Tissue Invasion Research Articles

Exploring the interplay between Porphyromonas gingivalis KGP gingipain, herpes virus MicroRNA-6, and Icp4 transcript in periodontitis: Computational and clinical insights.

Porphyromonas gingivalis, a major pathogen in periodontitis, produces KGP (Lys-gingipain), a cysteine protease that enhances bacterial virulence by promoting tissue invasion and immune evasion. Recent studies highlight microRNAs' role in viral latency, potentially affecting lytic replication through host mechanisms. Herpes virus (HSV) establishes latency via interactions between microRNA-6 (miRH-6) and the ICP4 transcription factor in neural ganglia. This suggests a potential link between periodontitis and HSV-induced latency. This study aims to identify and validate the insilico inhibitory interaction of P. gingivalis KGP with ICP4 transcripts and correlate the presence of viral latency-associated transcript micro-RNA-6 with periodontitis. Computational docking analysis was performed to investigate the potential interaction between ICP4 and KGP gingipain. The binding energy and RMSD ligand values were calculated to determine the interaction's strength. Ten patients with recurrent clinical attachment loss despite conventional therapy were included in the clinical study. Subgingival tissue samples were collected post-phase I therapy, and HSV microRNA-6 presence was detected via polymerase chain reaction and confirmed through gel electrophoresis. Computational docking identified the ICP4-KGP gingipain complex with the lowest binding energy (-288.29 kJ mol^1) and an RMSD ligand of 1.5 Angstroms, indicating strong interaction potential. Gel electrophoresis confirmed miRH-6 presence in all samples. The identification of miRNA-6 in periodontitis patients and the strong interaction potential between P. gingivalis KGP gingipain and ICP4 transcripts indicate a possible link between bacterial virulence factors and viral latency dynamics in periodontal tissues. These results highlight the complex interplay between oral pathogens, viral microRNAs, and host immune responses in periodontitis.

Identification of the First Case of Dedifferentiated Liposarcoma in Amphibians: Insights from Maculopaa medogensis

Dedifferentiated liposarcoma (DDLPS) is a rare and aggressive type of cancer primarily reported in humans, with no documented cases in animals. In this study, we present the first case of DDLPS in a wild amphibian species, Maculopaa medogensis. The tumor was discovered during a routine examination and diagnosed through a combination of advanced diagnostic methods, including micro-CT imaging, gross anatomical inspection, histological analysis, and immunohistochemistry. The tumor exhibited both well-differentiated and dedifferentiated components, characteristic of DDLPS, with evidence of tissue invasion and multiple metastases. Immunohistochemical analysis revealed the strong positive expression of markers such as S100A4, CDK4, MDM2, and CD34, while Leptin expression was negative, further confirming the diagnosis. This is the first reported case of DDLPS in a non-human species, expanding our understanding of cancer in wildlife and underscoring the significance of amphibians as environmental indicators. These findings provide valuable insights for veterinary medicine and wildlife conservation, particularly regarding the role of environmental stressors in cancer development. This study highlights the need for comprehensive diagnostic approaches in wildlife pathology.

Maxillary Giant Radicular Cyst: A Case Presentation and Management

Objectives: Radicular cysts are the most frequent odontogenic cystic lesions, they are inflammatory cysts that involve the apex of affected tooth and appear as well-defined radiolucencies. Most radicular cysts are small, but they can grow quite large due to their capacity for significant expansion, invasion of adjacent tissues, and rapid growth. They also have a high recurrence rate. We present here a rare case of a giant maxillary radicular cyst in a 60-year-old patient, aiming to highlight the clinical and radiological aspects, as well as the importance of enucleation with extraction of the offending tooth/teeth in the surgical management of these cysts. Methods: a 60-year-old male patient presented with an extensive involving the left anterior area of the maxilla. The cone-beam computed tomography (CBCT) image suggested the presence of an odontogenic cyst at the size of 50 mm × 30 mm in the affected side. For treatment, an enucleation of the cyst, along with the extraction of the association tooth, was performed. Results: The diagnosis of radicular cyst was established on the resected specimen. There were no signs of recurrence two years following the surgery. Conclusions: Imaging plays a crucial role in accurately diagnosing and assessing the extent of the cyst. Surgical treatment primarily relies on enucleation with extraction of the offending tooth which is essential for effective management and to minimize recurrence.

