Association of high-density lipoprotein cholesterol with all-cause and cause-specific mortality in a Chinese population of 3.3 million adults: a prospective cohort study.

Background: High-density lipoprotein cholesterol (HDL-C) has been inversely associated with cardiovascular disease (CVD) risk, but recent evidence suggests that extremely high levels of HDL-C are paradoxically related to increased CVD incidence and mortality. This study aimed to comprehensively examine the associations of HDL-C with all-cause and cause-specific mortality in a Chinese population. Methods: The China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART) project included 3,397,547 participants aged 35-75 years with a median follow-up of 3.9 years. Baseline HDL-C levels were measured, and mortality data was ascertained from the National Mortality Surveillance System and Vital Registration of Chinese Center for Disease Control and Prevention. Findings: This study found U-shaped associations of HDL-C with all-cause, cardiovascular and cancer mortality. When compared with the groups with the lowest risk, the adjusted hazard ratios (95% CIs) for HDL-C <30 mg/dL was 1.23 (1.17-1.29), 1.33 (1.23-1.45) and 1.18 (1.09-1.28) for all-cause, CVD and cancer mortality, respectively. For HDL-C >90 mg/dL, the corresponding HR (95% CIs) was 1.10 (1.05-1.15), 1.09 (1.01-1.18) and 1.11 (1.03-1.19). Similar U-shaped patterns were also found in associations of HDL-C with ischemic heart disease, ischemic stroke, and liver cancer. About 3.25% of all-cause mortality could be attributed to abnormal levels of HDL-C. The major contributor to mortality was ischemic heart disease (16.06 deaths per 100,000 persons, 95% UI: 10.30-22.67) for HDL-C <40 mg/dL and esophageal cancer (2.29 deaths per 100,000 persons, 95% UI: 0.57-4.77) for HDL-C >70 mg/dL. Interpretation: Both low and high HDL-C were associated with increased mortality risk. We recommended 50-79 mg/dL as the optimal range of HDL-C among Chinese adults. Individuals with dyslipidemia might benefit from proper management of both low and high HDL-C. Funding: The CAMS Innovation Fund for Medical Science (2021-1-I2M-011), the National High Level Hospital Clinical Research Funding (2022-GSP-GG-4), the Ministry of Finance of China and National Health Commission of China, and the 111 Project from the Ministry of Education of China (B16005), the Program for Guangdong Introducing Innovative and Enterpreneurial Teams (2019ZT08Y481), Sanming Project of Medicine in Shenzhen (SZSM201811096), the Young Talent Program of the Academician Fund, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen (YS-2022-006) and Guangdong Basic and Applied Basic Research Foundation (2023A1515010076 & 2021A1515220173).

Healthy lifestyle, statin, and mortality in people with high CVD risk: A nationwide population-based cohort study.

Objective: To examine the joint association of healthy lifestyles and statin use with all-cause and cardiovascular mortality in high-risk individuals, and evaluate the survival benefits by life expectancy. Methods: During 2015-2021, participants aged 35-75 years were recruited by the China Health Evaluation And risk Reduction through nationwide Teamwork. Based on number of healthy lifestyles related to smoking, alcohol drinking, physical activity, and diet, we categorized them into: very healthy (3-4), healthy (2), and unhealthy (0-1). Statin use was determined by self-report taking statin in last two weeks. Results: Among the 265,209 included participants at high risk, 6979 deaths were observed, including 3236 CVD deaths during a median 3.6 years of follow-up. Individuals taking statin and with a very healthy lifestyle had the lowest risk of all-cause (HR: 0.70; 95 %CI: 0.57-0.87) and cardiovascular mortality (0.56; 0.40-0.79), compared with statin non-users with an unhealthy lifestyle. High-risk participants taking statin and with a very healthy lifestyle had the highest years of life gained (5.90 years at 35-year-old [4.14-7.67; P < 0.001]) compared with statin non-users with an unhealthy lifestyle among high-risk people. And their life expectancy was comparable with those without high risk but with a very healthy lifestyle (4.49 vs. 4.68 years). Conclusion: The combination of preventive medication and multiple healthy lifestyles was associated with lower risk of all-cause and cardiovascular mortality and largest survival benefits. Integrated strategy to improve long-term health for high-risk people was urgently needed.

