Ethyl pyruvate attenuates cellular adhesion and proliferation of diffuse large B-cell lymphoma by targeting c-Jun.

Diffuse large B-cell lymphoma (DLBCL) stands out as the most common type of malignant cancer, representing the majority of cases of non-Hodgkin's lymphoma. Ethyl pyruvate (EP) is a derivative of pyruvic acid and found to have potent anti-tumor properties. Despite its potential benefits, the impact of EP on DLBCL remains ambiguous. Our objective is to elucidate the role of EP in modulating the development of DLBCL. Analysis of cholecystokinin-8 (CCK-8) revealed that treatment with EP significantly diminished the viability of DLBCL cells. Furthermore, EP administration suppressed colony formation and hindered cell adhesion and invasion in DLBCL cells. Examination of cell cycle progression showed that EP treatment induced arrest at the G1 phase and subsequently reduced the S phase population in DLBCL cells. EP treatment consistently exhibited apoptosis-inducing properties in Annexin-V assays, and notably downregulated the expression of Bcl-2 while increasing levels of proapoptotic cleaved caspase 3 and BAX in DLBCL cells. Additionally, EP treatment decreased the overexpression of c-Jun in c-Jun-transfected DLBCL cells. Further, EP demonstrated DNA-damaging effects in TUNEL assays. In vivo, xenograft animal models revealed that EP treatment significantly mitigated DLBCL tumor growth and suppressed DLBCL cell adhesion to bone marrow stromal cells. In summary, these findings suggest that EP mitigates DLBCL progression by inducing apoptosis, inducing cell cycle arrest, and promoting DNA damage.

Macrophage Gpx4 deficiency aggravates foam cell formation by regulating the expression of scavenger receptors, ABCA1, and ABCG1.

Macrophage-derived foam cell formation is critical for the initiation and development of atherosclerosis, which contributes to atherosclerotic cardiovascular disease (ASCVD). Glutathione peroxidase 4 (GPX4), a crucial ferroptosis regulator, protects cells from excessive oxidative stress by neutralizing lipid peroxidation. However, the role of macrophage GPX4 in foam cell formation remains unknown. We reported that oxidized low-density lipoprotein (oxLDL) upregulated GPX4 expression in macrophages. Using the Cre-loxP system, we generated myeloid cell-specific Gpx4 knockout (Gpx4myel-KO ) mice. Bone marrow-derived macrophages (BMDMs) were isolated from WT and Gpx4myel-KO mice and incubated with modified low-density lipoprotein (LDL). We found that Gpx4 deficiency promoted foam cell formation and increased the internalization of modified LDL. Mechanistic studies unveiled that Gpx4 knockout upregulated scavenger receptor type A and LOX-1 expression and downregulated ABCA1 and ABCG1 expression. Collectively, our study lends a novel insight into the role of GPX4 in suppressing macrophage-derived foam cell formation and suggests GPX4 as a promising therapeutic target to interfere with atherosclerosis-related diseases.

Trends in deaths and disability-adjusted life-years of stroke attributable to low physical activity worldwide, 1990-2019.

BACKGROUND: Low physical activity (LPA) is linked to the risk of stroke, but the disease burden of stroke attributable to LPA needs to be understood to develop effective preventive strategies. We aim to assess spatiotemporal trends in the global burden of stroke attributable to LPA from 1990 to 2019. METHODS: Based on the Global Burden of Disease, Injuries, and Risk Factors Study, our research examined deaths, the Disability-Adjusted Life Years (DALYs), the Age-Standardized Mortality Rate (ASMR), the Age-Standardized DALY Rate (ASDR), and the Estimated Annual Percentage Change (EAPC) for stroke attributable to LPA. RESULTS: Deaths and DALYs were on the rise worldwide from 1990 to 2019, with increases of 72.72% for the former and 67.41% for the latter; ASMR and ASDR decreased, with the ASMR-related EAPC of -1.61 (95% CI:-1.71--1.5) and ASDR-related EAPC of -1.35 (95% CI:-1.43--1.27); females had more numbers of deaths and DALYs, and the majorities of deaths and DALYs were shared by those aged ≥ 70. The highest burden rates were shared by North Africa, the Middle East, and Tropical Latin America; the ASMR-related EAPC was associated with the ASMR in 1990 (R = -0.26, P < 0.001) and the Socio-Demographic Index (SDI) across different countries in 2019 (R = -0.61, P < 0.001), respectively, and such patterns were similar to what ASDR and the ASDR-related EAPC had; the Human Development Index (HDI) in 2019 was associated with the ASMR-related EAPC (R = 0.63, P < 0.001) and the ASDR-related EAPC across different countries (R = -0.62, P < 0.001), respectively. CONCLUSIONS: Globally, deaths and DALYs of stroke attributable to LPA were on the rise, although their age-standardized rates presented downward over the past three decades; the burden of stroke attributable to LPA showed upward trends especially in those aged ≥ 70 and females in the regions of East Asia, North Africa, and the Middle East, which need more attention to the effects of physical activity on health interventions.

