A meta-analysis of the effects of vitamin C supplementation for pregnant smokers on the pulmonary function of their offspring.

BACKGROUND: At present, the need for vitamin C supplementation for pregnant smokers has not been fully studied. This study is aimed at investigating whether vitamin C supplementation for pregnant smoking women can improve the pulmonary function of their offspring. METHODS: Four databases were searched from inception to April 1, 2023 for studies on the effect of vitamin C supplementation to pregnant smokers on the pulmonary function of their offspring. Meanwhile, the reference lists of relevant studies were manually searched. The risk of bias in the included studies was assessed using the Cochrane Collaboration tool, and the data was analyzed using STATA/SE 17.0. RESULTS: Four randomized controlled trials (RCTs), all of high quality, were enrolled in this meta-analysis, including 787 pregnant women. The offspring of pregnant smokers who received vitamin C supplementation exhibited improved Forced Expiratory Flow between 25 and 75% (FEF25-75), FEF50, FEF75, and Forced Vital Capacity (FVC) compared to those who did not receive vitamin C supplementation. However, there was no statistically significant difference in Forced Expiratory Volume at 0.5 s (FEV0.5) and the ratio of FEV0.5 to FVC between the offspring of pregnant smokers who received vitamin C and the control group. CONCLUSION: Vitamin C supplementation for smoking pregnant women may enhance the pulmonary function of their offspring, particularly in FEF25-75, FEF50, FEF75, and FVC. Nevertheless, there are no significant differences in FEV0.5 and the FEV0.5/FVC ratio. These findings suggest that vitamin C supplementation has potential benefits for specific pulmonary function. Further studies are needed to comprehensively assess the effects of vitamin C on pulmonary function in the context of maternal smoking during pregnancy.

Supplemental low-dose esketamine to propofol versus propofol alone on perioperative characteristics in children undergoing surgery: a prospective randomized controlled trial.

BACKGROUND: Limited data exist regarding the use of the esketamine-propofol combination (esketofol) in pediatric surgery. This study aimed to investigate the effect of esketofol versus propofol alone on the perioperative characteristics of children undergoing minor surgery. METHODS: Eighty-four children aged two to six years were randomly assigned to either the propofol group or the esketofol group. Intraoperative outcomes included bispectral index, dosage of anesthetics, and extubation time. Postoperative outcomes comprised oropharyngeal airway usage, time to orientation, time to eye-opening, length of stay in the post-anesthesia care unit, the need for rescue opioids, pain rating using the Face, Legs, Activity, Cry, Consolability (FLACC) Scale, Pediatric Anesthesia Emergence Delirium Score, nausea and vomiting, and psychotomimetic symptoms. The FLACC pain score was the primary outcome, and the remaining parameters were considered secondary outcomes. RESULTS: The FLACC Score (2 [1, 3.3] vs. 4 [3, 5.3], P<0.001) and frequency of rescue opioids (14.3% vs. 33.3%, P=0.040) were significantly lower, while Bispectral Index (BIS) was higher (P<0.001) in the esketofol group compared with the propofol group. Moreover, the time to orientation and length of stay in the post-anesthesia care unit (PACU) were significantly longer in the esketofol group compared with the propofol group (P=0.029 and P=0.025, respectively). The other outcomes were similar between the two groups. CONCLUSIONS: Esketofol reduces postoperative pain and the need for rescue opioids, but it extends recovery time in the PACU and increases BIS without affecting other outcomes.

Quality evaluation index development for nutritional management in patients with nasopharyngeal carcinoma during peri-radiotherapy.

