Squamous Epithelial Cells Research Articles

Single-Cell RNA Sequencing Reveals the Cellular Origin and Evolution of Small-Cell Neuroendocrine Carcinoma of the Cervix.

Small-cell neuroendocrine cancer (SCNEC) of the uterine cervix is an exceedingly rare, highly aggressive tumor with an extremely poor prognosis. The cellular heterogeneity, origin, and tumorigenesis trajectories of SCNEC of the cervix remain largely unclear. We performed single-cell RNA sequencing and whole-exome sequencing on tumor tissues and adjacent normal cervical tissues from two patients diagnosed with SCNEC of the cervix. Here, we provide the first comprehensive insights into the cellular composition, HPV infection-related features, and gene expression profiles of SCNEC of the cervix at single-cell resolution. Correlation analyses suggested that SCNEC of the cervix may originate from squamous epithelial cells, and this observation was validated with bulk RNA-seq data from external cervical neuroendocrine cancer. Furthermore, sex-determining region Y-box 2 (SOX2), a key transcription factor that functions in direct neural differentiation, was located in the copy number gain region and highly expressed in neuroendocrine tumor cells from both patients. Notable, the distributions of the HPV-infected epithelium and SOX2 highly expressed epithelium were consistent with each other. Therefore, we supposed that high-risk HPV infection and amplification of SOX2 in the squamous epithelium may contribute to the progression of small-cell neuroendocrine tumorigenesis in the cervix.

Hyperproteinemia, Hematuria, and Squamous Cell Shedding in Elderly Cervical Cancer Patients and the Potential Alternative Screening Tool.

In Saudi Arabia, cervical cancer, frequently caused by human papillomavirus (HPV) infection, is a common cancer. The usual procedures for screening and diagnosing cervical cancer include Pap smears and HPV tests, even though they have considerable drawbacks, particularly for older women (> 60 years) who have limited access to or compliance with these tests. Urinalysis is a simple, noninvasive test that has been suggested as an alternative procedure. This study aimed to investigate the change in urinalysis characteristics in cervical cancer patients in elderly females and the possible use of urinalysis as a screening or diagnostic tool for cervical cancer in older women. This was an exploratory cross-sectional study of 190 cervical cancer patients diagnosed between January 2018 and August 2021. Based on age, the study included two groups, < 60 years and ≥ 60 years. Urinalysis characteristics, including bacterial count, blood level, protein level, and squamous epithelial cell shedding, were compared between the age groups by using the chi-squared and Kruskal-Walli tests. The results showed a significant difference between aged females and younger females with cervical cancer at the blood level, protein level, and squamous epithelial cell shedding in the urine. The older women (≥ 60 years) had higher incidences of increased bacterial count, blood levels, protein levels, and squamous epithelial cell shedding than the younger women (< 60 years). The main finding of the study implies that there are significant changes in urine characteristics in cervical cancer patients including hyperproteinemia, hematuria, and squamous cell shedding in elderly patients compared to younger patients, and it proposes a potential role for urinalysis as a screening tool for cervical cancer in older women. Urinalysis could be a potential screening tool for cervical cancer in older women who have not been screened or have no screening access. Further studies are needed to validate these findings.

Prospects for Narrow Band Imaging Magnification Endoscopy in Oral Lesions: Recommendations from Oral and Maxillofacial Surgeons and a Gastroenterologist

Narrow band imaging (NBI) magnification endoscopy for the diagnosis of early-stage oral cavity-related cancer and precancerous lesions can recognize oral lesions as brownish areas, and can observe intraepithelial papillary capillary loops (IPCLs) in the mucosa and submucosa to make a qualitative diagnosis of the lesion and highlight the mucosal surface microstructure to facilitate appropriate diagnosis and early treatment. IPCLs are classified from Type 0 to IV: Type 0 is normal mucosa or no blood vessels observed, e.g., in keratinization; Type I is mainly normal mucosa; Type II is mainly inflammatory sites or non-malignant lesions; Type III is mainly precancerous or suspected malignant lesions; and Type IV is cancerous or malignant lesions. NBI magnification endoscopy is a useful noninvasive method for identifying the malignant transformation of oral potentially malignant disorders (OPMDs). Oral lesions classified as IPCL Type II or higher are atypical epithelial or oral squamous cell carcinoma (OSCC); oral biopsy is recommended for early and accurate diagnosis, and is an indicator of the appropriate biopsy site in the follow-up for OPMDs. In the future, the accuracy of NBI magnification endoscopy for malignant transformation of OPMDs and OSCC will be further confirmed.

