Assessment of the role of false-positive alerts in computer-aided polyp detection for assistance capabilities.

BACKGROUND AND AIM: False positives (FPs) pose a significant challenge in the application of artificial intelligence (AI) for polyp detection during colonoscopy. The study aimed to quantitatively evaluate the impact of computer-aided polyp detection (CADe) systems' FPs on endoscopists. METHODS: The model's FPs were categorized into four gradients: 0-5, 5-10, 10-15, and 15-20 FPs per minute (FPPM). Fifty-six colonoscopy videos were collected for a crossover study involving 10 endoscopists. Polyp missed rate (PMR) was set as primary outcome. Subsequently, to further verify the impact of FPPM on the assistance capability of AI in clinical environments, a secondary analysis was conducted on a prospective randomized controlled trial (RCT) from Renmin Hospital of Wuhan University in China from July 1 to October 15, 2020, with the adenoma detection rate (ADR) as primary outcome. RESULTS: Compared with routine group, CADe reduced PMR when FPPM was less than 5. However, with the continuous increase of FPPM, the beneficial effect of CADe gradually weakens. For secondary analysis of RCT, a total of 956 patients were enrolled. In AI-assisted group, ADR is higher when FPPM ≤ 5 compared with FPPM > 5 (CADe group: 27.78% vs 11.90%; P = 0.014; odds ratio [OR], 0.351; 95% confidence interval [CI], 0.152-0.812; COMBO group: 38.40% vs 23.46%, P = 0.029; OR, 0.427; 95% CI, 0.199-0.916). After AI intervention, ADR increased when FPPM ≤ 5 (27.78% vs 14.76%; P = 0.001; OR, 0.399; 95% CI, 0.231-0.690), but no statistically significant difference was found when FPPM > 5 (11.90% vs 14.76%, P = 0.788; OR, 1.111; 95% CI, 0.514-2.403). CONCLUSION: The level of FPs of CADe does affect its effectiveness as an aid to endoscopists, with its best effect when FPPM is less than 5.

Integrated analysis of lncRNA, miRNA and mRNA reveals novel insights into the fertility regulation of large white sows.

BACKGROUND: Improving sow fertility is extremely important as it can lead to increased reproductive efficiency and thus profitability for swine producers. There are considerable differences in fertility rates among individual animals, but the underlying molecular mechanisms remain unclear. In this study, by using different types of RNA libraries, we investigated the complete transcriptome of ovarian tissue during the luteal (L) and follicular (F) phases of the estrous cycle in Large White pigs with high (H) and low (L) fecundity, and performed a comprehensive analysis of long noncoding RNAs (lncRNAs), mRNAs and micro RNAs (miRNAs) from 16 samples by combining RNA sequencing (RNA-seq) with bioinformatics. RESULTS: In total, 24,447 lncRNAs, 27,370 mRNAs, and 216 known miRNAs were identified in ovarian tissues. The genomic features of lncRNAs, such as length distribution and number of exons, were further analyzed. We selected a threshold of P < 0.05 and |log2 (fold change)| ≥ 1 to obtain the differentially expressed lncRNAs, miRNAs and mRNAs by pairwise comparison (LH vs. LL, FH vs. FL). Bioinformatics analysis of these differentially expressed RNAs revealed multiple significantly enriched pathways (P < 0.05) that were closely involved in the reproductive process, such as ovarian steroidogenesis, lysosome, steroid biosynthesis, and the estrogen and GnRH signaling pathways. Moreover, bioinformatics screening of differentially expressed miRNAs that share common miRNA response elements (MREs) with lncRNAs and their downstream mRNA targets were performed. Finally, we constructed lncRNA-miRNA-mRNA regulation networks. The key genes in these networks were verified by Reverse Transcription Real-time Quantitative PCR (RT-qRCR), which were consistent with the results from RNA-Seq data. CONCLUSIONS: These results provide further insights into the fertility of pigs andcan contribute to further experimental investigation of the functions of these genes.

Human papillomavirus DNA, HPV L1 capsid protein and p16INK4a protein as markers to predict cervical lesion progression.

