Oxygen-Vacancy-Reinforced Vanadium Oxide/Graphene Heterojunction for Accelerated Zinc Storage with Long Life Span.

Vanadium trioxide (V6 O13 ) cathode has recently aroused intensive interest for aqueous zinc-ion batteries (AZIBs) due to their structural and electrochemical diversities. However, it undergoes sluggish reaction kinetics and significant capacity decay during prolonged cycling. Herein, an oxygen-vacancy-reinforced heterojunction in V6 O13- x /reduced graphene oxide (rGO) cathode is designed through electrostatic assembly and annealing strategy. The abundant oxygen vacancies existing in V6 O13- x weaken the electrostatic attraction with the inserted Zn2+ ; the external electric field constructed by the heterointerfaces between V6 O13- x and rGO provides additional built-in driving force for Zn2+ migration; the oxygen-vacancy-enriched V6 O13- x highly dispersed on rGO fabricates the interconnected conductive network, which achieves rapid Zn2+ migration from heterointerfaces to lattice. Consequently, the obtained 2D heterostructure exhibits a remarkable capacity of 424.5 mAh g-1 at 0.1 A g-1 , and a stable capacity retention (96% after 5800 cycles) at the fast discharge rate of 10 A g-1 . Besides, a flexible pouch-type AZIB with real-life practicability is fabricated, which can successfully power commercial products, and maintain stable zinc-ion storage performances even under bending, heavy strikes, and pressure condition. A series of quantitative investigation of pouch batteries demonstrates the possibility of pushing pouch-type AZIBs to realistic energy storage market.

Baseline lymphocyte and cholinesterase levels may be the predictors of chronic herbal drug-induced liver injury.

Objective: To investigate the factors influencing the chronicity of drug-induced liver injury (DILI) caused by Chinese herbal medicine. Methods: Patients with DILI diagnosed by using the RUCAM score were enrolled retrospectively. The subjects were patients with DILI induced by taking Chinese herbal medicine and were followed up for 48 weeks. These patients were divided into a cure group and a chronic group. The biochemical indicators were monitored at baseline and every 3 months. Logistic regression was used to analyze the risk factors of DILI chronicity. The ROC (receiver operator characteristic) curve was used to analyze the diagnostic efficiency of each factor. Results: A total of 420 patients with DILI were enrolled; 122 of them were caused by Chinese herbal medicine, 70.5% (86/122) of them were female, chronic group 31.2% (39/122), and cure group 68.0% (83/122); cholinesterase (ChE) in the chronic group was lower than that in the cure group (5467.10 ± 2010.40 U/L vs. 6248.52 ± 1901.78 U/L, p = 0.04, t = 2.078). There was no significant difference in the age between cured patients and chronic patients (p = 0.156, Z = -1.417). There was no significant difference between the prognosis of different genders (p = 0.521, Z = -0.639). The logistic regression analysis showed that baseline lymphocyte (OR = 0.429, 95%CI = 0.205-0.898, p = 0.025) and cholinesterase (OR = 0.088, 95%CI = 0.008-0.994, p = 0.049) were independent risk factors of drug-induced chronicity. Conclusion: Baseline lymphocyte and cholinesterase may be the predictive factors for the chronicity of Chinese herbal medicine-induced liver injury.

Cytokine Profiles and Virological Marker Monitoring during 48 Weeks Peginterferon Alfa Treatment for HBeAg-Positive Chronic Hepatitis B.