DEK::AFF2 fusion-associated middle ear non-keratinizing squamous cell carcinoma: A case report

BACKGROUND Primary squamous cell carcinoma (SCC) of the middle ear is rare, with non-keratinizing basaloid types being exceptionally uncommon. Distinguishing these cancers, often caused by viral factors (e.g. , human papillomavirus or Epstein-Barr virus), or specific genetic alterations (e.g. , bromodomain-containing protein 4-nuclear protein in testis fusion gene or Ewing sarcoma breakpoint region 1 gene fused with FLI chromosomal rearrangement), from other cranial conditions, is difficult. The recently identified DEK::AFF2 non-keratinizing SCC (NKSCC) is a novel subtype, fitting the World Health Organization classification of head and neck neoplasms. Less than 30 cases have been reported, highlighting the need for further studies. CASE SUMMARY A 55-year-old female patient first exhibited signs of illness over 10 years ago with persistent discomfort in the left external auditory canal, accompanied by skin irritation and bleeding. One month prior to seeking professional help, she experienced hearing loss and a sensation of obstruction in the affected ear, intermittently accompanied by ringing sounds, but no dizziness. An unusual mass was detected in the left auditory canal, confirmed through biopsy as moderately differentiated epithelial squamous cancer cells. This led to her admission to our hospital, where the final diagnosis confirmed as “NKSCC linked to a positive DEK::AFF2 fusion”. The patient underwent surgical excision, followed by three cycles of local radiation therapy. Yet, metastasis to the lumbar vertebrae occurred 19 months post-treatment, followed by neck lymph node swelling detected three months after a physical examination. The patient died nine months later despite surgical removal of the metastatic lesion. CONCLUSION DEK::AFF2 gene fusion-associated NKSCC of the middle ear carries a grim prognosis and presents an emerging challenge.

Primary sarcomatoid carcinoma of the trachea: A case report and literature review.

Primary sarcomatoid carcinoma of the trachea (PSCT) is a rare malignant tumor of the lower respiratory tract. Pathological types of tracheal sarcomatoid carcinoma (TSC)s include pleomorphic carcinomas, giant cell carcinomas, spindle cell carcinomas, pulmonoblastomas, and carcinosarcomas. At present, there are limited reports on PSCT, and pathologists lack sufficient knowledge about it. Here, we report a case of malignant neoplasm involving the left posterior wall of the initial tracheal segment, characterized by atypical spindle cells and a small number of high-grade squamous intraepithelial neoplasia. Spindle-shaped cells were moderately heterotypic, with 8/10 nuclear divisions (high-magnification field), and no obvious inflammatory cell infiltration was observed in the interstitium. Squamous epithelial cells showed moderate-to-severe atypia with regional cytoplasmic transparency. Immunohistochemistry: Fusiform tumor cells expressed vimentin, epithelial markers were negative, the Ki-67 proliferation index was 40%, and epithelial markers were expressed in squamous intraepithelial neoplasia. After the biopsy diagnosis was confirmed, part of the tumor was removed by tracheoscopy under general anesthesia in the respiratory department of a superior hospital. A pathological diagnosis of TSC was made and local radiotherapy was performed. As the tumor could not be completely cured, the patient experienced repeated coughing and shortness of breath and died of the disease 15 months later. Pathological morphology and immunohistochemical analyses deepen our understanding of the pathological features of TSC and provide a diagnostic reference for clinicians who will encounter such cases in the future.

Application of Human Papillomavirus-DNA Test on Salivary Gland Fine Needle Aspiration Cytology Samples Confirms the Absence of the Virus in Primary Neoplasms and Demonstrates for the First Time Its Presence in Salivary Intraglandular Cysts.

