Blocking group 2 innate lymphoid cell activation and macrophage M2 polarization: potential therapeutic mechanisms in ovalbumin-induced allergic asthma by calycosin.

BACKGROUND: Calycosin, a flavonoid compound extracted from Astragalus membranaceus, has shown anti-asthma benefits in house dust mite-induced asthma. Recent studies have suggested that innate-type cells, including group 2 innate lymphoid cells (ILC2s) and macrophages, serve as incentives for type 2 immunity and targets for drug development in asthma. This work focuses on the effects of calycosin on the dysregulated ILC2s and macrophages in allergic asthma. METHODS: In vivo, the asthmatic mouse model was established with ovalbumin (OVA) sensitization and challenge, and calycosin was intraperitoneally administered at doses of 20 and 40 mg/kg. In vivo, mouse primary ILC2s were stimulated with interleukin (IL)-33 and mouse RAW264.7 macrophages were stimulated with IL-4 and IL-13 to establish the cell models. Cells were treated with calycosin at doses of 5 and 10 µM. RESULTS: In vivo, we observed significantly reduced numbers of eosinophils, neutrophils, monocyte macrophages and lymphocytes in the bronchoalveolar lavage fluid (BALF) of OVA-exposed mice with 40 mg/kg calycosin. Histopathological assessment showed that calycosin inhibited the airway inflammation and remodeling caused by OVA. Calycosin markedly decreased the up-regulated IL-4, IL-5, IL-13, IL-33, and suppression tumorigenicity 2 (ST2) induced by OVA in BALF and/or lung tissues of asthmatic mice. Calycosin repressed the augment of arginase 1 (ARG1), IL-10, chitinase-like 3 (YM1) and mannose receptor C-type 1 (MRC1) levels in the lung tissues of asthmatic mice. In vivo, calycosin inhibited the IL-33-induced activation as well as the increase of IL-4, IL-5, IL-13 and ST2 in ILC2s. Calycosin also repressed the increase of ARG1, IL-10, YM1 and MRC1 induced by IL-4 and IL-13 in RAW264.7 macrophages. In addition, we found that these changes were more significant in 40 mg/kg calycosin treatment than 20 mg/kg calycosin. CONCLUSIONS: Collectively, this study showed that calycosin might attenuate OVA-induced airway inflammation and remodeling in asthmatic mice via preventing ILC2 activation and macrophage M2 polarization. Our study might contribute to further study of asthmatic therapy.

Efficacy and safety of apatinib plus chemotherapy vs. chemotherapy alone for the treatment of advanced­stage non­small cell lung cancer: A meta­analysis.

Apatinib has been widely applied for the treatment of gastrointestinal cancer since its development; however, available conclusive data regarding its use in non-small cell lung cancer (NSCLC) are lacking. Thus, the present meta-analysis aimed to compare the efficacy and safety of the use of apatinib plus chemotherapy vs. chemotherapy alone for the treatment of patients with advanced-stage NSCLC. Published studies reporting the treatment response, progression-free survival (PFS), overall survival (OS) and adverse events in patients with advanced-stage NSCLC treated with apatinib plus chemotherapy or chemotherapy alone were searched using the PubMed, China National Knowledge Infrastructure, EMBASE, Chongqing VIP Information, Cochrane and Wanfang databases until February 2023. Finally, 18 studies involving 677 patients with NSCLC receiving apatinib plus chemotherapy and 672 patients with NSCLC receiving chemotherapy were included in the present analysis. Apatinib plus chemotherapy was found to increase the objective response rate [relative risk (RR), 1.60; 95% confidence interval (CI), 1.38-1.86] and disease control rate (RR, 1.29; 95% CI, 1.21-1.38) compared to chemotherapy alone. Of note, apatinib plus chemotherapy also prolonged PFS compared with chemotherapy alone (hazard ratio, 0.54; 95% CI, 0.35-0.73), while no OS data were retrievable from the included studies. With regard to safety, apatinib plus chemotherapy elevated the risk of developing hypertension (RR, 3.78; 95% CI, 1.81-7.93) and hand-foot syndrome (RR, 6.51; 95% CI, 3.70-11.46) vs. chemotherapy alone; however, no difference was observed between the two regimens in terms of the incidence of other adverse events. Furthermore, the bias was low and the pooled findings were reliable/stable, as indicated by a sensitivity analysis. On the whole, the present study demonstrates that apatinib plus chemotherapy increases the treatment response and PFS vs. chemotherapy alone, while it also elevates the risk of developing hypertension and hand-foot syndrome in patients with advanced-stage NSCLC.