OBJECTIVES: It is necessary to construct an evaluation index for patients with nasopharyngeal carcinoma during peri-radiotherapy to provide a reference for the evaluation of the quality of nutritional management of patients with nasopharyngeal carcinoma during peri-radiotherapy. The aim of this study was to construct a set of scientific, comprehensive, and feasible indicators for evaluating the quality of nutrition management in patients with nasopharyngeal carcinoma during peri-radiotherapy to provide a unified reference basis for objective nutritional evaluation of these patients during the peri-radiotherapy period and to provide insights to the clinical treatment and care of these patients. METHODS: A multidisciplinary research team was set up from December 2021 to April 2022. We took the three-dimensional quality structure model as the theoretical framework; based on the literature review, the first draft of the nutrition management quality evaluation index for patients with nasopharyngeal carcinoma during peri-radiotherapy was formed by a semi-structured interview. The Delphi correspondence method was used to survey 18 experts from 12 cities in China. The multidimensional analytical hierarchy process was used to determine the evaluation index and weight of nutrition management quality of patients with nasopharyngeal carcinoma during peri-radiotherapy. RESULTS: The effective questionnaire recovery rates of the two rounds of letters were 90.005% and 100%, respectively, and the expert authority coefficients were 0.906 and 0.918, respectively. The Kendall harmony coefficients of the two rounds of letters were 0.271 to 0.313 and 0.309 to 0.349, respectively. The nutrition management quality evaluation index of patients with nasopharyngeal carcinoma during peri-radiotherapy was constructed and included 3 first-level indexes, 10 second-level indexes, and 71 third-level indexes. CONCLUSION: The evaluation index of the nutrition management quality of patients with nasopharyngeal carcinoma during peri-radiotherapy is scientific and reliable, and it may have a certain guiding significance for nurses to evaluate the quality of nutrition management of these patients during this period.

Giant breast phyllodes tumor with silent thromboembolism: A case report.

BACKGROUND: Phyllodes tumor (PT) is a solid fibroepithelial breast lesion with proliferation of stromal and epithelial elements, usually presents with a rapidly expanding feature. Venous thromboembolism (VTE) have been reported to increase the burden in terms of mortality and morbidity of malignant tumor, and associate with worsened survival. However, benign PTs with silent thromboembolism that have not yet been reported, we report an unusual case of massive benign PT that grew on the left side of the breast in a cauliflower-shaped form and presented severe chronic blood loss and deep VTE. CASE: A 37-year-old woman with uncontrolled pain presented a rapidly enlarging left breast mass, measuring approximately 30 × 20 × 15 cm3 that first started 25 years ago. color Doppler ultrasound showed a large mass lesion on the left breast and deep VTE, several enlarged lymph nodes in the left axilla and mediastinum, which presented a malignant character. However, the biopsies of the mass did not show evidence of malignancy and the pathology result was considered to be benign PT. The patient was treated with an inferior vena cava and anticoagulation, the operation was arranged according to the surgical procedure, the patient recovered very well after mastectomy. CONCLUSION: This case is unique in that the giant breast mass presented with malignant character, was eventually pathologically confirmed to be benign PT, and it's rare that the benign tumor accompanied with silent thromboembolism. This finding describes the atypia features of giant benign PT and reminds the surgeon to consider the factor of VTE and risk when encountering ulcerative benign breast tumor and avoid excessive treatment.

Novel insights into tumorigenesis and prognosis of endometrial cancer through systematic investigation and validation on mitophagy-related signature.

In-depth studies on the pathogenesis of endometrial cancer (EC) are critical because of the increasing global incidence of EC. Mitophagy, a mitochondrial quality control process, plays an important role in carcinogenesis and tumor progression. This study aimed to develop a novel mitophagy-based signature to predict the tumorigenesis and prognosis of EC. Data was downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases, and 29 mitophagy-related genes were downloaded from the Pathway Unification Database. EC patients were classified into two risk groups based on the two-key- gene signature, TOMM40 and MFN1, which were constructed using Cox regression analysis. A better prognosis was noted in the low-risk group. The model was validated for four aspects: clinical features, mutation status, clinical therapeutic response, and immune cell infiltration status. Moreover, according to the contribution to the risk model, TOMM40 was selected for further in vitro experiments. The silencing of TOMM40 inhibited mitochondrial degradation; suppressed cell proliferation; induced cell apoptosis and G1 phase cell cycle arrest; inhibited migration, invasion, and epithelial-mesenchymal transition; and suppressed cell stemness. In conclusion, the mitophagy-related risk score provides a novel perspective for survival and drug selection during the individual treatment of EC patients. TOMM40 serves as an oncogene in EC and promotes tumor progression via a mitophagy-related pathway. Thus, TOMM40 is a potential therapeutic target in EC.