The correlation between Human Papillomavirus (HPV) and salivary gland neoplasms is still controversial. Data in the literature are conflicting, reporting the presence of the HPV-DNA in a significant percentage of cases or none. We investigated the presence of HPV in a series of salivary gland neoplasms using fine needle aspiration cytology (FNAC) samples to explore its potential oncogenic role in salivary gland tumor development. The study included 66 salivary gland lesions from 65 patients. For all cases, residual cytological material in the needle hub, once direct smears were obtained, was fixed by rinsing the needle in Cytolyt hemolytic and preservative solution (Hologic Inc. Marlborough, MA 01752 USA). The samples fixed in the Cytolyt hemolytic and preservative solution (Hologic Inc. Marlborough, MA 01752 USA) were centrifuged at 252 g, then the sediment was transferred to the Preservcyt solution and used for the detection of HPV-DNA. We found evidence of the presence of HPV in two salivary intraglandular cysts lined by squamous cell epithelium. Furthermore, we also found HPV in three metastatic oropharyngeal squamous cell carcinomas (SCC) located in the parotid gland. Regarding primary salivary gland tumors, the HPV test produced negative results in all cases. HPV testing produced negative results in all primary salivary gland tumors, failing to confirm the potential involvement of HPV infection in the pathogenesis of salivary gland tumors. Instead, the presence of HPV DNA in samples of salivary intraglandular cysts, never reported before, may be an interesting fact, which however requires further evaluation.

Symptomatic Giant Skene’s Gland Cyst During Second Trimester Pregnancy and Surgical Excision: A Case Report

Introduction: A Skene’s gland cyst is a rare gynecological disorder, and the cause of an adult onset is largely unknown. However, periurethral and perineal cystic lesions are common, causing often indistinguishable symptoms. Therefore, accurate diagnosis is crucial because it can significantly alter clinical management. Methods: A 27-year-old woman was gravida 2 para 1 with the onset of a unique, progressively large vulvar mass that began at approximately 6 weeks of gestation. At 22 weeks of gestation, the mass became more symptomatic and measured approximately 9 cm × 7 cm × 6 cm in size, with some areas of excoriation on the lateral surface. Results: The patient had a pelvic MRI without contrast, and it showed that the mass was most likely a giant Skene’s gland cyst. At 24 weeks, the mass was surgically removed under spinal anesthesia and followed by vulvar reconstruction. Histopathology showed a benign cyst lined by transitional and squamous epithelium cells, which was consistent with a benign Skene’s gland cyst. She recovered fully, continued with the pregnancy and delivered vaginally at 39 weeks and 3 days without complications. Conclusions: A case of excoriating giant Skene’s gland cyst in pregnancy that caused significant discomfort to the patient. To this day, there has been no reported literature of a Skene’s gland cyst this large, especially during pregnancy. Hence, Skene’s gland cysts should be part of the differential diagnosis of a large vulvar mass of this magnitude during pregnancy.

TAp73 and ΔTAp73 isoforms show cell-type specific distributions and alterations in cancer

TP73 is a member of the TP53 gene family and produces N- and C-terminal protein isoforms through alternative promoters, alternative translation initiation and alternative splicing. Most notably, p73 protein isoforms may either contain a p53-like transactivation domain (TAp73 isoforms) or lack this domain (ΔTAp73 isoforms) and these variants have opposing or independent functions. To date, there is a lack of well-characterised isoform-specific p73 antibodies. Here, we produced polyclonal and monoclonal antibodies to N-terminal p73 variants and the C-terminal p73α isoform, the most common variant in human tissues. These reagents show that TAp73 is a marker of multiciliated epithelial cells, while ΔTAp73 is a marker of non-proliferative basal/reserve cells in squamous epithelium. We were unable to detect ΔNp73 variant proteins, in keeping with recent data that this is a minor form in human tissues. Most cervical squamous cell carcinomas (79%) express p73α, and the distribution of staining in basal cells correlated with lower tumour grade. TAp73 was found in 17% of these tumours, with a random distribution and no association with clinicopathological features. These data indicate roles for ΔTAp73 in maintaining a non-proliferative state of undifferentiated squamous epithelial cells and for TAp73 in the production of differentiated multiciliated cells.

Comparison of Mast Cell Count in Oral Epithelial Dysplasia and Squamous Cell Carcinoma.

