Role of Endoplasmic Reticulum Stress in Nano-Selenium Alleviating Prehierarchical Follicular Atresia Induced by Mercury in Laying Hens.

This study investigated that the effect of nano-selenium (nano-Se) addition preventing prehierarchical follicular atresia induced by mercury (Hg) exposure in laying hens. Furthermore, endoplasmic reticulum (ER) stress pathway was explored to reveal the protective mechanism of nano-Se in vitro. The results revealed that Hg could significantly reduce laying performance (P < 0.05) and egg quality (P < 0.05), whereas nano-Se addition partially reversed the reductions. Besides, Hg significantly induced the deposition of Hg in prehierarchical follicles (P < 0.05) and prehierarchical follicular atresia (P < 0.05), whereas nano-Se addition could alleviate these toxicities in vitro. In addition, Hg exposure could significantly reduce cell viability (P < 0.05) and induce pyknotic nucleus in prehierarchical granulosa cells, while nano-Se addition reversed these effects. The levels of follicle-stimulating hormone (P < 0.05), luteinizing hormone (P < 0.05), progesterone (P < 0.05), and estradiol (P < 0.05) were significantly decreased after Hg exposure in vitro. However, nano-Se addition reversed the decreases of sex hormone levels. Furthermore, Hg exposure significantly increased the gene expressions of CHOP (P < 0.05), PERK (P < 0.05), ATF4 (P < 0.05), ATF6 (P < 0.05), ASK1 (P < 0.05), IRE1α (P < 0.05), TRAF2 (P < 0.05), caspase-9 (P < 0.05), caspase-3 (P < 0.05), and Bax/Bcl-2 (P < 0.05), whereas nano-Se addition reversed these increases of gene expressions in vitro. In summary, this study provides that Hg can induce prehierarchical follicular atresia, whereas nano-Se addition can ameliorate it, and elucidates an important role of ER stress in nano-Se alleviating prehierarchical follicular atresia induced by Hg in laying hens.

Status quo of exercise participation among gastric cancer patients after radical gastrectomy and analysis of the influencing factors.

BACKGROUND: To investigate the status quo of participation in exercise among gastric cancer patients after radical gastrectomy and analyze the influencing factors. METHODS: Convenient sampling was used to conduct a questionnaire survey of 163 patients after radical gastric cancer surgery from January to December 2020. The survey content included general information, exercise participation, exercise knowledge, attitude, and social support. Descriptive statistics, single factor analysis, and multiple linear regression analysis were performed using Statistical Product and Service Solutions 24.0 (SPSS24.0, IBM, USA). RESULTS: After radical gastrectomy, the form of exercise that patients participated in was relatively simple. The average amount of exercise involved was 8.10 Mets-h/week, which was at the level of almost no exercise. Univariate analysis showed that differences in age, gender, education level, work status, main caregivers and sports knowledge, attitudes, and social support levels all led to different levels of exercise participation. Multiple linear regression analysis showed that the factors affecting the patient's level of participation in exercise included age, degree of self-care in life, attitude towards exercise after surgery, and level of social support. CONCLUSIONS: The status quo of exercise participation among gastric cancer patients after radical gastrectomy is not ideal. In this study, we found that age, level of self-care in life, sports attitude, and level of social support were the main factors affecting the exercise participation of patients. Therefore, improving patients' self-care ability, exercise attitude, and increasing social support may play an important role in improving the status quo of patients' exercise participation after radical gastric cancer surgery.

Effectiveness of aerobic exercise on upper limb function following breast cancer treatment: a systematic review and meta-analysis.