Advances in the Study of the Pathogenesis of Vogt-Koyanagi-Harada Syndrome.

Vogt-Koyanagi-Harada syndrome (VKHS) is a common type of uveitis characterized by the invasion of melanocyte-rich tissues. In recent years, the incidence of VKHS has been increasing yearly, and its specific pathogenesis has not yet been elucidated. However, its pathogenesis has been a hot topic of research. The clinical course of VKHS is characterized by the early involvement of the posterior segment of the eye, including exudative retinal detachment, optic papillitis, bilateral diffuse chorioretinitis, etc. If treated improperly or with delayed treatment, the inflammation may gradually spread to the anterior segment of the eye, leading to vision loss or even vision. This study examines the pathogenesis of VKHS. It reviews the progress of research on the pathogenesis of VKHS, which will help to improve the understanding of VKHS and provide a reference for subsequent studies.

Stoichiometry of ligand binding and role of C-terminal lysines in Mycobacterium tuberculosis and human GAPDH multifunctionality.

Glyceraldehyde-3-phosphate-dehydrogenase (GAPDH; EC1.2.1.12) has several functions in Mycobacterium tuberculosis (Mtb) and the human host. Apart from its role in glycolysis, it serves both as a cell surface and a secreted receptor for plasmin(ogen) (Plg/Plm), transferrin (Tf), and lactoferrin (Lf). Plg sequestration by Mtb GAPDH facilitates bacterial adhesion and tissue invasion, while an equivalent interaction with host GAPDH regulates immune cell migration. In both, host and microbe, internalization of Tf/Lf-GAPDH complexes serves as a route for iron acquisition. To date, the structure of Mtb GAPDH or the residues involved in these moonlighting interactions have not been identified. This study provides the first known X-ray crystal structure of Mtb GAPDH. Through further mutagenesis and functional assays, we found that the C-terminal lysines of Mtb and human GAPDH affect enzyme activity and ligand binding. We also establish the stoichiometry of Plg, Tf and Lf interactions with the GAPDH tetramer. Lastly, molecular simulation studies reveal the interactions of the C-terminal lysine residues.

Optimizing surgical approaches for lacrimal gland adenoid cystic carcinoma to minimize cross-organ invasion.

To evaluate the outcomes of eye-sparing surgery for lacrimal gland adenoid cystic carcinoma and the impact on tumor recurrence and orbital integrity. The study enrolled four patients with recurrent lacrimal gland adenoid cystic carcinoma. The outcome focused on the relevance of the integrity of the lateral orbital wall to the occurrence of extraorbital metastasis in the local recurrence of lacrimal gland adenoid cystic carcinoma. Three patients underwent eye-sparing surgery via lateral orbitotomy without postoperative radiotherapy, and one patient who underwent eye-sparing surgery via sub-brow approach. These four patients all demonstrated a recurrence involving the invasion of extraorbital tissues as metastatic form through surgical bone seams. Preserving intact orbital bone tissue is crucial for mitigating direct cross-organ metastasis of lacrimal gland adenoid cystic carcinoma. The findings suggest avoiding the lateral orbitotomy approach with no or limited orbital bone wall invasion.

Surgical Treatment and Clinical Evaluation of Calvarial Metastases.