Associations between Chinese visceral adiposity index and risks of all-cause and cause-specific mortality: A population-based cohort study.

AIM: To determine the associations between the Chinese visceral adiposity index (CVAI) and the risks of all-cause and cause-specific mortality. MATERIALS AND METHODS: A total of 3 916 214 Chinese adults were enrolled in a nationwide population cohort covering all 31 provinces of mainland China. The CVAI was calculated based on age, body mass index, waist circumference, and triglyceride and high-density lipoprotein cholesterol concentrations. We used a Cox proportional hazards regression model to determine the hazard ratios and 95% confidence intervals (CIs) for risk of mortality associated with different CVAI levels. RESULTS: The median follow-up duration was 3.8 years. A total of 86 158 deaths (34 867 cardiovascular disease [CVD] deaths, 29 884 cancer deaths, and 21 407 deaths due to other causes) were identified. In general, after adjusting for potential confounding factors, a U-shaped relationship between CVAI and all-cause mortality was observed by restricted cubic spline (RCS). Compared with participants in CVAI quartile 1, those in CVAI quartile 4 had a 23.0% (95% CI 20.0%-25.0%) lower risk of cancer death, but a 23.0% (95% CI 19.0-27.0) higher risk of CVD death. In subgroup analysis, a J-shaped and inverted U-shaped relationship for all-cause mortality and cancer mortality was observed in the group aged < 60 years. CONCLUSIONS: The CVAI, an accessible indicator reflecting visceral obesity among Chinese adults, has predictive value for all-cause, CVD, and cancer mortality risks. Moreover, the CVAI carries significance in the field of health economics and secondary prevention. In the future, it could be used for early screening purposes.

Human neural stem cells.

'Human neural stem cells' jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research, is the first guideline for human neural stem cells (hNSCs) in China. This standard specifies the technical requirements, test methods, test regulations, instructions for use, labelling requirements, packaging requirements, storage requirements, transportation requirements and waste disposal requirements for hNSCs, which is applicable to the quality control for hNSCs. It was originally released by the China Society for Cell Biology on 30 August 2022. We hope that publication of the guideline will facilitate institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of hNSCs for clinical development and therapeutic applications.

Associations of remnant cholesterol with cardiovascular and cancer mortality in a nationwide cohort.

The health significance of triglyceride-rich lipoproteins, also known as remnant cholesterol, has been increasingly recognized. However, evidence of their associations with cause-specific mortality in the general population was previously insufficient. To explore these associations and their heterogeneities across subgroups, a prospective cohort study was conducted including 3,403,414 community-based participants from ChinaHEART, an ongoing government-funded public health program throughout China, from November 2014 through December 2022. The study assessed mortality risk of all-cause mortality, cardiovascular disease (CVD) mortality (including mortality from ischemic heart diseases (IHD), ischemic stroke (IS), and hemorrhagic stroke (HS), separately), and cancer mortality (including lung cancer, stomach cancer, and liver cancer, separately). During the 4-year follow-up, 23,646 individuals died from CVD (including 8807 from IHD, 3067 from IS, and 5190 from HS), and 20,318 from cancer (including 6208 from lung cancer, 3013 from liver cancer, and 2174 from stomach cancer). Compared with individuals with remnant cholesterol <17.9 mg/dL, multivariable-adjusted mortality hazard ratios (HRs) for individuals with remnant cholesterol ≥27.7 mg/dL were 1.03 (1.00-1.05) for all-cause mortality, 1.17 (1.12-1.21) for CVD (1.19 (1.12-1.27) for IHD mortality, and 1.22 (1.09-1.36) for IS mortality), and 0.90 (0.87-0.94) for all-cancer mortality (0.94 (0.87-1.02) for lung cancer, 0.59 (0.53-0.66) for liver cancer, and 0.73 (0.64-0.83) for stomach cancer). In summary, this study revealed a correlation between increased remnant cholesterol levels and an elevated risk of cardiovascular disease mortality, as well as a reduced risk of mortality for certain types of cancer.

