Maternal cardiovascular health in early pregnancy and the risk of congenital heart defects in offspring.

BACKGROUND: Congenital heart disease (CHD) is the predominant birth defect. This study aimed to explore the association between maternal cardiovascular health (CVH) and the CHD risk in offspring. METHODS: We used the prospective data from the Fujian Birth Cohort Study, collected from March 2019 to December 2022 on pregnant women within 14 weeks of gestation. Overall maternal CVH was assessed by seven CVH metrics (including physical activity, smoking, sleep duration, body mass index, blood pressure, total cholesterol, and fasting plasma glucose), with each metric classified as ideal, intermediate or poor with specific points. Participants were further allocated into high, moderate and low CVH categories based on the cumulative CVH score. The association with offspring CHD was determined with log-binominal regression models. RESULTS: A total of 19810 participants aged 29.7 (SD: 3.9) years were included, with 7846 (39.6%) classified as having high CVH, 10949 (55.3%) as having moderate CVH, and 1015 (5.1%) as having low CVH. The average offspring CHD rate was 2.52%, with rates of 2.35%, 2.52% and 3.84% across the high, moderate and low CVH categories, respectively (P = 0.02). Adjusted relative risks (RRs) of having offspring CHD were 0.64 (95% CI: 0.45-0.90, P = 0.001) for high CVH and 0.67 (95% CI: 0.48-0.93, P = 0.02) for moderate CVH compared to low CVH. For individual metrics, only ideal total cholesterol was significantly associated with lower offspring CHD (RR: 0.73, 95% CI: 0.59-0.83, P = 0.002). CONCLUSIONS: Pregnant women of high or moderate CVH categories in early pregnancy had reduced risks of CHD in offspring, compared to those of low CVH. It is important to monitor and improve CVH during pre-pregnancy counseling and early prenatal care.

LSM14B controls oocyte mRNA storage and stability to ensure female fertility.

Controlled mRNA storage and stability is essential for oocyte meiosis and early embryonic development. However, how to regulate mRNA storage and stability in mammalian oogenesis remains elusive. Here we showed that LSM14B, a component of membraneless compartments including P-body-like granules and mitochondria-associated ribonucleoprotein domain (MARDO) in germ cell, is indispensable for female fertility. To reveal loss of LSM14B disrupted primordial follicle assembly and caused mRNA reduction in non-growing oocytes, which was concomitant with the impaired assembly of P-body-like granules. 10× Genomics single-cell RNA-sequencing and immunostaining were performed. Meanwhile, we conducted RNA-seq analysis of GV-stage oocytes and found that Lsm14b deficiency not only impaired the maternal mRNA accumulation but also disrupted the translation in fully grown oocytes, which was closely associated with dissolution of MARDO components. Moreover, Lsm14b-deficient oocytes reassembled a pronucleus containing decondensed chromatin after extrusion of the first polar body, through compromising the activation of maturation promoting factor, while the defects were restored via WEE1/2 inhibitor. Together, our findings reveal that Lsm14b plays a pivotal role in mammalian oogenesis by specifically controlling of oocyte mRNA storage and stability.

New biopsy after antibiotic treatment: effect on outcomes of assisted reproduction in patients with infertility and chronic endometritis.

