Deubiquitinase Mysm1 regulates neural stem cell proliferation and differentiation by controlling Id4 expression.

Neural stem cells (NSCs) are critical for brain development and maintenance of neurogenesis. However, the molecular mechanisms that regulate NSC proliferation and differentiation remain unclear. Mysm1 is a deubiquitinase and is essential for the self-renewal and differentiation of several stem cells. It is unknown whether Mysm1 plays an important role in NSCs. Here, we found that Mysm1 was expressed in NSCs and its expression was increased with age in mice. Mice with Mysm1 knockdown by crossing Mysm1 floxed mice with Nestin-Cre mice exhibited abnormal brain development with microcephaly. Mysm1 deletion promoted NSC proliferation and apoptosis, resulting in depletion of the stem cell pool. In addition, Mysm1-deficient NSCs skewed toward neurogenesis instead of astrogliogenesis. Mechanistic investigations with RNA sequencing and genome-wide CUT&Tag analysis revealed that Mysm1 epigenetically regulated Id4 transcription by regulating histone modification at the promoter region. After rescuing the expression of Id4, the hyperproliferation and imbalance differentiation of Mysm1-deficient NSCs was reversed. Additionally, knockdown Mysm1 in aged mice could promote NSC proliferation. Collectively, the present study identified a new factor Mysm1 which is essential for NSC homeostasis and Mysm1-Id4 axis may be an ideal target for proper NSC proliferation and differentiation.

Short-term association of fine particulate matter and its constituents with oxidative stress, symptoms and quality of life in patients with allergic rhinitis: A panel study.

BACKGROUND: Short-term exposure to fine particulate matter (PM2.5) and its specific constituents might exacerbate allergic rhinitis (AR) conditions. However, the evidence is still inconclusive. METHOD: We conducted a panel study of 49 patients diagnosed with AR > 1 year prior to the study in Taiyuan, China, to investigate associations of individual exposure to PM2.5 and its constituents with oxidative parameters, symptoms, and quality of life among AR patients. All participants underwent repeated assessments of health and PM exposure at 4 time points in both the heating and nonheating seasons from June 2017 to January 2018. AR patients' oxidative parameters were assessed using nasal lavage, and their subjective symptoms and quality of life were determined through in-person interviews using a structured questionnaire. Short-term personal exposure to PM2.5 and its constituents was estimated using the time-microenvironment-activity pattern and data from the nearest air sampler, respectively. We applied mixed-effects regression models to estimate the short-term effects of PM2.5 and its constituents. RESULTS: The results showed that exposure to PM2.5 and its constituents, including BaP, PAHs, SO42-, NH4+, V, Cr, Cu, As, Se, Cd, and Pb, was significantly associated with increased oxidative stress, as indicated by an increase in the malondialdehyde (MDA) index. Exposure to PM2.5 and its components (V, Mn, Fe, Zn, As, and Se) was associated with decreased antioxidant activity, as indicated by a decrease in the superoxide dismutase (SOD) index. Additionally, increased visual analog scale (VAS) and rhinoconjunctivitis quality of life questionnaire (RQLQ) scores indicated that exposure to PM2.5 and its constituents exacerbated inflammatory symptoms and affected quality of life in AR patients. CONCLUSION: Exposure to PM2.5 and specific constituents, could exacerbate AR patients' inflammatory symptoms and adversely affect their quality of life in the heavily industrialized city of Taiyuan, China. These findings may have potential biological and policy implications.

A Novel Sample-to-Answer Visual Nucleic Acid Detection System for Adenovirus Detection.

