Tissue Reaction Research Articles

Multi-Layered Implant Approach for Hemilaryngectomy Reconstruction in a Porcine Model.

Partial laryngectomies result in voice, swallowing, and airway impairment for thousands of patients in the United States each year. Treatment options for dynamic restoration of laryngeal function are limited. Thus, there is a need for new reconstructive approaches. Here, we evaluated early (4 week) outcomes of multi-layered mucosal-myochondral (MMC) implants when used to restore laryngeal form and function after hemilaryngectomy in a porcine model. Six Yucatan minipigs underwent transmural hemilaryngectomies followed by reconstruction with customized MMC implants aiming to provide site-appropriate localization of regenerated laryngeal tissues, while supporting laryngeal function. All implants were fabricated from polymeric collagen, with a subset of muscle and cartilage implants containing motor endplate-expressing muscle progenitor cells or cartilage-like cells differentiated from adipose stem cells, respectively. Vocalization and laryngeal electromyography (L-EMG) measurements with nerve conduction studies were performed post-operatively and compared with baseline along with gross and histological analyses of the healing response. All animals (n = 6) survived and maintained airway patency, safe swallowing, and phonation, without the use of tracheostomy and/or gastrostomy tubes. Histological evaluation indicated no adverse tissue reaction or implant degradation, showing progressive regenerative remodeling with mucosa reformation and ingrowth of new muscle and cartilage. Preliminary L-EMG suggested weak but detectable motor unit action potentials. Although vocalization duration, frequency, and intensity decreased post-operatively, all animals retained vocal capacity and parameter recovery was evident over the study duration. Engineered collagen polymeric implants in the presence or absence of autologous cell populations may serve as a feasible reconstructive option to restore dynamic function after hemilaryngectomy. Long-term follow-up is needed to further assess functional outcomes. NA Laryngoscope, 2024.

Hematological Response to Particle Debris Generated During Wear–Corrosion Processes of CoCr Surfaces Modified with Graphene Oxide and Hyaluronic Acid for Joint Prostheses

Various surface modifications to increase the lifespan of cobalt–chromium (CoCr) joint prostheses are being studied to reduce the wear rate in bone joint applications. One recently proposed modification involves depositing graphene oxide functionalized with hyaluronic acid (a compound present in joints) on CoCr surfaces, which can act as a solid lubricant. This paper analyzes the biological alterations caused by wear–corrosion phenomena that occur in joints, both from the perspective of the worn surface (in vitro model) and the particles generated during the wear processes (in vivo model). The analysis of the inflammatory response of macrophage was performed on CoCr surfaces modified with graphene oxide and functionalized with hyaluronic acid (CoCr-GO-HA), before and after wear–corrosion processes. The wear particles released during the wear–corrosion tests of the CoCr-GO-HA/CoCr ball pair immersed in 3 g/L hyaluronic acid were intra-articularly injected into the experimental animals. The hematological analysis in vivo was made considering a murine model of intra-articular injection into the left knee in male adult Wistar rats, at increasing concentrations of the collected wear particles dispersed in 0.9% NaCl. Non-significant differences in the inflammatory response to unworn CoCr-GO-HA surfaces and control (polystyrene) were obtained. The wear–corrosion of the CoCr-GO-HA disk increased the inflammatory response at both 72 and 96 h of material exposure compared to the unworn CoCr-GO-HA surfaces, although the differences were not statistically significant. The pro-inflammatory response of the macrophages was reduced on the worn surfaces of the CoCr modified and functionalized with graphene oxide (GO) and hyaluronic acid (HA), compared to the worn surfaces of the unmodified CoCr. The hematological analysis and tissue reactions after intra-articular injection did not reveal pathological damage, with average hematological values recorded, although slight reductions in creatinine and protein within non-pathological ranges were found. Some traces of biomaterial particles in the knee at the highest concentration of injected particles were only found but without inflammatory signs. The results show the potential benefits of using graphene in intra-articular prostheses, which could improve the quality of life for numerous patients.

