Cells Lining Research Articles

New line of mesenchymal stem cell isolated from warton’s jelly of the umbical cord of male human donor

A new non-immortalized fibroblast-like cell line, named MSCWJ-3, was generated and characterized. Characteristics during long-term cultivation (6–24 passages) confirm the status of MSCs. It is shown: 1) a gradual increase in the proportion of senescent cells during long-term cultivation; 2) a significant decrease in the proliferation index by the 24th passage; 3) preservation of the normal diploid karyotype of the man (46, XY) during the entire period of cultivation, trisomy for different autosomes in single cells, absence of structural chromosomal rearrangements; 4) a high proportion of cells carrying surface antigens characteristic of MSCs: CD44, CD73, CD90, CD105, HLA-ABC and a low proportion with antigens CD34, CD45 and HLA-DR over 24 passages. Cells of the MSCWJ-3 line are capable of differentiation in the osteogenic and adipogenic directions at early and late passages; differentiation in the chondrogenic direction is absent. In general, there are some differences with previously obtained lines isolated from the same source and are associated mainly with the degree of expression of a number of status characteristics.

The survival prediction analysis and preliminary study of the biological function of YEATS2 in hepatocellular carcinoma.

Our study aims to develop and validate a novel molecular marker for the prognosis and diagnosis of hepatocellular carcinoma (HCC) MATERIALS & METHODS: We retrospectively analyzed mRNA expression profile and clinicopathological data of HCC patients fetched from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and The International Cancer Genome Consortium (ICGC) datasets. Univariate Cox regression analysis was performed to collect differentially expressed mRNA (DEmRNAs) from HCC and non-tumor tissues, and YEATS2, a prognostic marker, was identified by further analysis. ROC curve, survival analysis and multivariate Cox regression analysis as well as nomograms were used to evaluate the prognosis of this gene. Finally, the biological function of this gene was preliminarily discussed by using single gene Gene Set Enrichment Analysis (GSEA), and the YEATS2 overexpression and knockdown hepatoma cell line was used to verify the results in vitro and in vivo. Based on the clinical information of HCC in TCGA, GEO and ICGC databases, the gene YEATS2 with significant differences from HCC was identified. There was a statistical difference in the survival prognosis between the two databases and the ROC curve showed that the survival of HCC in both TCGA, GSE14520 and ICGC groups had a satisfactory predictive effect. Univariate and multivariate Cox regression analysis showed that YEATS2 was an independent prognostic factor for HCC, and Nomograms, which combined this prognostic feature with significant clinical features, provided an important reference for the clinical prognostic diagnosis of HCC. Next, we constructed overexpression and knockdown YEATS2 cell line in Hep3B and LM3 cells, and further proved that overexpression YEATS2 promote the proliferation and migration of HCC cells by CCK8, colony formation experiment, and transwell assays, and knockdown YEATS2 inhibited the proliferation and migration of HCC cells by CCK8, colony formation experiment, and transwell assays. Finally, the biological function of YEATS2 was preliminarily explored through GSEA analysis of a single gene, and it was found that it was significantly correlated with cell cycle and DNA repair, which provided us with ideas for further analysis. Furthermore, the knockdown of YEATS2 promoted radiation-induced DNA damage, enhanced radiosensitivity, and ultimately inhibited the proliferation of hepatocellular carcinoma cells in vitro and in vivo. Our study identified a promising prognostic marker for hepatocellular carcinoma that is useful for clinical decision-making and individualized treatment.

The Tumor-Associated Calcium Signal Transducer 2 (TACSTD2) oncogene is upregulated in cystic epithelial cells revealing a potential new target for polycystic kidney disease.

