Autophagy was activated against the damages of placentas caused by nano-copper oral exposure.

Nano-copper (nano-Cu) is widely used in the pharmaceutical field as well as a feed additive for animals owing to its unique physicochemical characteristics and bioactivities. In our previous study, nano-Cu was found to hamper fetal development; however, the toxicity of nano-Cu and its effects in placental function have not been elucidated. Therefore, we investigated the toxic effects of nano-Cu using rat placenta. Pregnant Sprague-Dawley rats were orally exposed to different copper sources from the third day of gestation (GD 3) to GD 18. We found that nano-Cu (180 mg/kg) and CuCl2.2 H2O increased the accumulation of copper. Besides, nano-Cu and CuCl2.2 H2O disrupted the placental morphology and induced oxidative stress. Micro-copper (micro-Cu) caused similar toxicity in the placenta, but its effects were weaker than that of nano-Cu and CuCl2.2 H2O. In addition, exposure to nano-Cu (180 mg/kg) and CuCl2.2 H2O induced inflammation in the rat placenta. Furthermore, nano-Cu, micro-Cu, and CuCl2.2 H2O upregulated the expression of the autophagy-related proteins, Beclin-1 and LC3 II/ LC3 I, and downregulated that of p62. Moreover, nano-Cu, micro-Cu, and CuCl2.2 H2O downregulated the protein expression of PI3K, p-AKT/AKT, and p-mTOR/mTOR in rat placentas, whereas the protein expression of p-AMPK/AMPK was upregulated. Taken together, our data indicated that prenatal exposure to nano-Cu induced autophagy via the PI3K/AKT/mTOR and AMPK/mTOR pathways, which associated with oxidative stress and inflammation in rat placenta.

Long noncoding RNA MEG3 is a tumor suppressor in choriocarcinoma by upregulation of microRNA-211.

Tumor suppressor long noncoding RNA maternally expressed gene 3 (lncRNA MEG3) exists in various cancers. Nonetheless, the functions of lncRNA MEG3 in choriocarcinoma (CC) are still not well studied. We explored the effects of lncRNA MEG3 on human CC JEG-3 and BeWo cells. lncRNA MEG3 was overexpressed, and the effects of lncRNA MEG3 on cell viability, proliferation, apoptosis, migration, and invasion were assessed by the cell counting kit-8 assay, western blot analysis, flow cytometry (plus western blot analysis), and transwell assay (plus western blot analysis), respectively. Then, the expression level of miR-211 was detected by real-time quantitative polymerase chain reaction. After that, the effects of dysregulated microRNA-211 (miR-211) with overexpressing lncRNA MEG3 on JEG-3 cells and BeWo cells were testified. Western blot analysis was used to study the involvements of the signaling pathways in the lncRNA MEG3-associated modulation. We found that lncRNA MEG3 upregulation reduced cell viability, inhibited proliferation, migration and invasion, and promoted apoptosis. Expression of miR-211 was upregulated after lncRNA MEG3 overexpression. Effects of lncRNA MEG3 overexpression were augmented by miR-211 overexpression, while they were declined by miR-211 silencing. Phosphorylated levels of PI3K, AKT, and AMP-activated protein kinase (AMPK) were decreased by lncRNA MEG3 overexpression via regulation of miR-211. To sum up, lncRNA MEG3 could repress proliferation, migration and invasion, and promote apoptosis of JEG-3 and BeWo cells through upregulating miR-211. The PI3K/AKT and AMPK pathways were inhibited by lncRNA MEG3 overexpression via regulation of miR-211.

Investigating the temporal link between PM2.5 exposure and acceleration of myocardial ischemia reperfusion injury: Emphasizing the hazardous presence of metals in inhaled air.

Exposure to PM2.5 is widely acknowledged to induce cardiotoxic effects, leading to decreased myocardial tolerance to revascularization procedures and subsequent ischemia reperfusion injury (IR). However, the temporal relationship between PM2.5 exposure and vulnerability to IR, along with the underlying mechanisms, remains unclear and is the focus of this study. Female Wistar rats were exposed to PM2.5 at a concentration of 250 µg/m³ for 3 h daily over varying durations (7, 14, and 21 days), followed by IR induction. Our results demonstrated a significant increase in cardiac injury, as evidenced by increased infarct size and elevated cardiac injury markers, starting from day 14 of PM2.5 exposure, accompanied by declined cardiac function. These adverse effects were associated with apoptosis and impaired mitochondrial function, including reduced bioenergetics, mitochondrial DNA copy number and quality control mechanisms, along with inactivation of the PI3K/AKT/AMPK signalling pathways. Furthermore, analysis of myocardial tissue revealed elevated metal accumulation, particularly within mitochondria. Chelation of PM2.5 -associated metals using EDTA significantly mitigated the toxic effects on cardiac IR pathology, as confirmed in both rat myocardium and H9c2 cells. These findings suggest that metals in PM2.5 play a crucial role in inducing cardiotoxicity, impairing myocardial resilience to stress through mitochondrial accumulation and dysfunction.

