Jiedu Xiaozheng Yin Inhibits the Progression of Colitis Associated Colorectal Cancer by Stimulating Macrophage Polarization Towards an M1 Phenotype via the TLR4 Pathway.

To investigate the effect of Jiedu Xiaozheng Yin (JXY) on the polarization of macrophages in colitis-associated colon cancer (CAC). An orthotopic model of CAC was established to monitor changes in the pathological state of mice. Colon length, number of colon tumors were recorded, and indices for liver, spleen, and thymus were calculated. Hematoxylin and eosin (H&E) staining was employed to observe intestinal mucosal injury and tumor formation. Immunohistochemistry (IHC) staining was utilized to investigate the effect of JXY on M1 and M2 polarization of macrophages in the colonic mucosa of CAC mice. For in vitro experiments, RT-qPCR (Reverse Transcription-quantitative PCR) and flow cytometry were used to observe the effect of JXY on various M1-related molecules such as IL-1ß, TNF-α, iNOS, CD80, CD86, and its phagocytic function as well as M2-related molecules including Arg-1, CD206, and IL-10. Subsequently, after antagonizing the TLR4 pathway with antagonists (TAK242, PDTC, KG501, SR11302, LY294002), the expression of IL-6, TNF-α, iNOS, and IL-1ß mRNA were detected by RT-qPCR. In vivo experiments, the results showed that JXY improved the pathological condition of mice in general. And JXY treatment decreased the shortening of colon length and number of tumors as compared to non-treated CAC mice. Additionally, JXY treatment improved the lesions in the colonic tissue and induced a polarization of intestinal mucosal macrophages towards the M1 phenotype, while inhibiting polarization towards the M2 phenotype. In vitro experiments further confirmed that JXY treatment promoted the activation of macrophages towards the M1 phenotype, leading to increased expression of IL-1ß, TNF-α, iNOS, CD80, CD86, as well as enhanced phagocytic function. JXY treatment concomitantly inhibited the expression of M2-phenotype related molecules Arginase-1 (Arg-1), CD206, and IL-10. Furthermore, JXY inhibited M1-related molecules such as IL-6, TNF-α, iNOS, and IL-1ß after antagonizing the TLR4 pathway. Obviously, JXY could exhibit inhibitory effects on the development of colon tumors in mice with CAC by promoting M1 polarization through TLR4-mediated signaling and impeding M2 polarization of macrophages.

Correlation between omega-3 intake and the incidence of diabetic retinopathy based on NHANES from 2005 to 2008.

AIMS: To identify correlations between omega-3 intake and incidence of diabetic retinopathy (DR). METHODS: This was a cross-sectional study using data from participants over age 40 in the National Health and Nutrition Examination Survey (NHANES) 2005-2008. Metrics included participants' intake of omega-3 fatty acids, specifically three types of representative polyunsaturated fatty acids, DR prevalence, and demographic characteristics. Multiple logistic regression models were used to assess the relationship between omega-3 intake and DR. RESULTS: Of the 1243 participants included in this study, omega-3 intake was lower in patients with DR relative to those without DR. Of the three polyunsaturated fatty acids within the omega-3 fatty acid family that we focused on, participants without DR consumed more docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) than those with DR. In contrast, there was no significant difference in the intake of eicosapentaenoic acid (EPA). Higher omega-3 intake was associated with a decreased risk of DR. In a crude model, the odds ratio (OR) was 0.548 (95% CI 0.315, 0.951; p = 0.033). In the fully adjusted model of omega-3 (model II), the adjusted OR was 0.525 (95% CI 0.306, 0.901; p = 0.021). DPA and DHA were also associated with a decreased risk of DR. In the full adjustment model (model II) of DPA and DHA, the adjusted ORs were 0.0002 (95% CI 0.000, 0.166; p = 0.014) and 0.293 (95% CI 0.105, 0.819; p = 0.020). Subgroup analysis showed that the protective effect of omega-3 against DR was more significant in younger patients (p value = 0.015). CONCLUSIONS: In this cross-sectional study of the U.S. general population, we found that increased intake of omega-3 and its components, specifically DPA and DHA were negatively associated with DR incidence. This suggests that omega-3 may be a potential protective factor for DR and may help to prevent or delay the onset and progression of DR.

Associations of Urinary Nickel with NAFLD and Liver Fibrosis in the USA: A Nationwide Cross­Sectional Study.