Function and regulation of miR-186-5p, miR-125b-5p and miR-1260a in chordoma.

BACKGROUND: The function and regulation of miRNAs in progression of chordoma were unclear. METHODS: Five miRNAs were identified by the machine learning method from the miRNA expression array. CCk-8 assay, EDU assay, wound healing migration assay, and trans-well assay were used to reveal the effect of the miRNAs in chordoma cell lines. Moreover, bioinformation analysis and the mRNA expression array between the primary chordomas and recurrent chordomas were used to find the target protein genes of miRNAs. Furthermore, qRT-PCR and luciferase reporter assay were used to verify the result. RESULTS: miR-186-5p, miR-30c-5p, miR-151b, and miR-125b-5p could inhibit proliferation, migration, and invasion of chordoma while miR-1260a enhances proliferation, migration, and invasion of chordoma. Recurrent chordoma has a worse disease-free outcome than the primary chordoma patients. AMOT, NPTX1, RYR3, and P2RX5 were the target protein mRNAs of miR-186-5p; NPTX1 was the target protein mRNAs of miR-125b-5p; and AMOT and TNFSF14 were the target protein mRNAs of miR-1260a. CONCLUSIONS: miR-186-5p, miR-125b-5p, miR-1260a, and their target protein mRNAs including AMOT, NPTX1, RYR3, P2RX5, TNFSF14 may be the basement of chordoma research.

Associations of long-term fine particulate matter exposure with all-cause and cause-specific mortality: results from the ChinaHEART project.

Background: The chronic effects of fine particulate matter (PM2.5) at high concentrations remains uncertain. We aimed to examine the relationship of long-term PM2.5 exposure with all-cause and the top three causes of death (cardiovascular disease [CVD], cancer, and respiratory disease), and to analyze their concentration-response functions over a wide range of concentrations. Methods: We enrolled community residents aged 35-75 years from 2014 to 2017 from all 31 provinces of the Chinese Mainland, and followed them up until 2021. We used a long-term estimation dataset for both PM2.5 and O3 concentrations with a high spatiotemporal resolution to assess the individual exposure, and used Cox proportional hazards models to estimate the associations between PM2.5 and mortalities. Findings: We included 1,910,923 participants, whose mean age was 55.6 ± 9.8 years and 59.4% were female. A 10 µg/m3 increment in PM2.5 exposure was associated with increased risk for all-cause death (hazard ratio 1.02 [95% confidence interval 1.012-1.028]), CVD death (1.024 [1.011-1.037]), cancer death (1.037 [1.023-1.052]), and respiratory disease death (1.083 [1.049-1.117]), respectively. Long-term PM2.5 exposure nonlinearly related with all-cause, CVD, and cancer mortalities, while linearly related with respiratory disease mortality. Interpretation: The overall effects of long-term PM2.5 exposure on mortality in the high concentration settings are weaker than previous reports from settings of PM2.5 concentrations < 35 µg/m³. The distinct concentration-response relationships of CVD, cancer, and respiratory disease mortalities could facilitate targeted public health efforts to prevent death caused by air pollution. Funding: The Chinese Academy of Medical Sciences Innovation Fund for Medical Science, the National High Level Hospital Clinical Research Funding, the Ministry of Finance of China and National Health Commission of China, the 111 Project from the Ministry of Education of China.

Correlations between serum levels of microRNA-148a-3p and microRNA-485-5p and the progression and recurrence of prostate cancer.

