Serum matrix metalloproteinase-7 for discriminating biliary atresia: a diagnostic accuracy and validation study.

BACKGROUND: Prompt and precise differential diagnosis of biliary atresia (BA) among cholestatic patients is of great importance. Matrix metalloproteinase-7 (MMP-7) holds great promise as a diagnostic marker for BA. This study aimed to investigate the accuracy of age-specific serum MMP-7 for discriminating BA from other cholestatic pediatric patients. METHODS: This was a single center diagnostic accuracy and validation study including both retrospective and prospective cohorts. Serum MMP-7 concentrations were measured using an ELISA kit, the trajectory of which with age was investigated in a healthy infants cohort aged 0 to 365 days without hepatobiliary diseases (n = 284). Clinical BA diagnosis was based on intraoperative cholangiography and subsequent histological examinations. The diagnostic accuracy of age-specific cutoffs of serum MMP-7 were assessed in a retrospective cohort of cholestatic patients (n = 318, with 172 BA) and validated in a prospective cohort (n = 687, including 395 BA). RESULTS: The MMP-7 concentration declines non-linearly with age, showing higher levels in healthy neonates as well as higher cutoff value in neonatal cholestasis. The area under the ROC curve (AUROC) was 0.967 (95% confidence interval [CI]: 0.946-0.988) for the retrospective cohort, and the cutoff of 18 ng/mL yielded 93.0% (95%CI: 88.1-96.3%), 93.8% (95%CI: 88.6-97.1%), 94.7% (95%CI: 90.1-97.5%), and 91.9% (95%CI: 86.4-95.8%) for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), respectively. The performance of MMP-7 was successfully validated in the larger prospective cohort, resulting in a diagnostic sensitivity of 95.9% (379/395; 95% CI: 93.5-97.7%), a specificity of 87.3% (255/292; 95% CI: 83.0-90.9%), a PPV of 91.1% (379/416; 95% CI: 87.9-93.7%), and a NPV of 94.1% (255/271; 95% CI: 90.6-96.6%), respectively. Besides, higher cutoff value of 28.1 ng/mL achieved the best sensitivity, specificity, PPV, and NPV for infants aged 0-30 days, which was 86.4% (95% CI: 75.0-94.0%), 95.5% (95% CI: 77.2-99.9%), 98.1% (95% CI: 89.7-100%), and 72.4% (95% CI: 52.8-87.3%), respectively. CONCLUSIONS: The serum MMP-7 is accurate and reliable in differentiating BA from non-BA cholestasis, showing its potential application in the diagnostic algorithm for BA and significant role in the future research regarding pathogenesis of BA.

Clinicopathological features and cancer transcriptomic profiling of poorly cohesive gastric carcinoma subtypes.

Gastric poorly cohesive carcinoma (PCC) manifests with a diffuse pattern and diverse tumor cell morphologies, often indicating a more unfavorable prognosis. Recent consensus has reclassified PCC based on the proportion of signet-ring cells (SRCs) in tumors for research purposes. The two most distinct subtypes, poorly cohesive carcinoma not otherwise specified (PCC-NOS) and signet-ring cell carcinoma (SRCC), are characterized by less than 10% and more than 90% SRCs, respectively. However, research comparing the clinicopathological and transcriptomic differences between these subtypes remains limited. In this study, we conducted a comparative analysis of clinicopathological features in 55 advanced-stage PCCs, consisting of 43 PCC-NOS and 12 SRCC cases. Subsequently, 12 PCC-NOS and 5 SRCC cases were randomly selected for initial cancer-related gene expression profiling and pathway enrichment analysis using the GeoMx digital spatial profiler, followed by validation in a separate validation group comprising 16 PCC-NOS and 6 SRCC cases. These transcriptomic findings were then correlated with tumor morphology and clinicopathological data. PCC-NOS cases exhibited larger tumor size, a higher prevalence of pathological N3 disease, and a worse 1-year progression-free survival rate compared to SRCC cases. Clustering of PCC-NOS and SRCC was successfully achieved using the GeoMx Cancer Transcriptome Atlas. Among all studied genes, only MMP7 showed differential expression, with its overexpression significantly associated with the PCC-NOS subtype, increased perineural invasion, and earlier disease progression. Pathway analysis revealed significantly enriched pathways in PCC-NOS related to vesicle-mediated transport, adaptive immune systems, oncogenic signaling, and extracellular matrix organization, while SRCC displayed significant enrichment in pathways associated with respiratory electron transport and the cell cycle. In conclusion, this study compares and correlates clinicopathological features and transcriptomic data between PCC-NOS and SRCC at advanced stages, employing the latest consensus classification and a novel platform for analysis.