OBJECTIVES: Cervical cancer is the most common malignant tumors in women leading to serious morbidity and mortality worldwide, especially among developing countries. A main cause of the disease is the high-risk human papillomavirus (HR-HPV) infection. HSIL usually progress to cervical cancer, and low-grade lesions, including LSIL and ASCUS, mostly turn to normal or benign lesions, but there are still a small number of patients who will progress to HSIL. Up to now there is no efficient biomarker clinically available to predict people with high risk to progress into HSIL. This study was conducted to evaluate the value of human papillomavirus (HPV) DNA, p16INK4a protein, and HPV L1 capsid protein in predicting HSIL and minimizing unnecessary colposcopy treatments. METHODS: 1222 patients with HR-HPV infection or with abnormal Thinprep cytologic test (TCT) were chosen to conduct colposcopy in the cervical out-patient clinic of Shanghai First Maternity and Infant Hospital affiliated to Shanghai Tongji University from June 2014 to January 2017. TCT, cervical biopsy, HPV DNA and HPVL1 were performed on all patients. 110 patients were selected to detect p16INK4a protein. Hybrid capture 2 (HC-2) was used to detect HPV DNA, and their subgroups using gene typing system. Immunohistochemical technology was used to detect HPV L1 and p16. RESULTS: HPV DNA was positive in 1097 cases, with the positive rate of 89.7% (1097/1222). In particular, the positive expression rates of HPV DNA were 82.3, 95.7, 96.6 and 100% in Normal/CC, LSIL, HSIL and cervical cancer groups, respectively (p < 0.001). HPV L1 was negative in 781 cases with HR-HPV infection, and the overall negative rate is 71.1%. In patients with Normal/CC, LSIL and HSIL, the negative expression rates of HPV L1 were 91.3, 40 and 81.2%, respectively (p value < 0.001). In the 110 patients, HPV L1 was negative in 98.1% (53/54) of Normal/CC, 42.9% (12/28) of LSIL and 85.1% (23/27) of HSIL (p value = 0.0043). P16-positive rates in patients with Normal/CC, LSIL and HSIL were 33.3% (18/54), 75% (21/28) and 96.2% (26/27), respectively (p value < 0.001). 18 out of 28 cases express low positive (+) in LSIL, 25 out of 27 cases express strong positive (3+) in HSIL. Patients with L1(-) p16(+) including 18.5% (10/54) of normal/cervicitis, 60.7% (17/28) of LSIL and 85.1% (23/27) of HSIL (p value < 0.005). Furthermore, patients with L1(-) p16(1+) included 37% (10/27) of normal/cervicitis 59.3% (16/27) of LSIL and 3.7% (1/27) of HSIL; patients with L1(-) p16(2+) consisted of 0% of normal/cervicitis/LSIL and 100% (1/1) of HSIL; patients with L1(-) p16(3+) were composed of 0% of normal/cervicitis, 4.5% (1/22) of LSIL and 95.5% (21/22) of HSIL (p value < 0.005) (Table 6). CONCLUSION: With the increase in the degree of the cervical lesions, the expression of HPV DNA and p16 is up-regulated while HPV L1 protein is down-regulated. HPV DNA, HPV L1 and p16 are useful markers for the prediction of HSIL. Combined detection of these three markers has important potential to predicting HSIL and minimizing unnecessary colposcope examination.

Mitochondria-targeted iridium(III) complexes encapsulated in liposome induce cell death through ferroptosis and gasdermin-mediated pyroptosis.

This paper unveils a novel perspective on synthesis and characterization of the ligand 5-bromo-2-amino-2'-(phenyl-1H-imidazo[4,5-f][1,10]phenanthroline) (BAPIP), and its iridium(III) complexes [Ir(PPY-)2(BAPIP)](PF6) (1a, with PPY- as deprotonated 2-phenylpyridine), [Ir(PIQ-)2(BAPIP)](PF6) (1b, piq- denoting deprotonated 1-phenylisoquinoline), and [Ir(BZQ-)2(BAPIP)](PF6) (1c, bzq- signifying deprotonated benzo[h]quinoline). Systematic evaluation of the cytotoxicity of 1a, 1b, and 1c across diverse cell lines encompassing B16, HCT116, HepG2, A549, HeLa, and LO2 using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Unexpectedly, compounds 1b and 1c demonstrated no cytotoxicity against the above cell lines. Motivated by the pursuit of heightened anti-proliferative potential, a strategic encapsulation approach yielded liposomes 1alip, 1blip, and 1clip. As expectation, 1alip, 1blip, and 1clip displayed remarkable anti-proliferative efficacy, particularly noteworthy in A549 cells, exhibiting IC50 values of 4.9 ± 1.0, 5.9 ± 0.1, and 7.6 ± 0.2 µM, respectively. Moreover, our investigation illuminated the mitochondrial accumulation of these liposomal entities, 1alip, 1blip, and 1clip, evoking apoptosis through the mitochondrial dysfunction mediated by reactive oxygen species (ROS). The ferroptosis was confirmed by decrease in glutathione (GSH) concentrations, the downregulation of glutathione peroxidase 4 (GPX4), increase of high mobility group protein 1 (HMGB1), and lipid peroxidation. Simultaneously, pyroptosis as another mode of cell death was undertaken. RNA-sequencing was employed to investigate intricate signalling pathways. In vivo examination provided tangible evidence of 1alip in effectively curbing tumor growth. Collectively, this study provides a multifaceted mode of cellular demise orchestrated by 1a, 1alip, 1blip, and 1clip, involving pathways encompassing apoptosis, ferroptosis, and pyroptosis.

