Targeting the mTOR-Autophagy Axis: Unveiling Therapeutic Potentials in Osteoporosis DOI Creative Commons

Rongjin Chen,

Chenhui Yang,

Fei Yang

и другие.

Biomolecules, Год журнала: 2024, Номер 14(11), С. 1452 - 1452

Опубликована: Ноя. 15, 2024

Osteoporosis (OP) is a widespread age-related disorder marked by decreased bone density and increased fracture risk, presenting significant public health challenge. Central to the development progression of OP dysregulation mechanistic target rapamycin (mTOR)-signaling pathway, which plays critical role in cellular processes including autophagy, growth, proliferation. The mTOR-autophagy axis emerging as promising therapeutic due its regulatory capacity metabolism homeostasis. This review aims (1) elucidate mTOR signaling OP, (2) explore interplay between autophagy context cell activity, (3) assess potential targeting pathway with modulators innovative strategies for treatment. By examining interactions among mTOR, insights from various types impact on different cells, this underscores complexity mTOR's health. Despite advances, gaps remain understanding detailed mechanisms effects function, highlighting need comprehensive clinical trials establish efficacy safety inhibitors management. Future research directions include clarifying molecular investigating combined benefits modulation other approaches. Addressing these challenges crucial developing more effective treatments improving outcomes individuals thereby unveiling potentials prevalent disease.

Язык: Английский

Multiple myeloma: clinical characteristics, current therapies and emerging innovative treatments targeting ribosome biogenesis dynamics DOI Creative Commons

Mohamed Halaby Elbahoty,

Bhavyasree Papineni,

Rajeev S. Samant

и другие.

Clinical & Experimental Metastasis, Год журнала: 2024, Номер 41(6), С. 829 - 842

Опубликована: Авг. 20, 2024

Multiple myeloma (MM) is a clinical disorder characterized by aberrant plasma cell growth in the bone marrow microenvironment. Globally, prevalence of MM has been steadily increasing at an alarming rate. In United States, more than 30,000 cases will be diagnosed 2024 and it accounts for about 2% cancer diagnoses deaths, double worldwide figure. Both symptomatic active are distinguished uncontrolled growth, which results severe renal impairment, anemia, hypercalcemia, loss. drugs have approved FDA now widely used practice MM. Although triplet quadruplet induction regimens, autologous stem transplantation (ASCT), maintenance treatment used, continues to incurable illness relapses that may occur various phases its progression. patients with frailty, extramedullary disease, leukemia, central nervous system recurrence, functional high risk, elderly among those greatest current unmet needs. The cost care additional challenge. cells highly protein secretary thus dependent on activation certain translation pathways. also chance altering ribosomal protein-encoding genes like MYC mutation. this article we discuss importance ribosome biogenesis promoting RNA polymerase I inhibition as upcoming potential promise patients.

Язык: Английский

Процитировано

5
Exploring the Role of Hypoxia and HIF-1α in the Intersection of Type 2 Diabetes Mellitus and Endometrial Cancer DOI Creative Commons

A Geetha,

Kannan Harithpriya, Kumar Ganesan

и другие.

Current Oncology, Год журнала: 2025, Номер 32(2), С. 106 - 106

Опубликована: Фев. 13, 2025

Diabetes and Cancer are the most complex chronic diseases, accounting for significant global mortality morbidity. The association between Type 2 DM (T2DM) endometrial cancer (EC) is multifaced, sharing numerous risk factors, including insulin resistance, obesity, hypoxia, oxidative stress. Hypoxia plays a vital role in T2DM pathogenesis by altering level pancreatic β-cell failure through an imbalance antioxidant enzymes cellular levels, while inflammation contributes to EC malignancy. HIF-1α potent transcription factor involved modulating responses hypoxia within disease environment. Targeting signaling cascade, major metabolic regulator may contribute advanced therapeutic advances. This review focuses on EC, especially focusing HIF pathways. These intersect with key pathways pathology, such as signaling, PI3K/AKT, mTOR pathway, MUC1/HIF-1α hormonal imbalance. Understanding this relationship paves way future researchers develop HIF-1α-targeted therapies that could lead novel combination treat these comorbid conditions.

Язык: Английский

Процитировано

0
The Effect of Valine on the Synthesis of α-Casein in MAC-T Cells and the Expression and Phosphorylation of Genes Related to the mTOR Signaling Pathway DOI Open Access

Min Yang,

Xinyu Zhang, Yu Ding

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3179 - 3179

Опубликована: Март 29, 2025

This study utilized MAC-T cells cultured in vitro as a model to investigate the effects of varying concentrations valine on α-casein synthesis and its underlying regulatory mechanisms. In this experiment, were subjected 12 h starvation period, followed by addition range (a total seven concentrations: 0.000, 1.596, 3.192, 6.384, 12.768, 25.536, 51.072 mM, well 10% Fetal Bovine Serum). The suitable was determined using enzyme-linked immunosorbent assays (ELISAs). Real-time fluorescent quantitative PCR (RT-qPCR) Western blot analyses employed evaluate expression levels phosphorylation states casein alpha s1 gene (CSN1S1), s2 (CSN1S2) mTOR signaling pathway-related genes. functionality pathway further validated through rapamycin (100.000 nM) inhibition experiments. Results indicated that 1× Val (6.384 mM), 2× (12.768 4× (25.536 8× (51.072 mM) significantly enhanced (p < 0.01). Within concentration range, upregulated CSN1S1, CSN1S2, genes including RagA (RRAGA), RagB (RRAGB), RagC (RRAGC), RagD (RRAGD), mTOR, raptor (RPTOR), 4EBP1 (EIF4EBP1), eukaryotic initiation factor 4E (EIF4E), S6 Kinase 1 (S6K1) Notably, elongation 2 (EEF2) peaked at while other reached their maximum mM). Additionally, increased S6K1, 4E-binding protein-1 (4EBP1), ribosomal protein (RPS6), eEF2 0.01), with highest RPS6 observed Rapamycin treatment inhibited 0.01); however, partially mitigated inhibitory effect. conclusion, promotes activating pathway, an optimal

Язык: Английский

Процитировано

0
Targeting the mTOR-Autophagy Axis: Unveiling Therapeutic Potentials in Osteoporosis DOI Creative Commons

Rongjin Chen,

Chenhui Yang,

Fei Yang

и другие.

Biomolecules, Год журнала: 2024, Номер 14(11), С. 1452 - 1452

Опубликована: Ноя. 15, 2024

Osteoporosis (OP) is a widespread age-related disorder marked by decreased bone density and increased fracture risk, presenting significant public health challenge. Central to the development progression of OP dysregulation mechanistic target rapamycin (mTOR)-signaling pathway, which plays critical role in cellular processes including autophagy, growth, proliferation. The mTOR-autophagy axis emerging as promising therapeutic due its regulatory capacity metabolism homeostasis. This review aims (1) elucidate mTOR signaling OP, (2) explore interplay between autophagy context cell activity, (3) assess potential targeting pathway with modulators innovative strategies for treatment. By examining interactions among mTOR, insights from various types impact on different cells, this underscores complexity mTOR's health. Despite advances, gaps remain understanding detailed mechanisms effects function, highlighting need comprehensive clinical trials establish efficacy safety inhibitors management. Future research directions include clarifying molecular investigating combined benefits modulation other approaches. Addressing these challenges crucial developing more effective treatments improving outcomes individuals thereby unveiling potentials prevalent disease.

Язык: Английский

Процитировано

3