BACKGROUND: Aerobic exercise is currently considered to be an effective method of rehabilitation in breast cancer patients. Studies have shown that aerobic exercise after breast cancer surgery can improve upper limb function, cardiopulmonary function, and quality of life. Breast cancer rehabilitation guidelines encourage patients to actively participate in aerobic exercise to promote rehabilitation, the current study is to evaluate the effectiveness of aerobic exercise on upper limb muscle strength and range of motion (ROM) following breast cancer treatment. METHODS: Electronic databases (Cochrane Library, PubMed, Web of Science, EBSCO and Embase) were searched for randomized controlled trials (RCTs) published before September 1, 2019, using the search terms "aerobic exercise", "exercise", "breast cancer", "muscle strength", "strength", "flexibility" and "function". Grip strength and shoulder joint ROM were used to evaluate upper limb strength and upper limb flexibility respectively. All statistical tests were performed using RevMan5.3 software. RESULTS: Nine RCTs (421 patients) were included for analysis, with JBI scores ranging from 19 to 23, and bias grade B for all studies among which, there were six studies reported change in grip strength, and five studies reported change in shoulder joint ROM. Meta-analysis showed a statistically significant difference in shoulder flexion ROM (MD =4.97, 95% CI: 0.47-9.46, P=0.03), shoulder abduction ROM (MD =8.95, 95% CI: 0.99-16.91, P=0.03), shoulder internal rotation ROM (MD =3.45, 95% CI: 1.80-5.09, P<0.0001), shoulder external rotation ROM (MD =7.69, 95% CI: 0.06-15.32, P=0.05) between the intervention and control groups following completion of the aerobic exercise intervention, while there were no significant improvement with respect to grip strength and shoulder extension ROM (P>0.05). CONCLUSIONS: Aerobic exercise could improve shoulder joint ROM in breast cancer survivors, but shows no obvious effect on the improvement of upper limb strength.

The rational discovery of multipurpose inhibitors of the ornithine decarboxylase.

Metabolic reprograming is a hallmark of cancer, and the polyamine metabolic network is dysregulated in many cancers. Ornithine decarboxylase (ODC) is a rate-limiting enzyme for polyamine synthesis in the polyamine metabolic network. In many cancer cells, ODC is over-expressed, so this enzyme has been an attracting anti-cancer drug target. In the catalysis axis (pathway), ODC converts ornithine to putrescine. Meanwhile, ODC's activity is regulated by protein-protein interactions (PPIs), including the ODC-OAZ1-AZIN1 PPI axis and its monomer-dimer equilibrium. Previous studies showed that when ODC's activity is inhibited, the PPIs might counteract the inhibition efficiency. Therefore, we proposed that multipurpose inhibitors that can simultaneously inhibit ODC's activity and perturb the PPIs would be very valuable as drug candidates and molecular tools. To discover multipurpose ODC inhibitors, we established a computational pipeline by combining positive screening and negative screening. We used this pipeline for the forward screening of multipurpose ligands that might inhibit ODC's activity, block ODC-OAZ1 interaction and enhance ODC non-functional dimerization. With a combination of different experimental assays, we identified three multipurpose ODC inhibitors. At last, we showed that one of these inhibitors is a promising drug candidate. This work demonstrated that our computational pipeline is useful for discovering multipurpose ODC inhibitors, and multipurpose inhibitors would be very valuable. Similar with ODC, there are a lot of proteins in human proteome that act as both enzymes and PPI components. Therefore, this work is not only presenting new molecular tools for polyamine study, but also providing potential insights and protocols for discovering multipurpose inhibitors to target more important protein targets.

Discovery of Covalent Ligands via Noncovalent Docking by Dissecting Covalent Docking Based on a "Steric-Clashes Alleviating Receptor (SCAR)" Strategy.

Covalent ligands modulating protein activities/signals have attracted unprecedented attention in recent years, but the insufficient understanding of their advantages in the early days of drug discovery has hindered their rational discovery and development. This also left us inadequate knowledge on the rational design of covalent ligands, e.g., how to balance the contribution from the covalent group and the noncovalent group, respectively. In this work, we dissected the noncovalent docking from covalent docking by creating SCARs (steric-clashes alleviating receptors). We showed that the SCAR method outperformed those specifically developed but more complicated covalent docking protocols. We furthermore provided a "proof-of-principle" example by implementing this method in the first high-throughput screening and discovery of novel covalent inhibitors of S-adenosylmethionine decarboxylase. This work demonstrated that noncovalent groups play a predeterminate role in the design of covalent ligands, and would be of great value in accelerating the discovery and development of covalent ligands.