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Disruption of colonic homeostasis caused by aberrant M1/M2 macrophage polarization contributes to the development of inflammatory bowel disease (IBD). Lycium barbarum polysaccharide (LBP) is the primary active constituent of traditional Chinese herbal Lycium barbarum L., which has been widely demonstrated to have important functions in regulating immune activity and anti-inflammatory. Thus, LBP may protect against IBD. To test this hypothesis, the DSS-induced colitis model was established in mice, then the mice were treated with LBP. The results indicated that LBP attenuated the weight loss, colon shortening, disease activity index (DAI), and histopathological scores of colon tissues in colitis mice, suggesting that LBP could protect against IBD. Besides, LBP decreased the number of M1 macrophages and the protein level of Nitric oxide synthase 2(NOS2) as a marker of M1 macrophages and enhanced the number of M2 macrophages and the protein level of Arginase 1(Arg-1) as a marker of M2 macrophages in colon tissues from mice with colitis, suggesting that LBP may protect against IBD by regulating macrophage polarization. Next, the mechanistic studies in RAW264.7 cells showed that LBP inhibited M1-like phenotype by inhibiting the phosphorylation of STAT1, and promoted M2-like phenotype by promoting the phosphorylation of STAT6. Finally, immunofluorescence double-staining results of colon tissues showed that LBP regulated STAT1 and STAT6 pathways in vivo. The results in the study demonstrated that LBP could protect against IBD by regulating macrophage polarization through the STAT1 and STAT6 pathways.

IntroductionIt is necessary to explore a noninvasive method to stratify head and neck squamous cell carcinoma (HNSCC)’s prognosis and to seek new indicators for individualized precision treatment. As a vital inflammatory cytokine, IL1B might drive a new tumor subtype that could be reflected in overall survival (OS) and predicted using the radiomics method.MethodsA total of 139 patients with RNA-Seq data from The Cancer Genome Atlas (TCGA) and matched CECT data from The Cancer Image Archive (TCIA) were included in the analysis. The prognostic value of IL1B expression in patients with HNSCC was analyzed using Kaplan-Meier analysis, Cox regression analysis and subgroup analysis. Furthermore, the molecular function of IL1B on HNSCC was explored using function enrichment and immunocytes infiltration analyses. Radiomic features were extracted with PyRadiomics and processed using max-relevance minredundancy, recursive feature elimination, and gradient boosting machine algorithm to construct aradiomics model for predicting IL1B expression. The area under the receiver operating characteristic curve (AUC), calibration curve, precision recall (PR) curve, and decision curve analysis (DCA) curve were used to examine the performance of the model.ResultsIncreased IL1B expression in patients with HNSCC indicated a poor prognosis (hazard ratio [HR] = 1.56, P = 0.003) and was harmful in patients who underwent radiotherapy (HR = 1.87, P = 0.007) or chemotherapy (HR = 2.514, P < 0.001). Shape_Sphericity, glszm_SmallAreaEmphasis, and firstorder_Kurtosis were included in the radiomics model (AUC: training cohort, 0.861; validation cohort, 0.703). The calibration curves, PR curves and DCA showed good diagnostic effect of the model. The rad-score was close related to IL1B (P = 4.490*10-9), and shared the same corelated trend to EMT-related genes with IL1B. A higher rad-score was associated with worse overall survival (P = 0.041).DiscussionThe CECT-based radiomics model provides preoperative IL1B expression predictionand offers non-invasive instructions for the prognosis and individualized treatment of patients withHNSCC.

IFT20 is a subunit of the intraflagellar transport (IFT) system essential for the formation and function of cilia. Besides predominant research in the cilia field, some IFT subunits perform extraciliary roles in non-ciliated cancer cells. However, the specific roles of IFT subunits in tumorigenesis remain unknown. Here, we found that knockout of IFT20 in mouse breast cancer cells lacking primary cilia promoted epithelial mesenchymal transitions (EMTs), active lamellipodia formation, and cell migration. IFT20 localized at the trans-Golgi and trans-Golgi network (TGN), and displayed vesicular co-distributions with Rab8a, the marker of TGN-to-plasma membrane vesicular trafficking. Proximity-dependent biotin identification (BioID) and colocalization analyzes showed that Numb and Ctnnal1, whose depletion promoted cell migration, co-localized with IFT20 at the trans-Golgi/TGN or intracellular transport vesicles. Furthermore, Strep-Tactin pulldown assays revealed an interaction between IFT20 and Ctnnal1 or Numb. Loss of IFT20 lowered the expression of actin-associated Tagln2, whose knockdown promoted cell migration. Thus, the extraciliary function of ITF20 in breast cancer cell was associated with the negative regulation of migration.