A network meta-analysis of different acupuncture modalities in the treatment of bronchial asthma.

BACKGROUND: Glucocorticoids and Beta-2 receptor agonists are commonly used for the treatment of asthma in clinical practice, while these agents are accompanied by adverse reactions of different kinds. Studies have shown that acupuncture is effective in treating bronchial asthma. However, different acupuncture modalities have different costs and skill requirements, and there remains a lack of comparisons between different acupuncture modalities. This study aims to assess the efficacy of various acupuncture modalities in the treatment of asthma. METHODS: The following databases were searched for randomized controlled trials (RCTs) on acupuncture for the treatment of bronchial asthma from database inception to August 26, 2022: PubMed, Embase, The Cochrane Library, Web of Science, Chinese Journal Full-text Database (CNKI), Wanfang Database (Wanfang Date), VIP Database (VIP), China Biology Medicine disc (CBM). Stata 15.1 software was used to conduct network meta-analysis. The risk of bias in the included studies was evaluated using the Cochrane Risk of Bias Assessment Tool 2 (RoB2). RESULTS: A total of 8,693 relevant studies were found, and 30 RCTs were included, involving 2,722 patients with bronchial asthma and eight acupuncture modalities: manual acupuncture, moxibustion, electroacupuncture, ignipuncture, flying needle acupuncture, acupoint catgut embedding, acupoint application, and warm-needle moxibustion. The other 29 studies had certain risks, with the quality graded as "moderate". Among the pair-wise comparisons of statistical significance (p < 0.05), acupoint application was the most effective in improving pulmonary function (FEV1: Traditional medicine therapy-acupoint application [-7.29 (-12.11,-2.47)]; acupoint application-moxibustion [7.20 (0.28,14.11)]; FVC: acupoint application-Traditional medicine therapy [8.02 (2.54,13.50)]). Acupoint catgut embedding was the most effective in improving the ACT score of the patients (Traditional medicine therapy-acupoint catgut embedding [-4.29 (-7.94, -0.65)]; acupoint catgut embedding-moxibustion [5.52 (1.05,9.99)]). CONCLUSION: Acupoint application has evident merits in improving the clinical response rate and pulmonary function, while acupoint catgut embedding can improve other secondary indicators. For the clinical treatment of asthma, acupoint application can be selected as a complementary and alternative therapy, while the other acupuncture therapies can also be considered according to the examination results of the patients.

The Role of Macrophage Autophagy in Asthma: A Novel Therapeutic Strategy.

Asthma is a chronic respiratory disease frequently associated with airway inflammation and remodeling. The development of asthma involves various inflammatory phenotypes that impact therapeutic effects, and macrophages are master innate immune cells in the airway that exert diverse functions including phagocytosis, antigen presentation, and pathogen clearance, playing an important role in the pathogeneses of asthma. Recent studies have indicated that autophagy of macrophages affects polarization of phenotype and regulation of inflammation, which implies that regulating autophagy of macrophages may be a potential strategy for the treatment of asthma. Thus, this review summarizes the signaling pathways and effects of macrophage autophagy in asthma, which will provide a tactic for the development of novel targets for the treatment of this disease.

Icariin alleviates transforming growth factor-ß1-induced epithelial-mesenchymal transition by targeting Smad and MAPK signaling pathways.

