Serotonin/5-HT7 receptor provides an adaptive signal to enhance pigmentation response to environmental stressors through cAMP-PKA-MAPK, Rab27a/RhoA, and PI3K/AKT signaling pathways.

Serotonin (5-HT), a neurotransmitter, is essential for normal and pathological pigmentation processing, and its receptors may be therapeutical targets. The effect and behavior of the 5-HT7 receptor (5-HT7R) in melanogenesis in high vertebrates remain unknown. Herein, we examine the role and molecular mechanism of 5-HT7R in the pigmentation of human skin cells, human tissue, mice, and zebrafish models. Firstly, 5-HT7R protein expression decreased significantly in stress-induced depigmentation skin and vitiligo epidermis. Stressed mice received transdermal serotonin 5-HT7R selective agonists (LP-12, 0.01%) for 12 or 60 days. Mice might recover from persistent stress-induced depigmentation. The downregulation of tyrosinase (Tyr), microphthalmia-associated transcription factor (Mitf) expression, and 5-HT7R was consistently restored in stressed skin. High-throughput RNA sequencing showed that structural organization (dendrite growth and migration) and associated pathways were activated in the dorsal skin of LP-12-treated animals. 5-HT7R selective agonist, LP-12, had been demonstrated to enhance melanin production, dendrite growth, and chemotactic motility in B16F10 cells, normal human melanocytes (NHMCs), and zebrafish. Mechanistically, the melanogenic, dendritic, and migratory functions of 5-HT7R were dependent on the downstream signaling of cAMP-PKA-ERK1/2, JNK MAPK, RhoA/Rab27a, and PI3K/AKT pathway activation. Importantly, pharmacological inhibition and genetic siRNA of 5-HT7R by antagonist SB269970 partially/completely abolished these functional properties and the related activated pathways in both NHMCs and B16F10 cells. Consistently, htr7a/7b genetic knockdown in zebrafish could blockade melanogenic effects and abrogate 5-HT-induced melanin accumulation. Collectively, we have first identified that 5-HT7R regulates melanogenesis, which may be a targeted therapy for pigmentation disorders, especially those worsened by stress.

Impact of air pollutants on influenza-like illness outpatient visits under COVID-19 pandemic in the subcenter of Beijing, China.

This study aimed to explore the association between air pollutants and outpatient visits for influenza-like illnesses (ILI) under the coronavirus disease 2019 (COVID-19) stage in the subcenter of Beijing. The data on ILI in the subcenter of Beijing from January 1, 2018 to December 31, 2020 were obtained from the Beijing Influenza Surveillance Network. A generalized additive Poisson model was applied to examine the associations between the concentrations of air pollutants and daily outpatient visits for ILI when controlling meteorological factors and temporal trend. A total of 171 943 ILI patients were included. In the pre-coronavirus disease 2019 (COVID-19) stage, an increased risk of ILI outpatient visits was associated to a high air quality index (AQI) and the high concentrations of particulate matter less than 2.5 (PM2.5 ), particulate matter 10 (PM10 ), sulphur dioxide (SO2 ), nitrogen dioxide (NO2 ), and carbon monoxide (CO), and a low concentration of ozone (O3 ) on lag0 day and lag1 day, while a higher increased risk of ILI outpatient visits was observed by the air pollutants in the COVID-19 stage on lag0 day. Except for PM10 , the concentrations of other air pollutants on lag1 day were not significantly associated with an increased risk of ILI outpatient visits during the COVID-19 stage. The findings that air pollutants had enhanced immediate effects and diminished lag-effects on the risk of ILI outpatient visits during the COVID-19 pandemic, which is important for the development of public health and environmental governance strategies.

Association between ambient carbon monoxide levels and hospitalization costs of patients with myocardial infarction: Potential effect modification by ABO blood group.

Previous researches have reported the association between air pollution and various diseases. However, few researches have investigated whether air pollutants are associated with the economic loss resulting from patients' hospitalization, especially the economic loss of hospitalization due to acute cardiovascular events. The purpose of our research was to explore the association between the levels of carbon monoxide (CO), taken as an index of pollution, and the hospitalization costs of myocardial infarction (MI), and the potential effect modification by the ABO blood group. A total of 3237 MI inpatients were included in this study. A multiple linear regression model was used to evaluate the association between ambient CO levels and hospitalization costs of MI patients. Moreover, we performed stratified analyses by age, gender, body mass index (BMI), season, hypertension, and ABO blood types. There was a positive association between the levels of CO in the air and the costs of hospitalization caused by MI. Furthermore, such association was stronger in males, BMI ≥25, <65 years, with hypertension, and non-O blood group. Interestingly, we found the association was particularly significant in patients with blood group B. Overall, our study first found that ambient CO levels could have an impact on the hospitalization costs for MI patients, and those with blood group B can be more sensitive.