Despite the robust correlation between metabolic disorders and heavy metals, there has been limited research on the associations between nickel levels and non-alcoholic fatty liver disease (NAFLD) as well as liver fibrosis. This study aimed to examine the associations among urinary nickel, NAFLD, and liver fibrosis. The data utilized in this study were obtained from the National Health and Nutrition Examination Survey 2017-2020. A comprehensive screening process was conducted, resulting in the inclusion of a total of 3169 American adults in the analysis. The measurement of urinary nickel was conducted through inductively coupled-plasma mass spectrometry. Vibration-controlled transient elastography was employed to assess the controlled attenuation parameter and liver stiffness measurement as indicators for NAFLD and liver fibrosis, respectively. Multivariable logistic regression models were employed to evaluate the associations among urinary nickel, NAFLD, and liver fibrosis. Restricted cubic splines were employed to explored the nonlinear associations. After adjusting for all covariates, the correlation between the highest quartile of urinary nickel and NAFLD was found to be significant (OR = 1.65; 95% CI, 1.19-2.27). Subgroup analysis revealed that the correlation was significant only in men. A significant association occurred between the second quartile of urinary nickel and liver fibrosis (OR 1.88; 95% CI, 1.22-2.90). Restricted cubic spline showed that the relationship was linear between urinary nickel and NAFLD and non-monotonic, inverse U-shaped between urinary nickel and liver fibrosis. This cross-sectional study indicated that the risk of NAFLD is associated with urinary nickel, and this correlation was only present among males.

The adverse effects of developmental exposure to polystyrene nanoparticles on cognitive function in weaning rats and the protective role of trihydroxy phenolacetone.

Polystyrene nanoplastic(PS-NP) can originate from sources such as plastic waste and industrial wastewater and have been shown to have deleterious effects on abnormal neurobehaviors. However, evidence regarding the health impacts, biological mechanisms, and treatment strategies underlying developmental exposure to low dose PS-NP is still lacking. This study aimed to fill this knowledge gap by administering low doses of PS-NP(50 and 100 µg/L) to weaning rats for 4 consecutive weeks. Behavioral and morphological experiments were performed to evaluate hippocampal damage, and transcriptomics and Assay for Transposase Accessible Chromatin with hight-throughput sequencing(ATAC) analyses were conducted to identify potential key targets. Additionally, Connectivity Map(CMap) database, Limited proteolysis-mass spectrometry(LiP-SMap), and molecular-protein docking were used to examine potential phytochemicals with therapeutic effects on key targets. The results indicated that developmental exposure to PS-NP can induce hippocampal impairment and aberrant neurobehaviors in adulthood. Multi-omics analyses consistently showed that apoptosis-related signaling pathways were sensitive to PS-NP exposure, and mitogen-activated protein kinase 3(Mapk3) was identified as the core gene by the gene network, which was further validated in vitro experiments. The CMap database provided a series of phytochemicals that might regulate Mapk3 expression, and trihydroxy-phenolacetone(THP) was found to have directly binding sites with Mapk3 through LiP-SMap and molecular docking analysis. Furthermore, THP administration could significantly alleviate apoptosis induced by PS-NP exposure in primary hippocampal cells through down-regulation of Mapk3. These findings suggested that developmental exposure to PS-NP has adverse effects on cognitive function and that THP can alleviate these effects by directly binding to Mapk3.

Maternal smoking, nutritional factors at different life stage, and the risk of incident type 2 diabetes: a prospective study of the UK Biobank.