RESEARCH QUESTION: What is the effect of chronic endometritis on patients with infertility, the necessity of endometrial re-examination and the effect of improving chronic endometritis after one cycle of antibiotic treatment on pregnancy outcomes? DESIGN: Infertile patients (n = 4003) who underwent IVF and intracytoplasmic sperm injection treatment were included. Pregnancy outcomes of groups positive for chronic endometritis were compared with groups that were negative (group 1). Patients that were positive were divided into the chronic endometritis new biopsy group (group 2) and chronic endometritis non-re-examination group (group 3). After doxycycline treatment and re-examination, the chronic endometritis new biopsy group was divided into improved chronic endometritis group (ICE) and not-improved chronic endometritis group (NICE), and their general indicators and reproductive outcomes were compared. RESULTS: No significant difference was observed in embryo implantation, early or late pregnancy loss, ectopic pregnancy, clinical pregnancy and live birth rates between groups 2 and 3. The clinical pregnancy and live birth rates in the NICE group were significantly lower than those in the ICE group (P = 0.008 and P = 0.001, respectively). After controlling for potential confounding factors, age, average number of high-quality embryos, endometrial thickness on the day of embryo transfer and number and type of embryo transfer were factors associated with live birth rates. CONCLUSIONS: Endometrial re-examination of women with chronic endometritis treated with doxycycline had no effect on pregnancy outcomes. The first cycle of doxycycline treatment could effectively improve reproductive outcomes of women with five or more CD138+ cells/high-power field.

Effects of Long-Acting Somatostatin Analogues on Lipid Metabolism in Patients with Newly Diagnosed Acromegaly: A Retrospective Study of 120 Cases.

The short-term effects of long-acting somatostatin analogues (SSAs) on lipid profiles in patients with acromegaly are not well studied. We retrospectively analyzed the effects of SSAs on lipid profiles and associated cardiovascular risk factors in a cohort of 120 newly diagnosed acromegaly patients. In this study, 69 females and 51 males were included. These patients were treated with either octreotide LAR (OCT) or lanreotide SR (LAN) for 3 months. After SSAs treatment, both GH and IGF-1 significantly decreased (p<0.001). Triglyceride (TG), total to high-density lipoprotein cholesterol (HDL-C) ratio, and lipoprotein (a) [Lp(a)] levels were significantly decreased, while HDL-C levels were increased (p<0.05). The reduction of mean serum GH (GHm) was positively associated with the decrease of TG (r=0.305, p=0.001) and Lp(a) (r=0.257, p=0.005), as well as the increase of HDL-C (r=-0.355, p<0.001). The changes of lipid profiles were observed only in OCT group, but not in LAN group. In addition, systolic blood pressure (SBP) had significantly declined after SSAs treatment, with an average reduction of 4.4 mmHg (126.7±1.28 vs. 122.3±1.44 mmHg, p=0.003), while no change was observed regarding diastolic blood pressure (DBP) (p>0.05). Fasting insulin, fasting C-peptide, and HOMA-IR were significantly decreased after SSAs treatment. In conclusion, our current study revealed that short-term SSAs treatment improves lipid profiles and other cardiovascular risk factors in patients with acromegaly.

Development of Broadband High-Frequency Piezoelectric Micromachined Ultrasonic Transducer Array.

Piezoelectric micromachined ultrasonic transducers (PMUT) are promising elements to fabricate a two-dimensional (2D) array with a pitch small enough (approximately half wavelength) to form and receive arbitrary acoustic beams for medical imaging. However, PMUT arrays have so far failed to combine the wide, high-frequency bandwidth needed to achieve a high axial resolution. In this paper, a polydimethylsiloxane (PDMS) backing structure is introduced into the PMUTs to improve the device bandwidth while keeping a sub-wavelength (λ) pitch. We implement this backing on a 16 × 8 array with 75 µm pitch (3λ/4) with a 15 MHz working frequency. Adding the backing nearly doubles the bandwidth to 92% (-6 dB) and has little influence on the impulse response sensitivity. By widening the transducer bandwidth, this backing may enable using PMUT ultrasonic arrays for high-resolution 3D imaging.

Attention-deficit/hyperactivity disorder medication and risk of suicide attempt: A meta-analysis of observational studies.

