Analgesic Effect of Perineural Injection of BoNT/A on Neuropathic Pain Induced by Chronic Constriction Injury of Sciatic Nerve in Rats.

This study was designed to investigate the analgesic effect of perineural injection of BoNT/A on neuropathic pain induced by sciatic nerve chronic constriction injury (CCI) and possible mechanisms. SD rats were randomly divided into Sham group, CCI group and BoNT/A group. Paw mechanical withdrawal threshold (pMWT) and paw thermal withdrawal latency (pTWL) of each group were detected at different time points after surgery. The expression of myelin markers, autophagy markers and NLRP3 inflammasome-related molecules in injured sciatic nerves were examined at 12 days after surgery. Moreover, C-fiber evoked potential in spinal dorsal horn was recorded. The expression of SNAP-25, neuroinflammation and synaptic plasticity in spinal dorsal horn of each group were examined. Then rats treated with BoNT/A were randomly divided into DMSO group and Wnt agonist group to further explore the regulatory effect of BoNT/A on Wnt pathway. We found that pMWT and pTWL of ipsilateral paw were significantly decreased in CCI group compared with Sham group, which could be improved by perineural injection of BoNT/A at days 7, 9 and 12 after surgery. The peripheral analgesic mechanisms of perineural injection of BoNT/A might be related to the protective effect on myelin sheath by inhibiting NLRP3 inflammasome and promoting autophagy flow, while the central analgesic mechanisms might be associated with inhibition of neuroinflammation and synaptic plasticity in spinal dorsal horn due to inhibiting SNAP-25 and Wnt pathway. As a new route of administration, perineural injection of BoNT/A can relieve CCI induced neuropathic pain probably via both peripheral and central analgesic mechanisms.

Prenatal environmental antibiotics and fetal and postnatal growth: A biomonitoring-based prospective study in Eastern China.

Thus far, the effect of environmental antibiotics exposure to offspring's growth remains unclear. Here we aimed to evaluate whether and to what extent environmental antibiotics exposure is associated with fetal and postnatal growth. A total of 735 pregnant women and their full-term offspring from the Shanghai Obesity Birth Cohort were involved in the study. Maternal urine specimen was collected during the third trimester, and urinary concentration of fifteen environmental antibiotics was measured by liquid chromatography-tandem mass spectrometry and enzymatic method. Children were followed at birth, 12, 24 and 60 months, and growth parameters of the weight and height of children were recorded. Linear regression model was applied, and it was found that maternal veterinary antibiotic (VA) concentration was negatively associated with birth weight and ponderal index [per natural-logarithm (ln)-unit: adjusted ß (95% confidence interval, CI) = - 42.1 (- 74.0, - 10.3) for birth weight, -0.11 (- 0.19, - 0.02) for birth weight z-score, and - 0.03 (- 0.05, - 0.002) for ponderal index]. Regarding specific VA, each ln-unit increment of florfenicol concentrations was likely to be associate with 39.7 g (95%CI: - 69.3, - 10.1) reduced birth weight, 0.10 (95%CI: - 0.18, - 0.02) reduced birth weight z-score, and 0.02 g/cm3 (95%CI: - 0.04, - 0.00) reduced ponderal index. Ciprofloxacin, a preferred-as-veterinary antibiotic, showed a similar dose-response relationship with neonatal anthropometric parameters to florfenicol. However, these adverse effects diminished as children grew up to 12-, 24- and 60-month-old. Larger prospective cohort studies and animal experiments are warranted to verify the hypothesis that environmental antibiotics exposure in early life, even at low doses, may cause fetal growth restriction.

Interaction of tetrahydrofuran and methyl tert-butyl ether in waste gas treatment by a biotrickling filter bioaugmented with Piscinibacter caeni MQ-18 and Pseudomonas oleovorans DT4.

