological concentrations.

Language: Английский

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