Human adenoviruses (HAdVs) are common viruses that can cause local outbreaks in schools, communities and military camps, posing a huge threat to public health. An ideal POCT device for adenovirus detection in resource-limited settings is critical to control the spread of the virus. In this study, we developed an integrated and electricity-independent sample-to-answer system that can complete nucleic acid extraction, amplification, and detection at room temperature. This system is suitable for field and on-site detection because of its rapidity, sensitivity, lack of contamination, and lack of requirements of high-precision instruments and skilled technicians. It consists of two separate modules, ALP FINA (alkaline lysis with the paper-based filtration isolation of nucleic acid) and SV RPA (sealed and visual recombinase polymerase amplification). The extraction efficiency of ALP FINA can reach 48 to 84%, which is close to that of the conventional centrifuge column. The detection sensitivity of SV RPA is close to 10 copies/µL of AdvB and AdvE without aerosol contamination after repeated operations. When SV RPA was applied to the detection of nasopharyngeal swab samples of 19 patients who were infected with AdvB or AdvE as well as 10 healthy volunteers, its sensitivity and specificity reached 100%, respectively. IMPORTANCE HAdV infections are readily transmittable and, in some instances, highly contagious. Early and rapid diagnosis is essential for disease control. In this work, we developed a portable, disposable, and modularized sample-to-answer detection system for AdvB and AdvE, which rendered the entire test to be completely independent of electricity and other laboratory infrastructure. Thus, this detection system can be applied in resource-limited settings, and it has the potential to be further developed as an early diagnosis method in the field.

Effects of subchronic exposure of perfluorooctane sulfonate on cognitive function of mice and its mechanism.

Perfluorooctane sulfonate (PFOS) is an emerging persistent organic pollutant, and its potential impact on cognitive function remains unclear. We adopted the C57BL/6J mouse model to investigate the effect of PFOS on cognitive function, as well as the underlying mechanisms. Subchronic exposure was performed by administering PFOS via drinking water for 6 months (at doses of 0, 0.2, and 2.0 mg/kg/day), starting from 10.5 months old. The object recognition ability was tested at 2, 4, and 6 months of exposure, and spatial learning and memory were assessed at endpoint. The apoptosis of neurons and astrocytes in the cortex and hippocampus was analyzed, as well as the potential apoptotic signaling pathways. Our results showed that exposure to PFOS for 6 months caused a decrease in object recognition ability and a decline in learning and spatial memory. PFOS selectively increased apoptosis in neurons of the cerebral cortex and specifically activated the endoplasmic reticulum stress PERK/CHOP signaling pathway. In conclusion, our results confirmed that subchronic exposure to PFOS can lead to cognitive impairment in mice, which might be closely associated with the specific activation of an endoplasmic reticulum stress-induced pro-apoptosis pathway in the cerebral cortex neurons.

The screening and expression of polysaccharide deacetylase from Caulobacter crescentus and its function analysis.

The bacterium Caulobacter crescentus secretes an adhesive polysaccharide called holdfast, which is the known strongest underwater adhesive in nature. The deacetylase encoded by hfs (holdfast synthesis) H gene is a key factor affecting the adhesion of holdfast. Its structure and function are not yet clear, and whether other polysaccharide deacetylases exist in C. crescentus is still unknown. The screening of both HfsH and its structural analogue as well as their purification from the artificial expression products of Escherichia coli is the first step to clarify these questions. Here, we determined the conserved domains of HfsH via sequence alignment among carbohydrate esterase family 4 enzymes and screened out its structural analogue (CC_2574) in C. crescentus. The recombinant HfsH and CC_2574 were effectively expressed in E. coli. Both of them were purified by chromatography from their corresponding productions in E. coli and were then functionally analyzed. The results indicated that a high deacetylase activity (61.8 U/mg) was observed in recombinant HfsH but not in CC_2574, which suggesting that HfsH might be the irreplaceable gene mediating adhesion of holdfast in C. crescentus. Moreover, the divalent metal ions Zn2+ , Mg2+ , and Mn2+ could promote the activity of recombinant HfsH at the concentration from 0.05 to 1 mM, but inhibit its activity when the concentration exceeds 1 mM. In sum, our study first realized the artificial production of polysaccharide deacetylase HfsH and its structural analogue, and further explored their functions, both of which laid the foundation for the development of new adhesive materials.

