Understanding of Endomucin: a Multifaceted Glycoprotein Functionality in Vascular Inflammatory-Related Diseases, Bone Diseases and Cancers.

Endomucin (MUC14), encoded by EMCN gene, is an O-glycosylated transmembrane mucin that is mainly found in venous endothelial cells (ECs) and highly expressed in type H vessels of bone tissue. Its main biological functions include promoting endothelial generation and migration through the vascular endothelial growth factor (VEGF) signaling pathway and inhibiting the adhesion of inflammatory cells to ECs. In addition, it induces angiogenesis and promotes bone formation. Due to the excellent functions of Endomucin in the above aspects, it provides a new research target for the treatment of vascular inflammatory-related diseases and bone diseases. Based on the current understanding of its function, the research of Endomucin mainly focuses on the above two diseases. As it is known, the progression of cancer is closely related to angiogenesis. Endomucin recently is found to be differentially expressed in a variety of tumors and correlated with survival rate. The biological role of Endomucin in cancer is opaque. This article introduces the research progress of Endomucin in vascular inflammatory-related diseases and bone diseases, discusses its application value and prospect in the treatment, and collects the latest research situation of Endomucin in tumors, to provide meaningful evidence for expanding the research field of Endomucin.

Application of chiral recyclable catalysts in asymmetric catalysis.

Chiral drugs hold a significant position within the contemporary pharmaceutical market, and the chiral catalysts play a crucial role in their synthesis. However, current chiral catalysts encounter challenges pertaining to their separation from products and the recycling process. The utilization of chiral recyclable catalysts not only reduces production costs but also aligns with the growing emphasis on environmentally-friendly chiral synthetic chemistry. These recyclable catalysts exhibit diverse carriers and distinct characteristics. Chemists employ the distinctive attributes of individual carriers to render them recyclable, thereby yielding time and cost savings. This review examines the asymmetric recyclable catalytic reactions reported between January 2017 and October 2023, categorizing them based on carrier solubility, and elucidates the loading techniques, catalytic impacts, recovery approaches, and recycling processes associated with these carriers.

Identification of a 5-Gene Cuproptosis Signature Predicting the Prognosis for Colon Adenocarcinoma Based on WGCNA.

Background: Colorectal cancer is a highly aggressive malignant tumor that primarily affects the digestive system. It is frequently diagnosed at an advanced stage. Cuproptosis is a copper-dependent form cell death mechanism, distinct from all other known pathways underlying cell death, tumor progression, prognosis, and immune response. Although the role of cuproptosis in colorectal cancer has been investigated over time, there is still an urgent need to explore new methods and insights to understand its potential function. Methods: The Gene Expression Omnibus and The Cancer Genome Atlas gene expression data were systematically explored to investigate the role of cuproptosis in colon adenocarcinoma. The weighted gene coexpression network analysis was used to construct a gene coexpression network and identify the critical module and cuproptosis-related genes correlated with colon adenocarcinoma prognosis. A cuproptosis-related genes prognostic signature for colon adenocarcinoma was identified and validated. To validate the identified gene signature, quantitative reverse transcription-polymerase chain reaction was performed. Cell proliferation assays were analyzed by CCK8 and cell cycle detection. In addition, reactive oxygen species assay was also analyzed. Results: Five hub cuproptosis-related genes (Dihydrolipoamide S-acetyltransferase, Cyclin-dependent kinase inhibitor 2A, ATOX1, VEGFA, and ULK1) were screened and a prognostic risk model for predicting overall survival was established based on these genes. The model was successfully tested in the validation cohort and the GEPIA database. Colon adenocarcinoma patients were categorized into high-risk and low-risk groups based on risk scores. The study revealed that patients with higher risk scores were more likely to have a poor prognosis. Moreover, Dihydrolipoamide S-acetyltransferase was a tumor suppressor gene that can induce cell death and affected the redox reactions in the colon cancer cell line. Conclusions: These findings suggest that the newly identified 5-gene signature may serve as a more reliable prognostic factor than clinical factors such as age and stage of disease. These findings offer a theoretical foundation for further investigation into potential cuproptosis-related biomarkers for predicting colon adenocarcinoma prognosis in the future.

The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System.

