Antimigratory effects of a new NF-κB inhibitor, (S)-b-salicyloylamino-a-exo-methylene-Æ´-butyrolactone, in 2D and 3D breast cancer models.

One of the pharmacological approaches to neoplastic disease aims to target the metastatic capacity of tumor cells to reduce their aggressive behavior. In this study, we analyzed the antimigratory capacity of the compound SEMBL, (S)-ß-salicyloylamino-a-exo-methylene-Æ´-butyrolactone, a new analog of (-)-Dehydroxymethylepoxyquinomicin ((-)-DHMEQ), in three different breast cancer cell lines: MCF-7, MCF-7R and MDA-MB-231. This molecule is characterized by intense antiproliferative activity, evaluated by MTS assay, showing greater potency than DHMEQ. SEMBL was able to inhibit nuclear factor κappa B (NF-κB) activation observed through TransAM™ assay, while cell invasion and wound healing assays revealed a strong reduction in invasive capacity mediated by metalloproteinase 2 (MMP-2) and Vimentin decrease. These results, obtained in vitro, were corroborated on 3D systems made up of Poly-L-Lactic Acid (PLLA) scaffolds. In summary, SEMBL exerts interesting anti-tumor activities in preclinical breast cancer models and therefore it could be a promising new molecule to be studied also in other types of neoplastic disease.

[Molecular alterations of podocytes in primary focal segmental glomerulosclerosis and IgA nephropathy. (An exploratory study)]. / Molekulyarnye al'teratsii podotsitov pri pervichnom fokal'no-segmentarnom glomeruloskleroze i IgA-nefropatii. (Poiskovoe issledovanie).

OBJECTIVE: An evaluation of podocyte's molecular phenotype alterations in primary focal segmental glomerulosclerosis (pFSGS) and IgA nephropathy (IgAN). MATERIAL AND METHODS: The exploratory study included 14 cases of morphologically confirmed pFSGS, 14 cases of IgAN, and 12 negative controls. The negative controls comprised samples of the unaltered renal cortex obtained during laparoscopic nephrectomy in patients with malignant neoplasms of the kidney and bladder and without proteinuria. A quantitative immunomorphological study of Wilms tumour protein (WT1) expression and mesenchymal markers of podocytes (desmin and vimentin) was conducted on all kidney samples. The co-expression of the aforementioned molecules was analysed using confocal microscopy. RESULTS: Cases of pFSGS exhibited nephrotic syndrome with proteinuria of 9.3 (3.1-14) g/24 and typical glomerular alterations in light microscopy and ultrastructural analysis. In the IgAN group, proteinuria was less severe (1.2 (0.7-1.6) g/24). The estimated glomerular filtration rate in pFSGS and IgAN was similar (pFSGS: 85 (53-103) ml/min/1.72 m², IgAN: 76 (52-87) ml/min/1.72 m²; p=0.40). In both pFSGS and IgAN, there was a reduction in WT1 expression in podocytes and an increase in vimentin expression when compared to negative controls. Compared to IgAN and controls, pFSGS exhibited a lower prevalence of glomerular WT1 expression and higher expression of desmin, which was predominantly localised in WT1-negative glomerular areas in confocal microscopy. In pFSGS, decreased nuclear expression of WT1 and increased expression of desmin were observed in the parietal epithelium of the glomerular capsule. CONCLUSION: Bidirectional alterations in the glomerular expression of WT1 and intermediate filament proteins are apparent in pFSGS and IgAN. These findings are suggestive for the genomic reprogramming of podocytes and the parietal epithelium of the glomerulus as part of the epithelial-mesenchymal transition, determining the structural and functional disorders of these cells, more prominent in pFSGS.

Columbianadin ameliorates rheumatoid arthritis by attenuating synoviocyte hyperplasia through targeted vimentin to inhibit the VAV2/Rac-1 signaling pathway.

INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disease pathologically characterized by synovial inflammation. The abnormal activation of synoviocytes seems to accompany the progression of RA. The role and exact molecular mechanism in RA of columbianadin (CBN) which is a natural coumarin is still unclear. OBJECTIVES: The present research aimed to investigate the effect of vimentin on the abnormal growth characteristics of RA synoviocytes and the targeted regulatory role of CBN. METHODS: Cell migration and invasion were detected using the wound healing and transwell method. Mechanistically, the direct molecular targets of CBN were screened and identified by activity-based protein profiling. The expression of relevant proteins and mRNA in cells and mouse synovium was detected by western blotting and qRT-PCR. Changes in the degree of paw swelling and body weight of mice were recorded. H&E staining, toluidine blue staining, and micro-CT were used to visualize the degree of pathological damage in the ankle joints of mice. Small interfering RNA and plasmid overexpression of vimentin were used to observe their effects on MH7A cell proliferation, migration, apoptosis, and downstream molecular signaling. RESULTS: The TNF-α-induced proliferation and migration of MH7A cells could be significantly repressed by CBN (25,50 µM), and the expression of apoptosis and autophagy-associated proteins could be modulated. Furthermore, CBN could directly bind to vimentin and inhibit its expression and function in synoviocytes, thereby ameliorating foot and paw swelling and joint damage in CIA mice. Silencing and overexpression of vimentin might be involved in developing RA synovial hyperplasia and invasive cartilage by activating VAV2 phosphorylation-mediated expression of Rac-1, which affects abnormal growth characteristics, such as synoviocyte invasion and migration. CONCLUSION: CBN-targeted vimentin restrains the overactivation of RA synoviocytes thereby delaying the pathological process in CIA mice, which provides valuable targets and insights for understanding the pathological mechanisms of RA synovial hyperplasia.

Is Immunohistochemical Galectin-3 Expression Associated with the Epithelial-Mesenchymal Transition in High- and Low-Grade Invasive Urothelial Carcinomas of the Bladder?

Background/Objectives: Bladder cancer, predominantly urothelial carcinoma, is an important malignancy of the urinary system. Despite the same histologic grade and stage, some patients seem to have a worse prognosis. In this context, the epithelial-mesenchymal transition (EMT), characterized by the loss of E-cadherin and gain of vimentin expression, is an important process in tumor progression. Galectin-3, a lactose-binding protein involved in various cellular processes, has been associated with increased tumor cell migration, invasion, and treatment resistance. Methods: In this study, 223 bladder cancer cases were examined, and E-cadherin, vimentin, and galectin-3 expression was evaluated by immunohistochemical staining in tumor budding areas and invasive components. These markers were also correlated with clinicopathological parameters, including tumor grade and stage. Results: The results indicated a significant decrease in E-cadherin expression and an increase in vimentin staining in higher-grade and higher-stage tumors, supporting EMT involvement. Galectin-3 expression was notably higher in T1 high-grade tumors but decreased in T2 stage tumors. Despite this, no significant correlation was found between galectin-3 and E-cadherin or vimentin, suggesting a complex role of galectin-3 in EMT. Conclusions: High galectin-3 expression in T1 high-grade tumors highlights its potential role in early tumor progression and as a therapeutic target. However, the decrease in its expression in advanced stages underscores the need for further research to understand its multifaceted involvement in bladder cancer. These findings suggest that while galectin-3 may contribute to the EMT and early tumor progression, its exact role and potential as a therapeutic target require more detailed investigation.

Flow cytometry of non-hematopoietic cells in canine effusions.

The identification of non-hematopoietic cells in effusions is a diagnostic challenge in cytology. Biopsies from mesothelium or primary lesions are infrequently performed in clinical settings and immunochemistry on smears or immunohistochemistry on cell blocks are the most common ancillary test to refine the cytological diagnosis. Cavitary effusions are an ideal matrix for flow cytometry and the availability of a cytometric panel to describe non-hematopoietic cells would represent a useful tool. Here we present the results of the flow cytometric and immunohistochemical determination of cytokeratin (CK), vimentin (VIM) and desmin (DES) in 36 canine effusions. The concordance between the two methods was perfect for CK (100%), substantial for VIM (77.8%), and almost perfect for DES (97.2%). The panel was interpreted to define the epithelial (CK+VIM-DES-), mesothelial (CK+VIM+DES+), or mesenchymal (CK-VIM+DES-) origin of the cells. Unexpected profiles were considered doubtful and observed patterns were individually discussed. The concordance of the panel interpretation between two methods was 75%. The evaluation of discordant and doubtful cases suggests a lower sensitivity of flow cytometry in detecting VIM expression and revealed a high frequency of VIM+ epithelial cells, variable expression of VIM in mesothelial cells, and an important role of DES in excluding an epithelial origin when positive. Multicentric studies based on histopathological diagnoses are necessary to confirm these findings and evaluate the diagnostic utility of the panel to refine cytological diagnosis. Our results show that flow cytometry can be a timesaving alternative to IHC on cell blocks in clinical settings to detect CK, VIM and DES expression. The interpretation of the panel is similar in most cases; however, occasional discordant results, particularly for VIM, may occur.

