Development of the nonreceptor tyrosine kinase FER-targeting PROTACs as a potential strategy for antagonizing ovarian cancer cell motility and invasiveness.

Aberrant overexpression of nonreceptor tyrosine kinase FER (Fps/Fes Related) has been reported in various ovarian carcinoma-derived tumor cells and is a poor prognosis factor for patient survival. It plays an essential role in tumor cell migration and invasion, acting concurrently in both kinase-dependent and -independent manners, which is not easily suppressed by conventional enzymatic inhibitors. Nevertheless, the PROteolysis-TArgeting Chimera (PROTAC) technology offers superior efficacy over traditional activity-based inhibitors by simultaneously targeting enzymatic and scaffold functions. Hence in this study, we report the development of two PROTAC compounds that promote robust FER degradation in a cereblon-dependent manner. Both PROTAC degraders outperform a Food and Drug Administration-approved drug, brigatinib, in ovarian cancer cell motility suppression. Importantly, these PROTAC compounds also degrade multiple oncogenic FER fusion proteins identified in human tumor samples. These results lay an experimental foundation to apply the PROTAC strategy to antagonize cell motility and invasiveness in ovarian and other types of cancers with aberrant expression of FER kinase and highlight PROTACs as a superior strategy for targeting proteins with multiple tumor-promoting functions.

Signaling repurposable drug combinations against COVID-19 by developing the heterogeneous deep herb-graph method.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spurred a boom in uncovering repurposable existing drugs. Drug repurposing is a strategy for identifying new uses for approved or investigational drugs that are outside the scope of the original medical indication. MOTIVATION: Current works of drug repurposing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are mostly limited to only focusing on chemical medicines, analysis of single drug targeting single SARS-CoV-2 protein, one-size-fits-all strategy using the same treatment (same drug) for different infected stages of SARS-CoV-2. To dilute these issues, we initially set the research focusing on herbal medicines. We then proposed a heterogeneous graph embedding method to signaled candidate repurposing herbs for each SARS-CoV-2 protein, and employed the variational graph convolutional network approach to recommend the precision herb combinations as the potential candidate treatments against the specific infected stage. METHOD: We initially employed the virtual screening method to construct the 'Herb-Compound' and 'Compound-Protein' docking graph based on 480 herbal medicines, 12,735 associated chemical compounds and 24 SARS-CoV-2 proteins. Sequentially, the 'Herb-Compound-Protein' heterogeneous network was constructed by means of the metapath-based embedding approach. We then proposed the heterogeneous-information-network-based graph embedding method to generate the candidate ranking lists of herbs that target structural, nonstructural and accessory SARS-CoV-2 proteins, individually. To obtain precision synthetic effective treatments forvarious COVID-19 infected stages, we employed the variational graph convolutional network method to generate candidate herb combinations as the recommended therapeutic therapies. RESULTS: There were 24 ranking lists, each containing top-10 herbs, targeting 24 SARS-CoV-2 proteins correspondingly, and 20 herb combinations were generated as the candidate-specific treatment to target the four infected stages. The code and supplementary materials are freely available at https://github.com/fanyang-AI/TCM-COVID19.

Development of high-performance point-of-care aqueous VEGF detection system and proof-of-concept validation in RVO patients.