PURPOSE: Epidemiologic findings are inconsistent regarding the association between attention-deficit/hyperactivity disorder (ADHD) medication exposure and suicide attempt in individuals with ADHD. METHODS: A systematic literature search of PubMed, Embase and Cochrane Library up to February 2020 was performed. A meta-analysis was conducted for outcomes in which a summary risk ratio (RR) was calculated when taking heterogeneity into account. RESULTS: Both population-level and within-individual analyzes showed that ADHD medication was associated with lower odds of suicide attempts (RR = 0.76, 95% confidence interval [CI], 0.58-1.00; P = .049 and RR = 0.69; 95% CI, 0.49-0.97; P = .049, respectively). However, the association only existed for participants who were treated with stimulants (RR = 0.72; 95% CI, 0.53-0.99; P = .042 on population-level analysis and RR = 0.75; 95% CI, 0.66-0.84; P < .001 on within-individual analysis). Furthermore, a lower risk of suicide attempts was not observed in subjects who took ADHD medication for 1 to 90 days (RR = 0.91; 95% CI, 0.74-1.13; P = .416 on within-individual analysis). CONCLUSION: The results indicate that non-stimulant treatment is not associated with a higher risk of suicide attempt, but stimulant treatment is associated with a lower risk of suicide attempt.

Adipose-derived mesenchymal stem cells protect against CMS-induced depression-like behaviors in mice via regulating the Nrf2/HO-1 and TLR4/NF-κB signaling pathways.

Increasing studies show that inflammatory processes may be involved in depressive disorders. Nuclear factor erythroid-2 related factor 2 (Nrf2) modulates tissue microglial M1 phenotypic changes to the M2 phenotype, which is implicated in protection against inflammatory diseases. We have reported that the adipose-derived mesenchymal stem cells (ADSCs) display anti-inflammatory activity. In this study we explored whether the mechanism of anti-inflammatory activity of ADSCs was related to Nrf2. ADSCs were isolated from mouse fat pads and intravenously administered to chronic mild stress (CMS)-exposed C57BL/6 mice at the dose of 1 × 106 once a week for 3 weeks. We showed that ADSC administration significantly remedied CMS-induced depressive-like behaviors in sucrose preference test, tail suspension test, and forced swim test accompanied by suppressing microglial activation and the expression of inflammatory factors including MCP-1, TNF-α, IL-1ß, and IL-6. Furthermore, ADSC administration promoted both the expression of BDNF and TrkB, and promoted Nrf2/HO-1 signaling but suppressed TLR4/NF-κB signaling in brain tissue. In order to elucidate the role of Nrf2/HO-1 signaling in ADSC-caused neuroprotection, Nrf2-modified ADSCs were cocultured with BV2 microglial cells, then exposed to lipopolysaccharide (LPS). Downregulation of Nrf2 in ADSCs decreased the protective effects of ADSCs against LPS-induced microglial activation and M1 polarization. Nrf2 overexpression in ADSCs markedly suppressed LPS-induced TLR4 and NF-κB expression in microglial cells. These results suggest a possible antidepressive mechanism correlated with microglial polarization for anti-inflammatory agents, which may provide a new microglia-targeted strategy for depression therapy.

Usefulness of sialic acid for diagnosis of sepsis in critically ill patients: a retrospective study.

BACKGROUND: Early diagnosis of sepsis is very important. It is necessary to find effective and adequate biomarkers in order to diagnose sepsis. In this study, we compared the value of sialic acid and procalcitonin for diagnosing sepsis. METHODS: Newly admitted intensive care unit patients were enrolled from January 2019 to June 2019. We retrospectively collected patient data, including presence of sepsis or not, procalcitonin level and sialic acid level. Receiver operating characteristic curves for the ability of sialic acid, procalcitonin and combination of sialic acid and procalcitonin to diagnose sepsis were carried out. RESULTS: A total of 644 patients were admitted to our department from January 2019 to June 2019. The incomplete data were found in 147 patients. Finally, 497 patients data were analyzed. The sensitivity, specificity and area under the curve for the diagnosis of sepsis with sialic acid, procalcitonin and combination of sialic acid and procalcitonin were 64.2, 78.3%, 0.763; 67.9, 84.0%, 0.816 and 75.2, 84.6%, 0.854. Moreover, sialic acid had good values for diagnosing septic patients with viral infection, with 87.5% sensitivity, 82.2% specificity, and 0.882 the area under the curve. CONCLUSIONS: Compared to procalcitonin, sialic acid had a lower diagnostic efficacy for diagnosing sepsis in critically ill patients. However, the combination of sialic acid and procalcitonin had a higher diagnostic efficacy for sepsis. Moreover, sialic acid had good value for diagnosing virus-induced sepsis.