BACKGROUND: Unpredicted postoperative recurrence of prostate cancer, one of the most common malignancies among males worldwide, has become a prominent issue affecting patients after treatment. Here, we investigated the correlation between the serum miR-148a-3p and miR-485-5p expression levels and cancer recurrence in PCa patients, aiming to identify new biomarkers for diagnosis and predicting postoperative recurrence of prostate cancer. METHODS: A total of 198 male PCa cases treated with surgery, postoperative radiotherapy, and chemotherapy were involved in the presented study. Serum levels of miR-148a-3p and miR-485-5p were measured before the initial operation for the involved cases, which were then followed up for two years to monitor the recurrence of cancer and to split the cases into recurrence and non-recurrence groups. Comparison of the relative expressions of serum miR-148a-3p and miR-485-5p were made and related to other clinic pathological features. RESULTS: Pre-surgery serum levels of miR-148a-3p in patients with TNM stage cT1-2a prostate cancer (Gleason score < 7) were significantly lower (P < 0.05) than levels in patients with TNM Classification of Malignant Tumors (TNM) stage cT2b and higher prostate cancer (Gleason score ≥ 7). pre-surgery serum levels of miR-485-5p in patients with TNM stage cT1-2a prostate cancer (Gleason score < 7) were significantly higher (P < 0.05) than in patients with TNM stage cT2b and higher cancer (Gleason score ≥ 7). Serum miR-148a-3p level in recurrence group is higher than the non-recurrence group (P < 0.05) while serum miR-485-5p level in recurrence group is lower than non-recurrence group (P < 0.05). ROC curve analysis showed the AUCs of using miR-148a-3p, miR-485-5p, and combined detection for predicting recurrence of prostate cancer were 0.825 (95% CI 0.765-0.875, P < 0.0001), 0.790 (95% CI 0.726-0.844, P < 0.0001), and 0.913 (95% CI 0.865-0.948, P < 0.0001). CONCLUSION: Pre-surgery serum miR-148a-3p level positively correlates while miR-485-5p level negatively correlates with prostate cancer's progressing and postoperative recurrence. Both molecules show potential to be used for predicting postoperative recurrence individually or combined.

Ectoderm-derived frontal bone mesenchymal stem cells promote traumatic brain injury recovery by alleviating neuroinflammation and glutamate excitotoxicity partially via FGF1.

BACKGROUND: Traumatic brain injury (TBI) leads to cell and tissue impairment, as well as functional deficits. Stem cells promote structural and functional recovery and thus are considered as a promising therapy for various nerve injuries. Here, we aimed to investigate the role of ectoderm-derived frontal bone mesenchymal stem cells (FbMSCs) in promoting cerebral repair and functional recovery in a murine TBI model. METHODS: A murine TBI model was established by injuring C57BL/6 N mice with moderate-controlled cortical impact to evaluate the extent of brain damage and behavioral deficits. Ectoderm-derived FbMSCs were isolated from the frontal bone and their characteristics were assessed using multiple differentiation assays, flow cytometry and microarray analysis. Brain repairment and functional recovery were analyzed at different days post-injury with or without FbMSC application. Behavioral tests were performed to assess learning and memory improvements. RNA sequencing analysis, immunofluorescence staining, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to examine inflammation reaction and neural regeneration. In vitro co-culture analysis and quantification of glutamate transportation were carried out to explore the possible mechanism of neurogenesis and functional recovery promoted by FbMSCs. RESULTS: Ectoderm-derived FbMSCs showed fibroblast like morphology and osteogenic differentiation capacity. FbMSCs were CD105, CD29 positive and CD45, CD31 negative. Different from mesoderm-derived MSCs, FbMSCs expressed the ectoderm-specific transcription factor Tfap2ß. TBI mice showed impaired learning and memory deficits. Microglia and astrocyte activation, as well as neural damage, were significantly increased post-injury. FbMSC application ameliorated the behavioral deficits of TBI mice and promoted neural regeneration. RNA sequencing analysis showed that signal pathways related to inflammation decreased, whereas those related to neural activation increased. Immunofluorescence staining and qRT-PCR data revealed that microglial activation and astrocyte polarization to the A1 phenotype were suppressed by FbMSC application. In addition, FGF1 secreted from FbMSCs enhanced glutamate transportation by astrocytes and alleviated the cytotoxic effect of excessive glutamate on neurons. CONCLUSIONS: Ectoderm-derived FbMSC application significantly alleviated neuroinflammation, brain injury, and excitatory toxicity to neurons, improved cognition and behavioral deficits in TBI mice. Therefore, ectoderm-derived FbMSCs could be ideal therapeutic candidates for TBI which mostly affect cells from the same embryonic origins as FbMSCs.