OBJECTIVES: To develop a sensitive point-of-care testing (POCT) aqueous vascular endothelial growth factor (VEGF) detection system, and assess its role for predicting the response to anti-VEGF treatment in macular edema secondary to retinal vein occlusion (RVO-ME) patients. METHODS: An automatic point-of-care aqueous humor Magnetic Particle Chemiluminescence Enzyme Immuno-Assay (MPCLEIA) VEGF detection system was developed. The predictive values of aqueous cytokine levels, in combination with imaging parameters, on anatomical treatment response (ATR, the relative central macular thickness change [ΔCMT/bl-CMT]) were analyzed. RESULTS: The automatic MPCLEIA system was able to provide results in 45 min with only 20 µL sample. Among the 57 eyes with available pre- and post-treatment evaluation, ATR significantly correlated with levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and VEGF measured by Luminex xMAP platform, and VEGF measured by MPCLEIA. Optimal cut-off values for these biomarkers were 13.26 ng/L, 23.57 ng/L, 1,110.12 ng/L, 105.52 ng/L, and 85.39 ng/L, respectively. Univariate analysis showed significant associations between ATR category (good response if ATR≤-25 % or poor response otherwise) and IL-6, IL-8, MCP-1, VEGF-xMAP, and VEGF-MPCLEIA (p<0.05). Multivariate logistic regression revealed that ATR category was significantly associated with aqueous VEGF-MPCLEIA (p=0.006) and baseline(bl)-CMT (p=0.008). Receiver operating characteristics analysis yielded an AUC of 0.959 for the regression model combining VEGF-MPCLEIA and bl-CMT, for predicting ATR category. CONCLUSIONS: Our novel MPCLEIA-based automatic VEGF detection system enables accurate POCT of aqueous VEGF, which shows promise in predicting the treatment response of RVO-ME to anti-VEGF agents when combined with bl-CMT.

Clinical Impact of Metformin Therapy on Gestational Diabetes Mellitus and Maternal-Infant Health Outcomes.

Objective: This study aimed to assess the impact of metformin treatment on clinical parameters (blood glucose, inflammation, hormone levels) and outcomes for both mothers and infants in cases of gestational diabetes mellitus (GDM). Methods: A comparative study with a retrospective cohort design was conducted. A total of 96 patients diagnosed with gestational diabetes mellitus over the past three years in our hospital were included. The participants were divided into two groups: a control group receiving insulin treatment and a study group receiving metformin treatment. We compared the clinical effects between the two groups. Results: After treatment, the levels of postprandial 2-hour blood glucose, fasting blood glucose, and glycosylated hemoglobin significantly improved in both groups compared to pre-treatment levels. Moreover, the study group exhibited superior outcomes compared to the control group (P < .05). The levels of interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) demonstrated improvement in both groups, with the study group outperforming the control group (P < .05). Additionally, the levels of Cystatin C (CysC) and Homocysteine (Hcy) in both groups improved post-treatment, with the study group showing better results than the control group (P < .05). Notably, the study group exhibited a lower incidence of adverse outcomes than the control group (P < .05). Conclusions: Metformin therapy demonstrated a significant clinical impact on gestational diabetes mellitus. Compared to insulin therapy, metformin showed superior effects on blood glucose, inflammation, hormone levels, and maternal and infant outcomes, suggesting its adoption for patient consideration.

Effectiveness of exercise-based cardiac rehabilitation for patients with left ventricular assist device: A systematic review and meta-analysis.

PURPOSE: Exercise-based cardiac rehabilitation (EBCR) improves functional capacity in heart failure (HF). However, data on the effect of EBCR in patients with advanced HF and left ventricular assist devices (LVADs) are limited. This meta-analysis aimed to evaluate the impact of EBCR on the functional ability of LVAD patients by comparing the corresponding outcome indicators between the EBCR and ST groups. METHODS: PubMed, Embase, Clinical Trials, and Cochrane Library databases were searched for studies assessing and comparing the effects of EBCR and standard therapy (ST) in patients following LVAD implantation. Using pre-defined criteria, appropriate studies were identified and selected. Data from selected studies were extracted in a standardized fashion, and a meta-analysis was performed using a fixed-effects model. The protocol was registered on INPLASY (202340073). RESULTS: In total, 12 trials involving 477 patients were identified. The mean age of the participants was 52.9 years, and 78.6% were male. The initiation of EBCR varied from LVAD implantation during the index hospitalization to 11 months post-LVAD implantation. The median rehabilitation period ranged from 2 weeks to 18 months. EBCR was associated with improved peak oxygen uptake (VO2) in all trials. Quantitative analysis was performed in six randomized studies involving 214 patients (EBCR: n = 130, ST: n = 84). EBCR was associated with a significantly high peak VO2 (weighted mean difference [WMD] = 1.64 mL/kg/min; 95% confidence interval [CI], 0.20-3.08; p = .03). Similarly, 6-min walk distance (6MWD) showed significantly greater improvement in the EBCR group than in the ST group (WMD = 34.54 m; 95% CI, 12.47-56.42; p = .002) in 266 patients (EBCR, n = 140; ST, n = 126). Heterogeneity was low among the included trials. None of the included studies reported serious adverse events related to EBCR, indicating the safety of EBCR after LVAD implantation. CONCLUSION: This study demonstrated that EBCR following LVAD implantation is associated with greater improvement in functional capacity compared with ST as reflected by the improved peak VO2 and 6MWD values. Considering the small number of patients in this analysis, further research on the clinical impact of EBCR in LVAD patients is warranted.