CTIM-04. MODULATION OF THE INTRATUMORAL IMMUNE MICROENVIRONMENT BY LOCAL THERAPY WITH NATURAL KILLER CELLS ENGINEERED WITH A HER2-TARGETED CHIMERIC ANTIGEN RECEPTOR IN COMBINATION WITH SYSTEMIC ANTI-PD-1 CHECKPOINT INHIBITION IN PATIENTS WITH RECURRENT GLIOBLASTOMA

Abstract Glioblastoma (GB) is characterized by a marked immunosuppressive tumor microenvironment. In the multicenter CAR2BRAIN phase I first-in-human clinical trial, we investigated the modulation of the tumor microenvironment by repetitive local injection of clonal chimeric antigen receptor (CAR)-NK cells (NK-92/5.28.z) targeting HER2 alone and in combination with systemic anti-PD-1 checkpoint inhibitor therapy in patients with recurrent HER2-positive GB. 6 patients were treated with repetitive doses of CAR-NK cells as monotherapy and 12 patients received a combination therapy with the anti-PD-1 checkpoint inhibitor ezabenlimab. In three of those, we were able to implement a biopsy-treat-resect-treat strategy. After initial biopsy, combination treatment was initiated before planned tumor resection, enabling analysis of the transformation of the tumor immune microenvironment by highplex multispectral fluorescent analyses and cytokine quantification. None of the patients developed a cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Profound alterations of the immune cell distribution in the cerebrospinal fluid (CSF) and in the tumor were observed. In CSF sampled from the resection cavity, combination immunotherapy induced a local immune response with elevated pro-inflammatory cytokines and cell counts. In post-treatment tissue samples, we observed an increase of CD4+ and CD8+ T cells, and a decrease of regulatory CD4+FoxP3+ T cells. The three patients treated following the biopsy-treat-resect-treat strategy achieved a median progression-free survival (PFS) of 24 weeks, compared to 10 weeks for patients with upfront resection. Local immunotherapy with HER2-targeted CAR-NK cells is feasible and safe both as monotherapy and in combination with the systemic checkpoint inhibitor ezabenlimab and induces local immune reactions in CSF and tumor tissue. Given the signal for possible clinical benefit provided by the increase in PFS in the patients of the biopsy-treat-resect-treat cohort, further trials are warranted.

SNAP25 as a prognostic marker in transcriptome analysis of meningioma.

Meningiomas are the most common intracranial tumors and their diagnosis relies mostly on neuroimaging and histology. However, the histology grades cannot predict the outcome exactly and some meningiomas tend to recur after resection of even benign tumors. Therefore, it is necessary to explore prognostic and diagnostic molecular targets. Differential expression analysis between meningiomas and meninges was performed based on the merged data of GSE43290 and GSE84263. Next, we performed gene set enrichment analysis (GSEA), immune cell infiltration analysis, protein-protein interaction analysis, and survival analysis using public data. The expression level of Synaptosome-associated-protein-25kDa (SNAP25) was verified by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blotting in meningioma tissues. There were 263 upregulated and 592 downregulated genes identified in meningiomas by differential expression analysis. GSEA results revealed that meningiomas were negatively related to the pathway of soluble N-ethylmaleimide sensitive factor attachment protein receptor interactions in vascular transport and chemokine signaling. SNAP25 was characterized as a hub gene and downregulated in meningiomas. The Kaplan-Meier plot indicated that high expression of SNAP25 is a favorable factor. SNAP25 was downregulated and identified as a potential prognostic marker in meningioma.

Effects of Losartan and Fisetin on Microfracture-Mediated Cartilage Repair of Ankle Cartilage in a Rabbit Model.