Shortwave infrared diffuse optical wearable probe for quantification of water and lipid content in emulsion phantoms using deep learning.

Significance: The shortwave infrared (SWIR, ∼900 to 2000 nm) holds promise for label-free measurements of water and lipid content in thick tissue, owed to the chromophore-specific absorption features and low scattering in this range. In vivo water and lipid estimations have potential applications including the monitoring of hydration, volume status, edema, body composition, weight loss, and cancer. To the best of our knowledge, there are currently no point-of-care or wearable devices available that exploit the SWIR wavelength range, limiting clinical and at-home translation of this technology. Aim: To design and fabricate a diffuse optical wearable SWIR probe for water and lipid quantification in tissue. Approach: Simulations were first performed to confirm the theoretical advantage of SWIR wavelengths over near infrared (NIR). The probe was then fabricated, consisting of light emitting diodes at three wavelengths (980, 1200, 1300 nm) and four source-detector (S-D) separations (7, 10, 13, 16 mm). In vitro validation was then performed on emulsion phantoms containing varying concentrations of water, lipid, and deuterium oxide (D2O). A deep neural network was developed as the inverse model for quantity estimation. Results: Simulations indicated that SWIR wavelengths could reduce theoretical water and lipid extraction errors from ∼6% to ∼1% when compared to NIR wavelengths. The SWIR probe had good signal-to-noise ratio (>32 dB up to 10 mm S-D) and low drift (<1.1% up to 10 mm S-D). Quantification error in emulsion phantoms was 2.1±1.1% for water and -1.2±1.5% for lipid. Water estimation during a D2O dilution experiment had an error of 3.1±3.7%. Conclusions: This diffuse optical SWIR probe was able to quantify water and lipid contents in vitro with good accuracy, opening the door to human investigations.

Evaluation of the antimicrobial mechanism of biogenic selenium nanoparticles against Pseudomonas fluorescens.

Selenium nanoparticles (SeNPs) can be biosynthesized by most Lactic acid bacteria thereby converting toxic sodium into SeNPs. However, few studies have reported the antimicrobial activity of biogenic SeNPs against Pseudomonas fluorescens which are the main species of psychrotrophic bacteria in raw milk. This study reported the synthesis and characterization of SeNPs from Lactobacillus casei ZK-AS 1.1482, and the antimicrobial mechanism against P. fluorescens ATCC 13525. The synthesized SeNPs were amorphous with sizes ranging from 52 to 103 nm. Fourier transform infrared spectroscopy (FT-IR) spectra showed the presence of proteins, polysaccharides, and lipids on the surface of particles, which evidently stabilized the SeNPs structure and morphology. Energy-dispersive X-ray (EDX) analysis revealed that the nanoparticles contained selenium. In addition, the minimal inhibitory concentration (MIC) of SeNPs against P. fluorescens ATCC 13525 was 0.1 mg ml-1 and the biofilm inhibition rate was 43.52 ± 0.26%. SeNPs decreased the number of living bacteria observed by confocal laser scanning microscopy (CLSM). Meanwhile, after SeNPs treatment, the intracellular adenosine triphosphate (ATP) concentration and antioxidant enzyme activity decreased, the content of reactive oxygen species (ROS) and the malondialdehyde (MDA) content increased, and lipid peroxidation intensified. Real-time fluorescence quantitative PCR (RT-qPCR) assay showed that the expression of flgA, luxR, lapD, MCP, cheA, c-di-GMP, phoB, and pstC gene were down-regulated after SeNPs treatment. The rfbC and DegT/DnrJ/EryC1/StrS gene were significantly up-regulated, indicating that SeNPs could destroy the integrity of cell membrane and thus play an antimicrobial role. Biogenic SeNPs are expected to be developed as an efficient and novel antimicrobial agent for application in the food industry.

Verteporfin reverses progestin resistance through YAP/TAZ-PI3K-Akt pathway in endometrial carcinoma.