The pathogenesis of airway remodeling and airway inflammation is related to epithelial-mesenchymal transition (EMT), which is correlated with TGF-ß1 levels. Icariin is one of the major compounds in Epimedium brevicornum Maxim, and plays emerging roles in relieving cough and asthma, enhancing immunity, and anti-allergy. In the present study, we investigated the mechanism through which Icariin inhibits inflammatory and airway remodeling in vitro and in vivo. In vitro, 16HBE cells were stimulated with 10 ng/ml TGF-ß1 for 24 hours to induce EMT model. Whereas pretreatment with Icariin could alleviate EMT both in concentration- and time-dependent manner, as was evidenced by the improved cell morphology, reduced migration, down-regulation of mesenchymal markers (N-cadherin, α-SMA), and up-regulation of epithelial marker (E-cadherin). In vivo, female BALB/c mice were exposed to 25 mg/ml house dust mites (HDM) extract for 5 days and followed by 2 days rest for 5 weeks to induce chronic asthma model. Of note, administration of Icariin could attenuate airway responsiveness, inflammation, and fibrosis, with improved scores based on the staining of H&E, PAS, and Sirius Red. In addition, Icariin reduced the levels of TGF-ß1 in bronchoalveolar lavage fluid (BLAF), serum, and lung tissue, and regulated the expression of EMT markers. At the molecular level, Icariin inhibits the phosphorylation of Smad-2, Smad-3, Erk, JNK, and p38 both in vitro and in vivo. Taken together, Icariin inhibits airway remodeling by attenuating TGF-ß1-induced EMT through targeting Smad and MAPK signaling.

Icariside II attenuates eosinophils-induced airway inflammation and remodeling via inactivation of NF-κB and STAT3 in an asthma mouse model.

Asthma is a chronic inflammatory airway disease. Icariside II has been reported to exert anti-inflammatory effect in multiple human diseases. The present study aimed to investigate the effects and mechanisms of Icariside II on airway inflammation and remodeling in asthma. We established an asthma mouse model with ovalbumin (OVA) immunization. Histological analysis using H&E, PAS and Masson staining showed that administration of Icariside II attenuated OVA-induced airway inflammation and remodeling. Icariside II reduced the numbers of total white blood cells and eosinophils in bronchoalveolar lavage fluid (BALF). The levels of interleukin (IL)-4, IL-5, IL-13 and transforming growth factor (TGF)-ß1 in peripheral blood and the expression of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), eotaxin-1, CC-chemokine receptor-3 (CCR-3), Toll-like receptor (TLR)-2 and TLR-4 were significantly down-regulated in lung tissues of OVA-induced mouse model. These results suggested that Icariside II inhibited eosinophil activation and thus decreased eosinophils-induced airway inflammation and remodeling in asthma. Moreover, Icariside II suppressed TGF-ß1-induced cell proliferation, migration, and CTGF expression in airway smooth muscle cells (ASMCs). In both OVA-induced mouse model of asthma and TGF-ß1-induced ASMCs, Icariside II decreased IκBα degradation, nuclear translocation of NF-κB p65 and STAT3 phophorylation, indicating an inactivation of NF-κB and STAT3 in the presence of Icariside II. Therefore, we demonstrate that Icariside II attenuates eosinophils-induced airway inflammation and remodeling in asthmatic mice and inhibits TGF-ß1-induced cell proliferation and migration in ASMCs via suppressing NF-κB and STAT3 signalings.

A multi-responsive crown ether-based colorimetric/fluorescent chemosensor for highly selective detection of Al3+, Cu2+ and Mg2.