Bioaugmented biotrickling filter (BTF) seeded with Piscinibacter caeni MQ-18, Pseudomonas oleovorans DT4, and activated sludge was established to investigate the treatment performance and biodegradation kinetics of the gaseous mixtures of tetrahydrofuran (THF) and methyl tert-butyl ether (MTBE). Experimental results showed an enhanced startup performance with a startup period of 9 d in bioaugmented BTF (25 d in control BTF seeded with activated sludge). The interaction parameter I2,1 of control (7.462) and bioaugmented BTF (3.267) obtained by the elimination capacity-sum kinetics with interaction parameter (EC-SKIP) model indicated that THF has a stronger inhibition of MTBE biodegradation in the control BTF than in the bioaugmented BTF. Similarly, the self-inhibition EC-SKIP model quantified the positive effects of MTBE on THF biodegradation, as well as the negative effects of THF on MTBE biodegradation and the self-inhibition of MTBE and THF. Metabolic intermediate analysis, real-time quantitative polymerase chain reaction, biofilm-biomass determination, and high-throughput sequencing revealed the possible mechanism of the enhanced treatment performance and biodegradation interactions of MTBE and THF.

Ultrasound-Guided Nerve Hydrodissection With 5% Dextrose 4 Weeks After Steroid Injection in Treatment of Carpal Tunnel Syndrome: A Retrospective Study.

OBJECTIVE: To investigate the efficacy and safety of ultrasound-guided nerve hydrodissection (HD) with 5% dextrose (D5W) as add-on therapy after corticosteroid injection in carpal tunnel syndrome (CTS), and provide a novel strategy. METHODS: In this retrospective study, patients with CTS who received ultrasound-guided nerve HD with D5W as add-on therapy after corticosteroid injection (combination group) were enrolled. Patients who received corticosteroid injection without add-on therapy (steroid group) were recruited as the control group. Ultrasound-guided nerve HD with D5W was performed 4 weeks after corticosteroid injection. Treatment effectiveness were assessed by visual analog scale (VAS) and Boston Carpal Tunnel Syndrome Questionnaire (BCTQ). The assessment was performed at baseline and 4, 8, and 12 weeks after corticosteroid injection. In addition, adverse events were recorded in this study. RESULTS: A total of 49 patients and 62 wrists meeting the criteria were included, with 24 patients and 31 wrists in the steroid group and 25 patients and 31 wrists in the combination group. Compared with baseline data, both groups showed greater improvement in VAS, BCTQs (BCTQ severity), and BCTQf (BCTQ function) at 4, 8, and 12 weeks follow-up. VAS, BCTQs, and BCTQf scores at baseline and week 4 were comparable between steroid group and combination group. Compared with steroid group, combination group exhibited a significant reduction in VAS, BCTQs, and BCTQf at 8- and 12-week follow-up (P ≤ 0.01). No adverse event occurred in any group. CONCLUSIONS: Our results showed that ultrasound-guided nerve HD with D5W as add-on therapy after corticosteroid injection was efficacious and safe in CTS, and combination therapy is more beneficial than corticosteroid monotherapy in the improvement of symptoms and function at 8- and 12-week follow-up.

The Impact of the COVID-19 Pandemic on Pediatric Clinical Practice in Wenzhou, China: A Retrospective Study.

Introduction: The COVID-19 pandemic has affected all aspects of life worldwide. The aim of the present study was to review and describe and acknowledge the impact of COVID-19 on the pediatric health care system at a pediatric tertiary hospital in Wenzhou. Methods: A retrospective study was conducted at Yuying Children's Hospital of Wenzhou Medical University, a public pediatric tertiary hospital in Southern Zhejiang Province that specializes in pediatrics. The data regarding the primary diagnosis of patients were extracted from the electronic medical records system of the hospital. Data for outpatients and inpatients treated at the pediatric department were analyzed in the time frame of 22 weeks since the beginning of the pandemic (from December 30, 2019 to June 2, 2020) and compared with data from the same period in 2019. Results: The total number of outpatient cases in the previous 22 weeks of the year declined from 560,620 in 2019 to 247,030 in 2020, and inpatient cases decreased from 14,177 to 7,555. This negative trend settled by week 6 and 7 and subsequently approached the 2019 numbers. The most noticeable decrease in the number of cases was observed in children of preschool age. Moreover, the number of weekly visits decreased at the beginning of the epidemic, reached the lowest value during the lockdown period, and recovered after the lockdown. Conclusion: Based on the results of this study, clinical practice in a pediatric department in Wenzhou was substantially affected by the epidemic and measures such as physical distancing and increased personal hygiene, particularly in preschool-age children. An understanding of the trends and impacts of the pandemic on pediatric patients and health systems will facilitate better preparation of pediatricians in the future.

Synergistic effect of glucocorticoids and IGF-1 on myogenic differentiation through the Akt/GSK-3ß pathway in C2C12 myoblasts.