Non-traditional lipid parameters as potential predictors of carotid plaque vulnerability and stenosis in patients with acute ischemic stroke.

OBJECTIVE: Lipid abnormalities are important risk factors in patients with large atherosclerotic strokes. Recent studies have shown that non-traditional lipid parameters are crucial to the development of atherosclerosis and are closely related to the clinical outcome of acute ischemic stroke (AIS). Therefore, we aimed to investigate the relationship between non-traditional lipid parameters and carotid plaque stability and stenosis degree in patients with large atherosclerotic stroke. METHODS: We retrospectively analyzed 336 patients with AIS. All patients were divided into the non-plaque group, stable plaque group, and vulnerable plaque group according to ultrasound examination. At the same time, the patients were divided into non-stenosis, mild stenosis, moderate stenosis, and severe stenosis groups according to the degree of stenosis. Non-traditional lipid parameters, including residual lipoprotein cholesterol (RLP-C), non-high-density lipoprotein cholesterol (non-HDL-C), non-HDL-C to high-density lipoprotein cholesterol ratio (non-HDL-C/HDL-C), triglyceride to HDL-C ratio (TG/HDL-C), Castelli's risk index (CRI), and the atherogenic index of plasma (AIP). Receiver operating characteristic (ROC) curves and multivariate logistic regression analyses were used to investigate the associations between the non-traditional lipid parameters and carotid plaque vulnerability. Spearman linear correlation analysis was used to test the correlation between variables and the degree of carotid plaque stenosis. RESULTS: This study population included 336 patients with AIS, of whom 294 had a carotid plaque. Multivariate logistic regression model showed that RLP-C (OR, 3.361; 95%CI, 1.311-8.617), non-HDL-C/HDL-C (OR, 1.699; 95%CI, 1.279-2.258), non-HDL-C (OR, 1.704; 95%CI, 1.143-2.540), CRI-I (OR, 1.573; 95%CI, 1.196-2.068), and CRI-II (OR, 2.022; 95%CI, 1.369-2.985) were independent risk factors for carotid plaque vulnerability. In addition, Spearman correlation analysis showed that the values of RLP-C, non-HDL-C/HDL-C, non-HDL-C, TG/HDL-C, CRI-I, CRI-II, and AIP on admission were positively correlated with the degree of carotid plaque stenosis (all P < 0.001). CONCLUSION: This study provides evidence that non-traditional lipid parameters (LP-C, non-HDL-C/HDL-C, non-HDL-C, CRI-I, and CRI-II) were potential predictors of carotid plaque vulnerability in patients with AIS. However, no significant correlation was observed between TG/HDL-C and AIP. RLP-C, non-HDL-C/HDL-C, non-HDL-C, TG/HDL-C, CRI-I, CRI-II, and AIP were closely related to the degree of carotid plaque stenosis. Non-traditional lipid parameters can be used as novel biomarkers of carotid plaque vulnerability and stenosis.

Radiomics under 2D regions, 3D regions, and peritumoral regions reveal tumor heterogeneity in non-small cell lung cancer: a multicenter study.