Microfracture is one surgical treatment strategy for osteochondral lesions of the talus (OLTs) but results in fibrocartilage repair tissue, which has inferior mechanical properties to native hyaline cartilage. Biological regulation of microfracture has been suggested to improve the quality of cartilage repair in patients. To determine if administration of losartan, fisetin, or losartan and fisetin combined can enhance microfracture-mediated cartilage repair of OLTs in a rabbit model. Controlled laboratory study. Four-month-old female rabbits were divided into the following groups (8 rabbits per group): microfracture only (microfracture), microfracture plus losartan (losartan), microfracture plus fisetin (fisetin), and microfracture plus losartan and fisetin (losartan+fisetin). A 2.7-mm osteochondral defect and 4 microfracture holes were created in the talar dome cartilage. The rabbits were administered losartan (10 mg/kg/day), fisetin (20 mg/kg/day), or losartan and fisetin orally until euthanized 12 weeks after surgery. Gross evaluation, micro-computed tomography, histology, and immunohistochemistry evaluations of the osteochondral defects were performed as well as quantitative polymerase chain reaction of capsule tissue and enzyme-linked immunosorbent assay of serum. The losartan and fisetin groups had increased International Cartilage Regeneration & Joint Preservation Society macroscopic scores with improved cartilage repair and enhanced subchondral bone healing compared with the microfracture group. However, the losartan+fisetin group did not show a synergistic effect. O'Driscoll histology scores were higher in the losartan and fisetin groups compared with the microfracture group, while the losartan+fisetin group had a lower score than the losartan, fisetin, and microfracture groups. Collagen type 2 staining revealed organized chondrocytes in the losartan and fisetin groups, but the losartan+fisetin group did not show improvement when compared with other groups. Fisetin treatment decreased catalase and transforming growth factor-β1-activated kinase 1 expression in capsular tissue. Concomitant microfracture and biological regulation, using oral administration of either losartan or fisetin, may improve cartilage healing of OLTs; however, losartan and fisetin combined in the current drug administration regimen does not appear to provide synergistic effects. Oral intake of losartan or fisetin may result in beneficial effects on microfracture-mediated cartilage repair of OLTs.

Deep Learning Based Detection of Silicosis from Computed Tomography Images

Artificial intelligence has increasingly been used in interpreting medical images to support the timely treatment of diseases by providing early and accurate diagnosis. Pneumoconiosis is a tissue reaction that develops as a result of the accumulation of inorganic dust in the lungs. The most common types of pneumoconiosis include diseases such as coal worker's pneumoconiosis, silicosis, asbestosis, and siderosis. Silicosis, which has maintained its importance since the 1900s and has seen over 182,000 articles published in the last 10 years, is a global health problem. The automated detection and recognition of silicosis in lung computed tomography (CT) images can be considered the backbone of assisting the silicosis diagnosis process. Automated medical assistance systems developed using artificial intelligence can simplify the medical examination process and reduce the time required to start accurate treatment. Although the literature contains various studies that benefit silicosis diagnosis using chest X-ray images or pneumoconiosis diagnosis using CT images, there is not enough classification study that can particularly aid the diagnosis of silicosis in CT images.The method of early detection of silicosis from chest radiographs and CT images has been a challenging task due to the high variability among pneumoconiosis readers. Based on the success of deep learning in the classification and segmentation of medical images, this study has shown that deep learning networks and transfer learning algorithms can detect silicosis with high accuracy by classifying CT images. The performance of the six algorithms examined in the study is compared, and the algorithm with the best performance is recommended. Performance criteria such as accuracy, precision, specificity, and F1-score of the algorithms used in the study were calculated. The accuracy rates of the models were obtained as 92.62%, 93.03%, 92.76%, 95.38%, 97.29%, and 95.17% for AlexNet, VGG16, ResNet50, InceptionV3, Xception, and DenseNet121, respectively. These results show that Xception outperformed the other algorithms and was the most successful algorithm in the automatic detection of silicosis with an accuracy rate of 97.29%.Additionally, a new dataset consisting of tomography images from silicosis patients is presented in this study. Experimental results have shown that transfer learning algorithms can significantly benefit the diagnosis of silicosis by successfully classifying CT images. The findings of the study highlight the clinical importance of artificial intelligence methods in medical image analysis and early disease diagnosis.

Results of the study on the baseline status of flight-associated periodontal pathology in civil aviation flight personnel

Aim. To assess the baseline condition of periodontal structures in civil aviation flight personnel in order to improve the algorithm for treatment and preventive dental care.Materials and Methods. A periodontal examination of the oral cavity was conducted for 120 flight personnel at the physician-sanitary unit of Dushanbe International Airport. The participants were divided into five groups: flight personnel with mild chronic gingivitis, moderate chronic gingivitis, mild chronic periodontitis, moderate chronic periodontitis, and a control group of flight personnel with healthy periodontium. The clinical course of chronic gingivitis and periodontitis was evaluated using oral hygiene and periodontal indices.Results and Discussion. Inflammatory periodontal diseases, such as chronic gingivitis and periodontitis of moderate severity (Groups II and IV), presented with more pronounced symptoms, including severe inflammatory reactions of the periodontal tissues and poor oral hygiene, compared to those in Groups I and III.Conclusion. The study demonstrated that papillary-marginal-alveolar (PMA) index, bleeding index, and oral hygiene scores were significantly elevated in flight personnel with mild to moderate chronic periodontitis, highlighting the need for targeted treatment and preventive care.