Overexpression of heat shock protein 47 is associated with increased proliferation and metastasis in gastric cancer.

Here, we investigated that the heat shock protein 47 (HSP47) plays a crucial role in the progression of gastric cancer (GC). We analyzed HSP47 gene expression in GC cell lines and patient tissues. The HSP47 mRNA and protein expression levels were significantly higher in GC cell lines and tumor tissues compared to normal gastric mucosa. Using siRNA to silence the expression of HSP47 in GC cells resulted in a significant reduction in their proliferation, wound healing, migration, and invasion capacities. Additionally, we also showed that the mRNA expression of matrix metallopeptidase-7 (MMP-7), a metastasis-promoting gene, was significantly reduced in HSP47 siRNA-transfected GC cells. We confirmed that the HSP47 promoter region was methylated in the SNU-216 GC cell line expressing low levels of HSP47 and in most non-cancerous gastric tissues. It means that the expression of HSP47 is regulated by epigenetic regulatory mechanisms. These findings suggest that targeting HSP47, potentially through its promoter methylation, could be a useful new therapeutic strategy for treating GC.

Relationships of serum MMP-7 and clinical characteristics in choledochal cyst children.

BACKGROUND: Matrix metalloproteinase-7 (MMP-7) is associated with biliary injury. This study aimed to evaluate the relationships of serum MMP-7 with clinical characteristics in choledochal cysts (CDC) children. METHODS: Between June 2020 and July 2022, we conducted a prospective study of CDCs who underwent one-stage definitive operation at our center. Serum MMP-7 was measured using an enzyme-linked immunosorbent assay. We evaluated the relationships between serum MMP-7 and age, laboratory tests, imaging examinations, liver fibrosis, MMP-7 expression, and perforation. RESULTS: A total of 328 CDCs were enrolled in the study, with a median serum MMP-7 of 7.67 ng/mL. Higher serum MMP-7 was correlated with younger age at diagnosis (p < 0.001), larger cyst sizes (p < 0.001), higher liver fibrosis stages (p < 0.001), and higher incidence of perforation (p < 0.01). Liver MMP-7 was mainly expressed in intrahepatic and extrahepatic biliary epithelial cells. The area under the receiver operating characteristic curve (AUROC) was 0.630 (p < 0.001) for serum MMP-7 in predicting perforation. When serum MMP-7 was combined with γ-glutamyl transferase (GGT), the AUROC increased to 0.706 (p < 0.001). CONCLUSIONS: Serum MMP-7 was associated with biliary obstruction in CDCs. Patients with high serum MMP-7 were more likely to have severe liver damage and biliary injury, with higher incidences of liver fibrosis and perforation.

Contribution of Matrix Metalloproteinase-7 Genotypes to Endometriosis Risk in Taiwan.

BACKGROUND/AIM: The activity and expression of matrix metalloproteinase-7 (MMP7) have been found to be upregulated in the late stages of endometriosis. However, the contribution of MMP7 genotype to endometriosis has seldom been examined. This study aimed to investigate the role of MMP7 promoter A-181G (rs11568818) and C-153T (rs11568819) genotypes in determining personal susceptibility to endometriosis in a Taiwanese cohort. PATIENTS AND METHODS: In this hospital-based case-control study, MMP7 genotypes were analyzed in 153 endometriosis and 636 individuals without endometriosis using typical polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The statistical analysis revealed that MMP7 rs11568818 genotypes were differentially distributed between the endometriosis and control groups (p for trend=0.0048). Specifically, the MMP7 rs11568818 homozygous variant GG was associated with endometriosis risk compared to the wild-type AA genotype (OR=4.59, 95% CI=1.46-14.48, p=0.0136). However, the MMP7 rs11568818 heterozygous variant AG was not associated with endometriosis risk (OR=1.57, 95% CI=0.97-2.53, p=0.0854). The frequency of than variant allele G of MMP7 rs11568818 was 12.7% in the endometriosis group, significantly higher than the 7.2% observed in the control group (OR=1.90, 95% CI=1.27-2.82, p=0.0021). CONCLUSION: MMP7 rs11568818 GG genotype was found to be a novel marker for endometriosis risk in Taiwanese.