Polycystic kidney disease (PKD) is an important cause of kidney failure, but treatment options are limited. While later stages of the disease have been extensively studied, mechanisms driving the initial conversion of kidney tubules into cysts are not understood. To identify genes with the potential to promote cyst initiation, we deleted polycystin-2 (Pkd2) in mice and surveyed transcriptional changes before and immediately after cysts developed. We identified 74 genes which we term cyst initiation candidates (CICs). To identify conserved changes with relevance to human disease we compared these murine CICs to single cell transcriptomic data derived from patients with PKD and from healthy controls. Tumor-associated calcium signal transducer 2 (Tacstd2) stood out as an epithelial-expressed gene with elevated levels early in cystic transformation that further increased with disease progression. Human tissue biopsies and organoids show that TACSTD2 protein is low in normal kidney cells but is elevated in cyst lining cells, making it an excellent candidate for mechanistic exploration of its role in cyst initiation. While TACSTD2 has not been studied in PKD, it has been studied in cancer where it is highly expressed in solid tumors while showing minimal expression in normal tissue. This property is being exploited by antibody drug conjugates that target TACSTD2 for the delivery of cytotoxic drugs. Our finding that Tacstd2/TACSTD2 is prevalent in cysts, but not normal tissue, suggests that it should be explored as a candidate for drug development in PKD. More immediately, our work suggests that PKD patients undergoing TACSTD2-directed treatment for breast and urothelial cancer should be monitored for kidney effects.

Diagnosis of liver hemangioma using magnetic resonance diffusion-derived vessel density (DDVD) pixelwise map: a preliminary descriptive study.

Liver hemangiomas (HGs) are characterized by cavernous venous spaces delineated by a lining of vascular endothelial cells and interspersed with connective tissue septa. Typically, a liver HG has higher apparent diffusion coefficient (ADC) and T2 values than those of hepatocellular carcinomas (HCCs) and liver metastases, and lower ADC and T2 values than those of liver simple cysts. However, a portion of HGs shows ADC and T2 overlapping with those of HCC, liver metastasis, and simple cyst. When MRI is the first line examination for the liver, contrast enhanced imaging is commonly used to confirm the diagnosis of liver HG. Magnetic resonance diffusion-derived vessel density (DDVD) is a physiological surrogate of the area of microvessels per unit tissue area. DDVD is calculated according to: DDVD(b0b2) = Sb0/ROIarea0 - Sb2/ROIarea2, where Sb0 and Sb2 refer to the tissue signal when b is 0 or 2 (s/mm2). Sb2 and ROIarea2 can also be approximated by other low b-values (such as b=10) diffusion-weighted imaging (DWI). In this study, we conducted a preliminary evaluation of magnetic resonance DDVD pixelwise map (DDVDm) for liver HG diagnosis. Three testing datasets were included. All imaging data were acquired at 3.0T. Dataset-1 consisted of 16 HGs (lesion diameter: 1.5-8.85 cm), 4 focal nodular hyperplasia (FNHs, lesion diameter: 1.72-5.7 cm), and 24 HCCs (lesion diameter: 1.83-12.77 cm), and DDVDm was reconstructed with b=0 and b=2 images. Dataset-2 consisted of 6 HGs (lesion diameter: 1.14-6.2 cm), and DDVDm was reconstructed with b=0 and b=10 images. Dataset-3 consisted of 28 HCCs (lesion diameter: 1.91-3.52 cm), and DDVDm was reconstructed with b=0 and b=2 images. For dataset-1 and dataset-2, a trained reader was required to make a diagnosis for a lesion solely based on DDVDm with 4 choices: (I) HG with confidence; (II) HG without confidence; (III) solid mass-forming lesion (MFL) with confidence; (IV) solid MFL without confidence. Then, three readers attempted to confirm whether DDVDm features summarized from dataset-1 and dataset-2 would be generalizable to dataset-3. For dataset-1 and dataset-2 together, the correct diagnosis was made by the trained reader in 90.9% (20/22) of the HGs (77.7% with confidence) and 96.4% (27/28) of the MFLs (85.7% with confidence). HG generally showed substantially higher DDVD signal relative to background liver parenchyma. Though not necessarily, HG DDVD signals could be similar to those of blood vessels. Some HGs showed DDVD signals higher or similar to that of kidneys which have a higher perfusion than the liver. MFL generally showed DDVD signals only slightly higher, similar to, or even slightly lower, than that of background liver parenchyma. The DDVDm features of dataset-3 were all consistent with MFL. When DDVDm is used to evaluate the liver, HG can be diagnosed with confidence in a substantial portion of patients without the need for a contrast enhanced scan. Our result will be relevant for HG confirmation when MRI is the first line examination for the liver.