Purpose: Glucocorticoids are the only therapeutics that can delay the progression of Duchenne musculardystrophy (DMD), the most prevalent type of inherited neuromuscular disorder in males. However, beyond theiranti-inflammatory effects, glucocorticoids have other underlying mechanisms that remain unclear. Moreover, muscleand circulating levels of insulin growth factor-1 (IGF-1) often decrease in response to glucocorticoids. Therefore, wehypothesized that glucocorticoids, either alone or in combination with IGF-1, can improve myogenic differentiation.Materials and methods: Established C2C12 myoblasts were employed as an in vitro model of myogenic differentiation,and myogenic differentiation markers, as assessed by Western blot (myogenin, MyoD, and MyHC protein expression),cellular morphology analysis (fusion index) and RT-PCR (MCK mRNA expression), were measured.Results: Myogenic differentiation markers were increased by glucocorticoid treatment. Furthermore, this effect was furtherenhanced by IGF-1, and these results suggest that glucocorticoids, either alone or together with IGF-1, can promotemyogenic differentiation. Akt and GSK-3ß play important roles in myogenic differentiation. Interestingly, the levels ofboth phosphorylated Ser473-Akt and phosphorylated Ser9-GSK-3ß were increased by glucocorticoid and IGF-1 cotreatment.Pharmacological manipulation with LY294002 and LiCl was employed to inhibit Akt and GSK-3ß, respectively.We found that cellular differentiability was inhibited by LY294002 and enhanced by LiCl, indicating that theAkt/GSK-3ß signaling pathway is activated by glucocorticoid and IGF-1 treatment to promote myogenic differentiation.Conclusions: Glucocorticoids together with IGF-1 promote myogenic differentiation through the Akt/GSK-3ßpathway. Thus, these results further our knowledge of myogenic differentiation and may offer a potential alternativestrategy for DMD treatment based on glucocorticoid and IGF-1.

Long-term treatment of blepharospasm with botulinum toxin A: a service-based study over a 16-year follow-up in southern China.

OBJECTIVE: To elucidate the effect of long-term treatment with botulinum toxin A (BTX-A) for blepharospasm. Prevalence data and clinical features in southern China and influencing factors for selecting BTX-A treatment were explored. METHODS: We collected data retrospectively from 338 consecutive patients diagnosed with blepharospasm over 16 years to assess prevalence data and clinical features. Thereafter, all patients were classified into BTX-A (n = 135) or non-BTX-A (n = 203) treatment groups according to the patients' requests in order to explore the factors influencing whether BTX-A treatment was chosen. Furthermore, dynamic follow-up data were analyzed to evaluate the long-term efficacy in the BTX-A group. RESULTS: The prevalence was 23.3 per million, with an onset age of 50.3 ± 12.3 years and a female:male ratio of 2.4:1; the most common symptom was excessive blinking (91.2%). The symptom severity and psychological assessment scores were significantly decreased by treatment with BTX-A (p < 0.01), and there was no significant difference in response duration with the prolongation of BTX-A injections. Adverse events occurred 52 times (5.0%) among 1038 injections. The symptom severity and psychological assessment scores and the occurrence of eye-opening difficulty were higher, and medical expenses and the symptom tolerability rate were lower in the BTX-A group than in the non-BTX-A group (p < 0.05). CONCLUSION: The onset age was earlier than that in Western countries. However, starting BTX-A treatment early is justified, even though a higher dosage was needed to maintain reliable long-term efficacy. Additionally, symptom severity and medical expenses are the primary factors affecting whether patients select BTX-A treatment.

Wnt/ß-catenin signaling pathway regulates asthma airway remodeling by influencing the expression of c-Myc and cyclin D1 via the p38 MAPK-dependent pathway.