PURPOSE: Lung cancer has significant genetic and phenotypic heterogeneity, leading to poor prognosis. Radiomic features have emerged as promising predictors of the tumor phenotype. However, the role of underlying information surrounding the cancer remains unclear. MATERIALS AND METHODS: We conducted a retrospective study of 508 patients with NSCLC from three institutions. Radiomics models were built using features from six tumor regions and seven classifiers to predict three prognostically significant tumor phenotypes. The models were evaluated and interpreted by the mean area under the receiver operating characteristic curve (AUC) under nested cross-validation and Shapley values. The best-performing predictive models corresponding to six tumor regions and three tumor phenotypes were identified for further comparative analysis. In addition, we designed five experiments with different voxel spacing to assess the sensitivity of the experimental results to the spatial resolution of the voxels. RESULTS: Our results demonstrated that models based on 2D, 3D, and peritumoral region features yielded mean AUCs and 95% confidence intervals of 0.759 and [0.747-0.771] for lymphovascular invasion, 0.889 and [0.882-0.896] for pleural invasion, and 0.839 and [0.829-0.849] for T-staging in the testing cohort, which was significantly higher than all other models. Similar results were obtained for the model combining the three regional features at five voxel spacings. CONCLUSION: Our study revealed the predictive role of the developed methods with multi-regional features for the preoperative assessment of prognostic factors in NSCLC. The analysis of different voxel spacing and model interpretability strengthens the experimental findings and contributes to understanding the biological significance of the radiological phenotype.

The architecture of intra-organism mutation rate variation in plants.

Given the disposability of somatic tissue, selection can favor a higher mutation rate in the early segregating soma than in germline, as seen in some animals. Although in plants intra-organismic mutation rate heterogeneity is poorly resolved, the same selectionist logic can predict a lower rate in shoot than in root and in longer-lived terminal tissues (e.g., leaves) than in ontogenetically similar short-lived ones (e.g., petals), and that mutation rate heterogeneity should be deterministic with no significant differences between biological replicates. To address these expectations, we sequenced 754 genomes from various tissues of eight plant species. Consistent with a selectionist model, the rate of mutation accumulation per unit time in shoot apical meristem is lower than that in root apical tissues in perennials, in which a high proportion of mutations in shoots are themselves transmissible, but not in annuals, in which somatic mutations tend not to be transmissible. Similarly, the number of mutations accumulated in leaves is commonly lower than that within a petal of the same plant, and there is no more heterogeneity in accumulation rates between replicate branches than expected by chance. High mutation accumulation in runners of strawberry is, we argue, the exception that proves the rule, as mutation transmission patterns indicate that runner has a restricted germline. However, we also find that in vitro callus tissue has a higher mutation rate (per unit time) than the wild-grown comparator, suggesting nonadaptive mutational "fragility". As mutational fragility does not obviously explain why the shoot-root difference varies with plant longevity, we conclude that some mutation rate variation between tissues is consistent with selectionist theory but that a mechanistic null of mutational fragility should be considered.

The Diversity of Viral Community in Invasive Fruit Flies (Bactrocera and Zeugodacus) Revealed by Meta-transcriptomics.

RNA viruses are extremely diverse and rapidly evolving in various organisms. Our knowledge on viral evolution with interacted hosts in the manner of ecology is still limited. In the agricultural ecosystem, invasive insect species are posing a great threat to sustainable crop production. Among them, fruit flies (Diptera: Tephritidae Bactrocera and Zeugodacus) are destructive to fruits and vegetables, which are also closely related and often share similar ecological niches. Thus, they are ideal models for investigating RNA virome dynamics in host species. Using meta-transcriptomics, we found 39 viral sequences in samples from 12 fly species. These viral species represented the diversity of the viromes including Dicistroviridae, negev-like virus clades, Thika virus clades, Solemoviridae, Narnaviridae, Nodaviridae, Iflaviridae, Orthomyxoviridae, Bunyavirales, Partitiviridae, and Reoviridae. In particular, dicistrovirus, negev-like virus, orthomyxovirus, and orbivirus were common in over four of the fly species, which suggests a positive interaction between fly viromes that exist under the same ecological conditions. For most of the viruses, the virus-derived small RNAs displayed significantly high peaks in 21 nt and were symmetrically distributed throughout the viral genome. These results suggest that infection by these viruses can activate the host's RNAi immunity. Our study provides RNA virome diversity and evidence on their infection activity in ecologically associated invasive fruit fly species, which could help our understanding of interactions between complex species and viruses.