Cellular senescence is associated with the spatial evolution toward a higher metastatic phenotype in colorectal cancer.

In this study, we explore the dynamic process of colorectal cancer progression, emphasizing the evolution toward a more metastatic phenotype. The term "evolution" as used in this study specifically denotes the phenotypic transition toward a higher metastatic potency from well-formed glandular structures to collective invasion, ultimately resulting in the development of cancer cell buddings at the invasive front. Our findings highlight the spatial correlation of this evolution with tumor cell senescence, revealing distinct types of senescent tumor cells (types I and II) that play different roles in the overall cancer progression. Type I senescent tumor cells (p16INK4A+/CXCL12+/LAMC2-/MMP7-) are identified in the collective invasion region, whereas type II senescent tumor cells (p16INK4A+/CXCL12+/LAMC2+/MMP7+), representing the final evolved form, are prominently located in the partial-EMT region. Importantly, type II senescent tumor cells associate with local invasion and lymph node metastasis in colorectal cancer, potentially affecting patient prognosis.

Neurotensin contributes to cholestatic liver disease potentially modulating matrix metalloprotease-7.

The diagnosis and treatment of biliary atresia pose challenges due to the absence of reliable biomarkers and limited understanding of its etiology. The plasma and liver of patients with biliary atresia exhibit elevated levels of neurotensin. To investigate the specific role of neurotensin in the progression of biliary atresia, the patient's liver pathological section was employed. Biliary organoids, cultured biliary cells, and a mouse model were employed to elucidate both the potential diagnostic significance of neurotensin and its underlying mechanistic pathway. In patients' blood, the levels of neurotensin were positively correlated with matrix metalloprotease-7, interleukin-8, and liver function enzymes. Neurotensin and neurotensin receptors were mainly expressed in the intrahepatic biliary cells and were stimulated by bile acids. Neurotensin suppressed the growth and increased expression of matrix metalloprotease-7 in biliary organoids. Neurotensin inhibited mitochondrial respiration, oxidative phosphorylation, and attenuated the activation of calmodulin-dependent kinase kinase 2-adenosine monophosphate-activated protein kinase (CaMKK2-AMPK) signaling in cultured biliary cells. The stimulation of neurotensin in mice and cultured cholangiocytes resulted in the upregulation of matrix metalloprotease-7 expression through binding to its receptors, namely neurotensin receptors 1/3, thereby attenuating the activation of the CaMKK2-AMPK pathway. In conclusion, these findings revealed the changes of neurotensin in patients with cholestatic liver disease and its mechanism in the progression of the disease, providing a new understanding of the complex mechanism of hepatobiliary injury in children with biliary atresia.

Urine MMP7 as a kidney injury biomarker.

Matrix metalloproteinase 7 (MMP-7) is a secreted endopeptidase involved in the degradation of extracellular matrix components and the activation of cytokines and growth factors. The regulation of MMP-7 can be transcriptionally regulated by AP-1 or Wnt/ß-catenin or post-translationally by proteolytic activation. MMP-7 expression is low or absent in the healthy kidney, but is significantly upregulated in kidney injury, including AKI and CKD. The function of MMP-7 in kidney disease may differ for CKD and AKI; it may have a profibrotic role in CKD and an anti-apoptotic and regenerative function in AKI. Additionally, the potential of MMP-7 as a biomarker has been studied in different kidney diseases, and the results are promising. Recently, combined unbiased kidney proteomics and transcriptomics approaches identified kidney MMP-7 as the protein having the strongest association with both fibrosis and eGFR and confirmed the predictive role of plasma MMP-7 levels for kidney function decline in over 11 000 individuals. Additionally, urinary MMP-7, combined with urinary cystatin C (CysC) and retinol binding protein (RBP) was reported to provide information on tubular injury in focal segmental glomerulosclerosis and minimal change disease. We now present an overview of research on MMP-7 expression and function in kidney diseases and discuss its potential as a biomarker of kidney diseases.

Matrix metalloproteinase-7 and claudin-7 as novel identified therapeutic targets for restoration of intestinal epithelial barrier in inflammatory bowel diseases.

