Gut microbiota, circulating cytokines and dementia: a Mendelian randomization study.

BACKGROUND: Some studies have shown that gut microbiota may be associated with dementia. However, the causal effects between gut microbiota and different types of dementia and whether cytokines act as a mediator remain unclear. METHODS: Gut microbiota, cytokines, and five dementia types, including Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy body (DLB), vascular dementia (VD), and Parkinson's disease dementia (PDD) were identified from large-scale genome-wide association studies (GWAS) summary data. We used Mendelian randomization (MR) to investigate the causal relationships between gut microbiota, cytokines, and five types of dementia. Inverse variance weighting (IVW) was used as the main statistical method. In addition, we explored whether cytokines act as a mediating factor in the pathway from gut microbiota to dementia. RESULTS: There were 20 positive and 16 negative causal effects between genetic liability in the gut microbiota and dementia. Also, there were five positive and four negative causal effects between cytokines and dementias. Cytokines did not act as mediating factors. CONCLUSIONS: Gut microbiota and cytokines were causally associated with five types of dementia, and cytokines seemed not to be the mediating factors in the pathway from gut microbiota to dementia.

Effect of exposures to multiple metals on blood pressure and hypertension in the elderly: a community-based study.

A chronic disease, hypertension (HTN) is prevalent among the elderly. Exploring the factors that influence HTN and blood pressure (BP) changes is of great public health significance. However, mixed exposure to multiple serum metals has had less research on the effects on BP and HTN for the elderly. From April to August 2019, 2372 people participated in the community physical examination program for the elderly in Tongling City, Anhui Province. We measured BP and serum levels of 10 metals and collected basic demographic information. We analyzed the relationship between metal levels and changes in BP and HTN by the least absolute shrinkage and selection operator regression, Bayesian kernel machine regression model, and generalized linear model. In multiple models, lead (Pb) and cadmium (Cd) were still significantly associated with HTN occurrence after adjusting for potential confounders (Pb: ORquartile 4 VS quartile 1 = 1.20, 95% CI 1.01-1.43; Cd: ORquartile 4 VS quartile 1 = 1.37, 95% CI 1.16-1.62). In the male subgroup, results were similar to those of the general population. In the female group, Cd was positively correlated with HTN and systolic blood pressure, while Pb was not. According to this study, Pb and Cd were correlated with BP and HTN positively, and there was a certain joint effect. To some extent, our findings provide clues for the prevention of hypertension in the elderly.

CCK1R2R-/- ameliorates myocardial damage caused by unpredictable stress via altering fatty acid metabolism.

The heart is the main organ of the circulatory system and requires fatty acids to maintain its activity. Stress is a contributor to aggravating cardiovascular diseases and even death, and exacerbates the abnormal lipid metabolism. The cardiac metabolism may be disturbed by stress. Cholecystokinin (CCK), which is a classical peptide hormone, and its receptor (CCKR) are expressed in myocardial cells and affect cardiovascular function. Nevertheless, under stress, the exact role of CCKR on cardiac function and cardiac metabolism is unknown and the mechanism is worth exploring. After unpredictable stress, a common stress-inducing model that induces the development of mood disorders such as anxiety and reduces motivated behavior, we found that the abnormal contraction and diastole of the heart, myocardial injury, oxidative stress and inflammation of mice were aggravated. Cholecystokinin A receptor and cholecystokinin B receptor knockout (CCK1R2R-/-) significantly reversed these changes. Mechanistically, fatty acid metabolism was found to be altered in CCK1R2R-/- mice. Differential metabolites, especially L-tryptophan, L-aspartic acid, cholesterol, taurocholic acid, ADP, oxoglutaric acid, arachidonic acid and 17-Hydroxyprogesterone, influenced cardiac function after CCK1R2R knockout and unpredictable stress. We conclude that CCK1R2R-/- ameliorated myocardial damage caused by unpredictable stress via altering fatty acid metabolism.