BACKGROUND: This study aims to investigate potential interactions between maternal smoking around birth (MSAB) and type 2 diabetes (T2D) pathway-specific genetic risks in relation to the development of T2D in offspring. Additionally, it seeks to determine whether and how nutritional factors during different life stages may modify the association between MSAB and risk of T2D. METHODS: This study included 460,234 participants aged 40 to 69 years, who were initially free of T2D from the UK Biobank. MSAB and breastfeeding were collected by questionnaire. The Alternative health eating index(AHEI) and dietary inflammation index(DII) were calculated. The polygenic risk scores(PRS) of T2D and pathway-specific were established, including ß-cell function, proinsulin, obesity, lipodystrophy, liver function and glycated haemoglobin(HbA1c). Cox proportion hazards models were performed to evaluate the gene/diet-MSAB interaction on T2D. The relative excess risk due to additive interaction (RERI) were calculated. RESULTS: During a median follow-up period of 12.7 years, we identified 27,342 cases of incident T2D. After adjustment for potential confounders, participants exposed to MSAB had an increased risk of T2D (HR=1.11, 95%CI:1.08-1.14), and this association remained significant among the participants with breastfeeding (HR= HR=1.10, 95%CI: 1.06-1.14). Moreover, among the participants in the highest quartile of AHEI or in the lowest quartile of DII, the association between MSAB and the increased risk of T2D become non-significant (HR=0.94, 95%CI: 0.79-1.13 for AHEI; HR=1.09, 95%CI:0.99-1.20 for DII). Additionally, the association between MSAB and risk of T2D became non-significant among the participants with lower genetic risk of lipodystrophy (HR=1.06, 95%CI:0.99-1.14), and exposed to MSAB with a higher genetic risk for ß-cell dysfunction or lipodystrophy additively elevated the risk of T2D(RERI=0.18, 95%CI:0.06-0.30 for ß-cell function; RERI=0.16, 95%CI:0.04-0.28 for lipodystrophy). CONCLUSIONS: This study indicates that maintaining a high dietary quality or lower dietary inflammation in diet may reduce the risk of T2D associated with MSAB, and the combination of higher genetic risk of ß-cell dysfunction or lipodystrophy and MSAB significantly elevate the risk of T2D in offspring.

MICROVASCULATURE ALTERATIONS OF PERIPAPILLARY RETINA AND MACULA IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS WITHOUT OCULAR INVOLVEMENT BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To evaluate microvasculature alterations of the peripapillary retina and macula and to assess whether the changes can detect preclinical retinopathy in systemic lupus erythematosus patients. METHODS: Cross-sectional study of 32 systemic lupus erythematosus patients without retinopathy and 22 normal controls. Optical coherence tomography angiography was used to measure the microvasculature of the peripapillary retina and macula. Vessel densities (VD, %) and fractal dimensions of superficial capillary plexus (SCP) and deep capillary plexus were calculated. RESULTS: Compared with controls, macular vessel densities of the whole image SCP (macular vessel density of SCP-wi) and macular vessel density of inferior SCP (macular vessel density of SCP-i) were significantly reduced in systemic lupus erythematosus patients ( P < 0.05). The peripapillary vessel densities (peripapillary vessel density [pVD]) of a 2.5-mm circle of SCP (pVD of SCP Φ2.5 ), pVD of SCP Φ3.5 , and pVD of inferior region of the inner circle of SCP (pVD of SCP-ii) were significantly reduced in patients treated with hydroxychloroquine >5 years. Macular vessel density of SCP-wi declined with age (ß = -0.12; P < 0.01) and pVD of SCP-ii declined with hydroxychloroquine cumulative dose (ß = -0.01; P < 0.01). Macular vessel density of SCP-i had the best discrimination power of 0.77 ( P < 0.01). CONCLUSION: Systemic lupus erythematosus patients without ocular involvement had microvasculature alterations that were particularly evident in the SCP. Peripapillary retina microvasculature may be reduced in patients with longer hydroxychloroquine treatment.

The Association of Food Groups and Consumption Time with Hyperuricemia: The U.S. National Health and Nutrition Examination Survey, 2005-2018.

Hyperuricemia (HUA) is associated with a wide range of diseases and increases the public health burden on society as a whole. In addition to genetic variation, diet plays a crucial role in the prevention and treatment of HUA as an important modifiable behavior. The purpose of this study is to investigate whether food groups and consumption time are associated with HUA. A total of 41,230 participants from the National Health and Nutrition Examination Survey between 2005 and 2018 were included in the study. All meals, including breakfast, lunch, and dinner, were obtained according to their corresponding Food Patterns Equivalents Database dietary data. The binary logistic regression model was used to analyze the relationship between food groups, food consumption time and HUA. We found that the intake of fruit (mixed in various forms) (OR = 0.942, 95% CI: 0.909-0.976) or freshly squeezed juices (OR = 0.915, 95% CI: 0.859-0.975), milk (OR = 0.839, 95% CI: 0.808-0.872), and eggs (OR = 0.881, 95% CI: 0.839-0.924), poultry (OR = 1.055, 95% CI: 1.033-1.077) and seafood high in n-3 fatty acids (OR = 1.068, 95% CI: 0.1.018-1.120) at dinner, eating refined grains at breakfast (OR = 0.954, 95% CI: 0.924-0.985) and dinner (OR = 0.962, 95% CI: 0.944-0.980), eating whole grains (OR = 0.908, 95% CI: 0.845-0.976) at lunch, consuming alcoholic beverages or foods at breakfast (OR = 0.748, 95% CI: 0.564-0.990)/lunch (OR = 1.118, 95% CI: 1.008-1.240)/dinner (OR = 1.127, 95% CI: 1.073-1.185) were associated with HUA. Eating particular meals at particular times of the day was related to a lower risk of HUA.

