Mitochondrial alterations in fatty liver diseases

Journal of Hepatology, Год журнала: 2022, Номер 78(2), С. 415 - 429

Опубликована: Окт. 7, 2022

Fatty liver diseases can result from common metabolic diseases, as well xenobiotic exposure and excessive alcohol use, all of which have been shown to exert toxic effects on hepatic mitochondrial functionality dynamics. Invasive or complex methodology limits large-scale investigations mitochondria in human livers. Nevertheless, abnormal function, such impaired fatty acid oxidation oxidative phosphorylation, drives stress has identified an important feature steatohepatitis. On the other hand, be flexible adapt ambient condition prevent triglyceride lipotoxin accumulation obesity. Experience studies xenobiotics provided insights into regulation mitochondria. Increasing awareness joint presence disease-related (lipotoxic) alcohol-related further highlights need better understand their mutual interaction potentiation disease progression. Recent clinical assessed diets bariatric surgery mitochondria, are also evolving interesting therapeutic target non-alcoholic disease. This review summarises current knowledge with a focus linked obesity, type 2 diabetes xenobiotics.

Язык: Английский

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Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Июль 18, 2022

Drug resistance represents a major obstacle in cancer management, and the mechanisms underlying stress adaptation of cells response to therapy-induced hostile environment are largely unknown. As central organelle for cellular energy supply, mitochondria can rapidly undergo dynamic changes integrate signaling pathways provide bioenergetic biosynthetic flexibility cells, which contributes multiple aspects tumor characteristics, including drug resistance. Therefore, targeting therapy overcoming has attracted increasing attention various types cancer. Multiple mitochondrial processes, dynamics, metabolism, apoptotic regulatory machinery, have been demonstrated be potential targets. However, recent insights into revealed complexity structure functions, elusive functions biology, inaccessibility mitochondria, posed challenges clinical application mitochondrial-based therapeutic strategies. discovery both novel mitochondria-targeting agents innovative approaches is urgently required. Here, we review most literature summarize molecular their intricate connection with In addition, an overview emerging strategies target effectively chemoresistance highlighted, emphasis on repositioning delivery approaches, may accelerate compounds therapy.

Язык: Английский

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Metformin in aging and aging-related diseases: clinical applications and relevant mechanisms

Theranostics, Год журнала: 2022, Номер 12(6), С. 2722 - 2740

Опубликована: Янв. 1, 2022

Aging is a natural process, which plays critical role in the pathogenesis of variety diseases, i.e., aging-related such as diabetes, osteoarthritis, Alzheimer disease, cardiovascular cancers, obesity and other metabolic abnormalities.Metformin, most widely used antidiabetic drug, has been reported to delay aging display protective effect on attenuating progression various diseases by impacting key hallmark events aging, including dysregulated nutrient sensing, loss proteostasis, mitochondrial dysfunction, altered intercellular communication, telomere attrition, genomic instability, epigenetic alterations, stem cell exhaustion cellular senescence.In this review, we provide updated information knowledge applications metformin prevention treatment diseases.We focus our discussions roles underlying mechanisms modulating treating diseases.

Язык: Английский

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Oxidative stress, the blood–brain barrier and neurodegenerative diseases: The critical beneficial role of dietary antioxidants

Acta Pharmaceutica Sinica B, Год журнала: 2023, Номер 13(10), С. 3988 - 4024

Опубликована: Июль 16, 2023

In recent years, growing awareness of the role oxidative stress in brain health has prompted antioxidants, especially dietary to receive attention as possible treatments strategies for patients with neurodegenerative diseases (NDs). The most widely studied antioxidants include active substances such vitamins, carotenoids, flavonoids and polyphenols. Dietary are found usually consumed foods fresh fruits, vegetables, nuts oils gaining popularity due recently their potential preventive protective agents against NDs, well abundant natural sources, generally non-toxic nature, ease long-term consumption. This review article examines development explores ‘two-sidedness’ blood–brain barrier (BBB) a nervous system an impeding use drug medicinal products and/or supplements prevention therapy reviews BBB permeability common suplements efficacy treatment NDs. Finally, current challenges future directions NDs using discussed, useful information on is provided.