Understanding dental pulp inflammation: from signaling to structure.

The pulp is a unique tissue within each tooth that is susceptible to painful inflammation, known as pulpitis, triggered by microbial invasion from carious lesions or trauma that affect many individuals. The host response involves complex immunological processes for pathogen defense and dentin apposition at the site of infection. The interplay of signaling between the immune and non-immune cells via cytokines, chemokines, neuropeptides, proteases, and reactive nitrogen and oxygen species leads to tissue reactions and structural changes in the pulp that escalate beyond a certain threshold to irreversible tissue damage. If left untreated, the inflammation, which is initially localized, can progress to pulpal necrosis, requiring root canal treatment and adversely affecting the prognosis of the tooth. To preserve pulp vitality and dental health, a deeper understanding of the molecular and cellular mechanisms of pulpitis is imperative. In particular, elucidating the links between signaling pathways, clinical symptoms, and spatiotemporal spread is essential to develop novel therapeutic strategies and push the boundaries of vital pulp therapy.

PEDF upregulated in Ngfr-positive cells suppresses proliferation of pulmonary artery smooth muscle cells

Abstract Background Pulmonary arterial hypertension (PAH) is a disease with poor prognosis that causes right heart failure due to progressive pulmonary artery remodeling. Although existing pulmonary vasodilators contribute to pulmonary artery reverse remodeling by reducing share stress, the development of therapeutic agents that directly target pulmonary vascular remodeling is desired. Nerve growth factor receptor (Ngfr) is involved in the inflammatory reaction and repair process of damaged tissues. We have previously reported that Ngfr-positive cells are increased in the peripheral blood (PB) of PAH patients and are associated with disease progression. We also found that Ngfr inhibited the pathogenetic progression of pulmonary hypertension in a model of hypoxia-induced pulmonary hypertension. However, it remains unclear how Ngfr positive cells are involved in the pathology of PAH. Purpose In this study, we investigate how Ngfr-positive cells affect the pathogenesis of PAH. Methods & Results To evaluate the localization of Ngfr-positive cells in lung tissue, WT mice (C57BL/6) transplanted with bone marrow (BM) of GFP-Tg mice were kept under hypoxia for 3 weeks to create hypoxia-induced pulmonary hypertension (PH) model. Immunostaining of lung tissue sections indicated that double positive cells (Ngfr+GFP+) were present in the interstitial tissue around the small pulmonary artery. To examine the cellular characteristics of Ngfr-positive cells, RNA sequencing of Ngfr-positive and Ngfr-negative cells in PB was performed. Significantly 78 genes were upregulated in Ngfr-positive cells, including 11 secreted proteins. Among these, we focused on pigment epithelium-derived factor (PEDF), a secreted protein involved in angiogenesis. PEDF mRNA expression was decreased in the lung of Ngfr-KO mice compared to WT mice. We next examined the effect of PEDF on pulmonary artery smooth muscle cells (PASMCs). Platelet-derived growth factor (PDGF)-induced cell proliferation of PASMC was inhibited by PEDF stimulation. Furthermore, PEDF stimulation significantly inhibited PDGF-induced mRNA expressions of TNF and MMP9 in PASMCs. Conclusion In this study, we show that PEDF expression is upregulated in Ngfr-positive cells and that PEDF inhibits PDGF-induced hPASMC proliferation, suggesting that NGFR-positive cells may suppress pulmonary vascular remodeling through PEDF-mediated paracrine effects. PEDF might be a new therapeutic target for PH.