Zhuanggu Jianxi Decoction reduces synovial tissue inflammation in human knee osteoarthritis by regulating LXRs/NF-κB signaling pathway

This study aims to explore the mechanism of Zhuanggu Jianxi Decoction in reducing synovial tissue inflammation in human knee osteoarthritis(KOA) via the liver X receptors(LXRs)/nuclear factor(NF)-κB signaling pathway. The synovial tissue samples were collected from 5 healthy volunteers and 30 KOA synovitis patients and cultured in vitro. The samples from the heathy volunteers were set as the normal group, and those from KOA synovitis patients were randomized into synovitis, Zhuanggu Jianxi Decoction, LXRα inhibitor, and N-CoR inhibitor groups. The synovitis tissue samples of the 5 groups were treated with 10% blank serum, 10% blank serum, 10% drug-containing serum, 10% drug-containing serum+LXRα inhibitor, and 10% drug-containing serum+N-CoR inhibitor, respectively, for 7 days. After intervention, the synovial tissue samples of each group were collected and stained with hematoxylin-eosin for observation and scoring of the pathological changes. The expression intensity of the fibroblast-specific marker α-smooth musle actin(α-SMA) in the synovial tissue was observed by immunofluorescence staining. The levels of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), matrix metalloproteinase-3(MMP-3), and matrix metalloproteinase-13(MMP-13) in the supernatant of synovium homogenate were determined by ELISA. The mRNA and protein levels of LXRα, N-CoR, P50, and P65 in the synovial tissue were determined by RT-qPCR and Western blot, respectively. The results showed that compared with the normal group, the synovitis group showcased obvious synovial lining cell proliferation, inflammatory cell infiltration, synovial cell disarrangement, increased histopathological score(P<0.05), enhanced α-SMA fluorescence intensity and increased number of synovial fibroblasts(P<0.05), elevated levels of IL-1β, TNF-α, MMP-3, and MMP-13 in the synovial tissue(P<0.05), down-regulated mRNA and protein levels of LXRα and N-CoR, and up-regulated mRNA and protein levels of P50 and P65(P<0.05). Compared with the synovitis group, the Zhuanggu Jianxi Decoction group showed alleviated pathological changes, declined histopathological score of the synovial tissue(P<0.05), decreased α-SMA fluorescence intensity and number of synovial fibroblasts(P<0.05), lowered levels of IL-1β, TNF-α, MMP-3, and MMP-13(P<0.05), up-regulated mRNA and protein levels of LXRα and N-CoR, and down-regulated mRNA and protein levels of P50 and P65(P<0.05) in the synovial tissue. Compared with the Zhuanggu Jianxi Decoction group, the LXRα inhibitor group and N-CoR inhibitor group showed aggravated pathological changes, risen histopathological score of the synovial tissue(P<0.05), enhanced α-SMA fluorescence intensity and increased number of synovial fibroblasts(P<0.05), elevated levels of IL-1β, TNF-α, MMP-3, and MMP-13(P<0.05), down-regulated mRNA and protein levels of LXRα and N-CoR, and up-regulated mRNA and protein levels of P50 and P65(P<0.05). The results above indicated that Zhuanggu Jianxi Decoction could alleviate the synovial tissue inflammation in KOA patients by upregulating the mRNA and protein levels of LXRα and N-CoR in the LXRs/NF-κB pathway to downregulate the mRNA and protein levels of P50 and P65 and reduce the activity of the NF-κB pathway in the synovial tissue.