Objective: This study aimed to investigate whether cytokine profiles and virological markers might add value in monitoring the effects of peginterferon (PEG-IFN) therapy for hepatitis B e-antigen (HBeAg) positive chronic hepatitis B (CHB). Methods: HBeAg positive patients with CHB were treated with PEG-IFN for 48 weeks. Clinical biochemical, and HBV serological indexes, as well as cytokines, were detected at baseline and every 12 weeks. Results: A total of 116 patients with CHB were enrolled in this study; 100 patients completed the 48-week treatment and follow-up, of whom 38 achieved serum HBeAg disappearance, 25 achieved HBeAg seroconversion, 37 showed HBsAg decreases ≥ 1 log 10 IU/mL, 9 showed HBsAg disappearance, and 8 became HBsAb positive. The cytokine levels at baseline and during treatment were similar between the HBeAg disappearance group and non-disappearance group. The disappearance of HBeAg was independently associated with HBeAg levels at weeks 12 and 24, and with the HBeAg decline at week 24 ( P < 0.05). The HBsAg response was independently associated with HBsAg, the HBsAg decline, HBeAg, the HBeAg decline at week 12, and HBsAg at week 24 ( P< 0.05). Conclusion: There was no significant correlation between the response to interferon (IFN) and cytokines during PEG-IFN treatment. The changes in virological markers predicted the response to IFN after 48 weeks.

Combination and Intermittent Therapy Based on Pegylated Interferon Alfa-2a for Chronic Hepatitis B with Nucleoside (Nucleotide) Analog-Experienced Resulting in Hepatitis B Surface Antigen Clearance: A Case Report.

Interferon (IFN) and nucleoside (nucleotide) analogs (NAs) are two effective antiviral drugs for chronic hepatitis B (CHB). More and more evidence shows that the combination of the two drugs can better inhibit viral replication and even achieve clinical cure. IFN intermittent therapy is also considered to be an important measure to resolve IFN fatigue when hepatitis B surface antigen (HBsAg) decline appears stagnated during IFN-based antiviral therapy. A 36-year-old male NA-experienced patient with hepatitis B e antigen (HBeAg)-positive CHB was admitted to our hospital. After a poor response to tenofovir disoproxil fumarate (TDF) monotherapy for 1 year, the patient was treated with pegylated interferon alfa-2a combination therapy and finally achieved HBsAg clearance. During the treatment and follow-up, HBsAg, HBeAg, hepatitis B virus (HBV) DNA, and serum alanine aminotransferase, etc. were monitored every 3 months. Between weeks 58 and 71 of combination therapy, IFN was discontinued because of a slow decline in HBsAg, and TDF alone was used for maintenance therapy. Complete virological response, HBeAg and HBsAg seroconversion were observed at weeks 44, 96, and 122, respectively. After 24 weeks of consolidation therapy, HBsAg, HBeAg, and HBV DNA were consistently negative, and hepatitis B surface antibody was 729.30 mIU/mL at week 146 of the combination therapy, then we stopped drugs. Following up after 28 weeks of cessation therapy, the patient still remained clinically cured.

Transforming growth factor ß as a possible independent factor in chronic hepatitis B.

To investigate the association between immune-cell-related cytokines and the development of chronic hepatitis B (CHB), patients with chronic hepatitis B virus (HBV) infection in the immunotolerant (IT) phase (n = 30) or hepatitis B envelope antigen (HBeAg)-positive CHB (n = 250) were enrolled in this study. Serological indicators and plasma cytokine levels were measured at the time of enrollment. The results showed that there were significant differences in the median age of the patients (27 vs. 31 years), alanine aminotransferase levels (ALT, 29.85 vs. 234.70 U/L), alanine aminotransferase levels (AST, 23.40 vs. 114.90 U/L), HBsAg levels (4.79 vs. 3.88 log10 IU/ml), HBeAg levels (1606.36 vs. 862.47 S/CO), and the HBV DNA load (8.17 vs. 6.71 log10 IU/ml) between the IT and CHB groups (all P < 0.01). The median values of Fms-like tyrosine kinase 3 ligand (FLT3-L), interferon-gamma (IFN-γ), interleukin- 17A (IL-17A), and transforming growth factor beta (TGF-ß1) were significantly higher in the IT group than in the CHB group (FLT3-L, 41.62 vs. 27.47 pg/ml; IFN-γ, 42.48 vs. 33.18 pg/ml; IL-17A, 15.66 vs. 8.90 pg/ml; TGF-ß1, 4921.50 vs. 2234 pg/ml; all P < 0.01). The median IFN-α2, TGF-ß3 and IL-10 levels in the IT group were significantly lower than those in the CHB group (IFN-α2, 15.24 vs. 35.78 pg/ml, P = 0.000; TGF-ß3, 131.69 vs. 162.61 pg/ml, P = 0.025; IL-10, 5.02 vs. 7.9 pg/ml, P = 0.012). Multivariate logistic regression analysis indicated that TGF-ß 1 (OR = 0.999, 95% CI 0.999-1.000, P < 0.001) and TGF-ß2 levels (OR = 1.008, 95%CI 1.004-1.012, P < 0.001) were modestly but significantly associated with the incidence of CHB. The results suggest that TGF-ß level might be an independent factor related to the occurrence of CHB.