Investigating the theragnostic potential of 131I-caerin peptide in thyroid cancer.

OBJECTIVE: Caerin is a new peptide with tumour toxicity and its uptake by tumour cells is independent of the sodium iodide symporter (NIS). Thyroid cancer is the most common cancers of endocrine malignancy. Radioiodine (131I)-refractory thyroid cancer is the most lethal subtype of the thyroid cancers and remains a clinical challenge. In the current study, we investigated the 131I radiolabeling efficiency of Caerin and the effects of Caerin, 131I-Caerin and free 131I on differentiated and undifferentiated human thyroid cancer cell lines (B-CPAP and CAL-62) in vitro. MATERIALS AND METHODS: Cell Counting Kit-8 was used to assess the cytotoxic effect of Caerin, 131I-Caerin and free 131I on B-CPAP and CAL-62 cells. Laser scanning confocal microscope was exploited to evaluate the uptake and internalization of Caerin by thyroid cancer cells. The Chloramine-T method was used to label the peptide with 131I. And the stability and water partition coefficient (Log P) of 131I-Caerin were studied. RESULTS: Our results demonstrated that Caerin and 131I-Caerin could be accumulated by B-CPAP and CAL-62 cells, resulting in killing of the thyroid cancer cells in vitro. The efficacy of 131I-Caerin is much higher than 131I, especially to undifferentiated CAL-62 cells. The results prove the feasibility of radioiodination of the 131I-Caerin via the Chloramine-T method. Moreover, the result indicate the hydrophobic 131I-Caerin was stable in 72 hours. CONCLUSION: Iodine-131-Caerin can inhibit the cell viability of thyroid cancer and hold certain promise as a theragnostic tool for human thyroid cancers.

[Regulatory effect of the lipid metabolic pathways of TMAO, FMO3 and FXR on compound stress-induced ED in rats and mechanisms of Yimusake intervention].

OBJECTIVE: To study of the regulatory effects of the lipid metabolic pathways of trimethylamine-N-oxide (TMAO), flavin-containingmonooxidase 3 (FMO3) and farnesoid X receptor (FXR) on compound stress-induced ED (CSED) rats and the mechanisms of Yimusake Tablets (YMSK) intervention. METHODS: Based on the results of metabonomics analysis, we determined the concentration of TMAO in the serum of the rats in the normal control (n = 30), the CSED model control (n = 30) and the YMSK intervention group (intragastrical administration of YMSK at 250 mg/kg once daily for 2－3 weeks after modeling, n = 30) by nuclear magnetic resonance (NMR) spectroscopy test. We also detected the expressions of the FMO3, FXR1 and FXR2 proteins in the liver tissue of the three groups of rats by Western blot. RESULTS: The serum TMAO level was significantly elevated in the CSED model control compared with that in the normal control group (ï¼»46.64 ± 5.16ï¼½ vs ï¼»34.98 ± 3.69ï¼½ µg/mL, P < 0.01) but remarkably decreased after YMSK intervention (ï¼»39.63 ± 4.81ï¼½ µg/mL) in comparison with that in the CSED model control group (P < 0.01). The rats in the CSED model control group, compared with the normal controls, showed significantly upregulated expressions of FMO3 (1.75 ± 0.90 vs 0.86 ± 0.62, P < 0.01),FXR1 (1.29 ± 0.38 vs 0.78 ± 0.25, P < 0.01) and FXR2 in the liver tissue (1.90 ± 0.63 vs 0.42 ± 0.27, P < 0.01), but all the three expressions were markedly decreased after YMSK intervention (FMO3: 1.05 ± 0.38, P < 0.05; FXR1: 1.07 ± 0.42, P < 0.05; FXR2: 1.04 ± 0.46, P < 0.01) as compared with those in the CSED model control group. CONCLUSIONS: The lipid metabolic pathways of TMAO, FMO3 and FXR underwent significant changes in the rat model of compound stress-induced ED, which could be improved by YMSK intervention, suggesting that YMSK may play an important role in protecting erectile function by regulating the lipid metabolic pathways of TMAO, FMO3 and FXR.