Progestin resistance is a problem for patients with endometrial carcinoma (EC) who require conservative treatment with progestin, and its underlying mechanisms remain unclear. YAP and TAZ (YAP/TAZ), downstream transcription coactivators of Hippo pathway, promote viability, metastasis and also drug resistance of malignant tumors. According to our microarray analysis, YAP/TAZ were upregulated in progestin resistant IshikawaPR cell versus progestin sensitive Ishikawa cell, which implied that YAP/TAZ may be a vital promotor of resistance to progestin. We found YAP/TAZ had higher expression levels among the resistant tissues than sensitive tissues. In addition, knocking down YAP/TAZ decreased cell viability, inhibited cell migration and invasion and increased the sensitivity of IshikawaPR cell to progestin. On the contrary, overexpression of YAP/TAZ increased cell proliferation, metastasis and promoted progestin resistance. We also confirmed YAP/TAZ were involved in progestin resistant process by regulating PI3K-Akt pathway. Furthermore, Verteporfin as an inhibitor of YAP/TAZ could increase sensitivity of IshikawaPR cells to progestin in vivo and in vitro. Our study for the first time indicated that YAP/TAZ play an important role in progestin resistance by regulating PI3K-Akt pathway in EC, which may provide ideas for clinical targeted therapy of progestin resistance.

ABX-1431 inhibits the development of endometrial adenocarcinoma and reverses progesterone resistance by targeting MGLL.

Endometrial cancer is a common gynecological malignancy. With the onset of EC patients younger, conservative treatment with progesterone has become an important option for patients trying to preserve reproductive function. However, progesterone resistance is a key factor affecting the efficacy of therapy and it is urgent to clarify the mechanism so as to propose a potential target and inhibit the development of endometrial adenocarcinoma and progesterone resistance. MGLL, an important factor involved in lipid mobilization, is overexpressed in many tumors, however the biological function of MGLL in the development of endometrial adenocarcinoma and the process of progesterone resistance still remains unclear. In this study, we first found MGLL was highly expressed in progesterone resistant samples of endometrial adenocarcinoma, and then we verified its expression was increased in endometrial adenocarcinoma. Through in vitro and in vivo experiments, we demonstrated that overexpression of MGLL promoted tumor proliferation, metastasis and the occurrence of progestogen resistance, knockdown MGLL inhibited tumor proliferation, metastasis and reversed progestogen resistance. In addition, knockdown of MGLL can sensitize endometrial adenocarcinoma cells to progesterone, possibly by affecting ROS generation and reducing the expression of AKR1C1. Finally, it was verified that ABX-1431, MGLL inhibitor, reversed progesterone resistance and enhanced the sensitivity of endometrial adenocarcinoma to progesterone both in vitro and in vivo. In conclusion, the high expression of MGLL is involved in the occurrence and development of endometrial adenocarcinoma and progesterone resistance. Targeted inhibition of MGLL by inhibitors may be an effective method for the treatment of progesterone resistance in endometrial adenocarcinoma.

Mahuang Decoction Attenuates Airway Inflammation and Remodeling in Asthma via Suppression of the SP1/FGFR3/PI3K/AKT Axis.

Background/Purpose: Mahuang decoction (MHD) is a classic famous traditional Chinese medicine and has various pharmacological effects, including anti-inflammation and anti-asthma. In this study, we aimed to investigate the potential protective effect of MHD against asthma and elucidated the underlying mechanism. Materials and Methods: A mouse model of asthma was induced by ovalbumin (OVA) treatment, and then treated with MHD to evaluate its effect on the asthma. Gain- or loss-of-function approaches were performed in SP1 and FGFR3 to study their roles in asthma via measurement of airway inflammation, airway remodeling and airway smooth muscle cell (ASMC) proliferation-related factors. Results: MHD reduced airway inflammation and remodeling. Additionally, MHD contributed to diminished expression of SP1, which was shown to repress airway inflammation and remodeling. Furthermore, SP1 bound to the FGFR3 promoter, resulting in the FGFR3 transcription promotion and ASMC proliferation. Conversely, FGFR3 knockdown abolished airway inflammation and remodeling, the mechanism of which was related to suppression of the PI3K/AKT signaling pathway. Meanwhile, MHD hindered airway inflammation and remodeling following asthma by suppressing the SP1/FGFR3/PI3K/AKT axis. Conclusion: Taken together, MHD may retard airway inflammation and remodeling by suppressing the SP1/FGFR3/PI3K/AKT axis, which contributes to an extensive understanding of asthma and may provide novel therapeutic options for this disease.