Effectiveness and biocompatibility of a novel Schlemm’s canal microstent for glaucoma management

To evaluate the effectiveness and biocompatibility of Wistend, a novel Schlemm’s canal (SC) microstent made of Nitinol designed to improve aqueous humor outflow. New Zealand white (NZW) rabbits were divided into blank, sham-operated and Wistend groups. ICare® Tonovet Plus®, swept-source optical coherence tomography (SS-OCT), slit lamp biomicroscopy, retinal camera and scanning electron microscopy (SEM) were used for preoperative and postoperative observations. Hematoxylin and Eosin (H&E) tissue staining was adopted for biocompatibility. A significant difference in intraocular pressure (IOP) between the Wistend group and the control groups was observed during the six-month follow-up. SS-OCT identified arc line internal reflections within the SC in the anterior chamber angle. Conjunctival congestion and edema gradually diminished in the early stages. No corneal vascularization, no anterior chamber inflammatory response and no significant tissue reactions were noted in any groups. SEM showed the Wistend’s windows and orifices remained clear, encircled by minimal incidental ocular tissue and free from blockage. Histopathological examination revealed no discernible differences between the Wistend-implanted and sham-operated eyes. These in vivo studies demonstrate the effectiveness and biocompatibility of the microstent. Our findings suggest a promising potential for Wistend in significantly reducing IOP and effectively facilitating the outflow of aqueous humor.

Modern views on the etiology and role of microbial persistence in the development of inflammatory processes in the periodontal complex (review)

Alveolar tissue diseases cause the appearance of dentition defects, thereby reducing the patients' work capacity and quality of life. The purpose of this research was to investigate, modern views on the etiology of periodontitis and the role of microbial persistence in the development of inflammatory processes of periodontal complex basing on a review of literary sources. Literature review was conducted using PubMed, Web of Science, Scopus, Google Scholar from 2018 to March 2024. There were no restrictions on the date of publication or the language of scientific sources. Searches were conducted according to MeSH (Medical Subject Headings) with using the following search terms: "periodontitis", "oral mucosa", "gums", "dental plaque", "periodontium", "traumatic occlusion", "microorganisms". In total, during the initial analysis 82 literary sources were selected and processed, after further systematization of the selected information using general scientific methods, 70 of them remained. Used methods: bibliographic and analytical. Generalized perio­dontitis is a chronic inflammatory-dystrophic process that occurs as a result of various factors. In the pathogenesis of this disease, the key role is played by the inflammatory process, which is a complex interaction of microcirculatory, he­matological and connective tissue reactions to the lesion. Local (exogenic) and general (endogenic) causative factors are distinguished. The main factors that cause pathological changes in periodontium are bacterial biofilm, traumatic occlusion and various anatomical anomalies. Dental plaque occupies a special and main place among the causes of periodontitis. At present, leading pathogenetic links in the development of the inflammation in the periodontium, in par­ticular, the disruption of free radical oxidation, the processes of peroxide oxidation of lipids and proteins, the disorder of the functional state of the antioxidant system, the formation of oxidative stress, as well as the humoral link of adaptive immune protection and cytokinesis, have not been sufficiently studied. There is no doubt about the role of the microbial factor in the etiology of periodontal diseases, but the penetration of microbes into the periodontium does not always lead to the development of the disease, because the organism has a number of protective mechanisms that counteract the development of inflammation.

In Vivo Feasibility of Arterial Embolization with a New Permanent Agar-agar-Based Agent.

Evaluate the safety and efficacy of an eco-friendly permanent agar-agar-based embolization agent (ABEA) (EmboBio®) for intra-arterial use. Six pigs embolized with one ABEA torpedo (6 lower polar renal and 6 lumbar arteries) and one coil (6 lower polar renal and 6 lumbar arteries). Technical success was defined as a complete occlusion with no residual flow in DSA. Short-term endpoints included safety (non-targeted embolization), ease of use (embolization preparation time, occlusion time), and DSA controls at day 7, month 1, and month 3. Tissue reaction was assessed via [18F]-FDG PET/CT at month 2 and histological study at month 3. ABEA torpedoes achieved immediate and persistent occlusion at month 3 for all kidney and lumbar embolizations (n = 12/12). Control coils had technical success for 12/12, with a persistent occlusion at month 3 for 2/12. No off-target embolization occurred. ABEA torpedoes demonstrate faster occlusion (ABEA: 6 ± 4s; coils: 427 ± 469s; p = 0.0022, n = 12) and preparation times (ABEA: 96.9 1 ± 23s; coils: 150.33 ± 58s; p = 0.0432, n = 12) after device placement than coil. No significant difference in inflammation between ABEA and coil groups at month 2 (ABEA: 3.35e-6 ± 1.7e-6%ID/mm3; coils: 2.24e-6 ± 8.5e-7%ID/mm3; p = 0.5) on PET imaging. These results were confirmed by histological analysis at month 3. Permanent dry foam torpedo comprising agar-agar is effective for arterial embolization. In animal model, one ABEA torpedo demonstrates a faster and more persistent occlusion than one fiber coil. Not applicable.