Bone marrow hematopoiesis drives multiple sclerosis progression.

Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system (CNS). Bone marrow hematopoietic stem and progenitor cells (HSPCs) rapidly sense immune activation, yet their potential interplay with autoreactive T cells in MS is unknown. Here, we report that bone marrow HSPCs are skewed toward myeloid lineage concomitant with the clonal expansion of T cells in MS patients. Lineage tracing in experimental autoimmune encephalomyelitis, a mouse model of MS, reveals remarkable bone marrow myelopoiesis with an augmented output of neutrophils and Ly6Chigh monocytes that invade the CNS. We found that myelin-reactive T cells preferentially migrate into the bone marrow compartment in a CXCR4-dependent manner. This aberrant bone marrow myelopoiesis involves the CCL5-CCR5 axis and augments CNS inflammation and demyelination. Our study suggests that targeting the bone marrow niche presents an avenue to treat MS and other autoimmune disorders.

Role of Immune and Inflammatory Mechanisms in Stroke: A Review of Current Advances.

Stroke accounts for a large proportion of morbidity and mortality burden in China. Moreover, there is a high prevalence of the leading risk factors for stroke, including hypertension and smoking. Understanding the underlying mechanisms and developing effective therapeutic interventions for patients with stroke is a key imperative. The pathophysiology of stroke involves a complex interplay between the immune and inflammatory mechanisms. Focal brain inflammation triggered by neuronal cell death and the release of factors such as damage-associated molecular patterns can further exacerbate neuronal injury; in addition, impairment of the blood-brain barrier, oxidative stress, microvascular dysfunction, and brain edema cause secondary brain injury. Immune cells, including microglia and other infiltrating inflammatory cells, play a key role in triggering focal and global brain inflammation. Anti-inflammatory therapies targeting the aforementioned mechanisms can alleviate primary and secondary brain injury in the aftermath of a stroke. Further experimental and clinical studies are required to explore the beneficial effects of anti-inflammatory drugs in stroke.

Wild-Type p53-Induced Phosphatase 1 Plays a Positive Role in Hematopoiesis in the Mouse Embryonic Head.

The first adult repopulating hematopoietic stem cells (HSCs) are found in the aorta-gonad-mesonephros (AGM) region, which are produced from hemogenic endothelial cells. Embryonic head is the other site for HSC development. Wild-type p53-induced phosphatase 1 (Wip1) is a type-2Cδ family serine/threonine phosphatase involved in various cellular processes such as lymphoid development and differentiation of adult HSCs. Most recently, we have shown that Wip1 modulates the pre-HSC maturation in the AGM region. However, it is not clear whether Wip1 regulates hematopoiesis in the embryonic head. Here we reported that disruption of Wip1 resulted in a decrease of hematopoietic progenitor cell number in the embryonic head. In vivo transplantation assays showed a reduction of HSC function after Wip1 ablation. We established that Wip1 deletion reduced the frequency and cell number of microglia in the embryonic head. Further observations revealed that Wip1 absence enhanced the gene expression of microglia-derived pro-inflammatory factors. Thus, it is likely that Wip1 functions as a positive regulator in HSC development by regulating the function of microglia in the embryonic head.

Transfer characteristic of fluorine from atmospheric dry deposition, fertilizers, pesticides, and phosphogypsum into soil.