Squamous cell carcinomas (SCCs) and premalignant disorders such as leukoplakia are common oral cavity lesions. Although these lesions are epithelial in nature, they are also associated with juxta-epithelial chronic inflammation. Mast cells play a significant role in inflammation initiation and propagation. Previous studies have yielded conflicting results in this field. Therefore, this research aimed to assess the number of mast cells in oral SCC and dysplastic leukoplakia and explore their possible role in these lesions. In this retrospective cross-sectional study, sixty-three archival cases, including 22 OSCCs, 28 dysplastic leukoplakias as epithelial dysplasia (ED), and 13 normal oral mucosal tissues, were examined for mast cells, using toluidine blue staining. Hotspot areas were identified at 10× magnification and mast cells were counted in 5 fields at 40× magnification. The average cell numbers were calculated, and the severity of inflammation was scored. Statistical analysis was performed using SPSS statistical software 20, including One-way ANOVA, Two-way ANOVA, paired-t test, and independent t-test. p Value < 0.05 was considered significant. Among the 51 pathologic lesions, 54.9% were males and 45.1% were females, with a mean age of 56.34±15.35 years. The most common locations were the tongue and buccal mucosa. The mast cell count was significantly lower in SCC compared to ED (p= 0.009). There was no correlation between mast cell count and inflammation score (p= 0.345). In this study, the mast cell count was higher in ED compared to OSCC, suggesting an increase in these cells during the pre-malignant stages. However, the number of mast cells decreased after connective tissue invasion and microenvironmental changes occurred.

Investigation of genetic instability in patients with Diabetes Mellitus type I, II and LADA using buccal micronucleus cytome assay

The aim of our pilot study was to investigate the frequency of micronuclei (MN) and other nuclear anomalies in exfoliated cells of the oral mucosa in patients with type I, II, and LADA (Latent Autoimmune Diabetes in Adults, classified as type 1.5 intermediate, slowly progressing diabetes) types of diabetes mellitus (DM) and compare them with healthy individuals of the Armenian population using the MN test. For each participant essential clinical and biochemical parameters were studied, including blood pressure, duration of illness, glycosylated hemoglobin (HbA1c), blood glucose, plasma glucose, urea, total protein, creatinine, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, HOMA-IR (insulin resistance), insulin, and triglycerides, as well as necessary anthropometric, genealogical, and genetic data. All participants were surveyed regarding habits that might affect MN levels, such as smoking, alcohol consumption, drug use, hereditary diseases, and viral infections. Cytogenetic analyses of exfoliated cells showed that the level of MN in exfoliated cells of DM patients was elevated approximately two to three times compared to healthy individuals. However, statistical significance was only reached in type I DM and LADA patients. The levels of other nuclear anomalies in the squamous epithelial cells of DM patients were also analyzed, and a significant increase in their levels was observed in all three DM types, indicating cytotoxic and genotoxic effects. The results of this study also revealed a high correlation between the total number of MN, cells with MN, blood glucose concentration, and glycosylated hemoglobin.

Successful therapeutic management of canine oral papillomatosis using analogous autohaemotherapy

A five months old, male Beagle pup with several cauliflower-like outgrowths on oral mucous membrane and lips was brought to University Veterinary Hospital, Kokkalai. The growths were rounded, moist, pink in colour and with a narrow stalk. Resection of two growths was done under local anaesthesia and subjected to histopathology, which revealed proliferation of keratinized squamous cell epithelium with fibovascular stalk, indicating papillomas. Based upon the clinical signs and histopathology result, the disease was diagnosed as canine oral papillomatosis. Analogous autohaemotherapy (AHT) was selected as the method of therapeutic management. Resolution of the papillomas started within a week of administration of 5 mL of the animals’s own blood as intramuscular injection, and complete recovery occurred within one month. This article discusses AHT for canine oral papillomatosis along with its hematological and histopathological results. Keywords: Canine papillomatosis, analogous autohaemotherapy, wart, canine oral papilloma virus

Performance of Gram Stain Characteristics for Predicting Culture Growth in Lower Respiratory Specimens Across Multiple Institutions

