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Cancers Jul 2023Cancer development is a multifactorial procedure that involves changes in the cell microenvironment and specific modulations in cell functions. A tumor microenvironment... (Review)
Review
Cancer development is a multifactorial procedure that involves changes in the cell microenvironment and specific modulations in cell functions. A tumor microenvironment contains tumor cells, non-malignant cells, blood vessels, cells of the immune system, stromal cells, and the extracellular matrix (ECM). The small leucine-rich proteoglycans (SLRPs) are a family of nineteen proteoglycans, which are ubiquitously expressed among mammalian tissues and especially abundant in the ECM. SLRPs are divided into five canonical classes (classes I-III, containing fourteen members) and non-canonical classes (classes IV-V, including five members) based on their amino-acid structural sequence, chromosomal organization, and functional properties. Variations in both the protein core structure and glycosylation status lead to SLRP-specific interactions with cell membrane receptors, cytokines, growth factors, and structural ECM molecules. SLRPs have been implicated in the regulation of cancer growth, motility, and invasion, as well as in cancer-associated inflammation and autophagy, highlighting their crucial role in the processes of carcinogenesis. Except for the class I SLRP decorin, to which an anti-tumorigenic role has been attributed, other SLPRs' roles have not been fully clarified. This review will focus on the functions of the class I and II SLRP members biglycan and lumican, which are correlated to various aspects of cancer development.
PubMed: 37509212
DOI: 10.3390/cancers15143549 -
Alternative Therapies in Health and... Oct 2023This study aims to investigate the role of decorin in the adhesion process of Treponema pallidum subspecies pallidum (T. pallidum) to human brain microvascular...
OBJECTIVE
This study aims to investigate the role of decorin in the adhesion process of Treponema pallidum subspecies pallidum (T. pallidum) to human brain microvascular endothelial cells.
METHODS
The study involved an in vitro experimental design. Western blot analysis was conducted to determine the protein expression level of decorin in the cells. The cells were divided into four groups: Tp group, inactivated Tp group, LPS group, and negative control group. The adhesion of T. pallidum to the cells was analyzed using darkfield microscopy counting and quantitative polymerase chain reaction (qPCR). The cells were divided into four groups based on different preprocessing treatments: control group, decorin group, DCN-siRNA group, and DCN-siRNA+decorin group. Changes in the F-actin of the cells were explored using confocal laser scanning microscopy. The cells were divided into the Tp group, Tp+decorin group, and control group.
RESULTS
Western blot analysis showed high expression of decorin in the Tp group and LPS group. Darkfield microscopy counting revealed a significantly higher number of T. pallidum adhered to a single cell in the decorin group compared to the control group. Conversely, the number of adhered T. pallidum was significantly lower in the DCN-siRNA group compared to the control group. qPCR results indicated a considerably higher T. pallidum load in the decorin group compared to the control group. In the Tp group, T. pallidum treatment induced the reorganization of F-actin, while the distribution of F-actin in the Tp+decorin group was comparable to that of the control group.
CONCLUSIONS
Decorin enhances the adhesion of T. pallidum to human brain microvascular endothelial cells, suggesting that decorin may act as one of the receptors regulating the adhesion of T. pallidum to cells. Furthermore, T. pallidum treatment triggers the rearrangement of F-actin in cells, and decorin plays a protective role in this process.
Topics: Humans; Treponema pallidum; Decorin; Endothelial Cells; Actins; Globus Pallidus; Lipopolysaccharides
PubMed: 37471666
DOI: No ID Found -
Journal of Experimental & Clinical... Jul 2023The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is largely unknown. Here, we elucidated the...
BACKGROUND
The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is largely unknown. Here, we elucidated the functional role of B. adolescentis and its possible mechanism on the manipulation of Decorin macrophages in colorectal cancer.
METHODS
The relative abundance of B. adolescentis in tumor or para-tumor tissue of CRC patients was analyzed. The role of B. adolescentis was explored in the CRC animal models. The single cell-RNA sequencing (scRNA-seq) was used to investigate the myeloid cells subsets in TME. The expression level of TLR2/YAP axis and its downstream Decorin in macrophages were tested by Western blot and qRT-PCR. Knockdown of Decorin in Raw264.7 was performed to investigate the effect of Decorin macrophages on subcutaneous tumor formation. Multi-immunofluorescence assay examined the number of Decorin macrophages on the CRC tissue.