Chronic hearing loss turns out being a calcified chondroid mesenchymal neoplasm with FN1::FGFR2 fusion.

A 53 year old female presented with a six-year history of right-sided slow deterioration in hearing and a feeling of pressure in the right ear. The patient had not experienced any pain but reported some paresthesia of the right half of the tongue, whereas no further other cranial nerve deficits were evident. The otoscopy was unremarkable as well as the rest of the clinical ENT examination except for a slight asymptomatic swelling of the right cheek. Imaging findings showed an expansive tumor infiltrating and destroying the right lateral skull base. The tumor was partially composed of cystic/regressive lesions with high contrast media uptake. The tumor had high-signal intensity with water-sensitive sequences (T2w) and was hypointense on T1w images. We performed a tumor resection via a transparotideal-infratemporal approach. Histologically, the tumor was composed of granular variably calcified chondroid matrix with extensive regressive changes and granulation-like tissue reaction associated with calcinosis and crystal deposition. Molecular analysis of the tumor via the TruSight- RNA-Fusion panel detected a fusion involving FN1::FGFR2, consistent with "calcified chondroid mesenchymal neoplasm" (CCMN), a rare tumor entity recently defined by Liu et al 2021. In regular follow-up care no residual tumor has been detected in imaging studies (MRI and CT) within 2 years and 4 months. The biology and consequently the radio sensitivity cannot be defined precisely since long term results are missing due to the first description of this entity in 2021. As a consequence, surgical resection is recommended as the treatment of choice. Thorough clinical and radiological follow-up is mandatory as local recurrences are to be expected due to the infiltrative behavior. In case of a loco regional recurrence the fusion with FGFR2 may represent a therapeutic option for a targeted therapy on molecular level.

A Specific Targeted Enhanced Nanotherapy Strategy for Inducing Ferroptosis by Regulating the Iron Pool Levels in Tumor Cells.

Ferroptosis is an iron-dependent cell death pathway triggered by the toxic accumulation of lipid peroxides on cellular membranes. However, an imbalance in iron metabolism in tumor cells leads to the insufficient accumulation of iron ions in the iron pool, which inhibits ferroptosis. Nonspecific delivery of iron species may increase the risk of promoting tumor proliferation as well as trigger undesirable detrimental effects such as anaphylactic reactions in normal tissues. This study found that a constructed self-enhancing targeted nanocarrier can accurately regulate the iron pool levels in tumor cells. We constructed a programmatic targeted enhanced nanotherapy strategy by loading the ferroptosis inducer erastin into a self-enhancing targeted nanocarrier. This nanosystem was more effective at inducing tumor ferroptosis after upregulating the iron pool levels in tumor cells with self-enhancing targeted nanocarriers. Both in vitro and in vivo outcomes demonstrated notable anticancer ferroptosis efficacy, indicating that self-enhancing targeted nanocarriers can effectively regulate the level of the iron pool in tumor cells and promote ferroptosis. The combination of this nanotherapy strategy with self-enhancing targeted chemotherapy nanomedicines can achieve complete tumor clearance. Moreover, this self-enhancing targeted ferroptosis nanotherapy strategy is expected to be beneficial for future progress in the field of cancer self-enhancing targeted therapy.

Biocompatibility of Water-Dispersible Pristine Graphene and Graphene Oxide Using a Close-to-Human Animal Model: APilot Study on Swine.