Abstract Data from Gram stains performed on clinical specimens can guide clinical decision-making and downstream laboratory workflows. However, the extent to which Gram stain results predict gold-standard culture results, and the generalizability of this performance across sites, warrants additional exploration. We sought to discover which Gram stain features would be associated with clinically significant culture growth (“growth”). To do so, 574 remnant specimens from the lower respiratory tract collected from four institutions were analyzed. A standardized Gram stain and culture protocol was performed across all study sites. Final reference organism identification was assigned using MALDI-ToF MS, and clinically significant growth was defined as any organism reported to the medical record. Gram stains with mixed microorganisms detected were considered concordant if ≥2 organisms of different Gram stain appearances were identified in culture. Growth was observed in 53% of specimens, including 25% of specimens in which Gram stain demonstrated no organisms. The 95% confidence intervals (CI) of the site-wise growth rates were 30-42%, 42-52%, 51-67%, and 60-77% (p &amp;lt; 0.001 by Chi-squared). By Gram stain morphology, 53-69% of specimens with Gram-positive cocci grew any clinically significant bacteria, while 31-49% grew a concordant Gram-positive cocci. 65-85% of specimens with Gram-negative bacilli grew any clinically significant bacteria, while 59-74% grew a concordant Gram-negative bacilli. 63-83% of specimens with mixed microorganisms grew 2 or more clinically relevant bacteria of differing Gram stain morphologies. Specimens from bronchoalveolar lavages (BALs) were less likely to have growth (30-42%) than endotracheal aspirates (66-77%). Polymorphonuclear leukocyte (PMNs) abundance was associated with culture growth, with Gram stains showing no, rare, few, moderate, or abundant PMNs demonstrating growth 28, 44, 52, 60, and 67% of the time (p &amp;lt; 0.001). Specimens with None and few squamous epithelial cells on Gram stain demonstrated growth 38-52% and 59-68% of the time (p &amp;lt; 0.001). No significant difference in growth was observed for red blood cells. Organism abundance on Gram stain was significantly associated with culture growth, with growth rate CIs being 20-32% for no organisms, 44-62% for rare, 58-77% for few, 70-93% for moderate, and 81-95% for abundant organisms seen. The extent to which these associations could guide the development of decision rules or machine learning models that demonstrate acceptable negative predictive value for pathogen growth to alleviate the operational burden of low-utility cultures is an exciting future direction to explore.

Immune Responses of Club Cells in Fish: A Review

The primary line of defense against pathogens from the environment is often fish epidermis tissue. Nevertheless, little is understood about the physiological mechanisms that underlie the non-specific and/or specific protection that these cells can offer. The exact nature of the relationship between the evolution of ostariophysan fish club cells and chemical warning signals is still unknown and controversial. Fish epidermis layer cells comprise mucus cells, lymphocytes, macrophage cells, cuboidal and squamous epithelial cells, and cells specific to certain fish species. Club cells, also called "alarm cells," are chemical alarms that sound in the event of a potentially hazardous scenario. These cells will burst in the presence of a predator, releasing pheromones that, if the skin is physically damaged, trigger an avoidance and terror reaction. In sturgeon larvae, mucus cells were visible in week 1, but club cells did not appear until week 4. Due to their later development during ontogenesis and after wounding, club cells may not have as much of a protective effect during wound healing as filament or mucus cells. Club cells are mostly found in the epidermis of the skin, and it is thought that when they work in tandem with mucus and goblet cells to fight infections, they serve as the body's first line of defense.

B-006 Use of Sysmex UN-3000 Research Parameters for Semiquantitative Analysis of Urine Microscopic Elements

Abstract Background Microscopic examination of urine is an important component of urine analysis. However, it is labor-intensive and requires a skilled microscopist. The Sysmex UN-3000 (Kobe, JP) combines a Siemens CLINITEK Novus (Munich, GER) with a Sysmex UF-5000 flow cytometer and Sysmex UD-10 digital imaging device for fully automated urine analysis. It is FDA-approved for quantitation of red and white blood cells, epithelial cells, casts, and bacteria. It also flags for other particles such as sperm, yeast, pathologic casts, and crystals, which can then be confirmed on the UD-10. We sought to determine if and how the UF-5000 research parameter results could be used for semi-quantitative grading of pathologic casts, squamous epithelial cells, non-squamous epithelial cells, and crystals to match our reporting system. Methods Urine samples were analyzed by the UN-3000 and by manual review of urine sediment per laboratory protocols. Epithelial cells and crystals grades were none seen, few, moderate, many. Cast grades were 0, 1-3, 4-10, and &amp;gt;10. Results of manual microscopy were used to determine numerical cutoffs for the UF-5000 results which would agree within one grade in ≥90% of samples. Sperm and yeast are reported as either present or absent. For these particles, manual microscopy was compared to the results of the UF-5000 flagging and subsequent review of the UD-10 images. Results Rate of agreement between the methods is shown in the table. For sperm the UN-3000 showed 91.7% sensitivity and 100% specificity; for yeast, 93.8% sensitivity and 97.7% specificity. Conclusions We were able to use the research parameters from the UF-5000, in conjunction with the UD-10, to perform semi-quantitative grading. Adoption of this analyzer increases automation, with 70% of samples auto-validating per our protocols, while still conforming to our previous reporting system.