Intestinal tight junction disruption and mucosal immune dysregulation contribute to pathogenesis and progression of inflammatory bowel diseases (IBD). A proteolytic enzyme matrix metalloproteinase 7 (MMP-7), which is highly expressed in intestinal tissue, is implicated to IBD and other immune overactivation-associated diseases. In the issue of the Frontiers in Immunology, Ying Xiao and colleagues demonstrate that MMP-7-mediated claudin-7 degradation promotes IBD pathogenesis and disease progression. Therefore, inhibition of MMP-7 enzymatic activity can be a therapeutic strategy for the treatment of IBD.

Expression of Matrix Metalloproteinases in Human Cystic Echinococcosis.

BACKGROUND: Cystic echinococcosis (CE) is a zoonotic disease caused by the Echinococcus granulosus senso lato (E. granulosus s.l.) larval stages. Parasitederived products have been shown to regulate host matrix metalloproteinases (MMPs), contributing to CE pathogenesis and progressive liver fibrosis in intermediate hosts. The current study aimed to investigate the potential role of MMP1, 7, 8, and 13 in E. granulosus s.l-induced liver fibrosis. METHODS: Thirty CE patients with active, transitional, or inactive hydatid cysts were enrolled in this study to determine the inductive effects of E. granulosus on the expression of MMP-1, MMP-7, MMP-8, and MMP-13 in healthy liver tissue and fibrotic liver tissue using qRT-PCR. RESULTS: According to the WHO-IWGE classification, patients with functional cysts (CE1 and CE2) had the highest percentage (46.6%). MMP-1, MMP-7, MMP-8, and MMP-13 expression levels were significantly higher in fibrotic liver than in normal liver tissue. MMP-13 and MMP-1 had the highest and lowest expression levels among MMPs. Compared to the normal group, the fold change for MMP-13 in the fibrotic group was greater than 12 and had the highest AUC value (AUC= 0.8283). CONCLUSION: Our findings suggest that E. granulosus-derived products might be involved in regulating host MMPs. Thus, MMPs may be considered potential biomarkers for predicting CE prognosis. Because of the non-normal distribution of our patients' CE types, further research, particularly on circulation MMPs, is needed to confirm the potential role of MMPs in CE pathogenesis and to follow up on CE patients.

Accurate prediction of biliary atresia with an integrated model using MMP-7 levels and bile acids.

BACKGROUND: Biliary atresia (BA) is a rare fatal liver disease in children, and the aim of this study was to develop a method to diagnose BA early. METHODS: We determined serum levels of matrix metalloproteinase-7 (MMP-7), the results of 13 liver tests, and the levels of 20 bile acids, and integrated computational models were constructed to diagnose BA. RESULTS: Our findings demonstrated that MMP-7 expression levels, as well as the results of four liver tests and levels of ten bile acids, were significantly different between 86 BA and 59 non-BA patients (P < 0.05). The computational prediction model revealed that MMP-7 levels alone had a higher predictive accuracy [area under the receiver operating characteristic curve (AUC) = 0.966, 95% confidence interval (CI): 0.942, 0.989] than liver test results and bile acid levels. The AUC was 0.890 (95% CI 0.837, 0.943) for liver test results and 0.825 (95% CI 0.758, 0.892) for bile acid levels. Furthermore, bile levels had a higher contribution to enhancing the predictive accuracy of MMP-7 levels (AUC = 0.976, 95% CI 0.953, 1.000) than liver test results. The AUC was 0.983 (95% CI 0.962, 1.000) for MMP-7 levels combined with liver test results and bile acid levels. In addition, we found that MMP-7 levels were highly correlated with gamma-glutamyl transferase levels and the liver fibrosis score. CONCLUSION: The innovative integrated models based on a large number of indicators provide a noninvasive and cost-effective approach for accurately diagnosing BA in children. Video Abstract (MP4 142103 KB).

Identification of Differentially Expressed Genes in Human Colorectal Cancer Using RNASeq Data Validated on the Molecular Level with Real-Time PCR.