Graphene-based materials (GBMs) are of considerable interest for biomedical applications, and the pilot study on the toxicological and immunological impact of pristine graphene (GR) and graphene oxide (GO) using swine as a close-to-human provides valuable insights. First, ex vivo experiments are conducted on swine blood cells, then GBMs are injected intraperitoneally (i.p.) into swine. Hematological and biochemical analyses at various intervals indicate that neither GO nor GR cause systemic inflammation, pro-coagulant responses, or renal or hepatic dysfunction. Importantly, no systemic toxicity is observed. Analysis of a panel of 84 immune-related genes shows minimal impact of GO and GR. The animals are sacrificed 21 days post-injection, and transient absorption imaging and Raman mapping show the presence of GO and GR in the mesentery only. Histological evaluation reveals no signs of alterations in other organs. Thus, clusters of both materials are detected in the mesentery, and GO aggregates are surrounded only by macrophages with the formation of granulomas. In contrast, modest local reactions are observed around the GR clusters. Overall, these results reveal that i.p. injection of GBMs resulted in a modest local tissue reaction without systemic toxicity. This study, performed in swine, provides essential guidance for future biomedical applications of graphene.

An injectable hydrogel of porcine cholecyst extracellular matrix for accelerated wound healing.

Hydrogel formulations of xenogeneic extracellular matrices have been widely used for topical wound care because of their exceptional tunability over other formulations like lyophilized sheets, powders, non-injectable gels, pastes, and ointments. This is important in the treatment of wounds with irregular shapes and depth. This study identified an injectable hydrogel formulation of porcine cholecyst extracellular matrix (60%) in medical-grade carboxymethyl cellulose (40%) as vehicle and evaluated its biomaterial properties. Further, an in-depth evaluation of in vivo wound healing efficacy was conducted in a rat full-thickness skin excision wound healing model, which revealed that the hydrogel formulation accelerated wound healing process compared to wounds treated with a commercial formulation and untreated wounds. The hydrogel appeared to have promoted a desirable pro-regenerative tissue reaction predominated by Th2 helper lymphocytes and M2 macrophages as well as an effective collagen remodeling indicative of diminished scarring. In conclusion, the porcine cholecyst extracellular matrix injectable hydrogel formulation appeared to be a promising candidate formulation as an advanced wound care biomaterial for faster healing of skin wounds with minimal scarring.

C/EBPδ deficiency delays infection-induced preterm birth.

Parturition is an inflammation process. Exaggerated inflammatory reactions in infection lead to preterm birth. Although nuclear factor kappa B (NF-κB) has been recognized as a classical transcription factor mediating inflammatory reactions, those mediated by NF-κB per se are relatively short-lived. Therefore, there may be other transcription factors involved to sustain NF-κB-initiated inflammatory reactions in gestational tissues in infection-induced preterm birth. Cebpd-deficient mice were generated to investigate the role of CCAAT enhancer-binding protein δ (C/EBPδ) in lipopolysaccharide (LPS)-induced preterm birth, and the contribution of fetal and maternal C/EBPδ was further dissected by transferring Cebpd-/- or WT embryos to Cebpd-/- or WT dams. The effects of C/EBPδ pertinent to parturition were investigated in mouse and human myometrial and amnion cells. The interplay between C/EBPδ and NF-κB was examined in cultured human amnion fibroblasts. The mouse study showed that LPS-induced preterm birth was delayed by Cebpd deficiency in either the fetus or the dam, with further delay being observed in conceptions where both the dam and the fetus were deficient in Cebpd. Mouse and human studies showed that the abundance of C/EBPδ was significantly increased in the myometrium and fetal membranes in infection-induced preterm birth. Furthermore, C/EBPδ participated in LPS-induced upregulation of pro-inflammatory cytokines as well as genes pertinent to myometrial contractility and fetal membrane activation in the myometrium and amnion respectively. A mechanistic study in human amnion fibroblasts showed that C/EBPδ, upon induction by NF-κB, could serve as a supplementary transcription factor to NF-κB to sustain the expression of genes pertinent to parturition. C/EBPδ is a transcription factor to sustain the expression of gene initiated by NF-κB in the myometrium and fetal membranes in infection-induced preterm birth. Targeting C/EBPδ may be of therapeutic value in the treatment of infection-induced preterm birth.

Parasitic Infections and Host Tissue Response in Histopathology: A Rare Retrospective Research Study from Rural India.

