TBK1, a prioritized drug repurposing target for amyotrophic lateral sclerosis: evidence from druggable genome Mendelian randomization and pharmacological verification in vitro.

BACKGROUND: There is a lack of effective therapeutic strategies for amyotrophic lateral sclerosis (ALS); therefore, drug repurposing might provide a rapid approach to meet the urgent need for treatment. METHODS: To identify therapeutic targets associated with ALS, we conducted Mendelian randomization (MR) analysis and colocalization analysis using cis-eQTL of druggable gene and ALS GWAS data collections to determine annotated druggable gene targets that exhibited significant associations with ALS. By subsequent repurposing drug discovery coupled with inclusion criteria selection, we identified several drug candidates corresponding to their druggable gene targets that have been genetically validated. The pharmacological assays were then conducted to further assess the efficacy of genetics-supported repurposed drugs for potential ALS therapy in various cellular models. RESULTS: Through MR analysis, we identified potential ALS druggable genes in the blood, including TBK1 [OR 1.30, 95%CI (1.19, 1.42)], TNFSF12 [OR 1.36, 95%CI (1.19, 1.56)], GPX3 [OR 1.28, 95%CI (1.15, 1.43)], TNFSF13 [OR 0.45, 95%CI (0.32, 0.64)], and CD68 [OR 0.38, 95%CI (0.24, 0.58)]. Additionally, we identified potential ALS druggable genes in the brain, including RESP18 [OR 1.11, 95%CI (1.07, 1.16)], GPX3 [OR 0.57, 95%CI (0.48, 0.68)], GDF9 [OR 0.77, 95%CI (0.67, 0.88)], and PTPRN [OR 0.17, 95%CI (0.08, 0.34)]. Among them, TBK1, TNFSF12, RESP18, and GPX3 were confirmed in further colocalization analysis. We identified five drugs with repurposing opportunities targeting TBK1, TNFSF12, and GPX3, namely fostamatinib (R788), amlexanox (AMX), BIIB-023, RG-7212, and glutathione as potential repurposing drugs. R788 and AMX were prioritized due to their genetic supports, safety profiles, and cost-effectiveness evaluation. Further pharmacological analysis revealed that R788 and AMX mitigated neuroinflammation in ALS cell models characterized by overly active cGAS/STING signaling that was induced by MSA-2 or ALS-related toxic proteins (TDP-43 and SOD1), through the inhibition of TBK1 phosphorylation. CONCLUSIONS: Our MR analyses provided genetic evidence supporting TBK1, TNFSF12, RESP18, and GPX3 as druggable genes for ALS treatment. Among the drug candidates targeting the above genes with repurposing opportunities, FDA-approved drug-R788 and AMX served as effective TBK1 inhibitors. The subsequent pharmacological studies validated the potential of R788 and AMX for treating specific ALS subtypes through the inhibition of TBK1 phosphorylation.

Gastric adenosquamous carcinoma with an elevated serum level of alpha-fetoprotein: A case report.

BACKGROUND: Gastric adenosquamous carcinoma (ASC) is rare and characterized by coexisting of adenocarcinoma andsquamous carcinoma within the same tumor. We present a female patient with gastric ASC who had an elevated serum level of alpha-fetoprotein (AFP), which decreased to normal levels after a laparoscopic distant radical gastrectomy in a short period. The clinicopathological features in AFP-producing gastric cancer (GC) are discussed, as well as potentially available prognostic predictors. CASE SUMMARY: A 50-year-old woman presented to our department with a chief complain of a 6-mo history of bloating. She had no basic diseases including heart diseases and respiratory diseases, and she also denied any prior history of dysphagia, hematemesis, melena, rectal bleeding, hematochezia, or unintentional weight loss. Based on her symptoms, an esophagogastroduodenoscopy was performed, showing an annular cavity lesion 3 cm from the pylorus with a diameter of 6 cm. A biopsy of the lesion showed gastric ASC, whereas the pylorus biopsy showed normal mucosa. The patient further received an enhanced computed tomography scan which demonstrated an invasive lesion close to the pylorus with a still clear margin of the tumor to peripheral organs such as the pancreas and liver. Scattered lymph nodes were visible around, whereas no sign of liver metastasis was discovered. Serum tumor markers including carcinoembryonic antigen (CEA), cancer antigen 199 (CA199), CA724, CA125, and CA242 were all normal, while the level of serum AFP increased to 172 ng/mL. A laparoscopic distant radical gastrectomy was performed after exclusion of surgical contraindications. Postoperative pathology results showed that the tumor displayed an ulcerated ASC phenotype (90% of medium to highly-differentiated squamous cell carcinoma, 10% of poorly differentiated adenocarcinoma. Surprisingly, the serum level of AFP decreased to normal level on post operation day 5. The tumor cells were positive for CK5/6, p63, and CEA, and negative for AFP and Epstein-Barr encoding region. CONCLUSION: We presented a rare case of gastric ASC with elevated serum AFP level, which may be new subtype of AFP-producing GC. Follow-up detection of serum AFP might be a useful tool to predict patient prognosis.