Nutritional Adequacy in Adolescent Towards the Menstrual Cycle

Improving the health and well-being of teenagers is essential, especially during puberty. Teenage girls undergo a variety of changes, both physically and mentally. Adequate nutrition is necessary to support the completion of puberty. Menstruation, which involves the shedding of the uterine lining and egg cells is one of primary bodily changes young women experience during puberty. Adolescent girls’ menstrual cycles are influenced by hormonal changes during puberty. Menstrual problems or disorders that need to be known and frequently become complaints include dysmenorrhea (pain during menstruation), menorrhagia (large blood volume during menstruation), amenorrhea (menstruation that abruptly stops for no apparent reason or has not occurred since the age of 16), and oligomenorrhea. This study, conducted at the women's dormitory at Tribhuwana Tunggadewi University in Malang, aimed to assess young women's nutritional adequacy during their menstrual cycle. Utilizing a robust correlational research design, the study was carried out from July to August 2024 to ensure the reliability of the results. A total of 32 respondents participated. Statistical analysis with the Chi-square test yielded significant findings: adolescent girls' BMI had a significantly impacts on nutritional adequacy, with a p-value (2-tailed) of 0.000 (p 0.05). The analysis showed 19 respondents had a normal BMI (59.4%), while 12 (37.5%) were classified as underweight. Additionally, 28 respondents (87.5%) were have adequate nutrition, demonstrating the effectiveness of the study's methodology in assessing nutritional adequacy during the menstrual cycle. It is recommended to increase the number of study sample and examine other factors that may contribute to irregular menstrual cycle.

Polycomb protein Bmi1 promotes odontoblast differentiation by accelerating Wnt and BMP signaling pathways.

Bmi1 is a polycomb protein localized in stem cells and maintains their stemness. This protein is also reported to regulate the expression of various differentiation genes. In this study, to analyze the role of Bmi1 during dentinogenesis, we examined the immunohistochemical localization of Bmi1 during rat tooth development as well as after cavity preparation. Bmi1 localization was hardly detected in the dental mesenchyme at the bud and cap stages. After the bell stage, however, this protein became detectable in preodontoblasts and early odontoblasts just beginning dentin matrix secretion. As dentin formation progressed, Bmi1 immunoreactivity in the odontoblasts decreased in intensity. After cavity preparation, cells lining the dentin and some pulp cells under the cavity were immunopositive for Bmi1 at 4days. Odontoblast-like cells forming reparative dentin were immunopositive for Bmi1 at 1week, whereas their immunoreactivity was not detected after 8weeks. We further analyzed the function of Bmi1 using KN-3 cells, a dental mesenchymal cell line. Overexpression of Bmi1 in KN-3 cells promoted mineralized tissue formation. In contrast, siRNA knockdown of Bmi1 in KN-3 cells reduced alkaline phosphatase activity and the expression of odontoblast differentiation marker genes such as Runx2, osterix, and osteocalcin. Additionally, KN-3 cells transfected with siRNA against Bmi1 showed reduced nuclear transition of β-catenin and expression of phosphorylated-Smad1/5/8. Taken together, these findings suggest that Bmi1 was localized in the odontoblast-lineage cells in their early differentiation stages. Bmi1 might positively regulate their differentiation by accelerating Wnt and BMP signaling pathways.

Comparative transcriptomic and metabolomic analysis of FTO knockout and wild-type porcine iliac artery endothelial cells

The fat mass and obesity associated (FTO) gene, previously identified as a pivotal genetic locus associated with adiposity, has recently been linked to various cancers. In this study, we established an FTO knockout (KO) cell line in porcine iliac artery endothelial cells (PIECs) utilizing CRISPR/Cas9 technology to systematically investigate the gene’s function and effect through transcriptomic and metabolomic analysis. Our results revealed significant gene expression and metabolic profiles differences between the FTO KO and wild-type (WT) cells. Furthermore, enrichment analysis highlighted the involvement of differentially expressed genes in metabolic processes, cellular components, and molecular functions, as well as in complement and coagulation cascades, mineral absorption, glutathione metabolism, insulin signaling, fluid shear stress, and atherosclerosis pathways. The metabolomic profiling revealed clear distinctions between the FTO KO and WT cells, indicating profound modifications in cellular metabolism. Correlation analysis of transcriptomic and metabolomic data revealed a significant association between six metabolites and twenty genes, with melatonin showing specific correlations with the expression of several genes, indicating a complex regulatory network between gene expression and metabolic changes. This study provides a foundation for further research on the FTO gene’s role in cellular processes and molecular mechanisms underlying physiological and pathological conditions.

Ubiquitin-Specific Protease 1 Promotes Bladder Cancer Progression by Stabilizing c-MYC.