Implementation of sprinkling location with restructure-monochrome-dot on diffusivity mutational-status of fabricated function agent on porous

The recognition technology that determines the sprinkling mutation status in simple squamous epithelium cells produces a monochromatic dot pattern in an echo state using the instantaneous recognition rate (MPR) and vacuum recognition rate (VPR). The diffusivity echo system was created in the form of sprinkler recognition to control recognition rate conditions. The mutation status of simple squamous epithelium cells is displayed as a sprinkling porous value according to the sprinkling location layer by a diffusivity-down structure to search as a jagged monochrome-dot pattern. In the sprinkling porous, the perception rate concept is verified by referencing the instantaneous rate and vacuum rate to the mutant state signal through the sprinkling echo conformation. The jagged mutation state of MPR-VPR appears from a sprinkling porous to a maximum-minimum sprinkling-echo conformation. Sprinkling echo locations are found in the sprinkling porous values of the mutant state. Wr-af-FA-τMED is far mutational-status of 18.12±5.16 units, Wr-af-CO-τMED is convenient mutational-status of 6.89±0.30 units, Wr-af-FL-τMED is flank mutational-status of 2.34±1.53 units, Wr-af-VI-τMED is vicinage mutational-status of 0.48±0.20 units. Diffusivity echo calculates the jagged momentary vacuum conformation that appears through the perception rate system in simple squamous epithelium cells, and the ability to estimate the sprinkling-echo conformation for the jagged degree perception rate of MPR-VPR can be confirmed. We can estimate the shape through the vacuum signal in the sprinkling porous and estimate the diffusion data of the diffusivity echo rate through the diffusivity perception system.

Cervical cytology screening using the fused deep learning architecture with attention mechanisms

Cervical cancer remains a significant global health concern. Given the disparity between limited medical resources and the requisite professional personnel, the coverage of cervical screening is inadequate, particularly in underdeveloped areas. Computer-assisted liquid-based cytology diagnostic systems offer favorable solutions.Detection of small nuclei within a complex liquid-based environment poses a challenge, exacerbated by the restricted availability of manual annotations. In this study, we propose FuseDLAM, a comprehensive computer-aided diagnostic system, which employs enhanced YOLOv8 with transformers for rapid localization of individual squamous epithelial cells. We leverage artificial intelligence-generated content techniques for data augmentation, effectively reducing the need for costly manual annotations. By integrating multiple deep convolutional neural network models with self-attention mechanisms, the system extracts crucial features from cell nuclei. These features are then fused through a fully connected layer to facilitate robust cell classification. FuseDLAM achieves an F1-score of 99.3% on the public SIPaKMeD dataset, demonstrating comparability with state-of-the-art approaches. It also proves its practical applicability in real-world clinical scenarios, achieving an F1-score of 91.2 % in identifying abnormal cervical squamous cells. Additionally, ablation experiments in both datasets validate the model's effectiveness. This underscores its potential for widespread application in medical imaging tasks.

Impact of Low-grade Intraepithelial Lesions with High-risk Human Papillomavirus (Part I)

One of the cervical cancer screening tests that has been prevalent in low- and mid-level income countries has been the cytology test, which uses a system of standardized reports such as the Bethesda. This system allows the detection of anomalies in squamous epithelial cells, including the squamous intraepithelial lesion (SIL), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), invasive squamous cell carcinoma, and adenocarcinoma. This categorization in two levels (LSIL and HSIL) has allowed to differentiate the carcinogenic potential of the human papillomavirus (HPV). LSIL are described as transient changes associated with an infection caused by HPV and asymptomatic infections with viral vacuolization within a two-year interval with no specific treatment. In case of HSIL, reference is made to its pre-cancer potential. Several factors have an impact in the onset of a LSIL: the presence of HPV (as one of the key etiologic agents) and other risk factors such as hormones, microbiome, first intercourse at early age, multiple sexual partners, other infections, immune status, and tobaco. All that contribute to the transient nature of the infection, or to its persistence, which in turn may promote the development and progression into an HSIL. The persistence of a high-risk HPV infection (HR-HPV) (or more rarely of low-grade too) plays an important role in the development of cervical cancer.

Dimethyl Fumarate-Loaded Gellan Gum Hydrogels Can Reduce In Vitro Chemokine Expression in Oral Cells.