Physiological and antioxidant responses of Euryale ferox salisb seedlings to microcystins.

Lake Taihu is the third largest freshwater lake located in eastern China. In recent years, it has experienced extensive cyanobacterial (Microcystis spp.) blooms that produce toxic microcystins (MCs), which may have acute and chronic hepatotoxic effects in animals and humans. Although the impact of MCs on both terrestrial and aquatic plants is well documented, the effects and underlying mechanisms of the harmful toxin MC-LR on Euryale ferox Salisb seedlings have rarely been reported. Thus, herein, the antioxidant response mechanisms and the biosynthesis of secondary metabolites during the exposure of E. ferox Salisb seedlings to varying MC-LR concentrations (0.05, 0.2, 1, and 5 µg/L) were thoroughly investigated after exposure periods (7, 14, 21 d). Our study revealed that the seedling growth was inhibited with increasing MC-LR exposure concentration that significantly induced at 1 µg/L and reached a maximum level at 5 µg/L, whereas the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) in the seedling cells increased gradually with increasing MC-LR concentration and longer exposure time. The maximum malondialdehyde (MDA) content was 4.3-fold higher than that of the control group under an MC-LR concentration of 5.0 µg/L after 7 days of exposure treatment. The study of the seedling detoxification mechanism revealed that the content of total glutathione (tGSH) and reduced glutathione (GSH), as well as the activities of GSH sparse transferase (GST) and glutathione reductase (GR), increased to varying degrees and reached a maximum level at 1 µg/L. Therefore, the exposure to MC-LR can promote the accumulation of secondary metabolites and increase the activities of secondary metabolic enzymes in the seedlings. Further investigation of these antioxidative mechanisms will provide additional information for the identification and development of bio-indicators to evaluate the environmental impact of MCs on aquatic ecosystems.

Papillary thyroid carcinoma with hyperthyroidism and multiple metastases: A case report.

RATIONALE: Papillary thyroid carcinoma (PTC) is the most common type of primary thyroid cancer with a low incidence of distant metastases. PTC represents more than 70% to -90% of thyroid malignancies. Distant metastases have only been observed in only 1% to 15% of patients with PTC. In this article, we reported the case of a patient with PTC and hyperthyroidism as well as simultaneous multiple metastases. PATIENT CONCERNS: A 47-year-old man was admitted to our hospital on February 22, 2019, with several neck masses that had been present for 12 months, low back pain for 9 months, and lower limb paraplegia for 3 months. DIAGNOSES: According to the patient physical examination, adjuvant examination (e.g., ultrasound, computed tomography, magnetic resonance imaging, blood test, and biopsy) and medical history, the clinical diagnosis was as follows: thyroid papillary carcinoma; cervical lymph node metastasis; multisite bone metastasis (6th and 7th cervical vertebrae, left clavicle proximal, right scapula bone, thoracic vertebrae, lumbar vertebrae, sacral vertebrae, bilateral ilium, and left pubic bone); muscular metastasis (the right medial femoral muscle, the vastus lateralis muscle, left thigh muscle, and the flexor superficialis of the left forearm); possible mediastinal lymph node metastasis; and paraplegia due to the soft-tissue metastasis around the 9th thoracic vertebral spine; and hyperthyroidism (free thyroxine: 36.59 pmol/L, free triiodothyronine: 9.58 pmol/L, thyroid-stimulating hormone: 0.005 µIU/mL, thyroid autoantibody: 2.53 IU/L). INTERVENTIONS AND OUTCOMES: The patient refused to undergo further intervention or follow-up. LESSONS: In summary, this is the 1st case of in which a patient with PTC and hyperthyroidism, as well as simultaneous multiple skeletal muscles and bone metastases, lymph node metastasis, and paraplegia was observed. In practice, in cases where patients have PTC and hyperthyroidism, practitioners should perform further examinations to rule out the presence of distant metastases. We believe that the use of ultrasound has a unique advantage in the diagnosis of PTC and skeletal muscle metastasis.