The Regulation of Microglial Cell Polarization in the Tumor Microenvironment: A New Potential Strategy for Auxiliary Treatment of Glioma-A Review.

Glioma is the most common primary tumor of the central nervous system and normally should be treated by synthetic therapy, mainly with surgical operation assisted by radiotherapy and chemotherapy; however, the therapeutic effect has not been satisfactory, and the 5-year survival rates of anaplastic glioma and glioblastoma are 29.7% and 5.5%, respectively. To identify a more efficient strategy to treat glioma, in recent years, the influence of the inflammatory microenvironment on the progression of glioma has been studied. Various immunophenotypes exist in microglial cells, each of which has a different functional property. In this review, references about the phenotypic conversion of microglial cell polarity in the microenvironment were briefly summarized, and the differences in polarized state and function, their influences on glioma progression under different physiological and pathological conditions, and the interactive effects between the two were mainly discussed. Certain signaling molecules and regulatory pathways involved in the microglial cell polarization process were investigated, and the feasibility of targeted regulation of microglial cell conversion to an antitumor phenotype was analyzed to provide new clues for the efficient auxiliary treatment of neural glioma.

Air Pollution Health Impact Monitoring and Health Risk Assessment Technology and Its Application - China, 2006-2019.

Air pollution is a significant risk factor contributing to the burden of disease in China. Health risk assessment and management are important to reduce the impact of air pollution on public health. To help formulate standardized health risk assessment techniques, a series of studies were conducted from 2006 to 2019. Through systematic review, study of molecular mechanisms, epidemiological investigation, and health effect monitoring, the overall project established a monitoring and evaluation indicator system, a comprehensive information platform, software for automatic data cleaning, and standardized health risk assessment techniques. Technical specifications have been issued by the National Health Commission for promoting health risk assessments across China. This paper introduces the project, the research approach, its main research accomplishments, innovations, and public health significance, and describes directions for further research.

Research Progress in the Application of Exosomes in Immunotherapy.

Exosomes are nanoscale extracellular vesicles (EVs), which are present in all body fluids tested. They are secreted by a variety of cells including macrophages, dendritic cells, mast cells, granulocytes, lymphocytes, and tumor cells. Exosomes secreted by different cells have different biological components and functional characteristics and play an important role in many pathophysiological activities. Recent studies have revealed that exosomes can regulate the occurrence and development of inflammatory immune diseases and tumors by transmitting their unique proteins, lipids, and nucleic acids as signaling molecules to other cells. Exosomes serve as a novel class of diagnostic biomarkers and drug delivery systems with promising applications in immunotherapy, particularly because breakthroughs in nanotechnology have led to the development and exploration of engineered exosomes for immunotargeted therapies. Therefore, here we review the progress being made on the application of exosomes in immunotherapy and its multiple regulatory mechanisms and explore the potential application of exosomes in immunotherapy in the future.

The association between urine elements and fasting glucose levels in a community-based elderly people in Beijing.

Epidemiological studies have demonstrated that various kinds of urinary element concentrations were different between healthy, prediabetes, and diabetes patients. Meanwhile, many studies have explored the relationship between element concentration and fasting blood glucose (FBG), but the association between joint exposure to co-existing elements and FBG level has not been well understood. The study explored the associations of joint exposure to co-existing urinary elements with FBG level in a cross-sectional design. 275 retired elderly people were recruited from Beijing, China. The questionnaire survey was conducted, and biological samples were collected. The generalized linear model (GLM) and two-phase Bayesian kernel machine regression (BKMR) model were used to perform in-depth association analysis between urinary elements and FBG. The GLM analysis showed that Zn, Sr, and Cd were significantly correlated with the FBG level, under control potential confounding factors. The BKMR analysis demonstrated 8 elements (Zn, Se, Fe, Cr, Ni, Cd, Mn, and Al) had a higher influence on FBG (posterior inclusion probabilities > 0.1). Further intensive analyses result of the BKMR model indicated that the overall estimated exposure of 8 elements was positively correlated with the FBG level and was statistically significant when all creatinine-adjusted element concentrations were at their 65th percentile. Meanwhile, the BKMR analysis showed that Cd and Zn had a statistically significant association with FBG levels when other co-existing elements were controlled at different levels (25th, 50th, or 75th percentile), respectively. The results of the GLM and BKMR model were inconsistent. The BKMR model could flexibly calculate the joint exposure to co-existing elements, evaluate the possible interaction effects and nonlinear correlations. The meaningful conclusions were found that it was difficult to get by traditional methods. This study will provide methodological reference and experimental evidence for the association between joint exposure to co-existing elements and FBG in elderly people.