The aim of this study is to explore surgical treatment techniques and clinical attributes associated with calvarial metastases, while providing a comprehensive review of the treatment experiences relevant to this particular type of tumor. This study involves a retrospective analysis of clinical data from 12 patients diagnosed with calvarial metastatic tumors who underwent surgical intervention. Among these patients, 5 had a history of previous malignant tumor resections, while 7 presented with calvarial metastatic tumors as their initial symptom. In all cases, the surgical approach consisted of calvarial tumor resection followed by titanium mesh repair. Following the surgical intervention, all patients underwent a comprehensive course of treatment, encompassing both local radiotherapy and systemic chemotherapy. In 1 instance, a patient presented with multiple tumors located in the central area of the frontal bone and the right temporal bone. The larger tumor situated in the middle of the frontal bone was surgically excised, while the tumor in the right temporal bone was treated using radiotherapy. In 2 cases characterized by multiple metastases within the skull, a comprehensive excision of all tumors was accomplished in a single surgical procedure. In the remaining cases featuring a solitary metastatic growth, the respective tumors were surgically removed. There were 10 instances of dura mater invasion and 3 cases involving the invasion of brain tissue. Pathologic examinations revealed 1 case of metastatic lung adenocarcinoma, 1 case of metastatic paraganglioma, 1 case of metastatic hepatocellular carcinoma, 2 cases of metastatic thyroid carcinoma, and 7 cases of metastatic clear cell renal cell carcinoma. Throughout the follow-up period, spanning from 14 to 90 months, various outcomes were noted. These included three occurrences of in situ recurrence. In addition, 1 patient required 3 distinct surgical interventions, while 2 other patients underwent 2 separate surgical procedures each. Notably, 1 of these cases involved the exposure of the titanium mesh on the scalp, necessitating the removal of the titanium mesh. Regrettably, there have been 9 recorded fatalities among the patients, while 3 individuals have survived. Solitary metastasis of calvarium region is rare, and surgical resection is effective. However, it is necessary to extend the resection range and combine with local radiotherapy to avoid local recurrence. Surgical intervention can significantly enhance the quality of life for affected patients. The prognosis of the patients mainly depends on the treatment of the primary disease and the situation of important organ dissemination and treatment.

Adaptive segmentation-to-survival learning for survival prediction from multi-modality medical images

Early survival prediction is vital for the clinical management of cancer patients, as tumors can be better controlled with personalized treatment planning. Traditional survival prediction methods are based on radiomics feature engineering and/or clinical indicators (e.g., cancer staging). Recently, survival prediction models with advances in deep learning techniques have achieved state-of-the-art performance in end-to-end survival prediction by exploiting deep features derived from medical images. However, existing models are heavily reliant on the prognostic information within primary tumors and cannot effectively leverage out-of-tumor prognostic information characterizing local tumor metastasis and adjacent tissue invasion. Also, existing models are sub-optimal in leveraging multi-modality medical images as they rely on empirically designed fusion strategies to integrate multi-modality information, where the fusion strategies are pre-defined based on domain-specific human prior knowledge and inherently limited in adaptability. Here, we present an Adaptive Multi-modality Segmentation-to-Survival model (AdaMSS) for survival prediction from multi-modality medical images. The AdaMSS can self-adapt its fusion strategy based on training data and also can adapt its focus regions to capture the prognostic information outside the primary tumors. Extensive experiments with two large cancer datasets (1380 patients from nine medical centers) show that our AdaMSS surmounts the state-of-the-art survival prediction performance (C-index: 0.804 and 0.757), demonstrating the potential to facilitate personalized treatment planning.

The Streptococcus agalactiae LytSR two-component regulatory system promotes vaginal colonization and virulence in vivo.