Dimethyl fumarate (DMF), originally proposed to treat multiple sclerosis, is considered to have a spectrum of anti-inflammatory effects that effectively control periodontitis, mainly when applied with a hydrogel delivery system. Chemokine expression by gingival fibroblasts is a significant driver of periodontitis; thus, hydrogel-based strategies to deliver DMF, which in turn dampen chemokine expression, are of potential clinical relevance. To test this approach, we have established a bioassay where chemokine expression is induced by exposing gingival fibroblast to IL1β and TNFα, or with saliva. We show herein that DMF effectively reduced the expression of CXCL8, CXCL1, CXCL2, and CCL2-and lowered the phosphorylation of ERK and JNK-without affecting cell viability. This observation was confirmed by immunoassays with CXCL8. Consistently, the forced chemokine expression in HSC2 oral squamous epithelial cells was greatly diminished by DMF. To implement our hydrogel-based delivery system, gingival fibroblasts were cocultured with gellan gum hydrogels enriched for DMF. In support of our strategy, DMF-enriched gellan gum hydrogels significantly reduced the forced chemokine expression in gingival fibroblasts. Our data suggest that DMF exerts its anti-inflammatory activity in periodontal cells when released from gellan gum hydrogels, suggesting a potential clinical relevance to control overshooting chemokine expression under chronic inflammatory conditions.

Multicellular 3D bioprinted human gallbladder carcinoma for in vitro mimicry of tumor microenvironment and intratumoral heterogeneity

Gallbladder carcinoma (GBC) is a malignant hepatobiliary cancer characterized by an intricate tumor microenvironments (TME) and heterogeneity. The traditional GBC 2D culture models cannot faithfully recapitulate the characteristics of the TME. Three-dimensional (3D) bioprinting enables the establishment of high-throughput and high-fidelity multicellular GBC models. In this study, we designed a concentric cylindrical tetra-culture model to reconstitute the spatial distribution of cells in tumor tissue, with the inner portion containing GBC cells, and the outer ring containing a mixture of endothelial cells, fibroblasts, and macrophages. We confirmed the survival, proliferation, biomarker expression and gene expression profiles of GBC 3D tetra-culture models. Hematoxylin-eosin (HE) and immunofluorescence staining verified the morphology and robust expression of GBC/endothelial/fibroblast/macrophage biomarkers in GBC 3D tetra-culture models. Single-cell RNA sequencing revealed two distinct subtypes of GBC cells within the model, glandular epithelial and squamous epithelial cells, suggesting the mimicry of intratumoral heterogeneity. Comparative transcriptome profile analysis among variousin vitromodels revealed that cellular interactions and the TME in 3D tetra-culture models reshaped the biological processes of tumor cells to a more aggressive phenotype. GBC 3D tetra-culture models restored the characteristics of the TME as well as intratumoral heterogeneity. Therefore, this model is expected to have future applications in tumor biology research and antitumor drug development.

Penyuluhan Kesehatan tentang Kanker Serviks pada Wanita Usia Subur (WUS) di Desa Kertawinangun Kecamatan Kedawung Kabupaten Cirebon

Cervical cancer is a primary malignant tumor originating from squamous epithelial cells or cells originating from the vagina and urethra, usually occurring in the cervix or cervix which is located between the uterus and the sexual canal (vagina). According to WHO 2018, cervical cancer is the fourth leading cause of death in women throughout the world, estimated at 570,000, while new cases in 2018 or 6.6% of all cancers in women. Human papilloma virus or commonly called (HPV) is known to cause cervical cancer which can be transmitted through sexual intercourse, infection with several types of viruses, and personal hygiene. Symptoms of cervical cancer can be recognized by the presence of fluid from the birth canal, namely abnormal vaginal discharge, contact bleeding (bleeding during intercourse), and feeling pain during coitus / sexual intercourse as well as bleeding even after entering menopause. Early symptoms of pre-cancerous conditions are generally characterized by the discovery of abnormal cells. These abnormal cells develop into cervical cancer and then the following symptoms of cervical cancer appear; the appearance of pain and bleeding during sexual intercourse (contact bleeding), abnormal vaginal bleeding, such as bleeding outside the menstrual cycle, bleeding between regular menstrual periods, menstrual periods that are longer and more abundant than usual, bleeding after menopause, vaginal discharge excessive and abnormal, if the cancer has spread to the pelvis, the patient will suffer from complaints of pelvic pain, difficulty urinating, and enlarged kidneys. Cervical cancer can be prevented 100% by HPV vaccination, using condoms, avoiding tobacco consumption, and early detection and treatment of precancerous lesions.