Aberrant overexpression of the autoantigen protein vimentin promotes Th17 cell differentiation and autoimmune arthritis via activation of STAT3 signaling.

Vimentin contributes to the positioning and function of organelles, cell migration, adhesion, and division. However, secreted vimentin accumulates on the cell surface (Mor-Vaknin et al., 2003; Ramos et al., 2020 [1,2]) where it acts as a coreceptor for viral infection and as an autoantigen in inflammatory and autoimmune diseases. The roles of vimentin in Th17 cells were examined in mice with knockdown of vimentin. We also examined whether STAT3 is required for vimentin expression. Vimentin expression was significantly increased in Th17 cells through STAT3 activation, and vimentin+ IL-17+ T cells were markedly increased in the joint and spleen tissues of CIA mice. The arthritis score and expression levels of proinflammatory cytokines were significantly decreased in CIA mice treated with vimentin shRNA vector. In this study, we demonstrated that vimentin is significantly expressed in Th17 cells through STAT3 activation. Our results provide new insights into the role of vimentin in Th17 cells and the complex pathogenesis of RA.

NF-кB promotes aggresome formation via upregulating HDAC6 and in turn maintaining Vimentin cage.

Proteasome inhibitors have been applied to anticancer therapy by accumulating toxic misfolded proteins. However, chemical inactivation of proteasome generates aggresome, a Vimentin cage-enclosed subcellular structure quarantining HDAC6-Dynein-transported misfolded proteins before the protein toxicants are degraded by autophagy. Hence, aggresome may attenuate proteasome inhibitor drug-induced cytotoxicity. To solve the problem, it is imperative to characterize how cells assemble aggresome. By examining aggresomes in six cell lines, A549 cells were selectively studied for their bigger cell size and moderate aggresome-forming activity. Aggresome grew in size upon continuous exposure of A549 cells to proteasome inhibitor MG132 and reached a mature size around the 16th to 24th hour of treatment. Mechanistic studies revealed that NF-кB translocated to the nucleus in MG132-treated cells, and chemical activation or knockdown of NF-кB enhanced or prohibited aggresome assembly. Further analyses showed that NF-кB upregulated HDAC6, and HDAC6 maintained the Vimentin cage by interacting with Vimentin p72, a key modification of the intermediate filament contributing to aggresome formation. Remarkably, chemical inactivation of NF-кB synergized MG132-induced cell mortality. All the findings suggest that NF-кB dictates aggresome assembly via upregulating HDAC6, and NF-кB inhibitor may serve as a potential drug potentiating proteasome inhibitor medicine-induced cytotoxicity during the treatment of cancer cells.NEW & NOTEWORTHY The study reveals a new mechanism guiding MG132-triggered aggresome formation. NF-кB is quickly activated upon exposure to MG132, and NF-кB upregulates the misfolded protein recognizing factor HDCA6. In addition to collecting misfolded proteins, HDAC6 also binds Vimentin and maintains the Vimentin cage, which quarantines toxic misfolded proteins and protects cells from being toxified by those protein toxicants. Therapeutically, chemical inactivation of NF-кB synergizes MG132-induced cytotoxicity, providing a new strategy to defeat cancers.

Mycoplasma synoviae surface-located elongation factor G functions as a cytoadhesin to promote adhesion to synovial sheath cells through binding to vimentin.