Synthesis and mitochondria-localized iridium (III) complexes induce cell death through pyroptosis and ferroptosis pathways.

This paper introduces a new ligand, 4,6-dichloro-5-(1H-imidazo [4,5-f]phenanthroline-2-yl)pyrimidin-2-amine (DPPA), and its corresponding new iridium(III) complexes: [Ir(ppy)2(DPPA)](PF6) (2a) (where ppy represents deprotonated 2-phenylpyridine), [Ir(bzq)2(DPPA)](PF6) (2b) (with bzq indicating deprotonated benzo[h]quinoline), and [Ir(piq)2(DPPA)](PF6) (2c) (piq denoting deprotonated 1-phenylisoquinoline). The cytotoxic effects of both DPPA and 2a, 2b, and 2c were evaluated against human lung carcinoma A549, melanoma B16, colorectal cancer HCT116, human hepatocellular carcinoma HepG2 cancer cell lines, as well as the non-cancerous LO2 cell line using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. While DPPA exhibited moderate anticancer activity toward A549, B16, HCT116 and HepG2 cells, complexes 2a, 2b, and 2c displayed remarkable efficacy against A549, B16, and HCT116 cells. The cell colonies and wound healing were investigated. Moreover, various aspects of the anticancer mechanisms were explored. The cell cycle analyses revealed that the complexes block cell proliferation of A549 cells during the S phase. Complex 2c induce an early apoptosis, while 2a and 2b cause a late apoptosis. The interaction of 2a, 2b and 2c with endoplasmic reticulum and mitochondria was identified, leading to elevated ROS and Ca2+ amounts. This resulted in a reduced mitochondrial membrane potential, mitochondrial permeability transition pore opening, and an increase of cytochrome c. Also, ferroptosis was investigated through measurements of intracellular glutathione (GSH), malondialdehyde (MDA), and recombinant glutathione peroxidase (GPX4) protein expression. The pyroptosis was explored via cell morphology, release of lactate dehydrogenase (LDH) and expression of pyroptosis-related proteins. RNA sequencing was applied to examine the signaling pathways. Western blot analyses illuminated that the complexes regulate the expression of Bcl-2 family proteins. Additionally, an in vivo antitumor study demonstrated that complex 2c exhibited a remarkable inhibitory rate of 58.58% in restraining tumor growth. In summary, the findings collectively suggest that the iridium(III) complexes induce cell death via ferroptosis, apoptosis by a ROS-mediated mitochondrial dysfunction pathway and GSDMD-mediated pyroptosis.

Synthesis, characterization and irradiation enhances anticancer activity of liposome-loaded iridium(III) complexes.