Streptococcus agalactiae (or group B Streptococcus, GBS) is a leading cause of neonatal sepsis and meningitis globally. To sense and respond to variations in its environment, GBS possesses multiple two-component regulatory systems (TCSs), such as LytSR. Here, we aimed to investigate the role of LytSR in GBS pathogenicity. We generated an isogenic lytS knockout mutant in a clinical GBS isolate and used a combination of phenotypic in vitro assays and in vivo murine models to investigate the contribution of lytS to the colonization and invasive properties of GBS. Deletion of the lytS gene in the GBS chromosome resulted in significantly higher survival rates in mice during sepsis, accompanied by reduced bacterial loads in blood, lung, spleen, kidney, and brain tissues compared to infection with the wild-type strain. In a mouse model of GBS vaginal colonization, we also observed that the lytS knockout mutant was cleared more readily from the vaginal tract compared to its wild-type counterpart. Interestingly, lower levels of proinflammatory cytokines were found in the serum of mice infected with the lytS mutant. Our results demonstrate that the LytSR TCS plays a key role in GBS tissue invasion and pathogenesis, and persistence of mucosal colonization.IMPORTANCEStreptococcus agalactiae (group B Streptococcus, or GBS) is a common commensal of the female urogenital tract and one of WHO's priority pathogens. The bacterium has evolved mechanisms to adapt and survive in its host, many of which are regulated via two-component signal transduction systems (TCSs); however, the exact contributions of TCSs toward GBS pathogenicity remain largely obscure. We have constructed a TCS lytS-deficient mutant in a CC-17 hypervirulent GBS clinical isolate. Using murine models, we showed that LytSR regulatory system is essential for vaginal colonization via promoting biofilm production. We also observed that lytS deficiency led to significantly attenuated virulence properties and lower levels of proinflammatory cytokines in blood. Our findings are of significant importance in that they unveil a previously unreported role for LytSR in GBS and pave the way toward a better understanding of its ability to transition from an innocuous commensal to a deadly pathogen.

In-silico and In-vitro Investigation of Flavonoids and Alkaloids from Artocarpus heterophyllus, Tinospora cordifolia, and Glycosmis pentaphylla as Potential NF-κB Inhibitors in Oral Cancer.

Oral cancer is a global health concern, particularly because of its aggressive tissue invasion and metastases, holding 16th position on occurrence among all carcinoma worldwide. The aberrated transcription factor NF-κB1 influences development and spread of oral cancer, making it a potential therapeutic target. This study investigated the therapeutic potential of a few natural compounds from Artocarpus heterophyllus, Tinospora cordifolia, and Glycosmis pentaphylla in the treatment of oral cancer. Two FDA-approved drugs (5-fluorouracil, Docetaxel) and 16 natural compounds, including Artocarpin, Artocarpanone, Cycloartocarpin from Artocarpus heterophyllus; Berberine, Hydrastine, Magnoflorine, Palmatine Chloride, Tetrahydropalmatine from Tinospora cordifolia; and 5-Hydroxyarborinine, 5-Hydroxynoracronycine, 1-Hydroxy-3-methoxy-10-methyl-9-acridone, Des-N-methylacronycine, Des-N-methylnoracronycine, Kokusagenine, Noracronycin, Skimmianine from Glycosmis pentaphylla were examined using in-silico techniques. Among the 16 natural compounds studied, Hydrastine shown the highest binding energy (-6.87 kcal/mol) against NF-κB1, surpassing all other drugs, including the standards 5-fluorouracil (-4.04 kcal/mol) and docetaxel (-2.4 kcal/mol). Further molecular dynamics simulations and in-vitro experiments verified Hydrastine's exceptional anti-cancer activity. The results of in-vitro were well-aligned with the findings of in-silico, revealing considerable cytotoxicity, apoptosis induction, and cell cycle arrest. The findings revealed natural compounds' potential as safer, more effective alternatives to current cancer therapeutics, opening up new avenues for oral cancer treatment.

Bone augmentation using bioresorbable mesh domes containing bone graft granules

Bone graft granules are valuable tools for ridge area bone grafting owing to their ease of manipulation and interconnected porous structure. Guided bone regeneration (GBR) using barrier membranes is commonly used for alveolar ridge augmentation; however, the surgical procedures are technically complicated. In this study, we fabricated bioresorbable mesh domes (BMDs) using two types of Vicryl mesh (woven and knitted types) containing carbonate apatite granules. BMD samples were prepared in three groups: upper sides made from the woven type (UW) and lower sides made from the woven type (LW) (the UW/LW group), upper sides made from the woven type (UW) and lower sides made from the knitted type (LK) (the UW/LK group), and upper sides made from the knitted type (UK) and lower sides made from the knitted type (LK) (the UK/LK group). The samples were subsequently implanted into rabbit calvaria, and radiomorphometric and histological analyses were conducted. The UK/LK group exhibited enhanced appositional bone formation because the knitted mesh on the skin side prevented the infiltration of a substantial amount of fibrous tissue. This increase in bone formation could be attributed to the interaction between granules and osteoprogenitors that pass through the mesh from the host bone. Conversely, the UW/LW and UW/LK groups presented limited appositional bone formation. Compared with knitted mesh, woven mesh might tend to be absorbed over a short span, allowing fibrous tissue invasion and inhibiting new bone formation. Additionally, BMDs could retain granules in a targeted location and avoid displacement of the granules to unintended locations.Graphical

