Associations Between Serum Estrogen Levels and Urinary Incontinence in Women: A Cross-sectional Analysis of NHANES 2013 to 2016.

OBJECTIVE: To explore the relationship between serum estrogen levels and urinary incontinence in a nationally representative female population. MATERIALS AND METHODS: We included women who had serum estradiol measurements and self-reported urinary incontinence problems in the 2013-2016 National Health and Nutrition Examination Survey cycles. A weighted multivariable logistic regression model was used to determine the association between urinary incontinence and serum estrogen levels after adjusting for age, race, Body Mass Index, diabetes, venipuncture, hypertension, poverty-to-income ratio, smoking, marital status, alcohol use, education, and menopause. RESULT: A total of 4114 individuals were ultimately included in our study. Of these women, 1200 (29.17%) complained of urge urinary incontinence (UUI), 1674 (40.69%) complained of stress urinary incontinence (SUI), 730 (17.74%) complained of mixed urinary incontinence (MUI). Women in the lowest quartile of serum estrogen were more likely to complain of UUI compared to those in the highest quartile (OR=1.885; 95% CI=1.042-3.412, P = .039). No association was noted between serum estrogen levels and SUI or MUI. CONCLUSION: Our study shows a significant association between low serum estrogen level and the increased likelihood of UUI in women. Further research is required to validate our findings, elucidate the physiological mechanisms that underlie them, and assess potential therapeutic implications.

CircRBM23 regulates the switch between osteogenesis and adipogenesis of mesenchymal stem cells via sponging miR-338-3p.

BACKGROUND: The disruption of the balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) in bone marrow contributes to the adipocytes accumulation and bone loss, which leads to the development of osteoporosis (OP). The circular RNA (circRNA), circRBM23, was generated from the RNA binding motif protein 23 (RBM23) gene. It was reported that circRBM23 was down-regulated in OP patients, but it remains unknown whether its down-regulation is involved in the lineage switch of MSCs. OBJECTIVE: We aimed to explore the role and mechanism of circRBM23 in regulating the switch between osteogenic and adipogenic differentiation of MSCs. METHODS: The expression and function of circRBM23 in vitro were detected by qRT-PCR, alizarin red staining, and oil Red O staining. The interactions between circRBM23 and microRNA-338-3p (miR-338-3p) were analyzed by RNA pull-down assay, FISH, and dual-luciferase reporter assay. MSCs treated with lentivirus overexpression of circRBM23 was applied for both in vitro and in vivo experiments. RESULTS: CircRBM23 was expressed at lower levels in OP patients. Besides, circRBM23 was up-regulated during osteogenesis and down-regulated during adipogenesis of MSCs. CircRBM23 could promote the osteogenic differentiation but inhibit the adipogenic differentiation of MSCs. Mechanistically, circRBM23 acted as a sponge for microRNA-338-3p (miR-338-3p) to enhance the expression of RUNX family transcription factor 2 (RUNX2). CONCLUSIONS: Our research indicates that circRBM23 could promote the switch from adipogenic to osteogenic differentiation of MSCs via sponging miR-338-3p. It might improve the understanding of the lineage switch of MSCs and provide a potential target for diagnosing and treating OP.

MOF-74/polystyrene-derived Ni-doped hierarchical porous carbon for structure-oriented extraction of polycyclic aromatic hydrocarbons and their metabolites from human biofluids.

Polycyclic aromatic hydrocarbons (PAHs), as a major source that significantly increase the risk of developing lung cancer, severely jeopardize public health in modern society. The analysis of PAHs and their metabolites (hydroxylated PAHs, OH-PAHs) is important for biomonitoring and exposure assessment. However, due to the difference in their physico-chemical properties and matrix interference, realizing high-performance extraction of both PAHs and OH-PAHs is still a challenge. Herein, a nickel-doped hierarchical porous carbon (Ni/HPC) is synthesized by carbonizing the polystyrene (PS) infiltrated metal-organic frameworks (MOF-74(Ni)). The obtained Ni/HPC exhibits hierarchical pores and evenly distributed Ni atoms, providing efficient diffusion pathways and adsorption sites. The custom Ni/HPC-coated solid-phase microextraction (SPME) fiber shows superior enrichment capabilities for PAHs and their metabolites under various interfering conditions, verifying its practicability in real sample analysis. The proposed method provides a new strategy to synthesize carbon-based adsorbents that achieves matrix-resistant enrichment of PAHs and OH-PAHs, which simplifies the related sample preparation process for environmental analysis and clinical diagnosis.