Comparison of miRNA landscapes between the human oocytes with or without arrested development.

PURPOSE: By exploring the role of miRNAs in human oocyte development, the study was conducted to investigate the epigenetic mechanism contributing to the arrest of oocyte development. METHODS: In total, 140 oocytes from 22 patients were collected in the developmentally arrested oocyte (DAO) group, whereas 420 oocytes from 164 patients were harvested in the control group. The pooled RNA was extracted from all 20 oocytes to establish a RNA library. The total RNA of every ten oocytes was extracted for qPCR validation of miRNA candidates. Bioinformatic software was applied to explore the miRNA candidates and their target genes. RESULTS: Generally, the expression levels of miRNAs altered slightly during normal oocyte development but changed dramatically in the DAOs. Among the top 10 differential miRNAs, let-7a-5p and let-7g-5p, which were abundantly expressed throughout the oocyte development stages, had the broadest biological impact on oogenesis. Validated by qRT-PCR, both miRNAs were profoundly suppressed in the DAOs. During normal oocyte development, the expression levels of let-7a-5p and let-7g-5p at the GV stage were significantly higher than at MI and MII stages. Bioinformatic analysis demonstrated that let-7a-5p and let-7g-5p might regulate oocyte development by targeting PI3K-Akt, P53, cell cycle, and FoxO signaling pathways. CONCLUSIONS: There are dramatic differences in miRNA landscapes between the human oocytes with or without development arrest. In addition, the suppression of let-7a-5p and let-7g-5p might be associated with the occurrence of development arrest. The findings could provide therapeutic targets to correct the arrest of oocyte development in the future.

Disrupted expression of long non-coding RNAs in the human oocyte: the possible epigenetic culprits leading to recurrent oocyte maturation arrest.

PURPOSE: To depict the lncRNA expression during human oocyte maturation and explore the lncRNAs leading to recurrent oocyte maturation arrest. METHODS: LncRNA sequencing was performed on pooled RNA from 20 oocytes of each group (recurrent oocyte maturation arrest (ROMA), of germinal vesicle (GV), metaphase I (MI), or metaphase II (MII) stages. Bioinformatics software was deployed to compare the lncRNA differential expression between the normal and ROMA oocytes. The co-expression of lncRNA/mRNA was illustrated with the Cytoscape software. The pooled RNA from every 10 oocytes of each group (ROMA, GV, MI, MII) was extracted for further qPCR validation. RESULTS: There were 17 downregulated and 3 upregulated lncRNAs in the ROMA oocyte. Among them, co-expression analysis indicated that NEAT1 and NORAD were both downregulated. Basing on the KEGG enrichment analysis, PRCKA and JAK3 might be the target genes in the PI3K-Akt pathway and modulated by NEAT1 and NORAD. As validated by qPCR, the expressional levels of lncRNA candidates (NEAT1 and NORAD) and their target genes (PRKCA and JAK3) were confirmed to be extremely lower in the ROMA oocyte than in the normal oocyte. CONCLUSION: By targeting the PI3K-Akt pathway genes PRKCA and JAK3, the abnormal expression of NEAT1 and NORAD is suggested to impede oocyte maturation and impair oocyte genome integrity.

GMP-grade microcarrier and automated closed industrial scale cell production platform for culture of MSCs.