A single copy of large tumor suppressor 1 or large tumor suppressor 2 is sufficient for normal hematopoiesis.

BACKGROUND: Hematopoietic stem cells (HSCs) have the ability to differentiate into all subsets of blood cells and self-renew. Large tumor suppressor 1 (LATS1) and large tumor suppressor 2 (LATS2) kinases are essential for cell cycle regulation, organism fitness, genome integrity, and cancer prevention. Here, we investigated whether Lats1 and Lats2 are critical for the maintenance of the self-renewal and quiescence capacities of HSCs in mice. METHODS: Quantitative reverse transcription-polymerase chain reaction was used to determine the expression levels of Lats1 and Lats2 in subsets of progenitor cells and mature bone marrow cells. A clustered regularly interspaced short palindromic repeats system was used to generate Lats1 or Lats2 knockout mice. Complete blood cell counts were used to compare the absolute number of white blood cells, lymphocytes, monocytes, neutrophils, and platelets between Lats1 or Lats2 heterozygotes and littermates. Flow cytometry was used to assess the size of hematopoietic progenitor cells (HPCs) and HSC pools in Lats1 or Lats2 heterozygotes and littermates. The comparison between the two groups was analyzed using Student's t test. RESULTS: Lats1 and Lats2 were widely expressed in hematopoietic cells with higher expression levels in primitive hematopoietic cells than in mature cells. Lats1 or Lats2 knockout mice were generated, with the homozygotes showing embryonic lethality. The size of the HPC and HSC pools in Lats1 (HPC: wild-type [WT] vs. heterozygote, 220,426.77 ±â€Š54,384.796 vs. 221,149.4 ±â€Š42,688.29, P = 0.988; HSC: WT vs. heterozygote, 2498.932 ±â€Š347.856 vs. 3249.763 ±â€Š370.412, P = 0.105) or Lats2 (HPC: WT vs. heterozygote, 425,540.52 ±â€Š99,721.86 vs. 467,127.8 ±â€Š89,574.48, P = 0.527; HSC: WT vs. heterozygote, 4760.545 ±â€Š1518.01 vs. 5327.437 ±â€Š873.297, P = 0.502) heterozygotes were not impaired. Moreover, the depletion of Lats1 or Lats2 did not affect the overall survival of the heterozygotes (Lats1: P = 0.654; Lats2: P = 0.152). CONCLUSION: These results indicate that a single allele of Lats1 or Lats2 may be sufficient for normal hematopoiesis.

Association of cytokines with hepatitis B virus and its antigen.