RESULTS
We found that the abundance of B. adolescentis was significantly reduced in tumor tissue of CRC patients. Supplementation with B. adolescentis suppressed AOM/DSS-induced tumorigenesis in mice. ScRNA-seq and animal experiment revealed that B. adolescentis increased Decorin macrophages. Mechanically, Decorin was activated by TLR2/YAP axis in macrophages. The abundance of B. adolescentis was correlated with the number of Decorin macrophages and the expression level of TLR2 in tumor tissue of CRC patients.
CONCLUSIONS
These results highlight that B. adolescentis induced Decorin macrophages and provide a novel therapeutic target for probiotic-based modulation of immune microenvironment in CRC.
Topics: Animals; Mice; Bifidobacterium adolescentis; Decorin; Toll-Like Receptor 2; Carcinogenesis; Macrophages; Colorectal Neoplasms; Tumor Microenvironment
PubMed: 37464382
DOI: 10.1186/s13046-023-02746-6 -
International Journal of Molecular... Jul 2023Previously, we found that human pancreatic preadipocytes (PPAs) and islets influence each other and that the crosstalk with the fatty liver via the hepatokine...
Previously, we found that human pancreatic preadipocytes (PPAs) and islets influence each other and that the crosstalk with the fatty liver via the hepatokine fetuin-A/palmitate induces inflammatory responses. Here, we examined whether the mRNA-expression of pancreatic extracellular matrix (ECM)-forming and -degrading components differ in PPAs from individuals with normal glucose regulation (PPAs-NGR), prediabetes (PPAs-PD), and type 2 diabetes (PPAs-T2D), and whether fetuin-A/palmitate impacts ECM-formation/degradation and associated monocyte invasion. Human pancreatic resections were analyzed (immuno)histologically. PPAs were studied for mRNA expression by real-time PCR and protein secretion by Luminex analysis. Furthermore, co-cultures with human islets and monocyte migration assays in Transwell plates were conducted. We found that in comparison with NGR-PPAs, TIMP-2 mRNA levels were lower in PPAs-PD, and TGF-β1 mRNA levels were higher in PPAs-T2D. Fetuin-A/palmitate reduced fibronectin, decorin, TIMP-1/-2 and TGF-ß1 mRNA levels. Only fibronectin was strongly downregulated by fetuin-A/palmitate independently of the glycemic status. Co-culturing of PPAs with islets increased TIMP-1 mRNA expression in islets. Fetuin-A/palmitate increased MMP-1, usherin and dermatopontin mRNA-levels in co-cultured islets. A transmigration assay showed increased monocyte migration towards PPAs, which was enhanced by fetuin-A/palmitate. This was more pronounced in PPAs-T2D. The expression of distinct ECM components differs in PPAs-PD and PPAs-T2D compared to PPAs-NGR, suggesting that ECM alterations can occur even in mild hyperglycemia. Fetuin-A/palmitate impacts on ECM formation/degradation in PPAs and co-cultured islets. Fetuin-A/palmitate also enhances monocyte migration, a process which might impact on matrix turnover.
Topics: Humans; Diabetes Mellitus, Type 2; Fibronectins; Tissue Inhibitor of Metalloproteinase-1; Prediabetic State; alpha-2-HS-Glycoprotein; Extracellular Matrix; Pancreatic Hormones; Palmitates; RNA, Messenger; Adipocytes; Glucose
PubMed: 37446346
DOI: 10.3390/ijms241311169 -
International Journal of Molecular... Jul 2023Lesions in the human anterior cruciate ligament (ACL) are frequent, unsolved clinical issues due to the limited self-healing ability of the ACL and lack of treatments...
Lesions in the human anterior cruciate ligament (ACL) are frequent, unsolved clinical issues due to the limited self-healing ability of the ACL and lack of treatments supporting full, durable ACL repair. Gene therapy guided through the use of biomaterials may steadily activate the processes of repair in sites of ACL injury. The goal of the present study was to test the hypothesis that functionalized poly(sodium styrene sulfonate)-grafted poly(ε-caprolactone) (pNaSS-grafted PCL) films can effectively deliver recombinant adeno-associated virus (rAAV) vectors as a means of overexpressing two reparative factors (transforming growth factor beta-TGF-β and basic fibroblast growth factor-FGF-2) in primary human ACL fibroblasts. Effective, durable rAAV reporter red fluorescent protein and candidate TGF-β and FGF-2 gene overexpression was achieved in the cells for at least 21 days, especially when pNaSS-grafted PCL films were used versus control conditions, such as ungrafted films and systems lacking vectors or films (between 1.8- and 5.2-fold differences), showing interactive regulation of growth factor production. The expression of TGF-β and FGF-2 from rAAV via PCL films safely enhanced extracellular matrix depositions of type-I/-III collagen, proteoglycans/decorin, and tenascin-C (between 1.4- and 4.5-fold differences) in the cells over time with increased levels of expression of the specific transcription factors Mohawk and scleraxis (between 1.7- and 3.7-fold differences) and without the activation of the inflammatory mediators IL-1β and TNF-α, most particularly with pNaSS-grafted PCL films relative to the controls. This work shows the value of combining rAAV gene therapy with functionalized PCL films to enhance ACL repair.