Single-base editing in IGF2 improves meat production and intramuscular fat deposition in Liang Guang Small Spotted pigs.

BACKGROUND: Chinese indigenous pigs are popular with consumers for their juiciness, flavour and meat quality, but they have lower meat production. Insulin-like growth factor 2 (IGF2) is a maternally imprinted growth factor that promotes skeletal muscle growth by regulating cell proliferation and differentiation. A single nucleotide polymorphism (SNP) within intron 3 of porcine IGF2 disrupts a binding site for the repressor, zinc finger BED-type containing 6 (ZBED6), leading to up-regulation of IGF2 and causing major effects on muscle growth, heart size, and backfat thickness. This favorable mutation is common in Western commercial pig populations, but absent in most Chinese indigenous pig breeds. To improve meat production of Chinese indigenous pigs, we used cytosine base editor 3 (CBE3) to introduce IGF2-intron3-C3071T mutation into porcine embryonic fibroblasts (PEFs) isolated from a male Liang Guang Small Spotted pig (LGSS), and single-cell clones harboring the desired mutation were selected for somatic cell nuclear transfer (SCNT) to generate the founder line of IGF2T/T pigs. RESULTS: We found the heterozygous progeny IGF2C/T pigs exhibited enhanced expression of IGF2, increased lean meat by 18%-36%, enlarged loin muscle area by 3%-17%, improved intramuscular fat (IMF) content by 18%-39%, marbling score by 0.75-1, meat color score by 0.53-1.25, and reduced backfat thickness by 5%-16%. The enhanced accumulation of intramuscular fat in IGF2C/T pigs was identified to be regulated by the PI3K-AKT/AMPK pathway, which activated SREBP1 to promote adipogenesis. CONCLUSIONS: We demonstrated the introduction of IGF2-intron3-C3071T in Chinese LGSS can improve both meat production and quality, and first identified the regulation of IMF deposition by IGF2 through SREBP1 via the PI3K-AKT/AMPK signaling pathways. Our study provides a further understanding of the biological functions of IGF2 and an example for improving porcine economic traits through precise base editing.

Curcumin (CUMINUP60®) mitigates exercise fatigue through regulating PI3K/Akt/AMPK/mTOR pathway in mice.

Curcumin is a chemical constituent extracted from Curcuma longa L. Several clinical and preclinical studies have demonstrated that it can mitigate exercise fatigue, but the exact mechanism is still unknown. Therefore, we applied a mouse model of exercise fatigue to investigate the possible molecular mechanisms of curcumin's anti-fatigue effect. Depending on body mass, Kunming mice were randomly divided into control, caffeine (positive drug), and curcumin groups, and were given 28 days intragastric administration. Both the caffeine group and curcumin group showed significant improvement in exercise fatigue compared to the control group, as evidenced by the increase in time to exhaustion, as well as the higher quadriceps coefficient, muscle glycogen (MG) content, and increase in the expression of Akt, AMPK, PI3K, and mTOR proteins. While the curcumin group also significantly improved the exercise fatigue of the mice, demonstrating a lower AMP/ATP ratio and lactic acid (LA) content, and increased glycogen synthase (GS), and myonectin content compared to the caffeine group. Therefore, in the present study, we found that curcumin can exert a similar anti-fatigue effect to caffeine and may act by regulating energy metabolism through modulating the expression of the proteins in the PI3K/Akt/AMPK/mTOR pathway.

10-Gingerol, a Phytochemical Derivative from "Tongling White Ginger", Inhibits Cervical Cancer: Insights into the Molecular Mechanism and Inhibitory Targets.

With the aim of evaluating anticancerous activities of 10-gingerol (10-G) against HeLa cells, it was purified and identified from "Tongling white ginger" by HSCCC, UPLC-TOF-MS/MS, and NMR analysis, respectively. 10-G inhibited the proliferation of HeLa cells at IC50 (29.19 µM) and IC80 (50.87 µM) with altered cell morphology, increased cytotoxicity, and arrested cell cycle in the G0/G1 phase. Most cell cycle related genes and protein expression significantly decreased, followed by a slight decrease in a few without affecting cyclin B1 and cyclin E1 (protein). Both death receptors significantly up-regulated and activated apoptosis indicators (caspase family). Furthermore, significant changes in mitochondria-dependent pathway markers were observed and led to cell death. 10-G led to PI3K/AKT inhibition and AMPK activation to induce mTOR-mediated cell apoptosis in HeLa cells. These results can be an asset to exploit 10-G with other medicinal plant derivatives for future applications.