Fluorine (F) is widely dispersed in the environment and frequently used in industry and agriculture with a high migration ability. Thus, it is essential to understand the leaching characteristic of F in soil from industry and agriculture sources. Several sources of F pollutants in soil, including fertilizers, pesticides, phosphogypsum, and atmospheric deposition, were selected to investigate leaching characteristics of F in soil by leaching experiments. The addition of phosphate fertilizer and compound fertilizer (N:P:K = 20:10:15) enhanced the leachability of F in soil and the proportion of F leached out from soil treated by these fertilizers were 0.25% and 0.24%, respectively. However, unanticipated lower leachability of F appeared in compound fertilizer (N:P:K = 17:17:17), nitrogen fertilizer, dipterex, fluoroglycofen, fluopimomide, simulative dry deposition (YF3), and phosphogypsum loaded soils compared with additive-absent treatment. Although phosphogysum had a high F concentration, minimum proportion of F released (0.18%) was observed in phosphogypsum-coverd soil. The amounts of F leaching-out from surface soils (0-25 cm) treated with nitrogen fertilizer decreased 1.03 kg ha-1 comparing with blank control. Soil with phosphate fertilizer leached 5.47 kg F ha-1 a year, having the highest environment risk to deeper soil and groundwater. However, phosphogypsum and dry deposition of airbone F chemical had few effects on F leaching in soil. F-containing materials from agricultural process may leach more F from surface soils than industrial sources.

Identification of a potent antagonist of smoothened in hedgehog signaling.

BACKGROUND: Hedgehog signaling is essential to the regulation of embryonic development, tissue homeostasis, and stem cell self-renewal, making it a prime target for developing cancer therapeutics. Given the close link between aberrant Hedgehog signaling and cancers, many small molecular compounds have been developed to inhibit Smoothened, a key signal transducer of this pathway, for treating cancer and several such compounds have been approved by the United States Food and Drug Administration (GDC-0449 and LDE-225). However, acquired drug resistance has emerged as an important obstacle to the effective use of these first generation Hedgehog pathway blockers. Thus, new Smoothened inhibitors that can overcome such resistance is an urgent need going forward. RESULTS: We established the Smoothened/ßarrestin2-GFP high-throughput screening platform based on the mechanistic discovery of Hedgehog signaling pathway, and discovered several active small molecules targeting Smoothened including 0025A. Here we show that 0025A can block the translocation of ßarrestin2-GFP to Smoothened, displace Bodipy-cyclopamine binding to wild-type Smoothened or mutant Smoothened-D473H, reduce the accumulation of Smo on primary cilia and the expression of Gli upon Hedgehog stimulation. In addition, we show that 0025A can effectively suppress hair follicle morphogenesis and hair growth in mice. CONCLUSIONS: Our results demonstrate that 0025A is a potent antagonist targeting Smoothened wild-type and mutant receptors in the Hedgehog signaling pathway and may provide a new therapy for refractory cancers.

Innovative technology of municipal wastewater treatment for rapid sludge sedimentation and enhancing pollutants removal with nano-material.

This study aims to develop a novel technology for actual municipal wastewater treatment to achieve rapid sludge sedimentation and high pollutants removal efficiency. The SBRs were modified and operated with periodic addition of 20 µL·L-1 nanofloc®. Results revealed that NH4+-N and chemical oxygen demand (COD) was efficiently removed in both laboratory- and pilot-scale SBRs, and the average removal efficiency of total nitrogen (TN) and total phosphorus (TP) was as high as 72.43 ± 2.66% and 98.63 ± 0.74%, respectively, with hydraulic retention time (HRT) of 8 h. Besides, the sludge volume index at 30 min (SVI30) was only 40.06 ± 1.99 mL·g-1, comparable with aerobic granular sludge (AGS). This novel technology could be proposed as a competitive method to upgrade, reconstruct and delay the expansion of municipal wastewater treatment plants (WWTPs) due to its rapid sludge sedimentation and efficient pollutants removal with low HRT.

Neuroblast senescence in the aged brain augments natural killer cell cytotoxicity leading to impaired neurogenesis and cognition.

Normal aging is accompanied by escalating systemic inflammation. Yet the potential impact of immune homeostasis on neurogenesis and cognitive decline during brain aging have not been previously addressed. Here we report that natural killer (NK) cells of the innate immune system reside in the dentate gyrus neurogenic niche of aged brains in humans and mice. In situ expansion of these cells contributes to their abundance, which dramatically exceeds that of other immune subsets. Neuroblasts within the aged dentate gyrus display a senescence-associated secretory phenotype and reinforce NK cell activities and surveillance functions, which result in NK cell elimination of aged neuroblasts. Genetic or antibody-mediated depletion of NK cells leads to sustained improvements in neurogenesis and cognitive function during normal aging. These results demonstrate that NK cell accumulation in the aging brain impairs neurogenesis, which may serve as a therapeutic target to improve cognition in the aged population.