Trends in Prevalence Cases and Disability-Adjusted Life-Years of Parkinson's Disease: Findings from the Global Burden of Disease Study 2019.

BACKGROUND: Parkinson's disease is a common, age-related progressive neurodegenerative disorder with considerable socioeconomic burdens, although the studies in incremental burdens to the disease's rapid growth are incomplete and lag behind. We aim to assess global burdens of Parkinson's disease based on a public database online. METHODS: Based on the Global Burden of Disease, Injuries, and Risk Factors Study, we screened a range of indicators including prevalence cases, disability-adjusted life-years (DALYs), age-standardized prevalence rates (ASPRs), and age-standardized DALY rate (ASDR). The join point regression was used to assess the indicators, wherein the ASPR and the ASDR were referred to temporal trends for burdens of Parkinson's disease. RESULTS: Prevalence cases of global Parkinson's disease were on the rise for 30 years, with an increase of 155.51% during 1990-2019. Temporal trend of ASDRs was on the rise during 1990-2002 but in decline during 2002-2019. The ASPRs had a turning point in 2017 and a decline during 2017-2019 (annual percentage change = -0.51%, p > 0.05). China, India, the USA, Japan, and Germany shared the five highest prevalence cases and DALYs in 2019. The Socio-Demographic Index (SDI) was in relation to a significantly positive ASPR (R = 0.61, p < 0.001) but not a significantly negative ASDR (R = -0.044, p = 0.53), respectively. CONCLUSIONS: In this study, a range of indicators for global burdens of Parkinson's disease were on the rise during 1990-2019. Tremendous efforts should be in place to prevent Parkinson's disease, especially among the populations of males, with advanced ages, in East Asia, and in regions with high SDI.

Association of platelet-to-white blood cell ratio and platelet-to-neutrophil ratio with the risk of fatal stroke occurrence in middle-aged to older Chinese.

BACKGROUND: White blood cell (WBC) and neutrophil (NEUT) counts, which are commonly inflammatory markers, have been related to an increased risk of fatal stroke. However, it is unclear whether platelet-to-white blood cell ratio (PWR) and platelet-to-neutrophil ratio (PNR) are related to the risk of fatal stroke in middle-aged to older populations. METHOD: In total, 27,811 participants without a stroke history at baseline were included and followed up for a mean of 14.3 years (standard deviation = 3.2), and 838 stroke deaths were recorded. The Cox proportional hazards regression was used to assess the relationships between the PWR and the PNR and the risk of fatal strokes. RESULTS: Compared to the 1st quartile, an increased risk of fatal all stroke showed among the participants in the highest quartiles of both the WBC (adjusted hazard ratio (aHR) = 1.35, 95% confidence interval (CI) 1.09-1.66) and the NEUT (aHR = 1.45, 95% CI 1.18-1.79). The restricted cubic splines showed decreased trends in associations of the PWR and the PNR with the risk of fatal all stroke. A decreased risk of fatal all stroke showed in those with the highest quartiles for both the PWR (aHR = 0.73, 95% CI 0.53-1.00) and the PNR (aHR = 0.74, 95% CI 0.54-1.01). The participants with the 2nd, the 3rd and the 4th change quartiles for the PWR and the PNR had weak decreasing trends for the risk of fatal all stroke, compared to those in the 1st change quartile, and the significant associations were observed in those with an increase of 20% for the PWR with the risk of fatal haemarragic stroke (aHR = 0.47, 95% CI 0.22-0.95) and a decrease of 20% for the PNR with the risk of fatal all stroke (aHR = 1.33, 95% CI 0.99-1.79), compared to those with stable dynamic changes. CONCLUSIONS: Higher neutrophil count and platelet-to-neutrophil ratio were associated with a contrary risk of fatal stroke, with an increased for the former and a decreased for the later. A potentially chronic inflammation should be paid close attention to stroke occurrence in relatively healthy middle-aged to older populations.