MiR-200c-3p inhibits LPS-induced M1 polarization of BV2 cells by targeting RIP2.

BACKGROUND: Microglia are important immune cells, which can be induced by lipopolysaccharide (LPS) into M1 phenotype that express pro-inflammatory cytokines. Some studies have shown that microRNAs play critical roles in microglial activation. OBJECTIVE: This study was designed to investigate the role of miR-200c-3p in regulating inflammatory responses of LPS-treated BV2 cells. METHODS: The expression of miR-200c-3p in BV2 cells was detected by real-time PCR. Receptor-interacting protein 2 (RIP2) was predicted as a target gene of miR-200c-3p. Their relationship was verified by dual-luciferase reporter assay. The function of miR-200c-3p and RIP2 in microglial polarization and NF-κB signaling was further evaluated. RESULTS: LPS treatment reduced miR-200c-3p expression in a dose-dependent and time-dependent manner in BV2 cells. LPS treatment increased the expression of M1 phenotype markers inducible nitric oxide synthase (iNOS) and major histocompatibility complex class (MHC)-II, promoted the release of pro-inflammatory cytokines interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α, and enhanced the nuclear translocation and phosphorylation of nuclear factor-kappaB (NF-κB) p65. Reversely, miR-200c-3p mimics down-regulated the levels of these inflammatory factors. Furthermore, RIP2 was identified to be a direct target of miR-200c-3p. RIP2 knockdown had a similar effect to miR-200c-3p mimics. Overexpression of RIP2 eliminated the inhibitory effect of miR-200c-3p on LPS-induced M1 polarization and NF-κB activation in BV2 cells. CONCLUSIONS: MiR-200c-3p mimics suppressed LPS-induced microglial M1 polarization and NF-κB activation by targeting RIP2. MiR-200c-3p/RIP2 might be a potential therapeutic target for the treatment of neuroinflammation-associated diseases.

TRIM24 promotes stemness and invasiveness of glioblastoma cells via activating Sox2 expression.

BACKGROUND: Glioblastoma stem cells (GSCs) are a subpopulation of glioblastoma (GBM) cells that are critical for tumor invasion and treatment resistance. However, little is known about the function and mechanism of tripartite motif-containing 24 (TRIM24) in GSCs. METHODS: Immunofluorescence, flow cytometry, and western blot analyses were used to evaluate TRIM24 and cluster of differentiation (CD)133 expression profiles in GBM surgical specimens and GSC tumorspheres. Different TRIM24 expression levels in patients' tumors, as measured by both immunohistochemistry and western blot, were related to their corresponding MRI data. Wound healing, Matrigel invasion, and xenograft immunohistochemistry were conducted to determine GBM cell invasion. RESULTS: We identified that TRIM24 was coexpressed with CD133 and Nestin in GBM tissues and tumorsphere cells. Limiting dilution assays and xenotransplantation experiments illustrated that knockdown of TRIM24 expression reduced GSC self-renewal capacity and invasive growth. TRIM24 expression levels were positively associated with the volumes of peritumoral T2 weighted image abnormality. Rescue experiments indicated TRIM24 participation in GBM infiltrative dissemination. Chromatin immunoprecipitation, reporter gene assay, PCR, western blot, and immunohistochemistry demonstrated that TRIM24 activated the expression of the pluripotency transcription factor sex determining region Y-box 2 (Sox2) to regulate GBM stemness and invasion in vitro and in vivo. Finally, the close relationship between TRIM24 and Sox2 was validated by testing samples enrolled in our study and exploring external databases. CONCLUSIONS: Our findings uncover essential roles of the TRIM24-Sox2 axis in GBM stemness and invasiveness, suggesting TRIM24 as a potential target for effective GBM management.