Airway remodeling is the main characteristic of asthma; however, the mechanisms underlying this pathophysiological change have not been fully elucidated. Previous studies have indicated that the Wnt/ß-catenin and mitogen-activated protein kinase (MAPK) signaling pathway are involved in the development of airway remodeling during asthma. Therefore, the present study established an airway remodeling rat model, after which ß-catenin, cyclin D1 and c-Myc protein expressions were analyzed via western blotting in the lung tissue and airway smooth muscle cells (ASMCs) of rats. The mRNA expression of the aforementioned proteins were evaluated via reverse transcription-quantitative PCR. ß-catenin, cyclin D1 and c-Myc are core transcription factors and target genes of the Wnt/ß-catenin and MAPK signaling pathways. Furthermore, ß-catenin, c-Myc and cyclin D1 protein expression were determined following blocking of the p38 MAPK signaling pathway in vitro. The results demonstrated that higher expressions of ß-catenin, cyclin D1 and c-Myc were detected in lung tissues and ASMCs in the asthma group compared with the control. Blocking the p38 MAPK signaling pathway with a specific inhibitor SB203580 also downregulated the expressions of ß-catenin, cyclin D1 and c-Myc in vitro. Taken together, these results indicated that the Wnt/ß-catenin signaling pathway may regulate the process of airway remodeling via the p38 MAPK-dependent pathway.

Two-dimensional transition-metal halide CoBr3 with spin-polarized Dirac cone.

Recently, the discovery of two-dimensional transition-metal materials with non-trivial magnetic and electronic properties has spurred huge interest in investigating their applications in nanotechnology. Here, we report that the monolayer of CoBr3 possesses a quantum anomalous Hall insulating phase generated on the basis of first-principles calculations. We find that the CoBr3 monolayer is an intrinsic two-dimensional ferromagnetic material with a Curie temperature Tc = 264 K predicted from Monte Carlo simulations. The phonon spectra analysis indicates that the CoBr3 monolayer is dynamically stable. Taking into account spin-orbit coupling, this makes the electronic structure of the CoBr3 monolayer topologically non-trivial with a global band gap of 8.7 meV. The anomalous Hall conductivity calculation shows a Chern number C = 2, meaning the presence of a two edge state in nanoribbons of finite width. These findings not only add an experimentally feasible member to the quantum anomalous Hall insulator family, but also pave the way for highly promising application potentials in nanoelectronics and spintronics.

Vitamin D alleviates airway remodeling in asthma by down-regulating the activity of Wnt/ß-catenin signaling pathway.

Vitamin D exerts a protective role in asthma; however, the molecular mechanisms underlying the vitamin D-attenuated asthma airway remodeling are yet to be elucidated. In this study, Sprague-Dawley (SD) rats were randomly divided into four groups: control, asthma, vitamin D 50 ng/mL, and vitamin D 100 ng/mL. The treatment with 100 ng/mL vitamin D remarkably reduced the thickness of the airway smooth muscle, collagen deposition, and the alpha-smooth muscle actin (α-SMA) mass and airway inflammation. Conversely, the treatment by vitamin D significantly up-regulated the serum levels of 25(OH)2D3 that were decreased in asthma. The putative signaling pathway of vitamin D was based on Wnt5a and ß-catenin expression assessed by quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) and Western blot, which revealed that the administration of vitamin D significantly decreased the activity of Wnt/ß-catenin signaling pathway. These results suggested that administration of vitamin D alleviated the airway remodeling in asthma by down-regulating the activity of Wnt/ß-catenin signaling pathway.

Predictors of oedema type in reversible posterior leukoencephalopathy syndrome with preeclampsia or eclampsia.

OBJECTIVE: To explore the predictive factors of oedema types in reversible posterior leukoencephalopathy syndrome (RPLS) with preeclampsia (PE) and eclampsia, which is closely related to reversible lesions and clinical recovery. METHOD: We collected data from 44 consecutive patients diagnosed with RPLS in PE or eclampsia between 2013 and 2017. All patients were classified into vasogenic oedema (n = 31) or cytotoxic oedema (n = 13) groups according to magnetic resonance imaging (MRI) results. General information, clinical data, biochemical indicators and imaging features were collected retrospectively to explore the differences between the groups. Furthermore, we analysed potential predictive factors by logistic regression. RESULTS: The occurrence rates of immune disease and stillbirth, hospitalization time and the levels of serum albumin (ALB), lactate dehydrogenase (LDH), aspartate transaminase (AST) and alanine aminotransferase (ALT) were higher, while the values of systolic blood pressure (SBP), mean arterial pressure (MAP) and 24-h urine protein were lower in the cytotoxic oedema patients than those in the vasogenic oedema patients (p < .05). The ALB concentration was closely correlated with vasogenic oedema, while AST and ALT were closely correlated with cytotoxic oedema by logistic regression (p < .05). CONCLUSION: The levels of ALB, AST and ALT are potential predictors for the development of oedema in RPLS. ALB is related to vasogenic oedema by a possible mechanism of decreased colloid osmotic pressure, while AST and ALT are related to cytotoxic oedema by a possible mechanism of endothelial dysfunction.