Mesenchymal stem cells alleviate AQP-4-dependent glymphatic dysfunction and improve brain distribution of antisense oligonucleotides in BACHD mice.

Huntington's disease (HD) is a neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene that results in the production of neurotoxic mutant HTT (mHTT) protein. Suppressing HTT production with antisense oligonucleotides (ASOs) is a promising treatment strategy for HD; however, the difficulty of delivering ASOs to deep brain structures is a major barrier for its clinical application. The glymphatic system of astrocytes involving aquaporin 4 (AQP-4) controls the entry of macromolecules from the cerebrospinal fluid into the brain. Mesenchymal stem cells (MSCs) target astrocytes to inhibit neuroinflammation. Here we examined the glymphatic distribution of ASO in the brain and the therapeutic potential of combining intravenously injection of mesenchymal stem cells (IV-MSC) and ASOs for the treatment of HD. Our results show that Cy3-labeled ASOs entered the brain parenchyma via the perivascular space following cisternal injection, but the brain distribution was significantly lower in AQP-4-/- as compared with wild-type mice. Downregulation of the AQP-4 M23 isoform was accompanied by decreased brain levels of ASOs in BACHD mice as well as an increase in astrogliosis and phosphorylation of nuclear factor κB (NF-κB) p65. IV-MSC treatment restored AQP-4 M23 expression, attenuated astrogliosis, and decreased NF-κB p65 phosphorylation; it also increased the brain distribution of ASOs and enhanced the suppression of mHTT in BACHD mice. These results suggest that modulating glymphatic activity using IV-MSC is a novel strategy for improving the potency of ASO in the treatment of HD.

New pectic polysaccharides from Codonopsis pilosula and Codonopsis tangshen: structural characterization and cellular antioxidant activities.

BACKGROUND: Codonopsis pilosula and Codonopsis tangshen are plants widely used in traditional Chinese medicine. Two pectic polysaccharides from the roots of C. pilosula and C. tangshen named as CPP-1 and CTP-1 were obtained by boiling water extraction and column chromatography. RESULTS: The core structures of both CPP-1 and CTP-1 comprise the long homogalacturonan region (HG) as the backbone and the rhamnogalacturonan I (RG-I) region as the side chains. CPP-1 has methyl esterified galacturonic acid units and a slightly lower molecular weight than CTP-1. Biological testing suggested that CPP-1 and CTP-1 can protect IPEC-J2 cells against the H2 O2 -induced oxidative stress by up-regulating nuclear factor-erythroid 2-related factor 2 and related genes in IPEC-J2 cells. The different antioxidative activities of polysaccharides from different source of C. pilosula may be result of differences in their structures. CONCLUSION: All of the results indicated that pectic polysaccharides CPP-1 and CTP-1 from different species of C. pilosula roots could be used as a potential natural antioxidant source. These findings will be valuable for further studies and new applications of pectin-containing health products. © 2021 Society of Chemical Industry.

Characterization of inulin-type fructans from two species of Radix Codonopsis and their oxidative defense activation and prebiotic activities.

BACKGROUND: Codonopsis pilosula and C. tangshen are both plants widely used in traditional Chinese medicine. Polysaccharides, which are their primary active components, are thought to be important in their extensive use. In this study, two neutral polysaccharide fractions of C. pilosula (CPPN) and C. tangshen (CTPN) were obtained by fractionation on a DEAE-Sepharose column and characterized. RESULTS: It was confirmed that the neutral polymers CPPN and CTPN were ß-(2,1)-linked inulin-type fructans with non-reducing terminal glucose, and degree of polymerization (DP) of 19.6 and 25.2, respectively. The antioxidant and prebiotic activities in vitro were assayed based on IPEC-J2 cell lines and five strains of Lactobacillus. Results indicated that the effects of CPPN and CTPN were increased antioxidant defense in intestinal epithelial cells through enhanced cell viability, improved expression of total antioxidant capacity, glutathione peroxidase, superoxide dismutase and catalase, and reduced levels of malondialdehyde and lactic dehydrogenase. The prebiotic activity of CPPN and CTPN was demonstrated by the promoting effect on Lactobacillus proliferation in vitro. The different biological activities obtained between the two fractions are probably due to the different DP and thus molecular weights of CPPN and CTPN. CONCLUSION: The inulin fractions from C. pilosula and C. tangshen were natural sources of potential intestinal antioxidants as well as prebiotics, which will be valuable in further studies and new applications of inulin-containing health products. © 2020 Society of Chemical Industry.