Influencing factors of self-regulated learning of medical-related students in a traditional Chinese medical university: a cross-sectional study.

BACKGROUND: In recent years, self-regulated learning (SRL) has become a hot topic in medical education. However, the factors that affect the SRL ability of medical-related specialties, such as clinical medicine, traditional Chinese medicine (TCM), and nursing specialty in TCM colleges and universities are unclear. Whether the teaching of learning strategies can help improve students' SRL also needs to be further examined. METHOD: A cross-sectional survey was distributed, and 878 medical-related students who were from a TCM university were recruited for this study. Descriptive statistics illustrated the status quo of SRL and learning strategies, and an independent t-test and analysis of variance were used to analyze the factors associated with SRL. The relationship between SRL and learning strategies was analyzed with multi-linear regression analysis. RESULTS: The scores of SRL on learning motivation, learning setting, self-regulation, and total scores were 34.76 ± 4.62, 41.14 ± 4.30, 39.26 ± 4.74, and 115.16 ± 12.42, respectively. The metacognitive, emotion, cognitive, resource management and total scores of learning strategies were 58.54 ± 12.02, 43.24 ± 8.42, 35.49 ± 7.34, 22.89 ± 4.20, 160.16 ± 29.45, and the mean was all above the midpoint. Learning strategies were positively correlated with SRL (r = 0.421, P < 0.01). Some factors can predict 32% of the variation of SRL, including whether they liked their specialty, educational system, specialty, score ranking, scholarship, whether they were taught by a tutor in middle school, gender, monthly family income, the father's educational background, metacognitive strategy, resource management strategy, and cognitive strategy. CONCLUSIONS: The SRL of medical-related students was better. Learning strategies, as well as personal or social factors, can affect SRL. Educators should pay more attention to the cultivation of learning strategies, exercising learning skills, and monitoring, adjustment, and guidance of learning time. It should adopt various methods to improve the SRL of medical-related students according to the different factors.

Construction and validation of postoperative hypothermia prediction model for patients undergoing joint replacement surgery.

AIM: To construct and validate a postoperative hypothermia prediction model for patients undergoing joint replacement surgery. BACKGROUND: Postoperative hypothermia is one of the harmful perioperative complications in patients undergoing joint replacement surgery. The previous studies mainly focused on intraoperative hypothermia prediction models. The prediction model for postoperative hypothermia in patients with joint replacement surgery was understudied. DESIGN: Cohort study. METHODS: We collected data from 503 participants undergoing joint replacement surgery in a tertiary hospital from January 2019 to December 2021. Of those, 404 cases were assigned to the modelling and 99 to the validation groups. Logistic regression was used to construct the model. The AUC was used to test the predictive effect of the model. Finally, 99 cases were used to verify the application effect of the model. A TRIPOD checklist was used to guide the reporting of this study. RESULTS: The factors entered into the prediction model were age, intraoperative hypothermia, BMI, heat preservation measures and platelet (PLT). The model was constructed as follows: Logit (P) = .537 + 3.669 × 1 (intraoperative hypothermia) + .030 × age - .289 × BMI + 2.857 × 1 (intraoperative insulation measures) + .003 × PLT. Hosmer-Lemeshow test, p = .608, the area under the receiver operating characteristic curve (AUC) was .861. The Youden index was .530, the sensitivity was .599 and the specificity was .93. The incidence of postoperative hypothermia in the modelling group was 42.93% (173/404), and that in the verification group was 43.43% (43/99), χ2 = .012, p = .912. The correct practical application rate was 87.88%. This model has a good application effect. CONCLUSION: The current prediction model provided a reference for clinical screening of patients with high-risk hypothermia after joint replacement surgery. RELEVANCE TO CLINICAL PRACTICE: Clinical nurses can use the developed prediction model to predict the occurrence of postoperative hypothermia and provide a reference for the preventive measure.

Dynamics of influenza-like illness under urbanization procedure and COVID-19 pandemic in the subcenter of Beijing during 2013-2021.