PM2.5 exposure induces vascular dysfunction via NO generated by iNOS in lung of ApoE-/- mouse.

PM2.5 exposure exacerbates cardiovascular diseases via oxidative stress and inflammation, the detailed mechanism of which is unclear. In this study, the effects of oxidative stress and inflammation, as well as vascular structure and function were studied by multiple PM2.5 exposure model of ApoE-/- mice. The results indicated that NO produced by iNOS not cNOS might play important roles in inducing vascular dysfunction after PM2.5 exposure. The occurrence order and causality among NO, other oxidative stress indicators and inflammation is explored by single PM2.5 exposure. The results showed that NO generated by iNOS occurred earlier than that of other oxidative stress indicators, which was followed by the increased inflammation. Inhibition of NOS could effectively block the raise of NO, oxidative stress and inflammation after PM2.5 exposure. All in all, we firstly confirmed that NO was the initiation factor of PM2.5 exposure-induced oxidative stress, which led to inflammation and the following vascular dysfunction.

PM2.5 aggravates diabetes via the systemically activated IL-6-mediated STAT3/SOCS3 pathway in rats' liver.

PM2.5 exposure aggravates type 2 diabetes, in which inflammatory factors play an important role. In this study, we aimed to explore the mechanisms responsible for aggravating diabetes after PM2.5 exposure, and study the roles of inflammatory factors in insulin-resistant type 2 diabetes. Our study indicated that short-time PM2.5 exposure enhances insulin resistance in type 2 diabetic rats and significantly raises inflammatory factors, including IL-6, TNF-α, and MCP-1, in lungs. However, we found that of these inflammatory factors only IL-6 levels are elevated in blood, liver, adipose tissue, and macrophages, but not in skeletal muscle. IL-6 induced activation of the STAT3/SOCS3 pathway in liver, but not other downstream pathways including STAT1, ERK1/2, and PI3K. Both STAT3 inhibition and IL-6 neutralization effectively alleviated the disorders of glucose metabolism after PM2.5 exposure. Taken together, this suggests that the systemic increase in IL-6 may play an important role in the deterioration of the type 2 diabetes via IL-6/STAT3/SOCS3 pathway in liver after short-time exposure to PM2.5. Besides, we unexpectedly found a stronger resistance to the PM2.5 exposure-induced increase in IL-6 in skeleton muscle than those of many other tissues.

Construction of a novel Staphylokinase (SAK) mutant with low immunogenicity and its evaluation in rhesus monkey.

The heterologous nature of SAK, a thrombolytic drug, elicits high titers of neutralizing antibodies, which limits its clinical use. Here, we aim to establish a SAK mutant with equivalent activity to the wild type but reduced antigenicity, which may allow for multiple injections. Biosun software was used to predict SAK antigenic epitopes, and several main epitopes were modified by gene deletion and mutation. Ten SAK mutants were constructed, and their thrombolytic activity and immunogenicity were analyzed in vitro. SAK6, with a high expression level (45%), similar thrombolytic activity, and lower antibody reaction, was chosen for in vivo analysis in rhesus monkey. In the nearly 8-month experimental period, the antibody level of the SAK6 group was significantly lower than that of the SAK group. Moreover, only 5% of SAK activity was retained, whereas 75.6% of SAK6 activity was retained after incubating with respective antiserum. Overall, these results demonstrated that SAK6, established through comprehensive site-directed mutagenesis program, had identical thrombolytic activity to SAK, low immunogenicity, and less side effects, demonstrating its efficient clinical potential for thrombus disease.