K562 cell-derived exosomes suppress the adhesive function of bone marrow mesenchymal stem cells via delivery of miR-711.

A failure of bone marrow mesenchymal stem cells (BM-MSCs) to adhere to hematopoietic cells is an essential cause of the progression of chronic myelogenous leukemia and is also a cause of failure of bone marrow (BM) transplantation, but the exact mechanisms of this have not been fully elucidated. Recent studies have indicated that microRNAs (miRNAs) are contained in leukemia-derived exosomes and are involved in modulating the BM microenvironment. In this study, we found that K562 cell-derived exosomes transfer miR-711 to BM-MSCs and suppress the adhesive function of BM-MSCs. Using qRT-PCR, we also confirmed a significantly higher level of miR-711 in exosomes derived from K562 cells than in exosomes derived from parental cells. The BM-MSCs co-cultured with exosomes derived from K562 cells showed a lower adhesion rate than did controls. We further demonstrated that exosomal transfer of miR-711 induced decreased adhesive abilities by inhibiting expression of adhesion molecule CD44 in BM-MSCs. In conclusion, our study reveals that K562 cell-derived exosomal miR-711 can be transferred to BM-MSCs and weaken adhesive abilities by silencing the expression of the adhesion molecule CD44.

Exosomes: Potential Therapies for Disease via Regulating TLRs.

Exosomes are small membrane vesicles that retain various substances such as proteins, nucleic acids, and small RNAs. Exosomes play crucial roles in many physiological and pathological processes, including innate immunity. Innate immunity is an important process that protects the organism through activating pattern recognition receptors (PRRs), which then can induce inflammatory factors to resist pathogen invasion. Toll-like receptor (TLR) is one member of PRRs and is important in pathogen clearance and nervous disease development. Although exosomes and TLRs are two independent materials, abundant evidences imply exosomes can regulate innate immunity through integrating with TLRs. Herein, we review the most recent data regarding exosome regulation of TLR pathways. Specifically, exosome-containing materials can regulate TLR pathways through the interaction with TLRs. This is a new strategy regulating immunity to resist pathogens and therapy diseases, which provide a potential method to cure diseases.

CeNETs analysis reveals the prognostic value of a signature integration from five lncRNAs in breast cancer.

BACKGROUND: The competitive endogenous RNA (ceRNA) hypothesis is a novel effective theory that can enable us to deeply understand the mechanisms of comprehensive diseases. METHODS: In this study, we first downloaded RNAseq data and microRNA (miRNA) seq data of breast cancer from The Cancer Genome Atlas and further explored the regulation of ceRNA network in breast cancer using comprehensive bioinformatics tools. RESULTS: The results revealed that five miRNAs, including hsa-miR-10b, hsa-miR-21, hsa-miR-183, hsa-miR-1258, and hsa-miR-3200 formed the core of ceRNA network. Moreover, five long noncoding RNAs that could competitively bind with miR-10b, respectively, named ACTA2-AS1, RP11-384P7.7, RP11-327J17.9, RP11-124N14.3, and RP11-645C24.5, were discovered as an integration signature with great potential in the prediction of survival outcomes in patients with different stages of breast cancer. CONCLUSIONS: This indicates that these five long noncoding RNAs may be potential novel diagnostic and prognostic biomarkers of breast cancer.

Circular RNA CDR1as sponges miR-7-5p to enhance E2F3 stability and promote the growth of nasopharyngeal carcinoma.