Impact of endometrial thickness during menstruation and endometrial scratching on the pregnancy in frozen-thawed embryo transfer.

AIM: This study aimed to investigate the impact of endometrial thickness (EMT) during menstruation and endometrial scratching on the pregnancy in frozen-thawed embryo transfer (FET). METHODS: About 1298 patients receiving FET were retrospectively analyzed and divided according to EMT on the 4th or 5th day of menstruation. Group A: EMT ≤ 3.0 mm; Group B: EMT 3.1-5.0 mm; Group C: EMT 5.1-7.0 mm and Group D: EMT > 7.0 mm. Patients in Group D were further divided to scratching group and nonscratching group. Endometrial growth was defined as the change in EMT from 4th or 5th day of menstruation to the day of embryo transferred. RESULTS: We found no significant differences in general conditions among four groups (P > 0.05). The average EMT during menstruation and differences in inter-group endometrial growth of four groups had statistical significance (P < 0.05). The pregnancy rate and implantation rate of Group D were significantly lower than other groups (P < 0.001). Pregnancy rate (68.29% vs 53.26%) and implantation rate (52.67% vs 36.34%) in endometrial scratching group were higher than those in nonscratching group (P < 0.05). CONCLUSION: Higher EMT during menstruation adversely affects pregnancy outcomes following FET. Endometrial scratching may improve the receptivity of endometrium and increase the rate of embryo implantation and pregnancy.

[Differentially expressed proteins in the penile tissue of rats with compound stress-induced ED after intervention with Yimusake Tablets: A bioinformatics analysis].

OBJECTIVE: To search for specific protein makers and target proteins for intervention with Yimusake Tablets (YT) in the penile tissue of rats with ED induced by compound cold stress and explore the molecular mechanisms underlying the development and progression of ED. METHODS: Eighty adult male rats were screened and divided into three groups, normal control (n = 10), ED model control (n = 15) and YT intervention (n = 15). The model of compound cold stress-induced ED was established in the latter two groups, and meanwhile the animals in the YT intervention group were treated with oral YT for 2 weeks. After that, proteins were extracted from the penile tissues of the rats for screening and identification by iTRAQ labeling combined with LC-MS-MS proteomics, and the IPA bioinformatics software was used for analysis of differentially expressed proteins. RESULTS: A total of 48 differentially expressed proteins were identified from the penile tissue of the ED model controls, of which 18 were associated with endothelial function, 5 with smooth muscle activity and 4 with inflammation, involving the biological processes of glucose metabolism and alcohol catabolism and the signaling pathways of glucose metabolism, calcium and RXR activation. In comparison, 29 differentially expressed proteins were identified from the rats in the YT intervention group, of which 5 were associated with endothelial function, 1 with smooth muscle activity and 4 with inflammation, involving the biological processes of glucose metabolism, vasodilation and acute-phase response and the signaling pathways glucose metabolism, RXR activation and acute-phase response. Seven ED-associated candidate biomarkers were obtained from the differentially expressed proteins in the ED model control and YT intervention group, including Collagen alpha-1(III) chain（COL3α1）, Collagen alpha-1(I) chain（COL1α1）, Collagen alpha-2(I) chain（COL1α2）, Glyceraldehyde-3-phosphate dehydrogenase（GAPDH）, T-kininogen 1（MAP1）,Biglycan（BGN）, and Myosin-11（MYH11）. CONCLUSIONS: Changes of vascular endothelial and smooth muscle functions in the penile tissue are likely to be the key mechanisms underlying the development and progression of compound stress-induced ED, which is also associated with inflammation as well as the interaction of the identified differentially expressed proteins and their participation in the relevant signaling pathways. The 7 proteins obtained can be used as the markers of compound stress-induced ED in the rat penile tissue, of which MAP1, GAPDH, BGN and MYH11 may serve as target proteins for YT intervention.

