OBJECTIVE: To study the regulatory effect of Cheng's Juanbi Decoction (JBT) on autophagy in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and role of PI3K/Akt/mTOR signaling axis in the mechanism mediating this effect. METHODS: CCK8 assay was used to determine the optimal concentration and treatment time of JBT for inhibiting the viability of RA- FLS. The effect of freeze-dried powder of JBT, RAPA, or both on morphology of the autophagosomes in RA-FLS was observed under transmission electron microscope, and the changes in the number of autophagosomes and autolysosomes were observed with autophagy double-labeled adenovirus experiment. RT-qPCR and Western blotting were used to detect the expression levels of the related indicators. RESULTS: The results of CCK8 assay showed that treatment with 0.5 mg/mL JBT for 12 h produced the optimal effect for inhibiting RA-FLS viability. Observation with transmission electron microscope and the results of the autophagy double-labeled adenovirus experiment both showed the presence of a small number of autophagosomes in control RA-FLS group, and treatment with JBT significantly increased the number of autophagosomes and lowered the number of autophagolysosomes in the cells. Compared with the control cells and the cells treated with JBT or RAPA alone, the cells treated with both JBT and RAPA showed significantly decreased mRNA levels of PI3K, Akt and mTOR (P < 0.01) but without significant changes in their protein expressions (P > 0.05); the combined treatment significantly inhibited the protein expressions of p-PI3K, p-Akt, p-mTOR, and P62 (P < 0.05) and upregulated the protein expressions of Beclin-1 and LC3B (P < 0.05) in the cells. CONCLUSION JBT can inhibit the survival rate of RA-FLS and increase the level of autophagy possibly through a mechanism that down-regulates PI3K/Akt/mTOR signaling pathway.
Humans ; Phosphatidylinositol 3-Kinases ; Autophagy ; Fibroblasts ; Synoviocytes ; Arthritis, Rheumatoid ; Adenoviridae ; TOR Serine-Threonine Kinases

Amino acids are fundamental nutrients for protein synthesis and cell growth (increase in cell size). Recently, many compelling evidences have shown that the level of amino acids is sensed by extra- or intra-cellular amino acids sensor(s) and regulates protein synthesis/degradation. Mammalian target of rapamycin complex 1 (mTORC1) is placed in a central position in cell growth regulation and dysregulation of mTOR signaling pathway has been implicated in many serious human diseases including cancer, diabetes, and tissue hypertrophy. Although amino acids are the most potent activator of mTORC1, how amino acids activate mTOR signaling pathway is still largely unknown. This is partly because of the diversity of amino acids themselves including structure and metabolism. In this review, current proposed amino acid sensing mechanisms to regulate mTORC1 and the evidences pro/against the proposed models are discussed.
Amino Acids ; Humans ; Hypertrophy ; Multiprotein Complexes ; Sirolimus ; TOR Serine-Threonine Kinases

Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase, which plays an essential role in cell growth, proliferation and survival. mTOR regulates the transcription of mRNA, synthesis of ribosome and gene expression for metabolism. By forming mTOR complex, it regulates cellular activities by phosphorylating its downstream proteins, such as S6 protein kinase and 4E-BP1. In recent years, the role of mTORC1 in regulating aging is gradually recognized. Studies of physiological function and the regulatory mechanisms of mTOR signaling can not only help to better understand the aging mechanism for cells or organs, but also provide insights as to finding potential new drug targets for aging related diseases. This review focuses on recent advances of mTOR and aging related diseases in hematopoietic and other organ systems.
Aging ; Hematopoietic System ; metabolism ; Humans ; Signal Transduction ; TOR Serine-Threonine Kinases ; metabolism

Common amino acid nutrients mainly contain glutamine, arginine, leucine, methionine and cysteine, which are not only the components participating in body protein synthesis, but also regulate the patients' immune system and metabolism. Glutamine can improve the intestinal barrier, reduce inflammatory reaction, and promote immunity recovery, but the clinical effects of different patients with different diseases are still lack of clear conclusions. The catabolism of arginine can produce NO, promoting the inflammatory reaction, and can also generate ornithine, alleviating inflammatory reaction and promoting wound healing. Two competing ways coexist, but the specific effects on different diseases have no clear conclusions yet. Leucine promotes muscle protein synthesis mainly through mTOR pathway, however, the influence on metabolism is still debating. Sulfur-containing amino acids methionine and cysteine can promote the synthesis of connective tissue and collagen conducive to wound healing, and their beneficial effects on lipid metabolism are of value. The purpose of this review is to cover potential beneficial physiological mechanisms of amino acid nutrients, to describe their results of clinical applications and to evaluate the interactions among individual nutrients or between individual nutrients and body.
Amino Acids ; pharmacology ; Humans ; Muscle Proteins ; Muscles ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases

Epilepsy ; drug therapy ; metabolism ; Humans ; Signal Transduction ; TOR Serine-Threonine Kinases ; antagonists & inhibitors ; metabolism

Humans ; Osteosarcoma ; metabolism ; Signal Transduction ; physiology ; TOR Serine-Threonine Kinases ; metabolism

OBJECTIVE: This study aimed to investigate the expression patterns and relationship of microtubule-associated protein 1 light chain 3 (LC3B) and mammalian target of rapamycin (mTOR) in oral leukoplakia (OLK) in smokers and never-smokers. This work also analyzed the relationship between smoking and the carcinogenic potential of OLK. METHODS: Immunohistochemistry was used to detect the expression of LC3B and mTOR in 120 patients with OLK. Clinical data from 120 smokers and never-smokers with OLK were analyzed. Subsequently, the relationships among LC3B and mTOR expression, clinical factors, and smoking were analyzed. RESULTS: Smoking and nonsmoking patients with OLK differed in terms of gender, age, lesion location, pathological typing, and carcinogenic situation. The positive rate of LC3B in never-smokers was higher than that in smokers. Whereas the positive rate of mTOR in smokers was higher than that in the corresponding never-smokers, and the differences were statistically significant (P<0.05). Smoking was positively correlated with the positive rate of mTOR (P<0.05), and had no significant correlation with LC3B expression. The positive rates of LC3B and mTOR were negatively correlated with the intensity of smoking (P<0.05). CONCLUSIONS The effect of smoking habits on OLK may be linked to the expression of proteins that are directly associated with autophagy.
Animals ; Autophagy ; Humans ; Leukoplakia, Oral ; Microtubule-Associated Proteins ; Smokers ; TOR Serine-Threonine Kinases

Immune-mediated hemocytopenia is a common cytopenic diseases without bone marrow hematopoietic abnormalities, the patient's quality of life is significantly reduced when first-line treatments are ineffective. Rapamycin, possesses a clear mechanism of targeting mTOR protein, can upregulate regulatory T cells and induces apoptosis of specific cells, by regulating the lymphocyte subsets, so as to treat various types of immune-mediated hemocytopenia with a certain therapeutic effect. In this reviews, the action mechanism and clinical application of rapamycin in immune thrombocytopenia（ITP）, autoimmune hemolytic anemia（AIHA）, acquired aplastic anemia and autoimmune lymphoproliferative syndrome（ALPS） etc. are summarized.
Anemia, Aplastic ; Humans ; Quality of Life ; Sirolimus ; therapeutic use ; T-Lymphocytes, Regulatory ; TOR Serine-Threonine Kinases

Mammalian target of rapamycin (mTOR) is an intracellular signaling pathway molecule which regulates various fundamental physiological processes. The mTOR signaling pathway plays an important role in synaptic plasticity, information transmission and processing, and neuroregulation. Dysregulation of the mTOR signaling pathway is generally considered to be related to the pathogenesis of autism spectrum disorder (ASD); meanwhile, the mTOR inhibitor can ameliorate the symptoms of ASD. The role of mTOR in the pathogenesis of ASD is summarized in this article to provide a theoretical basis for targeted therapy of ASD.
Animals ; Autism Spectrum Disorder ; Humans ; Signal Transduction ; Sirolimus ; TOR Serine-Threonine Kinases

The mammalian target of rapamycin(mTOR)is a serine/threonine protein kinase that regulates protein synthesis and degradation,cytoskeletal formation,and cell longevity.Autophagy,a catabolic process necessary for the maintenance of intracellular homeostasis,is essential for cell survival,whereas mTOR is the crucial regulator of autophagy.Alzheimer's disease(AD)is the most common cause of progressive dementia in the elderly.It has been shown that disorders of mTOR and autophagy signaling pathways are closely related to AD.In the present review,we describe the regulatory roles of mTOR signaling and autophagy pathway in AD brain and introduce drugs for AD acting via modulation of autophagy and mTOR.
Alzheimer Disease ; pathology ; Autophagy ; Humans ; Signal Transduction ; TOR Serine-Threonine Kinases ; metabolism