BACKGROUND: Circular RNA (circRNA) CDR1as plays an important role in the occurrence and development of human tumors. The purpose of this study is to investigate the molecular mechanism of circRNA CDR1as in the development of nasopharyngeal carcinoma (NPC). METHODS: The mRNA expressions of circRNA CDR1as, miR-7-5p, and E2F3 were detected by qRT-PCR. The effects of circRNA CDR1as, miR-7-5p, and E2F3 on NPC cells were investigated using cell counting kit-8 (CCK8) method, colony formation assay, and representative metabolite assay. The molecular mechanism of circRNA CDR1 in NPC was studied by bioinformatics and luciferase reporter assay. In addition, the biological activity of circRNA CDR1as was also investigated in NPC xenograft tumor mice model. RESULTS: The results showed that the circRNA CDR1as expression was significantly up-regulated in NPC tissues by comparison with non-tumor NPE tissues (p < 0.01), suggesting that circRNA CDR1as was associated with poor prognosis in NPC patients. Moreover, circRNA CDR1as could up-regulate E2F3 expression by binding miR-7-5p, and promote the growth and glucose metabolism of NPC cells. Meanwhile, circRNA CDR1as could promote NPC progression through the negative regulation of miR-7-5p in the xenograft tumor model. CONCLUSION: CircRNA CDR1as promoted the occurrence and development of NPCs by successively up-regulating the expression of miR-7-5p and E2F3, suggesting CircRNA CDR1as as a potential target for the treatment of NPC patients.Trial registration The study was approved by the cancer center's institutional research ethics committee on Oct 18, 2008 (2008GZ2847462).

Long-term Follow-up of Patients Treated with Percutaneous Radiofrequency Thermocoagulation via the Foramen Rotundum for Isolated Maxillary Nerve Idiopathic Trigeminal Neuralgia.

OBJECTIVE: The purpose of this study is to evaluate the effectiveness and safety of percutaneous radiofrequency thermocoagulation (PRT) via the foramen rotundum (FR) for the treatment of isolated maxillary (V2) idiopathic trigeminal neuralgia (ITN) and assess the appropriate puncture angle through the anterior coronoid process to reach the FR. METHODS: Between January 2011 and October 2016, 87 patients with V2 ITN refractory to conservative treatment were treated by computed tomography (CT)-guided PRT via the FR at our institution. The outcome of pain relief was assessed by the visual analog scale (VAS) and Barrow Neurological Institute (BNI) pain grade and grouped as complete pain relief (BNI grades I-III) or unsuccessful pain relief (BNI grades IV-V). Recurrence and complications were also monitored and recorded. The puncture angle for this novel approach was assessed based on intraoperative CT images. RESULTS: Of the 87 treated patients, 85 (97.7%) achieved complete pain relief, and two patients (2.3%) experienced unsuccessful pain relief immediately after operation. During the mean follow-up period of 44.3 months, 15 patients (17.2%) experienced recurring pain. No severe complications occurred, except for hypoesthesia restricted to the V2 distribution in all patients (100%) and facial hematoma in 10 patients (11.5%). The mean puncture angle to reach the FR was 33.6° ± 5.7° toward the sagittal plane. DISCUSSION: CT-guided PRT via the FR for refractory isolated V2 ITN is effective and safe and could be a rational therapy for patients with V2 ITN.

Comparison of health-related quality of life between the Han and Yi ethnicity elderly in the Yi autonomous areas of Yunnan Province.

BACKGROUND: The purpose of this research was to assess the health-related quality of life (HRQOL) and functional abilities of Yi and Han elderly who resided in Yi Autonomous prefecture or Counties in Yunnan Province, as well as to compare their differences in HRQOL, functional abilities and other factors. METHODS: A total of 1636 older subjects, which included 863 Han and 773 Yi, were recruited from 10 Yi Autonomous regions. Their HRQOL and functional capabilities were assessed by the MOS 36-Item Short Form Health Survey (SF-36), activities of daily living (ADL), and instrumental activities of daily living (IADL) scales. RESULTS: The Han elderly performed better in every domain of SF-36 than the Yi elderly. Both of the two ethnic groups could perform their ADL independently but the Yi elderly showed greater dependency in IADL abilities. The HRQOL was positively associated with their ADL, IADL, and education levels. Moreover, age, health insurance status, and living arrangement were negatively correlated with HRQOL. CONCLUSION: The HRQOL and IADL capabilities of the Han elderly were higher than that of the Yi counterparts in the Yi Autonomous regions. The HRQOL of both the two ethnic groups was positively connected with ADL, IADL abilities as well as education levels, whereas it was negatively correlated with age and health insurance. The elderly-care policy on the Yi autonomous areas should focus more on the HRQOL, ADL improvement, education background, age needs, and health insurance, etc.