Topics: Humans; Transforming Growth Factor beta; Dependovirus; Anterior Cruciate Ligament; Fibroblast Growth Factor 2; Fibroblasts
PubMed: 37446318
DOI: 10.3390/ijms241311140 -
Cancer Science Aug 2023Gastric cancer (GC) has high rates of morbidity and mortality, and this phenomenon is particularly evident in coastal regions where local dietary habits favor the...
Gastric cancer (GC) has high rates of morbidity and mortality, and this phenomenon is particularly evident in coastal regions where local dietary habits favor the consumption of pickled foods such as salted fish and vegetables. In addition, the diagnosis rate of GC remains low due to the lack of diagnostic serum biomarkers. Therefore, in this study, we aimed to identify potential serum GC biomarkers for use in clinical practice. To identify candidate biomarkers of GC, 88 serum samples were first screened using a high-throughput protein microarray to measure the levels of 640 proteins. Then, 333 samples were used to validate the potential biomarkers using a custom antibody chip. ELISA, western blot, and immunohistochemistry were then used to verify the expression of the target proteins. Finally, logistic regression was performed to select serum proteins for the diagnostic model. As a result, five specific differentially expressed proteins, TGFβ RIII, LAG-3, carboxypeptidase A2, Decorin and ANGPTL3, were found to have the ability to distinguish GC. Logistic regression analysis showed that the combination of carboxypeptidase A2 and TGFβ RIII had superior potential for diagnosing GC (area under the ROC curve [AUC] = 0.801). The results suggested that these five proteins alone and the combination of carboxypeptidase A2 and TGFβ RIII may be used as serum markers for the diagnosis of GC.
Topics: Humans; Biomarkers, Tumor; Protein Array Analysis; Stomach Neoplasms; Carboxypeptidases A; Early Detection of Cancer; ROC Curve; Angiopoietin-Like Protein 3
PubMed: 37290894
DOI: 10.1111/cas.15876 -
Microbiology Spectrum Aug 2023The Lyme disease spirochete Borrelia burgdorferi can cause a multitude of clinical manifestations because of its ability to disseminate into any organ system via...
The Lyme disease spirochete Borrelia burgdorferi can cause a multitude of clinical manifestations because of its ability to disseminate into any organ system via migration through soft tissue, the lymphatic system, and the circulatory system. The latter is believed to constitute the predominant pathway for dissemination to distal sites from the inoculating tick bite. In spite of its importance, the hematogenous dissemination process remains largely uncharacterized, particularly due to difficulties studying this process in a living host and the lack of an system that recapitulates animal infection. In the current work, we provide the first information regarding the stage of the vascular transmigration pathway where three important adhesins function during invasion of mouse knee joint peripheral tissue from postcapillary venules. Using intravital imaging coupled with genetic experiments employing sequential double infection, we show a complex temporal choreography of P66, decorin binding proteins (DbpA/B), and outer surface protein C (OspC) at discrete steps along the pathway of vascular escape, underscoring the importance of B. burgdorferi adhesins in hematogenous dissemination in the mouse knee joint and the complexity of vascular transmigration by a disseminating pathogen. Lyme disease is caused by the spirochete Borrelia burgdorferi, which is transmitted by a bite from an infected tick. Disease development involves a complex series of host-pathogen interactions as well as dissemination of the infecting organisms to sites distal to the original tick bite. The predominant pathway for this is believed to be hematogenous dissemination. The mechanism by which the spirochetes escape circulation is unknown. Here, using intravital microscopy, where the Lyme spirochete can be observed in a living mouse, we have studied the stage in the vascular escape process where each of three surface adhesins functions to facilitate escape of the spirochete from postcapillary venules to invade mouse knee joint peripheral tissue. A complex pattern of involvement at various locations in the multistage process is described using a unique experimental approach that is applicable to other disseminating pathogens.
Topics: Mice; Animals; Borrelia burgdorferi; Tick Bites; Adhesins, Bacterial; Lyme Disease; Borrelia burgdorferi Group
PubMed: 37255427
DOI: 10.1128/spectrum.01254-23 -
The Journal of Maternal-fetal &... Dec 2023This study analyzed the levels of peripheral blood tumor necrosis factor-α (TNF-α), Decorin (DCN) and Mitogen-activated protein kinase 1 (MAPK1) mRNA in neutrophils...