A novel multi-response chemosensor L based on coumarin-chalcone-crown ether was designed and synthesized, which exhibited a high selectivity for the colorimetric detecting Al3+ and Cu2+ and fluorescent recognizing Al3+ and Mg2+ in ethanol. L can monitor Al3+ and Cu2+ via distinct color changes from a slight yellow to pink and to orange, respectively. The sensor L can also monitor Al3+ and Mg2+ by fluorescence emission responses at 592 nm and 547 nm with low detection limits of 0.31 µM and 0.23 µM, respectively. The selectivity of L toward Al3+, Cu2+ and Mg2+ was not interfered by a large number of coexisting ions and was found to be reversible. By means of spectrometric titration, Job's plot, mass spectrometry, 1H NMR titration and IR spectroscopy analysis, it was unanimously confirmed that the sensor L had a stoichiometric ratio of 1:1 with Cu2+ and Mg2+, and 1:2 with Al3+. The order of the stability of the complexes formed by L and Al3+, Cu2+, Mg2+ was as follows: L-Al3+ > L-Cu2+ > L-Mg2+. At the same time, some possible bonding modes and sensing mechanisms were further proposed, and the optimized structure of the sensor L and its sensing mechanism for Al3+, Cu2+ and Mg2+ were confirmed by the calculations of DFT/B3LYP and TD-DFT methods in a suite of Gaussian 09 programs.

Procalcitonin-guided antibiotic therapy in acute exacerbation of chronic obstructive pulmonary disease: An updated meta-analysis.

BACKGROUND: The benefit of a procalcitonin (PCT)-guided antibiotic strategy in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains uncertain. OBJECTIVES: This updated meta-analysis was performed to reevaluate the therapeutic potential of PCT-guided antibiotic therapy in AECOPD. DATA SOURCES: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov up to February 2019 to identify randomized controlled trials (RCTs) investigating the role of PCT-guided antibiotic strategies in treating adult patients with AECOPD. Relative risk (RR) or mean differences (MD) with accompanying 95% confidence intervals (CIs) were calculated with a random-effects model. RESULTS: Eight RCTs with a total of 1376 participants were included. The results suggested that a PCT-guided antibiotic strategy reduced antibiotic prescriptions (RR: 0.55; 95% CI: 0.39-0.76; P = .0003). However, antibiotic exposure duration (MD: -1.34; 95% CI: -2.83-0.16; P = .08), antibiotic use after discharge (RR: 1.61; 95% CI: 0.61-4.23; P = .34), clinical success (RR: 1.02; 95% CI: 0.96-1.08; P = .47), all-cause mortality (RR: 1.05; 95% CI: 0.72-1.55; P = .79), exacerbation at follow-up (RR: 0.97; 95% CI: 0.80-1.18; P = .78), readmission at follow-up (RR: 1.12; 95% CI: 0.82-1.53; P = .49), length of hospital stay (MD: -0.36; 95% CI: -1.36-0.64; P = .48), and adverse events (RR: 1.33; 95% CI: 0.79-2.23; P = .28) were similar in both groups. IMPLICATIONS OF KEY FINDINGS: A PCT-guided antibiotic strategy is associated with fewer antibiotic prescriptions, and has similar efficacy and safety compared with standard antibiotic therapy in AECOPD patients.

-254C>G SNP in the TRPC6 Gene Promoter Influences Its Expression via Interaction with the NF-κB Subunit RELA in Steroid-Resistant Nephrotic Syndrome Children.

This study is aimed at exploring the mechanism by which the -254C>G single nucleotide polymorphism (SNP) on the transient receptor potential cation channel 6 (TRPC6) gene promoter could increase its activation in steroid-resistant nephrotic syndrome children of China. Plasmids containing the TRPC6 promoter region (with the -254C or G allele) were constructed and then transfected into human embryonic kidney (HEK) 293T cells and human podocytes. Luciferase assays were used to test the promoter activity in both cell lines with or without tumor necrosis factor-α (TNF-α) treatment, and chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR) analysis was used to verify the transcription factor that could bind to this mutant sequence. Luciferase results indicate that the activity of the mutant promoter was greater than that of the normal promoter of the TRPC6 gene in both cell lines. We further predicted and verified that this variation was mediated by the nuclear factor kappa B (NF-κB) subunit RELA, and TNF-α significantly enhanced the transcription activity of TRPC6 with the -254G allele. In conclusion, the -254C>G SNP is a gain-of-function variation of the TRPC6 gene, and it is also an early and effective factor for predicting steroid-resistant nephrotic syndrome (SRNS) in Chinese children.