7295 Giant Pituitary Adenoma with Rapid Symptomatic Progression and Postoperative Mortality

Abstract Disclosure: R.D. Kennedy: None. M. Nicholson: None. Introduction: Giant pituitary adenomas, defined as pituitary adenomas measuring greater than 4 cm, present a therapeutic challenge because of their size, clinical features, and increased potential for complications following surgical intervention. Early detection and intervention to prevent growth and progression is paramount. We present a case of a patient with a giant 6.3 cm pituitary adenoma who had significant neurologic compromise, requiring surgical intervention, with resultant postoperative complications and death. Case:Patient is a 41 year old male with known history of pituitary adenoma who presented on 11/1/2023, from outside hospital, to the Neuroendocrine clinic with complaints of excessive truncal obesity, impotence, fatigue, and apathy. Vital signs were within normal limits. Physical exam revealed clouding of consciousness, grossly intact cranial nerve function, truncal obesity, and diminished power, tone, and bulk of the extremities. Formal visual field testing revealed bitemporal hemianopsia. A head CT scan revealed a 6.3 cm sellar mass with expansion of the sella, invasion of soft tissue into the sphenoid sinus, and extension of soft tissue cranially to the level of the third ventricle eccentric to the left. There was no evidence of apoplexy. Lab results revealed Prolactin of 924 ng/mL. The patient had been taking Bromocriptine, 2.5 mg daily, for at least three weeks. Less than three weeks after his initial evaluation, he returned to the hospital with complaint of acute ataxia. Pituitary MRI revealed 6.3 cm sellar mass with evidence of acute and subacute blood products, stretching of the optic chiasm from mass effect, extension into the bilateral cavernous sinuses, superior left MCA displacement, posterior left PCA displacement, 5 mm midline shift, uncal herniation and descending transtentorial herniation. The patient underwent endoscopic transsphenoidal resection with subsequent craniotomy for debulking. Postoperatively, he developed new right sided hemiplegia with aphasia with subsequent MRI finding of watershed infarct at the left MCA/PCA lateral posterior border zone territories with increasing mass effect over a 30 day hospital stay. He developed progressive global edema with worsening uncal and tonsillar herniations. Brain death was pronounced on 11/30/23. Discussion:This case highlights the importance of early intervention in patients with giant pituitary adenomas. Our patient had been experiencing right sided weakness for at least one year prior to his admission to our facility. In this case, earlier treatment with a dopamine agonist may have decreased the size of the adenoma or prevented rapid growth. This may have precluded the need for surgical intervention on an adenoma of this size, which carries increased risk for postoperative complications. Presentation: 6/2/2024

Orbital solitary fibrous tumor

Introduction: Solitary fibrous tumor (SFT) is a rare borderline mesenchymal tumor typically arising in the pleura and involving the orbit as its most common extra-pleural locationCase description: We herein describe two cases of orbital SFT arising in both a 69-year-old woman presenting with progressive proptosis of the left eye and a 49-year-old woman presenting with binocular diplopia. The diagnoses relied on histopathological analysis of biopsy samples. Because of the poor local prognosis, we decided to perform an orbital exenteration in the first case. In the second case, a complete resection surgery was performed.Conclusion: SFT presents classics histological features and immunohistochemical markers that are essential to the diagnosis.SFT is classified as a benign tumor, but in some cases, it can show aggressive behavior with the potential for local tissue invasion and, more scarcely, distant metastasis. This is why complete resection remains the treatment of choice for SFT.

The Role of Chitosan and Gelatin-Based Scaffolds in Bone Regeneration: A Systematic Review.