Herein, we synthesized and characterized two novel iridium (III) complexes: [Ir(bzq)2(PPD)](PF6) (4a, with bzq = deprotonated benzo[h]quinoline and PPD = pteridino[6,7-f][1,10]phenanthroline-11,13-diamine) and [Ir(piq)2(PPD)](PF6) (4b, with piq = deprotonated 1-phenylisoquinoline). The anticancer efficacy of these complexes, 4a and 4b, was investigated using 3-(4,5-dimethylthiazole)-2,5-diphenltetraazolium bromide (MTT). Complex 4a exhibited no cytotoxic activity, while 4b demonstrated moderate efficacy against SGC-7901, A549, and HepG2 cancer cells. To enhance their anticancer potential, we explored two strategies: (I) light irradiation and (II) encapsulation of the complexes in liposomes, resulting in the formation of 4alip and 4blip. Both strategies significantly increased the ability of 4a, 4b to kill cancer cells. The cellular studies indicated that both the free complexes 4a, 4b and their liposomal forms 4alip and 4blip effectively inhibited cell proliferation. The cell cycle arrest analysis uncovered 4alip and 4blip arresting cell growth in the S period. Additionally, we investigated apoptosis and ferroptosis pathways, observing an increase in malondialdehyde (MDA) levels, a reduction of glutathione (GSH), a down-regulation of GPX4 (glutathione peroxidase) expression, and lipid peroxidation. The effects on mitochondrial membrane potential and intracellular Ca2+ concentrations were also examined, revealing that both light-activated and liposomal forms of 4alip and 4blip caused a decline in mitochondrial membrane potential and an enhancement in intracellular Ca2+ levels. In conclusion, these complexes and them encapsulated liposomes induce cell death through apoptosis and ferroptosis.

Iridium(III) complexes inhibit the proliferation and migration of BEL-7402 cells through the PI3K/AKT/mTOR signaling pathway.

Iridium(III) complexes are largely studied as anti-cancer complexes due to their excellent anti-cancer activity. In this article, two new iridium(III) complexes [Ir(piq)2(THPIP)]PF6 (THPIP = 2,4-di-tert-butyl-6-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol, piq = deprotonated 1-phenylisoquinoline) (Ir1) and [Ir(bzq)2(THPIP)]PF6 (bzq = deprotonated benzo[h]quinolone) (Ir2) were synthesized. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays showed that complex Ir1 exhibits moderate activity (IC50 = 29.9 ± 4.6 µM) and Ir2 shows high cytotoxicity (IC50 = 9.8 ± 1.8 µM) against BEL-7402 cells. Further studies on the mechanism showed that Ir1 and Ir2 induced apoptosis by changing the mitochondrial membrane potential, Ca2+ release, ROS accumulation, and cell cycle arrest at the S phase. The complexes can effectively inhibit cell colony formation and migration. The expression of B-cell lymphoma-2 (Bcl-2) family proteins, PI3K (phosphatidylinositol 3-kinase), AKT (protein kinase B), mTOR (mammalian target of rapamycin), and p-mTOR was studied by immunoblotting. Complexes Ir1 and Ir2 downregulated the expression of anti-apoptotic protein Bcl-2 and increased the expression of autophagy-related proteins of Beclin-1 and LC3-II. Further experiments showed that the complexes inhibited the production of glutathione (GSH) and increased the amounts of malondialdehyde (MDA). Fluorescence of HMGB1 was significantly increased. We also investigated the effect of the complexes on the expression of genes using RNA-sequence analysis, we further calculated the lowest binding energies between the complexes and proteins using molecular docking. Taken together, the above results indicated that complexes Ir1 and Ir2 induce apoptosis in BEL-7402 cells through a ROS-mediated mitochondrial dysfunction and inhibition of the PI3K/AKT/mTOR signaling pathway.

Synthesis, characterization, molecular docking, RNA-sequence and anticancer efficacy evaluation in vitro of ruthenium(II) complexes on B16 cells.

In recent years, the studies of the ruthenium(II) complexes on anticancer activity have been paid great attention, many Ru(II) complexes possess high anticancer efficiency. In this paper, three ligands CPIP (2-(4-chlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline), DCPIP (2-(3,4-dichlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline), TCPIP (2-(2,3,5-trichlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) and their three ruthenium (II) complexes [Ru(dip)2(CPIP)](PF6)2 (1, dip = 4,7-diphenyl-1,10-phenanthroline), [Ru(dip)2(DCPIP)](PF6)2 (2) and [Ru(dip)2(TCPIP)](PF6)2 (3) were synthesized and characterized. 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) assay was used to investigate in vitro cytotoxicity of complexes against various cancer cells. The results showed that complexes 1-3 exhibited pronounced cytotoxic effect on B16 cells with low IC50 values of 7.2 ± 0.1, 11.7 ± 0.6 and 1.2 ± 0.2 µM, respectively. The 3D model demonstrated that the complexes can validly prevent the cell proliferation. Apoptosis determined using Annexin V-FITC/PI double staining revealed that complexes 1-3 can effectively induce apoptosis in B16 cells. The intracellular localization of 1-3 in the mitochondria, the levels of intracellular reactive oxygen species (ROS), the opening of mitochondrial permeability transition pore as well as the decline of mitochondrial membrane potential were investigated, which demonstrated that the complexes 1-3 led to apoptosis via a ROS-mediated mitochondrial dysfunction pathway. The RNA-sequence indicated that the complexes upregulate the expression of 74 genes and downregulate the expression of 81 genes. The molecular docking showed that the complexes interact with the proteins through hydrogen bond, π-cation and π-π interaction. The results show that ruthenium(II) complexes 1, 2 and 3 can block tumor cell growth and induce cell death through autophagy and ROS-mediated mitochondrial dysfunction pathways.

