Associations between particulate matter exposure during pregnancy and executive function of toddlers in a prospective cohort study.

BACKGROUND: Exposure to particulate matter (PM) has been found to be associated with impaired cognitive function. However, limited evidence is available on the relationship between PM exposure in the prenatal period and toddler executive function (EF), and the potential influence of breastfeeding. METHODS: The study included 1106 mother-toddler pairs recruited between 2015 and 2019. We assessed mothers' PM1, PM2.5, and PM10 prenatal exposure with a satellite-based dataset at a 1 × 1 km spatial resolution and assigned to participants based on residential addresses. Toddler EF was measured using the Behavior Rating Inventory of Executive Function for Preschoolers (BRIEF-P) questionnaire, higher BRIEF-P scores indicated poorer EF in toddlers. We determined the associations of PM exposure during pregnancy with BRIEF-P scores using multiple linear regression models. RESULTS: In the first trimester, a 10 µg/m3 increase of PM was associated with 1.49 (95% confidence interval [CI]: 0.14-2.83; PM1), 0.68 (95% CI: 0.10-1.26; PM2.5), and 0.63 (95% CI: 0.07-1.20; PM10) elevated toddler global executive composite index scores, respectively. In the stratified analysis, a 10 µg/m3 increase in first trimester PM1 exposure was related to 0.54 (95% CI: 0.19-0.89) higher inhibition scores in toddlers who received complementary breastfeeding for less than six months and -0.15 (95% CI: 0.81-0.51) higher inhibition scores in toddlers who received complementary breastfeeding for six months or more (P for interaction: 0.046). Additionally, a 10 µg/m3 increment in first trimester PM1 exposure was related to 0.36 (95% CI: 0.13-0.59) higher emotional control scores in toddlers who received breastfeeding for less than 12 months and -0.54 (95% CI: 1.25-0.18) higher inhibition scores in toddlers who received breastfeeding for no less than 12 months (P for interaction: 0.043). CONCLUSIONS: PM exposure during the first trimester, especially PM1, has been linked to lower toddler EF performance in toddlers; feeding with breast milk may be a potential protective measure.

Association Between Preeclampsia and Blood Pressure in Offspring: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: Pregnancy-induced preeclampsia is a severe pregnancy complication and preeclampsia has been associated with an increased risk of chronic hypertension for offspring. However, the magnitude of the overall effect of exposure to preeclampsia in pregnancy on blood pressure (BP) in offspring is unknown. This systematic review and meta-analysis was sought to systematically assess the effects of preeclampsia on the BP of the offspring. RECENT FINDINGS: Of 2550 publications identified, 23 studies were included. The meta-analysis indicated that preeclampsia increases the potential risk of hypertension in offspring. Systolic blood pressure (SBP) was 2.0 mm Hg (95% CI: 1.2, 2.8) and diastolic blood pressure (DBP) was 1.4 mm Hg (95% CI: 0.9, 1.9) higher in offspring exposed to pre-eclampsia in utero, compared to those born to normotensive mothers. The correlations were similar in stratified analyses of children and adolescents by sex, geographic area, ages, and gestational age. During childhood and young adulthood, the offspring of pregnant women with preeclampsia are at an increased risk of high BP. It is crucial to monitor their BP.

Insulinemic and inflammatory dietary patterns show enhanced predictive potential for gestational diabetes mellitus risk.