Comparative efficacy of different treatments for menstrual migraine: a systematic review and network meta-analysis.

BACKGROUND: Menstrual migraine is a subtype of migraine disease that is typically more disabling, longer-lasting, and more challenging to treat. The purpose of this network meta-analysis (NMA) is to compare the relative efficacy of treatments for menstrual migraine. METHODS: We systematically searched databases, including PubMed, EMBASE, and Cochrane, and included all eligible randomized controlled trials in the study. We conducted the statistical analysis using Stata version 14.0, based on the frequentist framework. We used the Cochrane Risk of Bias tool for randomized trials version 2 (RoB2) to assess the risk of bias of the included studies. RESULTS: This network meta-analysis included 14 randomized controlled trials with 4601 patients. For short-term prophylaxis, frovatriptan 2.5 mg twice daily had the highest probability of effectiveness [OR = 1.87 (95% CI: 1.48 to 2.38)] compared to placebo. For acute treatment, the results showed that sumatriptan 100 mg [OR = 4.32 (95% CI: 2.95 to 6.34)] was the most effective treatment compared to placebo. CONCLUSIONS: These findings suggest that frovatriptan 2.5 mg twice daily was best for short-term prevention, sumatriptan 100 mg were best for acute treatment. More high-quality randomized trials are required to determine the most effective treatment.

Sodium tanshinone IIA sulphate inhibits angiogenesis in lung adenocarcinoma via mediation of miR-874/eEF-2K/TG2 axis.

CONTEXT: Sodium tanshinone IIA sulphate (STS) is a product originated from Salvia miltiorrhiza Bunge [Lamiaceae], which exerts an antitumour effect. However, the role of STS on lung adenocarcinoma (LUAD) remains unexplored. OBJECTIVE: Our study explores the effect and mechanism of STS against LUAD. MATERIALS AND METHODS: LUAD cells were treated with 100 µM STS for 24 h and control group cells were cultured under normal medium conditions. Functionally, the viability, migration, invasion and angiogenesis of LUAD cells were examined by MTT, wound healing, transwell and tube formation assay, respectively. Moreover, cells were transvected with different transfection plasmids. Dual luciferase reporter and RNA immunoprecipitation (RIP) assays were used to verify the relationship between miR-874 and eEF-2K. RESULTS: STS significantly decreased the viability (40-50% reduction), migration (migration rate of A549 cells from 0.67 to 0.28, H1299 cells from 0.71 to 0.41), invasion (invasion numbers of A549 cells from 172 to 55, H1299 cells from 188 to 35) and angiogenesis (80-90% reduction) of LUAD cells. Downregulation of miR-874 partially abolished the antitumour effect of STS. EEF-2K was identified to be the target of miR-874, and its downregulation markedly abolished the effects of miR-874 downregulation on tumourigenesis of LUAD. Moreover, silencing of TG2 abrogated eEF-2K-induced progression of LUAD. DISCUSSION AND CONCLUSIONS: STS attenuated the tumourigenesis of LUAD through the mediation of the miR-874/eEF-2K/TG2 axis. STS is a promising drug to fight against lung cancer, which might effectively reverse drug resistance when combined with classical anticancer drugs.

Clinical study on the effect of Bi-level positive airway pressure therapy on COPD complicated with Anxiety and Depression.