Nasal microbes in allergic rhinitis children with or without sublingual immunotherapy.

The mechanism of allergic rhinitis (AR) remains unclear. Most researchers believe that AR is the result of a combination of environmental and genetic factors. Sublingual immunotherapy (SLIT) is a treatment that can change the natural course of AR through immunomodulatory mechanism and maintain efficacy after the treatment. Nasal cavity is the main site where AR patients contact with external allergens, produce inflammatory reactions and nasal symptoms. Therefore, in this study, we investigate the nasal microbiome in AR patients, and the changes after SLIT. In this cross-sectional study, nasal swabs for microbiome analysis were collected from 3 groups: SLIT-naïve AR patients (AR group), AR patients undergoing SLIT treatment over 2 years (SLIT group) and a control group (CG). The characteristics of nasal microbiome of each groups were produced by 16s-rDNA sequencing technology. The Simpson index of AR group was significantly higher than that of CG and SLIT groups, but not different between SLIT group and CG group. The abundance of Bacteroidete and Firmicutes remarkably increased in the AR group, but Bacteroidete reduced to CG level after SLIT. AR patients have different nasal microbiome composition, but we do not know how it happened and whether the AR condition affected nasal microbiome composition or nasal microbiome affected AR.

Torus Tubarius Hypertrophy After Adenoidectomy.

Backgrounds: Adenoidectomy is widely used to cure sleep-disordered breathing symptoms in children, torus tubarius hypertrophy (TTH) after adenoidectomy causing recurred snoring, sleep apnea, nasal obstruction, or mouth breathing was rarely reported, and the causes of TTH are still unclear. Objectives: To report a rare complication TTH after adenoidectomy, and the features of TTH. Material and Methods: A total of 36 pediatric patients with TTH diagnosed by our hospital from January 2017 to 2023 were included in this study. All children were treated conservatively for a month at first, and 13 patients underwent partial resection of TTH. The influencing factors (sex, age, allergic rhinitis [AR], and first operation way) were analyzed. Results: There were 36 patients with TTH: 27 boys and 9 girls. The age of the first operation ranged from 20 to 63 months, and the interval time of TTH after operation ranged from 3 to 55 months. Thirteen patients underwent partial resection of TTH. Thirteen children had definite symptoms and signs of AR. Conclusions and Significance: TTH is a rare complication after adenoidectomy, which is common in male children (75.0%) and in patients who took adenoidectomy before the age of 5 years (94.4%). TTH can occur as early as 3 months after adenoidectomy. AR and the operation way might have relationships with TTH.

The mechanism of carbon source utilization by microalgae when co-cultivated with photosynthetic bacteria.

Microalgae-photosynthetic bacteria (PSB) co-culture, which is promising for wastewater treatment and lipid production, is lacking of study. In this work, the combinations of 3 microalgae and 3 PSB strains were firstly screened and then different inoculation ratios of the co-cultures were investigated. It was found the best promotion was Chlorella pyrenoidosa/Rhodobacter capsulatus co-culture (1:1), where the biomass productivity, acetate assimilation rate and lipid productivity were 1.64, 1.61 and 2.79 times than that of the sum of pure microalgae and PSB cultures, respectively. Meanwhile, the inoculation ratio significantly affected the growth rate and lipid productivity of co-culture systems. iTRAQ analysis showed that PSB played a positive effect on acetate assimilation, TCA cycle and glyoxylate cycle of microalgae, but decreased the carbon dioxide utilization and photosynthesis, indicating PSB promoted the microalgae metabolism of organic carbon utilization and weakened inorganic carbon utilization. These findings provide in-depth understanding of carbon utilization in microalgae-PSB co-culture.

Netting Gut Disease: Neutrophil Extracellular Trap in Intestinal Pathology.