Effectiveness of Chinese herbal medicine Ping Chuan Ke Li for the management of mild/moderate persistent asthma.

This study assessed the effectiveness and safety of Chinese herbal medicine Ping Chuan Ke Li (PCKL) for the treatment of patients with mild/ moderate persistent asthma.A total of 108 eligible patients with persistent asthma were included and were divided into a treatment group and a control group in this retrospective study. All 108 patients underwent oral montelukast. Additionally, subjects in the treatment group also received PCKL therapy. All patients in both groups were treated for a total of 1 month. The primary outcome of lung function was evaluated by the forced expiratory volume in one second (FEV1) and FEV1/forced vital capacity (FVC). The secondary outcome of quality of life was assessed by St. George's Respiratory Questionnaire (SGRQ). Moreover, adverse events (AEs) were also recorded in this study. All outcome measurements were assessed after 1-month treatment.After 1-month treatment, patients in the treatment group did not demonstrate better outcome in the improvement of lung function, measured by FEV1 (P =.57, table 2), and FEV1/FVC (P =.29); and enhancement of quality of life, measured by SGRQ scale (total, P =.37; symptom, P =.32; activity, P =.39; impact, P =.83). In addition, no AEs differ between 2 groups.The results of this study showed that Chinese herbal PCKL may not benefit for patients with mild/moderate persistent asthma after 1-month treatment.

A retrospective study of Yiqibushenhuoxue decoction for the treatment of chronic obstructive pulmonary disease.

This retrospective study aimed to investigate the effect and safety of Yiqibushenhuoxue decoction (YQBSHXD) for the treatment of chronic obstructive pulmonary disease (COPD).This study involved 120 cases of patients with COPD. These cases were assigned to an intervention group and a control group equally, 60 subjects each group. Patients in both groups underwent Salmeterol. In addition, the cases in the intervention group also received YQBSHXD. All cases received a total of 12 weeks treatment. The primary outcome of lung function was measured by forced expiratory volume in 1 second (FEV1), and FEV1/forced vital capacity (FVC). The secondary outcomes included severity of dyspnea on exertion, evaluated by 6-minute walk test (6MWT) with measurement of 6-minute walk distance (6MWD); and quality of life, assessed by the St. George's Respiratory Questionnaire (SGRQ). In addition, adverse events (AEs) were also recorded in this study. All outcome measurements were assessed before and after 12-week treatment.After 12-week treatment, cases in the intervention group underwent YQBSHXD did not show better outcome in lung function improvement, measured by the FEV1 (P = .11), and FEV1/FVC (P = .15), compared with those in the control group. However, YQBSHXD may help to alleviate the severity of dyspnea on exertion, as measured by 6MWD (P = .03), and to improve the quality of life, as assessed by the SGRQ (P < .01). Additionally, no significant differences in AEs were detected between the 2 groups.The results of this study showed that YQBSHXD may help to manage COPD after 12-week treatment, although the lung function has not been improved.

Triptolide suppresses paraquat induced idiopathic pulmonary fibrosis by inhibiting TGFB1-dependent epithelial mesenchymal transition.

Idiopathic pulmonary fibrosis (IPF) and tumor are highly similar to abnormal cell proliferation that damages the body. This malignant cell evolution in a stressful environment closely resembles that of epithelial-mesenchymal transition (EMT). As a popular EMT-inducing factor, TGFß plays an important role in the progression of multiple diseases. However, the drugs that target TGFB1 are limited. In this study, we found that triptolide (TPL), a Chinese medicine extract, exerts an anti-lung fibrosis effect by inhibiting the EMT of lung epithelial cells. In addition, triptolide directly binds to TGFß and subsequently increase E-cadherin expression and decrease vimentin expression. In in vivo studies, TPL improves the survival state and inhibits lung fibrosis in mice. In summary, this study revealed the potential therapeutic effect of paraquat induced TPL in lung fibrosis by regulating TGFß-dependent EMT progression.

Traditional Chinese medicine as an adjunctive therapy to oral montelukast for treating patients with chronic asthma.