Objectives: To investigate the effect of bi-level positive airway pressure (BIPAP) therapy on chronic obstructive pulmonary disease (COPD) complicated with anxiety and depression. Methods: This is a retrospective study. One hundred patients with COPD complicated with anxiety and depression who were admitted to the Respiratory Department of The First Affiliated Hospital of Hebei North University from August 2021 to August 2022 were selected and randomly divided into two groups. Patients in the control group were given conventional symptomatic treatment, while those in the observation group were given BIPAP therapy in addition to the treatment in the control group. The two groups were compared and analyzed in terms of respiratory function indicators, the changes in the scores of St. George's Hospital Respiratory Questionnaire (SGRQ) and COPD assessment test (CAT), blood gas analysis indicators, the levels of serum neurokinin A (NKA), serum interleukin-6 (IL-6), and serum serotonin (5-HT), as well as the changes in the scores of Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD). Results: After treatment, the levels of lung function indicators in both groups increased, SGRQ and CAT scores decreased, and pH levels remained unchanged. In addition, PaO2 levels increased, PCO2, 5-HT, NKA and IL-6 levels decreased, and HAMA and HAMD scores decreased. The improvement degree of each indicator in the observation group was superior to that in the control group. Conclusion: In the clinical treatment of COPD complicated with anxiety and depression, BIPAP boasts effective amelioration of lung function and relief of anxiety and depression symptoms, and its mechanism of action may have a close bearing on ameliorating the levels of 5-HT, NKA, and IL-6 in patients.

CdS-Based Catalysts Derived from TMeQ[6]/[CdxCly]n--Based Frameworks for Oxidation Benzylamine.

The anion-induced outer surface interaction of Q[n]s is an important driving force in the construction of Q[n]-based supramolecular frameworks. In this work, a symmetric tetramethyl-substituted cucurbit[6]uril (TMeQ[6]) is selected as the basic structural block. Using the anion-induced outer surface interaction of Q[n]s derived from [CdxCly]n- anions formed by Cd2+ cations in a HCl medium, four different TMeQ[6]-[CdxCly]n--based supramolecular frameworks are constructed. Three of the most common TMeQ[6]-[CdxCly]n--based supramolecular frameworks are selected for further vulcanization, and three different CdS/TMeQ[6]-based framework catalysts with different structures and properties are obtained. The catalytic activities of these three CdS/TMeQ[6]-based framework catalysts are investigated by the coupling photocatalytic reaction of aminobenzyl, and the results showed that the catalytic activities of the three catalysts are all higher than that of pure CdS. Therefore, this work establishes that it is possible to establish a method for synthesizing the Q[n]-based framework-supported catalysts by first synthesizing TMeQ[6]-[CdxCly]n--based supramolecular frameworks and then forming Q[n]-based framework supported catalysts by sulfurization or reduction.

eEF-2K knockdown synergizes with STS treatment to inhibit cell proliferation, migration, and invasion via the TG2/ERK pathway in A549 cells.

Emerging research has suggested the anticancer potential of tanshinone IIA, the bioactive ingredient isolated from the traditional Chinese herb Salvia miltiorrhiza. However, the molecular mechanism of sodium tanshinone IIA sulfonate (STS) antilung cancer effect is not very clear. In this study, our purpose is to investigate the roles of STS and elongation factor-2 kinase (eEF-2K) in regulating the proliferation, migration, and invasion of A549 cells and explore the implicated pathways. We found that STS suppressed A549 cell survival and proliferation in a time- and xdose-dependent manner. Knockdown of eEF-2K and treatment with STS synergistically exerted antiproliferative, -migratory, and -invasive effects on A549 cells. These effects were caused by attenuation of the extracellular signal-regulated kinase (ERK) pathway via inhibition of tissue transglutaminase (TG2). In summary, the inhibition of eEF-2K synergizes with STS treatment, exerting anticancer effects on lung adenocarcinoma cells through the TG2/ERK signaling pathway, which provides a potential therapeutic target for treating lung adenocarcinoma.

Variations in the toxicity and condition index of five bivalve species throughout a red tide event caused by Alexandrium catenella: A field study.