Many gut disease etiologies are attributed to the presence of robust inflammatory cell recruitment. The recruitment of neutrophils plays a vital role in inflammatory infiltration. Neutrophils have various antimicrobial effector mechanisms, including phagocytosis, oxidative burst, and degranulation. It is suggested that neutrophils could release neutrophil extracellular traps (NETs) to kill pathogens. However, recent evidence indicates that neutrophil infiltration within the gut is associated with disrupted local immunological microenvironment and impaired epithelial barrier. Growing evidence implies that NETs are involved in the progression of many diseases, including cancer, diabetes, thrombosis, and autoimmune disease. Increased NET formation was found in acute or chronic conditions, including infection, sterile inflammation, cancer, and ischemia/reperfusion injury (IRI). Here, we present a comprehensive review of recent advances in the understanding of NETs, focusing on their effects in gut disease. We also discuss NETs as a potential therapeutic target in gut disease.

Structure-Guided Design of the First Noncovalent Small-Molecule Inhibitor of CRM1.

Nuclear export factor chromosome region maintenance 1 (CRM1) is an attractive anticancer and antiviral drug target that spurred several research efforts to develop its inhibitor. Noncovalent CRM1 inhibitors are desirable, but none is reported to date. Here, we present the crystal structure of yeast CRM1 in complex with S109, a substructure of CBS9106 (under clinical test). Superimposition with the LFS-829 (another covalent CRM1 inhibitor) complex inspired the design of a noncovalent CRM1 inhibitor. Among nine synthesized compounds, noncovalent CRM1 inhibitor 1 (NCI-1) showed a high affinity to human and yeast CRM1 in the absence or presence of GST-bound Ras-related nuclear protein (RanGTP). Unlike covalent inhibitors, the crystal structure showed that NCI-1 is bound in the "open" nuclear export signal (NES) groove of CRM1, simultaneously occupying two hydrophobic pockets. NCI-1 additionally inhibited the nuclear export and proliferation of cells harboring the human CRM1-C528S mutant. Our work opens up the avenue of noncovalent CRM1 inhibitor development toward a more potent, less toxic, and broad-spectrum anticancer/antiviral therapy.

Steroidal alkaloids from the bulbs of Fritillaria pallidiflora Schrenk and their anti-inflammatory activity.

Steroidal alkaloids (1-11), including one new 24-hydroxylated cevanine-type steroidal alkaloid, named yibeinone F (1), were isolated from the bulbs of Fritillaria pallidiflora Schrenk. Their structures were elucidated by analyses of extensive spectroscopic data and comparison of the NMR data with those reported previously, and the structures of compounds 1, 7 and 11 were further confirmed by X-ray single crystal diffraction analyses. The anti-inflammatory effects of all the isolated alkaloids were evaluated in LPS-activated RAW264.7 macrophages. Among them, compounds 9 (stenanzine) and 10 (hapepunine) showed significant inhibitory effects against LPS-induced NO production with IC50 values of 8.04 µM and 20.85 µM, respectively. Furthermore, compound 9 effectively inhibited the release of cytokines such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2), and suppressed the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) in LPS-stimulated RAW264.7 cells. Further experiments revealed the underlying mechanism that 9 blocked LPS-induced phosphorylation and degradation of inhibitor-α of nuclear transcription factor κB (IκBα) and c-Jun N-terminal kinase (JNK) in RAW264.7 cells. Taken together, compound 9 may be a valuable candidate for the treatment of inflammatory diseases.

Ferroptosis inhibitory constituents from the fruits of Cullen corylifolium.

In current study, we studied the phytochemicals of Cullen corylifolium (fruits) in which we identify twenty compounds, including two coumarins (1 and 2), three coumestans (3-5), fourchalcone (6-9), three dihydroflavones (10-12), four isoflavones (13-16), one flavonoid (17) and three meroterpenes (18-20). Among these, compounds 4, 5 and 12 were isolated from C. corylifolium for the first time. The ferroptosis inhibitory effects of the isolated phytochemicals were assessed using erastin-exposed HT22 mouse hippocampal cells. Compounds 3 and 18 showed the most potent inhibition with the IC50 values of 5.21 µM and 5.41 µM, respectively. Moreover, molecular docking study showed that compound 3 possessed tremendous inhibitory affinity for human 5-lipoxygenase (5-LOX) and Kelch-like ECH-related protein 1: nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) protein-protein interactions, two important ferroptosis-related targets. These findings indicate that compound 3 (psoralidin) may be a potential therapeutic agent for the treatment of ferroptosis-related diseases.