Cognitive training program improves cognitive ability and daily living ability in elderly patients with mild cognitive impairment.

BACKGROUND: Mild cognitive impairment (MCI) is a clinical syndrome of mild memory or other cognitive impairment without dementia and is a clinical transition state between normal aging and dementia. Careful and meticulous nursing intervention can improve the clinical symptoms of MCI and delay the progression of the disease. AIMS: This research aimed to evaluate the efficacy of cognitive function training interventions in elderly patients with MCI. METHODS: 106 patients were randomized into the intervention group or the control group. They received conventional nursing intervention and those in the intervention group received additional cognitive training program for 6 weeks. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), activities of daily living (ADL) scales, and Barthel index (BI) were evaluated before and 6 weeks after the intervention, as well as the serum levels of S100ß and neuron-specific enolase (NSE) at two time points. RESULTS: After intervention, the MMSE scores and MoCA scores in both groups were significantly increased and the score in the intervention group was significantly higher. In the intervention group, the performance of conventional nursing intervention and cognitive training program significantly increased the scores of ADL and BI (p < 0.001). The serum levels of NSE and S100ß in the intervention group were significantly lower. DISCUSSION: The performance of cognitive training program alleviated the brain tissue damage in elderly patients with MCI. CONCLUSIONS: The performance of cognitive training program in elderly patients with MCI improved their cognitive ability and daily living ability.

Sevoflurane alleviates lung injury and inflammatory response compared with propofol in a rat model of VV ECMO.

INTRODUCTION: Although venovenous extracorporeal membrane oxygenation (VV ECMO) is a reasonable salvage treatment for acute respiratory distress syndrome (ARDS), it requires sedating the patient. Sevoflurane and propofol have pulmonary protective and immunomodulatory properties. This study aimed to compare the effectiveness of sevoflurane and propofol on rats with induced ARDS undergoing VV ECMO. METHODS: Fifteen sprague-dawley (SD) rats were randomly divided into three groups: Con group, sevoflurane (Sevo) group and propofol (Pro) group. Arterial blood gas tests were performed at time pointsT0 (baseline), T1 (the time to ARDS), and T2 (weaning from ECMO). Oxygenation index (PaO2/FiO2) was calculated, and lung edema assessed by determining the lung wet:dry ratio. The protein concentration in bronchial alveolar lavage fluid (BALF) was determined by using bicinchoninic acid assay. Haematoxylin and eosin staining was used to evaluate the lung pathological scores in each group. IL-1ß and TNF-α were also measured in the BALF, serum and lung. RESULTS: Oxygenation index showed improvement in the Sevo group versus Pro group. The wet:dry ratio was reduced in the Sevo group compared with propofol-treated rats. Lung pathological scores were substantially lower in the Sevo group versus the Pro group. Protein concentrations in the BALF and levels of IL-1ß and TNF-α in the Sevo group were substantially lower versus Pro group. CONCLUSION: This study demonstrates that compared with propofol, sevoflurane was more efficacious in improving oxygenation and decreasing inflammatory response in rat models with ARDS subject to VV ECMO treatment.

Progress in Electrohydrodynamic Atomization Preparation of Energetic Materials with Controlled Microstructures.

Constructing ingenious microstructures, such as core-shell, laminate, microcapsule and porous microstructures, is an efficient strategy for tuning the combustion behaviors and thermal stability of energetic materials (EMs). Electrohydrodynamic atomization (EHDA), which includes electrospray and electrospinning, is a facile and versatile technique that can be used to process bulk materials into particles, fibers, films and three-dimensional (3D) structures with nanoscale feature sizes. However, the application of EHDA in preparing EMs is still in its initial development. This review summarizes the progress of research on EMs prepared by EHDA over the last decade. The morphology and internal structure of the produced materials can be easily altered by varying the operation and precursor parameters. The prepared EMs composed of zero-dimensional (0D) particles, one-dimensional (1D) fibers and two-dimensional (2D) films possess precise microstructures with large surface areas, uniformly dispersed components and narrow size distributions and show superior energy release rates and combustion performances. We also explore the reasons why the fabrication of 3D EM structures by EHDA is still lacking. Finally, we discuss development challenges that impede this field from moving out of the laboratory and into practical application.