Association between outdoor PM2.5 and prevalence of COPD: a systematic review and meta-analysis.

There were conflictions and differences among the results of cross-sectional studies association between PM2.5 and COPD prevalence. We aimed to explore the real association between outdoor PM2.5 and COPD prevalence, analyze the possible cause to the differences and conflictions in previous cross-sectional studies. Cross-sectional literatures about the association between outdoor PM2.5 and COPD prevalence were selected up to 12 September 2018. Subgroup analysis was performed to explore the source of the heterogeneity. Publication bias was tested via funnel plot. Leave-one-out method was used to conduct influential analysis. Variance analysis was used to analyze the influence of concentration, literature quality and age (over 60 or not) on the ln (aOR) values. The initial search revealed 230 studies, of which 8 were selected. The heterogeneity in this study was significant (I2=62, P<0.01), and random effects model was used. The pooled OR for the association between PM2.5 and COPD prevalence is 2.32(95%CI, 1.91-2.82). There was no evidence of publication bias. Subgroup analysis showed the subgroup of age seemed to be the source of heterogeneity (P=0.0143, residual I2=0%). Variance analysis showed that the differences of ln (aOR) among each concentration group(p=0.0075) were statistically significant, the same as age groups(P=0.0234). This meta-analysis study demonstrated a conclusive association between PM2.5 and prevalence of COPD (OR: 2.32, 95%CI 1.91-2.82). The significant heterogeneity among selected studies was mainly caused by age (over 60 or not). High PM2.5 concentration should be needed in further research of the relationship between PM2.5 and chronic diseases.

Construction and evaluation of SAK-HV protein oral dosage form based on chitosan quaternary ammonium salt-PLGA microsphere.

The aim of this study was to realize the oral delivery of SAK-HV protein and improve its oral bioavailability based on chitosan quaternary ammonium salt-PLGA microsphere. The results showed that the SAK-HV-loaded microsphere can overcome the multiple obstacles for oral adsorption and adhere effectively to the jejunal segment of a rat. The pharmacokinetic analysis of the oral drug-loaded microspheres in rats showed that the blood drug concentration of SAK-HV reached the peak value at 4 h after oral administration, and the relative oral bioavailability of SAK-HV was 3.4%. Additionally, after oral administration to the mice, a higher level of antibody against SAK-HV was produced on day 21 compared with that in the control and injection groups, and the antibody titre was 7.2 times that of the tail vein group. This work suggests that the microsphere of the chitosan quaternary ammonium salt-PLGA may be a promising drug delivery system for the oral administration of SAK-HV protein.

The protective role of IL-1Ra on intestinal ischemia reperfusion injury by anti-oxidative stress via Nrf2/HO-1 pathway in rat.

BACKGROUND: Intestinal ischemia reperfusion injury is a frequent clinical damage, in which the oxidative stress and inflammation play an important role. Interleukin-1 receptor antagonist (IL-1Ra) is a natural anti-inflammatory factor, however, its effect on intestinal ischemia reperfusion injury remains unclear. METHODS: The rat model of intestinal I/R was induced by occlusion (for 60 min) and reopening (for 60 min) of superior mesenteric artery. The rats were randomly divided into the following 5 groups: sham-operation(S), model (I/R),10 mg/kgIL-1Ra + I/R (C1),20 mg/kgIL-1Ra + I/R (C2), and30 mg/kgIL-1Ra + I/R (C3). RESULTS: In this study it was the first time to confirm that IL-1Ra had a significant protection against the intestinal ischemia reperfusion injury. IL-1Ra not only effectively inhibited the expression of inflammatory factors (such as IL-1ß, IL-6 and TNF-α) and the activation of neutrophil in intestinal tissues, but also decreased the death of intestinal cells and the damages of intestinal tissues. Interestingly, besides anti-inflammation effect, it was also found that IL-1Ra possessed a significant inhibitory effect on the oxidative stress caused by ischemia/reperfusion injury. Furthermore, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1), and the phosphorylation level of Nrf2 were greatly promoted by IL-1Ra. At the same time, IL-1Ra inhibited the mitogen-activated protein kinase (MAPKs) pathway. CONCLUSION: IL-1Ra had the protective effect against intestinal ischemia reperfusion injury, its mechanism included anti-inflammation and anti-oxidative stress in which the Nrf2/HO-1 pathway played an important role. The above-mentioned results may extend the clinical application of IL-1Ra in the treatment of intestinal ischemia reperfusion injury.