Inverse correlations between serum carotenoids and respiratory morbidity and mortality: the Third National Health and Nutrition Examination Survey.

The objective was to evaluate the association between serum carotenoid levels and respiratory morbidity and mortality in a nationally representative sample of US adults. We assessed the association of serum carotenoid levels with respiratory morbidity and mortality using logistic regression and proportional hazards regression models. Meanwhile, a series of confounders were controlled in regression models and restricted cubic spline, which included age, sex, race, marriage, education, income, drinking, smoking, regular exercise, BMI, daily energy intake, vitamin E, vitamin C, fruit intake, vegetable intake, diabetes, hypertension, asthma, emphysema and chronic bronchitis. Compared with participants in the lowest tertiles, participants in the highest tertiles of serum total carotenoids, ß-cryptoxanthin and lutein/zeaxanthin levels had a significantly lower prevalence of emphysema (ORtotal carotenoids = 0·61, 95% CI: 0·41-0·89, ORß-cryptoxanthin = 0·67, 95% CI: 0·49-0·92), chronic bronchitis (ORß-cryptoxanthin = 0·66, 95% CI: 0·50-0·87) and asthma (Q2: ORlutein/zeaxanthin = 0·78, 95% CI: 0·62-0·97); participants in the highest tertiles of total carotenoids, α-carotene, lutein/zeaxanthin and lycopene had a lower risk of respiratory mortality (hazard ratio (HR)total carotenoids = 0·62, 95% CI: 0·42-0·90, HRα-carotene = 0·54, 95% CI: 0·36-0·82, HRlutein/zeaxanthin = 0·48, 95% CI: 0·33-0·71, HRlycopene = 0·66, 95% CI: 0·45-0·96) than those in the lowest tertiles. Higher serum total carotenoids and ß-cryptoxanthin levels is associated with decreased prevalence of emphysema and chronic bronchitis, and higher serum total carotenoids, α-carotene, lutein/zeaxanthin and lycopene levels had a lower mortality of respiratory disease.

The association of homocysteine level with the risk of diabetic nephropathy and diabetic retinopathy in NHANES.

AIMS: To examine the association of homocysteine (Hcy) with diabetic nephropathy (DN) and diabetic retinopathy (DR) in a representative United States population. METHODS: This was a cross-sectional study using data from participants in the National Health and Nutrition Examination Survey 2005-2006. Metrics including Hcy level, urinary albumin to creatinine ratio, estimated glomerular filtration rate, and retinopathy grading were collected. Multiple logistic regression models were employed to assess the association of Hcy with DN and DR. RESULTS: 630 participants were included in this study. The Hcy level was significantly higher in those with DN and DR than those without DN and DR. Hcy was associated with an increased risk of DN (OR = 1.31, 95% CI 1.18-1.46; P < 0.001). In the fully adjusted model of DN (model II), compared to participants in quartiles 1 of Hcy, the adjusted ORs for participants in quartiles 2-4 were 1.49 (95% CI 0.52-4.26; P = 0.426), 3.81 (95% CI 1.35-10.73; P = 0.015), and 14.08 (95% CI 3.84-51.66; P = 0.001), respectively. Hcy was also associated with an increased risk of DR (OR = 2.260, 95% CI 1.212-4.216; P = 0.014), but this association was non-significant in the fully adjusted model of DR (model II). CONCLUSIONS: In diabetic patients, Hcy was associated with increased risk of DN in a non-linear manner. In addition, Hcy was associated with the risk of DR, but the association was attenuated after adjusting for confounders. In the future, Hcy can potentially be used as an early screening indicator for diabetic microvascular complications.

Dysregulation of the microbiota-brain axis during long-term exposure to polystyrene nanoplastics in rats and the protective role of dihydrocaffeic acid.