Guided bone regeneration facilitates the growth of new bone in areas where there is a bone defect or insufficiency. This technique involves placing a barrier membrane over the bone graft site, and the membrane prevents the invasion of soft tissue (such as gingival tissue) into the bone graft area. This allows the slower-growing bone cells to populate the area without competition, promoting proper bone regeneration. When combined, chitosan and gelatin create composite scaffolds that leverage the strengths of both materials. Chitosan provides structural integrity and antimicrobial properties, and gelatin enhances cell attachment and proliferation, which improves mechanical properties and makes it more suitable for supporting bone regeneration in load-bearing areas.This systematic review aims to evaluate the effectiveness ofchitosan and gelatin-based scaffolds in bone regeneration. Various databases such as PubMed, Cochrane Library, LILAC, and Google Scholar were screened to adhere to the eligibility criteria. The included studies in the review were the in vivo and in vitro assessment of the chitosan and gelatin efficiency as a scaffold. Six studies were investigated for the involvement of chitosan and gelatin-based scaffolds in bone regeneration. Of these, two in vivostudies examined bone regeneration by measuring alkaline phosphatase activity (ALP) using different staining techniques, while the remaining four in vitro studies used histologic and histometric analysis where stem cells, chemicals, and other biopolymers were compared. Chitosan and gelatin scaffolds consistently showed better results in terms of bone repair throughout all six experiments. Gelatin's capacity for regeneration can be increased by mixing itwith chitosan. For additional advancement, future researchers need to focus on incorporating biopolymers.The potential of scaffolds composed of gelatin and chitosan to replace tissue lost due to periodontitis shows great clinical significance.

Ume6-dependent pathways of morphogenesis and biofilm formation in Candida auris.

Candida auris is a yeast pathogen causing nosocomial outbreaks of candidemia. Its ability to adhere to inert surfaces and to be transmitted from one patient to another via medical devices is of particular concern. Like other Candida spp., C. auris has the ability to transition from the yeast form to pseudohyphae and to build biofilms. Moreover, some isolates have a unique capacity to form aggregates. These morphogenetic changes may impact virulence. In this study, we demonstrated the role of the transcription factor Ume6 in C. auris morphogenesis. Genetic hyperactivation of Ume6 induced filamentation and aggregation. The Ume6-hyperactivated strain (UME6HA) also exhibited increased adhesion to inert surface and formed biofilms of higher biomass compared to the parental strain. Transcriptomic analyses of UME6HA revealed enrichment of genes encoding for adhesins, proteins involved in cell wall organization, sterol biosynthesis, and aspartic protease activities. The three most upregulated genes compared to wild-type were those encoding for the agglutin-like sequence adhesin Als4498, the C. auris-specific adhesin Scf1, and the hypha-specific G1 cyclin-related protein Hgc1. The deletion of these genes in the UME6HA background showed that Ume6 controls filamentation via Hgc1 and aggregation via Als4498 and Scf1. Adhesion to inert surface was essentially triggered by Scf1. However, Als4498 and Hgc1 were also crucial for biofilm formation. Our data show that Ume6 is a universal regulator of C. auris morphogenesis via distinct modulators.IMPORTANCEC. auris represents a public health threat because of its ability to cause difficult-to-treat infections and hospital outbreaks. The morphogenetic plasticity of C. auris, including its ability to filament, to form aggregates or biofilms on inert surfaces, is important to the fungus for interhuman transmission, skin or catheter colonization, tissue invasion, antifungal resistance, and escape of the host immune system. This work deciphered the importance of Ume6 in the control of distinct pathways involved in filamentation, aggregation, adhesion, and biofilm formation of C. auris. A better understanding of the mechanisms of C. auris morphogenesis may help identify novel antifungal targets.

