Relationship between chromatin configuration and in vitro maturation ability in guinea pig oocytes.

BACKGROUND: Germinal vesicle (GV) chromatin configurations of oocytes are proposed to be related to oocyte competence and may reflect the quality of oocyte. Currently, a limited number of published studies investigated the GV chromatin configurations of guinea pig oocytes. OBJECTIVE: In this study on the in vitro maturation (IVM) of guinea pig oocytes, we examined the changes in their GV chromatin configurations during meiotic progression. METHODS: Based on the degree of chromatin compaction, the GV chromatin configurations of guinea pig oocytes could be divided into three categories depending on whether the nucleolus-like body (NLB) was surrounded or partly surrounded by compacted chromatin, namely the uncondensed (NSN), the intermediate type (SN-1) and the compacted type (SN-2). RESULTS: The percentage of cells displaying the SN-2 configuration increased with the growth of guinea pig oocytes, suggesting that this configuration presents the potential for maturation in oocytes. Oocytes derived from larger follicle exhibited increased meiotic potential. Serum starvation affected the GV chromatin configurations of guinea pig oocytes. CONCLUSIONS: Collectively, these results suggest that the SN-2 type might be a more mature form of configuration in guinea pig oocyte, whose proportion was associated with the follicle size and susceptible to the environment (e.g. serum concentration).

Research advances in molecular mechanisms underlying the pathogenesis of cystic fibrosis: From technical improvement to clinical applications (Review).

Cystic fibrosis (CF) is a chronic disease causing severe impairment to the respiratory system and digestive tracts. Currently, CF is incurable. As an autosomal recessive disorder, the morbidity of CF is significantly higher among Caucasians of European descent, whereas it is less pervasive among African and Asian populations. The disease is caused by identical mutations (homozygosity) or different mutations (heterozygosity) of an autosomal recessive mutation at position 7q31.2­q31.1 of chromosome 7. Diagnostic criteria and guidelines work concurrently with laboratory detection to facilitate precise CF detection. With technological advances, the understanding of CF pathogenesis has reached an unprecedented level, allowing for increasingly precise carrier screening, more effective early stage CF intervention and improved prognostic outcomes. These advances significantly increase the life quality and expectancy of patients with CF. Given the numerous improvements in the field of CF, the current review summarized the technical advances in the study of the molecular mechanisms underlying CF, as well as how these improvements facilitate the clinical outcomes of CF. Furthermore, challenges and obstacles to overcome are discussed.

Cystic fibrosis transmembrane conductance regulator ameliorates lipopolysaccharide-induced acute lung injury by inhibiting autophagy through PI3K/AKT/mTOR pathway in mice.

OBJECTIVE: The beneficial role of Cystic fibrosis transmembrane conductance regulator (CFTR) was reported in acute lung injury (ALI), however, there was no direct evidence supporting the relationship between CFTR and cell autophagy in ALI. Here, this study is to analyze the protective role of CFTR on autophagy in lipopolysaccharide (LPS)-induced ALI mice and its special mechanism. METHODS: ALI mouse models were established by the stimulation of LPS. ALI mice were subjected to tail vein injection of Lv-CFTR, intraperitoneal injection of autophagy activator RAPA or tail vein injection of Lv-sh-HMGB1 before lung tissues and bronchoalveolar lavage fluid (BALF) were collected. The expression levels of CFTR, HMGB1, Beclin-1, p62, p-AKT, p-mTOR, and LC3-II/LC3-I ratio were estimated by qRT-PCR and Western blot. The lung edema in ALI mice was inspected by wet/dry weight (W/D) ratio. Hematoxylin and eosin (H&E) staining was utilized to observe pathological features of lung tissue. Immunofluorescence was applied to determine the expression intensity of LC-3. The superoxidase dismutase (SOD) and myeloperoxidase (MPO) activity and malondialdehyde (MDA) content were assayed, and inflammatory response in ALI mice was measured. RESULTS: ALI mouse models were successfully induced by LPS, evidenced by an enhanced inflammatory response in lung tissues, heightened W/D ratio and cell autophagy markers. ALI mice had suppressed expression of CFTR, while injection of CFTR overexpression in ALI mice attenuated inflammation, autophagy, MPO activity and MDA content in addition to elevating SOD activity. Moreover, CFTR overexpression could increase the p-AKT, and p-mTOR. Overexpression of HMGB1 could reverse the expression pattern in mice injected with CFTR overexpression. CONCLUSION: CFTR could inhibit cell autophagy by enhancing PI3K/AKT/mTOR signaling pathway, thereby playing a protective role in LPS-induced ALI in mice.