Terpenoid and phenolic derivatives from the aerial parts of Elsholtzia rugulosa and their anti-inflammatory activity.

Seven undescribed terpenoids, including three pairs of enantiomers, named (±)-rugulolides A-C, and one cyclopentenone derivative, named rugulolide D, together with twenty-six known compounds, were isolated from the aerial parts of Elsholtzia rugulosa. The chiral separation of rugulolides A-C was achieved by high-performance liquid chromatography using the chiral column. Their structures were elucidated unambiguously based on comprehensive spectroscopic analysis in conjunction with electronic circular dichroism (ECD) and single-crystal X-ray diffraction experiments. Rugulolides A-D are rare naturally occurring terpenoid derivatives featuring a methylated α,ß-unsaturated-γ-lactone or a cyclopent-2-en-1-one nucleus. All the isolates were evaluated for their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 cell, among them, four compounds showed moderate inhibition with IC50 values ranging from 12.46 to 23.10 µM.

Efficacy of a 3-year course of sublingual immunotherapy for mite-induced allergic rhinitis with a 3-year follow-up.

Aim: To evaluate the long-term efficacy of sublingual immunotherapy (SLIT) in treating mite-sensitized allergic rhinitis (AR). Materials & methods: 150 AR children were randomly divided into SLIT and pharmacotherapy (PT) groups, receiving a 3-year course of SLIT along with PT or PT only. Results: The symptom and medication scores at the 3- and 6-year follow-up were significantly lower compared with the baseline levels in both groups, while the values were significantly lower in SLIT group than in PT group. No significant differences were observed between 3- and 6-year follow-up in SLIT group. Conclusion: 3-year SLIT along with PT appeared more effective compared with PT only for mite-induced AR in children, and the treatment was effective for at least 3 consecutive years even after SLIT ceased.

Costunolide improved dextran sulfate sodium-induced acute ulcerative colitis in mice through NF-κB, STAT1/3, and Akt signaling pathways.

Costunolide (CTL) is the major sesquiterpene lactone from Radix Aucklandiae, which is widely used on the treatment of gastrointestinal diseases. However, the therapeutic effect of costunolide in ulcerative colitis (UC) is still unknown. Herein, we sought to evaluate the therapeutic effects and underlying mechanisms of costunolide on UC. ICR mice were intraperitoneally administered with costunolide (10 mg/kg) for 10 days. Beginning on the 4th day of drug administration, acute colitis was induced by feeding 4% dextran sulfate sodium (DSS) for additional 7 days. Costunolide markedly attenuated DSS-induced body weight loss, colonic shortening, elevation in disease activity index, and pathological damage of colon, and decreased the number of CD4+ T cells in colon tissues. Furthermore, costunolide significantly inhibited myeloperoxidase (MPO) activity and nitric oxide (NO) level in colon tissues in DSS-exposed mice. Meanwhile, costunolide also suppressed DSS-induced expression of induced nitric oxide synthase (iNOS), interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in both mRNA and protein levels. Mechanistically, costunolide repressed the phosphorylation of nuclear factor kappa-B (NF-κB) p65 and degradation of inhibitor of NF-κB (IκB), as well as the excessive activation of signal transducers and activators of transcription 1/3 (STAT1/3) and serine/threonine protein kinase Akt (Akt) in colon tissues in DSS-challenged mice. These findings successfully demonstrated that costunolide ameliorated DSS-induced murine acute colitis by suppressing inflammation through inactivation of NF-κB, STAT1/3, and Akt pathways. These results also suggested that costunolide may be a potential therapeutic agent for the treatment of acute UC.

MicroRNA-675-3p regulates IL-1ß-stimulated human chondrocyte apoptosis and cartilage degradation by targeting GNG5.

Growing evidence has indicated that microRNAs (miRNAs) are modulators of osteoarthritis (OA) development and progression. In this study, we first evaluated the anti-apoptosis and chondroprotective effects of microRNA-675-3p (miR-675-3p) on interleukin-1ß (IL-1ß)-stimulated human chondrocytes. The overexpression of miR-675-3p inhibited apoptosis and cartilage matrix degradation and promoted cell proliferation in human chondrocytes. Target gene prediction and luciferase reporter assays suggested that G-protein subunit γ 5 (GNG5) may be the target gene of miR-675-3p. The overexpression of miR-675-3p inhibited IL-1ß-stimulated chondrocyte apoptosis, and this effect was reversed by the overexpression of GNG5. Finally, we used bioinformatic tools and biological methods to show that the long noncoding RNA X-inactive specific transcript (lncRNA XIST) could bind to miR-675-3p, which affects the expression of GNG5 mRNA. Our findings may substantiate miR-675-3p as a new treatment for OA.