Drug delivery system (DDS) realizes the drug delivery process through the drug carrier. As an important part of DDS, the selection of the drug carrier material is extremely critical, which requires the carrier material to possess excellent biocompatibility and targeting and not affect the pharmacological action of the drug. As one of the endogenous extracellular vesicles, exosomes are 30-100 nm in diameter, which are considered a new generation of a natural nanoscale delivery system. Exosomes secreted by different types of cells carry signaling molecules (such as proteins and nucleic acid) playing an important role in cell behaviors. Owing to their ability to specialize in intercellular communication, exosomes provide a distinctive method to deliver therapeutic drugs to target cells. In this concept, exosomes as the natural liposomes carry endogenous biomolecules, have excellent biocompatibility, and could be loaded with cargo both in vivo and in vitro. In addition, modifications by genetic and/or chemical engineering to part of the exosome surface or complement the desired natural effect may enhance the targeting with drug loading capability. Notably, exosomes weakly react with serum proteins prolonging cargo half-life. Overall, exosomes as natural carriers integrate the superiority of synthetic nanocarriers and cellular communication while precluding their limitations, which provides novel and reliable methods for drug delivery and treatment. Our review focuses on the therapeutic potentials and clinical values of exosomes as a carrier of drug delivery system in multiple diseases, including cancer, nervous, immune, and skeletal system diseases.

Distinct clinicopathological features of pulmonary primary angiomatoid fibrous histiocytoma: A report of four new cases and review of the literature.

BACKGROUND: The aim of this study was to highlight the clinicopathological features of pulmonary primary angiomatoid fibrous histiocytoma (PPAFH) to assist with a differential diagnosis. METHODS: There were 10 previous reports in the literature and four new PPAFH cases reviewed in this study. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and DNA and RNA-based next-generation sequencing (NGS) was performed in the four new cases reported here. RESULTS: In the four new PPAFH cases, the ages of occurrence were in patients age from 33 to 55 years and tumor sizes were from 1.5 to 8 cm. Three of four (75.0%) tumors were located in the endobronchus. The most common morphological changes included delineated fibrous capsule (100%, 4/4), lymphoplasmacytic cuff (100%, 4/4), and dense or richly lymphoplasmatic infiltration (100%, 4/4). IHC analysis revealed that the tumor cells of four cases expressed vimentin and TLE1, ALK and CD163 or CD68 was positive in three cases, epithelial membrane antigen (EMA), desmin was positive in two cases, and SMA focal positive expression was observed in two cases. EWSR1 gene rearrangement was positive in all PPAFH cases (100%, 4/4) by FISH detections and four cases were confirmed as EWSR1-CREB1 fusion variant by DNA and RNA based NGS. No regional lymph nodes and distal metastasis, recurrences and death of disease after surgical excision were recorded in all four cases. CONCLUSIONS: PPAFH is a very unusual pulmonary primary mesenchymal tumor and the clinicopathological features are like other unusual sites counterparts, but with a smaller tumor size, related with large airway, with a tendency to exhibit benign biological behavior, with EWSR1 gene rearrangement and higher frequency of EWSR1-CREB1 gene fusion. KEY POINTS: Significant findings in the study: In comparison with "classic somatic" and nonpulmonary visceral angiomatoid fibrous histiocytoma, pulmonary primary angiomatoid fibrous histiocytoma display distinct clinicopathological features and prognosis. What this study adds The study provided the pathological differential diagnostic criteria and clinico-pathological features for pulmonary primary angiomatoid fibrous histiocytoma.

Hepatoid adenocarcinoma of the extrahepatic duct.

Hepatoid carcinoma is a unique type of extrahepatic tumor associated with hepatic differentiation and displays the morphological and functional features of hepatocellular carcinoma. Hepatoid carcinoma of the extrahepatic duct has rarely been reported in the literature. We report a 62-year-old man who presented with epigastric discomfort, xanthochromia, dull pain of the right shoulder, nausea and pruitus. Microscopic examination of the extrahepatic duct indicated that the tumor was primarily composed of "hepatoid cells", which were characterized by an eosinophilic cytoplasm, enlarged nucleus and prominent nucleoli. The cells were arranged in nests or proliferated in a trabecular pattern. Immunohistochemistry indicated that the tumor cells were positive for hepatocyte paraffin 1 and cytokeratins 8 and 18. Based on these findings, this case was diagnosed as hepatoid carcinoma of the extrahepatic duct.

