Cold exposure and capsaicin promote 1,2-dimethylhyrazine-induced colon carcinogenesis in rats correlates with extracellular matrix remodeling

BACKGROUND Extracellular matrix(ECM)remodeling and stiffening,which are correlated with tumor malignancy,drives tumor development.However,the relationship between ECM remodeling and rat experimental model of 1,2-dimethylhyrazine(DMH)-induced colorectal cancer(CRC)imposed by cold and capsaicin exposure remains unclear.AIM To explore the effects of cold exposure and capsaicin on ECM remodeling and ECM enzymes in DMH-induced CRC.METHODS For histopathological analysis,the sections of colon tissues were stained with hematoxylin and eosin,Masson’s trichrome,Picrosirius red,and Weigert’s Resorcin-Fuchsin to observe the remodeling of collagen and elastin.Additionally,the protein expression level of type I collagen(COL I),type 3 collagen(COL III0,elastin,matrix metalloproteinase(MMP)1,MMP2,MMP9,and tissue-specific matrix metalloproteinase 1(TIMP1)was assessed by immunohistochemistry.The messenger RNA(mRNA)levels of COL I,COL III,elastin,and lysyl oxidase-like-2(LOXL2)in the colon tissues of rats was measured by reverse-transcriptase quantitative polymerase chain reaction.RESULTS Although no differences were observed in the proportion of adenomas,a trend towards the increase of invasive tumors was observed in the cold and capsaicin group.The cold exposure group had a metastasis rate compared with the other groups.Additionally,abnormal accumulation of both collagen and elastin was observed in the cold exposure and capsaicin group.Specifically,collagen quantitative analysis showed increased length,width,angle,and straightness compared with the DMH group.Collagen deposition and straightness were significantly increased in the cold exposure group compared with the capsaicin group.Cold exposure and capsaicin significantly increased the protein levels of COL I,elastin,and LOXL2 along with increases in their mRNA levels in the colon tissues compared with the DMH group,while COL III did not show a significant difference.Furthermore,in immunohistochemical evaluations,MMP1,MMP2,MMP9,and TIMP1 staining increased in the cold exposure and capsaicin group compared with the DMH group.CONCLUSION These results suggest that chronic cold and capsaicin exposure further increased the deposition of collagen and elastin in the colonic tissue.Increased COL I and elastin mRNA and protein levels expression may account for the enhanced ECM remodel and stiffness variations of colon tissue.The upregulated expression of the LOXL2 and physiological imbalance between MMP/TIMP activation and deactivation could contribute to the progression of the CRC resulting from cold and capsaicin exposure.

Bioactive fibrous scaffolds with programmable release of polypeptides regulate inflammation and extracellular matrix remodeling

Inflammation manipulation and extracellular matrix(ECM)remodeling for healthy tissue regeneration are critical requirements for tissue engineering scaffolds.To this end,the bioactive polycaprolactone(PCL)-based scaffolds are fabricated to release aprotinin and thymosinβ4(Tβ4)in a programmable manner.The core part of the fiber is composed of hyaluronic acid and Tβ4,and the shell is PCL,which is further coated with heparin/gelatin/aprotinin to enhance biocompatibility.The in vitro assay demonstrates that the controlled release of aprotinin prevents initial excessive inflammation.The subsequent release of Tβ4 after 3 days induces the transition of macrophages from M1 into M2 polarization.The manipulation of inflammatory response further controls the expression of transforming growth factor-βand fibroblast activation,which oversee the quantity and quality of ECM remodeling.In addition,the gradual degradation of the scaffold allows cells to proliferate within the platform.In vivo implant evaluation convinces that PCL-based scaffolds possess the high capability to control the inflammatory response and restore the ECM to normal conditions.Hence,our work paves a new way to develop tissue engineering scaffolds for inflammation manipulation and ECM remodeling with peptide-mediated reactions.

The effect of diet-induced obesity on extracellular matrix remodeling during skeletal muscle regeneration

Diet-induced obesity has previously been shown to occur with the concomitant rise in the expression of proin-flammatory cytokines and increases in collagen deposition.While it has been known that the regenerative process of skeletal muscle is altered in obese mice following an acute muscle injury,we sought to examine differences in the expression of various markers of extracellular matrix remodeling and repair.Our laboratory has previously reported an impaired inflammatory and protein synthetic signaling in these mice that may contribute negatively to the muscle regenerative process.To expand upon this previous investigation,tissues from these animals un-derwent further analysis to determine the extent of changes to the regenerative response within the extracellular matrix,including transcriptional changes in CollagenⅠ,CollagenⅢ,and Fibronectin.Here,we show that the expression of CollagenⅢ:Ⅰis significantly increased at 3-days post-injury in obese injured animals compared to lean injured animals(p=0.0338),and by 28-days the obese injured animals exhibit a significantly lower CollagenⅢ:Ⅰthan their lean injured counterparts(p=0.0035).We demonstrate an impaired response to an acute muscle injury in obese mice when compared with lean counterparts.However,further studies are required to elucidate translational consequences of these changes,as well as to determine any causative mechanisms that may be driving this effect.

Potential biomarkers for diagnosis and disease evaluation of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis(IPF)is a chronic progressive lung disease characterized by progressive lung fibrogenesis and histological features of usual interstitial pneumonia.IPF has a poor prognosis and presents a spectrum of disease courses ranging from slow evolving disease to rapid deterioration;thus,a differential diagnosis remains challenging.Several biomarkers have been identified to achieve a differential diagnosis;however,comprehensive reviews are lacking.This review summarizes over 100 biomarkers which can be divided into six categories according to their functions:differentially expressed biomarkers in the IPF compared to healthy controls;biomarkers distinguishing IPF from other types of interstitial lung disease;biomarkers differentiating acute exacerbation of IPF from stable disease;biomarkers predicting disease progression;biomarkers related to disease severity;and biomarkers related to treatment.Specimen used for the diagnosis of IPF included serum,bronchoalveolar lavage fluid,lung tissue,and sputum.IPF-specific biomarkers are of great clinical value for the differential diagnosis of IPF.Currently,the physiological measurements used to evaluate the occurrence of acute exacerbation,disease progression,and disease severity have limitations.Combining physiological measurements with biomarkers may increase the accuracy and sensitivity of diagnosis and disease evaluation of IPF.Most biomarkers described in this review are not routinely used in clinical practice.Future large-scale multicenter studies are required to design and validate suitable biomarker panels that have diagnostic utility for IPF.