Retraction notice to "Pulmonary route of administration is instrumental in developing therapeutic interventions against respiratory diseases" [Saudi Pharm. J. 28(12) (2020) 1655-1665].

[This retracts the article DOI: 10.1016/j.jsps.2020.10.012.].

Intravenous Recombinant Tissue-Type Plasminogen Activator Thrombolysis for Acute Central Retinal Artery Occlusion.

INTRODUCTION: Central retinal artery occlusion (CRAO), an ocular stroke, causes severe and permanent visual impairment. Thrombolytic therapy is currently the main treatment option for CRAO. Intravenous thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) has been extensively applied in the treatment of CRAO with the proven advantages of effectiveness and safety. This meta-analysis aimed to assess the efficacy of intravenous rt-PA thrombolysis for the management of CRAO by evaluating the pooled evidence. METHODS: A comprehensive literature search of electronic databases including PubMed, OVID, and Cochrane Library was conducted up to and including March 2019. All studies reporting visual outcomes after CRAO with thrombolytic therapy were collected. Data on visual acuity and adverse events were recorded and assessed in this analysis. Data were inputted into the statistical software of STATA. The studies were weighed by the inverse of the variance and merged in a random-effects model. RESULTS: The systematic review process yielded 7 eligible studies including 121 patients with CRAO who received the intravenous rt-PA treatment. Sixty-two patients showed improvement in visual acuity (52.0%; 95% CI, 34.0%-70.0%) following rt-PA intravenous thrombolytic therapy. The observed improvement rate in the intravenous rt-PA treatment group was significantly higher than the conservative treatment group (40.4% vs. 13.0%; OR = 5.16; 95% CI, 1.90-14.05). The incidence rate of complications was relatively low (11 out of the 121 patients). Hemorrhage (9/11) was the major reported complication. Mortality was zero. DISCUSSION: This meta-analysis indicated that intravenous rt-PA thrombolysis could be an effective and safe strategy for the management of CRAO. However, a more detailed large-scale clinical trial is warranted to strengthen the evidence-based therapeutic guidance.

Automated delineation of corneal layers on OCT images using a boundary-guided CNN.

Accurate segmentation of corneal layers depicted on optical coherence tomography (OCT) images is very helpful for quantitatively assessing and diagnosing corneal diseases (e.g., keratoconus and dry eye). In this study, we presented a novel boundary-guided convolutional neural network (CNN) architecture (BG-CNN) to simultaneously extract different corneal layers and delineate their boundaries. The developed BG-CNN architecture used three convolutional blocks to construct two network modules on the basis of the classical U-Net network. We trained and validated the network on a dataset consisting of 1,712 OCT images acquired on 121 subjects using a 10-fold cross-validation method. Our experiments showed an average dice similarity coefficient (DSC) of 0.9691, an intersection over union (IOU) of 0.9411, and a Hausdorff distance (HD) of 7.4423 pixels. Compared with several other classical networks, namely U-Net, Attention U-Net, Asymmetric U-Net, BiO-Net, CE-Net, CPFnte, M-Net, and Deeplabv3, on the same dataset, the developed network demonstrated a promising performance, suggesting its unique strength in segmenting corneal layers depicted on OCT images.

Dietary patterns of Chinese puerperal women and their association with postpartum weight retention: Results from the mother-infant cohort study.