Efficient and large-scale expansion of mesenchymal stem/stromal cells (MSCs) has always been a formidable challenge to researchers in cell-based therapies and regenerative medicine. To reconcile major drawbacks of 2D planar culturing system, we innovatively developed an automated closed industrial scale cell production (ACISCP) platform based on GMP-grade microcarrier for culture of umbilical cord-mesenchymal stem/stromal cells (UCMSCs), in accordance with the criteria of stem cell bank. ACISCP system is a fully closed system, which employs different models of vivaSPIN bioreactors (CytoNiche Biotech, China) for scale-up cell culture and vivaPREP (CytoNiche Biotech, China) for automated cell harvesting and cell dosage preparation. To realize industrial scale expansion of UCMSCs, a three-stage expansion was conducted with 1 L, 5 and 15 L vivaSPIN bioreactors. Using 3D TableTrix® and ACISCP system, we inoculated 1.5 × 107 of UCMSCs into 1 L vivaSPIN bioreactor and finally scaled to two 15 L bioreactor. A final yield of 2.09 × 1010 cells with an overall expansion factor of 1975 within 13 days. The cells were harvested, concentrated, washed and prepared automatically with vivaPREP. The entire process was realized with ACISCP platform and was totally enclosed. Critical quality attributes (CQA) assessments and release tests of MSCs, including sterility, safety, purity, viability, identity, stability and potency were performed accordingly. The quality of cells harvested from 3D culture on the ACISCP and conventional 2D planar culture counterpart has no significant difference. This study provides a bioprocess engineering platform, harnessing GMP-grade 3D TableTrix® microcarriers and ACISCP to achieve industrial-scale manufacturing of clinical-grade hMSCs.

Overexpression of LPCAT1 enhances endometrial cancer stemness and metastasis by changing lipid components and activating the TGF/ß-Smad2/3 signaling pathway.

The incidence of endometrial cancer (EC) increases annually and tends to occur in younger women. A particularly important relationship exists between EC and metabolic disorders. As one of the most important components of lipid metabolism, phospholipids play an indispensable role in metabolic balance. LPCAT1 is a key enzyme regulating phospholipid metabolism. In this study, we perform further investigations to seek mechanistic insight of LPCAT1 in EC. Our results demonstrate that silencing of LPCAT1 inhibits the growth of endometrial cancer, while overexpression of LPCAT1 results in enhanced stemness and metastasis in endometrial cancer cell lines. Meanwhile, the contents of various phospholipids including phosphatidylethanolamine (PE), phosphatidylcholine (PC), and triglyceride (TG) change significantly after overexpression of LPCAT1. In addition, through RNA-sequencing and western blot analysis, we observe that the TGF-ß/Smad2/3 signaling pathway is of great importance in the tumor-promoting function of LPCAT1. LPCAT1 promotes the expressions of stem cell-related transcription factors and epithelial-mesenchymal transition (EMT) related proteins through the TGF-ß/Smad2/3 signaling pathway. Moreover, we find that TSI-01, which can inhibit the activity of LPCAT1, is able to restrain the proliferation of EC cell lines and promote cell apoptosis. Collectively, we demonstrate that LPCAT1 enhances the stemness and metastasis of EC by activating the TGF-ß/Smad2/3 signaling pathway and that TSI-01 may have potential use for the treatment of EC.

CRABP1 in Non-Canonical Activities of Retinoic Acid in Health and Diseases.

In this review, we discuss the emerging role of Cellular Retinoic Acid Binding Protein 1 (CRABP1) as a mediator of non-canonical activities of retinoic acid (RA) and relevance to human diseases. We first discuss the role of CRABP1 in regulating MAPK activities and its implication in stem cell proliferation, cancers, adipocyte health, and neuro-immune regulation. We then discuss an additional role of CRABP1 in regulating CaMKII activities, and its implication in heart and motor neuron diseases. Through molecular and genetic studies of Crabp1 knockout (CKO) mouse and culture models, it is established that CRABP1 forms complexes with specific signaling molecules to function as RA-regulated signalsomes in a cell context-dependent manner. Gene expression data and CRABP1 gene single nucleotide polymorphisms (SNPs) of human cancer, neurodegeneration, and immune disease patients implicate the potential association of abnormality in CRABP1 with human diseases. Finally, therapeutic strategies for managing certain human diseases by targeting CRABP1 are discussed.

A system based on deep convolutional neural network improves the detection of early gastric cancer.