To investigate the characteristics of cytokines in patients with different HBV infection status and their correlation with HBV DNA, HBsAg, and HBeAg levels. Peripheral blood samples were collected from patients with chronic HBV infection in immune tolerance phase (IT), HBeAg-positive chronic hepatitis B (CHB), and acute hepatitis B (AHB) groups, and levels of cytokines were detected by Luminex technique, and analyzed by FLEXMAP 3D analyzer. The correlation between cytokines and HBV DNA load, HBsAg, HBeAg, and alanine aminotransferase (ALT) level in patients with chronic HBV infection was analyzed. In total 312 subjects (184 males and 128 females) were enrolled in the study. There were significant differences among IT, CHB, and AHB groups in Flt-3L value (P = .003; H = 12.312), IFN-γ (P = .001; H = 11.723), IL-10 (P = .001; H = 18.736), IL-17A ((P = .001; H = 12.735), and TGF-ß1 (P = .001; Z = 48.571). IFN-α2 levels in CHB group were significantly higher than those in IT and AHB groups (15.24 vs 35.78 pg/mL, P = .000; Z = 3.727; 13.88 vs 35.78 pg/mL, P = .024; Z = -2.258. In CHB group, the levels of HBsAg and ALT were positively correlated with the levels of IL-10 (r = .173; P = .006; r = 0.176; P = .006, respectively), while HBeAg level was positively correlated with the IFN-α2 level (r = .153; P = .016). In AHB group, the HBsAg level was positively correlated with Flt-3L, IFN-α2, IL-10, and IL-6 (r = .402; P = .023; r = .436; P = .016; r = .524, P = .002; r = .405; P = .022, respectively). HBeAg level was positively correlated with IFN-γ and IL-17A levels (r = .400; P = .023; r = .373; P = .036, respectively), and ALT level was positively correlated with IL-6 levels (r = .367; P = .039). In either AHB or CHB group, HBV DNA load was only related to TGF-ß level (r = .493; P = .004; r = -.218, P = 0.009 respectively). The correlation between Flt-3L and HBsAg (F = 7.422; P = .007); IL-17, IL-6, and HBeAg (F = 5.757; P = .017; F = 6.156; P = .014) were statistically significant. There was significant correlation between TGF-ß2 and HBV DNA (F = 11.795; P = .001), and between ALT and HBsAg, HBV DNA (F = 26.089; P = .000; F = 4.724; P = .031). HBsAg, HBeAg, and HBV DNA were correlated with cytokines and ALT in patients with HBV infection. The level of IFN-α2 was significantly higher in patients with CHB. HBV DNA load was only correlated with the level of TGF-ß in acute or CHB.

Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins.

The ongoing outbreak of viral pneumonia in China and across the world is associated with a new coronavirus, SARS-CoV-21. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection2. Although bats are probable reservoir hosts for SARS-CoV-2, the identity of any intermediate host that may have facilitated transfer to humans is unknown. Here we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity in the receptor-binding domain to SARS-CoV-2. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of new coronaviruses and should be removed from wet markets to prevent zoonotic transmission.

Leonurine Exerts Anti-Catabolic and Anti-Apoptotic Effects via Nuclear Factor kappa B (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) Signaling Pathways in Chondrocytes.

BACKGROUND Leonurine confers neuroprotection, inhibits myocardial apoptosis, ameliorates endothelial dysfunction, and shows anti-inflammatory effects, and may be beneficial for clinical applications. However, the effects of leonurine on chondrocytes remain unknown. Here, we investigated the protective role of leonurine in rat chondrocytes. MATERIAL AND METHODS To explore the potential therapeutic effect of leonurine against osteoarthritis (OA), rat chondrocytes were treated with IL-1ß along with different concentrations of leonurine in vitro. The levels of matrix metalloproteinases (MMPs), ADAMTS, Bax, and Bcl-2 were measured by PCR, ELISA, and Western blotting. Caspase-3 activity in chondrocytes was determined using a caspase-3 activity assay. Western blotting was also performed to examine activation of the NF-kappaB and mitogen-activated protein kinase (MAPK) pathways to elucidate the likely regulatory mechanisms. RESULTS Leonurine counteracted IL-1ß-induced production of MMP-1, MMP-13, ADAMTS-4, and ADAMTS-5. Leonurine treatment reduced both the mRNA and protein levels of Bax and increased the level of Bcl-2. Leonurine also inhibited the activity of caspase-3 in IL-1ß-induced chondrocytes. Furthermore, the activation of MAPK and phosphorylation of p65 were suppressed by leonurine. CONCLUSIONS The results of this study indicate that leonurine exerts anti-catabolic and anti-apoptotic effects in chondrocytes in vitro via suppression of the NF-kappaB and MAPK signaling pathways.

Tricetin Protects Rat Chondrocytes against IL-1ß-Induced Inflammation and Apoptosis.