Dietary intake may affect maternal health, but it remains unclear about puerperal dietary intake and its association with maternal health. This study investigated the dietary patterns and their related factors and association with postpartum weight retention (PPWR) in Chinese puerperal women. Participants were from the mother-infant cohort study, in which both mothers and infants were followed up from childbirth to the next 2 years, in seven cities around China. Maternal puerperal dietary patterns were derived by a food frequency questionnaire and principal component analysis (PCA) within 1 month postpartum. PPWR was assessed by the difference of weight at 42 days and 6 months postpartum minus the pre-pregnancy weight. Of 503 postpartum women, four dietary patterns were identified, including 'plant food' pattern (rice and vegetables as dominant foods), 'diverse' pattern (starchy roots, fruit, livestock meat and aquatic products), 'traditional northern' pattern (poultry, eggs and soup) and 'marine-flour' pattern (flour, coarse food grains and marine fish). The diverse pattern was associated with professional puerperal family care and counselling service (p < .05). PPWRs at 42 days and 6 months postpartum were 6.37 and 4.70 kg averagely. The plant food dietary pattern tended to be associated with higher 42-day PPWR (ß = .105, p < .05), and diverse pattern was associated with lower 6-months PPWR (ß = -.137, p < .05). Conclusively, this study presented four dominant dietary patterns in Chinese postpartum women and showed a lower PPWR in adherence to diverse dietary pattern. The results would provide evidence to furtherly guide dietary practice and improve maternal health.

Effects of latanoprost on the expression of TGF-ß1 and Wnt / ß-catenin signaling pathway in the choroid of form-deprivation myopia rats.

In this study, we investigated the effect of latanoprost on the expression of TGF- ß1 and Wnt / ß - Catenin signal pathway in the choroid of form-deprivation myopia model rats. Forty rats were randomly divided into two groups: the control group and the FDM model group. Each group had 20 rats. The FDM model group was established by feeding latanoprost daily for 28 days. 15 rats in each group were used to measure the length of the ocular axis and the level of TGF-ß1 in choroidal tissue; the remaining 5 rats in each group were used for choroidal fibroblast culture. After modeling, the rats were killed, the length of the ocular axis was measured with a vernier caliper, and the level of TGF - ß1 protein and mRNA in the choroidal tissue of each group were measured with RT-PCR method. Results showed that compared with the control group, there was a significant difference in the axial length of the FDM model group (P< 0.05). There was a significant difference in the expression of TGF- ß1 protein and mRNA between the two groups (P<0.05). The cultured cells were identified as choroidal fibroblasts by immunocytochemistry. There was no significant difference (P>0.05) in the comparison of GSK3 ß protein in choroidal fibroblasts of rats in each group. TGF-ß 1 and APC protein in FDM group were significantly lower than those in the control group (P<0.05), while dcl3, p21-gsk3 ß and ß - Catenin proteins were significantly higher (P<0.05), and there was no significant difference (P>0.05) in the ratio of various indexes protein in FDM + ddk1 group and the comparison of TGF - ß1 and APC protein in FDM + ddk1 group and FDM group The expression of dcl3, p21-gsk3 ß and ß - Catenin decreased significantly (P<0.05). There was no significant difference in the expression of GSK3 ß mRNA in the choroidal fibroblasts of each group (P>0.05). The expression of TGF - ß 1 and APC mRNA in FDM group was significantly lower than that in the control group (P<0.05), while the expression of dcl3, p21-gsk3 ß and ß-catenin mRNA in FDM + ddk1 group was significantly higher than that in the control group (P<0.05) >In FDM + ddk1 group, TGF-ß 1 and APC mRNA were significantly lower than those in FDM group (P<0.05), while dcl3, p21-gsk3 ß and ß-Catenin mRNA were significantly higher (P<0.05).

Design, synthesis and in vitro evaluation of fangchinoline derivatives as potential anticancer agents.

The isolation and modification of natural products play an important role in the synthesis of anti-tumor drugs for the treatment of cancer. The present study was designed to evaluate the effects of fangchinoline derivatives against cancer cells. In vitro cytotoxicity of all derivatives against five cancer cell lines (A549, Hela, HepG-2, MCF-7 and MDA-MB-231 cell lines) and HL-7702 normal cells was assessed using the CCK-8 assay, and the results showed that most of the synthesized compounds displayed better cytotoxic effects on all the tested cells compared to that of the parent fangchinoline. In particular, compound 3i had the strongest inhibitory effect on cell proliferation, with an IC50 value of 0.61 µM against A549 cells. Compared with fangchinoline and HCPT (hydroxycamptothecine), the anti-proliferative activity of compound 3i was significantly increased. More interestingly, compound 3i had slight toxic side effects on normal cells, with an IC50 value of 27.53 µM. Moreover, the cell viability and cell cycle assays revealed that compound 3i inhibited A549 cell proliferation and arrested A549 cells at the G2/M-phase. The apoptosis-inducing effects of compound 3i and the associated molecular mechanisms were assessed using flow cytometry, cell staining, reactive oxygen species assays, RT-qPCR and Western blot analysis. These results suggested that compound 3i induces apoptosis through a mitochondria-mediated intrinsic pathway. This study revealed that compound 3i is a promising candidate for future development as an anti-tumor drug.