This study analyzed the levels of peripheral blood tumor necrosis factor-α (TNF-α), Decorin (DCN) and Mitogen-activated protein kinase 1 (MAPK1) mRNA in neutrophils of patients with preeclampsia and their correlations, in order to provide more thoughts on the diagnosis and treatment of clinical patients. 81 patients with preeclampsia who had regular prenatal checkups and delivered in our hospital from June 2020 to April 2022 were analyzed, including 26 patients with early-onset and 55 patients with late-onset, and 50 pregnant women with normal pregnancy who had prenatal checkups and delivered in our hospital during the same period were selected as the control group. Record the clinical data of patients, record the expression of peripheral blood TNF-α, DCN and neutrophils MAPK1 mRNA of patients with early-onset, late-onset and the control group, and record the correlation between DCN level, MAPK1 mRNA expression and TNF-α level of patients with preeclampsia. The diastolic and systolic blood pressures were significantly higher in early-onset and late-onset patients, and the gestational week of delivery was significantly lower in early-onset and late-onset patients, respectively ( < .05); there was no statistically significant difference in the average age, BMI, average pregnancy time, and average births between the three groups ( > .05). The expressions of peripheral blood TNF-α, DCN, and neutrophils MAPK1 mRNA of the early-onset and late-onset groups were all higher than those in the control group ( < .05); and the expressions of TNF-α, DCN, and MAPK1 mRNA in the peripheral blood of the early-onset group were all higher than those in the late-onset group ( < .05); correlation analysis showed that DCN level and TNF-α level in patients with preeclampsia were positively correlated ( = 0.98639, < .05); Neutrophils MAPK1 mRNA expression and TNF-α level were positively correlated ( = 0.9611, < .05). TNF-α, DCN and neutrophils MAPK1 mRNA were all highly expressed in the peripheral blood of patients with pre-eclampsia and were more significantly elevated in patients with early-onset preeclampsia, and the expression levels of DCN and MAPK1 mRNA were positively correlated with TNF-α levels. It is possible that all three factors are involved in the pathogenesis of preeclampsia, and are expected to be used as indicators for early prediction and diagnosis.
Topics: Female; Humans; Pregnancy; Clinical Relevance; Decorin; Mitogen-Activated Protein Kinase 1; Neutrophils; Pre-Eclampsia; Tumor Necrosis Factor-alpha; RNA, Messenger
PubMed: 36852440
DOI: 10.1080/14767058.2023.2183745 -
Archives of Dermatological Research Aug 2023Alopecia areata (AA) is a common cause of hair loss with no available universally successful treatment. Thus, new innovative treatments are urgently needed. This...
Alopecia areata (AA) is a common cause of hair loss with no available universally successful treatment. Thus, new innovative treatments are urgently needed. This research aimed to evaluate the effectiveness of fractional carbon dioxide laser (FCL) alone or combined with triamcinolone acetonide (TA) solution, platelet-rich plasma (PRP), or vitamin D3 solution in treating AA. Sixty-four AA patients with 185 lesions were recruited and divided into four treatment groups. All patients received FCL either alone (group A, n = 19) or followed by topical TA (group B, n = 16) or PRP (group C, n = 15), or vitamin D3 solution (group D, n = 14). The response was assessed using Alopecia Areata Severity Index (AASI), MacDonald Hull and Norris grading, and trichoscopy. Histopathological features and immunohistochemical decorin expression were studied. All groups showed significant improvement in AASI compared to the baseline, with insignificant differences between them. Post-treatment, trichoscopic features of disease activity significantly decreased in all groups. Compared to control biopsies, both anagen follicles and decorin expression were significantly decreased in all pretreatment specimens. After treatment, all groups showed significantly increased anagen follicles and decorin expression compared to the baseline. Accordingly, FCL is an effective treatment for AA alone or combined with TA, PRP, or vitamin D3 solution. In AA, Decorin expression was downregulated, while enhanced expression following successful treatment occurred. This suggests the role of decorin in AA pathogenesis. However, further research is still recommended to clarify the exact role of decorin in AA pathogenesis and to investigate the therapeutic benefits of decorin-based therapy.
Topics: Humans; Alopecia Areata; Pharmaceutical Preparations; Lasers, Gas; Decorin; Treatment Outcome; Triamcinolone Acetonide; Cholecalciferol
PubMed: 36809409
DOI: 10.1007/s00403-023-02565-x