Influenza-like illness (ILI) varies in intensity year by year, generally keeping a stable pattern except for great changes of its epidemic pattern. Of the most impacting factors, urbanization has been suggested as shaping the intensity of influenza epidemics. Besides, growing evidence indicates the nonpharmaceutical interventions (NPIs) to severe acute respiratory syndrome coronavirus 2 offer great advantages in controlling infectious diseases. The present study aimed to evaluate the impact of urbanization and NPIs on the dynamic of ILI in Tongzhou, Beijing, during January 2013 to March 2021. ILI epidemiological surveillance data in Tongzhou district were obtained from Beijing Influenza Surveillance Network and separated into three periods of urbanization and four intervals of coronavirus disease 2019 pandemic. Standardized average incidence rates of ILI in each separate stages were calculated and compared by using Wilson method and time series model of seasonal ARIMA. Influenza seasonal outbreaks showed similar epidemic size and intensity before urbanization during 2013-2016. Increased ILI activity was found during the process of Tongzhou's urbanization during 2017-2019, with the rate difference of 2.48 (95% confidence interva [CI]: 2.44, 2.52) and the rate ratio of 1.75 (95% CI: 1.74, 1.76) of ILI incidence between preurbanization and urbanization periods. ILI activity abruptly decreased from the beginning of 2020 and kept at the bottom level almost in every epidemic interval. The top decrease in ILI activity by NPIs was shown in 5-14 years group in 2020-2021 influenza season, as 92.2% (95% CI: 78.3%, 95.2%). The results indicated that both urbanization and NPIs interrupted the epidemic pattern of ILI. We should pay more attention to public health when facing increasing population density, human contact, population mobility, and migration in the process of urbanization. NPIs and influenza vaccination should be implemented as necessary measures to protect people from common infectious diseases like ILI.

An edible molecularly imprinted material prepared by a new environmentally friendly deep eutectic solvent for removing oxalic acid from vegetables and human blood.

A novel deep eutectic solvent-magnetic molecularly imprinted polymer (DES-MMIP) for the specific removal of oxalic acid (OA) was prepared by an environmentally friendly deep eutectic solvent, consisting of betaine, citric acid, and glycerol, which acted as the functional monomer for polymerization. The structure and morphology of DES-MMIPs were studied by X-ray diffraction, scanning and transmission electron microscopy, thermal gravimetric analysis, Fourier transform infrared spectroscopy, and vibrating sample magnetometer. DES-MMIPs had a core-shell structure, with magnetic iron oxide as the core, and showed good thermal stability and high adsorption capacity (18.73 mg/g) for OA. The adsorption process of OA by DES-MMIPs followed the pseudo-second-order kinetic model and Langmuir isotherm model. DES-MMIPs had significant selectivity for OA and their imprinting factor was 3.26. When applied to real samples, high performance liquid chromatography analysis showed that DES-MMIPs could remove OA from both spinach and blood serum. These findings provide potential methods for removal of OA from vegetables and for specific removal of OA in renal dialysis.

The association between short-term exposure to ambient carbon monoxide and hospitalization costs for bronchitis patients: A hospital-based study.

Ambient carbon monoxide (CO) is associated with bronchitis morbidity, but there is no evidence concerning its correlation with hospitalization costs for bronchitis patients. This study aimed to investigate the relationship between short-term ambient CO exposure and hospitalization costs for bronchitis patients in Chongqing, China. Baseline data for 3162 hospitalized bronchitis patients from November 2013 to December 2019 were collected. Multiple linear regression analysis was used to determine the association, delayed and cumulative, between short-term CO exposure and hospitalization costs. Additionally, subgroup analyses were performed by gender, age, season, and comorbidity. Positive association between CO and hospitalization costs for bronchitis patients was observed. The strongest association was observed at lag 015 days, with per 1 mg/m3 increase of CO concentrations corresponded to 5834.40 Chinese Yuan (CNY) (95% CI: 2318.71, 9350.08; P < 0.001) (845.97 US dollars) increment in hospitalization costs. Stratified analysis results showed that the association was more obvious among those males, elderly, with comorbidities, and in warm seasons. More importantly, there was strongest correlation between CO and bronchitis patients with coronary heart disease. In summary, short-term exposure to ambient CO, even lower than Chinese and WHO standards, can be associated with increased hospitalization costs for bronchitis. Controlling CO exposure can be helpful to reduce medical burden associated with bronchitis patients. The results also suggest that when setting air quality standards and formulating preventive measures, susceptible subpopulations ought to be considered.