Enediyne-activated, EGFR-targeted human ß-defensin 1 has therapeutic efficacy against non-small cell lung carcinoma.

Human ß-defensins contain an oncolytic motif that binds to tumor cell membranes and mediate permeabilization, rapid induction of cytolysis, and apoptosis. Previous studies have indicated that a fragment of the mature human ß-defensin-1 (HBD1) peptide (DF) has antitumor properties. While targeted drug treatments using fusion proteins have been shown to increase drug efficacy, this phenomenon has not been studied for this defensin. Thus, in this study, we designed and prepared a fusion protein containing this HBD1 fragment and an epidermal growth factor receptor (EGFR)-targeting oligopeptide (Ec) as well as lidamycin (LDM), an extremely potent cytotoxic antitumor antibiotic, which consists of an apoprotein (LDP) and a highly active enediyne (AE). The fusion protein (Ec-LDP-DF) and its enediyne-integrated fusion protein (Ec-LDP(AE)-DF) were then purified and used to treat lung carcinoma cells in culture as well as lung carcinoma xenograft mouse models. The multifunctional fusion protein Ec-LDP-DF was shown to effectively bind to EGFR-expressing tumor cells. Furthermore, the enediyne-energized Ec-LDP(AE)-DF analog exhibited extremely potent cytotoxicity in NSCLC cell lines and an IC50 less than 10-10 mol/L. Ec-LDP(AE)-DF also significantly inhibited the growth of human carcinoma A549 and H460 xenografts in athymic mice at well-tolerated doses. Treatment resulted in cell cycle arrest and apoptosis in a dose-dependent manner. EGF-stimulated EGFR phosphorylation was also abolished by Ec-LDP(AE)-DF. In summary, our understanding of the role of defensins in cancer development and progression is continually expanding, and Ec-LDP(AE)-DF is a promising cancer cell-targeting agent for NSCLC.

EGFR-targeting, ß-defensin-tailored fusion protein exhibits high therapeutic efficacy against EGFR-expressed human carcinoma via mitochondria-mediated apoptosis.

Defensins play an essential role in innate immunity. In this study, a novel recombinant ß-defensin that targets the epidermal growth factor receptor (EGFR) was designed and prepared. The EGFR-targeting ß-defensin consists of an EGF-derived oligopeptide (Ec), a ß-defensin-1 peptide (hBD1) and a lidamycin-derived apoprotein (LDP), which serves as the "scaffold" for the fusion protein (Ec-LDP-hBD1). Ec-LDP-hBD1 effectively bound to EGFR highly expressed human epidermoid carcinoma A431 cells. The cytotoxicity of Ec-LDP-hBD1 to EGFR highly expressed A431 cells was more potent than that to EGFR low-expressed human lung carcinoma A549 and H460 cells (the IC50 values in A431, A549, and H460 cells were 1.8 ± 0.55, 11.9 ± 0.51, and 5.19 ± 1.21 µmol/L, respectively); in addition, the cytotoxicity of Ec-LDP-hBD1 was much stronger than that of Ec-LDP and hBD1. Moreover, Ec-LDP-hBD1 suppressed cancer cell proliferation and induced mitochondria-mediated apoptosis. Its in vivo anticancer action was evaluated in athymic mice with A431 and H460 xenografts. The mice were administered Ec-LDP-hBD1 (5, 10 mg/kg, i.v.) two times with a weekly interval. Administration of Ec-LDP-hBD1 markedly inhibited the tumor growth without significant body weight changes. The in vivo imaging further revealed that Ec-LDP-hBD1 had a tumor-specific distribution with a clear image of localization. The results demonstrate that the novel recombinant EGFR-targeting ß-defensin Ec-LDP-hBD1 displays both selectivity and enhanced cytotoxicity against relevant cancer cells by inducing mitochondria-mediated apoptosis and exhibits high therapeutic efficacy against the EGFR-expressed carcinoma xenograft. This novel format of ß-defensin, which induces mitochondrial-mediated apoptosis, may play an active role in EGFR-targeting cancer therapy.