BACKGROUND: This study aimed to explore the efficacy and safety of Ping Chuan Ke Li (PCKL) as an adjunctive therapy to oral montelukast compared with placebo plus montelukast for treating patients with chronic asthma (CAS). METHODS: This randomized controlled trial involved 72 patients with CAS. They were randomly allocated to an intervention group or a control group, 36 subjects per group. Participants in the intervention group received PCKL and oral montelukast, while those in the control group received placebo and oral montelukast. The primary outcome was lung function, measured by forced expiratory volume in 1 second (FEV1). The secondary outcomes included quality of life, measured by St. George's Respiratory Questionnaire (SGRQ), and adverse events (AEs). RESULTS: Compared to placebo plus montelukast, PCKL and montelukast revealed greater efficacy in lung function, measured by FEV1 (P <.05), and quality of life, measured by the SGRQ scale (P <.05). Additionally, no significant differences were found in AEs between the 2 groups. CONCLUSION: Traditional Chinese medicine PCKL as an adjunctive therapy to oral montelukast alleviated the symptoms of CAS. Future studies with larger sample sizes are still needed to verify the efficacy and safety of PCKL plus montelukast in patients with CAS.

[Application and Thinking of Constitution Theory of Chinese Medicine in Stable Phase Chronic Ob- structive Pulmonary Disease].

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease, but seriously threatens to patients' body and mind. Constitutions of Chinese medicine (CM) are closely relat- ed to diseases. Individuals with different constitutions of CM have different responses to the same envi- ronment and the same pathogenic factor. Therefore, studying the application of constitution theory of CM in stable phase COPD is of great significance. In this paper clinical applications of constitution theory of CM in COPD were explored from etiology and mechanism, syndrome typing based treatment, prevention and care, aiming to prevent, diagnose, and treat COPD effectively.

The effects of harvesting media on biological characteristics and repair potential of neural stem cells after traumatic brain injury.

Various solutions are utilized widely for the isolation, harvesting, sorting, testing and transplantation of neural stem cells (NSCs), whereas the effects of harvesting media on the biological characteristics and repair potential of NSCs remain unclear. To examine some of these effects, NSCs were isolated from cortex of E14.5 mice and exposed to the conventional harvesting media [0.9% saline (Saline), phosphate-buffered saline (PBS) or artificial cerebrospinal fluid (ACSF)] or the proliferation culture medium (PCM) for different durations at 4°C. Treated NSCs were grafted by in situ injection into the lesion sites of traumatic brain injury (TBI) mice. In vitro, harvesting media-exposed NSCs displayed time-dependent reduction of viability and proliferation. S phase entry decreased in harvesting media-exposed cells, which was associated with upregulation of p53 protein and downregulation of cyclin E1 protein. Moreover, harvesting media exposure induced the necrosis and apoptosis of NSCs. The levels of Fas-L, cleaved caspase 3 and 8 were increased, which suggests that the death receptor signaling pathway is involved in the apoptosis of NSCs. In addition, exposure to Saline did not facilitate the neuronal differentiation of NSCs, suggesting that Saline exposure may be disadvantageous for neurogenesis. In vivo, NSC-mediated functional recovery in harvesting media-exposed NSC groups was notably attenuated in comparison with the PCM-exposed NSC group. In conclusion, harvesting media exposure modulates the biological characteristics and repair potential of NSCs after TBI. Our results suggest that insight of the effects of harvesting media exposure on NSCs is critical for developing strategies to assure the successful long-term engraftment of NSCs.

Effect of yiqibushenhuoxue decoction on chronic obstructive pulmonary disease measured by St. George's respiratory disease questionnaire scores and forced expiratory volume.