Polystyrene nano-plastics (PS-NPs) can be accumulated in the food chain and can penetrate biological barriers to affect multiple physiological functions. However, the adverse effects of nano-plastics on mammals and the underlying mechanism still remain unknown. To fill the gaps, our study administrated low-dose PS-NPs (50 and 100 µg/L) for 24 consecutive weeks in rats. Behavioral and morphological evaluations were performed to assess the neurobehavoirs. A combined analysis of multiple omics was used to evaluate the dysfunctions of the gut-microbe-brain axis. After dihydrochalcone(NHDC) treatment in the PS-NPs rat model, the inflammation response and apoptosis process were assessed and proteomics was used to explore the underlying mechanism. Our results indicated that long-term exposure to low-dose PS-NPs could induce abnormal neurobehaviors and amygdaloid nucleus impairment, and stimulate inflammatory responses and apoptosis. Metagenomics results revealed that four microbial phyla including Proteobacteria, Firmicutes, Defferibacteres, and Bacteroidetes changed significantly compared to the control. Targeted metabolomics analysis in the feces showed alteration of 122 metabolites induced by the PS-NPs exposure, among which the content of dihydrocaffeic acid was significantly associated with the different microbial genera and pivotal differential metabolites in the amygdaloid nucleus. And NHDC treatment significantly alleviated PS-NP-induced neuroinflammation and apoptosis and the cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/phosphorylated cAMP-response element binding protein(p-CREB)/plasma membrane calcium-transporting ATPase 2(Atp2b2) signaling pathway was identified in the proteomics. In conclusion, long-term exposure to low-dose PS-NPs has adverse effects on emotion through the dysregulation of the gut-brain axis, and dihydrocaffeic acid can alleviate these effects via the cAMP/PKA/p-CREB/Atp2b2 signaling pathway.

Hexavalent chromium (Cr(VI)) removal by ball-milled iron-sulfur @biochar based on P-recovery: Enhancement effect and synergy mechanism.

After the biochar recovery of phosphorus (P), its role in eliminating Cr(VI) is uncertain. In this study, the iron-sulfur biochar (Fe/S@BC) was made by grinding Fe0, S0, and biochar with a ball mill. P-loaded iron-sulfur biochar (P-Fe/S@BC) was produced after recovering P from simulated wastewater and then used to remove Cr(VI) contamination in waterbodies. P-Fe/S@BC got a rich pore structure and more reactive sites through P-recovery. The experiments revealed that P-Fe/S@BC had an enhancement effect on Cr(VI) pollution with removal efficiencies of 76.9 % ∼ 99.4 %, all greater than Fe/S@BC (58.2 %). In particular, 25P-Fe/S@BC (with 6.55 mg P/g) had the most significant advantage. The combination of physical adsorption, electrostatic attraction, and precipitation contributed to Cr(VI) removal. This is an efficient strategy for reusing Fe/S@BC followed by P-recovery, intending to improve the Cr(VI) removal effect and achieve the sustainable use of P resources and wastes.

Evolution of the combined effect of different irrigation solutions and activation techniques on the removal of smear layer and dentin microhardness in oval-shaped root canal: An in-vitro study.

The aim of this in vitro study was to evaluate the effect of three final irrigants, namely QMix, MTAD and EDTA, combined with three irrigation techniques, namely conventional needle irrigation (CNI), passive ultrasonic irrigation (PUI) and photon-induced photoacoustic streaming (PIPS), on smear layer removal, dentin mineral content and microhardness in oval-shaped canals.    130 decoronated premolars with single, oval root canals were equally divided into1 blank control group and 12 treatment groups (n=10) according to the final irrigation protocols. Roots in treatment groups were instrumented with ProTaper Gold to size F4 and subjected to final irrigation. Smear layer removal was assessed by using a four-level scoring system under an environmental scanning electron microscope. Energy dispersive X-ray spectroscopy was performed to measure the dentin mineral content. Dentin microhardness was measured by Knoop microhardness testing. Statistical analysis of the data was performed by using Kruskal-Wallis test, followed by Dunn's post hoc test with Bonferroni correction. PUI- and PIPS-activated QMix and EDTA removed smear layer more effectively than MTAD groups (p<0.05). Regarding the dentin mineral content and microhardness, QMix groups yielded the least calcium (Ca), phosphorus (P)  and Ca/P ratio, followed by EDTA groups and MTAD groups (p<0.05). QMix groups produced significantly lower dentin microhardness values and higher hardness reduction percentages than MTAD groups (p<0.05).  Within the limitations of the present study, it was concluded that QMix and EDTA were superior to MTAD in smear layer removal, especially when activated by PUI and PIPS, but these agents produced more pronounced effect on dentin mineral content and microhardness than MTAD.

Association of Urinary Nitrate With Diabetes Complication and Disease-Specific Mortality Among Adults With Hyperglycemia.