Significant increase of anticancer efficacy in vitro and in vivo of liposome entrapped ruthenium(II) polypyridyl complexes.

Two polypyridyl ruthenium(II) complexes [Ru(DIP)2(BIP)](PF6)2 (DIP = 4,7-diphenyl-1,10-phenanthrolie, BIP = 2-(1,1'-biphenyl-4-yl)-1H-imidazo[4,5-f][1,10]phenanthroline, Ru1) and [Ru(DIP)2(CBIP)](PF6)2 (CBIP = 2-(4'-chloro-1,1'-biphenyl-4-yl)-1H-imidazo[4,5-f][1,10]phenanthroline, Ru2) were synthesized. The cytotoxic activities in vitro of Ru1, Ru2 toward B16, A549, HepG2, SGC-7901, HeLa, BEL-7402, non-cancer LO2 were investigated using MTT method (3-(4,5-dimethylthiazole)-2,5-diphenltetraazolium bromide). Unexpectedly, Ru1, Ru2 can't prevent these cancer cells proliferation. To improve the anti-cancer effect, we used liposomes to entrap the complexes Ru1, Ru2 to form Ru1lipo, Ru2lipo. As expectation, Ru1lipo and Ru2lipo exhibit high anti-cancer efficacy, especially, Ru1lipo (IC50 3.4 ± 0.1 µM), Ru2lipo (IC50 3.5 ± 0.1 µM) display strong ability to block the cell proliferation in SGC-7901. The cell colony, wound healing, and cell cycle distribution show that the complexes can validly inhibit the cell growth at G2/M phase. Apoptotic studied with Annex V/PI doubling method showed that Ru1lipo and Ru2lipo can effectively induce apoptosis. Reactive oxygen species (ROS), malondialdehyde, glutathione and GPX4 demonstrate that Ru1lipo and Ru2lipo improve ROS and malondialdehyde levels, inhibit generation of glutathione, and finally result in a ferroptosis. Ru1lipo and Ru2lipo interact on the lysosomes and mitochondria and damage mitochondrial dysfunction. Additionally, Ru1lipo and Ru2lipo increase intracellular Ca2+ concentration and induce autophagy. The RNA-sequence and molecular docking were performed, the expression of Bcl-2 family was investigated by Western blot analysis. Antitumor in vivo experiments confirm that 1.23 mg/kg, 2.46 mg/kg of Ru1lipo possesses a high inhibitory rate of 53.53% and 72.90% to prevent tumor growth, hematoxylin-eosin (H&E) results show that Ru1lipo doesn't cause chronic organ damage and strongly promotes the necrosis of solid tumor. Taken together, we conclude that Ru1lipo and Ru2lipo cause cell death through the following pathways: autophagy, ferroptosis, ROS-regulated mitochondrial dysfunction, and blocking the PI3K/AKT/mTOR.

Design, synthesis and biological evaluation of liposome entrapped iridium(III) complexes toward SGC-7901 cells.