Displacement of the retina after idiopathic macular hole surgery with different internal limiting membrane peeling patterns.

AIM: To explore retinal displacement after surgical treatment for idiopathic macular hole (IMH) with different internal limiting membrane (ILM) peeling patterns. METHODS: Totally 22 eyes from 20 patients with IMH were randomly allocated into two groups, N-T group (11 eyes) and T-N group (11 eyes). For patients in N-T group, ILM was peeled off from nasal to temporal retina. For patients in T-N group, ILM was peeled off from temporal to nasal retina. Preoperative, postoperative 1, 3, and 6mo, autofluorescence fundus images were collected for manual measurement of distances of fixed nasal (N), temporal (T), superior (S), and inferior (I) retinal points (bifurcation or crossing of retinal vessels) around the macula to the optic disc (OD). These were respectively defined as N-OD, T-OD, S-OD, and I-OD. The retinal displacement, macular hole closure rate, and best corrected visual acuity (BCVA) were compared between the two groups after surgery. RESULTS: At postoperative 1, 3, and 6mo, the macula slipped toward the OD, manifested by the decreased T-OD, N-OD, S-OD, and I-OD (P<0.05). No significant difference was found in the T-OD, N-OD, S-OD, and I-OD between N-T group and T-N group. IMH closure rate was 100% both in N-T group and T-N group. There was no significant difference in BCVA between two groups (P<0.05). CONCLUSION: The macula slips toward the OD after successful macular hole surgery. The two different ILM peeling pattern show similar visual outcome and retinal displacement, which means ILM peeling directions are not the influencing factor of postoperative retinal displacement.

Ranibizumab plus fufang xueshuantong capsule versus ranibizumab alone for exudative age-related macular degeneration.

OBJECTIVE: To compare the efficacy of ranibizumab plus fufang xueshuantong capsule (cFXST) with the efficacy of ranibizumab alone in treatment of exudative age-related macular degeneration. METHODS: This prospective, randomized, controlled, pilot study included 38 eyes from 38 patients with exudative age-related macular degeneration (AMD) that were randomly allocated into two cohorts of 19 eyes each: ranibizumab (Cr) and ranibizumab plus cFXST (Cfr). All patients received three monthly injections of ranibizumab. Patients in Cfr also received daily oral supplementation of cFXST. Best corrected visual acuity (BCVA) and thickness of the choroidal neovascularization-pigment epithelial detachment (CNV-PED) complex (measured by optical coherence tomography) were recorded at baseline and at 1 and 3 months after the first intravitreal injection of ranibizumab. RESULTS: In the Cfr, the CNV-PED complex thickness was reduced by 31.7% and 36.1% at 1 and 3 months, respectively; these reductions were significantly greater than the 19.7% and 24.2% reductions in the Cr. BCVA improvement was significantly greater in the Cfr than in the Cr after 3 months; the proportion of patients with functional response was also greater in the Cfr than in the Cr (16/16 vs. 8/17). CONCLUSION: Oral cFXST increases the efficacy of short-term ranibizumab treatment for exudative AMD.

Dual-fiber solid-phase microextraction coupled with gas chromatography-mass spectrometry for the analysis of volatile compounds in traditional Chinese dry-cured ham.

For the purpose of obtaining a more comprehensive flavor profile, volatile compounds in traditional Chinese dry-cured hams were studied by dual-fiber solid-phase microextraction (SPME) using two fibers simultaneously. By using the selected pair of fibers and under the optimal extraction time, there were total seventy-two volatile compounds identified, which was higher than the mono-fiber SPME method using a single fiber. Out of the seventy-two compounds, twenty-six compounds were not detected by using mono-fiber SPME and five among them are classified as the major aromatic compounds in the literatures. Due to the higher coverage and less tendency for the occurrence of competition among the volatiles, the total amount of volatiles extracted by dual-fiber SPME (510.02 ng/kg) was higher than mono-fiber SPME. Three grades of dry-cured hams were successfully distinguished based on dual-fiber SPME. The volatile compounds belonged to nine chemical families and differed in different grades of dry-cured hams. These results show that dual-fiber SPME is capable of analyzing flavor profiles more comprehensively and distinguishing traditional Chinese dry-cured hams.