CONTEXT: The hyperglycemia condition disrupts metabolism of nitrate/nitrite and nitric oxide, and dietary nitrate intake can restore nitric oxide homeostasis. OBJECTIVE: This study aims to examine whether urinary nitrate is associated with diabetes complications and long-term survival among people with hyperglycemia. METHODS: A total of 6208 people with hyperglycemia who participated in the National Health and Nutrition Examination Survey from 2005 to 2014 were enrolled. Diabetes complications included congestive heart failure, coronary heart disease, angina, stroke, myocardial infarction, diabetic retinopathy, and nephropathy. Mortality was obtained from the National Death Index until 2015. Urinary nitrate was measured by ion chromatography coupled with electrospray tandem mass spectrometry, which was log-transformed and categorized into tertiles. Logistic regression models and Cox proportional hazards models were respectively performed to assess the association of urinary nitrate with the risk of diabetes complications and disease-specific mortalities. RESULTS: After adjustment for potential confounders, including urinary perchlorate and thiocyanate, compared with the participants in the lowest tertile of nitrate, the participants in the highest tertile had lower risks of congestive heart failure (odds ratio [OR] 0.41; 95% CI, 0.27-0.60) and diabetic nephropathy (OR 0.50; 95% CI, 0.41-0.62). Meanwhile, during a total follow-up period of 41 463 person-years, the participants in the highest tertile had lower mortality risk of all-cause (hazard ratio [HR] 0.78; 95% CI, 0.62-0.97), cardiovascular disease (CVD) (HR 0.56; 95% CI, 0.37-0.84), and diabetes (HR 0.47; 95% CI, 0.24-0.90), which showed dose-dependent linear relationships (P for nonlinearity > 0.05). Moreover, no association between nitrate and cancer mortality was observed (HR 1.13; 95% CI, 0.71-1.80). CONCLUSION: Higher urinary nitrate is associated with lower risk of congestive heart failure and diabetic nephropathy, and lower risk of all-cause, CVD, and diabetes mortalities. These findings indicate that inorganic nitrate supplementation can be considered as a supplementary treatment for people with hyperglycemia.

Altered Expression of Substance P and NK1R in CCR3+ and CD123+HLA-DR- Basophils Under Airway Allergic Conditions.

PURPOSE: To explore expression of SP and NK1R in basophils of allergic asthma (AA), allergic rhinitis (AR) and AR combined with AA (ARA), and influence of allergens and immunoglobulin E (IgE) mediated mechanisms on SP and NK1R expression. METHODS: Expression of SP and NK1R was detected by flow cytometry, NK1R mRNA expression was detected by real time quantitative polymerase chain reaction (qPCR), and mouse AR and AA models were employed for in vivo study. RESULTS: SP+ and NK1R+ cells increased in CCR3+ and CD123+HLA-DR- granulocytes of AA. PPE elevated proportions of SP+ cells in CCR3+ and CD123+HLA-DR- granulocytes, whereas ASWE and HDME augmented SP+ cells in CD123+HLA-DR- granulocytes of AR and ARA patients. ASWE, HDME and PPE increased proportions of NK1R+ cells in CCR3+ PBMC and CD123+HLA-DR- granulocytes of AR patients. OVA, Der p1, IL-33, IL-37, IgE and SP enhanced NK1R expression on KU812 cells. NK1R expressing basophils were increased in blood of OVA sensitized and challenged AR and AA mice. FcεRI-KO AA mice seemed to have less NK1R+ basophils than WT AA mice in their blood. CONCLUSION: CCR3+ and CD123+HLA-DR- cells are likely involved in AA and AR via SP and NK1R. IgE-related mechanism may participate in upregulation of NK1R expression.

Shaping ability of rotary and reciprocating single-file systems in combination with and without different glide path techniques in simulated curved canals.

Background/purpose: Glide path management (GPM) is a consequential clinical step that serves to influence predictably successful root canal therapy. However, the effect of GPM on the shaping ability of single-file system remains controversial. This study compared the performance of rotary single-file One Curve (OC) and reciprocating single-file Reciproc Blue (RCB) in combination with/without different glide path techniques: no glide path preparation (NG), PathFile (PF), ProGlider (PG) and WaveOne Gold Glider (WOGG), respectively. Materials and methods: 80 simulated curved canals (n = 10 canals/per group) were instrumented to an apical size of 0.25 mm using OC and RCB in combination with/without different glide path techniques, respectively. The amount of resin removal, canal transportation, and the degree of canal straightening were measured in Photoshop CS6 software. Statistical analysis of the data was performed by using Kruskal-Wallis test, followed by Dunn's post hoc test with Bonferroni correction (α = 0.05). Results: Post-glide path analysis found that WOGG and PG produced less canal transportation and curvature straightening than PF (P < 0.05). Post-shaping analysis showed that OC groups removed significantly less resin than RCB groups (P < 0.05). The PG and WOGG subgroups in both OC groups and RCB groups produced less transportation and curvature straightening than NG and PF subgroups (P < 0.05). OC + PG subgroup and OC + WOGG subgroup yielded the least canal transportation and curvature straightening (P < 0.05). Conclusion: PG and WOGG can improve the shaping ability of OC and RCB instrument. OC, especially when combined with PG and WOGG, has a less aggressive dentin cutting and more centered preparation than the RCB instrument.