Maternal postpartum feeding anxiety was associated with infant feeding practices: results from the mother-infant cohort study of China.

BACKGROUND: Maternal feeding anxiety (FA) was prevalent during puerperium and might affect infant feeding practices. This study was aimed to investigate the FA status in Chinese postpartum women and its relationship with infant feeding practices (FPs). METHODS: Participants were from the Mother-Infant Cohort Study of China, in which the dietary and feeding practices, physical and psychiatric health for both mothers and infants were followed up from childbirth to next 2 years. In this study the maternal feeding anxiety (FA) status at 0-3 months postpartum was assessed by Li's Self-rating Feeding Anxiety Scale (SFAS). Infant feeding practices (FPs) at 0-3 months, including breastfeeding-related behaviors, responsive feeding and infant food refusal were investigated by self-designed questionnaire. RESULTS: In total 456 mothers the average feeding anxiety scores (FAS) was 41.02 ± 8.02 (mean ± SD), and maternal FA prevalence were 61.4% (FAS>38) with severe FA being 8.6% (FAS>52) at 0-3 months postpartum. The FAS was related with infant FPs, and lower maternal FAS was significantly related with infant colostrum feeding (40.86 ± 8.02 vs 44.74 ± 11.33, P < 0.05), but higher FAS was related with bottle feeding (41.95 ± 8.28 vs 39.69 ± 7.92, P < 0.05). The mothers with severe feeding anxiety (FAS > 53) were more likely to feed infants with bottle (ORs, 95%CI: 2.41, 1.11 ~ 5.19). There were not significant association between FAS and exclusive breastfeeding and responsive feeding practices (P > 0.05). The higher FAS was associated with infant food refusal behaviors, the maternal scores whose infant "never", "rarely", "sometimes" and "often" spat out food when feeding were 39.86 ± 8.02, 41.47 ± 8.18, 41.36 ± 7.44 and 42.14 ± 12.03 increasingly (P > 0.05), and the FA prevalence was significantly different among groups (P < 0.05). The infants whose mother was identified as feeding anxiety were more likely to refuse opening the mouth when feeding (P < 0.05). Multivariate analysis indicated maternal FAS was positively related to infant bottle feeding (ßi = 2.487, P < 0.05) and outdoor sunshine exposure practice (ßi = 1.787, P < 0.05), and negatively related to household income level (ßi = - 0.118, P < 0.05). CONCLUSIONS: Maternal postpartum feeding anxiety was associated with some infant feeding practices, including bottle feeding and infant food refusal behaviors.

Discovery of talmapimod analogues as polypharmacological anti-inflammatory agents.

Twenty novel talmapimod analogues were designed, synthesised and evaluated for the in vivo anti-inflammatory activities. Among them, compound 6n, the most potent one, was selected for exploring the mechanisms underlying its anti-inflammatory efficacy. In RAW264.7 cells, it effectively suppressed lipopolysaccharides-induced (LPS-induced) expressions of iNOS and COX-2. As illustrated by the western blot analysis, 6n downregulated both the NF-κB signalling and p38 MAPK phosphorylation. Further enzymatic assay identified 6n as a potent inhibitor against both p38α MAPK (IC50=1.95 µM) and COX-2 (IC50=0.036 µM). By virtue of the concomitant inhibition of p38α MAPK, its upstream effector, and COX-2, along with its capability to downregulate NF-κB and MAPK-signalling pathways, 6n, a polypharmacological anti-inflammatory agent, deserves further development as a novel anti-inflammatory drug.