Hydrogen alleviates cellular senescence via regulation of ROS/p53/p21 pathway in bone marrow-derived mesenchymal stem cells in vivo.

Senescence has become a hot point issue in recent decades and requires urgent attention. As a novel and effective antioxidant, hydrogen has been proved to alleviate cellular senescence in endothelial cells in vitro. However, the effects and mechanisms of hydrogen on senescence in vivo are still unclear. In the present study, 12-month-old Sprague Dawley (SD) rats were intraperitoneal administration of hydrogen-rich saline (HRS, 10 ml/kg). Subsequently, bone marrow-derived stem cells (BMSCs) were harvested for the detection of hydrogen antisenescence effects and mechanisms. The results showed that the number of senescence-associated ß-galactosidase (SA-ß-Gal) positive cells was reduced in BMSCs from rats treated with HRS. BMSCs in rats treated with HRS possessed a better proliferation ability, showed more effectively tri-lineage differentiation potential, and had less percentage of cells in G1 cell cycle arrest than the control cells. Additionally, HRS administration inhibited the production of intracellular reactive oxygen species (ROS) and decreased the expression of senescence-related proteins p53 and p21. Our results revealed that hydrogen could alleviate cellular senescence in vivo. And the underlying mechanism of antisenescence effects of hydrogen in BMSCs was via the ROS/p53/p21 signaling pathway. Thus, hydrogen could be a new and convenient strategy for alleviating senescence and for therapy of age-related diseases.

Fabrication of powdery polymer aerogel as the stationary phase for high-resolution gas chromatographic separation.

Novel powdery polymer aerogel (PPA) prepared via the (micro)emulsion polymerization and the following hyper crosslinking reaction was fabricated as stationary phase of capillary column for the first time. Due to its powdery morphology, unique 3D nano-network structure, high surface area and good thermostability, the PPA-coated capillary column demonstrated high-resolution chromatographic separation towards nonpolar and weakly polar organic compounds, including benzene series, n-alkanes, ketone mixtures and trichlorobenzenes. Moreover, the reproducibility, quantitative analysis ability and thermostability of PPA-coated capillary column were also evaluated. The relative standard deviations for three replicate determinations of selected analytes were 0.02-0.11%, 0.12-0.26% and 1.2-3.6% for run-to-run, day-to-day and column-to-column analyses, respectively. The PPA demonstrated good thermostability, and the PPA-coated capillary column was proved to be heat-resistant (270 °C). The results of this study show PPA is an excellent candidate to be employed as stationary phase for gas chromatography capillary.

High-concentration hydrogen protects mouse heart against ischemia/reperfusion injury through activation of thePI3K/Akt1 pathway.

The study investigated the role of Akt1 through the cardioprotection of high-concentration hydrogen (HCH). C57BL/6 mice were randomly divided into the following groups: sham, I/R, I/R + HCH, I/R + HCH + LY294002 (PI3K inhibitor), I/R + HCH + wortmannin (PI3K inhibitor), I/R + LY294002, and I/R + wortmannin. After 45 min of ischemia, HCH (67% H2 and 33% O2) was administered to mice during a 90-min reperfusion. To investigate the role of Akt1 in the protective effects of HCH, mice were divided into the following groups: I/R + A-674563 (Akt1 selective inhibitor), I/R + HCH + A-674563, I/R + CCT128930 (Akt2 selective inhibitor), and I/R + HCH + CCT128930. After a 4-h reperfusion, serum biochemistry, histological, western blotting, and immunohistochemical analyses were performed to evaluate the role of the PI3K-Akt1 pathway in the protection of HCH. In vitro, 75% hydrogen was administered to cardiomyocytes during 4 h of reoxygenation after 3-h hypoxia. Several analyses were performed to evaluate the role of the Akt1 in the protective effects of hydrogen. HCH resulted in the phosphorylation of Akt1 but not Akt2, and Akt1 inhibition markedly abolished HCH-induced cardioprotection. Our findings reveal that HCH may exert cardioprotective effects through a PI3K-Akt1-dependent mechanism.