Ubiquitination is an important post-transcriptional modification crucial for maintaining cell homeostasis. As a deubiquitination enzyme, ubiquitin-specific protease 1 (USP1) is associated with tumor progression; however, its role in bladder cancer is unknown. This study aimed to analyze USP1 expression and study its roles in bladder cancer. The web server GEPIA was used to analyze the USP1 expression. To explore USP1's function in bladder cancer, we constructed USP1-knockout cell lines in UMUC3 cells. A FLAG-USP1 (WT USP1) plasmid and a plasmid FLAG-USP1 C90S (catalytic-inactive mutant) were used to overexpress USP1 in T24 cells. CCK8, colony formation, and Transwell assays were used to assess cell viability, proliferation, and migration. RNA-sequencing (RNA-seq) and dual-luciferase reporter assays were performed to screen the pathway. Co-immunoprecipitation and immunofluorescence were used to explore the interaction between USP1 and c-MYC. A xenograft mouse model was used to study the role of USP1 in bladder cancer. USP1 expression was upregulated in human bladder cancer cells and correlated with poor patient prognosis. USP1 overexpression promoted cell proliferation, clone formation, and migration, and this was attenuated by genetic ablation of USP1. Furthermore, we observed that USP1 deficiency inhibited tumor formation in vivo. Mechanistically, the c-MYC pathway was remarkably activated compared with the other pathways. Furthermore, USP1 could interact with c-MYC and increase c-MYC's stability depending on the catalytic activity of USP1. Our results suggested that high expression of USP1 promotes bladder cancer progression by stabilizing c-MYC; hence, USP1 may serve as a novel therapeutic target for treating bladder cancer.

Renal Toxic Effects of MgO NPs in Male Rats

Engineered nanomaterials are so tiny that they cannot be seen without special equipment; they are found in many industrial products today, consumer products, medicines, and food products. The small size and other properties of nanomaterials can make them very hazardous to human health. Magnesium oxide nanoparticles (MgO NPs), or metal oxides, have several advantages compared to other metal oxide nanoparticles because of their properties. Therefore, multiple uses of MgO NPs put human health at risk from prolonged exposure. The study aimed to determine how treatment with oral doses of MgO nanoparticles affects the kidneys of male rats through the oral route at 250 and 1000 mg/kg for 14 days, 28 days, and 56 days, respectively. Sixty mature male rats (2.5–3 months) were divided randomly into twelve groups of six rats each and gavaged with MgO NPs. The results observed a significant increase (p<0.01) in urea, creatinine, and uric acid; the histopathological examinations demonstrated necrotic debris inside the lumen of renal tubules; debris of lining epithelial cells inside the lumen of renal tubules; and the marked renal tubules were non-functional focal areas of necrosis and apoptosis. MgO NPs demonstrate potential issues with the kidneys and human health.

The collagenase-induced osteoarthritis (CIOA) model: Where mechanical damage meets inflammation

ObjectiveTo characterize inflammatory and mechanical changes in the collagenase-induced OA (CIOA) model in rats. DesignSkeletally mature, 6-month-old Wistar rats received unilateral intraarticular injections of saline, 500 U or 1000 U of collagenase on days 0 and 2 of the study. Joint tissues were harvested on either day 4 or 70 to evaluate the acute and long-term changes. Blood biomarkers, gait asymmetry and mechanical hyperalgesia were assessed repeatedly up until day 70. ResultsThe intraarticular injection of collagenase triggered an increase in cartilage degeneration and bone resorption over time, particularly for 1000 U. Similarly, mild synovitis was observed on day 70 with an increased number of synovial lining cells, increased fibrosis, and infiltration of peripheral macrophages. Mechanistically, these findings were linked to a dose-related mechanical weakening of the anterior cruciate ligament (ACL), which caused persistent joint destabilization throughout the study. Furthermore, the collagenase injection triggered acute inflammation and swelling of the synovium on day 4 and an acute systemic inflammatory response with increased cytokine and peripheral blood immune cell levels. While mild synovitis persisted until day 70, the systemic inflammatory response returned to control levels after 8 days. Similarly, the observed acute changes in gait and mechanical hyperalgesia also returned to baseline after 21 days. ConclusionBy evaluating inflammatory and mechanical factors at different doses and timepoints, our characterization enables a more targeted study design and increases the clinical relevance of future studies involving the CIOA model.