Harmful red tides in China have caused paralytic shellfish toxins (PSTs) pollution and led to severe socioeconomic effects in shellfish aquaculture. Although shellfish can survive harmful algal blooms, the effects on their Condition Index (CI) have been underestimated. This study sought to evaluate the effects of the profiles and levels of paralytic shellfish toxins on variations in the CI in bivalves under natural blooming conditions. We observed clear soft tissue lesions to varying degrees except in Mytilus galloprovincialis after toxin exposure. Among the five species of shellfish exposed in situ, only M. galloprovincialis accumulated PSTs content above the maximum permitted level (800 µg STX di-HCl eq./kg). The highest toxin content in all sample tissues was observed in Patinopecten yessoensis. Significant interspecies differences in PSTs accumulation among the five bivalve species were observed in the hepatopancreas. A total of nine PSTs components and four new C-11 hydroxyl metabolites (so-called M-toxins) toxins were detected, and detoxification diversity was observed among bivalves. We observed a higher proportion of M-toxin in early stages, and the proportions changed only slightly over time in M. galloprovincialis and Magallana gigas, thus accounting for the significantly higher metabolism rate. Notably, the CI in M. gigas and Argopecten irradians was positively correlated with lowest toxin accumulation of PSTs content, but significantly inhibited. In conclusion, our results revealed a significant inhibitory effect on the CI in shellfish, in a species specific manner, with distinct levels of inhibition correlated with different toxin metabolites. Our study revealed the toxin content of different bivalves exposed to a natural red tide environment and the consequent effects on growth, thus building a foundation for research on the mechanisms underlying the effects of PSTs on growth. These data establish the ecological and economic significance of the effects of harmful algal blooms on bivalves.

Evaluation of the reliability of the upper lip bite test and the modified mallampati test in predicting difficult intubation under direct laryngoscopy in apparently normal patients: a prospective observational clinical study.

BACKGROUND AND AIMS: Difficult endotracheal intubation is one of the most challenging operations in anesthesia. How to better predict difficult airway and make corresponding preparations to reduce the occurrence of accidents is a difficult task faced by anesthesiologists every day. This study decide to evaluate the value of the Upper Lip Bite Test (ULBT) and the Modified Mallampati Test (MMT) in predicting difficult intubation under direct laryngoscopy and find out the most intuitive and simple method to predict difficult intubation under direct laryngoscopy in apparently normal patients. PATIENTS AND METHODS: This descriptive-analytical study was performed on 450 patients for elective surgery under general anesthesia requiring endotracheal intubation. The ULBT and MMT grading were evaluated preoperatively and Cormack and Lehane's (CL) classification was recorded on the day of surgery during intubation under direct laryngoscopy. The accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR), Youden index and area under ROC curve of ULBT and MMT respectively and in combination were calculated and compared. And the consistency between the total scores of ULBT and MMT combined in different ways and CL grading was counted. RESULTS: Of the 450 patients, 69 (15.3%) were classified as difficult cases of direct laryngoscopy. The accuracy, sensitivity, specificity, PPV and NPV of ULBT were 81.33, 11.59, 93.96, 25.81, 85.44%; and those the corresponding values for MMT were 66.22, 62.32, 69.29, 26.88 and 91.03%. A combination of ULBT and MMT did not improve the sensitivity in the sample tested. The combined total scores of ULBT and MMT in both ways were less consistent with CL grading in predicting difficult intubation under direct laryngoscopy. CONCLUSION: Based on findings of current study, we conclude that ULBT and MMT for difficult intubation have only poor to moderate discriminative power when used alone. The combination of the two tests in fractional form is also not a good predictor of difficult intubation under direct laryngoscopy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100052987, Registered 07 November 2021, http://www.chictr.org.cn.

Altered functional connectivity of primary visual cortex in adults with strabismus and amblyopia: a resting-state fMRI study.