An Electrochemical Biosensor with Dual Signal Outputs: Toward Simultaneous Quantification of pH and O2 in the Brain upon Ischemia and in a Tumor during Cancer Starvation Therapy.

Herein, we develop a novel method for designing electrochemical biosensors with both current and potential signal outputs for the simultaneous determination of two species in a living system. Oxygen (O2 ) and pH, simple and very important species, are employed as model molecules. By designing and synthesizing a new molecule, Hemin-aminoferrocene (Hemin-Fc), we create a single electrochemical biosensor for simultaneous detection and ratiometric quantification of O2 and pH in the brain. The reduction peak current of the hemin group increases with the concentration of O2 from 1.3 to 200.6 µm. Meanwhile, the peak potential positively shifts with decreasing pH from 8.0 to 5.5, resulting in the simultaneous determination of O2 and pH. The Fc group can serve as an internal reference for ratiometric biosensing because its current and potential signals remain almost constant with variations of O2 and pH. The developed biosensor has high temporal and spatial resolutions, as well as remarkable selectivity and accuracy, and is successfully applied in the real-time quantification of O2 and pH in the brain upon ischemia, as well as in tumor during cancer therapy.

Hyperbaric Oxygen Reduces Infarction Volume and Hemorrhagic Transformation Through ATP/NAD+/Sirt1 Pathway in Hyperglycemic Middle Cerebral Artery Occlusion Rats.

BACKGROUND AND PURPOSE: Energy depletion is a critical factor leading to cell death and brain dysfunction after ischemic stroke. In this study, we investigated whether energy depletion is involved in hyperglycemia-induced hemorrhagic transformation after ischemic stroke and determined the pathway underlying the beneficial effects of hyperbaric oxygen (HBO). METHODS: After 2-hour middle cerebral artery occlusion, hyperglycemia was induced by injecting 50% dextrose (6 mL/kg) intraperitoneally at the onset of reperfusion. Immediately after it, rats were exposed to HBO at 2 atmospheres absolutes for 1 hour. ATP synthase inhibitor oligomycin A, nicotinamide phosphoribosyl transferase inhibitor FK866, or silent mating type information regulation 2 homolog 1 siRNA was administrated for interventions. Infarct volume, hemorrhagic volume, and neurobehavioral deficits were recorded; the level of blood glucose, ATP, and nicotinamide adenine dinucleotide and the activity of nicotinamide phosphoribosyl transferase were monitored; the expression of silent mating type information regulation 2 homolog 1, acetylated p53, acetylated nuclear factor-κB, and cleaved caspase 3 were detected by Western blots; and the activity of matrix metalloproteinase-9 was assayed by zymography. RESULTS: Hyperglycemia deteriorated energy metabolism and reduced the level of ATP and nicotinamide adenine dinucleotide and exaggerated hemorrhagic transformation, blood-brain barrier disruption, and neurological deficits after middle cerebral artery occlusion. HBO treatment increased the levels of the ATP and nicotinamide adenine dinucleotide and consequently increased silent mating type information regulation 2 homolog 1, resulting in attenuation of hemorrhagic transformation, brain infarction, as well as improvement of neurological function in hyperglycemic middle cerebral artery occlusion rats. CONCLUSIONS: HBO induced activation of ATP/nicotinamide adenine dinucleotide/silent mating type information regulation 2 homolog 1 pathway and protected blood-brain barrier in hyperglycemic middle cerebral artery occlusion rats. HBO might be promising approach for treatment of acute ischemic stroke patients, especially patients with diabetes mellitus or treated with r-tPA (recombinant tissue-type plasminogen activator).

Inhalation of high concentrations of hydrogen ameliorates liver ischemia/reperfusion injury through A2A receptor mediated PI3K-Akt pathway.