Colorectal cancer (CRC) is a prevalent cancer with high morbidity and mortality rates worldwide. Late diagnosis is a significant contributor to low survival rates in a minority of cases. The study aimed to perform a robust pipeline using integrated bioinformatics tools that will enable us to identify potential diagnostic and prognostic biomarkers for early detection of CRC by exploring differentially expressed genes (DEGs). In addition to, testing the capability of replacing chemotherapy with plant extract in CRC treatment by validating it using real-time PCR. RNA-seq data from cancerous and adjacent normal tissues were pre-processed and analyzed using various tools such as FastQC, Kallisto, DESeq@ R package, g:Profiler, GNEMANIA-CytoScape and CytoHubba, resulting in the identification of 1641 DEGs enriched in various signaling routes. MMP7, TCF21, and VEGFD were found to be promising diagnostic biomarkers for CRC. An in vitro experiment was conducted to examine the potential anticancer properties of 5-fluorouracile, Withania somnifera extract, and their combination. The extract was found to exhibit a positive trend in gene expression and potential therapeutic value by targeting the three genes; however, further trials are required to regulate the methylation promoter. Molecular docking tests supported the findings by revealing a stable ligand-receptor complex. In conclusion, the study's analysis workflow is precise and robust in identifying DEGs in CRC that may serve as biomarkers for diagnosis and treatment. Additionally, the identified DEGs can be used in future research with larger sample sizes to analyze CRC survival.

Measurement of MMP-7 in micro-volume peripheral blood: development of dried blood spot approach.

Purpose: Serum matrix metalloproteinase-7 (MMP-7) is significant in differentiating biliary atresia (BA). This study aims to develop a new peripheral blood quantitative collection device to detect MMP-7 levels via dried blood spot (DBS). Methods: This is a diagnostic accuracy test. Serum and DBS MMP-7 concentrations were measured using an ELISA kit. Intraoperative cholangiography and subsequent histological examinations were used to confirm BA diagnoses. Results: A total of 241 infants with obstructive jaundice were enrolled, among whom 168 were BA. Linear regression showed DBS MMP-7 correlated well with serum MMP-7 (R = 0.93, P < 0.001). The best cut-off value of serum MMP-7 for BA was 25.9 ng/ml, achieving the area under the ROC curve (AUC) of 0.962 (95% CI: 0.941, 0.983), and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 86.9%, 94.5%, 97.3% and 75.8%, respectively. The best cut-off value of DBS MMP-7 for BA was 12.5 ng/ml, achieving the AUC of 0.922 (95% CI: 0.888, 0.956), and the sensitivity, specificity, PPV, and NPV were 86.9%, 89.0%, 94.8%, and 74.7%, respectively. The dried blood spots were intervened under different storage conditions, including 1-5 days at room temperature, 2 or 3 days at 30 °C and 2 or 3 days at 37 °C. The DBS MMP-7 concentration under different storage conditions had good correlation and consistency with that at -80 °C. Conclusions: Serum and DBS MMP-7 correlate well, both of which have high accuracy in the diagnosis of BA, while the requirements for the storage of DBS are low.

Assessment of Matrix Metalloprotease - 7 (MMP7) Immunohistochemistry in Biliary Atresia and Other Pediatric Cholestatic Liver Diseases.

Background and aims: Biliary atresia (BA) is a progressive fibro-obliterative cholangiopathy. The histopathological diagnosis is often challenging and an immunohistochemical marker is often sought as an adjunct. We evaluated MMP7 immunohistochemistry in BA and other non-BA pediatric cholestatic liver diseases. Materials and methods: MMP7 immunohistochemistry was applied in 5 age-matched normal control, 23 cases of BA and 43 cases of non-BA pediatric cholestasis including 16 cases of choledochal cyst (CC), and a multiplication score was obtained by multiplying the intensity and percentage positivity in the cholangiocytes. Results: BA showed a high mean MMP7 multiplication score which was significantly different from the normal control and other non-BA pediatric cholestatic diseases including CC (p value < 0.001). The sensitivity, specificity, positive, and negative predictive values of MMP7 immunohistochemistry were 91.3%, 93.02%, 87.5%, and 95.2% respectively. Conclusion: MMP7 immunohistochemistry may be an adjunct to histomorphology in BA.

Association of MMP7 T > C Gene Variant (rs10502001) and Expression in Chronic Obstructive Pulmonary Disease.