Research progress of silk-based biomaterials for peripheral nerve regeneration

To describe the research progress of silk-based biomaterials in peripheral nerve repair and provide useful ideals to accelerate the regeneration of large-size peripheral nerve injury. The relative documents about silk-based biomaterials used in peripheral nerve regeneration were reviewed and the different strategies that could accelerate peripheral nerve regeneration through building bioactive microenvironment with silk fibroin were discussed. Many silk fibroin tissue engineered nerve conduits have been developed to provide multiple biomimetic microstructures, and different microstructures have different mechanisms of promoting nerve repair. Biomimetic porous structures favor the nutrient exchange at wound sites and inhibit the invasion of scar tissue. The aligned structures can induce the directional growth of nerve tissue, while the multiple channels promote the axon elongation. When the fillers are introduced to the conduits, better growth, migration, and differentiation of nerve cells can be achieved. Besides biomimetic structures, different nerve growth factors and bioactive drugs can be loaded on silk carriers and released slowly at nerve wounds, providing suitable biochemical cues. Both the biomimetic structures and the loaded bioactive ingredients optimize the niches of peripheral nerves, resulting in quicker and better nerve repair. With silk biomaterials as a platform, fusing multiple ways to achieve the multidimensional regulation of nerve microenvironments is becoming a critical strategy in repairing large-size peripheral nerve injury. Silk-based biomaterials are useful platforms to achieve the design of biomimetic hierarchical microstructures and the co-loading of various bioactive ingredients. Silk fibroin nerve conduits provide suitable microenvironment to accelerate functional recovery of peripheral nerves. Different optimizing strategies are available for silk fibroin biomaterials to favor the nerve regeneration, which would satisfy the needs of various nerve tissue repair. Bioactive silk conduits have promising future in large-size peripheral nerve regeneration.

Non-canonical IL-22 receptor signaling remodels the mucosal barrier during fungal immunosurveillance.

Mucosal barrier integrity is vital for homeostasis with commensal organisms while preventing pathogen invasion. We unexpectedly found that fungal-induced immunosurveillance enhances resistance to fungal outgrowth and tissue invasion by remodeling the oral mucosal epithelial barrier in mouse models of adult and neonatal Candida albicans colonization. Epithelial subset expansion and tissue remodeling were dependent on interleukin-22 (IL-22) and signal transducer and activator of transcription 3 (STAT3) signaling, through a non-canonical receptor complex composed of glycoprotein 130 (gp130) coupled with IL-22RA1 and IL-10RB. Immunosurveillance-induced epithelial remodeling was restricted to the oral mucosa, whereas barrier architecture was reset once fungal-specific immunity developed. Collectively, these findings identify fungal-induced transient mucosal remodeling as a critical determinant of resistance to mucosal fungal infection during early stages of microbial colonization.

Association of P53 Gene and Colorectal Cancer in Iran

Background: Colorectal cancer (CRC) is one of the leading causes of malignancies globally with a high mortality rate. Therefore, investigating the underlying mechanism and different risk factors contributing to this neoplasm is imperative, since P53 protein is a tumor suppressor protein, that has inhibiting effect on tumorigenesis, this study aims to assess the association of P53 gene and CRC within specific population, as geography is believed to be a risk factor for CRC. Materials and Methods: In this retrospective case-control study, 90 patients aged 18 years old and above, with CRC were enrolled. They were all scrutinized before and after their surgery. Data were extracted from their medical record, laboratory test results, standard questionnaire, imaging reports, physical exam, related symptoms and colonoscopy and biopsy reports. Data analysis was performed using SPSS software and the chi-square method. Results: 90 patients participated in this study, with the mean age of 71.57 years. There was no statistically significant association between age of patients and P53 mutation. Similarly, no correlation between any of the symptoms and P53 gene mutation was found. However, the risk of P53 mutation increased with larger tumor size (p<0.021), deeper tissue invasion (p<0.041) and higher levels of lymph node involvement (p<0.031). Conclusion: this study investigates the relationship between P53 mutation and various clinical and pathological parameters. A significant association was observed between P53 mutation and tumor characteristics, including larger tumor size, deeper tissue invasion, and increased lymph node involvement. These findings suggest that P53 mutation may serve as a potential biomarker for assessing tumor aggressiveness and prognosis in colorectal cancer

EP568 - A rare case of necrotizing fasciitis caused by Streptococcus Anginosus and Staphylococcus Lugdunensis