Cellular and molecular imaging for stem cell tracking in neurological diseases.

Stem cells (SCs) are cells with strong proliferation ability, multilineage differentiation potential and self-renewal capacity. SC transplantation represents an important therapeutic advancement for the treatment strategy of neurological diseases, both in the preclinical experimental and clinical settings. Innovative and breakthrough SC labelling and tracking technologies are widely used to monitor the distribution and viability of transplanted cells non-invasively and longitudinally. Here we summarised the research progress of the main tracers, labelling methods and imaging technologies involved in current SC tracking technologies for various neurological diseases. Finally, the applications, challenges and unresolved problems of current SC tracing technologies were discussed.

A role for macrophages in hematopoiesis in the embryonic head.

Along with the aorta-gonad-mesonephros region, the head is a site of hematopoietic stem and progenitor cell (HS/PC) development in the mouse embryo. Macrophages are present in both these embryonic hemogenic sites, and recent studies indicate a functional interaction of macrophages with hematopoietic cells as they are generated in the aorta. Whereas brain macrophages or "microglia" are known to affect neuronal patterning and vascular circuitry in the embryonic brain, it is unknown whether macrophages play a role in head hematopoiesis. Here, we characterize head macrophages and examine whether they affect the HS/PC output of the hindbrain-branchial arch (HBA) region of the mouse embryo. We show that HBA macrophages are CD45+F4/80+CD11b+Gr1- and express the macrophage-specific Csf1r-GFP reporter. In the HBA of chemokine receptor-deficient (Cx3cr1-/-) embryos, a reduction in erythropoiesis is concomitant with a decrease in HBA macrophage percentages. In cocultures, we show that head macrophages boost hematopoietic progenitor cell numbers from HBA endothelial cells > twofold, and that the proinflammatory factor tumor necrosis factor-α is produced by head macrophages and influences HBA hematopoiesis in vitro. Taken together, head macrophages play a positive role in HBA erythropoiesis and HS/PC expansion and/or maturation, acting as microenvironmental cellular regulators in hematopoietic development.

lncRNA HCG11 regulates cell progression by targeting miR-543 and regulating AKT/mTOR pathway in prostate cancer.

Prostate cancer (PCa) is a common cancer worldwide, which mostly occurs in males over the age of 50. Accumulating evidence have determined that long non-coding RNA/microRNA (lncRNA/miRNA) axis plays a critical role in cell progression of cancers, including PCa. However, the pathogenesis of PCa has not been fully indicated. In this study, quantitative real-time polymerase chain reaction was used to detect the expression of HCG11 and miR-543. Western blot was applied to measure the protein expression of proliferating cell nuclear antigen, cleavage-caspase 3 (cle-caspase 3), N-cadherin, E-cadherin, GAPDH, P-AKT, AKT, p-mTOR, and mTOR. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), transwell invasion, and transwell migration assay were used to detect cell proliferation, invasion, and migration, respectively. The function and mechanism of lncRNA HCG11 were confirmed in PCa cell and xenograft mice models. Luciferase assay indicated that miR-543 was a target miRNA of HCG11. Further investigation revealed that overexpression of HCG11 inhibited cell proliferation, invasion, and migration, whereas induced cell apoptosis by regulating miR-543 expression in vitro and in vivo. More than that, lncRNA HCG11 inhibited phosphoinositide-3 kinase/protein kinaseB (PI3K/AKT) signaling pathway to suppress PCa progression. Our data showed the overexpression of HGC11-inhibited PI3K/AKT signaling pathway by downregulating miR-543 expression, resulting in the suppression of cell growth in PCa. This finding proved a new regulatory network in PCa and provided a novel therapeutic target of PCa.