Andrographolide suppresses breast cancer progression by modulating tumor-associated macrophage polarization through the Wnt/ß-catenin pathway.

Andrographolide(ADE) has been demonstrated to inhibit tumor growth through direct cytotoxicity on tumor cells. However, its potential activity on tumor microenvironment (TME) remains unclear. Tumor-associated macrophages (TAMs), composed mainly of M2 macrophages, are the key cells that create an immunosuppressive TME by secretion of cytokines, thus enhancing tumor progression. Re-polarized subpopulations of macrophages may represent vital new therapeutic alternatives. Our previous studies showed that ADE possessed anti-metastasis and anoikis-sensitization effects. Here, we demonstrated that ADE significantly suppressed M2-like polarization and enhanced M1-like polarization of macrophages. Moreover, ADE inhibited the migration of M2 and tube formation in HUVECs under M2 stimulation. In vivo studies showed that ADE restrained the growth of MDA-MB-231 and HCC1806 human breast tumor xenografts and 4T-1 mammary gland tumors through TAMs. Wnt5a/ß-catenin pathway and MMPs were particularly associated with ADE's regulatory mechanisms to M2 according to RNA-seq and bioinformatics analysis. Moreover， western blot also verified the expressions of these proteins were declined with ADE exposure. Among the cytokines released by M2, PDGF-AA and CCL2 were reduced. Our current findings for the first time elucidated that ADE could modulate macrophage polarization and function through Wnt5a signaling pathway, thereby playing its role in inhibition of triple-negative breast cancer.

[Role of Piezo1 channel in cardiovascular diseases and its research progress in traditional Chinese medicine].

Piezo1 channel is a mechanosensitive ion channel that opens in response to shear stress, tension, torsion and a series of mechanical stimulation and turns them into biological signals. It plays an important role in vascular development, vasoconstriction and vasodilation, formation of arterial and venous valves, blood pressure regulation and red blood cell homeostasis, and thus is closely related to cardiovascular system. Recent studies have shown that traditional Chinese medicine(TCM) compounds and their active components can affect Ca~(2+) influx and endothelial cell and platelet function by mediating Piezo1 channel, and regulate thrombosis and endothelial homeostasis, thereby treating cardiovascular diseases. This study mainly reviewed the role of Piezo1 channel in cardiovascular diseases and the prevention and treatment of cardiovascular diseases based on Piezo1 channel in TCM, in order to provide effective reference for the further research of Piezo1 channel in the field of TCM.

Evaluation of piggyBac-mediated anti-CD19 CAR-T cells after ex vivo expansion with aAPCs or magnetic beads.

Adoptive immunotherapy is a new potential method of tumour therapy, among which anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T cell), is a typical treatment agent for haematological malignancies. Previous clinical trials showed that the quality and phenotype of CAR-T cells expanded ex vivo would seriously affect the tumour treatment efficacy. Although magnetic beads are currently widely used to expand CAR-T cells, the optimal expansion steps and methods have not been completely established. In this study, the differences between CAR-T cells expanded with anti-CD3/CD28 mAb-coated beads and those expanded with cell-based aAPCs expressing CD19/CD64/CD86/CD137L/mIL-15 counter-receptors were compared. The results showed that the number of CD19-specific CAR-T cells with a 4-1BB and CD28 co-stimulatory domain was much greater with stimulation by aAPCs than that with beads. In addition, the expression of memory marker CD45RO was higher, whereas expression of exhausted molecules was lower in CAR-T cells expanded with aAPCs comparing with the beads. Both CAR-T cells showed significant targeted tumoricidal effects. The CAR-T cells stimulated with aAPCs secreted apoptosis-related cytokines. Moreover, they also possessed marked anti-tumour effect on NAMALWA xenograft mouse model. The present findings provided evidence on the safety and advantage of two expansion methods for CAR-T cells genetically modified by piggyBac transposon system.

One new sesquiterpene pyridine alkaloid from the stems and leaves of Euonymus fortunei.