Impact of Temperature and Process Corners on Read Bit Line of 8T-SRAM Cell for NOR, NAND Operations

SRAM reliability is one of the major concerns as it suffers from variations in Static Noise Margin with temperature variations, which degrades the performance. It needs attention due to the increasing impact of process corners, which are variations in parameters due to the switching properties of transistors. Since the SRAM is also used as in-memory computation, stability plays a significant role in the computation. In this manuscript, 8T-SRAM stability for NOR, NAND logic is presented at process corners: Fast NMOS-Fast PMOS (FF), Fast NMOS-Slow PMOS (FS), and Slow NMOS-Slow PMOS (SS), with changes in temperature and monte-carlo simulations are also performed to predict the probability of Read Bit Line (RBL) voltage. The results are obtained using Cadence Virtuoso Simulations at the 45 nm technology node and show that the RBL voltage deviates by 10–30 mV for every 25°C rise in temperature from −25oC to 125oC.

In Silico Insights Reveal Fibronectin 1 as a Theranostic Marker in Gastric Cancer.

Gastric cancer (GC) is a complex and highly variable disease, ranking among the top five cancers diagnosed globally, and a leading cause of cancer-related deaths. Emerging from stomach lining cells amid chronic inflammation, it often advances to preneoplastic stages. Late-stage diagnoses and treatment challenges highlight the critical need for early detection and innovative biomarkers, motivating this study's focus on identifying theranostic markers through gene ontology analysis. By exploring deregulated biological processes, this study aims to uncover insights into cancer progression and associated markers, potentially identifying novel theranostic candidates in GC. Using public data from The Human Protein Atlas, this study pinpointed 299 prognostic genes, delineating 171 with unfavorable prognosis and 128 with favorable prognosis. Functional enrichment and protein-protein interaction analyses, supported by RNAseq results and conducted via Metascape and Cytoscape, highlighted five genes (vWF, FN1, THBS1, PCDH7, and F5) with promising theranostic potential. Notably, FN1 and THBS1 exhibited significant promise, with FN1 showing a 370% expression increase in cancerous tissue, and it is possible that FN1 can also indicate the stratification status in GC. While further validation is essential, these findings provide new insights into molecular alterations in GC and potential avenues for clinical application of theranostic markers.

Multiomics profiling of mouse polycystic kidney disease progression at a single-cell resolution

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and causes significant morbidity, ultimately leading to kidney failure. PKD pathogenesis is characterized by complex and dynamic alterations in multiple cell types during disease progression, hampering a deeper understanding of disease mechanism and the development of therapeutic approaches. Here, we generate a single-nucleus multimodal atlas of an orthologous mouse PKD model at early, mid, and late timepoints, consisting of 125,434 single-nucleus transcriptomic and epigenetic multiomes. We catalog differentially expressed genes and activated epigenetic regions in each cell type during PKD progression, characterizing cell-type-specific responses to Pkd1 deletion. We describe heterogeneous, atypical collecting duct cells as well as proximal tubular cells that constitute cyst epithelia in PKD. The transcriptional regulation of the cyst lining cell marker GPRC5A is conserved between mouse and human PKD cystic epithelia, suggesting shared gene regulatory pathways. Our single-nucleus multiomic analysis of mouse PKD provides a foundation to understand the earliest changes molecular deregulation in a mouse model of PKD at a single-cell resolution.

