[Correlation of nutritional status with clinical characteristics and lung function in children with cystic fibrosis]. / å›Šæ€§çº¤ç»´åŒ–å„¿ç«¥è¥å »çŠ¶å†µä¸Žä¸´åºŠç‰¹å¾å’Œè‚ºåŠŸèƒ½çš„ç›¸å ³æ€§åˆ†æž.

OBJECTIVES: To investigate the nutritional status of children with cystic fibrosis (CF) and understand the correlation between malnutrition and clinical characteristics as well as lung function. METHODS: A retrospective analysis was performed on clinical data of CF children admitted from January 2016 to June 2023. Clinical characteristics of CF children with different nutritional statuses were compared, and the correlation between malnutrition and lung function was analyzed. RESULTS: A total of 52 CF children were included, comprising 25 boys (48%) and 27 girls (52%), aged between 7 months and 17 years. Respiratory symptoms were the predominant clinical manifestations (96%, 50/52). The prevalence of malnutrition was 65% (34/52), with moderate/severe malnutrition being the most common (65%, 22/34). The malnutrition group had a longer duration of illness, higher proportion of digestive system symptoms, and lower levels of serum albumin (P<0.05). Pulmonary function parameters, including forced expiratory volume in one second as a percentage of the predicted value, ratio of forced expiratory volume in one second to forced vital capacity, forced expiratory flow at 25% of forced vital capacity exhaled, forced expiratory flow at 50% of forced vital capacity exhaled, forced expiratory flow at 75% of forced vital capacity exhaled, and maximum mid-expiratory flow as a percentage of the predicted value, were lower in the malnutrition group compared to the normal nutrition group (P<0.05). Correlation analysis showed body mass index Z-score was positively correlated with the above six pulmonary function parameters (P<0.05). CONCLUSIONS: The prevalence of malnutrition is high in CF children and is associated with decreased lung function. CF children with higher body mass index have better lung function. Therefore, screening and evaluation of nutritional status as well as appropriate nutritional intervention should be emphasized in CF children.

Silencing of CPNE1-TRAF2 Axis Restrains the Development of Pancreatic Cancer.

BACKGROUND: Copine 1 (CPNE1) acts as a promoter in the progression of many kinds of cancers with the exception of pancreatic cancer (PC). This research is designed to probe the function of the CPNE1-tumor necrosis factor receptor-associated factor 2 (TRAF2) axis in PC. METHODS: In vivo and in vitro models of PC were constructed, and a series of biological function tests, including MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], colony formation, flow cytometry, and immunohistochemistry, were performed. RESULTS: The level of CPNE1 elevated dramatically in PC cells. Downregulation of CPNE1in PC cells resulted in the inhibition of colony formation and proliferation. In addition, the silencing of CPNE1 induced the G1/S arrest and apoptosis in PC cells. Additionally, TRAF2 positively interacted with CPNE1 in PANC cells. CPNE1 silencing also inhibited the growth of tumors in in vivo mouse models. Functional experiments revealed that the anti-tumor effect of CPNE1 silencing was counteracted by TRAF2 overexpression, and the tumor-promoting effect of TRAF2 overexpression was reversed by CPNE1 silencing. CONCLUSIONS: In summary, our findings indicate that the silencing of the CPNE1-TRAF2 axis restrains PC development.

A Novel Dual PI3K/mTOR Inhibitor, XIN-10, for the Treatment of Cancer.

An imbalance in PI3K/AKT/mTOR pathway signaling in humans often leads to cancer. Therefore, the investigation of anti-cancer medications that inhibit PI3K and mTOR has emerged as a significant area of research. The aim of this study was to explore the effect of XIN-10, a dual PI3K/mTOR inhibitor, on the growth as well as antiproliferation of tumor cells and to investigate the anti-tumor mechanism of XIN-10 by further exploration. We screened three cell lines for more in-depth exploration by MTT experiments. From the AO staining, cell cycle and apoptosis, we found that XIN-10 had a more obvious inhibitory effect on the MCF-7 breast cancer cell line and used this as a selection for more in-depth experiments. A series of in vitro and in vivo experiments showed that XIN-10 has superior antiproliferative activity compared with the positive drug GDC-0941. Meanwhile, through the results of protein blotting and PCR experiments, we concluded that XIN-10 can block the activation of the downstream pathway of mTOR by inhibiting the phosphorylation of AKT(S473) as well as having significant inhibitory effects on the gene exons of PI3K and mTOR. These results indicate that XIN-10 is a highly potent inhibitor with low toxicity and has a strong potential to be developed as a novel PI3Kα/mTOR dual inhibitor candidate for the treatment of positive breast cancer.

Cellular Id1 inhibits hepatitis B virus transcription by interacting with the novel covalently closed circular DNA-binding protein E2F4.

Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), which required developing novel therapies targeting the inhibition of HBV transcription and replication due to current limited treatment options. We explored novel target for the development of novel therapies targeting the inhibition of HBV replication and transcription. The expression of Id1 and E2F4 in HCC cells and tissues was detected by qRT-PCR and western blot. We investigated the Id1 and E2F4-mediated transcription of HBV infection by using HepG2.2.15, HepAD38, HepG2-NTCP cell lines and AAV/HBV-infected mice. Interactions between the two host proteins and viral covalently closed circular DNA (cccDNA) were assessed using subcellular localization, protein-protein interaction, chromatin immunoprecipitation, and luciferase assays. Ectopic Id1 significantly reduced HBV transcription and replication in both HBV-expressing cells and AAV/HBV-infected mice. Id1 and E2F4 could form a heterodimer to prevent E2F4 from promoting HBV transcription and replication. E2F4 could directly bind to cccDNA and activate the HBV core promoter in cell lines. Furthermore, in vitro binding experiments confirmed that the sequence 1758'-TTAAAGGTC-1766', which is highly conserved among HBV genotypes, is the target site of the E2F4 homodimer. The findings suggest that E2F4 function as novel cccDNA-binding protein to directly activate HBV transcription by binding to Cp promoter region. Our results highlight the ability that E2F4 represent a pan-potential therapeutic target against HBV transcription and provide more clues to better understand the life cycle of HBV.

E2F4 Promotes the Proliferation of Hepatocellular Carcinoma Cells through Upregulation of CDCA3.

Liver cancer, the second most commonly diagnosed cancer, is associated with high mortality rates. E2F4 is a member of the E2F transcription factor family. There are limited studies on the role of E2F4 in hepatocellular carcinoma (HCC). In this study, the expression of E2F4 in HCC tissue samples and cell lines was analyzed using quantitative real-time polymerase chain reaction. E2F4 expression positively correlated with tumor size in patients with HCC. Additionally, E2F4 expression was greater in HCC cells than in normal LO2 cells. Furthermore, overexpression of E2F4 significantly enhanced the proliferation, migration, and invasion of HCC cells. The results of a luciferase assay revealed that E2F4 upregulated the expression of CDCA3 by binding to its promoter region (1863'-ACGCGCGAGAATG-1875') and consequently promoted proliferation and cell cycle progression of HCC cells. Taken together, these results demonstrated that E2F4 might play a vital role in HCC progression and could serve as a potential biomarker for the diagnosis and as a therapeutic target of HCC.

Circular RNA circSP3 promotes hepatocellular carcinoma growth by sponging microRNA-198 and upregulating cyclin-dependent kinase 4.

As a new class of endogenous noncoding RNAs, circular RNAs (circRNAs), have been found to influence cell development and function by sponging microRNAs. MicroRNA (miR)-198 is downregulated in various cancers, including hepatocellular carcinoma (HCC). We therefore searched for dysregulated circRNAs that could sponge miR-198 in HCC. By analyzing relevant circRNA databases (circBase, TargetScan and CircInteractome), we found that the miR-198-binding circRNA hsa_circSP3 is upregulated in HCC. CircSP3 expression correlated negatively with miR-198 expression in HCC tissues. Dual luciferase reporter assays indicated that circSP3 bound to miR-198. CircSP3 overexpression in HCC cells induced expression of cyclin-dependent kinase 4, a target gene of miR-198. Silencing circSP3 inhibited HCC cell proliferation and migration by downregulating cyclin-dependent kinase 4, whereas inhibiting miR-198 reversed those effects. In vivo experiments confirmed that circSP3 promoted xenograft tumor growth. These data suggest that circSP3 may be a novel biomarker for HCC.

Improving rehabilitation and quality of life after percutaneous transhepatic cholangiography drainage with a rapid rehabilitation model.

BACKGROUND: Percutaneous transhepatic cholangiography drainage (PTCD) effectively treats biliary obstruction. However, patients must maintain the drainage tube after hospital discharge, which may interfere with daily life and work, potentially causing psychological distress. Postoperative rehabilitation is crucial, and strengthened nursing interventions can shorten recovery time. AIM: The aim was to evaluate an inpatient model to shorten rehabilitation duration and improve quality of life after PTCD. METHODS: A total of 118 patients with malignant obstructive jaundice who were admitted to our hospital between May 2018 and January 2021 were included and divided into observational (with therapy) and control (no therapy) groups of 59 each. RESULTS: The observational group had fewer hospitalization days than the control group. The complication, the PTCD fixed-tube prolapse, and tube-related admission rates within 3 mo after PTCD were significantly lower in the observation group than in the control group (P < 0.05). The fatigue, pain, nausea, vomiting, pruritus, emaciation, and fever scores after PTCD decreased in both groups compared with the scores before PTCD (P < 0.05). The quality of life scores after the intervention were higher in the observation than in the control group (P < 0.05). CONCLUSION: The model promoted rehabilitation after PTCD, reduced post-PTCD complications, and the tube-related admissions in the 3 mo after the procedure, and improved the quality of life.

The HBx and HBc of hepatitis B virus can influence Id1 and Id3 by reducing their transcription and stability.