CONTEXT: The putative association between proinflammatory and hyperinsulinemic dietary patterns and susceptibility to gestational diabetes mellitus (GDM) remains unclear. OBJECTIVE: We aimed to compare the risk associated with the Mediterranean diet, as well as insulinemic and proinflammatory dietary patterns, in relation to the occurrence of GDM, and evaluate their predictive value. METHODS: We prospectively followed 8, 495 women from the Maternal and Infant Health cohort in Hefei, China (2015-2021). Using a food frequency questionnaire, we calculated the Empirical Dietary Inflammatory Pattern (EDIP), the Empirical Dietary Index for Hyperinsulinemia (EDIH) score, and the Mediterranean diet (MD) score. GDM was diagnosed based on a 2-hour 75-gram oral glucose tolerance test conducted between 24 to 28 weeks of gestation. Logistic regression was used to estimate the risk of GDM, while Receiver Operating Characteristic (ROC) curves were constructed to evaluate the predictive performance of the empirical dietary index for GDM. RESULTS: Participants who followed hyperinsulinemic or proinflammatory dietary patterns to the greatest extent had a higher risk of developing GDM. The OR for the highest quartile compared to the lowest quartile were 1.39 (95% CI: 1.30-1.49) for EDIH and 2.40 (95% CI: 1.88-3.01) for EDIP. The OR for the lowest quartile compared to the highest quartile was 1.33 (95% CI:1.14-1.55)for MD. The ROC curve analysis indicated that the combination of EDIP and EDIH (AUC = 0.81, 95% CI: 0.78-0.82, P = 0.003) can effectively predict the occurrence of GDM. CONCLUSIONS: Utilizing both empirical dietary indexes, EDIP and EDIH, might offer a potentially more effective approach in preventing GDM when compared to solely focusing on adherence to the Mediterranean diet pattern.

Human pluripotent stem cell-derived kidney organoids: Current progress and challenges.

Human pluripotent stem cell (hPSC)-derived kidney organoids share similarities with the fetal kidney. However, the current hPSC-derived kidney organoids have some limitations, including the inability to perform nephrogenesis and lack of a corticomedullary definition, uniform vascular system, and coordinated exit pathway for urinary filtrate. Therefore, further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development, regeneration, disease modeling, and drug screening. In this review, we discussed recent advances in the generation of hPSC-derived kidney organoids, how these organoids contribute to the understanding of human kidney development and research in disease modeling. Additionally, the limitations, future research focus, and applications of hPSC-derived kidney organoids were highlighted.

Association between exposure to outdoor artificial light at night during pregnancy and glucose homeostasis: A prospective cohort study.

BACKGROUND: Outdoor artificial light at night (ALAN) has been linked to an elevated risk of diabetes, but the available literature on the relationships between ALAN and glucose homeostasis in pregnancy is limited. METHODS: A prospective cohort study of 6730 pregnant women was conducted in Hefei, China. Outdoor ALAN exposure was estimated using satellite data with individual addresses at a spatial resolution of approximately 1 km, and the average ALAN intensity was calculated. Gestational diabetes mellitus (GDM) was diagnosed based on a standard 75-g oral glucose tolerance test. Multivariable linear regression and logistic regression were used to estimate the relationships between ALAN and glucose homeostasis. RESULTS: Outdoor ALAN was associated with elevated glucose homeostasis markers in the first trimester, but not GDM risk. An increase in the interquartile range of outdoor ALAN values was related to a 0.02 (95% confidence interval [CI]: 0.00, 0.03) mmol/L higher fasting plasma glucose, a 0.42 (95% CI: 0.30, 0.54) µU/mL increase in insulin and a 0.09 (95% CI: 0.07, 0.12) increase in homeostatic model assessment of insulin resistance (HOMA-IR) during the first trimester. Subgroup analyses showed that the associations between outdoor ALAN exposure and fasting plasma glucose, insulin, and HOMA-IR were more pronounced among pregnant women who conceived in summer and autumn. CONCLUSIONS: The results provided evidence that brighter outdoor ALAN in the first trimester was related to elevated glucose intolerance in pregnancy, especially in pregnant women conceived in summer and autumn, and effective strategies are needed to prevent and manage light pollution.

Association between the Maternal Mediterranean Diet and Perinatal Outcomes: A Systematic Review and Meta-Analysis.