Functional connectivity of the primary visual cortex was explored with resting functional magnetic resonance imaging among adults with strabismus and amblyopia and healthy controls. We used the two-sample test and receiver operating characteristic curves to investigate the differences in mean functional connectivity values between the groups with strabismus and amblyopia and healthy controls. Compared with healthy controls, functional connectivity values in the left Brodmann areas 17, including bilateral lingual/angular gyri, were reduced in groups with strabismus and amblyopia. Moreover, functional connectivity values in the right Brodmann area 17, including left cuneus, right inferior occipital gyrus, and left inferior parietal lobule, were reduced in adults with strabismus and amblyopia. Our findings indicate that functional connectivity abnormalities exist between the primary visual cortex and other regions. This may be the basis of the pathological mechanism of visual dysfunction and stereovision disorders in adults with strabismus and amblyopia.

Dysregulated Serum Cytokine Production in Pediatric Patients with ß-Thalassemia Major.

ß-Thalassemia major (ß-TM) is an inherited disorder of hemoglobin (Hb) production, which can cause severe anemia. A compromised immune system has been observed in patients with ß-TM, whereas cytokines have a major role in immune modulation. Interleukin-4 (IL-4), IL-8, IL-13 and transforming growth factor-ß (TGF-ß) are critical in initiating pro-inflammatory responses, and the serum levels of those cytokines may be involved in the pathophysiology of ß-thalassemia (ß-thal). To assess this hypothesis, we studied 23 pediatric patients with ß-TM by measuring serum levels of IL-4, IL-8, IL-13 and TGF-ß, as well as evaluating infection frequency per year, total number of transfusions and serum ferritin (SF) levels, together with age-matched healthy controls. We found that patients with ß-thal had higher IL-8, IL-13 and TGF-ß concentrations than normal controls, whereas markedly decreased serum IL-4 level was documented in patients with ß-TM. Serum IL-4 level of ß-thal patients showed a negative significant correlation with infection frequency, total number of transfusions and SF levels. On the contrary, serum levels of IL-8, IL-13 and TGF-ß exerted a positive relationship with those clinical parameters. Taken together, our study implies that dysregulated cytokine profile might contribute to iron overloads and impair immune cell functions, thus serving as useful biomarkers for diagnosis and evaluation of ß-TM in the future. Our study sheds new light on the pathogenesis of ß-TM.

Cucurbitacin B regulates lung cancer cell proliferation and apoptosis via inhibiting the IL-6/STAT3 pathway through the lncRNA XIST/miR-let-7c axis.

CONTEXT: Lung cancer, the most common type of cancer, has a high mortality rate. Cucurbitacin B (CuB), a natural compound extracted from Cucurbitaceae plants, has antitumor effects. OBJECTIVE: We investigated the role of CuB on lung cancer and its potential mechanisms. MATERIALS AND METHODS: A549 cells were treated with 0.1, 0.3, 0.6, and 0.9 µM CuB for 12, 24, and 48 h or untreated. Gene and protein levels were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Enzyme-linked immunosorbent assay (ELISA) detected inflammatory factors levels (TNF-α and IL-10). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and colony formation assays measured cell viability, apoptosis, and proliferation. The interaction between miR-let-7c and long non-coding RNA X inactive-specific transcript (XIST) or interleukin-6 (IL-6) was verified by dual-luciferase reporter assays. RESULTS: CuB treatment inhibited the proliferation of lung cancer cells and promoted cell apoptosis, and increased the expression of Bax and cleaved caspase3, decreased cyclin B1 and Bcl-2 expression. CuB suppressed XIST and IL-6 expression, and enhanced miR-let-7c expression. XIST silencing enhanced the inhibitory effect of CuB on cell proliferation and the promotion effect on apoptosis via upregulating miR-let-7c. Moreover, XIST targeted miR-let-7c to activate the IL-6/STAT axis. MiR-let-7c overexpression enhanced the regulatory effect of CuB on proliferation and apoptosis via suppressing the IL-6/STAT3 pathway. DISCUSSION AND CONCLUSION: CuB regulated cell proliferation and apoptosis by inhibiting the XIST/miR-let-7c/IL-6/STAT3 axis in lung cancer. These findings indicate CuB may have the possibility of clinical application in lung cancer treatment.