Comprehensive investigation of the relationship between organic content and waste activated sludge dewaterability.

The relationship between sludge organic fraction and its dewaterability is well known in practice. However, the formal study to reveal the underlying reason is limited. To improve understanding of the nature of organic content on sludge dewatering process, this study systematically evaluated the effects of sludge organic content on its dewaterability and revealed the underlying mechanism. Analysis of 10 waste activated sludge (WAS) samples with varying organic contents showed that capillary suction time (CST) increased linearly from 34.90 ± 0.10 s to 104.90 ± 0.30 s (R2 = 0.92, p < 0.01), whereas the solid content of centrifuge cake decreased from 21.23 %±0.45 % to 12.52 %±0.14 % (R2 = 0.89, p < 0.01) when organic fractionincreased from 35.72 % to 61.11 %. These results first confirmed that WAS dewatering performance was negatively correlated to its organic content. Then, the underlying mechanism was revealed by studying the basic physicochemical properties of WAS with various organic content. The results showed that sludge with a higher organic content generally had greater extracellular polymeric substances (EPS) content, lower density and higher negative zeta potential, which hinder the aggregation and flocculation of floc particles. These properties endow the WAS with a higher organic content generally possessed more bound water content, small pores, poorer fluidity, and stronger network strength. These characteristics can hamper the separation of water from sludge cake during dewatering. Based on which, this study discussed the potential of organic fraction as a surrogate of EPS for evaluating WAS dewaterability and indicated the organic fraction can be a useful and strong indicator of WAS dewaterability.

Anticancer activity of dietary xanthone α-mangostin against hepatocellular carcinoma by inhibition of STAT3 signaling via stabilization of SHP1.

Hepatocellular carcinoma (HCC) is one of the most lethal human cancers worldwide. The dietary xanthone α-mangostin (α-MGT) exhibits potent anti-tumor effects in vitro and in vivo. However, the anti-HCC effects of α-MGT and their underlying mechanisms are still vague. Aberrant activation of signal transducer and activator of transcription 3 (STAT3) is involved in the progression of HCC. We therefore investigated whether α-MGT inhibited the activation of STAT3 and thereby exhibits its anti-HCC effects. In this study, we found that α-MGT significantly suppressed cell proliferation, induced cell cycle arrest, and triggered apoptosis in HCC cells, including HepG2, SK-Hep-1, Huh7, and SMMC-7721 cells in vitro, as well as inhibiting tumor growth in nude mice bearing HepG2 or SK-Hep-1 xenografts. Furthermore, α-MGT potently inhibited the constitutive and inducible activation of STAT3 in HCC cells. In addition, α-MGT also suppressed IL-6-induced dimerization and nuclear translocation of STAT3, which led to inhibition of the expression of STAT3-regulated genes at both mRNA and protein levels. Mechanistically, α-MGT exhibited effective inhibition of the activation of STAT3's upstream kinases, including JAK2, Src, ERK, and Akt. Importantly, α-MGT increased the protein level of Src homology region 2 domain-containing phosphatase-1 (SHP1), which is a key negative regulator of the STAT3 signaling pathway. Furthermore, α-MGT enhanced the stabilization of SHP1 by inhibiting its degradation mediated by the ubiquitin-proteasome pathway. Knockdown of SHP1 using siRNA obviously prevented the α-MGT-mediated inhibition of the activation of STAT3 and proliferation of HCC cells. In summary, α-MGT exhibited a potent anti-HCC effect by blocking the STAT3 signaling pathway via the suppression of the degradation of SHP1 induced by the ubiquitin-proteasome pathway. These findings also suggested the potential of dietary derived α-MGT in HCC therapy.

Influential factors for visit time for tracheobronchial foreign bodies in pediatrics.

PURPOSE: This study aims to investigate the inflential factors for visit time for tracheobronchial foreign bodies in pediatrics, and to shorten the time of diagnosis and reduce complications. METHODS: A questionnaire survey was designed and conducted among the caretakers of children with tracheobronchial foreign bodies, and the related inflential factors for visit time were analyzed. RESULTS: The visit time for tracheobronchial foreign body was correlated with the age of the child, the type of foreign body, the educational level of the caretaker, a history of foreign body aspiration were provided, an examination was performed during the visit, the anti-inflammatory and anti-allergic treatment, and transfer to a higher level hospital. Age, history of foreign body aspiration were provided, and anti-inflammatory and anti-allergic treatment were the independent inflential factors for the time of diagnosis (P < 0.05). CONCLUSION: The visit time for tracheobronchial foreign bodies was affected by many factors. It is necessary to strengthen the publicity scope and intensity on health education for tracheobronchial foreign bodies in community doctors and parents, to shorten the time of diagnosis and reduce complications.