BACKGROUND AND AIMS: This study explored the hepatoprotection of high concentrations of hydrogen (HCH) inhalation in a mouse hepatic ischemia/reperfusion (I/R) injury model and the potential mechanism. METHODS: To explore the role of the PI3K-Akt pathway in the hepatoprotection of HCH, C57BL/6 mice were randomly divided into five groups: Sham, I/R, I/R+HCH, LY294002 (PI3K inhibitor)+I/R+HCH, and LY+I/R groups. Mice received inhalation of 66.7% hydrogen and 33.3% oxygen for 1h immediately after surgery. LY294002 was intravenously injected at 10mol/kg. To explore whether PI3K-Akt pathway activation was mediated by the A2A receptor, additional four groups were included: ZM241385 (A2A receptor antagonist)+I/R+HCH, ZM241385+I/R, bpv(HOpic) (PTEN inhibitor)+I/R, and ZM241385+bpv+I/R+HCH. Six hours after I/R, serum biochemistry, histological examination, Western blotting, and immunohistochemistry were performed to evaluate the hepatoprotection of HCH and the role of the PI3K-Akt pathway and A2A receptor in this protection. RESULTS: Liver dysfunction, hepatic pathological injury, infiltration of inflammatory cytokines, and hepatocyte apoptosis were observed after hepatic I/R, accompanied by inhibition of the PI3K-Akt pathway. HCH significantly improved liver function, reduced serum inflammatory cytokines, and inhibited hepatocyte apoptosis, and also induced the PI3K-Akt pathway activation. In the presence of LY294002 or ZM241385, the protective effects of HCH were markedly attenuated, but the effects of ZM241385 were reversed by bpv(HOpic). CONCLUSION: Our findings indicate that HCH may protect the liver against I/R injury through the A2A dependent PI3K-Akt pathway.

Corticosterone increases intracellular Zn(2+) release in hippocampal HT-22 cells.

The previous studies suggested that the hippocampal zinc dyshomeostasis and high glucocorticoid level might hurt hippocampal function. However, the effect of corticosterone (CORT) on hippocampus zinc homeostasis is not fully characterized. In this study, we investigated the intracellular Zn(2+) concentration in hippocampal HT-22 cells after CORT treatment. The cells were incubated with 10µM CORT for 0h-24h, 0µM-50µM CORT for 6h and 2.5µM glucocorticoid receptor antagonist RU486 administered 30min before CORT application. The results showed that 10µM CORT increased the intracellular Zn(2+) level after 6h, which was diminished by 2.5µM RU486. Co-treatment of ZnSO4 and CORT augmented the increase in Zn(2+) level. TPEN, a membrane-permeable chelator for intracellular Zn(2+) greatly attenuated the Zn(2+) increase by CORT, while DTPA, a chelator for extracellular Zn(2+), had no same effects. CCK-8 tests demonstrated that 10µM CORT treatment for 6h had no inhibition effect on cells. However, intracellular reactive oxygen species (ROS) production increased and adenosine triphosphate (ATP) level decreased significantly after same CORT treatment, which was corrected by TPEN and aggravated by ZnSO4. It could be suggested that the increased intracellular Zn(2+) by CORT was greatly dependent on intracellular Zn(2+) release, but not extracellular Zn(2+) intake. Meanwhile, our results demonstrated that increased intracellular Zn(2+) by CORT resulted in ROS generation and decreased ATP level in cells, which have possible roles in the hippocampal function disorder induced by stress.

The identification and characterization of novel N-glycan-based biomarkers in gastric cancer.

