Retraction Note: BNIP1 inhibits cell proliferation, migration and invasion, and promotes apoptosis by mTOR in cervical cancer cells.

The article "BNIP1 inhibits cell proliferation, migration and invasion, and promotes apoptosis by mTOR in cervical cancer cells", by F.-H. Li, L. Xiang, L. Ran, S. Zhou, Z. Huang, M. Chen, W.-F. Yu, published in Eur Rev Med Pharmacol Sci 2019; 23 (4): 1397-1407-DOI: 10.26355/eurrev_201902_17096-PMID: 30840260 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer regarding a possible overlap in Figure 2A, the Editor in Chief has started an investigation to assess the validity of the results as well as possible figure manipulation. The journal investigation revealed a duplication in Figure 2A between BNIP1 panels, migration and invasion, respectively and in Control and invasion panels. Consequently, the Editor in Chief mistrusts the results presented and has decided to withdraw the article. The authors have been informed about the journal's investigation but remained unresponsive. https://www.europeanreview.org/article/17096 This article has been retracted. The Publisher apologizes for any inconvenience this may cause.

Combined training prescriptions for improving cardiorespiratory fitness, physical fitness, body composition, and cardiometabolic risk factors in older adults: Systematic review and meta-analysis of controlled trials.

Background: Improved physical fitness is important for preventing COVID-19-related mortality. So, combined training can effectively increase peak oxygen consumption, physical fitness, body composition, blood pressure, and the healthrelated characteristics of adults; however, its impact in the elderly remains unclear. Methods: This systematic review and meta-analysis aimed to evaluate the effects of combined training on older adults. Four electronic databases (PubMed, Scopus, Medline, and Web of Science) were searched (until April 2021) for randomized trials comparing the effect of combined training on cardiorespiratory fitness, physical fitness, body composition, blood pressure, and cardiometabolic risk factors in older adults. Results: Combined training significantly improved peak oxygen consumption compared to no exercise (WMD = 3.10, 95% CI: 2.83 to 3.37). Combined resistance and aerobic training induced favorable changes in physical fitness (timed up-and-go = -1.06, 30-s chair stand = 3.85, sit and reach = 4.43, 6-minute walking test = 39.22, arm curl = 4.60, grip strength = 3.65, 10-m walk = -0.47, maximum walking speed = 0.15, one-leg balance = 2.71), body composition (fat mass = -2.91, body fat% = -2.31, body mass index = -0.87, waist circumference = -2.91), blood pressure (systolic blood pressure = -8.11, diastolic blood pressure = -4.55), and cardiometabolic risk factors (glucose = -0.53, HOMA-IR = -0.14, high-density lipoprotein = 2.32, total cholesterol = -5.32) in older individuals. Finally, the optimal exercise prescription was ≥ 30 min/session × 50-80% VO2peak, ≥ 3 times/week for ≥ 12 weeks and resistance intensity 70-75% one-repetition maximum, 8-12 repetitions × 3 sets. Conclusions: Combined training improved VO2peak and some cardiometabolic risk factors in older populations. The dose-effect relationship varied between different parameters. Exercise prescriptions must be formulated considering individual needs during exercise.

Contexte: L'amélioration de la condition physique est importante pour prévenir la mortalité liée au COVID-19. Ainsi, l'entraînement combiné peut augmenter efficacement la consommation maximale d'oxygène, la forme physique, la composition corporelle, la tension artérielle et les caractéristiques liées à la santé des adultes; cependant, son impact chez les personnes âgées reste incertain. Méthodes: Cette revue systématique et cette méta-analyse visaient à évaluer les effets de l'entraînement combiné chez les personnes âgées. Quatre bases de données électroniques (PubMed, Scopus, Medline et Web of Science) ont été consultées (jusqu'en avril 2021) pour trouver des essais randomisés comparant l'effet d'un entraînement combiné sur l'aptitude cardiorespiratoire, la forme physique, la composition corporelle, la tension artérielle et les facteurs de risque cardiométabolique chez les personnes âgées. Résultats: Au total, 37 publications ont été incluses dans cette étude. L'entraînement combiné a considérablement amélioré la consommation maximale d'oxygène par rapport à l'absence d'exercice (DMP = 3,10, IC95 % : 2,83 à 3,37). La combinaison résistance + entraînement aérobie a entraîné des changements favorables dans la forme physique (démarrage chronométré = −1,06, position assise pendant 30 s = 3,85, position assise et lever = 4,43, test de marche de 6 minutes = 39,22, flexion des bras = 4,60, adhérence force = 3,65, marche de 10 m = −0,47, vitesse de marche maximale = 0,15, équilibre sur une jambe = 2,71), composition corporelle (masse grasse = −2,91, pourcentage de graisse corporelle = −2,31, indice de masse corporelle = −0,87, taille circonférence = −2,91), tension artérielle (pression artérielle systolique = −8,11, pression artérielle diastolique = −4,55) et facteurs de risque cardiométabolique (glucose = −0,53, HOMA-IR = −0,14, lipoprotéines de haute densité = 2,32, cholestérol total = −5,32) chez les personnes âgées. Enfin, la prescription d'exercice optimale était ≥ 30 min/séance × 50­80 % VO2pic, ≥ 3 fois/semaine pendant ≥ 12 semaines et résistance à une intensité de 70­75 % une répétition maximale, 8­12 répétitions × 3 séries. Conclusions: L'entraînement combiné a amélioré la VO2pic et certains facteurs de risque cardiométabolique chez les populations âgées. La relation dose-effet variait entre les différents paramètres. Les prescriptions d'exercice doivent être formulées en tenant compte des besoins individuels pendant l'exercice.