Characterization of Inulin-Type Fructan from Platycodon grandiflorus and Study on Its Prebiotic and Immunomodulating Activity.

Platycodon grandiflorus is a plant widely used in traditional Chinese medicine, of which polysaccharides are reported to be the main components responsible for its bio-functions. In this work, the inulin-type fructan (PGF) was obtained by DEAE anion exchange chromatography from the water extracted from P. grandifloras. Characterization was performed with methanolysis, methylation, and NMR and the results showed that PGF is a ß-(2-1) linked fructan, with terminal glucose and with a degree of polymerization of 2⁻10. In order to study its biofunctions, the prebiotic and immunomodulation properties were assayed. We found that PGF exhibited good prebiotic activity, as shown by a promotion on six strains of lactobacillus proliferation. Additionally, the PGF also displayed direct immunomodulation on intestinal epithelial cells and stimulated the expressions of anti-inflammatory factors. These results indicated that the inulin from P. grandiflorus is a potential natural source of prebiotics as well as a potential intestinal immunomodulator, which will be valuable for further studies and new applications.

A Polysaccharide Isolated from Codonopsis pilosula with Immunomodulation Effects Both In Vitro and In Vivo.

In this study, an acidic polysaccharide from Codonopsis pilosula Nannf. var. modesta (Nannf.) L. T. Shen (WCP-I) and its main fragment, WCP-Ia, obtained after pectinase digestion, were structurally elucidated and found to consist of a rhamnogalacturonan I (RG-I) region containing both arabinogalactan type I (AG-I) and type II (AG-II) as sidechains. They both expressed immunomodulating activity against Peyer's patch cells. Endo-1,4-ß-galactanase degradation gave a decrease of interleukine 6 (IL-6) production compared with native WCP-I and WCP-Ia, but exo-α-l-arabinofuranosidase digestion showed no changes in activity. This demonstrated that the stimulation activity partly disappeared with removal of ß-d-(1→4)-galactan chains, proving that the AG-I side chain plays an important role in immunoregulation activity. WCP-Ia had a better promotion effect than WCP-I in vivo, shown through an increased spleen index, higher concentrations of IL-6, transforming growth factor-ß (TGF-ß), and tumor necrosis factor-α (TNF-α) in serum, and a slight increment in the secretory immunoglobulin A (sIgA) and CD4+/CD8+ T lymphocyte ratio. These results suggest that ß-d-(1→4)-galactan-containing chains in WCP-I play an essential role in the expression of immunomodulating activity. Combining all the results in this and previous studies, the intestinal immune system might be the target site of WCP-Ia.

CT-guided minimally invasive treatment for an extensive spinal epidural abscess: a case report and literature review.

PURPOSE: We present a case involving an extensive epidural abscess that was successfully treated with computed tomography (CT)-guided percutaneous needle drainage and systemic antibiotic therapy. METHODS: A 44-year-old woman with a history of spine injection procedures complained of severe backache and progressive radiating pain in her right lower extremity followed by sensory deficits in her right lower limb. A laboratory examination revealed leukocytosis and hyperglycemia. Magnetic resonance imaging of the lumbar region revealed an extremely large posterior spinal epidural abscess (SEA) extending from L2 to S2. Because the patient did not respond to intravenous antibiotics alone, she underwent CT-guided percutaneous needle drainage and irrigation. RESULTS: Staphylococcus aureus was detected in the purulent material from this abscess. Her clinical symptoms were dramatically and immediately relieved after this procedure. She achieved complete neurological recovery after 2 months of antibiotic therapy. CONCLUSION: CT-guided percutaneous needle drainage and irrigation may be a rational treatment choice for patients with SEA with the exception of patients with a chronic abscess, an anterior abscess or discitis.

Preterm birth and ambient temperature: Strong association during night-time and warm seasons.