Mycoplasma synoviae infection has caused serious economic losses to the poultry industry worldwide. The molecular mechanism by which M. synoviae colonizes the synovium and induces synovitis is unclear. In this study, desthiobiotin pull-down and liquid chromatography-tandem mass spectrometry analyses were used to screen M. synoviae membrane proteins that bind the membrane proteins of synovial sheath cells (SSCs). Among the 128 screened proteins, elongation factor G (EF-G) of M. synoviae was identified as a surface-located protein using colony blotting and dual fluorescence analyses. The immunogenicity of EF-G was confirmed by the preparation of a rabbit polyclonal antibody. EF-G was identified as a cytoadhesin that directly binds to SSCs using indirect immunofluorescence assay and ELISA plate binding assay. In addition, antibody adhesion inhibition and protein adhesion inhibition demonstrated that EF-G could significantly promote the adhesion of M. synoviae to SSCs. Co-IP, GST pull-down, bacterial two-hybridization, and ELISA plate binding assays were performed to demonstrate the binding of EF-G and vimentin in vivo and in vitro. Antibody adhesion inhibition, protein adhesion inhibition, and siRNA interference adhesion inhibition assays demonstrated that vimentin significantly affected M. synoviae adhesion to SSCs. These studies indicate that two interacting proteins, EF-G, a novel cytoadhesin, and vimentin, an important cell surface receptor, play important roles in the adhesion of M. synoviae to SSCs, laying a foundation for subsequent studies on the mechanism of M. synoviae-induced synovitis and providing meaningful targets for screening target drugs against M. synoviae infection.

Novel Chimeric Peptides Based on the Enolase Peptide Antigen (CEP-1) Bearing Three Post-Translational Modifications (Citrullination, Homocitrullination and Acetylation) for Determining the Diagnosis and Severity of Rheumatoid Arthritis.

With the aim of improving the uncertainties associated with the correct diagnosis of seronegative rheumatoid arthritis (RA) and identifying those at risk of developing interstitial lung disease (ILD), we have designed new peptide antigens bearing three post-translational modifications (PTMs) (citrulline, homocitrulline and acetyl-lysine) related to RA that could complement existing tests based on anti-citrullinated peptide/protein antibodies (ACPAs). Several chimeric peptides were synthesized and comparatively tested as antigens in ELISAs with two cohorts of sera: 178 RAs and 110 healthy blood donors. The results indicated that although chimeric peptides containing all three PTMs and vimentin and enolase domains do not significantly outperform existing ACPA tests in terms of sensitivity and specificity, they show potential to complement current assays, especially when detecting antibodies in some seronegative patients. Furthermore, the presence of these autoantibodies significantly identified patients with RA and ILD. We can conclude that the identification of specific autoantibody profiles using synthetic antigens containing peptide domains derived from proteins present in the human joint could help in the early detection of the risk of ILD in patients with RA and be useful for adapting follow-up strategies and guiding decisions during treatment.

Expression of Markers Associated with Epithelial-Mesenchymal Transition and Extracellular Matrix Degradation in Human Uveal Melanoma.

The expression of markers associated with epithelial-mesenchymal transition (EMT) and extracellular matrix degradation in human uveal melanoma tissue samples and postequatorial zone of the choroid was assessed by immunohistochemical staining. Increased expression of EMT markers E-cadherin and vimentin was observed in the tumor. The ratio of MMP-9 to TIMP-1 proteins related to the extracellular matrix degradation was higher in the tumor. These results may indicate activation of EMT-like process in the uveal melanoma cells and degradation of the extracellular matrix, which can contribute to the development of collective invasion in uveal melanoma.

Comparative Proteomics of ccRCC Cell Lines to Identify Kidney Cancer Progression Factors.

BACKGROUND/AIM: Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, accounting for approximately 75% of kidney cancers. The objective of this study was to identify novel progression markers for ccRCC based on proteomics, with the goal of stage determination and early diagnosis of kidney cancer patients. MATERIALS AND METHODS: We performed quantitative global proteomics coupled with Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and high-resolution tandem mass spectrometry on kidney-derived cells, including HEK-293, 786-O (primary ccRCC), and Caki-1 (metastatic ccRCC) cells, to investigate the novel progression factors of ccRCC. RESULTS: In this study, a total of 1,106 proteins were quantified. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for differentially expressed proteins (DEPs) that were increased in ccRCC cells compared to HEK-293 cells. Ultimately, 99 DEPs including 75 up-regulated and 24 down-regulated proteins, that were significantly altered in both ccRCC cells, were identified. Among DEPs, vimentin was identified as the most significantly changed protein. Its increased expression in ccRCC was verified through immunoblotting in ccRCC cell lines and immunohistochemistry in kidney tumors. CONCLUSION: From the global proteomics data detected in ccRCC, we propose 99 DEPs including vimentin as progression factors.