PCAT1 promotes the proliferative and migratory potentials of ovarian cancer via targeting NEK2.

OBJECTIVE: The aim of this study was to clarify the potential role of PCAT1 in the occurrence and development of ovarian cancer (OC). PATIENTS AND METHODS: Expression levels of PCAT1 and NEK2 in OC tissues and cell lines were detected by quantitative Real-time polymerase chain reaction (qRT-PCR). Correlation between PCAT1 expression with tumor stage and prognosis of OC patients was analyzed. Knockdown or over-expression of PCAT1 and NEK2 were achieved by siRNA or lentivirus transfection, respectively. Subsequently, cell viability, apoptosis, cell cycle progression and migration were determined by cell counting kit-8 (CCK-8), flow cytometry and transwell assay, respectively. Furthermore, the protein levels of relative genes in Wnt pathway were detected by Western blot. RESULTS: PCAT1 was highly expressed in OC tissues and cell lines, especially in tumor tissues with stage III-IV compared with stage I-II. The prognosis of OC patients with higher expression of PCAT1 was significantly worse than those with lower expression. In vitro experiments confirmed that PCAT1 knockdown obviously inhibited proliferative and migratory potentials, whereas induced apoptosis of OC cells. No significant changes were observed in cell cycle progression of OC cells after knockdown or overexpression of PCAT1. Meanwhile, overexpression of PCAT1 remarkably upregulated the expression level of NEK2, which was the target gene of PCAT1. Interestingly, NEK2 knockdown could obviously suppress cell migration. Furthermore, Western blot results elucidated that PCAT1 knockdown could inhibit the protein levels of relative genes in Wnt pathway in OC cells. CONCLUSIONS: PCAT1 was highly expressed in OC tissues than adjacent normal tissues. PCAT1 overexpression significantly promoted proliferative and migratory potentials, whereas inhibited apoptosis of OC cells through upregulating NEK2 expression via Wnt pathway.

Correlation between endometrial receptivity with expressions of IL-1 and VEGF in rats with polycystic ovary syndrome.

OBJECTIVE: To investigate the correlation between endometrial receptivity with expressions of interleukin-1 (IL-1) and vascular endothelial growth factor (VEGF) in rats with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: A total of 24 female Sprague-Dawley (SD) 21 days old were randomly divided into control group (n=12) and PCOS group (n=12). Rats in the control group were normally raised, and PCOS model was established in rats of the PCOS group. All the rats were sacrificed when they grew to 80 days old. Immunohistochemistry was applied to detect the expressions of IL-1 and VEGF. Western blotting was performed to measure the relative expressions of IL-1 and VEGF proteins. Quantitative Polymerase Chain Reaction (qPCR) was utilized to determine the relative messenger ribonucleic acid (mRNA) expressions of IL-1 and VEGF. Data related to endometrial receptivity were detected. RESULTS: The expression levels of IL-1 and VEGF in the PCOS group declined markedly compared with those in the control group, and the differences were statistically significant (p<0.05). PCOS group had notably lower protein expressions of IL-1 and VEGF than the control group, with statistically significant differences (p<0.05). The mRNA expressions of IL-1 and VEGF in PCOS group were significantly lower than those in the control group, displaying statistically significant differences (p<0.05). Compared with that in the control group, the endometrial receptivity of rats in the PCOS group was reduced evidently, and the difference was statistically significant (p<0.05). Both IL-1 and VEGF had positive correlations with the endometrial receptivity. CONCLUSIONS: Both IL-1 and VEGF are positively correlated with the endometrial receptivity in the case of PCOS, which can serve as therapeutic targets for PCOS and improve endometrial receptivity in the future.