BACKGROUND: Mounting evidence have linked high temperature with increased incidence of preterm birth (PTB), but which time period(s) of increase in temperature within a day and a year during pregnancy play an important role in PTB is not clarified. OBJECTIVE: This study aims to determine the critical time period(s) of heat exposure on the development of PTB by exploring the risk of PTB for temperature increase during 24 h of a whole day and each of four seasons during pregnancy. METHODS: A cohort study was performed with 3509 preschool children in Changsha, China, which evaluated the prevalence of PTB using a questionnaire filled out by the children's parents. The authors estimated the temperature at which each mother was exposed to outdoor air temperature during three trimesters and for 24 h in different seasons of pregnancy. The logistic regression models in regard to odds ratio (OR) and 95% confidence interval (CI) was applied to study associations of PTB with an increase in temperature during different time windows. RESULTS: Prevalence of PTB (4.1%) was associated with outdoor temperature with adjusted ORs (95% CI) = 1.34 (1.11-1.62) for increase of 1 °C in temperature exposure during pregnancy, and this association was significantly higher in spring and summer than autumn and winter. Specifically, high temperature during summer night posed the highest risk of PTB, with peaks during 03:00-04:00 a.m. We further found that PTB was associated with exposure to temperature and extreme heat day during the 2nd trimester, with ORs = 1.03 (1.00-1.06) and 1.01 (1.00-1.02) respectively. Foetus with male sex and older mothers were more sensitive to the impact of heat exposure during pregnancy on PTB, with higher risk observed during night time. CONCLUSION: Our study indicates that heat exposure was related to an elevated risk of PTB, with higher risk of PTB for nocturnal exposure and warm seasons. Our findings have implications for the adverse effect of elevated temperature in the future as global warming continues.

The Polysaccharides from Codonopsis pilosula Modulates the Immunity and Intestinal Microbiota of Cyclophosphamide-Treated Immunosuppressed Mice.

Based on previous studies about microflora regulation and immunity enhancement activities of polysaccharides from Codonopsis pilosula Nannf. var. modesta (Nannf.) L. T. Shen (CPP), there is little study on intestinal mucosal immunity, which is a possible medium for contacting microflora and immunity. In the present study, the BALB/c mice were divided into five groups (eight mice in each group), including a normal group (Con), a model control group (Model), and model groups that were administered CPP (50, 100, 200 mg/kg/d) orally each day for seven days after intraperitoneal injection of 60 mg/kg BW/d cyclophosphamide (CP) for three days. CPP recovered the spleen index and restored the levels of IFN-γ, IL-2, IL-10, as well as serum IgG. In addition, it elevated ileum secretory immunoglobulin A (sIgA), the number of Lactobacillus and acetic acid content in cecum. These results indicated that CPP plays an important role in the protection against immunosuppression, especially mucosa immune damage, and the inhibition of pathogenic bacteria colonization, which could be considered a potential natural source of immunoregulator.

Lymphangiogenesis in rat asthma model.

Although bronchial angiogenesis has been well documented in allergic asthma, lymphangiogenesis has not been widely studied. Therefore, we evaluated changes in lung lymphatics in a rat model of allergen-induced asthma using house dust mite (Der p 1; 100 µg/challenge). Additionally, properties of isolated lung lymphatic endothelial cells (CD45-, CD141+, LYVE-1+, Prox-1+) were studied in vitro. Three weeks after the onset of intranasal allergen exposure (twice-weekly), an increase in the number of lung lymphatic vessels was measured (34% increase) by lung morphometry. New lymphatic structures were seen predominantly in the peribronchial and periarterial interstitial space but also surrounding large airways. Isolated lymphatic endothelial cells from sensitized lungs showed enhanced proliferation (% Ki67+), chemotaxis, and tube formation (number and length) compared to lymphatic endothelial cells isolated from naive rat lungs. This hyper-proliferative lymphangiogenic phenotype was preserved through multiple cell passages (2-8). Lymphatic endothelial cells isolated from naive and HDM-sensitized rats produced similar in vitro levels of VEGF-C, VEGF-D, and VEGFR3 protein, each recognized as critical lymphangiogenic factors. Inhibition with anti-VEGFR (axitinib, 0.1 µM) blocked proliferation and chemotaxis. Results suggest that in vivo sensitization causes fundamental changes to lymphatic endothelium, which are retained in vitro, and may relate to VEGFR downstream signaling.