A new sesquiterpene pyridine alkaloid (1), along with four known compounds (2-5), were isolated from the stems and leaves of Euonymus fortunei. The new structure was determined by extensive spectroscopic analyses (IR, UV, NMR, HRESIMS and ECD). In addition, compound 3 showed a stronger anti-respiratory syncytial virus (RSV) activity with an IC50 value of 1.20 ± 0.10 µM than the positive control ribavirin with an IC50 value of 5.62 ± 0.49 µM.[Formula: see text].

MCTR1 alleviates lipopolysaccharide-induced acute lung injury by protecting lung endothelial glycocalyx.

Endothelial glycocalyx degradation, critical for increased pulmonary vascular permeability, is thought to facilitate the development of sepsis into the multiple organ failure. Maresin conjugates in tissue regeneration 1 (MCTR1), a macrophage-derived lipid mediator, which exhibits potentially beneficial effects via the regulation of bacterial phagocytosis, promotion of inflammation resolution, and regeneration of tissue. In this study, we show that MCTR1 (100 ng/mouse) enhances the survival of mice with lipopolysaccharide (LPS)-induced (15 mg/kg) sepsis. MCTR1 alleviates LPS (10 mg/kg)-induced lung dysfunction and lung tissue inflammatory response by decreasing inflammatory cytokines (tumor necrosis factor-α, interleukin-1ß [IL-1ß], and IL-6) expression in serum and reducing the serum levels of heparan sulfate (HS) and syndecan-1. In human umbilical vein endothelial cells (HUVECs) experiments, MCTR1 (100 nM) was added to the culture medium with LPS for 6 hr. MCTR1 treatment markedly inhibited HS degradation by downregulating heparanase (HPA) protein expression in vivo and in vitro. Further analyses indicated that MCTR1 upregulates sirtuin 1 (SIRT1) expression and decreases NF-κB p65 phosphorylation. In the presence of BOC-2 or EX527, the above effects of MCTR1 were abolished. These results suggest that MCTR1 protects against LPS-induced sepsis in mice by attenuating pulmonary endothelial glycocalyx injury via the ALX/SIRT1/NF-κB/HPA pathway.

Adenosquamous carcinoma of the digestive system: a literature review.

Adenosquamous carcinoma (ASC), containing both adenocarcinoma and squamous cell carcinoma components, is rare in the digestive system. Limited data is available on ASC of the digestive system (AS-ASC), and the current evidence is available mainly in the form of case reports and case series. We performed a thorough search of the available literature and compiled a review on the epidemiology, histopathology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis of AS-ASC. Non-specific clinical and imaging presentations and low diagnostic accuracy of biopsy lead to difficulties in preoperative diagnosis in a high proportion of patients and high malignancy. The pathogenesis remains obscure. Surgery remains the mainstay of treatment for AS-ASC. The role of chemoradiotherapy as an adjuvant treatment is still inconclusive. Key messages Metastatic linings and the lack of efficacious treatments lead to an unfavorable outcome in AS-ASC patients. Further research could help us understand the pathophysiology of AS-ASCand the unique needs of AS-ASC patients.

[Status analysis and thinking on experimental study on efficacy of Mori Fructus in treatment of cardiovascular diseases].

Cardiovascular diseases are the most important diseases that endanger national health, and its development process is complex and diverse. Various cardiovascular diseases caused by obesity, such as hyperlipidemia, hyperglycemia and atherosclerosis, are interrelated and interacted each other. Diet, as the main means of prevention and treatment, plays an important role in the occurrence and development of cardiovascular disease. Mori Fructus is one of the first ingredients that are listed in medicinal and edible food. With a wide range of applications in daily life, it contains polysaccharides(polysaccharide, APS), anthocyanins(anthocyanin, LCRA), flavonoids and other bioactive ingredients. With a wide range of antioxidant, anti-aging, hypoglycemic and hypolipidemic activities, these materials exert effects in alleviating diabetes, hyperglycemia, hyperlipidemia and other cardiovascular diseases. In this paper, we retrieved such databases as PubMed, Web of science, CNKI, VTTMS, Wan Fang, and collected literatures about the effect of single administration of mulberry on cardiovascular diseases in the past 15 years, with "mulberry and cardiovascular disease" as the key word, and summarized the latest progress. The results of many experimental studies have showed that different forms of mulberry can significantly alleviate obesity, diabetes, atherosclerosis, hyperlipidemia and hypertension, suggesting that the scope of action of Mori Fructus covers different pathological stages of cardiovascular diseases. This paper systematically analyzes and summarizes the application forms, efficacy and the existing problems of these experiments, and provides study thinking and development direction for the utilization and new product design of Mori Fructus-related products in the treatment of cardiovascular diseases.