Histopathological and immunohistochemical analysis of a suspected extraskeletal osteosarcoma in a rabbit (Oryctolagus cuniculus).

An 8-year-old male rabbit (Oryctolagus cuniculus) presented with a subcutaneous mass in the proximal region of the fourth and accessory digit measuring 5.5 x 3.5 x 5.2cm. The mass was non-alopecic and exhibited irregular surface, ulceration and necrosis with predominantly pale and light brown coloring. Radiography revealed no involvement of bone and adjacent periosteum. The mass was marginally resected and the electrochemotherapy (ECT) was performed on the surgical bed. Histopathology and immunohistochemical analysis revealed positive reactions for Vimentin, Runx-2 and ki-67, leading to a diagnosis of extraskeletal osteosarcoma (ESOS). This report described a case of ESOS in a rabbit, thereby delineating its clinical presentation, anatomopathological characteristics, diagnostic modalities and recommended therapeutic interventions.

Um coelho macho de 8 anos (Oryctolagus cuniculus) apresentava uma massa subcutânea na região proximal do quarto e acessório dígitos medindo 5,5 x 3,5 x 5,2 cm. A massa não era alopécica e exibia superfície irregular, ulceração e necrose com coloração predominantemente pálida e marrom clara. A radiografia não revelou envolvimento de tecido ósseo ou periósteo adjacente. A massa foi submetida à excisão marginal e foi realizada eletroquimioterapia do leito cirúrgico. Histopatologia e análise imuno-histoquímica revelaram reações positivas para vimentina, Runx-2 e ki-67, levando ao diagnóstico de osteossarcoma extraesquelético. Este relato descreve um caso de osteossarcoma extraesquelético em um coelho, delineando sua apresentação clínica, características anatomopatológicas, modalidades diagnósticas e intervenções terapêuticas recomendadas.

Intermediate Filaments in Breast Cancer Progression, and Potential Biomarker for Cancer Therapy: A Narrative Review.

Intermediate filaments are one of the three components of the cytoskeletons, along with actin and microtubules. The intermediate filaments consist of extensive variations of structurally related proteins with specific expression patterns in cell types. The expression pattern alteration of intermediate filaments is frequently correlated with cancer progression, specifically with the epithelial-to-mesenchymal transition process closely related to increasing cellular migration and invasion. This review will discuss the involvement of cytoplasmic intermediate filaments, specifically vimentin, nestin, and cytokeratin (CK5/CK6, CK7, CK8/CK18, CK17, CK19, CK20, CSK1), in breast cancer progression and as prognostic or diagnostic biomarkers. The potential for drug development targeting intermediate filaments in cancer will be reviewed.

ZEB1 Promotes Epithelial-Mesenchymal Transition of Endometrial Epithelial Cells and Plays a Critical Role in Embryo Implantation in Mice.

Zinc finger E-box binding homeobox 1 (ZEB1) promotes epithelial-mesenchymal transition (EMT) in carcinogenesis, but its role in embryo implantation has not yet been well studied. In the present study we evaluated the hypothesis that ZEB1-induced EMT is essential for embryo implantation in vivo. Endometrial epithelium from female Kunming mice (non-pregnant, and pregnant from day 2.5 to 6.5) were collected for assessment of mRNA/protein expression of ZEB1, and EMT markers E-cadherin and vimentin, by employment of real-time quantitative reverse transcription PCR, Western blot, and immunohistochemical staining. To test if knockdown of ZEB1 affects embryo implantation in vivo, mice received intrauterine injection of shZEB1 before the number of embryos implanted was counted. The results showed that, ZEB1 was highly expressed at both mRNA and protein levels in the mouse endometrium on day 4.5 of pregnancy, paralleled with down-regulated E-cadherin and up-regulated vimentin expression (P < 0.05). Intrauterine injection of shZEB1 markedly suppressed embryo implantation in mice (P < 0.01). Conclusively, the present work demonstrated that ZEB1 is essential for embryo implantation under in vivo condition, and is possibly due to its effect on modulation of endometrial receptivity through EMT.