Patients with chronic obstructive pulmonary disease (COPD) have obstructed airflow through their lungs. Single nucleotide polymorphisms in matrix metalloproteinases (MMPs) genes and the risk of COPD have been the subject of numerous studies, with conflicting results. This investigation was conducted to determine whether the MMP7 (T>C) gene variant (rs10502001) was associated with an increased risk of COPD. A case-control study was conducted with 360 subjects (180 healthy controls and 180 COPD cases). The polymerase chain reaction (PCR)-restriction fragment length polymorphism method was used to genotype the SNP rs1050200. mRNA expression of MMP7 was performed using RT-PCR. The genotypic/allelic frequencies and carriage rates of rs10502001 (T>C) polymorphism were evaluated in 180 each of healthy controls and COPD cases. Cases have higher TC/CC genotype frequencies than controls. The "CC" genotype was found to be significantly associated with increased COPD risk (p = 0.016). The "C" allele frequency was higher in cases than in controls and showed significant association with COPD (p = 0.005). The carriage rate frequencies of T(-) and C(+) were significantly higher in cases than in controls (p = 0.031 and 0.047, respectively). MMP7 expression was significantly upregulated (p = 0.001) in COPD cases as compared with the controls. In addition, comparisons of MMP7 expression between the COPD cases with different genotypes showed that the "CC" genotype cases had significantly higher expression than those with "TT" genotype. The present findings showed statistically significant correlation of MMP7 (T>C) polymorphism and expression with COPD. Therefore, MMP7 responsible for degradation of elastin has been strongly linked to the progression of COPD.

Clinical Significance of MMP7 Levels in Colorectal Cancer Patients Receiving FOLFOX4 Chemotherapy Treatment.

Objective: Various studies have shown an association between the anti-cancer drug 5-fluorouracil and matrix metalloproteinase 7 (MMP7). The expression of MMP7 in the serum of colorectal cancer patients, as well as their sensitivity to chemotherapy, were examined using the FOLFOX4 chemotherapy treatment. Methods: Serum samples were taken from 216 colorectal cancer patients who had undergone four cycles of gemcitabine and cisplatin treatment. The sera of 216 healthy persons were used as controls. MMP7 levels in the serum were measured by ELISA. Demographic and survival data were collected. Results: MMP7 levels were not associated with sex, age, peritoneal dissemination, liver metastasis, lymph node metastasis, lymphatic invasion, or venous invasion in CRC patients, but were associated with histological grade, tumor size, TNM stage, and depth of tumor invasion. Patients' serum MMP7 expression reduced after treatment. MMP7 expression was significantly lower chemotherapy-sensitive patients compared with chemotherapy-resistant patients. Elevated MMP7 expression was associated with worse prognosis and chemotherapy-sensitive patients had markedly better overall survival compared with chemotherapy-resistant patients. Conclusion: MMP7 expression was potentially associated with the development of colorectal cancer and elevated levels were associated with chemoresistance in CRC patients. Serum MMP7 levels can be used to screen for drug resistance during FOLFOX4 chemotherapy treatment.

SARS-CoV-2 S and N protein peptides drive invasion abilities of colon cancer cells through TGF-ß1 regulation.

The COVID-19 pandemic led to the delay of colorectal cancer (CRC) diagnosis, which causes CRC to be treated at more advanced, often metastatic stages. Unfortunately, there is no effective treatment for metastatic CRC stages, which are considered the leading cause of patients' death. The mortality induced by SARS-CoV-2 is significantly higher in cancer patients than in patients with other diseases. Interestingly, COVID-19 patients often develop fibrosis which depends on epithelial-mesenchymal transition (EMT) - the process also involved in cancer progression. The study aimed to verify whether SARS-CoV-2 induces EMT and consequently increases the invasion potential of colon cancer cells. CRC cells were stimulated with SARS-CoV-2 S and N protein peptides and epithelial and mesenchymal markers were analysed with Western blotting to detect the occurrence of the EMT. The migration, invasion assays and MMP-7 secretion were employed to evaluate the potential of SARS-CoV-2 to stimulate the cells invasion in vitro. ELISA assay, TGF-ß1 neutralizing antibodies, TGF-ßR silencing and inhibitors were used to investigate the role of the TGF-ß1 signalling pathways in the SARS-CoV-2-dependent CRC stimulation. The SARS-CoV-2 induced EMT, which increased the invasion ability of CRC cells. Moreover, the SARS-CoV-2 proteins drive colon cancer cell invasion through TGF-ß1. Additionally, secreted TGF-ß1 induced a bystander effect in colon cancer cells. However, blocking TGF-ß1/Smad- and -non-Smad-dependent pathways suppressed the SARS-CoV-2-induced invasiveness of CRC. In conclusion, we revealed that SARS-CoV-2 stimulates the invasion abilities of CRC by regulating TGF-ß1-induced EMT. Our results provide a theoretical basis for using anti-TGF-ß1 therapy to reduce the risk of CRC metastasis during SARS-CoV-2 infection.