HuoXueTongFu Formula Alleviates Intraperitoneal Adhesion by Regulating Macrophage Polarization and the SOCS/JAK2/STAT/PPAR-γ Signalling Pathway.

Intraperitoneal adhesion is a common complication after abdominal surgery, which seriously affects the quality of life of patients. HuoXueTongFu Formula (HXTF) plays an important role in the prevention and treatment of intraperitoneal adhesions. However, the molecular-related mechanisms are still not fully known. In this study, the model of Intrapetitoneal adhesion was established by cecum abrasion and treated with HXTF for one week. RAW264.7 cells were given LPS, IFN-γ, IL-4, HXTF-medicated serum, and PPAR-γ agonist/antagonist, respectively. Histopathology, flow cytometry, ELISA, real-time PCR, and Western blotting were used to further detect the related protein, M1/M2 polarization tendency, and PPAR-γ nuclear translocation. The deposition of collagen fibres reduced in the local area of rats after the operation with HXTF treatment. Similar to IL-4, HXTF induced a tendency for macrophages to polarize toward M2 and promoted peroxisome proliferator-activated receptor-gamma (PPAR-γ) nuclear translocation. Furthermore, the use of HXTF and PPAR-γ agonists downregulated macrophage M1 polarization-related factors IL-1, IL-6, and TNF-alpha and upregulated M2 polarization-related factors IL-4, IL-10, and TGF-beta 1. Meanwhile, the use of HXTF and PPAR-γ agonists downregulated the SOCS3/JAK2/STAT1 pathway and activated the SOCS1/STAT6/PPAR-γ pathway. These results show that HXTF may reduce intraperitoneal adhesion by inducing macrophage M2 polarization and regulating the SOCS/JAK2/STAT/PPAR-γ pathway.

Maresin1 Alleviates Metabolic Dysfunction in Septic Mice: A 1H NMR-Based Metabolomics Analysis.

Maresin1 (MaR1), a new anti-inflammatory and proresolving lipid mediator, has been proven to exert organ-protective effects in septic animal models. However, the potential mechanisms are still not fully elucidated. In this study, we sought to explore the impact of MaR1 on metabolic dysfunction in cecal ligation and puncture- (CLP-) induced septic mice. We found that MaR1 significantly increased the overall survival rate and attenuated lung and liver injuries in septic mice. In addition, MaR1 markedly reduced the levels of proinflammatory cytokines (TNF-α and IL-6) and alleviated mitochondrial damage. Based on a 1H NMR-based metabolomics analysis, CLP-induced septic mice had increased levels of acetate, pyruvate, and lactate in serum and decreased levels of alanine, aspartate, glutamate, and fumarate in lungs. However, these metabolic disorders, mainly involving energy and amino acid metabolism, can be recovered by MaR1 treatment. Therefore, our results suggest that the protective effects of MaR1 on sepsis could be related to the recovery of metabolic dysfunction and the alleviation of inflammation and mitochondrial damage.

Effects of MicroRNA-592-5p on Hippocampal Neuron Injury Following Hypoxic-Ischemic Brain Damage in Neonatal Mice - Involvement of PGD2/DP and PTGDR.

BACKGROUND/AIMS: This study aimed to explore the effect of microRNA-592-5p (miR-592-5p) on hypoxic-ischemic brain damage (HIBD)-induced hippocampal neuronal injury in a neonatal mouse model relative to the involvement of one target gene, PTGDR, and the PGD2/ DP signaling pathway. METHODS: A total of 30 neonatal mice aged 7 days were randomly selected to establish an HIBD mouse model. Hippocampal neuronal cells were transfected into a control group, a blank group, a negative control (NC) group, an miR-592-5p mimics group, an miR-592-5p inhibitors group, an siRNA-PTGDR group and an miR-592-5p inhibitors + siRNA-PTGDR group. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses were performed to detect the expression levels of miR-592-5p, PTGDR, DP2, Bcl-2 and Bax in tissues and cells. Cell proliferation, cell cycle and apoptosis were detected by MTT assay and flow cytometry, respectively. RESULTS: The expression levels of miR-592-5p and Bcl-2 decreased, while the expression levels of PTGDR, DP2 and Bax increased in the HIBD group. PTGDR is a target gene of miR-592-2p. Compared with the NC and blank groups, the expression levels of PTGDR, DP2 and Bax decreased, while the expression levels of miR-592-5p and Bcl-2 increased in the miR-592-5p mimics group. The siRNA-PTGDR group showed the same trend as that observed in the miR-592-5p mimics group, except with no difference in miR-592-5p expression. The miR-592-5p inhibitors group showed an opposite gene expression trend compared to that in the miR-592-5p mimics group. The S phase of the cell cycle was prolonged, the G1 phase was reduced, proliferation was increased, and the apoptosis rate was decreased in the siRNA-PTGDR and miR-592-5p mimics groups. Opposite trends for cell cycle, proliferation and apoptosis were observed in the miR-592-5p inhibitors group. CONCLUSIONS: Our study suggests that miR-592-5p upregulation protects against hippocampal neuronal injury caused by HIBD by targeting PTGDR and inhibiting the PGD2/DP signaling pathway.