An analysis of cyclin D1, cytokeratin 5/6 and cytokeratin 8/18 expression in breast papillomas and papillary carcinomas.

BACKGROUND: To evaluate the expression levels of cyclin D1 in breast papillomas and papillary carcinomas, and to analyze the types of cells that co-express cyclin D1 with cytokeratin 5/6 (CK 5/6) or with cytokeratin 8/18(CK 8/18). METHODS: Fifty-nine cases of papillary lesions including 36 papillomas and 23 intracystic papillary carcinomas were examined. Cyclin D1, CK 5/6 and CK 8/18 expression levels were evaluated by double immunostaining. RESULTS: Cyclin D1 is highly expressed in papillary carcinomas (27.54% ± 15.43%) compared with papillomas (8.81% ± 8.41%, p < 0.01). Cyclin D1 is predominantly expressed in cytokeratin 8/18- expressing cells, rather than in cytokeratin 5/6-expressing cells, regardless of the type of lesion. In papillomas, cyclin D1 exhibited a mean 11.42% (11.42% ± 10.17%) co-expression rate with cytokeratin 8/18 compared with a mean 2.50% (2.50% ± 3.24%) co-expression rate with cytokeratin 5/6 (p < 0.01). In papillary carcinomas, cyclin D1 exhibited a mean 34.74% (34.74% ± 16.32%) co-expression rate with cytokeratin 8/18 compared with a co-expression rate of 0.70% (0.70% ± 0.93%) with cytokeratin 5/6 (p < 0.01). CONCLUSIONS: The increase in cyclin D1 suggests an association of cyclin D1 staining with papillary carcinomas. Although cyclin D1 is an effective marker for the differential diagnosis of other papillary lesions, it cannot be used to distinguish between papilloma and papillary carcinoma lesions because its expression occurs in both lesions. Our results show that cyclin D1 and CK 5/6 staining could be used in concert to distinguish between the diagnosis of papilloma (cyclin D1 < 4.20%, CK 5/6 positive) or papillary carcinoma (cyclin D1 > 37.00%, CK 5/6 negative). In addition, our data suggest that cyclin D1 is expressed only in the cancer stem or progenitor cells that co-immunostained with CK 8/18 in papillary carcinomas, and predominantly with CK 8/18 in the papillomas. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7299340558756848.

Induction of cytomegalovirus-infected labyrinthitis in newborn mice by lipopolysaccharide: a model for hearing loss in congenital CMV infection.

Congenital cytomegalovirus (CMV) infection is the most common infectious cause of sensorineural hearing loss in children. Here, we established an experimental model of hearing loss after systemic infection with murine CMV (MCMV) in newborn mice. Although almost no viral infection was observed in the inner ears and brains by intraperitoneal (i.p.) infection with MCMV in newborn mice, infection in these regions was induced in combination with intracerebral (i.c.) injection of bacterial lipopolysaccharide (LPS). The susceptibility of the inner ears was higher than that of the brains in terms of viral titer per unit weight. In the labyrinths, the viral infection was associated with the mesenchymal vessels and accompanied by inflammatory cells induced by LPS, causing hematogenous targets of infection in the labyrinths. Viral infection also spread in the perilymph regions such as the scala tympani and scala vestibuli, probably from infected brains via meningogenic and cochlear nerve routes. Viral infection was not observed in the scala media in the endolymph, including the Corti organ. However, viral infection was observed in the spiral limbus, including the stria vascularis. These results suggest that hearing loss caused by labyrinthitis after congenital CMV infection may be enhanced by inflammation caused by systemic bacterial infection in the neonatal period.

Roles of neural stem progenitor cells in cytomegalovirus infection of the brain in mouse models.

