The mitochondrial permeability transition pore (mtPTP) plays a vital role in altering the structure and function of mitochondria. Cyclophilin D (CypD) is a mitochondrial protein that regulates mtPTP function and a known drug target for therapeutic studies involving mitochondria. While the effect of aromatase inhibition on the mtPTP has been studied previously, the effect of anastrozole on the mtPTP has not been completely elucidated. The role of anastrozole in modulating the mtPTP was evaluated by docking, molecular dynamics and network-guided studies using human CypD data. The peripheral blood mononuclear cells (PBMCs) of patients with mitochondrial disorders and healthy controls were treated with anastrozole and evaluated for mitochondrial permeability transition pore (mtPTP) function and apoptosis using a flow cytometer. Spectrophotometry was employed for estimating total ATP levels. The anastrozole-CypD complex is more stable than cyclosporin A (CsA)-CypD. Anastrozole performed better than cyclosporine in inhibiting mtPTP. Additional effects included inducing mitochondrial membrane depolarization and a reduction in mitochondrial swelling and superoxide generation, intrinsic caspase-3 activity and cellular apoptosis, along with an increase in ATP levels. Anastrozole may serve as a potential therapeutic agent for mitochondrial disorders and ameliorate the clinical phenotype by regulating the activity of mtPTP. However, further studies are required to substantiate our preliminary findings.Communicated by Ramaswamy H. Sarma.
- MeSH
- adenosintrifosfát metabolismus MeSH
- anastrozol farmakologie metabolismus MeSH
- cyklofiliny genetika metabolismus MeSH
- leukocyty mononukleární metabolismus MeSH
- lidé MeSH
- mitochondriální nemoci * metabolismus MeSH
- mitochondrie metabolismus MeSH
- peptidylprolylisomerasa F MeSH
- přechodový pór mitochondriální permeability * metabolismus farmakologie MeSH
- transportní proteiny mitochondriální membrány metabolismus farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Research confirms the negative relationship between early marriage and mothers' and children's health outcomes. This is why studies of the changes in age at marriage are an important task from the point of view of the health status and well-being of a mother and her offspring, especially in groups represented by extremely disadvantaged social strata in India. The results of such studies may influence the future family planning policy in the country. OBJECTIVES: This study aims to investigate the trend of age at marriage among the Scheduled Castes (SCs) women from two Indian states: Madhya Pradesh and Uttar Pradesh relative to the level of education and also to socioeconomic changes in the states. These states manifest the highest proportion of girls getting married below the age of 18 years-far above the proportion observed in entire India. METHODS: Women from Scheduled Caste, N = 1,612, aged 25-65, born in 1950-1990 were investigated. A modern semiparametric regression approach was used. To capture the relationship between age at marriage and year of birth, categories of women's level of education (illiterate; primary: 1st-5th standards; middle school: 6th-8th standards; high school: 9th-10th standards; higher secondary: 11th-12th standards), and categories of the profession (women working in the agricultural sector or the non-agricultural sector), flexible framework of the Generalized Additive Model (GAM) was applied. RESULTS: A significant impact of the cohort defined by the year of birth (<0.001), and women's education (<0.001) on age at marriage was noted, while the influence of women's occupation was not significant (p = 0.642). Mean age at marriage differed significantly with different education level. Women who graduated from primary school married 0.631 years later on average than illiterate ones, while those who graduated from middle schools, high schools (9th-10th standards) and higher secondary schools married significantly later than illiterate ones by 1.454 years and 2.463 years, respectively. Age at marriage increased over time: from slightly above 15 years in the cohort of illiterate women born in 1950 to almost 19 years in quite well-educated women born in 1990. The average age at marriage estimated for four education levels in 1990 ranged between 16.39 years (95%CI: 15.29-17.50) in the group of illiterate women and 18.86 years (95%CI: 17.76-19.95) in women graduated from high and higher secondary schools. CONCLUSION: The rise of age at marriage can be partly explained by the increase of females enrolled in schools, the alleviation of poverty, and the implementation of social programs for women.
- MeSH
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- politika plánování rodičovství * MeSH
- porod MeSH
- rozvojové země MeSH
- senioři MeSH
- školy MeSH
- socioekonomické faktory MeSH
- společenská třída * MeSH
- stupeň vzdělání MeSH
- těhotenství MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- senioři MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Indie MeSH
Head and neck cancer is the sixth most common cancer across the globe. This is generally associated with tobacco and alcohol consumption. Cancer in the pharynx majorly arises through human papillomavirus (HPV) infection, thus classifying head and neck squamous cell carcinoma (HNSCC) into HPV-positive and HPV-negative HNSCCs. Aberrant, mesenchymal-epithelial transition factor (c-MET) signal transduction favors HNSCC progression by stimulating proliferation, motility, invasiveness, morphogenesis, and angiogenesis. c-MET upregulation can be found in the majority of head and neck squamous cell carcinomas. c-MET pathway acts on several downstream effectors including phospholipase C gamma (PLCγ), cellular Src kinase (c-Src), phosphotidylinsitol-3-OH kinase (PI3K), alpha serine/threonine-protein kinase (Akt), mitogen-activated protein kinase (MAPK), and wingless-related integration site (Wnt) pathways. c-MET also establishes a crosstalk pathway with epidermal growth factor receptor (EGFR) and contributes towards chemoresistance in HNSCC. In recent years, the signaling communications of c-MET/HGF in metabolic dysregulation, tumor-microenvironment and immune modulation in HNSCC have emerged. Several clinical trials have been established against c-MET/ hepatocyte growth factor (HGF) signaling network to bring up targeted and effective therapeutic strategies against HNSCC. In this review, we discuss the molecular mechanism(s) and current understanding of c-MET/HGF signaling and its effect on HNSCC.
- MeSH
- chemorezistence genetika MeSH
- energetický metabolismus MeSH
- hepatocytární růstový faktor metabolismus MeSH
- imunita MeSH
- lidé MeSH
- management nemoci MeSH
- náchylnost k nemoci MeSH
- nádorové biomarkery MeSH
- nádorové mikroprostředí genetika imunologie MeSH
- nádory hlavy a krku etiologie metabolismus patologie terapie MeSH
- protokoly protinádorové kombinované chemoterapie škodlivé účinky terapeutické užití MeSH
- protoonkogenní proteiny c-met metabolismus MeSH
- signální transdukce * MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