TGF-ß1/miR-30d-5p axis regulating the expression of EMT key factors to induce apoptosis of lung cancer cells.

Purpose: Previous studies have reported that miR-30d-5p gene expression can inhibit tumor proliferation, but its mechanism has not been fully elucidated. Methods: Based on previous findings, TGF-ß1 was used to induce epithelial mesenchymal transformation in A549 cells. The expression levels of DUSP-1, E-cadherin and Vimentin were detected by Western blot. mRNA expression levels of DUSP-1, E-cadherin and Vimentin were determined by RT-qPCR. The expression level of miR-30d-5p was determined by RT-qPCR. Results: The induction effect of TGF-ß1 could be reversed by the intervention of miR-30d-5p in A549 cells. miRNA inhibition experiment showed that miR-30d-5p inhibitor could effectively inhibit the expression of miR-30d-5p in A549 cells. After miR-30d-5p intervention, TGF-ß1 was reversed on EMT-related genes (Dusp-1, E-cadherin, Vimentin). Conclusion: TGF-ß1 can induce epithelial mesenchymal transformation of A549 cells, and miR-30d-5p may be a key regulatory mechanism in regulating gene and protein expression of TGF-ß1-mediated DUSP-1, E-cadherin and Vimentin. This provides a new perspective for understanding the anti-tumor effect of miR-30d-5p gene.

Long-term zinc treatment alters the mechanical properties and metabolism of prostate cancer cells.

The failure of intracellular zinc accumulation is a key process in prostate carcinogenesis. Although prostate cancer cells can accumulate zinc after long-term exposure, chronic zinc oversupply may accelerate prostate carcinogenesis or chemoresistance. Because cancer progression is associated with energetically demanding cytoskeletal rearrangements, we investigated the effect of long-term zinc presence on biophysical parameters, ATP production, and EMT characteristics of two prostate cancer cell lines (PC-3, 22Rv1). Prolonged exposure to zinc increased ATP production, spare respiratory capacity, and induced a response in PC-3 cells, characterized by remodeling of vimentin and a shift of cell dry mass density and caveolin-1 to the perinuclear region. This zinc-induced remodeling correlated with a greater tendency to maintain actin architecture despite inhibition of actin polymerization by cytochalasin. Zinc partially restored epithelial characteristics in PC-3 cells by decreasing vimentin expression and increasing E-cadherin. Nevertheless, the expression of E-cadherin remained lower than that observed in predominantly oxidative, low-invasive 22Rv1 cells. Following long-term zinc exposure, we observed an increase in cell stiffness associated with an increased refractive index in the perinuclear region and an increased mitochondrial content. The findings of the computational simulations indicate that the mechanical response cannot be attributed exclusively to alterations in cytoskeletal composition. This observation suggests the potential involvement of an additional, as yet unidentified, mechanical contributor. These findings indicate that long-term zinc exposure alters a group of cellular parameters towards an invasive phenotype, including an increase in mitochondrial number, ATP production, and cytochalasin resistance. Ultimately, these alterations are manifested in the biomechanical properties of the cells.

Extraskeletal Chondromatosis in a 30-Year-Old Patient: A Rare Case Report.

The term chondroma refers to a slow-growing benign tumor. When the tumor arises from the medullary cavity, it is referred to as enchondroma, which is a very common bone tumor. However, if it arises from soft tissues, which is extremely rare, it is referred to as soft tissue chondroma or extraskeletal chondroma. Extraskeletal chondromas are uncommon; benign soft tissue tumors that mostly originate from hyaline cartilage are unrelated to the periosteum, tendon, or bone. The most common sites include fingers and toes. The frequent presentation is a slow-growing, firm, painless, and occasionally tender soft tissue mass. Morphologically, it exhibits lobular structures of hyaline cartilage, and hence it becomes difficult to differentiate it from low-grade chondrosarcoma, so the alarming sign of differentiation becomes a must. Recurrence is possible if it is incompletely removed. Complete removal with the capsule is a must to avoid recurrence. Immunohistochemistry remains the cornerstone for a definite diagnosis when S100 protein and vimentin show positivity for tumor cells and the proliferation index (Ki67%) is low. In this study, we present a very uncommon case of a 30-year-old patient with soft tissue chondromatosis of the palmer aspect of the index finger and palm.