PM2.5 Exposure Induces More Serious Apoptosis of Cardiomyocytes Mediated by Caspase3 through JNK/ P53 Pathway in Hyperlipidemic Rats.

Exposure to airborne particulate matter with an aerodynamic diameter less than or equivalent to 2.5 microns (PM2.5) easily induces acute myocardial infarction in populations with high-risk cardiovascular diseases such as hyperlipidemia, but its mechanism remains unclear. In this study, hyperlipidemic rats were used to examine the effects of PM2.5 exposure on the cardiovascular system and the mechanism for its induction of cardiovascular events. We found that PM2.5 exposure resulted in bigger changes in the myocardial enzyme profile (cTnI, LDH, CK, CK-MB) in hyperlipidemic rats than that of control rats, as well as a significant increase in the C-reactive protein (CRP) level and a decrease in the superoxide dismutase (SOD) activity. It promoted a hypercoagulable state, significantly increased blood pressure and heart rate, while decreased the variability of heart rate in hyperlipidemic rats. In addition, pathological test showed that PM2.5 exposure more easily deteriorated myocardial injury in hyperlipidemic rats. It upregulated the phosphorylation levels of myocardial c-Jun NH2-terminal kinase (JNK) and P53, resulting in the elevated expression of downstream effector protein Bax and the decreased expression of Bcl-2, and then increased caspase3 level leading to cardiomyocyte apoptosis, while little change of caspase2 was observed. Taken together, PM2.5 exposure induced more serious inflammation and oxidative stress in the circulation system of hyperlipidemic rats, promoted a hypercoagulable state and triggered cardiomyocyte apoptosis, in which JNK/P53 pathway played a key role.

Stimuli-responsive nanoscale drug delivery systems for cancer therapy.

Currently, with the rapid development of nanotechnology, novel drug delivery systems (DDSs) have made rapid progress, in which nanocarriers play an important role in the tumour treatment. In view of the conventional chemotherapeutic drugs with many restrictions such as nonspecific systemic toxicity, short half-life and low concentration in the tumour sites, stimuli-responsive DDSs can deliver anti-tumour drugs targeting to the specific sites of tumours. Owing to precise stimuli response, stimuli-responsive DDSs can control drug release, so as to improve the curative effects, reduce the damage of normal tissues and organs, and decrease the side effects of traditional anticancer drugs. At present, according to the physicochemical properties and structures of nanomaterials, they can be divided into three categories: (1) endogenous stimuli-responsive materials, including pH, enzyme and redox responsive materials; (2) exogenous stimuli-responsive materials, such as temperature, light, ultrasound and magnetic field responsive materials; (3) multi-stimuli responsive materials. This review mainly focuses on the researches and developments of these novel stimuli-responsive DDSs based on above-mentioned nanomaterials and their clinical applications.

Advance in oral delivery systems for therapeutic protein.

Oral delivery is the most common method of drug administration with high safety and good compliance for patients. However, delivering therapeutic proteins to the target site via oral route involves tremendous challenge due to unfavourable conditions like biochemical barrier, mucus barrier and epithelial barriers. According to the functional differences of various protein drug delivery systems, the recent advances in pH responsive polymer-based drug delivery system, mucoadhesive polymer-based drug delivery system, absorption enhancers-based drug delivery system and composite polymer-based delivery system all were briefly summarised in this review, which not only clarified the clinic potential of these novel drug delivery systems, but also described the way for increasing oral bioavailability of therapeutic protein.