Abstract Necrotizing fasciitis (NF) is a rare soft tissue infection involving the fascial planes, causing rapid and extensive tissue destruction. We present a unique case of NF in a patient with poor glycemic control caused by atypical pathogens. A 66-year-old female with a recent biopsy for a wart-like lesion developed a wound infection, with greenish-black exudate. Initial observations were: temperature: 39.4 degrees, heart rate: 105, GCS: 15/15. Physical examination revealed a grossly filiform lesion below her abdominal apron measuring 7cm in diameter. The patient was empirically treated with IV Co-Amoxiclav. Abnormal biochemistry results are shown below. Microbiological analysis revealed Streptococcus Anginosus, anaerobes and Staphylococcus Lugdunensis. CT abdomen revealed extensive inflammatory changes with gas and fluid collection and enlarged pelvic and inguinal lymph nodes. Two urgent surgical explorations and debridements, with meticulous wound care using negative pressure wound dressings (Prevena) were done. Intravenous Gentamicin, Benzylpenicillin, Clindamycin, Metronidazole and Flucloxacillin were administered for six weeks. The patient's clinical status gradually improved. Streptococcus Anginosus, that is part of the Streptococcus Milleri group and Staphylococcus Lugdunensis, a coagulase-negative Staphylococci (CoNS) are commensal organisms of the oral and gastrointestinal tracts. These organisms possess virulence factors that facilitate tissue invasion and destruction, causing an aggressive course of NF. This case highlights the importance of considering atypical pathogens, especially in patients with predisposing factors such as diabetes and obesity. Early recognition, prompt surgical intervention and a multidisciplinary approach are essential for improving outcomes in these cases.TestResultWhite Blood Cells (WBC)22,200 [WBCs per microliter]Sodium123 [mmol/L]Chloride88 [mmol/L]C-reactive protein (CRP)318 [mg/L]Blood Glucose19.3 [mmol/L]

Locally advanced rectal cancer in a young adult affected with dyskeratosis congenita (Zinsser–Cole–Engman syndrome): a case report

BackgroundDyskeratosis congenita (DKC), also known as Zinsser–Cole–Engman syndrome, is a progressive genetic disease with a triad of reticulate skin pigmentation, nail dystrophy, and leukoplakia. Approximately 8–10% of patients with DKC develop malignancies, and cases of colorectal cancer with DKC in young people have been reported previously.Case presentationA 25-year-old man with DKC since approximately 10 years of age developed fever and lower abdominal discomfort. Diagnostic imaging revealed locally advanced rectal cancer with lymph node metastasis, direct invasion of the prostate, and pelvic abscess due to tumor microperforation (cT4bN2M0 cStage IIIC). Biopsy showed well to moderately differentiated ductal adenocarcinoma. Genetic testing was negative for RAS and BRAF gene mutations, and microsatellite instability (MSI) testing was also negative. After sigmoid colostomy, the patient was treated with total neoadjuvant therapy (TNT) with systemic chemotherapy (six courses of FOLFOX + panitumumab) followed by chemoradiation therapy (50.4 Gy with capecitabine). After TNT, the primary tumor and metastatic lymph nodes shrank. According to the findings of colonoscopy and magnetic resonance image (MRI), we diagnosed near complete response (near-CR) and decided to follow the patient without surgery by every 3 months re-evaluation. However, 5 months after TNT, tumor regrowth was detected on colonoscopy and imaging, and the patient underwent total pelvic exenteration. He developed paralytic ileus as a postoperative complication, and was discharged on the 38th postoperative day. Pathological examination revealed a residual tumor with invasion of the periprostatic tissue. There was no metastasis in the pararectal and lateral pelvic lymph nodes, but one extramural non-contiguous cancerous extension (tumor deposit) was observed (ypT4bN1cM0 ypStage IIIC). The patient has been free of recurrence for one year after surgery.ConclusionsDKC often develops into various tumors in the digestive system at an early age; therefore, appropriate surveillance may be required. In addition, considering that cancers in patients with DKC occur at a young age, fertility preservation and survivorship are also important, and adequate explanations and care should be provided to patients before and after treatment.