The Mediterranean diet is a global, well-known healthy dietary pattern. This review aims to synthesize the existing evidence on the relationship between the maternal Mediterranean diet during pregnancy and perinatal outcomes, including randomized controlled trials (RCTs) and cohort studies. PubMed, Web of Science, and the Cochrane Library were searched from inception to 10 March, 2023, supplemented by manual screening. A random-effect model was used to estimate pooled sizes with 95% confidence intervals (CIs) for specific outcomes of interest. Data from 5 RCTs and 18 cohort studies with 107,355 pregnant participants were synthesized. In RCTs, it was observed that the maternal Mediterranean diet significantly reduced the incidence of gestational diabetes mellitus [odds ratio (OR), 0.56; 95% CI: 0.34, 0.93], as well as small for gestational age (0.55; 95% CI: 0.35, 0.88). In cohort studies, the highest adherence score to the maternal Mediterranean diet was inversely associated with a lower risk of various adverse pregnancy outcomes, including gestational diabetes mellitus (OR, 0.82; 95% CI: 0.67, 1.00), pregnancy-induced hypertension (0.73; 95% CI: 0.60, 0.89), pre-eclampsia (0.77; 95% CI: 0.64, 0.93), preterm delivery (0.67; 95% CI: 0.49, 0.91), low birth weight (0.70; 95% CI: 0.64, 0.78), intrauterine growth restriction (0.46; 95% CI: 0.23, 0.91), and increased gestational age at delivery (weighted mean difference, 0.11 wk; 95% CI: 0.03, 0.20). Meta-regression analyses did not identify the adjustment for confounders and geographical location as predictive factors for heterogeneity. The results suggest that adherence to the Mediterranean diet during pregnancy appears to be beneficial for perinatal outcomes. Future, larger, and higher-quality RCTs and cohort studies are warranted to confirm the present findings. PROSPERO registration no.: CRD42023406317.

Association between exposure to air pollution during preconception and risk of gestational diabetes mellitus: The role of anti-inflammatory diet.

BACKGROUND: Regarding the association between the sensitive time-windows of air pollution (AP) exposure and gestational diabetes mellitus (GDM), epidemiological findings are inconsistent. The dietary inflammatory potential has been implicated in the development of GDM, but it is unclear whether an anti-inflammatory diet during pregnancy reduces the association between AP and GDM. OBJECTIVE: We aimed to characterize the sensitive time-windows of AP to GDM risk. Further, to verify whether a maternal anti-inflammatory diet can reduce the risk of AP-induced GDM, by inhibiting inflammation. METHODS: A total of 8495 pregnant women were included between 2015 and 2021 in the Maternal & Infants Health in Hefei study. Weekly mean AP exposure to fine particles (PM2.5 and PM10), SO2, and NO2 was estimated from the data of Hefei City Ecology and Environment Bureau. High-sensitivity C-reactive protein (hs-CRP) concentrations were measured to evaluate systemic inflammation. The empirical dietary inflammatory pattern (EDIP) score based on a validated food frequency questionnaire was used to assess the dietary inflammatory potential of pregnant women. Logistic regression models with distributed lags were used to identify the sensitive time-window for the effect of AP on GDM. Mediation analysis estimated the mediated effect of hs-CRP, linking AP with GDM. Stratified analysis was used to investigate the potential effect of anti-inflammatory diet on GDM risk. RESULTS: The increased risks of GDM were found to be positively associated with exposure to PM2.5 (OR = 1.11, 95% CI:1.07-1.15), PM10 (OR = 1.12, 95% CI:1.09-1.16), and SO2 (OR = 1.42, 95% CI:1.25-1.60) by distributed lag models, and the critical exposure windows were 21st to 28th weeks of preconception. The proportion of association between PM2.5, PM10, and SO2 with GDM mediated by hs-CRP was 25.9%, 21.1%, and 19.4%, respectively, according to mediation analysis. In the stratified analyses by EDIP, the association between AP and GDM was not statistically significant among women those with anti-inflammatory diets. CONCLUSIONS: Exposure to AP, especially in 21st to 28th week of preconception, is associated with risk of GDM, which is partly mediated by hs-CRP. Adherence to the anti-inflammatory dietary pattern may reduce the risk of AP-induced GDM.

