Idiopathic pulmonary fibrosis (IPF) is a group of chronic interstitial pulmonary diseases characterized by myofibroblast proliferation and extracellular matrix deposition with limited treatment options. Based on our previous observation, we hypothesized microcystin-leucine arginine (LR), an environmental cyanobacterial toxin, could potentially suppress pulmonary fibrosis. In this study, we first demonstrated that chronic exposure of microcystin-LR by oral for weeks indeed attenuated the pulmonary fibrosis both on bleomycin-induced rat and fluorescein isothiocyanate-induced mouse models. Our data further indicated that treatment with microcystin-LR substantially reduced TGF-β1/Smad signaling in rat pulmonary tissues. The experiments in vitro found that microcystin-LR was capable of blocking epithelial-mesenchymal transition (EMT) and fibroblast-myofibroblast transition (FMT) through suppressing the differentiation of CD206 + macrophages. Mechanically, microcystin-LR was found to bind to glucose-regulated protein 78 kDa (GRP78) and suppress endoplasmic reticulum unfolded protein response (UPR ER) signaling pathways. These events led to the modulation of M2 polarization of macrophages, which eventually contributed to the alleviation of pulmonary fibrosis. Our results revealed a novel mechanism that may account for therapeutic effect of microcystin-LR on IPF.

Background: A positive surgical margin (PSM) following oral cancer resection results in local recurrence and poor prognosis. Mono-block tumor specimens, especially from the tumor base, are difficult to evaluate. This inaccurate sampling ultimately leads to a false pathological diagnosis. Lugol's iodine (I 2-IK)-enhanced micro-CT is an emerging method to image tumor specimens. This study explores the feasibility of I 2-IK-enhanced micro-CT to evaluate the surgical margin for tongue squamous cell carcinoma (TSCC) specimens and to further seek optimal staining parameters. Methods: Rabbit tongue tissues and human TSCC samples were imaged via I 2-IKenhanced micro-CT. The optimal I 2-IK concentration and staining time were determined before clinical application using tissue shrinkage, micro-CT image quality, and effect on pathological diagnosis as assessment criteria. Next, 6 TSCC specimens were used to verify the process feasibility of surgical margin imaging with the optimal parameters. Finally, the possible reason by which I 2-IK could enhance micro-CT imaging was validated in vitro. Results: I 2-IK staining influenced specimen shrinkage, micro-CT image quality, and pathological image quality in a concentration-and time-dependent manner. After comprehensively considering these indicators, 3% I 2-IK staining for 48 and 12 h were found to be optimal for rabbit tongue tissues and TSCC samples, respectively. This method could provide a detailed 3-D structure of TSCC samples compared with H&E sections. Moreover, tumor and normal tissues could be differentiated by their glycogen content, which has high affinity with I 2-IK. Conclusions: I 2-IK-enhanced micro-CT could, thus, indicate the tumor margin and assist pathological sampling in patients with TSCC postoperation.

Background: Accurate assessment of regional lymph node (LN) status is essential for the treatment of head and neck squamous cell carcinoma (HNSCC) patients. In this study, we aimed to compare the difference between intravenous injection of indocyanine green (ICG) and peritumoral injection of ICG in the location of metastatic LNs.Methods: Twenty-nine patients were enrolled in this study with 13 patients receiving intravenous injection of ICG and 16 patients receiving peritumoral injection of ICG. During the surgery, the fluorescence-positive LNs in vivo were sent to undergo frozen section after fluorescence intensity was recorded. After the cervical LN dissection, all LNs were sorted by region, and the fluorescence intensity was recorded before the LNs were sent for paraffin section.Results: During the surgery, both intravenous or peritumoral injections with near-infrared (NIR) fluorescence imaging of ICG had their respective pros and cons in vivo, with the sensitivity and specificity being 62.5%/75% and 98.1%/89.1% respectively. After the surgery, both methods could reduce the pathological workload by preselecting the LNs at-risk in the premise of accurate assessing the cervical LN stage. However, intravenous ICG administration was more valuable in determining all types of LN status according to the fluorescence intensity [area under the curve (AUC): 0.91 vs. 0.78, P<0.001].Conclusions: With the assistance of NIR fluorescence imaging using ICG, both administration methods could reduce the postoperative complication and the pathological workload, whereas the intravenous mode of ICG administration is superior in application value.

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