Tricetin is a well-studied flavonoid with a wide range of pharmacological activities in cancer and inflammation. However, the ability of tricetin to ameliorate the inflammation that occurs in osteoarthritis (OA) has not been determined. This study explored the effects of tricetin on interleukin- (IL-) 1ß-induced rat chondrocytes. Chondrocytes harvested from rat cartilage were incubated in vitro with tricetin in the presence of IL-1ß. The expression of matrix metalloproteinase- (MMP-) 1, MMP-3, MMP-13, nitric oxide (NO), prostaglandin E2 (PGE2), Bax, and Bcl-2 was evaluated by real-time-PCR, ELISA, Griess reaction, and western blotting. Caspase-3 activity in chondrocytes was determined using a caspase-3 activity assay and MAPK pathway activity by western blotting. Tricetin decreased the expression of MMP-1, MMP-3, and MMP-13 at both the gene and protein level in IL-1ß-induced rat chondrocytes. It also inhibited IL-1ß-induced NO and PGE2 production, by modulating inducible NO synthase and cyclooxygenase 2 gene expression. An antiapoptotic role of tricetin involving the Bax/Bcl-2/caspase-3 pathway was also determined. The chondroprotective effect of tricetin was shown to be partly related to the suppression of the MAPK signaling pathway. The results of this study demonstrate the chondroprotective role of tricetin, based on its anticatabolic, anti-inflammatory, and antiapoptotic effects in chondrocytes. The therapeutic potential of tricetin in OA patients should be explored in future studies.

Rhizoma Paridis saponins ameliorates hepatic fibrosis in rats by downregulating expression of angiogenesis­associated growth factors.

Previously, we demonstrated that Rhizoma Paridis saponins (RPS), the major active component of Rhizoma Paridis, may exhibit hepatoprotective effects. The present study aimed to identify the potential mechanism of RPS on hepatic injury and improvement in hepatic fibrosis (HF). A HF model was created in Sprague­Dawley rats by administration of carbon tetrachloride. RPS was administered for treatment following creation of the HF model. The protein and mRNA expression of vascular endothelial growth factor (VEGF), platelet­derived growth factor (PDGF), extracellular signal­regulated kinase (ERK)1/2 and α­smooth muscle actin (SMA) was detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. RPS was demonstrated to improve hepatic inflammation and decrease HF severity according to hematoxylin and eosin and Masson trichrome staining. Following RPS treatment, the level of alanine aminotransferase, aspartate aminotransferase and malondialdehyde, and expression levels of the mRNA and protein of VEGF, ERK1/2, PDGF and α­SMA in the model group was decreased. By contrast, the content of glutathione­PX and superoxide dismutase was increased. These data suggest that RPS may treat HF primarily through downregulation of the expression levels of the mRNA and phosphorylated VEGF, ERK1/2, PDGF and α­SMA proteins.

Follistatin-like protein 1 (FSTL1) promotes chondrocyte expression of matrix metalloproteinase and inflammatory factors via the NF-κB pathway.

BACKGROUND: The expression of follistatin-like protein 1 (FSTL1) is closely associated with diseases of the musculoskeletal system. However, despite being a well characterized inflammatory mediator, the effects of FSTL1 on chondrocytes are not completely understood. In this study, we investigated the effects of FSTL1 on the expression of inflammatory and catabolic factors in rat chondrocytes. METHODS: Rat chondrocytes were treated directly with various concentrations of FSTL1 in vitro. The levels of matrix metalloproteinases (MMPs), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-1ß, tumour necrosis factor (TNF)-α and IL-6 were measured by polymerase chain reaction, ELISA and Western blotting. In addition, activation of the nuclear factor kappa B (NF-κB) pathway was explored to identify potential regulatory mechanisms. RESULTS: Follistatin-like protein 1 directly increased the expression of MMP-1, MMP-13, iNOS, COX-2, IL-1ß, TNF-α and IL-6 at both gene and protein level in a dose-dependent manner. Activation of NF- κB and phosphorylation of p65 were also promoted by FSTL1 stimulation. CONCLUSIONS: Follistatin-like protein 1 exerts pro-inflammatory and catabolic effects on cultured chondrocytes via activation of the NF-κB signalling pathway. FSTL1 may therefore be a target in the treatment of OA.