Rare Seminal Vesicle Cystadenoma: Case Report and Literature Review

Abstract Introduction/Objective Primary neoplasms of seminal vesicles (SV) are rare, with the majority being metastatic tumors, often from prostatic carcinoma. SV cystadenoma is an exceedingly rare benign epithelial tumor that arises from the remnants of the Mullerian duct. The tumor formed of cysts of variable sizes lined by bland cuboidal epithelium. Herein we present a case of SV cystadenoma in a 38-year-old male, underscoring its rarity and risk of progression to higher grades, as outlined in literature review. Methods/Case Report A 38-year-old male with a history of left atrophic kidney and intermittent pelvic pain due to recurrent obstruction of the SV. Pelvic Magnetic Resonance Imaging revealed a 5.3 cm benign unilocular cyst within the SV, along the posterior aspect of the urinary bladder. The patient underwent successful laparoscopic excision of the left SV. Gross examination of the excised SV demonstrated a 3.5X 2.7X 1.5 cm cyst within the SV. Microscopic examination displayed a benign cyst lined by single to multiple layers of cuboidal epithelium, surrounded by unremarkable SV stroma. The epithelial lining cells exhibited round nuclei with inconspicuous nucleoli, lacking dysplasia. Immunohistochemistry revealed positive staining for cytokeratin 7 and PAX 8 in the epithelial cells, whereas prostatic specific antigen staining was negative. Results (if a Case Study enter NA) NA Conclusion Cystadenoma and mixed epithelial stromal tumors of the SV (MEST) are rare entities, with approximately 30 reported cases. This case demonstrates classic histologic features consistent with low-grade MEST, as per recently proposed grading criteria. Notably, a recent case report has suggested a potential for malignant transformation to high-grade dysplasia and adenocarcinoma in SV cystadenoma, as evidenced by focal epithelial dysplasia.

Drug Repurposing Using Computational Tools and Preventive Strategies for COVID-19 and Future Pandemics

Coronavirus disease-19 (COVID-19) was declared a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that targets the lower respiratory tract in human species. Since the target receptor molecule is angiotensin-converting enzyme 2 (ACE2), which is highly expressed on the cell lining of the respiratory tract, the virus is responsible for causing acute respiratory distress syndrome (ARDS). Computational tools such as artificial intelligence, machine learning and deep learning-based platforms are used for drug repurposing, identification, and selection of target molecules that can be used for vaccine development and antiviral drug production. Computer-aided drug designing, molecular docking and homology modelling are some of the most widely used in silico models for drug discovery against COVID-19. It is important to take preventive measures to control the spread of the virus. The present review focuses on the computational tools used for recognising the target molecules for vaccine production, the transmission networks of COVID-19 and the long-term strategies to prevent future pandemics such as COVID-19.

Synovial fluid analysis in healthy green turtles Chelonia mydas in Taiwan.

Septic arthritis is a frustrating disease in sea turtle rehabilitation because of its unclear pathogenesis, delayed onset during rehabilitation, long-term treatment requirements, and potentially poor prognosis. Radiography, blood cultures, and arthrocentesis have been used as diagnostic tools for suspected cases. However, there is currently a lack of data on the characteristics of synovial fluid in healthy sea turtles. To establish reference data for synovial fluid in sea turtles, we enrolled 14 green turtles Chelonia mydas rescued between 2019 and 2022 from 3 facilities using the following inclusion criteria: normal attitude and appetite, normal motor functions of the 4 limbs, no joint swelling, and no ongoing use of antibiotics for at least 1 mo. Bacterial cultures of blood and synovial fluid from the shoulder joints of these turtles were obtained and a qualitative analysis of the synovial fluid was performed. The results revealed bacterial culture-negative blood and synovial fluids at 37°C. Most characteristics of normal synovial fluid in green turtles, such as being transparent, colorless, and able to create a strand of over 2.5 cm by being pulled with a needle in viscosity trials, as well as the cytology of the normal synovial fluids being dominated by histiocytes and synovial lining cells, lymphocytes, and occasionally a few heterophils or erythrocytes were similar to those in mammals. This study provides information on the normal synovial fluid characteristics of green turtles in Taiwan, which may be beneficial for the diagnosis of joint diseases in sea turtles.

Case Report of a 2-year-old Child with Barrett’s Syndrome

Abstract Barrett’s esophagus (BE) is a condition characterized by a change in the cell lining of the esophagus accompanied by intestinal metaplasia. It is most common in people diagnosed with gastroesophageal reflux disease (GERD). It is the result of repeated exposure of the esophagus to stomach acid. BE prevalence in the general population is about 1.6%–1.7%. This case report concerns one case of a child with BE. This child was diagnosed with Barrett’s syndrome based on physical examination, abdominal ultrasound, endoscopy, as well as a stomach biopsy. The management aimed on symptomatic management of BE due to GERD and prevention of progression to carcinoma. The child was given a proton-pump inhibitor and prokinetic for symptomatic relief and advised to undergo endoscopy every 6 months to identify the level of tissue dysplasia.