Cytomegalovirus (CMV) is the most significant infectious cause of brain disorders in humans. Although the brain is the principal target organ for CMV infection in infants with congenital infection and in immunocompromised patients, little has been known about cellular events in pathogenesis of the brain disorders. Mouse models have been developed by the authors for studying the cell tropism, infectious dynamics of CMV infection and the effects of CMV infection on proliferation, regeneration and differentiation of neural cells. It has been shown, using brain slice cultures and neurospheres, that neural stem progenitor (NSP) cells are the most susceptible to CMV infection in developing brains. The NSP cells are also susceptible to CMV infection in adult and aged brains. The susceptibility can be enhanced by stimulation of neurogenesis. It was shown that latent murine CMV infection occurs in NSP cells by demonstrating the reactivation in brain slice culture or neurospheres. It is hypothesized that CMV brain disorder such as microcephaly is caused by disturbance of cellular events in the ventricular regions, including proliferation and differentiation of the neural stem cells, whereas neurons are also targets in persistent CMV infection, presumably resulting in functional disorders such as mental retardation.

Enhancement of susceptibility of adult mouse brain to cytomegalovirus infection by infusion of epidermal growth factor.

Neural precursor cells, including neural stem and progenitor cells, in the subventricular zone (SVZ) are the main targets for cytomegalovirus (CMV) infection in developing brains. The neural precursor cells in the SVZ of the adult brain have been reported to respond by proliferating after infusion with epidermal growth factor (EGF). Here we report the susceptibility of the precursor cells in the adult mouse brain to murine CMV (MCMV) infection. Adult mouse brains from 10-, 25-, and 70-week-old (W) mice were infused with either phosphate-buffered saline or EGF into the brain for 3 days, and then intracerebrally infected with MCMV for 5 days. The susceptibility of the adult brains to MCMV was significantly increased by infusion of EGF in terms of viral titers and viral antigen-positive cells. The susceptibility of the young adult brain from 10-week-old mice to MCMV was higher than that of the adult brains from 25-week-old or 70-week-old mice. Both the ependymal and the SVZ cells were susceptible to MCMV infection. The number of virus-infected cells in the SVZ was significantly increased by infusion of EGF, whereas the number of infected ependymal cells was not significantly increased. Among the virus-infected cells in the SVZ, 73% were positive for nestin, 87% were positive for Musashi, 86% were positive for GFAP, and 96% were positive for PCNA. These results indicate that the susceptibility of the adult brain to MCMV is correlated with the proliferative ability of the neural precursor cells in the SVZ of the adult brain.

BK virus subtype IV nephropathy occurring 5 years after kidney transplantation.

We report on a BK virus-associated nephropathy in a 28-year-old man. His symptoms occurred 5 years after he had received a kidney transplantation. He was treated with tacrolimus, azathioprine, and prednisolone. The progress of the disease was monitored by quantitative real-time polymerase chain reactions for BK virus DNA. An analysis of viral DNA showed that the BK virus in the patient's plasma belonged to genotype IV.

Phosphoglyceride (PG) crystal deposition disease: a novel acquired disease in which PG crystals are deposited in injured soft tissue and bone with phospholipid metabolism disturbance.

The clinical history and crystal characteristics of three published cases and three new cases of phosphoglyceride (PG) crystal deposition disease of soft tissues and bones were compared. All patients (age range, 51-64 years) were generally healthy without a genetic background of congenital immunodeficiency or lipidosis. Foreign body granulomas grew slowly, predominantly at postoperative or repeat injection lesions. In two cases, crystals were deposited in multiple locations, and in one case, lipophage accumulations were found in the bone marrow. The crystals characteristically dissolved in acetic acid with oxygen gas formation, easily dissolved in alkalis and showed positive staining for PG by the gold hydroxamic acid method. All crystals examined by infrared microscopy, mass spectrometry and X-ray microanalysis showed similar results, supporting the theory that the crystals were PG. Phosphoglyceride deposition disease is a lipid metabolic disorder in which PG crystals are slowly deposited, predominantly in injured soft tissues, forming foreign body granulomas. The diagnosis can be based on histological characteristics. The prognosis is favorable, although some cases showed systemic depositions with repetitions. Lysosomal phosphoglyceride metabolism in macrophages might be affected.

BK virus subtype 1 infection associated with tubulointerstitial nephritis in a renal allograft recipient.

The BK polyomavirus (BKV) infects most of the human population, but clinically relevant infections are usually limited to individuals who are in an immunosuppressed state. The significance of BKV infection was investigated in a 50-year-old man who underwent cadaveric kidney transplantation and was treated with tacrolimus, mycophenolate mofetil and prednisolone. By staining renal biopsy specimens with a monoclonal antibody against BK large T antigen, we were able to observe the relationship between the appearance of the BKV antigen and the extent of immunosuppression in this patient. We also determined that BKV belonged to genotype I by analysis of viral DNA from the patient's urine.