Modulation of Kalirin-7 expression by hippocampal CA1 5-HT1B receptors in spatial memory consolidation.

Serotonin 5-HT1B receptors (5-HT1BRs) are distributed in hippocampal CA1 and play a pivotal role in cognitive function. Activation of 5-HT1BRs regulates synaptic plasticity at the excitatory synapses in the hippocampus. However, the role and its underlying mechanism of 5-HT1BR activation-mediated glutamatergic synaptic plasticity in spatial memory are not fully understood. In this study, spatial memory of Sprague-Dawley (SD) rats was assessed in a Morris water maze after bilateral dorsal hippocampal CA1 infusion of the 5-HT1BR antagonist GR55562 (25 µg/µL) or agonist CP93129 (25 µg/µL). GR55562 did not affect the spatial memory acquisition but significantly increased the target quadrant preference during the memory consolidation probe performed 14 d after the training session, while CP93129 impaired the memory consolidation process. Moreover, GR55562 significantly increased, while CP93129 significantly decreased, the density of dendritic spines on the distal apical dendrites of CA1 pyramidal neurons. Furthermore, western blot experiments indicated that GR55562 significantly increased, but CP93129 significantly reduced, the expression of Kalirin-7 (Kal-7), PSD95, and GluA2/3 subunits of AMPA receptors. Our results suggest that Kal-7 and Kal-7-mediatedalteration of AMPA receptor subtype expression may play crucial roles in the impact of hippocampal CA1 5-HT1BR activation on spatial memory consolidation.

Paeoniflorin inhibits IL-1ß-induced MMP secretion via the NF-κB pathway in chondrocytes.

Paeoniflorin serves important cellular roles, exerting anti-cancer, anti-inflammatory and anti-pulmonary fibrosis effects and possesses immune-modulatory properties. However, the exact role of paeoniflorin in the pathogenesis of osteoarthritis (OA) remains unclear. The aim of the present study was to investigate the effects of paeoniflorin on articular surfaces in vitro. Rat chondrocytes were cultured in vitro and an MTT assay was performed to assess chondrocyte survival. Following treatment with interleukin (IL)-1ß and paeoniflorin, the production of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) was examined using reverse transcription-quantitative polymerase chain reaction and western blotting. The interleukin (IL)-1ß-induced nuclear factor (NF)-κB pathway activation was also investigated. The results demonstrated that paeoniflorin was able to downregulate the expression of MMP and increase the expression of TIMP-1ntmRNA and protein in IL-1ß-induced rat chondrocytes. Furthermore, treating chondrocytes with paeoniflorin blocked the activation of NF-κB. These results suggest that paeoniflorin may serve am anti-catabolic role in the progression of OA and may be an effective preventative treatment for OA.

Cigarette Smoke Modulates NOD1 Signal Pathway and Human ß Defensins Expression in Human Oral Mucosa.