Background: Early gastric cancer (EGC) has a high survival rate, but it is difficult to diagnosis. Recently, artificial intelligence (AI) based on deep convolutional neural network (DCNN) has made significant progress in the field of gastroenterology. The purpose of this study was to establish a DCNN assist system to improve the detection of EGC. Methods: 3400 EGC and 8600 benign images were collected to train the DCNN to detect EGC. Subsequently, its diagnostic ability was compared to that of endoscopists using an independent internal test set (ITS, including 1289 images) and an external test set (ETS, including 542 images) come from three digestive center. Results: The diagnostic time of DCNN and endoscopists were 0.028s, 8.05 ± 0.21s, 7.69 ± 0.25s in ITS, and 0.028s, 7.98 ± 0.19s, 7.50 ± 0.23s in ETS, respectively. In ITS, the diagnostic sensitivity and accuracy of DCNN are 88.08%(95% confidence interval,95%CI,85.24%-90.44%), 88.60% (95%CI,86.74%-90.22%), respectively. In ETS, the diagnostic sensitivity and accuracy are 92.08% (95%CI, 87.91%- 94.94%),92.07%(95%CI, 89.46%-94.08%),respectively. DCNN outperformed all endoscopists in ETS, and had a significantly higher sensitivity than the junior endoscopists(JE)(by18.54% (95%CI, 15.64%-21.84%) in ITS, also higher than JE (by21.67%,95%CI, 16.90%-27.32%) and senior endoscopists (SE) (by2.08%, 95%CI, 0.75%-4.92%)in ETS. The accuracy of DCNN model was higher (by10.47%,95%CI, 8.91%-12.27%) than that of JE in ITS, and also higher (by14.58%,95%CI, 11.84%-17.81%; by 1.94%,95%CI,1.25%-2.96%, respectively) than JE and SE in ETS. Conclusion: The DCNN can detected more EGC images in a shorter time than the endoscopists. It will become an effective tool to assist in the detection of EGC in the near future.

Crabp1 Modulates HPA Axis Homeostasis and Anxiety-like Behaviors by Altering FKBP5 Expression.

Retinoic acid (RA), the principal active metabolite of vitamin A, is known to be involved in stress-related disorders. However, its mechanism of action in this regard remains unclear. This study reports that, in mice, endogenous cellular RA binding protein 1 (Crabp1) is highly expressed in the hypothalamus and pituitary glands. Crabp1 knockout (CKO) mice exhibit reduced anxiety-like behaviors accompanied by a lowered stress induced-corticosterone level. Furthermore, CRH/DEX tests show an increased sensitivity (hypersensitivity) of their feedback inhibition in the hypothalamic-pituitary-adrenal (HPA) axis. Gene expression studies show reduced FKBP5 expression in CKO mice; this would decrease the suppression of glucocorticoid receptor (GR) signaling thereby enhancing their feedback inhibition, consistent with their dampened corticosterone level and anxiety-like behaviors upon stress induction. In AtT20, a pituitary gland adenoma cell line elevating or reducing Crabp1 level correspondingly increases or decreases FKBP5 expression, and its endogenous Crabp1 level is elevated by GR agonist dexamethasone or RA treatment. This study shows, for the first time, that Crabp1 regulates feedback inhibition of the the HPA axis by modulating FKBP5 expression. Furthermore, RA and stress can increase Crabp1 level, which would up-regulate FKBP5 thereby de-sensitizing feedback inhibition of HPA axis (by decreasing GR signaling) and increasing the risk of stress-related disorders.

Fatostatin reverses progesterone resistance by inhibiting the SREBP1-NF-κB pathway in endometrial carcinoma.