OBJECTIVE: To investigate the effects of Yiqibushenhuoxue decoction on stable chronic obstructive pulmonary disease (COPD) by observing its influences on patients' quality of life and airway inflammation. METHODS: Seventy patients with stable COPD were randomly divided into a treatment group (n = 35) treated with Yiqibushenhuoxue decoction plus Seretide and a control group (n = 35) treated with Seretide only. The dosage of Yiqibushenhuoxue decoction was 100 mL each time, twice a day, and the dosage of Seretide was salmeterol 50 microg/fluticasone 250 microg twice a day. Both groups were treated for 12 weeks. Before and after the treatment, St George's respiratory disease questionnaire (SGRQ) scores, forced expiratory volume, and forced expiratory volume in 1 second/forced vital capacity (FEV1/ FVC) were measured. RESULTS: The SGRQ scores in both groups were significantly lower than those before treatment (P < 0.05). After treatment, the total SGRQ scores and each subscore in the treatment group were significantly lower than those in the control group (P < 0.05). The percentage of the predicted FEV1% and FEV1/FVC were higher in both groups, but no statistical differences were detected from before to after the treatment or between the two groups (P > 0.05). CONCLUSION: Yiqibushenhuoxue decoction could significantly decrease the SGRQ scores in patients with stable COPD, which suggests that it is able to improve patient symptoms.

Inhibition of TROY promotes OPC differentiation and increases therapeutic efficacy of OPC graft for spinal cord injury.

Endogenous or graft-derived oligodendrocytes promote myelination and aid in the recovery from central nervous system (CNS) injury. Regulatory mechanisms underlying neural myelination and remyelination in response to injury, including spinal cord injury (SCI), are unclear. In the present study, we demonstrated that TROY serves as an important negative regulator of oligodendrocyte development and that TROY inhibition augments the repair potential of oligodendrocyte precursor cell (OPC) graft for SCI. TROY expression was detected by reverse transcriptase-polymerase chain reaction in OPCs as well as in differentiated premature and mature oligodendrocytes of postnatal mice. Pharmacological inhibition or RNAi-induced knockdown of TROY promotes OPC differentiation, whereas overexpression of TROY dampens oligodendrocyte maturation. Further, treatment of cocultures of DRG neurons and OPCs with TROY inhibitors promotes myelination and myelin-sheath-like structures. Mechanically, protein kinase C (PKC) signaling is involved in the regulation of the inhibitory effects of TROY. Moreover, in situ transplantation of OPCs with TROY knockdown leads to notable remyelination and neurological recovery in rats with SCI. Our results indicate that TROY negatively modulates remyelination in the CNS, and thus may be a suitable target for improving the therapeutic efficacy of cell transplantation for CNS injury.

[Effects of prenatal exposure to stress and lead on spatial learning and memory development in rats].

OBJECTIVE: To explore the effects of prenatal exposure to stress and lead on spatial learning and memory development in rats. METHODS: All 32 Sprague-Dawley (SD) pregnant rats were divided randomly into 4 groups, 8 per group in line with the Random Number Table. The four groups were: no maternal stress, no Pb exposure (NS/C); non-maternal stress, Pb exposure (NS/L), maternal stress, no Pb exposure (S/C), and maternal stress plus Pb exposure (S/L). The spatial learning and memory ability, the serum corticosterone level both pre and post-testing of 30-day old offsprings, and lead concentration in hippocampus were tested by means of Morris Water Maze, radioimmunoassay and Inductively Coupled Plasma Mass Spectrometry (ICP-MS). RESULTS: The residence time of male and female in NS/L was (16.08+/-3.41) s, (15.72+/-3.33) s, which were significantly shorter than NS/L (25.42+/-4.76) s, (24.55+/-4.43) s and S/C (20.96+/-3.45) s, (20.65+/-2.98) s, and significant difference was observed in the joint exposure effect (F=5.478, P<0.05). The effect of the joint exposure was significant on post-testing serum corticosterone. The hippocampus lead concentrations of NS/L and S/L were (0.4378+/-0.1041) microg/g and (0.4679+/-0.1243) microg/g without significant differences (F=0.298, P>0.05). CONCLUSION: Prenatal joint exposure to restraint stress and lead might increase the effects of single exposure on the spatial learning and memory ability and serum corticosterone level of offsprings, and the joint influence on corticosterone level might be one of the reasons of further impairment of learning and memory.