Perceived rather than objective weight status is associated with suicidal behaviors among Chinese adolescents: a school-based study.

BACKGROUND: We aimed to explore the relationship between body mass index (BMI) and body weight perception (BWP) with suicidal behaviors among mainland Chinese adolescents. METHODS: A nationally representative sample (N = 10 110) of Chinese adolescents was assessed in this study. Suicidal behaviors (ideation, plan and attempt) were evaluated by four self-reported questions. Generalized linear mixed model was used to estimate the adjusted odds ratios (ORs) for the association between BWP/BMI with suicidal behaviors. RESULTS: The prevalence of suicidal ideation, suicidal plan and suicidal attempt was 12, 5 and 2.1%, respectively. After adjusting potential covariates, perceiving oneself as obese was significantly associated with increased risks of suicidal ideation (OR: 2.4, 95% confidence intervals, CI: 1.6-4.0, P = 0.001), suicidal plan (OR: 3.1, 95% CI: 1.5-6.3, P = 0.002) and suicidal attempt (OR: 3.7, 95% CI: 1.5-9.1, P = 0.001) compared with perceiving as normal weight among male adolescents; the effect attenuated to null among female adolescents. Perceiving oneself as underweight and overweight both exhibited significant adverse effect on suicidal behaviors (only suicidal ideation and suicidal plan) compared with perceiving oneself as normal weight among male adolescents, but not among female adolescents. The actual measured BMI was not significantly associated with suicidal behaviors among neither gender. CONCLUSIONS: Self-perception of their body image rather than actual measured weight may have a gender-specific adverse effect on suicidal behaviors among Chinese adolescents.

[Effects of Interaction of Zinc and Cadmium on Growth and Cadmium Accumulation of Brassica campestris L.]

The interaction between different elements is an efficient means to control the heavy metal accumulation in crops. Phosphorus (P) and zinc (Zn), as essential nutrient elements of plants, have been shown to have important impacts on cadmium (Cd) accumulation in crops through interactions with each other. However, the function of the simultaneous interaction of P, Zn, and Cd on vegetable growth and Cd accumulation remains unclear. Herein, using a single-factor level design with two alternating fixed factors, pot experiments were conducted to study the impact and mechanism of this simultaneous interaction at different levels of P, Zn, and Cd on Brassica campestris L. growth, antioxidant enzyme activity, and Zn and Cd accumulation with neutral purple soil as the substrate. The results showed that the addition of an appropriate amount of P and Zn could promote the growth of Brassica campestris L. and inhibit its Cd accumulation, through different mechanisms. P mainly reduced the Cd availability in soil and improved the crop resistance, whereas Zn mainly promoted the dilution effect by the crop growth and its physiological antagonism. The antioxidant capacity of Brassica campestris L. was significantly inhibited when 1 mg·kg-1 exogenous Cd was added to the soil, along with decreased activities of CAT and POD and high accumulation of MDA. Notably, both P and Zn could improve the antioxidant capacity and relieve Cd toxicity by increasing CAT activity, without obviously influencing POD activity. The highest yield of Brassica campestris L. (55.72 g·pot-1) was attained when the ratio of stress concentration for exogenous P, Zn, and Cd[ω(Cd):ω(Zn):ω(P)] was 1:10:200. Furthermore, the Cd content in the edible part was also lower than the national standard requirement of 50 µg·kg-1for Cd in green leafy vegetables (GB 2762-2017). In addition, the accumulation of Cd was further decreased when the proportion of P and Zn was increased, along with a decreased yield of the vegetable. Therefore, a proper application of P and Zn fertilizers could simultaneously reduce Cd accumulation and increase crop yield and thus contribute to achieving safe vegetable production.

Two new cadinane-type sesquiterpenoid glycosides from Dryopteris fragrans with anti-inflammatory activities.