SBF2-AS1 and TreRNA: novel lncRNA players in triple-negative breast cancer pathogenesis.

BACKGROUND: Compared to other breast cancer subtypes, triple-negative breast cancer (TNBC) has always been challenging for clinicians due to its aggressive behavior and lack of a specific treatment. There is a confirmed association between invasive features of tumors and increased epithelial-mesenchymal transition (EMT) process, which is consistent with a higher rate of EMT in TNBC. METHODS AND RESULTS: We investigated the expression of EMT-related genes, SNAI1 and MMP7, and EMT-related lncRNAs, treRNA and SBF2-AS1, in 50 TNBC tumors and 50 non-TNBC tumors to reveal more regulators and effectors involved in TNBC malignancy. In the present study, we showed the overexpression of all the studied genes and lncRNAs in TNBC tumors compared to non-TNBC samples. Moreover, a significant association was observed between MMP7 and treRNA expression levels and larger tumor size. A positive correlation between SNAI1 and lncRNA treRNA expression levels was also detected. CONCLUSIONS: Due to the differential expression and the potential diagnostic power of the studied genes, SBF2-AS1 and treRNA can be proposed as new probable biomarkers and therapeutic targets in TNBC.

The Expression of MMP1 and MMP7 in Mice Liver after Exposure to Aflatoxin B1 Using Immunohistochemistry Technique.

Mycotoxin is a class of poisonous secondary metabolites generated by filamentous fungi and found in agricultural commodities worldwide. Therefore, the current study aimed to investigate how aflatoxin B1 affected hepatic cellular architecture and Matrix metalloproteinase expression in particular (MMP1 and MMP7) in the livers of experimental mice (IHC). A total of sixteen mice (four groups) were studied after being given pure aflatoxin B1 (9mg/kg B.W., 6mg/kg B.W., and 3mg/kg B.W.) (produced from Aspergillus flavus) or a control group (not treated). MMP1 and MMP7 expressions were also measured using the MMP1 and MMP7 expression assays (IHC). The degree of liver damage is related to the AFB1 concentration and the duration of exposure. IHC reveals a considerable rise in MMP1 and MMP7 expression in the livers of mice given a maximum concentration of 90% ((9 mg/B.W.) pure AFB1), which approached the toxin's effect toxic dosage. MMP1 and MMP7 expression were also increased by AFB1 at dosages of 60 and 30% (6mg/BW and 3mg/B.W., respectively), although not to the same extent as 90%. MMP1 was significantly more expressed than MMP7 compared to control, and AFB1 at 90, 60, and 30% concentrations caused changes in hepatic cellular architecture, organization, and liver tissue damage and dramatically increased MMP1 and MMP7 production in hepatic tissue following treatment. Increased levels of pure aflatoxin B1 will harm liver tissue and MMP1 and MMP7 expression. MMP1 was more substantially expressed than MMP7.

Comprehensive Analysis of the Prognostic Value of Circulating MMP-7 Levels in Urothelial Carcinoma: A Combined Cohort Analysis, Systematic Review, and Meta-Analysis.

Lymph node (LN) status is the most significant prognostic factor for invasive urothelial bladder cancer (UBC); however, the optimal extent of LN dissection (LND) is debated. We assessed circulating matrix metalloproteinase-7 (MMP-7) as a prognostic factor and decision-making marker for the extent of LND. Preoperative serum MMP-7 levels were determined in two independent UBC cohorts (n = 188; n = 68) and in one control cohort (n = 97) by using the ELISA method. A systematic review and meta-analysis on the prognostic role of circulating pretreatment MMP-7 levels were performed. Serum MMP-7 levels were higher in patients compared to controls (p < 0.001) with the highest levels in LN-positive cases. Half of LN-positive UBC patients had low MMP-7 levels, whereas the survival of LN-negative patients with high serum MMP-7 findings was poor. MMP-7 levels were independently associated with poor survival in both cohorts (p = 0.006, p < 0.001). Accordingly, our systematic review of six eligible publications revealed a 2.5-fold higher mortality risk in patients with high MMP-7 levels. In conclusion, preoperative MMP-7 level is a validated and independent prognostic factor in urothelial cancer. It cannot be used to decide between regional or extended LND but may be useful in identifying LN-negative high-risk patients with potentially undetected metastases.