The Functions of SARS-CoV-2 Receptors in Diabetes-Related Severe COVID-19.

Angiotensin-converting enzyme 2 (ACE2) is considered a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor of high importance, but due to its non-ubiquitous expression, studies of other proteins that may participate in virus internalisation have been undertaken. To date, many alternative receptors have been discovered. Their functioning may provide an explanation for some of the events observed in severe COVID-19 that cannot be directly explained by the model in which ACE2 constitutes the central point of infection. Diabetes mellitus type 2 (T2D) can induce severe COVID-19 development. Although many mechanisms associated with ACE2 can lead to increased SARS-CoV-2 virulence in diabetes, proteins such as basigin (CD147), glucose-regulated protein 78 kDa (GRP78), cluster of differentiation 4 (CD4), transferrin receptor (TfR), integrins α5ß1/αvß3, or ACE2 co-receptors neuropilin 2 (NRP2), vimentin, and even syalilated gangliosides may also be responsible for worsening the COVID-19 course. On the other hand, some others may play protective roles. Understanding how diabetes-associated mechanisms can induce severe COVID-19 via modification of virus receptor functioning needs further extensive studies.

The Antimicrobial Peptide Merecidin Inhibit the Metastasis of Triple-Negative Breast Cancer by Obstructing EMT via miR-30d-5p/Vimentin.

Purpose: To investigate the inhibitory effect of antimicrobial peptide merecidin on triple-negative breast cancer (TNBC) and the mechanism of inhibiting epithelial-mesenchymal transformation (EMT) by regulating miR-30d-5p/vimentin. Methods: TNBC cell lines (MDA-MB-231, MDA-MB-468) were treated with merecidin to assess proliferation, migration, invasion ability, and EMT. Confocal laser localization was used to examine the role of merecidin and TNBC cells. The relationship between merecidin and miR-30d-5p was determined through RT-qPCR and dual-luciferase reporter gene, and the relationship between merecidin and vimentin was verified through pulling down the experiment. The effects of miR-30d-5p on the migration and invasion ability of TNBC cells were confirmed through scratch and transwell experiments. Vimentin levels, tumor volume, shape, size, and weight were observed in the MDA-MB-231 subcutaneous tumor model in nude mice. Results: merecidin inhibited the proliferation, migration, invasion, and EMT of TNBC cells. merecidin was primarily located in the cytoplasm of TNBC cells, and the expression of miR-30d-5p was low in TNBC cells. merecidin significantly up-regulated the expression of miR-30d-5p. miR-30d-5p negatively regulated vimentin. merecidin could bind to vimentin in vitro. miR-30d-5p inhibited the migration and invasion ability of TNBC cells, while vimentin promoted their migration and invasion ability. Down-regulation of miR-30d-5p or overexpression of vimentin partially counteracted the inhibitory effects of merecidin on TNBC cell migration, invasion ability, and EMT. In nude mouse tumor models, merecidin significantly suppressed tumor growth. Conclusion: Merecidin effectively blocks the EMT process and inhibits the migration and invasion of TNBC cells by regulating miR-30d-5p/vimentin.

The prognostic and therapeutic potential of vimentin in colorectal cancer.

Several cells and molecules in the tumor microenvironment have been introduced as effective factors in the prognosis and progression of colorectal cancer. As a key element of the intermediate filament family, vimentin is expressed by mesenchymal cells in a ubiquitous manner and contributes significantly to cellular integrity and stress resistance in colorectal cancer. Recent studies have shown that alterations in the expression patterns of intermediate filaments are significantly related to cancer progression, especially in phenotypes associated with cellular migration and invasion. In addition to its multiple biological roles, vimentin also has a substantial function in mediating the epithelial-mesenchymal transition. Therefore, evaluating vimentin as an effective factor involved in the prognosis of colorectal cancer and targeting it as a novel approach to cancer therapy have become one of the main goals of many researchers worldwide. In this article, we will review the various biological functions of vimentin, as well as its relationship with colorectal cancer with the aim of providing novel insights into its clinical importance in the prognosis and treatment of colorectal cancer.