Two new cadinane-type sesquiterpenoid glycosides, dryopteristerpeneA (1) and dryopteristerpeneB (2), were isolated from the aqueous extract of Dryopterisfragrans. Their structures were determined by spectroscopic data analysis and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 exhibited inhibition on nitric oxide production in lipopolysaccharide induced RAW 264.7 macrophages with their IC50 values of 60.5 and 59.8 µM, respectively.

Osteogenesis, Osteoclastogenesis and their Crosstalk in Lipopolysaccharide-induced Periodontitis in Mice.

OBJECTIVE: To determine the crosstalk of osteogenesis and osteoclastogenesis of alveolar bone in lipopolysaccharide (LPS)-induced periodontitis in mice. METHODS: A representative periodontitis model was established by treating mice with LPS, and osteoblasts and osteoclasts were cultured. Osteoblasts and osteoclasts were cocultured to determine the effects of LPS on the crosstalk of osteogenesis and osteoclastogenesis. Quantitative polymerase chain reaction (qPCR) was performed to determine the expression of osteoclastogenesis makers underlying the potential mechanisms. RESULTS: The morphological and pathological changes in alveolar bone were observed in LPSinduced mice and LPS dose-dependently suppressed osteogenesis. The mRNA expression of cathepsin K, as a marker of osteoclasts, was accordingly downregulated in the coculture. The mRNA expression of osteoprotegerin was increased, while that of receptor activator of nuclear factor-κB ligand (RANKL) was decreased with an increased concentration of LPS. Moreover, the mRNA expression of toll-like receptor 4 (TLR4) was upregulated by LPS, whereas TLR4 knockout partially recovered osteoclast differentiation in the upper layer of the coculture. CONCLUSION: LPS dose-dependently suppressed osteogenesis but had a bidirectional effect on osteoclastogenesis. The combined effects of LPS on osteogenesis, osteoclastogenesis and their crosstalk via TLR4 account for alveolar bone loss in periodontitis.

[A new phloroglucinol compound from Dryopteris fragrans].

Two phloroglucinol compounds(1-2) were isolated and purified from 95% ethanol extract of Dryopteris fragrans through various column chromatographies on silica gel, Sephadex LH-20, medium pressure column chromatography, and preparative HPLC. Their structures were elucidated as 2',4',6'-trihydroxy-5'-methyl acetate-3'-methyl-1'-butyrophenone(1) and aspidinol B(2) based on their chemical and physicochemical methods and spectroscopic data. Compound 1 is a new phloroglucinol compound named "dryofraginol".

Differences in initial versus recurrent diabetic foot ulcers at a specialized tertiary diabetic foot care center in China.

OBJECTIVE: To investigate the characteristics of diabetic foot ulcer (DFU) recurrence. METHODS: A total of 573 patients with DFUs were recruited and divided into an initial group (395 patients) and a recurrence group (178 patients). The factors related to recurrence were analyzed using multivariate regression. RESULTS: The recurrence group had longer diabetes duration (odds ratio [OR] 192; 95% confidence interval 120, 252 vs. 156; 96, 240); lower glycated hemoglobin levels (OR 8.1; 95% CI 6.8, 9.6 vs. 9.1; 7.4, 10.5), and higher rates than the initial group of amputation (37.5% vs. 2.0%), history of vascular intervention (21.3% vs. 3.9%), retinopathy (77.7% vs. 64.7%), callus (44.4% vs. 20.8%), foot deformity (51.2% vs. 24.6%), and outdoor sports shoe wearing (34.0% vs. 21.2%). Multiple factor logistic regression analysis showed that diabetes duration (OR 1.004), callus (OR 2.769), vascular intervention (OR 2.824) and amputation (OR 22.256) were independent risk factors for DFU recurrence. CONCLUSION: Diabetes duration, callus, history of vascular intervention, and amputation were independent risk factors for recurrent DFUs in a cohort of Chinese patients with active DFU. The prevention and treatment of DFUs, especially callus treatment, foot care, and blood glucose control, should be improved in China.