Hepatitis B virus (HBV) infection is closely related with the occurrence and development of hepatocellular carcinoma (HCC), in which Hepatitis B virus x protein (HBx) and core protein (HBc) play crucial roles. Additionally, inhibitors of differentiation (Id) proteins exhibited significant correlation with liver cancer development. Here, we identified that HBV dramatically inhibited the expression of Id1 and Id3 in both protein and transcriptional levels for the first time, whereas there was little effect of the virus on Id2. Additionally, two HBV coded protein, HBc and HBx, could reduce the expression of Id1 and Id3 distinctly, whereas the other two viral proteins, HBs and HBp were unable to affect Id1 and Id3 proteins. Both the activity inhibitors and activators further confirmed that HBc inhibited the expression of Id1 and Id3 by BMP/Smad signaling pathway. HBx could interact with both Id1 and Id3 at residues 112-136 of HBx protein, and it could inhibit the two Id proteins by accelerating their degradation. This is the first report about HBc and HBx regulating Id1 and Id3, whereas the detailed mechanism associated with above needed further experiments to clarify.

The expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in the compression area during orthodontic relapse.

OBJECTIVE: This study investigated the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in the compression area during orthodontic relapse in rat molars. MATERIALS AND METHODS: Thirty Wistar rats (6 weeks old) underwent orthodontic tooth movement (OTM) of the left first maxillary molar for 21 days, followed by removal of the force device. The contralateral maxillary molar served as a control with no mechanical force stimuli. Animals were sacrificed at 0, 1, 3, 7, and 14 days of relapse after force withdrawal. Tooth relapse and alveolar bone parameters were measured using microcomputed tomography (micro-CT). Maxilla sections were obtained for haematoxylin and eosin (HE), immunohistochemical staining [EMMPRIN, nuclear factor kappa B ligand (RANKL) and vascular endothelial growth factor (VEGF)] and tartrate-resistant acid phosphatase (TRAP). Correlation analyses were then performed. RESULTS: After force removal, nearly 79.88% of the total relapse occurred within the initial 3 days. The number of osteoclasts clearly increased while the alveolar bone density decreased on the pressure side on Day 3 of relapse. Moreover, the EMMPRIN expression level significantly increased on Day 1, peaked up on Day 3 and decreased on Days 7 and 14. Statistically, a strong positive correlation was found between EMMRPIN expression and the osteoclast number and RANKL and VEGF expression. CONCLUSION: EMMPRIN was highly expressed on the pressure side during the orthodontic tooth relapse, which could be involved in osteoclastogenesis and alveolar bone resorption in association with RANKL and VEGF expression.

Effects of Twin Inclined Plane Device on Adaptation and Ultrastructure Variations in Condyle of Growing Rats.

OBJECTIVE: This study investigates the effects of using a twin inclined plane device (TIPD) on the remolding and ultrastructure variation of mandibular condyle in growing rats. MATERIALS AND METHODS: Forty-eight male Wistar rats (six weeks old, body weight of approximately 190-210 g) were divided into experimental group (wearing appliance, n = 32) and control group (no appliance, n = 16). Samples were collected on days 3, 14, 30, and 60. The immunohistochemical analysis for vascular endothelial growth factor (VEGF) and type II collagen was carried out. Tartrate-resistant acid phosphatase (TRAP) reaction was performed to evaluate the osteoclastic activity. Three-dimensional morphometric images were reconstructed for morphometric analysis by microcomputed tomography (micro-CT). The ultrastructure of the condylar surface was observed by scanning electron microscopy (SEM). RESULTS: The expression of VEGF significantly increased, while the expression of type II collagen decreased in the experimental group at days 30 and 60. Furthermore, the enhanced osteoclast activity was observed under the subchondral bone, which was highest at day 30, and decreased to the lowest at day 60 in the experimental group. In addition, adaptive subchondral bone remolding in the posterior part of the condyle was observed at day 60 in the experimental group, and the SEM revealed the ultrastructure variations after installation of the TIPD. However, these changes began to reverse after 30 days. CONCLUSION: Condylar tissue changes point to the osteoclastic activity in the posterior region of the condyle. These adaptive changes point to bone resorption in the posterior condyle. Type II collagen and VEGF contribute to the MCC remolding induced by the TIPD. The ultrastructural changes in the posterior condylar area in response to mechanical stresses are recoverable at the initial stage.

LC-MS guided identification of dimeric 2-(2-phenylethyl)chromones and sesquiterpene-2-(2-phenylethyl)chromone conjugates from agarwood of Aquilaria crassna and their cytotoxicity.

Four previously unreported dimeric 2-(2-phenylethyl)chromones (1-4a) and three unprecedented sesquiterpene-2-(2-phenylethyl)chromone conjugates (5-7), comprising a sesquiterpenoid and a 5,6,7,8-tetrahydroxy-2-(2-phenylethyl)-5,6,7,8 -tetrahydro-4H-chromone moiety, as well as three known dimeric 2-(2-phenylethyl)chromones (4b, 8a, 8b) were identified from agarwood originating from Aquilaria crassna in Cambodia by LC-MS guided separation. Their structures were elucidated by extensive NMR techniques, HRESIMS and CD. All compounds were evaluated for their cytotoxicity against four human cancer cell lines. Compounds 6, 7, 8a, 8b displayed a range of cytotoxic activities with IC50 values in the rang 10.93-49.0 µM.