Upregulated expression of substance P and NK1R in blood monocytes and B cells of patients with allergic rhinitis and asthma.

Increased expression of substance P (SP) and neurokinin-1 receptor (NK1R) has been noticed in patients with allergic rhinitis (AR) and allergic asthma (AA). However, little is known of the expression of SP and NK1R in monocytes and B cells of AR and AA. In the present study, the expression levels of SP and NK1R were determined by flow cytometry and mouse AR and AA models. The results showed that both percentages of SP+ monocytes and SP+ B cells, and mean fluorescence intensity (MFI) of SP in monocytes were elevated in the blood of AA and AR combined with AA (ARA) patients. Similarly, the percentages of NK1R+ monocytes were elevated in the blood of AR, AA, and ARA patients. Allergens Artemisia sieversiana wild allergen extract (ASWE), house dust mite extract (HDME), and Platanus pollen allergen extract (PPE) increased the expression density of SP molecules (determined by MFI) in an individual monocyte of AR patients. HDME and PPE appeared to enhance SP and NK1R expression in the B cells of ARA and AR patients. In the mouse AR and AA models, the percentages of NK1R+ monocytes and B cells were elevated in blood following OVA (ovalbumin) sensitization and challenge. Knocking out the FcεRI molecule completely abolished the OVA-induced upregulation of expression of NK1R in monocytes and B cells of AA mice. In conclusion, upregulated expressions of SP and NK1R may contribute to the pathogenesis of airway allergy.

A Newly Developed Indicator of Overeating Saturated Fat Based on Serum Fatty Acids and Amino Acids and Its Association With Incidence of Type 2 Diabetes: Evidence From Two Randomized Controlled Feeding Trials and a Prospective Study.

Objective: Hyper-caloric intake of saturated fatty acids (SFAs) is common in modern societies, probably contributing to the epidemic of type 2 diabetes mellitus (T2DM). This study conducted two randomized controlled trials (RCTs) for developing a new indicator that can assess the nutritional status and examined its association with incidence of T2DM. Methods: In RCT 1, healthy participants were randomly assigned into three groups, namely, control group (n = 40), overfeeding group 1 (100 g butter per day, n = 37), and overfeeding group 2 (120 g butter per day, n = 37). In RCT 2, healthy subjects were randomly assigned into two groups, namely, control group (n = 52) and high-fat group (300-extra kcal/day from diet that was designed by high-fat diet, n = 58). In the prospective cohort, 4,057 participants aged 20-74 years were enrolled and followed up over 5.3 years. Serum profiles of fatty acids and amino acids were measured. Results: In RCT 1, serum fatty acids, including C14:0 and C18:0, increased, whereas C18:2, C20:4, C22:5, and C22:6 decreased; serum amino acids, including tyrosine, alanine, and aminobutyric acid, increased, whereas histidine and glycine decreased (p < 0.05). Among these serum fatty acids and amino acids, changes in C14:0, C20:4, tyrosine, histidine, and glycine were also observed in RCT 2. An indicator was developed based on the five fatty acids and amino acids, namely, C14:0 × tyrosine × 1,000/[C20:4 × (glycine + histidine)], and it significantly identified participants in the intervention group with area under the curve (AUC) (95% CI) being 0.85 (0.77-0.92). The indicator was significantly associated with incidence of T2DM in the prospective cohort with HRs (95% CIs) from bottom quartile to top quartile being 1,1.21 (0.82-1.77), 1.60 (1.12-2.30), 2.04 (1.42-2.94). Conclusion: The newly developed indicator in RCTs can be used in assessing the nutritional status of hypercaloric intake of SFA and predicting the development of T2DM.

The Ameliorative Effect of JNK Inhibitor D-JNKI-1 on Neomycin-Induced Apoptosis in HEI-OC1 Cells.