Integrative analysis of epigenomics, transcriptomics, and proteomics to identify key targets and pathways of Weining granule for gastric cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Weining granule (WNG) is a "Qi-Enriching and Kidney-Tonifying, Spleen-Reinforcing and Stasis-Removing" formula for gastric cancer (GC). Past research we noted WNG inhibited cell growth and raised apoptosis in GC. However, the underlying mechanism of WNG for GC have yet to be systematically clarified. AIM OF THE STUDY: We sought to characterize the molecular landscape of GC cells in vitro after WNG treated, to identify the molecular targets and pathways that were associated with WNG for inducing the apoptosis of GC cells, and further to clarify underlying molecular mechanism of WNG for GC. MATERIALS AND METHODS: We performed the techniques of RNA sequencing, tandem mass tags (TMT) based quantitative proteomics, and reduced representation bisulfite sequencing (RRBS) in WNG-treated/or untreated SGC-7901 GC cells to gain a comprehensive molecular portrait of WNG treatment. Then we integrated methylomics, transcriptomics, and proteomics data to carry out the bioinformatics analysis, and constructed the protein-protein interaction (PPI) network to identify molecular targets, and to discover the underlying signaling pathways associated with WNG for GC by network analysis. Besides, we verified the candidate target genes by Kaplan-Meier plotter database. RESULTS: We identified 1249 significant differentially expressed genes (DEGs) from RNA expression datasets, 191 significant differentially abunabundant proteins (DAPs) from proteomics datasets, and 8293 significant differentially methylated regions (DMRs) from DNA methylation datasets. GO and KEGG analysis showed DEGs, DAPs, and DMRs enriched in the cancer-related biological processes of calcium signaling pathway, pathways in cancer, metabolic pathways, MAPK signaling pathway, PI3K-Akt signaling pathway, and transcriptional misregulation in cancer. We integrated three profile datasets and performed network analysis to distinguish the hub genes, and finally the genes of SOD2, HMOX1, MMP1, SRXN1, NOTCH1, MAPK14, TXNIP, VEGFA, POLR2F, and HSPA9 were identified. The Kaplan-Meier plotter confirmed that SOD2, MMP1, SRXN1, NOTCH1, MAPK14, TXNIP, VEGFA, and HSPA9 were significantly correlated with OS in GC patients (P < 0.01), while HMOX1 and POLR2F expression were not significantly relevant to survival of GC patients (P > 0.01). CONCLUSIONS: SOD2, MMP1, SRXN1, NOTCH1, MAPK14, TXNIP, VEGFA, and HSPA9 were the predictive pharmaceutical targets of WNG for GC. The anticancer function of WNG was significantly associated with the pathways of focal adhesion pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, and Wnt signaling pathway.

[The Study of Signal Pathway Regulating the Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells].

Osteogenesis of mesenchymal stem cells to differentiate between bone marrow by multiple signaling pathways that control, directly or indirectly affect small related transcription factor 2 (runt-related transcription factor 2, Runx2) and osteoblast specific transcription factor (osterix, Osx), the expression of osteogenesis key transcription factors, such as in the development and regeneration of the bone, bone repair has played a key role in the process of reconstruction. These pathways play their mechanism of action, but also intertwined associated constitute a complex signal transduction network, but due to the limitations of research methods, the osteogenic differentiation related signaling pathways of the specific mechanism is still unclear, if you can clarify these different signaling pathways play to the role of their relevant mechanism and the relationship between various pathways and the mechanism study of osteogenesis differentiation is of great importance. This article will review the progress of various signaling pathways in the regulation of osteogenic differentiation of bone marrow mesenchymal stem cells.

The effect of family doctor policy practice on primary health-care workers' health in Hongkou District of Shanghai, China: varied by occupational divisions?