BNIP1 inhibits cell proliferation, migration and invasion, and promotes apoptosis by mTOR in cervical cancer cells.

OBJECTIVE: BNIP1, a member of the BH3-only protein family, plays essential roles in a variety of biological processes. However, the mechanism and function of BNIP1 are still unknown in cervical cancer. We aim to explore the roles of BNIP1 on cervical cancer cell proliferation, apoptosis, migration, and invasion abilities by mTOR signaling pathway. PATIENTS AND METHODS: qRT-PCR and Western blot assays were performed to assess BNIP, mTOR, and p70S6K1 expressions. CCK-8, transwell and flow cytometry assays were used to measure the representative proliferation, migration, invasion, and apoptosis abilities. RESULTS: Our findings indicated that BNIP1 is down-expressed in cervical cancer tissues and cells, and was negatively associated with lymphatic metastasis. Overexpression of BNIP1 suppressed proliferation, migration and invasion, and promoted apoptosis of cervical cancer cells. Silence of BNIP1 by siRNAs accelerated proliferation, migration and invasion, and inhibited apoptosis of cervical cancer cells. In addition, we found that BNIP1 significantly inhibited mTOR, p70S6K1, and p-p70S6K1 expressions; BNIP1 affected the proliferation, apoptosis, migration, and invasion abilities of cervical cancer cells by regulating mTOR expression. CONCLUSIONS: BNIP1 can be considered a marker for cervical carcinoma therapy.

Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice.

Asthma is a chronic allergic disease characterized by airway inflammation, airway hyper-responsiveness (AHR), and mucus hypersecretion. T-lymphocytes are involved in the pathogenesis of asthma, mediating airway inflammatory reactions by secreting cytokines. The phosphoinositide 3-kinase (PI3K) and Notch signaling pathways are associated with T cell signaling, proliferation, and differentiation, and are important in the progression of asthma. Thus, compounds that can modulate T cell proliferation and function may be of clinical value. Here, we assessed the effects of tangeretin, a plant-derived flavonoid, in experimental asthma. BALB/c mice at postnatal day (P) 12 were challenged with ovalbumin (OVA). Separate groups of mice (n=18/group) were administered tangeretin at 25 or 50 mg/kg body weight by oral gavage. Dexamethasone was used as a positive control. Tangeretin treatment reduced inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) and also restored the normal histology of lung tissues. OVA-specific IgE levels in serum and BALF were reduced. AHR, as determined by airway resistance and lung compliance, was normalized. Flow cytometry analyses revealed a reduced Th17 cell population. Tangeretin reduced the levels of Th2 and Th17 cytokines and raised IFN-γ levels. PI3K signaling was inhibited. The expressions of the Notch 1 receptor and its ligands Jagged 1 and 2 were downregulated by tangeretin. Our findings support the possible use of tangeretin for treating allergic asthma.

Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice

Asthma is a chronic allergic disease characterized by airway inflammation, airway hyper-responsiveness (AHR), and mucus hypersecretion. T-lymphocytes are involved in the pathogenesis of asthma, mediating airway inflammatory reactions by secreting cytokines. The phosphoinositide 3-kinase (PI3K) and Notch signaling pathways are associated with T cell signaling, proliferation, and differentiation, and are important in the progression of asthma. Thus, compounds that can modulate T cell proliferation and function may be of clinical value. Here, we assessed the effects of tangeretin, a plant-derived flavonoid, in experimental asthma. BALB/c mice at postnatal day (P) 12 were challenged with ovalbumin (OVA). Separate groups of mice (n=18/group) were administered tangeretin at 25 or 50 mg/kg body weight by oral gavage. Dexamethasone was used as a positive control. Tangeretin treatment reduced inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) and also restored the normal histology of lung tissues. OVA-specific IgE levels in serum and BALF were reduced. AHR, as determined by airway resistance and lung compliance, was normalized. Flow cytometry analyses revealed a reduced Th17 cell population. Tangeretin reduced the levels of Th2 and Th17 cytokines and raised IFN-γ levels. PI3K signaling was inhibited. The expressions of the Notch 1 receptor and its ligands Jagged 1 and 2 were downregulated by tangeretin. Our findings support the possible use of tangeretin for treating allergic asthma.

The roles of MAPKs in rabbit nucleus pulposus cell apoptosis induced by high osmolality.