Early treatment with 2-deoxy-d-glucose reduces proliferative proteins in the kidney and slows cyst growth in a hypomorphic Pkd1 mouse model of autosomal dominant polycystic kidney disease (PKD)

In autosomal dominant polycystic kidney disease (ADPKD) there is cyst growth in the kidneys that leads to chronic kidney disease often requiring dialysis or kidney transplantation. There is enhanced aerobic glycolysis (Warburg effect) in the cyst lining epithelial cells that contributes to cyst growth. The glucose mimetic, 2-Deoxy-d-glucose (2-DG) inhibits glycolysis. The effect of early and late administration of 2-DG on cyst growth and kidney function was determined in Pkd1RC/RC mice, a hypomorphic PKD model orthologous to human disease. Early administration of 2-DG resulted in decreased kidney weight, cyst index, cyst number and cyst size, but no change in kidney function. 2-DG decreased proliferation. a major mediator of cyst growth, of cells lining the cyst. Late administration of 2-DG did not have an effect on cyst growth or kidney function. To determine mechanisms of decreased proliferation, an array of mTOR and autophagy proteins was measured in the kidney. 2-DG suppressed autophagic flux in Pkd1RC/RC kidneys and decreased autophagy proteins, ATG3, ATG5 and ATG12–5. 2-DG had no effect on p-mTOR or p-S6 (mTORC1) and decreased p-AMPK. 2-DG decreased p-4E-BP1, p-c-Myc and p-ERK that are known to promote proliferation and cyst growth in PKD. 2-DG decreased p-AKTS473, a marker of mTORC2. So the role of mTORC2 in cyst growth was determined. Knockout of Rictor (mTORC2) in Pkd1 knockout mice did not change the PKD phenotype. In summary, 2-DG decreases proliferation in cells lining the cyst and decreases cyst growth by decreasing proteins that are known to promote proliferation. In conclusion, the present study reinforces the therapeutic potential of 2-DG for use in patients with ADPKD.

Exploring the Potential of Saphenous Vein Grafts Ex Vivo: A Model for Intimal Hyperplasia and Re-Endothelialization.

Coronary artery bypass grafting (CABG) utilizing saphenous vein grafts (SVGs) stands as a fundamental approach to surgically treating coronary artery disease. However, the long-term success of CABG is often compromised by the development of intimal hyperplasia (IH) and subsequent graft failure. Understanding the mechanisms underlying this pathophysiology is crucial for improving graft patency and patient outcomes. Objectives: This study aims to explore the potential of an ex vivo model utilizing SVG to investigate IH and re-endothelialization. Methods: A thorough histological examination of 15 surplus SVG procured from CABG procedures at Hospital Canselor Tuanku Muhriz, Malaysia, was conducted to establish their baseline characteristics. Results: SVGs exhibited a mean diameter of 2.65 ± 0.93 mm with pre-existing IH averaging 0.42 ± 0.13 mm in thickness, alongside an observable lack of luminal endothelial cell lining. Analysis of extracellular matrix components, including collagen, elastin, and glycosaminoglycans, at baseline and after 7 days of ex vivo culture revealed no significant changes in collagen but demonstrated increased percentages of elastin and glycosaminoglycans. Despite unsuccessful attempts at re-endothelialization with blood outgrowth endothelial cells, the established ex vivo SVG IH model underscores the multifaceted nature of graft functionality and patency, characterized by IH presence, endothelial impairment, and extracellular matrix alterations post-CABG. Conclusions: The optimized ex vivo IH model provides a valuable platform for delving into the underlying mechanisms of IH formation and re-endothelialization of SVG. Further refinements are warranted, yet this model holds promise for future research aimed at enhancing graft durability and outcomes for CAD patients undergoing CABG.