Allergy march of Chinese children with infantile allergic symptoms: a prospective multi-center study.

BACKGROUND: Allergy march refers to progression of allergic diseases from infantile food allergy to the development of asthma and allergic rhinitis (AR). Evidence come mostly from studies in European countries. This study aimed to investigate allergy march in Chinese children with infantile food protein allergy (FPA) with a special focus on the effect of different formula interventions. METHODS: From 2008 to 2010, 153 infants diagnosed with FPA were recruited in five tertiary hospitals across China. They were randomly treated with amino-acid-based formula or soy-protein-based formula for a period of 3 months. Long-term follow-up was performed when they reached early school age, using questionnaires, physical examinations, and serum-specific immunoglobulin E. RESULTS: The overall follow-up rate was 73.20%. In patients who reached their early school years, the prevalence of physician-diagnosed AR and asthma were 43.75% and 23.21%, respectively. Only 40% of the subjects remained positive for food sensitizations upon follow-up. Twenty-six subjects receiving aeroallergen screening tests in infancy all proved negative, but upon follow-up, 65.57% were sensitized to aeroallergens (P=0.005). No significant difference between the effects of amino-acid-based formula and soy-protein-based formula on children's allergy march was observed. CONCLUSIONS: A high proportion (47.32%) of Chinese infants with early allergic symptoms developed respiratory allergies by their early school years. Most food-sensitized infants outgrew their condition several years later, but then aeroallergen sensitization often occurred. Amino-acid-based formula showed no advantages over soy protein-based formula with respect to arresting the allergy march.

Comparisons of presentations and outcomes of neuromyelitis optica patients with and without Sjögren's syndrome.

Patients with neuromyelitis optica (NMO) often have an accompanying autoimmune disease, most commonly, but not limited to Sjögren's syndrome (SS). The aim of this study was to compare clinical and laboratory features between NMO patients with and without SS and to investigate the prognosis of NMO in patients with and without SS. Twenty-three NMO patients with SS and 42 NMO patients without SS were included. Clinical and laboratory profiles were compared, including annual relapse rate and time from onset of NMO to Expanded Disability Status Scale (EDSS) scores of 4.0 and 6.0. More NMO patients with SS than those without SS had anti-nuclear antibody, anti-SS-A/Ro and anti-SS-B/La antibodies (91.3 vs. 35.7%, p < 0.001, 87.0 vs. 2.3%, p < 0.001, and 34.8 vs. 0.0%, p < 0.001, respectively). Serum immunoglobulins (IgA, IgM and IgG) were markedly increased in NMO patients with SS in comparison with those without SS. Annual relapse rate and the time from disease onset to an EDSS score of 4.0 and 6.0 were not significantly different between the two groups. No differences between the two groups were found for the other parameters, including AQP-4 antibody status, length of spinal cord lesion and brain lesions. These results imply that NMO in SS more likely represents coexistence with SS rather than representing the result of direct central nervous system involvement in SS. Autoimmune response appears to be more intense in the NMO group with SS, but did not cause a more severe prognosis in comparison with the group without SS, indicating that we should pay attention to the potential benefit of the antinuclear antibodies in NMO.

TGF-ß1 activates the canonical NF-κB signaling to promote cell survival and proliferation in dystrophic muscle fibroblasts in vitro.

Activated fibroblasts continue to proliferate at injury sites, leading to progressive muscular fibrosis in Duchenne muscular dystrophy (DMD). TGF-ß1 is a dominant profibrotic mediator thought to play a critical role in muscle fibrosis; however, the implicated mechanisms are not fully understood. Here we showed that TGF-ß1 increased the resistance to apoptosis and stimulated cell cycle progression in dystrophic muscle fibroblasts under serum deprivation conditions in vitro. TGF-ß1 treatment activated the canonical NF-κB pathway; and we found that pharmacological inhibition of IKKß with IMD-0354 and RelA gene knockdown with siRNA attenuated these effects of TGF-ß1 on dystrophic muscle fibroblasts. Collectively, our data suggest that TGF-ß1 prevents apoptosis and cell cycle arrest in dystrophic muscle fibroblasts through the canonical NF-κB signaling pathway.