High fatty acid productivity from Scenedesmus obliquus in heterotrophic cultivation with glucose and soybean processing wastewater via nitrogen and phosphorus regulation.

In this study, the effects of nitrogen and phosphorus supply on biodiesel production from Scenedesmus obliquus with glucose as the carbon source were investigated. It was found that sufficient phosphorus could further improve biodiesel production under nitrogen starvation. S. obliquus was cultivated in soybean processing wastewater. The removal efficiencies of carbon oxygen demand (COD), total nitrogen (TN), and total phosphorus (TP) after 8-day cultivation were 72%, 95%, and 54%, respectively. Moreover, the fatty acid productivity after eight-day cultivation reached as high as 99.3 mg·L-1·d-1, which was 1.15 times higher than the highest efficiency using a glucose culture. This result was due to two naturally-formed stages occurring with sufficient phosphorus: nitrogen sufficiency stage for biomass and nitrogen starvation stage for lipid accumulation. It verified the conclusion of the roles of nitrogen and phosphorus obtained in the glucose culture and provided an economic and environmentally friendly choice for biodiesel production with efficient soybean wastewater treatment.

Which coin is easier to pass esophagus spontaneously?

OBJECTIVE: To determine the factors associated with the spontaneous passage (SP) of coins lodged in the esophagus in children. SUBJECTS AND METHODS: A total of 351 pediatric patients with coin ingestion admitted to our hospital from March 2016 to March 2019 were included in the study. The patients underwent a period of overnight watch with a repeated chest x-ray within 24 h after the commencement of hospitalization. The influencing factors (sex, age, types of coin, time in the esophagus, and location) were analyzed. RESULTS: The repeated chest x-ray showed coins that had passed into the stomach or intestine in 68 patients. Sex, age, time in the esophagus, location in the esophagus or the types of coins were not associated with SP, but the distribution of the esophageal coins varied statistically significantly in the different ages. CONCLUSION: Coins pass spontaneously through the esophagus (19.4%) within 24 h, unrelated to sex, age, time of esophagus lodging, coin location in the esophagus, or coin types. Children approximately two years old were more likely to ingest small coins (10 or 50 cents), whereas children approximately five years old were more likely to ingest a large coin (1 Yuan).

Total flavonoids from sea buckthorn ameliorates lipopolysaccharide/cigarette smoke-induced airway inflammation.

The total flavonoids from sea buckthorn (TFSB) exhibit a potent anti-inflammatory activity; however, the effect of TFSB on respiratory inflammatory disease is not fully known. The present study evaluated the potential of TFSB to prevent airway inflammation and the underlying mechanism. The results showed that TFSB remarkably inhibited lipopolysaccharide/cigarette smoke extract (LPS/CSE)-induced expression of IL-1ß, IL-6, CXCL1, and MUC5AC at both mRNA and protein levels in HBE16 bronchial epithelial cells. TFSB also decreased the production of PGE2 through inhibition the expression of COX2 in LPS/CSE-stimulated HBE16 cells. Furthermore, bronchoalveolar fluid and histological analyses revealed that LPS/cigarette smoke exposure-induced elevated cell numbers of neutrophils and macrophages in bronchoalveolar fluid, inflammatory cell infiltration, and airway remodeling were remarkably attenuated by TFSB in mice. Immunohistochemical results also confirmed that TFSB decreased the expression of IL-1ß, IL-6, COX2, CXCL1, and MUC5AC in LPS/CS-exposed mice. Mechanistically, TFSB blocked LPS/CSE-induced activation of ERK, Akt, and PKCα. Molecular docking further confirmed that the main components in TFSB including quercetin and isorhamnetin showed potent binding affinities to MAPK1 and PIK3CG, two upstream kinases of ERK and Akt, respectively. In summary, TFSB exerts a potent protective effect against LPS/CS-induced airway inflammation through inhibition of ERK, PI3K/Akt, and PKCα pathways, suggesting that TFSB may be a novel therapeutic agent for respiratory diseases.