LncRNA XIST knockdown alleviates LPS-induced acute lung injury by inactivation of XIST/miR-132-3p/MAPK14 pathway : XIST promotes ALI via miR-132-3p/MAPK14 axis.

Acute lung injury (ALI) is a fatal inflammatory response syndrome. LncRNA XIST (XIST) is a lung cancer-related gene and participates in pneumonia. However, whether XIST participates in lipopolysaccharides (LPS)-induced ALI remains unclear. LPS-induced inflammation model was constructed in vitro, then cell viability, cytokines, cell apoptosis, protein, and mRNA expressions were individually detected by cell counting kit-8, enzyme-linked immunosorbent assay and flow cytometry, Western blot, and qRT-PCR. A dual-luciferase reporter assay confirmed the relationships among XIST, miR-132-3p, and MAPK14. Furthermore, inflammation and conditions after knockdown of XIST were assessed by hematoxylin and eosin staining, lung wet-to-dry weight ratio, PaO2/FiO2 ratio, and malondialdehyde (MDA) contents using LPS-induced in vivo model. Our findings indicated that the LPS challenge decreased cell viability, increased cell apoptosis, and caused secretions of pro-inflammatory cytokines. Noticeably, LPS significantly upregulated XIST, MAPK14, and downregulated miR-132-3p. Mechanistically, XIST acted as a molecular sponge to suppress miR-132-3p, and MAPK14 was identified as a target of miR-132-3p. Functional analyses demonstrated that XIST silencing remarkably increased cell survival and alleviated cell death and lung injury through decreasing TNF-α, IL-1ß, IL-6, accumulation of inflammatory cells, alveolar hemorrhage, MDA release, and increased PaO2/FiO2 ratio, as well as upregulating Bcl-2, and downregulating Bax, MAPK14, and p-extracellular signal-regulated kinases ½. In contrast, inhibition of the miR-132-3p antagonized the effects of XIST silencing. In conclusion, inhibition of XIST exhibited a protective role in LPS-induced ALI through modulating the miR-132-3p/MAPK14 axis.

Hepatitis B virus infection increases the risk of pancreatic cancer: a meta-analysis.

OBJECTIVE: The relationship between hepatitis B virus (HBV) and pancreatic cancer has been controversial for years, but more recently new information on this relationship has been updated Therefore, we performed a meta-analysis to provide summary estimates of the risk of pancreatic cancer associated with HBV infection. METHODS: A systematic literature search on HBV and pancreatic cancer in English was performed in Pubmed, Cochrane library and Embase up to July 2020. Pooled rate ratios (RRs) and 95% confidence intervals (CIs) were calculated by the random-effects model. Stata software version 15.1 was used to perform this meta-analysis of the 17 studies considered to be eligible. RESULTS: 17 studies including 7 case-control and 10 cohort studies met the selection criteria. Begg's and Egger's test results indicated that there was no publication bias. Individuals with Hepatitis B surface antigen (HBsAg) or HBV DNA seropositivity had a significantly increased risk of pancreatic cancer showing an RR (95% CI) of 1.39 (1.19, 1.63). Similar conclusions were drawn from the results of the subgroup analysis (subgroup by study design, population, sex ratio) except when subgrouped by patient's region: the RR and 95% CI in Europe and Oceania were 1.44 (0.88, 2.34) and 1.47(0.38, 5.71) respectively. CONCLUSIONS: The findings of this meta-analysis suggest that HBV infections may increase the risk of pancreatic cancer under most conditions, while there remains some doubt when comparison is made between European and Oceania patients.

Pigmentibacter ruber gen. nov., sp. nov., a novel bacterium of the family Silvanigrellaceae isolated from human blood.