In this study, two new iridium(III) polypyridyl complexes [Ir(bzq)2(DIPH)](PF6) (bzq = deprotonated benzo[h]quinoline, DIPH = 4-(2,5-dibromo-4-(1H-imidazo[4,5-f][1,10]phenanthrolim-2-yl)-4-hydroxybutan-2-one) (Ir1) and [Ir(piq)2(DIPH)](PF6) (piq = deprotonated 1-phenylisoquinoline) (Ir2) were synthesized and characterized by elemental analysis, HRMS, 1H and 13C NMR. The cytotoxic activity of Ir1, Ir2, Ir1lipo and Ir2lipo against cancer cells SGC-7901, HepG2, A549, HeLa, B16 and normal NIH3T3 cells in vitro was evaluated using 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) method. Ir1 and Ir2 showed no cytotoxic activity, but their liposome-entrapped Ir1 (Ir1lipo) and Ir2 (Ir2lipo) showed significant cellular activity, especially sensitive to SGC-7901 with IC50 values of 4.7 ± 0.2 and 12.4 ± 0.5 µM, respectively. The cellular uptake, endoplasmic reticulum (ER) localization, autophagy, tubulin polymerization, glutathione (GSH), malondialdehyde (MDA) and release of cytochrome c were investigated to explore the mechanisms of apoptosis. The calreticulin (CRT), heat shock protein 70 (HSP70), high mobility group box 1 (HMGB1) were also explored. Western blotting showed that Ir1lipo and Ir2lipo inhibited PI3K (phosphoinositide-3 kinase), AKT (protein kinase B), p-AKT and activated Bcl-2 (B-cell lymphoma-2) protein and apoptosis-regulated factor caspase 3 (cysteinyl aspartate specific proteinase-3) and cleaving PARP (poly ADP-ribose polymerase). The results demonstrated that Ir1lipo and Ir2lipo induce cell apoptosis through targeting the endoplasmic reticulum (ER), cause oxidative stress damage, inhibiting PI3K/AKT signaling pathway, immunogenic cell death (ICD) and inhibit the cell growth at G2/M phase.

Synthesis, RNA-sequence and evaluation of anticancer efficacy of ruthenium(II) polypyridyl complexes toward HepG2 cells.

In this article, four new Ru(II) complexes [Ru(dmbpy)2(TFBIP)](PF6)2 (dmbpy = 4,4'-dimethyl-2,2'-bipyridine, TFPIP = 2-(4'-trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1H-imidazo[4,5-f][1,10]phenanthroline) (Ru1), [Ru(bpy)2(TFBIP)](PF6)2 (bpy = 2,2'-bipyridine) (Ru2), [Ru(phen)2(TFBIP)](PF6)2 (phen = 1,10-phenanthroline) (Ru3) and [Ru(dmp)2(TFBIP)](PF6)2 (dmp = 2,9-dimethyl-1,10-phenanthroline) (Ru4) were synthesized and characterized by elemental analysis, HRMS, IR, 1H NMR, 13C NMR and 19F NMR. The in vitro anticancer effect of the complexes on HepG2, A549, B16, HeLa, BEL-7402 and non-cancer LO2 cells was screened using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The results illustrate that the complexes display moderate anticancer activity. Apoptotic assay with Annexin V/PI double staining method indicated that complexes induce apoptosis in HepG2 cells. Also, the complexes interfere with the mitochondrial functions, accompanied by the production of intracellular ROS as well as a reduction of mitochondrial membrane potential. The results obtained from the western blot demonstrated that the complexes upregulate pro-apoptotic Bax and downregulate anti-apoptotic Bcl-2, which further activates caspase 3 and promotes the cleavage of PARP. RNA-sequence showed that the complexes upregulate the expression of 40 genes and downregulate 66 genes. Antitumour in vivo demonstrated that Ru1 inhibits the tumor growth with a high inhibitory rate of 51.19%. Taken together, these results revealed that complexes Ru1, Ru2, Ru3 and Ru4 induce cell death in HepG2 cells via autophagy and a ROS-mediated mitochondrial apoptotic pathway.

Protective effect of orange essential oil on the formation of non-alcoholic fatty liver disease caused by high-fat diet.

The purpose of this study was to investigate the protective effect of sniffing orange essential oil (OEO) on the formation of non-alcoholic fatty liver disease (NAFLD) caused by a high-fat diet. The results confirmed that sniffing OEO could reduce obesity caused by a high-fat diet (HFD) by reducing the levels of triglycerides (TGs), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). In addition, the observation of liver tissue sections showed that sniffing OEO could reduce lipid accumulation in liver cells. Further analysis by western blot analysis showed that OEO treatment made the expression levels of acetyl-CoA carboxylase (ACC) and Cytochrome P450 2E1 (CYP2E1) down-regulated and the expression levels of peroxisome proliferator-activated receptor-α (PPAR-α) and carnitine palmitoyltransferase-1 (CPT-1) up-regulated. These results indicate that the treatment of sniffing OEO could enhance the antioxidant capacity of mice and reduce liver damage caused by a high-fat diet. Furthermore, sniffing OEO could inhibit lipid synthesis and oxidative stress stimulated by a high-fat diet. Overall, OEO treatment had a certain protective effect on NAFLD-related diseases caused by a high-fat diet. Therefore, aromatherapy may be introduced as a treatment of long-term chronic diseases.