Aminoglycosides can cause ototoxicity and lead to hair cell damage. Neomycin-induced ototoxicity is related to increased production of reactive oxygen species (ROS) and triggering hair cell apoptosis. The c-Jun-N-terminal kinase (JNK) pathway plays an essential role during hair cell damage. This study was designed to investigate an inhibitor of JNK, D-JNKI-1 (AM-111/brimapitide) in neomycin-induced HEI-OC1 cell apoptosis. The results demonstrate that neomycin increased intracellular ROS accumulation, which induces apoptosis. D-JNKI-1 decreased neomycin-induced ROS generation, reduced caspase-8 and cleavage of caspase-3 expression, sustained JNK activation and AMPK and p38 phosphorylation, downregulated Bax, and upregulated Bcl-2. Together, D-JNKI-1 plays an essential role in protecting against neomycin-induced HEI-OC1 cell apoptosis by suppressing ROS generation, which inhibited JNK activation and AMPK and p38 phosphorylation to ameliorate JNK-mediated HEI-OC1 cell apoptosis.

Combined central retinal vascular occlusion as the presenting feature in ß-thalassemia with iron deficiency anemia.

PURPOSE: To report a case of ß-thalassemia trait (ß-TT) with iron deficiency anemia (IDA) presenting as a combined central retinal vein and artery occlusion (CCRVAO). METHODS: Case report. A 22-year-old female presented with sudden-onset blurry vision in the left eye of 3-days duration. RESULTS: Best corrected visual acuity was 20/20 and 20/1000 in right and left eyes, respectively. Fundus examination of left eye revealed optic disc edema, macular whitening with a cherry-red spot, markedly dilated and tortuous retinal veins, and hemorrhages both around the disc and extending into the macula and the periphery. Fundus fluorescein angiography (FFA) showed delayed filling of retinal vasculature, dilated and tortuous retinal veins, blocked fluorescence around and beyond the optic disc. OCT scan at presentation showed hyperreflective inner retinal layers with neurosensory detachment. OCTA showed that the vessel densities of superficial and deep capillary plexus were remarkably reduced.A diagnosis of ß-TT combined with IDA was made after hematologic work-up. The patient was treated with a course of oral iron supplements, vasodilator (Compound Xueshuantong), inhalation of a mixture of 5% carbon dioxide and 95% oxygen, and a nutritional agent (compound anisoine). By six months later, her visual acuity improved to 20/60 in the left eye with complete resolution of all clinical signs. CONCLUSION: CCRVAO is a rare emergency leading to acute vision loss and can manifest in patients with ß-TT with IDA. Prompt diagnosis and early management is important to treat underlying systemic disorders and to prevent occurrence of a similar episode in fellow eye.

Pterygium epithelium abnormal differentiation related to activation of extracellular signal-regulated kinase signaling pathway in vitro.

AIM: To investigate whether the abnormal differentiation of the pterygium epithelium is related to the extracellular signal-regulated kinase (ERK) signaling pathway in vitro. METHODS: The expression levels of phosphorylated ERK (P-ERK), keratin family members including K19 and K10 and the ocular master control gene Pax-6 were measured in 16 surgically excised pterygium tissues and 12 eye bank conjunctiva. In colony-forming cell assays, the differences in clone morphology and in K10, K19, P-ERK and Pax-6 expression between the head and body were investigated. When cocultured with the ERK signaling pathway inhibitor PD98059, the changes in clone morphology, colony-forming efficiency, differentiated marker K10, K19 and Pax-6 expression and P-ERK protein expression level were examined by immunoreactivity and Western blot analysis. RESULTS: The expression of K19 and Pax-6 decreased in the pterygium, especially in the head. No staining of K10 was found in the normal conjunctiva epithelium, but it was found to be expressed in the superficial cells in the head of the pterygium. Characteristic upregulation of P-ERK was observed by immunohistochemistry. The clone from the head with more differentiated cells in the center expressed more K10, and the clone from the body expressed more K19. The P-ERK protein level increased in the pterygium epithelium compared with conjunctiva and decreased when cocultured with PD98059. The same medium with the ERK inhibitor PD98059 was more effective in promoting clonal growth than conventional medium with 3T3 murine feeder layers. It was observed that the epithelium clone co-cultured with the inhibitor had decreased K10 expression and increased K19 and Pax-6 expression. CONCLUSION: We suggest ERK signaling pathway activation might play a role in the pterygium epithelium abnormal differentiation.