Parasite are living organisms which survive on another living being for their nourishment and survival. When these parasites resides on human body, they bring about inflammatory response. This inflammatory response leads to tissue reaction. Tissue response on microscopy appear as an eosinophilia, abscess and granulomas. This study was planned with the objective to know the frequency of parasite infection, tissue response in parasite infection and its comparison in terms of variables like age, sex and the type of parasite. This is a retrospective study, conducted in the department of pathology. A total of 26 cases of parasitic infections in human specimens reported in our department from January 2008 to December 2019 were included in this study. On all archived cases hematoxylin and eosin and where ever required periodic acid schiff was applied. These slides were thoroughly examined and clinicopathological correlation was studied. Age range of patients was 5 years to 70 years. Maximum number of patients were belonging to 11-20 year age group. Male to female ratio was 1:2. Among the 26 cases, there were 9 cases (34.62%) of hydatid cyst, six cases of Entamoeba histolytica (23.07%), four cases of Enterobious vermicularis (15.38%), and two cases (7.69%) each of Ascaris lumbricoides, filaria and cysticercosis respectively. A specific tissue response seen in cysticercosis having chronic inflammatory cells, palisaded epithelioid cells granuloma and giant cell reaction while other showed inflammatory cells infiltration. Clinically diagnosis of parasitic infection in each and every case is not possible, similarly radiological investigation is also suggestive only. Histopathology examination is the benchmark investigation to diagnose parasite infection and tissue reaction to the host. Histopathology examination must be implicated in every case to identify parasite and tissue reaction so that the patients can be managed accordingly before the complications rises.

CuO nanoparticles for glioma treatment in vitro and in vivo.

Glioma is the most prevalent malignant brain tumor in adults. The development of engineered nanomaterials (ENMs) has led to the emergence of innovative therapeutic strategies for gliomas. Therefore, our aim is to investigate the therapeutic effect of CuO nanoparticles (NPs) on glioma and provide data support for future research. The therapeutic effect of CuO NPs on glioma rats was explored through the detection of inflammatory factors, oxidase, pathological sections, immunofluorescence, neurotransmitter, glioma biomarker proteins and genes, and rat behavioral tests. Additionally, the application prospect of CuO NPs was evaluated by treating U87MG human glioma cell line. In this study, it was found that CuO NPs can alleviate the inflammatory reaction in the hippocampus tissue of glioma rats, promote the production of ·OH and lead to the up-regulation of catalase (CAT) and superoxide dismutase (SOD) enzyme activities. Treatment with CuO NPs also inhibited the expression of matrix metalloproteinase-9 (MMP-9) biomarkers in model rats and glioma cells. Moreover, it enhanced the release of neurotransmitters, which subsequently improved spatial recognition and memory ability of glioma rats. In conclusion, CuO NPs is a potential glioma treatment for ENMs, but still needs modification and modification strategies to improve its biocompatibility and targeted delivery.

Nanofat Improves Vascularization and Tissue Integration of Dermal Substitutes without Affecting Their Biocompatibility.

Dermal substitutes require sufficient tissue integration and vascularization to be successfully covered with split-thickness skin grafts. To rapidly achieve this, we provide the proof of principle for a novel vascularization strategy with high translational potential. Nanofat was generated from subcutaneous adipose tissue of green fluorescence protein (GFP)+ C57BL/6J donor mice and seeded onto small samples (4 mm in diameter) of the clinically approved dermal substitute Integra®. These samples and non-seeded controls were then implanted into full-thickness skin defects in the dorsal skinfold chamber of C57BL/6J wild-type mice and analyzed by intravital fluorescence microscopy, histology and immunohistochemistry over a 14-day period. Nanofat-seeded dermal substitutes exhibited an accelerated vascularization, as indicated by a significantly higher functional microvessel density on days 10 and 14 when compared to controls. This was primarily caused by the reassembly of GFP+ microvascular fragments inside the nanofat into microvascular networks. The improved vascularization promoted integration of the implants into the surrounding host tissue, which finally exhibited an increased formation of a collagen-rich granulation tissue. There were no marked differences in the inflammatory host tissue reaction to nanofat-seeded and control implants. These findings demonstrate that nanofat significantly improves the in vivo performance of dermal substitutes without affecting their biocompatibility.