BACKGROUND AND AIMS: To identify and validate N-glycan biomarkers in gastric cancer (GC) and to elucidate their underlying molecular mechanism of action. METHODS: In total, 347 individuals, including patients with GC (gastric cancer) or atrophic gastritis and healthy controls, were randomly divided into a training group (n=287) and a retrospective validation group (n=60). Serum N-glycan profiling was achieved with DNA sequencer-assisted/fluorophore-assisted carbohydrate electrophoresis (DSA-FACE). Two diagnostic models were constructed based on the N-glycan profiles using logistic stepwise regression. The diagnostic performance of each model was assessed in retrospective, prospective (n=60), and follow-up (n=40) cohorts. Lectin blotting was performed to determine total core-fucosylation, and the expression of genes involved in core-fucosylation in GC was analyzed by reverse transcriptase-polymerase chain reaction. RESULTS: We identified at least 9 N-glycan structures (peaks) and the levels of core fucose residues and fucosyltransferase were significantly decreased in GC. Two diagnostic models, designated GCglycoA and GCglycoB, were constructed to differentiate GC from control and atrophic gastritis. The areas under the receiver operating characteristic (ROC) curves (AUC) for both GCglycoA and GCglycoB were higher than those for CEA, CA19-9, CA125 and CA72-4. Compared with CEA, CA19-9, CA125 and CA72-4, the sensitivity of GCglycoA increased 29.66%, 37.28%, 56.78% and 61.86%, respectively, and the accuracy increased 10.62%, 16.82%, 25.67% and 28.76%, respectively. For GCglycoB, the sensitivity increased 27.97%, 35.59%, 55.09% and 60.17% and the accuracy increased 21.26%, 24.64%, 31.40% and 34.30% compared with CEA, CA19-9, CA125 and CA72-4, respectively. After curative surgery, the core fucosylated peak (peak 3) and the total core fucosylated N-glycans (sumfuc) were reversed. CONCLUSIONS: The results indicated that the diagnostic models based on N-glycan markers are valuable and noninvasive alternatives for identifying GC. We concluded that decreased core-fucosylation in both tissue and serum from GC patients may result from the decreased expression of fucosyltransferase.

Chronic restraint stress aggravated arthritic joint swell of rats through regulating nitric oxide production.

Stress-related hormone norepinephrine (NE) displayed diverse effects on immune system including macrophages, which influenced many kinds of inflammatory diseases. Nitric oxide (NO) from activated macrophages played an important role in inflammatory diseases. In this study, we investigated under chronic restraint stress how NE influenced the joint swell of Complete Freund's Adjuvant (CFA)-induced arthritis of rats and whether NE regulated macrophage's production of NO through influencing phosphorylation of protein kinases C (PKC). The results showed chronic restraint stress exacerbated paw swell of rats with arthritis. Inhibitor of inducible nitric oxide synthase, S-methylisothiourea (SMT), and 6-hydroxydopamine (6-OHDA) could counteract the effect of restraint stress on arthritis. NE, NO and endotoxin in plasma of rats underwent restraint were improved significantly. In vitro experiments, NE could promote macrophage to produce more NO and iNOS when macrophage was activated by lipopolysaccharide (LPS). This effect could be inhibited by α adrenergic antagonist phentolamine. Nevertheless, through α receptor NE could promote the phosphorylation of PKC and PKC inhibitor staurosporine could counteract NE's enhancive effect on production of NO and iNOS of macrophages. This study revealed that NE could exacerbate arthritic joint swell through promoting NO production, which was in α receptor dependent way through enhancing phosphorylation of PKC for NE to enhance the iNOS expression of activated macrophage.

Enhanced phosphorylation of MAPKs by NE promotes TNF-α production by macrophage through α adrenergic receptor.

The aim of this study was to investigate whether norepinephrine (NE) could regulate macrophage production of tumor necrosis factor alpha (TNF-α) by influencing the phosphorylation of mitogen-activated protein kinases (MAPKs). Primary macrophages from male BALB/c mice were applied to explore the mechanism by which NE influences the the secretion of TNF-α when macrophages were activated by lipopolysaccharides (LPS). We found that NE could increase crophage production of TNF-α when macrophages were activated by LPS, and this effect could be inhibited by α adrenergic antagonist phentolamine. Also, NE could increase the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinases (ERK), and p38, through α receptor. Furthermore, JNK inhibitor SP600125, ERK inhibitor U0126, and p38 inhibitor SB203580 could all partially counteract NE's effect on the phosphorylation of MAPKs, as well as TNF-α production by macrophages. This study revealed that as macrophages were activated by LPS, NE promoted the secretion of inflammatory factors by increasing the phosphorylation of MAPKs through an α receptor-dependent pathway. Our results provide the evidence of a relationship between stress and diseases, as well as the mechanism by which stress induces or affects the inflammation-related diseases.