Nitric oxide induces monosaccharide accumulation through enzyme S-nitrosylation.

Nitric oxide (NO) is extensively involved in various growth processes and stress responses in plants; however, the regulatory mechanism of NO-modulated cellular sugar metabolism is still largely unknown. Here, we report that NO significantly inhibited monosaccharide catabolism by modulating sugar metabolic enzymes through S-nitrosylation (mainly by oxidizing dihydrolipoamide, a cofactor of pyruvate dehydrogenase). These S-nitrosylation modifications led to a decrease in cellular glycolysis enzymes and ATP synthase activities as well as declines in the content of acetyl coenzyme A, ATP, ADP-glucose and UDP-glucose, which eventually caused polysaccharide-biosynthesis inhibition and monosaccharide accumulation. Plant developmental defects that were caused by high levels of NO included delayed flowering time, retarded root growth and reduced starch granule formation. These phenotypic defects could be mediated by sucrose supplementation, suggesting an essential role of NO-sugar cross-talks in plant growth and development. Our findings suggest that molecular manipulations could be used to improve fruit and vegetable sweetness.

High glucose induced endothelial to mesenchymal transition in human umbilical vein endothelial cell.

BACKGROUND: Studies have shown that endothelial-to-mesenchymal transition (EndMT) could contribute to the progression of diabetic nephropathy, diabetic renal fibrosis, and cardiac fibrosis. The aim of this study was to investigate the influence of high glucose and related mechanism of MAPK inhibitor or specific antioxidant on the EndMT. METHODS: In vitro human umbilical vein endothelial cells (HUVEC) were cultured with 11mM, 30mM, 60mM and 120mM glucose for 0, 24, 48, 72 and 168h. Endothelial cell morphology was observed with microscope, and RT-PCR was used to detect mRNA expression of endothelial markers VE-cadherin and CD31, mesenchymal markers α-SMA and collagen I, and transforming growth factor TGF-ß1. Immunofluorescence staining was performed to detect the expression of CD31 and α-SMA. The concentration of TGF-ß1 in the supernatant was detected by ELISA. ERK1/2 phosphorylation level was detected by Western blot analysis. RESULTS: High glucose induced EndMT and increased the TGF-ß1 level in HUVEC cells. Cells in high glucose for 7 days showed a significant decrease in mRNA expression of CD31 and VE-cadherin, and a significant increase in that of α-SMA and collagen I, while lost CD31 staining and acquired α-SMA staining. ERK signaling pathway blocker PD98059 significantly attenuated the high glucose-induced increase in the ERK1/2 phosphorylation level. PD98059 and NAC both inhibited high glucose-induced TGF-ß1 expression and attenuated EndMT marker protein synthesis. CONCLUSION: High glucose could induce HUVEC cells to undergo EndMT. NAC and ERK signaling pathway may play important role in the regulation of the TGF-ß1 biosynthesis during high glucose-induced EndMT.

Effect of oil gauze silver dressings on diabetic foot ulcers in the elderly.