BACKGROUND: A key component of the 2009 medical reform in China was the change to family doctor (FD) policy practice. However, this led to an increased workload for primary health-care workers (PHCWs) at community health service centres. Their increasing workload may play a significant role in affecting PHCWs' health. METHODS: A questionnaire survey was conducted in Hongkou district of Shanghai amongst PHCWs including family doctors (FDs), family nurses (FNs), public health doctors (PHDs), and other PHCWs in early 2019. Ordered logistic regression models (Models 1 to 3) were performed to explore the differing health status amongst PHCWs, and their respective influential factors were also tested (Models 4 to 7). RESULTS: Five hundred sixty-two valid questionnaires were collected with a response rate of 96.4%. Other PHCWs' (OR = 2.03; 95% CI: 1.163-3.560) and FNs' (OR = 1.98; 95% CI: 1.136-3.452) self-rated health (SRH) were significantly better than that of FDs. In terms of FNs, the OR of SRH for those who strongly perceived the extra workload brought by FD-contracted services was only 12.0% (95% CI: 0.018-0.815) of that of the no-pressure group. Similarly, FNs with stronger work pressure had worse SRH, i.e., compared with "no" pressure, the SRH ORs for "neutral," "strong," and "very strong" evaluations of work pressure were 0.002 (95% CI: 0.000-0.055), 0.001 (95% CI: 0.000-0.033), and 0.000 (95% CI: 0.000-0.006), respectively. Information technology (IT) systems and performance incentives were suggested to improve SRH for FNs, while the former was found to be negatively correlated with other PHCWs. After one unit increase in the PHDs' team/department support, their OR was 10.7 times (95% CI: 1.700-67.352) higher. In addition, policy support had a negative effect on SRH for PHDs. The OR of "good" assessments of cultural environments was 25.98 times (95% CI: 1.391-485.186) higher than that of "very poor" for Other PHCWs. CONCLUSIONS: The influences of FD policy practice on FNs' SRH were the most significant amongst PHCWs, rather than FDs' as expected. The significant factors of SRH were varied over different occupational categories, that is team/department support and policy support (though negative) for PHDs, IT system and incentive for FNs, facility and equipment for FDs, and culture environment for other PHCWs respectively.

miR-632 Promotes Laryngeal Carcinoma Cell Proliferation, Migration, and Invasion Through Negative Regulation of GSK3ß.

Laryngeal cancer, one of the most common head and neck malignancies, is an aggressive neoplasm. Increasing evidence has demonstrated that microRNAs (miRNAs) exert important roles in oncogenesis and progression of diverse types of human cancers. miR-632, a tumor-related miRNA, has been reported to be dysregulated and implicated in human malignancies; however, its biological role in laryngeal carcinoma remains to be elucidated. The present study aimed at exploring the role of miR-632 in laryngeal cancer and clarifying the potential molecular mechanisms involved. In the current study, miR-632 was found to be significantly upregulated both in laryngeal cancer tissues and laryngeal cancer cell lines. Functional studies demonstrated that miR-632 accelerated cell proliferation and colony formation, facilitated cell migration and invasion, and enhanced the expression of cell proliferation-associated proteins, cyclin D1 and c-myc. Notably, miR-632 could directly bind to the 3'-untranslated region (3'-UTR) of glycogen synthase kinase 3ß (GSK3ß) to suppress its expression in laryngeal cancer cells. Mechanical studies revealed that miR-632 promoted laryngeal cancer cell proliferation, migration, and invasion through negative modulation of GSK3ß. Pearson's correlation analysis revealed that miR-632 expression was inversely correlated with GSK3ß mRNA expression in laryngeal cancer tissues. Taken together, our findings suggest that miR-632 functions as an oncogene in laryngeal cancer and may be used as a novel therapeutic target for laryngeal cancer.

Association of HIF-1α and NDRG2 Expression with EMT in Gastric Cancer Tissues.