Massive cryptogenic hemoptysis undergoing pulmonary resection: clinical and pathological characteristics and management.

Massive cryptogenic hemoptysis is a common presenting symptom and cause of hospitalization for respiratory diseases, and represents a challenging condition in the clinical. This study aimed to analyze the clinical and pathologic data and management of patients with massive cryptogenic hemoptysis. We retrospectively reviewed 12 patients with massive cryptogenic hemotysis in our hospital between January 2003 and December 2012. Bronchoscopy showed submucosal vascular abnormalities in 4 patients. Of 6 patients managed with conservative measures, bleeding was completely controlled in 2 patients. Of 10 hemoptysis patients, three were controlled by bronchial arterial embolization, and seven by surgery. Pathological examination showed a superficial dysplastic, tortuous and dilated bronchial artery under the bronchial epithelium in 4 patients, and bronchiole dilation in 2 patients, indicating Dieulafoy's disease of the bronchus and bronchiectasis. No malignance developed within the follow-up. In conclusion, Dieulafoy's disease of the bronchus and bronchiectasis should be suspected in patients with massive cryptogenic hemoptysis. BAE and surgical treatment should be considered in case that massive hemoptysis could not be controlled by conservative management.

Adjunctive dexamethasone therapy improves lung injury by inhibiting inflammation and reducing RIP3 expression during Staphylococcus aureus pneumonia in mice.

Antibiotic-induced immunopathology associated with the release of bacterial cell wall components has been suggested to contribute to poor outcomes in bacterial pneumonia. Adjunctive systemic glucocorticoid steroid (GC) therapy for pneumonia has been a controversial issue. In the present study, we first found that dexamethasone (2.5 mg/kg/day) in combination with oxacillin was beneficial for improving lung injury in mice inoculated intratracheally with live Staphylococcus aureus, and did not interfere with bacterial clearance. Alleviation of lung injury was evidenced by attenuated lung pathology, reduced total protein levels, soluble receptor for advanced glycation end-products (sRAGE), tumor necrosis factor alpha (TNF-α), and keratinocyte chemoattractant (KC) and interleukin (IL)-6 in bronchoalveolar lavage fluid (BALF). It was further confirmed by inhibition of receptor interacting protein-3 (RIP3) expression in pulmonary tissues. As in the live S. aureus experiments, dexamethasone (2.5 mg/kg/day) improved lung injury in mice challenged with heat-killed S. aureus (HKSA). In conclusion, our results demonstrated that an appropriate dose of adjunctive dexamethasone (2.5 mg/kg/day) with oxacillin alleviated experimental S. aureus-induced lung injury via its inhibition of inflammatory cytokine release and RIP3 expression.

Role of SIRT1 in Streptococcus pneumoniae-induced human ß-defensin-2 and interleukin-8 expression in A549 cell.

Streptococcus pneumoniae is an important pathogen of pneumonia in human. Human alveolar epithelium acts as an effective barrier and is an active participant in host defense against invasion of bacterial by production of various mediators. Sirtuin 1 (SIRT1), the prototypic class III histone deacetylase, is involved in the molecular control of lifespans and immune responses. This study aimed at examining the role of SIRT1 in mediating S. pneumoniae-induced human ß-defensin-2 (hBD2) and interleukin-8(IL-8) expression in the alveolar epithelial cell line A549 and the underlying mechanisms involved. A549 cells were infected with S. pneumoniae for indicated times. Exposure of A549 cells to S. pneumoniae increased the expressions of SIRT1 protein, hBD2 and IL-8 mRNA, and protein. The SIRT1 activator resveratrol enhanced S. pneumoniae-induced gene expression of hBD2 but decreased IL-8 mRNA levels. Blockade of SIRT1 activity by the SIRT1 inhibitors nicotinamide reduced S. pneumoniae-induced hBD2 mRNA expression but increased its stimulatory effects on IL-8 mRNA. S. pneumoniae-induced activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). SIRT1 expression was attenuated by selective inhibitors of ERK and p38 MAPK. The hBD2 mRNA production was decreased by pretreatment with p38 MAPK inhibitor but not with ERK inhibitor, whereas the IL-8 mRNA expression was controlled by phosphorylation of ERK. These results suggest that SIRT1 mediates the induction of hBD2 and IL-8 gene expression levels in A549 cell by S. pneumoniae. SIRT1 may play a key role in host immune and defense response in A549.