OBJECTIVE: To compare the clinical efficacy and safety of oil gauze silver dressing and silver ions dressing on diabetic ulcers in elderly outpatients. METHODS: Twenty-two patients with Type-2 diabetic foot ulcers were included in the study conducted at Yantai Yuhuangding Hospital between April 2013 and April 2014. At the time of enrolment they were divided into the silver ions and oil gauze silver groups based on the order of admission. Dressings were changed twice weekly until the ulcer had healed. Clinical efficacy measures were healing outcomes and speed of healing. Adverse events were recorded. RESULTS: The silver ions and oil gauze silver groups were comparable at baseline (P>0.05). Before treatment, the fasting blood glucose (FBG) and two hour postprandial blood glucose (2h PBG) levels were 6.88±0.50 mmol /L and 15.55±2.47 mmol/L in the oil gauze silver group, and 6.93±0.41 mmol/L and 15.23±2.58 mmol/L in the silver ions group, respectively. After treatment, the FBG and 2h PBG levels were 6.82±0.32 mmol/L and 8.67±0.86 mmol/L in the oil gauze silver group, and 6.85±0.27 mmol/L and 8.83 ± 0.61 mmol/L in the silver ions group, respectively. The healing time of foot ulcers was 23.8±2.7 days in the silver ions group and 15.8±2.5 days in the oil gauze silver group (P<0.05). CONCLUSION: Oil gauze silver dressings for diabetic foot ulcers were associated with favorable clinical outcomes compared with silver ion dressings, especially with respect to ulcer healing speed.

Different response of photosystem II to short and long-term drought stress in Arabidopsis thaliana.

Short- and long-term drought stress on photosystem II (PSII) and oxidative stress were studied in Arabidopsis thaliana. Under drought stress, chlorophyll (Chl) content, Chl fluorescence, relative water content and oxygen evolution capacity gradually decreased, and the thylakoid structure was gradually damaged. Short-term drought stress caused a rapid disassembly of the light-harvesting complex II (LHCII). However, PSII dimers kept stable under the short-term drought stress and significantly decreased only after 15 days of drought stress. Immunoblotting analysis of the thylakoid membrane proteins showed that most of the photosystem proteins decreased after the stress, especially for Lhcb5, Lhcb6 and PsbQ proteins. However, surprisingly, PsbS significantly increased after the long-term drought stress, which is consistent with the substantially increased non-photochemical quenching (NPQ) after the stress. Our results suggest that the PSII-LHCII supercomplexes and LHCII assemblies play an important role in preventing photo-damages to PSII under drought stress.

Plasma Inflammatory Cytokine IL-4, IL-8, IL-10, and TNF-α Levels Correlate with Pulmonary Function in Patients with Asthma-Chronic Obstructive Pulmonary Disease (COPD) Overlap Syndrome.

BACKGROUND The aim of this study was to investigate the plasma inflammatory cytokine levels and their correlations with pulmonary function in patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS). MATERIAL AND METHODS Between January 2013 and December 2014, a total of 96 patients with asthma, acute exacerbation of chronic obstructive pulmonary disease (AECOPD), or ACOS were enrolled, and 35 healthy people were included as a control group. Fasting plasma interleukin (IL)-4, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) levels were detected using enzyme-linked immunosorbent assay (ELISA). Correlations between the plasma inflammatory cytokine levels and forced expiratory volume in 1 second (FEV1), FEV1/predicted value ratio (FEV1%pred), and FEV1/forced vital capacity (FVC) were analyzed. RESULTS IL-4 and IL-8 levels showed statistically significant differences among the 3 groups of patients (both P<0.001); IL-4 level was significantly lower, while IL-8 level was significantly higher in the AECOPD group and ACOS group than those in the asthma group (all P<0.05). IL-10 level and TNF-α level were significantly different among the 3 patient groups (both P<0.001). IL-10 level was significantly different between each of the 2 groups (all P<0.001). TNF-α level in the asthma group was higher than in the AECOPD group and ACOS group (both P<0.001). IL-4 and IL-10 were positively and IL-8 and TNF-α were negatively related with FEV1, FEV1%pred, and FEV1/FVC. CONCLUSIONS Plasma levels of inflammatory cytokines IL-4, IL-8, IL-10, and TNF-α are related with severity of airway diseases and could be potential markers for the evaluation of asthma, COPD, and ACOS.