A Gram-negative, aerobic, non-motile, pleomorphic, red-pigmented bacterium, designated HNSRY-1T, was isolated from the blood sample of a near drowning patient in Republic of China. Strain HNSRY-1T grew at 15-37 °C (optimum, 35 °C), with pH 6.0-8.0 (optimum, pH 7.0) and 0-1.5% (W/V) NaCl (optimum, 1%). The predominant fatty acids (> 5%) in HNSRY-1T cells are iso-C15:0, C17:0, C17:1 ω8c, C16:0, and C16:1 ω6c/C16:1 ω7c. The major respiratory quinone is MK-8. The polar lipids are phosphatidylglycerol, phosphatidylethanolamine, three unidentified lipids and four unidentified aminolipids. The 16S rRNA gene sequence-based phylogenetic analysis indicated that strain HNSRY-1T belonged to the family Silvanigrellaceae, forming a distinct phylogenetic line distantly related (< 96.4% sequence similarity) to known species of the family. The ANI values of strain HNSRY-1T compared to the closely related species were below the determined genus division threshold limit (92-94% ANI), and AAI values were lower than the determined genus division threshold limit (80% AAI). Whole genome sequencing revealed a genome size of 3.63 Mb with a DNA G + C content at 29.6%. The half-lethal dose of strain HNSRY-1T on KM mice is about 1.12 × 108 CFU/ml. Virulence gene analysis showed that the pathogenicity of HNSRY-1T may be related to tufA, htpB, katA, wbtL, wbtM, pseB, clpP, cheY, cheV3, acpXL, pilB, fliN, ggt, flgG, fliP, nueB, pseA, bioB and flil. Based on these findings from the polyphasic taxonomy studies, a novel genus and species of the family Silvanigrellaceae. Pigmentibacter ruber gen. nov., sp. nov. is proposed, with type strain HNSRY-1T (= KCTC 72920T = CGMCC 1.18525T).

Potential effects of angiogenesis-related factors on the severity of APAC and surgical outcomes of trabeculectomy.

BACKGROUND: EPO (erythropoietin) and PDGF (platelet derived growth factor) families are thought to be associated with angiogenesis under hypoxic condition. The sharp rise of intraocular pressure in acute primary angle closure (APAC) results in an inefficient supply of oxygen and nutrients. We aimed to measure the expression of EPO and PDGF family members in APAC eyes and demonstrate their associations with APAC's surgical success rate. METHODS: Concentrations of EPO, PDGF-AA, -BB, -CC and -DD collected in aqueous humor samples of 55 patients recruited were measured. Before operations, correlations between target proteins and IOP (intraocular pressure) were detected between APAC (acute primary angle closure) and cataract patients. Based on the post-operative follow-up, the effects of EPO and PDGF family members on the successful rate of trabeculectomy were tested. RESULTS: The levels of EPO, PDGF-CC and -DD were significantly elevated in the APAC group compared to the cataract group. During the post-operative follow-up, EPO, PDGF-CC and -DD showed significant differences between the success and failure groups. In multivariable linear regression analyses, failed filtration surgery was more likely in APAC eyes with higher EPO level. The Kaplan-Meier survival plot suggested that the success rate in eyes with low EPO level was significantly higher than that in eyes with high EPO level. CONCLUSION: The levels of EPO, PDGF-CC and -DD were significantly elevated in failure group. EPO level correlated with preoperative IOP and numbers of eyedrops, and higher EPO level in aqueous humor is a risk factor for trabeculectomy failure. It can be a biomarker to estimate the severity of APAC and the success rate of surgery. The investigation of mechanism of EPO in APAC a may have potential clinical applications for the surgical treatment of APAC.

Developmental Pattern of Diurnal Cortisol Rhythm and Sex-Specific Associations With Psychopathological Symptoms During Pubertal Transition.