JTC-801 exerts anti-proliferative effects in human osteosarcoma cells by inducing apoptosis.

BACKGROUND: The research of G protein-coupled receptors (GPCRs) is a promising strategy for drug discovery. In cancer therapy, there is a need to discover novel agents that can inhibit proliferation and induce apoptosis in cancer cells. JTC-801 is a novel GPCR antagonist with the function of reversing pain and anxiety symptoms. This study aims to investigate the antitumor effects of JTC-801 on human osteosarcoma cells (U2OS) and elucidate the underlying mechanism. MATERIALS AND METHODS: The Cell Counting Kit-8 assay was used to detect the viability of U2OS cells treated with JTC-801 in vitro. The cell apoptosis was evaluated using a flow cytometry assay with Annexin V-FITC/PI double staining. The inhibitory effect of JTC-801 on invasion and migration of U2OS cells were determined by the Transwell assays. Western blot assay was performed to measure the levels of proteins related to cell apoptosis and its mechanism. RESULTS: The JTC-801 significantly decreased the viability of U2OS cells (p < .05) as a result of its anti-proliferative effect through induction of apoptosis associated with activation of BAX, Caspase-3 and down-regulating BCL-2 expression. The invasive and migratory cells were obviously reduced after JTC-801 treatment (p < .05). Further, the phosphorylated AKT, mTOR and active p70 S6 protein kinase in the PI3K/AKT signaling pathway were obviously lessened in the JTC-801 treated U2OS group (p < .05). CONCLUSIONS: JTC-801 may exert osteosarcoma cell growth inhibition by promoting cell apoptosis, through PI3K/AKT signaling pathway participation.

Short-term air pollution exposure is associated with hospital length of stay and hospitalization costs among inpatients with type 2 diabetes: a hospital-based study.

Air pollution is a risk factor for type 2 diabetes (T2D), exerting heavy economic burden on both individuals and societies. However, there is no apparent report regarding the influence of air pollutants such as particulate matter (PM2.5 and PM10), sulfur dioxide (SO2), carbon monoxide (CO), nitrogen dioxide (NO2), and ozone (O3) on financial burden to individuals and societies suffering from T2D. This study aimed to determine whether short-term (no more than 16 d) air pollution exposure was associated with T2D-related length of stay (LOS) and hospitalization expenses incurred by patients. This investigation examined 2840 T2D patients hospitalized from December 17, 2013 to May 31, 2016 in China. Multiple linear regression analysis was applied to determine the association between short-term (no more than 16 d) ambient air pollution, LOS, and hospitalization expenses, controlling for age, gender, ethnicity, marital status, and weather conditions. Sulfur dioxide (SO2) and carbon monoxide (CO) were significantly positively while nitrogen dioxide (NO2) was negatively associated with presence of T2D, LOS, and expenses. A 10-µg/m3 rise in 16-d (lag 0-15) average concentrations of SO2 and CO prior to hospitalization was correlated with a significant elevation in LOS and elevation in expenses in T2D patients. However, a 10-µg/m3 rise in 16-d average NO2 was associated with marked negative alterations in LOS and hospital costs in T2D patients. Taken together, data demonstrate that exposure to air pollutants impacts differently on LOS and hospitalization costs for T2D patients. This is the first apparent report regarding the correlation between air pollution exposure and clinical costs of T2D in China. It is of interest that air pollutants affected T2D patients differently as evidenced by LOS and clinical expenses where SO2 and CO exhibited a positive adverse relationship in contrast to NO2.