Disruption of colonic homeostasis caused by aberrant M1/M2 macrophage polarization contributes to the development of inflammatory bowel disease (IBD). Lycium barbarum polysaccharide (LBP) is the primary active constituent of traditional Chinese herbal Lycium barbarum L., which has been widely demonstrated to have important functions in regulating immune activity and anti-inflammatory. Thus, LBP may protect against IBD. To test this hypothesis, the DSS-induced colitis model was established in mice, then the mice were treated with LBP. The results indicated that LBP attenuated the weight loss, colon shortening, disease activity index (DAI), and histopathological scores of colon tissues in colitis mice, suggesting that LBP could protect against IBD. Besides, LBP decreased the number of M1 macrophages and the protein level of Nitric oxide synthase 2(NOS2) as a marker of M1 macrophages and enhanced the number of M2 macrophages and the protein level of Arginase 1(Arg-1) as a marker of M2 macrophages in colon tissues from mice with colitis, suggesting that LBP may protect against IBD by regulating macrophage polarization. Next, the mechanistic studies in RAW264.7 cells showed that LBP inhibited M1-like phenotype by inhibiting the phosphorylation of STAT1, and promoted M2-like phenotype by promoting the phosphorylation of STAT6. Finally, immunofluorescence double-staining results of colon tissues showed that LBP regulated STAT1 and STAT6 pathways in vivo. The results in the study demonstrated that LBP could protect against IBD by regulating macrophage polarization through the STAT1 and STAT6 pathways. [ABSTRACT FROM AUTHOR]

Background: Since the poor response to existing anti-tuberculosis drugs and low drug concentration in local bone tissues, the traditional drug therapy does not result in satisfactory treatment of osteoarticular tuberculosis. Thus, we report a rifapentine release system with imparted bone targeting potential using tetracycline (TC) -modified nanoparticles (NPs).Methods: TC was conjugated to PLGA-PEG copolymer via a DCC/NHS technique. Rifapentine-loaded NPs were prepared by premix membrane emulsification technique. The resulting NPs were characterized in terms of physicochemical characterization, hemolytic study, cytotoxicity, bone mineral binding ability, in vitro drug release, stability test and antitubercular activity. The pharmacokinetic and biodistribution studies were also performed in mice.Results: Rifapentine loaded TC-PLGA-PEG NPs were proved to be 48.8 nm in size with encapsulation efficiency and drug loading of 83.3% ± 5.5% and 8.1% ± 0.4%, respectively. The release of rifapentine from NPs could be maintained for more than 60 h. Most (68.0%) TC-PLGA-PEG NPs could bind to HAp powder in vitro. The cellular studies revealed that NPs were safe for intravenous administration. In vivo evaluations also revealed that the drug concentration of bone tissue in TC–PLGA–PEG group was significantly higher than that in other groups at all time (p < 0.05). Both NPs could improve pharmacokinetic parameters without evident organ toxicity. The minimal inhibitory concentration of NPs was 0.094 μg/mL, whereas this of free rifapentine was 0.25 μg/mL.Conclusion: Rifapentine loaded TC-PLGA-PEG NPs could increase the amount of rifapentine in bone tissue, prolong drug release in systemic circulation, enhance anti-tuberculosis activity, and thereby reducing dose and frequency of drug therapy for osteoarticular tuberculosis.

ObjectiveThe purpose of this study was to investigate the clinical efficacy of unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) for lumbar spinal stenosis (LSS).MethodsPatients who underwent UBE-TLIF due to single-segment LSS between August 2019 and July 2021 were retrospectively included in the study. Clinical outcomes evaluated include operative time, estimated blood loss (including postoperative drainage), time to ambulation, postoperative hospital stay, complications, visual analog scale (VAS) scores of low back pain and leg pain, Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), and modified Macnab criteria. Interbody bony fusion at the index level was assessed using Bridwell grading criteria.ResultsA total of 73 patients (29 males and 44 females) were enrolled in this study. All surgeries were successfully performed without intraoperative conversion to open surgery. Magnetic resonance imaging (MRI) revealed optimal direct neural decompression after UBE-TLIF. The mean operative time was 150.89 ± 15.58 min. The mean estimated blood loss was 126.03 ± 17.85 ml (postoperative drainage was 34.84 ± 8.31 ml). Time to ambulation was 2.0 ± 0.75 days after the procedure. Postoperatively, the mean hospital stay was 5.96 ± 1.38 days. VAS scores of low back pain and leg pain, JOA, and ODI were significantly improved postoperatively compared with those before the operation, and differences were statistically significant (P