OBJECTIVE: This study aimed to examine the developmental pattern of diurnal cortisol rhythm during pubertal transition and its prospective association with psychopathological symptoms. METHODS: A cohort of 1158 children consisting of 608 boys and 550 girls aged 7 to 9 years (mean [standard deviation] age = 8.04 [0.61] years) were recruited in the Anhui Province of China in 2015 (wave 1). A single awakening sample was collected at baseline, and three additional samples were collected at one weekday in wave 2 to wave 4. Four indices of cortisol activity were evaluated and calculated across the day: awakening cortisol level, cortisol awakening response, the area under the curve with respect to ground (AUC), and the diurnal cortisol slope. In each wave, pubertal development was assessed by testicular size in boys and Tanner scales in girls. Psychopathological symptoms were ascertained in waves 2 to 4. RESULTS: Multilevel mixed models revealed no significant pubertal changes in diurnal cortisol activity in girls. In boys, awakening cortisol (ß = -0.005, p = .004) and total cortisol output (lnAUC, ß = -0.005, p = .040) significantly decreased across pubertal transition. Higher awakening cortisol and total cortisol output (lnAUC) were associated with higher scores on internalizing symptoms in girls (ß = 0.82, p < .001; ß = 0.62, p = .012) and externalizing symptoms in boys (ß = 0.73, p = .001; ß = 0.55, p = .019) during the 3-year follow-up. In contrast, no associations were found between cortisol awakening response and diurnal cortisol slope with psychopathological symptom scores in boys or girls. CONCLUSIONS: Development of diurnal cortisol activity during pubertal transition occurs in a sex-specific manner. Awakening cortisol level and daily total cortisol output may serve as markers for psychopathology during pubertal transition.

Dihydroquercetin attenuates lipopolysaccharide-induced acute lung injury through modulating FOXO3-mediated NF-κB signaling via miR-132-3p.

BACKGROUND: Dihydroquercetin (DHQ) is a potent flavonoid which has been demonstrated to have multiple biological activities including anti-inflammation activity, antioxidant activity as well as anti-cancer activity etc. Recently, many studies have focused on the antioxidant activity of DHQ. However, the use of the anti-inflammation activity of DHQ in acute lung injury (ALI) has not been reported. METHODS: Cell viability was examined by CCK-8 assay. The relative expression of miR-132-3p, FOXO3 were detected by qPCR. The levels of TNF-α, IL-6 and IL-1ß were detected using enzyme-linked immunosorbent assay. The amount of apoptosis cells was detected by flow cytometry. The protein levels of Bcl-2, Bax, p-p65 and p-IκBα were measured by western blot. RESULTS: We found that DHQ-induced the expression of miR-132-3p in LPS-induced ALI. Overexpression of miR-132-3p resulted in the inhibition of FOXO3 expression and then suppressed FOXO3-activated NF-κB pathway, attenuating LPS-induced inflammatory response and apoptosis. CONCLUSION: We demonstrated FOXO3 to be a target of miR-132-3p, and DHQ could induce the expression of miR-132-3p, relieving LPS-induced ALI via miR-132-3p/FOXO3/NF-κB axis, providing a promising therapeutic target for ALI.

Three-dimensional structure and function of chromatin regulated by "liquid-liquid phase separation" of biological macromolecules.

Phase separation drives biomacromolecule condensation (phase separation) and is the main mechanism for the formation of membrane-less organelles in cells. Phase separation is involved in many biological processes and is closely associated to various human diseases, e.g., neurodegenerative diseases. Focusing on the molecular mechanism and functions, researchers have recently revealed close associations s between phase separation and various biological functions, such as signal transduction, chromosome structure, gene expression, and transcriptional regulation. These findings have provided new perspectives in understanding cell fate decisions and disease processes, thereby offering novel approaches for future drug discovery and development of disease treatments in medicine. In this review, we summarized the current progress in the field of phase separation research. We focused on its application on understanding how phase separation remodels the chromatin structure, assembles co-activators and super-enhancers in regulation of gene expression, in order to further understand the relationship between phase separation and chromatin spatial structures. Finally, we also outline the challenges in reference to future research directions in the field.