Progesterone resistance can significantly restrict the efficacy of conservative treatment for patients with endometrial cancer who wish to preserve their fertility or those who suffer from advanced and recurrent cancer. SREBP1 is known to be involved in the occurrence and progression of endometrial cancer, although the precise mechanism involved remains unclear. In the present study, we carried out microarray analysis in progesterone-sensitive and progesterone-resistant cell lines and demonstrated that SREBP1 is related to progesterone resistance. Furthermore, we verified that SREBP1 is over-expressed in both drug-resistant tissues and cells. Functional studies further demonstrated that the inhibition of SREBP1 restored the sensitivity of endometrial cancer to progesterone both in vitro and in vivo, and that the over-expression of SREBP1 promoted resistance to progesterone. With regards to the mechanism involved, we found that SREBP1 promoted the proliferation of endometrial cancer cells and inhibited their apoptosis by activating the NF-κB pathway. To solve the problem of clinical application, we found that Fatostatin, an inhibitor of SREBP1, could increase the sensitivity of endometrial cancer to progesterone and reverse progesterone resistance by inhibiting SREBP1 both in vitro and in vivo. Our results highlight the important role of SREBP1 in progesterone resistance and suggest that the use of Fatostatin to target SREBP1 may represent a new method to solve progesterone resistance in patients with endometrial cancer.

Elevated expression of LPCAT1 predicts a poor prognosis and is correlated with the tumour microenvironment in endometrial cancer.

BACKGROUND: Endometrial cancer (EC) is one of the three malignant reproductive tumours that threaten women's lives and health. Glycerophospholipids (GPLs) are important bioactive lipids involved in various physiological and pathological processes, including cancer. Immune infiltration of the tumour microenvironment (TME) is positively associated with the overall survival in EC. Exploring GPL-related factors associated with the TME in endometrial cancer can aid in the prognosis of patients and provide new therapeutic targets. METHODS: Differentially expressed GPL-related genes were identified from TCGA-UCEC datasets and the Molecular Signatures Database (MSigDB). Univariate Cox regression analysis was used to select GPL-related genes with prognostic value. The Random forest algorithm, LASSO algorithm and PPI network were used to identify critical genes. ESTIMATEScore was calculated to identify genes associated with the TME. Then, differentiation analysis and survival analysis of LPCAT1 were performed based on TCGA datasets. GSE17025 and immunohistochemistry (IHC) verified the results of the differentiation analysis. An MTT assay was then conducted to determine the proliferation of EC cells. GO and KEGG enrichment analyses were performed to explore the underlying mechanism of LPCAT1. In addition, we used the ssGSEA algorithm to explore the correlation between LPCAT1 and cancer immune infiltrates. RESULTS: Twenty-three differentially expressed GPL-related genes were identified, and eleven prognostic genes were selected by univariate Cox regression analysis. Four significant genes were identified by two different algorithms and the PPI network. Only LPCAT1 was significantly correlated with the tumour microenvironment. Then, we found that LPCAT1 was highly expressed in tumour samples compared with that in normal tissues, and lower survival rates were observed in the groups with high LPCAT1 expression. Silencing of LPCAT1 inhibited the proliferation of EC cells. Moreover, the expression of LPCAT1 was positively correlated with the histologic grades and types. The ROC curve indicated that LPCAT1 had good prognostic accuracy. Receptor ligand activity, pattern specification process, regionalization, anterior/posterior pattern specification and salivary secretion pathways were enriched as potential targets of LPCAT1. By using the ssGSEA algorithm, fifteen kinds of tumor-infiltrating cells (TICs) were found to be correlated with LPCAT1 expression. CONCLUSION: These findings suggested that LPCAT1 may act as a valuable prognostic biomarker and be correlated with immune infiltrates in endometrial cancer, which may provide novel therapy options for and improved treatment of EC.

Dual targeting, a new strategy for novel PARP inhibitor discovery.

As a hallmark for cancer treatment, PARP inhibitors can effectively kill tumor cells with a mechanism termed as synthetic lethality, and are used to treat various cancers including ovarian, breast, prostate, pancreatic and others with DNA repair defects. However, along with the clinical trials progressing, the limitations of PARP-1 inhibitors became apparent such as limited activity and indications. Studies have shown that a molecule that is able to simultaneously restrict two or more targets involving in tumors is more effective in preventing and treating cancers due to the enhancing synergies. In order to make up for the shortcomings of PARP inhibitors, reduce the development cost and overcome the pharmacokinetic defects, multiple works were carried out to construct dual targeting PARP inhibitors for cancer therapy. Herein, they were summarized briefly.