Radiation-induced laryngeal angiosarcoma after cervical tuberculosis and squamous cell carcinoma: case report and review of the literature.

Primary laryngeal angiosarcoma (LA) is quite rare with only 13 cases reported in English literature to date. A case of LA after radiation therapy for tuberculosis and squamous cell carcinoma is reported. A 70-year-old woman had a history of radiation therapy for left cervical tuberculosis at the age of 28. At 60 years of age a squamous cell carcinoma of the larynx was found and chemotherapy and radiotherapy, consisting of a total dose of 68.4 Gy, were administered. At the age of 68, recurrent squamous cell carcinoma was suspected from several biopsies, and a total laryngectomy with right thyroidectomy was performed. The tumor cells formed vascular spaces and expressed some endothelial markers, such as CD34, CD31, and Ulex europaeus agglutinin I, but no epithelial markers, such as cytokeratins or epithelial membrane antigen. No residual squamous cell carcinoma was found. In the present case, it was suspected that irradiation to the larynx for cervical tuberculosis and squamous cell carcinoma induced angiosarcoma. The patient was still alive despite multiple skin and soft tissue metastasis 3 years and 6 months after the radical operation. Distinction of postirradiation angiosarcoma from pseudoangiosarcomatous carcinoma seems difficult but is important because irradiation is not effective and an initial radical surgery is the only effective treatment. Although irradiation is a common treatment for laryngeal squamous cell carcinoma, this is only the second case of radiation-induced LA in English literature.

Primary prostatic endodermal sinus tumor (yolk sac tumor) combined with a small focal seminoma.

We report on a primary endodermal sinus tumor (EST) (yolk sac tumor) combined with a focal seminoma of the prostate occurring in a 24-year-old man. The prostate was widely infiltrated with neoplasms that penetrated the capsule and invaded into the bladder wall and urethra. Most areas of the tumor were composed of papillary and glandular epithelium in the fibrous or myxoid stroma. Schiller-Duval bodies and periodic acid-Schiff-positive hyaline bodies were focally present. In addition to yolk sac tumor, solid nests of seminoma were found in some areas. Immunohistochemistry using specific antibodies for alpha-fetoprotein and cytokeratin showed positive reaction on the EST portion, and placental alkaline phosphatase revealed positive staining in the seminoma portion and a part of EST. Tumor cells exhibited negative staining for prostate-specific antigen, prostatic acid phosphatase, carcinoembryonic antigen, vimentin, chromogranin A, and human chorionic gonadotropin. Despite radical surgery and ordinary cisplatin-based chemotherapy, the patient died 8 months after operation. At autopsy, only EST elements had metastasized to the lungs, liver, and brain, and no tumors were found in either testis. To our knowledge, this is the first reported case of a primary EST combined with a focal seminoma in the prostate.

Regression of congenital fibrosarcoma to hemangiomatous remnant with histological and genetic findings.

We report a rare case of congenital fibrosarcoma (CFS) showing regression during the course of disease, in which the histological and genetic alterations were investigated. This CFS, located on the patient's right hand, was a hemangiopericytomatous hypervascular tumor showing frequent mitosis and necrosis. Small lymphocytes, predominantly cytotoxic T cells and natural killer cells, infiltrated the tumor. At the age of 3 months, the patient received a partial resection of the tumor. At the age of 1 year, the hemangiopericytomatous tumor with a dilated vascular lumen remained, although most of the tumor cells exhibited focal necrosis with calcification and no mitotic activity. Lymphocytes increased in number and intermingled with the tumor cells. At the age of 4 years, vascular tissue consisting of inner endothelial cells and surrounding pericytomatous actin-positive cells remained at the previous tumor locus. With reverse transcription-polymerase chain reaction analysis, ETV6-NTRK3 fusion transcripts were detected in tumor samples at 3 months and at 1 year, but not from those at 4 years of age. These genetic and histological changes suggest that the CFS either completely disappeared by apoptosis or showed mature transformation to hemangiomatous tissue with aging.