Long non-coding RNA TCONS_00814106 regulates porcine granulosa cell proliferation and apoptosis by sponging miR-1343.

Recent evidence shows that long non-coding RNAs (lncRNAs), a class of non-coding RNAs, are involved in the regulation of reproductive processes. In this study, we identified a lncRNA, TCONS_00814106, that was upregulated in high-fecundity sow ovarian tissues and influenced by reproductive hormones. Bioinformatics analyses and luciferase reporter assays showed that TCONS_00814106 is a miR-1343 target. Cell counting kit (CCK)-8 and apoptosis assays showed that TCONS_00814106 promotes proliferation and inhibits apoptosis in porcine granulosa cells (GCs), and that this could be reversed by miR-1343. Also, we observed that transforming growth factor-ß receptor type I (TGFBR1) is a functional target of miR-1343 in GCs. TCONS_00814106 serves as a competing endogenous RNA to regulate TGFBR1 expression by sponging miR-1343, thereby exerting regulatory functions in GCs. Overall, these results provide new insights into the biological function of the lncRNA TCONS_00814106.

Comparative analysis of the ovarian transcriptome reveals novel insights into fertility differences in Large White sows.

BACKGROUND: Fertility is the most important economic trait in sows, as it is critical for profitability. Considerable phenotypic variation in litter size exists in Large White sows. However, relatively little is known about the underlying molecular and genetic bases. OBJECTIVE: An experiment was conducted to screen key genes that affect the fecundity of pigs during the luteal (L) and follicular phases (F) of the estrous cycle. METHODS: Eight sows (n = 4 for high fertility sows and n = 4 for low fertility sows) were sacrificed on day 14 (day 1 = first day of estrus) after estrus in the L phase. Another eight sows were slaughtered on day 20 of the estrous cycle in the F phase. Sixteen ovarian tissue samples were collected at the different sacrifice time points. Total RNA extracted was used to construct the library and then sequence on an Illumina HiSeq X10 system. Differentially expressed genes (DEGs) between high and low fertility in Large White sows were identified, and their potential biological functions were analyzed using bioinformatics analysis. RESULTS: In total, 457 DEGs (161 up-regulated and 296 down-regulated genes) were detected in the ovarian tissues of the high and low fertility groups in the L phase of the estrous cycle. Furthermore, 475 DEGs (253 up-regulated and 222 down-regulated genes) were identified in the F phase. Twenty-nine DEGs were common to both comparisons. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that the DEGs were mainly associated with steroid biosynthesis, the Hippo signaling pathway, and lysosomes. Others, such as MSMO1, CYP27B1, and CTSB, were related to reproduction. CONCLUSION: These results will contribute to a better understanding of the individual differences in fertility at the transcriptome level, which may provide useful information to explore new ways to improve fertility in pigs.

Association of HLA-DRB1/DQB1 polymorphism with high-risk HPV infection and cervical intraepithelial neoplasia women from Shanghai.

Persistent human papillomavirus (HPV) infection is the main causative agent for cervical intraepithelial neoplasia (CIN) and cancer. Variability in host immunogenetic factors is important in determining the overall cellular immune response to the HPV infection. This study was carried out to confirm the association of human leukocyte antigen (HLA) class II DRB1 and DQB1 alleles with CIN and HPV persistent infections in women from Shanghai in a case-controlled study. A total of 170 patients, including 105 HPV positive patients and 65 HPV negative women (control) participated in the study. HybriBio's proprietary flow-through hybridization technique was used to perform HPV genotyping. Low-resolution PCR-sequence specific priming (PCR-SSP) was used to genotype HLA class II for DRB1 and DQB1 loci. Binary and multivariate logistic regression analysis highlighted the association of specific alleles with CIN and HPV persistent infections after adjusting for the confounding factor of age. HLA-DQB1*02 and *06 is significantly associated with increased risk of HPV16 persistent infection (P c < 0.013). HLA-DRB1*09 is significantly associated with increased risk for CIN, whereas the -DRB1*16 exhibit protective to CIN (P < 0.05). Significant association is found for HLA-DQB1*04 and *06 with increased risk for CIN (P < 0.05). There were possible associations of specific HLA class II alleles either with risk of persistent HPV infection or with developing CIN.