BACKGROUND: Earlier work has suggested that the p38 MAPK, JNK1/2 and ERK1/2 signal pathway existed in nucleus pulposus cells and the cell growth, differentiation and apoptosis were regulated by them. Because osmotic fluctuations are inevitable in the physicochemical environment of intervertebral disc cells, high osmolality could activate p38 MAPK, JNK1/2 and ERK1/2 signal pathway. The effects of high osmolality on the catabolic program and proliferation of nucleus pulposus cells are still not clear. AIM: To explore the possible roles of MAPKs in rabbit nucleus pulposus cell apoptosis induced by high osmolality. MATERIALS AND METHODS: Rabbit nucleus pulposus cells were cultured and divided into different group at random. The cells were pretreated with inhibitor for p38 MAPK, JNK1/2 and ERK1/2 signal pathway respectively. In next step, the cells were cultured in different osmolality environment for different time at 37°C in 5% carbon dioxide incubator. After treatments, ratio of apoptosis was measured by flow cytometry, and western blotting was performed to quantify the expression of the activated forms of p38 MAPK, JNK1/2 and ERK1/2. Furthermore, immunofluorescence analysis with confocal microscopy was performed to confirm the hyperosmolality effects on activation of p38 MAPK, JNK1/2 and ERK1/2 signal pathways in nucleus pulposus cells. RESULTS: Our results show that in 500 and 600 mOsm/kg medium, rabbit nucleus pulposus cell apoptosis increased, and a persistent phosphorylation of p38 MAPK, JNK1/2 and ERK1/2 proteins were observed. In the same condition, the apoptotic cells death remarkably decreased when the p38 MAPK and JNK1/2 signal pathways were blocked by their inhibitors SB203580, SP600125 repectively. On the other side, the apoptotic cells death rate reraised greatly when the ERK1/2 signal pathways were blocked by its inhibitor PD98059. CONCLUSIONS: High osmolality activated p38MAPK, JNK1/2 and ERK1/2 in rabbit nucleus pulposus cell, and the activated p38 MAPK and JNK1/2 induced cell apoptosis, on the contrary, the activated ERK1/2 made the cell survived.

Adrenomedullin and adrenotensin regulate collagen synthesis and proliferation in pulmonary arterial smooth muscle cells

To understand the pathophysiological mechanisms of pulmonary arterial smooth muscle cell (PASMC) proliferation and extracellular-matrix accumulation in the development of pulmonary hypertension and remodeling, this study determined the effects of different doses of adrenomedullin (ADM) and adrenotensin (ADT) on PASMC proliferation and collagen synthesis. The objective was to investigate whether extracellular signal-regulated kinase (ERK1/2) signaling was involved in ADM- and ADT-stimulated proliferation of PASMCs in 4-week-old male Wistar rats (body weight: 100-150 g, n=10). The proliferation of PASMCs was examined by 5-bromo-2-deoxyuridine incorporation. A cell growth curve was generated by the Cell Counting Kit-8 method. Expression of collagen I, collagen III, and phosphorylated ERK1/2 (p-ERK1/2) was evaluated by immunofluorescence. The effects of different concentrations of ADM and ADT on collagen I, collagen III, and p-ERK1/2 protein expression were determined by immunoblotting. We also investigated the effect of PD98059 inhibition on the expression of p-ERK1/2 protein by immunoblotting. ADM dose-dependently decreased cell proliferation, whereas ADT dose-dependently increased it; and ADM and ADT inhibited each other with respect to their effects on the proliferation of PASMCs. Consistent with these results, the expression of collagen I, collagen III, and p-ERK1/2 in rat PASMCs decreased after exposure to ADM but was upregulated after exposure to ADT. PD98059 significantly inhibited the downregulation by ADM and the upregulation by ADT of p-ERK1/2 expression. We conclude that ADM inhibited, and ADT stimulated, ERK1/2 signaling in rat PASMCs to regulate cell proliferation and collagen expression.

Amplitude correction in image deconvolution for determining crystal defects at atomic level

A method is proposed to improve the image deconvolution technique based on the weak-phase object approximation for determining the crystal defects at atomic level. Originally, both the amplitude and phase modulation caused by the contrast transfer function (CTF) was removed for all reflections in the diffractogram of the image and then the deconvoluted image was obtained by carrying out the inverse FT. In this paper after removing the CTF modulation the amplitudes of reflections are further corrected by constraining the integral amplitudes to be equal to the corresponding structure factor amplitudes of perfect crystals. [110] high-resolution electron microscope images were simulated for a structure model of Si crystal containing the 60 degrees dislocation with different thickness. A comparison between deconvoluted images with the amplitudes corrected by the present method and those uncorrected is given to show the effectiveness of the method. The amplitude-crystal thickness dependence for images simulated close to the Scherzer defocus condition has been analysed and the result serves as an empirical basis of the method. The validity and limitation of the method are discussed.