Язык: Английский

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Functionalized Metal–Organic Framework‐Modified Hydrogel That Breaks the Vicious Cycle of Inflammation and ROS for Repairing of Diabetic Bone Defects

Small, Год журнала: 2023, Номер 19(36)

Опубликована: Май 14, 2023

The regeneration of diabetic bone defects remains challenging. Hyperglycemia causes inflammation state and excessive reactive oxygen species (ROS) during period. These two effects reinforce one another create an endless loop that is also accompanied by mitochondrial dysfunction. However, there still no effective inclusive method targeting at the aspects breaking vicious cycle. Herein, nanoparticles-Met@ZIF-8(metformin loaded zeolitic imidazolate frameworks) modified hydrogel capable releasing metformin Zn elements are constructed. This treats hyperglycemia while controlling function, reducing inflammation, restoring homeostasis. In addition, synergetic effect from ions inhibits ROS-inflammation cascade generation destroys continuous progress taking in both ROS further keeping organelles' Furthermore, with recovery mitochondria breakdown cycle, osteogenesis under a microenvironment enhanced vivo vitro. conclusion, study provides critical insight into biological mechanism potential therapy for regeneration.

Язык: Английский

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Biomaterials for diabetic bone repair: Influencing mechanisms, multi-aspect progress and future prospects

Composites Part B Engineering, Год журнала: 2024, Номер 274, С. 111282 - 111282

Опубликована: Фев. 5, 2024

Язык: Английский

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Nanozyme as a rising star for metabolic disease management

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

Опубликована: Май 6, 2024

Abstract Nanozyme, characterized by outstanding and inherent enzyme-mimicking properties, have emerged as highly promising alternatives to natural enzymes owning their exceptional attributes such regulation of oxidative stress, convenient storage, adjustable catalytic activities, remarkable stability, effortless scalability for large-scale production. Given the potent regulatory function nanozymes on stress coupled with fact that reactive oxygen species (ROS) play a vital role in occurrence exacerbation metabolic diseases, nanozyme offer unique perspective therapy through multifunctional achieving essential results treatment diseases directly scavenging excess ROS or regulating pathologically related molecules. The rational design strategies, nanozyme-enabled therapeutic mechanisms at cellular level, therapies several typical underlying are discussed, mainly including obesity, diabetes, cardiovascular disease, diabetic wound healing, others. Finally, pharmacokinetics, safety analysis, challenges, outlooks application also presented. This review will provide some instructive perspectives promote development strategies disease therapy. Graphical

Язык: Английский

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An injectable and pH-responsive hyaluronic acid hydrogel as metformin carrier for prevention of breast cancer recurrence

Carbohydrate Polymers, Год журнала: 2022, Номер 304, С. 120493 - 120493

Опубликована: Дек. 24, 2022

Язык: Английский

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Metformin in therapeutic applications in human diseases: its mechanism of action and clinical study

Molecular Biomedicine, Год журнала: 2022, Номер 3(1)

Опубликована: Дек. 9, 2022

Abstract Metformin, a biguanide drug, is the most commonly used first-line medication for type 2 diabetes mellites due to its outstanding glucose-lowering ability. After oral administration of 1 g, metformin peaked plasma concentration approximately 20–30 μM in 3 h, and then it mainly accumulated gastrointestinal tract, liver kidney. Substantial studies have indicated that exerts beneficial or deleterious effect by multiple mechanisms, apart from AMPK-dependent mechanism, also including several AMPK-independent such as restoring redox balance, affecting mitochondrial function, modulating gut microbiome regulating other signals, FBP1, PP2A, FGF21, SIRT1 mTOR. On basis these researchers tried repurpose this old drug further explored possible indications adverse effects metformin. Through investigating with clinical studies, concluded addition decreasing cardiovascular events anti-obesity, neurodegenerative disease, polycystic ovary syndrome, aging, cancer COVID-19, however, induces some effects, complaints, lactic acidosis, vitamin B12 deficiency, disease offspring impairment. Of note, dose much higher than clinically relevant dose, which may cast doubt on actual clinic. This review summarizes research developments mechanism action evidence discusses therapeutic potential safety.

Язык: Английский

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Placental Mitochondrial Function and Dysfunction in Preeclampsia

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(4), С. 4177 - 4177

Опубликована: Фев. 20, 2023

The placenta is a vital organ of pregnancy, regulating adaptation to gestational parent/fetal exchange, and ultimately, fetal development growth. Not surprisingly, in cases placental dysfunction-where aspects or function become compromised-adverse pregnancy outcomes can result. One common placenta-mediated disorder preeclampsia (PE), hypertensive with highly heterogeneous clinical presentation. wide array characteristics observed pregnant individuals neonates PE are likely the result distinct forms pathology underlying diagnosis, explaining why no one intervention has proven effective prevention treatment PE. historical paradigm highlights an important role for utero-placental malperfusion, hypoxia oxidative stress, critical mitochondrial dysfunction pathogenesis progression disease. In current review, evidence context will be summarized, highlighting how altered may feature across subtypes. Further, advances this field study therapeutic targeting mitochondria as promising discussed.

Язык: Английский

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