OBJECTIVE: This study aims to investigate the differences in the expression of hypoxia-inducible factor-1α (HIF-1α), N-myc downstream-regulated gene 2 (NDRG2) and epithelial mesenchymal transition (EMT)-related proteins in normal gastric tissues, gastric cancer tissues and lymph node metastasis. METHODS: Immunohistochemistry was used to detect the expression of HIF-1α, NDRG2, E-cadherin, Snail and Twist in normal gastric tissues, gastric cancer tissues and lymph node metastasis. RESULTS: In normal gastric tissues, HIF-1α was not expressed, NDRG2 was highly expressed. There was a significant between the expression of NDRG2 and Snail, as well as of NDRG2 and Twist. In gastric cancer tissues, there was no statistically difference between the expression of HIF-1α and E-cadherin, NDRG2 and E-cadherin. However, there was a significant difference in expression between the expression of HIF-1α and Snail, HIF-1α and Twist, NDRG2 and Snail, and NDRG2 and Twist. In lymph node metastasis tissues, we show that HIF-1α was highly expressed, while NDRG2 was not, and the difference between the expression of HIF-1α and E-cadherin, HIF-1α and Snail, HIF-1α and Twist was not significant. CONCLUSION: HIF-1α may promote EMT, possibly by inhibiting the expression of NDRG2.

Arylurea Derivatives: A Class of Potential Cancer Targeting Agents.

Arylurea derivatives, an important class of small molecules, have received considerable attention in recent years due to their wide range of biological applications. Various molecular targeted agents with arylurea scaffold as potential enzyme/receptor inhibitors were constructed with the successful development of sorafenib and regorafenib. This review focuses on those arylureas possessing anti-cancer activities from 2010 to date. According to their different mechanisms of action, these arylureas are divided into the following six categories: (1) Ras/Raf/MEK/ERK signaling pathway inhibitors; (2) tumor angiogenesis inhibitors, their targets include Vascular Endothelial Growth Factor Receptors (VEGFRs), Fibroblast Growth Factor Receptors (FGFRs), Platelet-Derived Growth Factor Receptors (PDGFRs), Epidermal Growth Factor Receptors (EGFRs), Insulin-Like Growth Factor 1 Receptor (IGF-1R), Fmslike Tyrosine Kinase 3 (FLT3), c-Kit, MET, and Smoothened (Smo); (3) PI3K/AKT/mTOR signaling pathway inhibitors; (4) cell cycle inhibitors, their targets include Checkpoint Kinases (Chks), Cyclin- Dependent Kinases (CDKs), Aurora, SUMO activating enzyme 1 (SUMO E1), tubulin, and DNA; (5) tumor differentiation, migration, and invasion inhibitors, their targets include Matrix Metalloproteinases (MMPs), LIM kinase (Limk), Nicotinamide Phosphoribosyltransferase (Nampt), and Histone Deacetylase (HDAC); (6) arylureas from the rational modification of natural products. This review focuses on the Structure-Activity Relationships (SARs) of these arylureas. The structural evolution and current status of some typical anti-cancer agents used in clinic and/or in clinical trials are emphasized.

Phthalazino[1,2-b]quinazolinones as p53 Activators: Cell Cycle Arrest, Apoptotic Response and Bak-Bcl-xl Complex Reorganization in Bladder Cancer Cells.

p53 inactivation is a clinically defined characteristic for cancer treatment-nonresponsiveness. It is therefore highly desirable to develop anticancer agents by restoring p53 function.1 Herein the synthesized phthalazino[1,2-b]quinazolinones were discovered as p53 activators in bladder cancer cells. 10-Bromo-5-(2-dimethylamino-ethylamino)phthalazino[1,2-b]quinazolin-8-one (5da) was identified as the most promising candidate in view of both its anticancer activity and mechanisms of action. 5da exhibited strong anticancer activity on a broad range of cancer cell lines and significantly reduced tumor growth in xenograft models at doses as low as 6 mg/kg. Furthermore, 5da caused cell cycle arrest at S/G2 phase, induced apoptosis, changed cell size, and led to cell death by increasing the proportion of sub-G1 cells. Molecular mechanism studies suggested that accumulation of phospho-p53 in mitochondria after 5da treatment resulted in conformational activation of Bak, thereby evoking cell apoptosis, finally leading to irreversible cancer cell inhibition. Our present studies furnish new insights into the molecular interactions and anticancer mechanisms of phospho-p53-dependent quinazolinone compound.