BACKGROUND/AIMS: Nucleotide binding oligomerization domain 1 (NOD1) signal pathway and human ß defensins (hBDs) play crucial roles in innate immune. Cigarette smoke has been confirmed to dampen innate immune in some human tissues, such as oral mucosa. The aim of this study was to evaluate potential effects of smoking on NOD1 signaling and hBDs expression in oral mucosa. METHODS: Tissue specimens of normal oral mucosa were collected from donors undergoing routine surgical treatment. All 20 participants were classified equally as two groups: non-smokers and smokers. By using Western blotting and immunohistochemistry, we investigated differential expression of crucial molecules in NOD1 signal pathway, hBD-1, -2, and -3 in oral mucosa tissues between non-smokers and smokers. Immortalized human oral mucosal epithelial (Leuk-1) cells were treated with various concentrations of cigarette smoke extract (CSE) for 24h. Western blotting and immunofluorescence assays were performed to study CSE-induced alteration of protein expression. Leuk-1 cells were treated with 4% CSE, iE-DAP (NOD1 agonist), CSE + iE-DAP, BAY 11-7082 (NF-κB inhibitor), 4% CSE + BAY 11-7082, respectively. Real-time PCR and ELISA were performed to detect the mRNA levels and secretion of hBD-1, -2, and -3, respectively. RESULTS: The levels of NOD1, NF-κB, hBD-1 and hBD-3 significantly reduced in oral mucosa tissues of smokers compared with non-smokers. The levels of RIP2 (receptor-interacting protein 2), phospho-NF-κB (P-NF-κB) and hBD-2 remarkably enhanced in oral mucosal tissues of smokers. CSE treatment suppressed NOD1 and NF-κB expression and activated RIP2 and P-NF-κB expression in Leuk-1 cells. The mRNA and secretory levels of hBD-1 and -3 were down-regulated by CSE, while the mRNA and secretory level of hBD-2 were up-regulated by CSE. The iE-DAP or BAY 11-7082 treatment reversed the regulatory effects of CSE on levels of hBDs. CONCLUSION: The present study indicated that cigarette smoke could potentially modulate the expression of crucial molecules of NOD1 signal pathway and hBDs in human oral mucosal epithelium. NOD1 signal pathway could play an important role in the regulatory effects of CSE on hBDs levels in oral mucosal epithelial cells.

Effects of whole cigarette smoke on human beta defensins expression and secretion by oral mucosal epithelial cells.

BACKGROUND: Cigarette smoke a recognized risk factor for many systemic diseases and also oral diseases. Human beta defensins (HBDs), a group of important antimicrobial peptides expressed by the epithelium, are crucial for local defense and tissue homeostasis of oral cavity. The aim of this study was to evaluate potential effects of whole cigarette smoke (WCS) exposure on the expression and secretion of HBDs by oral mucosal epithelial cells. METHODS: Immortalized human oral mucosal epithelial (Leuk-1) cells were exposed to WCS for various time periods. HBD-1, -2 and -3 expression and subcellular localization were detected by real time qPCR, immunofluorescence assay and confocal microscopy. According to the relative fluorescent intensity, the expression levels of HBD-1, -2 and -3 were evaluated by digital image analysis system. The alteration of HBD-1, -2 and -3 secretion levels was measured by the Enzyme-Linked Immunosorbent Assay. RESULTS: WCS exposure remarkably attenuated HBD-1 expression and secretion while clearly enhanced HBD-2, -3 expression levels and HBD-2 secretion by Leuk-l cells. It appeared that there was no significant effect of WCS exposure on HBD-3 secretion. CONCLUSIONS: WCS exposure could modulate expression and secretion of HBDs by oral mucosal epithelial cells, establishing a link between cigarette smoke and abnormal levels of antimicrobial peptides. The present results may give a new perspective to investigate smoking-related local defense suppression and oral disease occurrence.

Alterations of chemical composition, construction cost and payback time in needles of Masson pine (Pinus massoniana L.) trees grown under pollution.

Previous studies show that Masson pine (Pinus massoniana L.) stands grown at the industrially-polluted site have experienced unprecedented growth decline, but the causal mechanisms are poorly understood. In this study, to understand the mechanisms of growth decline of Mason pine strands under pollution stresses, we determined the reactive oxygen species levels and chemical composition of the current-year (C) and one-year-old (C + 1) needles, and calculated the needle construction costs (CCmass) of Masson pine trees grown at an industrially-polluted site and an unpolluted remote site. Pine trees grown at the polluted site had significantly higher levels of hydroxyl radical and superoxide anion in their needles than those grown at the unpolluted site, and the former trees eventually exhibited needle early senescence. The contents of lipids, soluble phenolics and lignins in C and C + 1 needles were significantly higher at the polluted site than at the unpolluted site, but the total amounts of non-construction carbohydrates were lower in non-polluted needles than in polluted needles. Elevated levels of the reactive oxygen species and early senescence in polluted needles together led to significant increases in CCmass and a longer payback time. We infer that the lengthened payback time and needle early senescence under pollution stress may reduce the Masson pine tree growth and consequently accelerate tree decline.