Presence Of Inflammatory Cells Research Articles

Abstract 4136234: Increased Reactive Oxygen Species using [18F]ROStrace PET and Dihydroethidium Staining in Myocardial Infarction Reperfusion injury

Introduction: Patients with reperfusion injury following myocardial infarction (MI) are at a higher risk of heart failure. Reactive oxygen species (ROS) activity can further damage cardiomyocytes and compromise heart function. Imaging methods are needed to assess ROS in vivo to investigate targeted adjunctive therapies. Our group developed a novel ROS-activated PET radiotracer [18F]ROStrace to fill this gap. In this study, we measured [18F]ROStrace fractional uptake rate (FUR) and for the first time compared it with histologic assessment of infarct and myocardium specimens. We hypothesized that [18F]ROStrace FUR was increased in the infarct and that [18F]ROStrace FUR was supported by [18F]ROStrace analogue dihydroethidium (DHE) staining. Methods: MI was induced in five swine, followed by reperfusion after 90 minutes. In vivo LGE CMR imaging and [18F]ROStrace and [82]Rb PET were performed at ~3-4 days after infarction. A terminal procedure was then performed. DHE and 4′,6-diamidino-2-phenylindole (DAPI) staining was done. Two swine received injections of DHE in the right and left coronary arteries to assess ROS. ROS activity was determined from [18F]ROStrace by computing the [82]Rb myocardial blood flow (MBF) corrected FUR. The linear relationship between infarct and MVO size, and MBF-corrected [18F]ROStrace FUR were calculated using the Pearson’s r. Results: There was a strong and positive correlation between infarct and MVO size (r=0.9, p=0.04). The MBF-corrected ROStrace FUR at baseline was 0.07±0.06 ml/g, infarct was 0.15 ± 0.05 ml/g, and remote was 0.09 ± 0.05 ml/g. We observed a significant difference between ROS in the infarct and remote region (p=0.01), which is also seen in the increased DHE staining in the infarct. We also observed increased DAPI staining in the infarct region compared to free wall due to the presence of inflammatory cells, thus increasing the number of nuclei. Conclusion: [18F]ROStrace is increased in the infarct during the subacute period post-MI compared to healthy and remote myocardium and supported by histological assessment. This work may lead to the use of in vivo [18F]ROStrace PET to support development of therapeutic strategies targeting ROS to reduce MI.

Cytological Characteristics of the Eye Conjunctiva in Dogs with Atopic Dermatitis

Atopic dermatitis is a chronic, pruritic inflammatory skin disease affecting approximately 10% of dogs worldwide. The disease typically manifests at an early age, causing pruritus and secondary skin lesions in specific anatomical regions. The pathophysiology of canine atopic dermatitis (CAD) remains incompletely understood, but recent research suggests a complex interplay between skin barrier dysfunction, allergic sensitisation, and microbial dysbiosis. Despite the well-established association between atopic dermatitis and conjunctivitis, the prevalence of conjunctivitis in dogs with CAD is often underestimated in clinical practice due to inadequate recognition of symptoms and a lack of specific diagnostic protocols. This study aimed to analyse the cytological characteristics of the conjunctiva in dogs affected by atopic dermatitis. Samples were collected from 24 dogs diagnosed with CAD and treated at the University Veterinary Hospital, Faculty of Veterinary Medicine, University of Zagreb. Cytological analysis was performed on samples obtained using a cytobrush. The results revealed the presence of inflammatory cells in all samples, with lymphocytes most prevalent (87.5%). A mild degree of conjunctival metaplasia was observed in all dogs, regardless of the type of inflammatory cells and the severity of conjunctivitis. These findings suggest that atopic dermatitis may induce changes in the conjunctiva that are not necessarily correlated with the intensity of the inflammatory response. The presence of lymphocytes, along with eosinophils in some cases, underscores the diagnostic value of conjunctival cytology in dogs with CAD. Furthermore, the increased density of goblet cells suggests similarities in the pathophysiology of ocular allergies in dogs and humans, opening avenues for further research to better understand and treat these conditions. This study highlights the importance of an interdisciplinary approach in the diagnosis and treatment of atopic dermatitis, including regular ophthalmologic examinations as part of standard clinical practice.

Comparative Study of the Protective Effects of Citral, Thymoquinone, and Silymarin on Methotrexate-induced Cardiotoxicity in Rats.

Methotrexate (MTX), an immunosuppressant and anti-cancer medication, can harm the heart. The goal of the current investigation was to assess the cardiotoxicity caused by MTX and the potential cardioprotective properties of silymarin, citral, and thymoquinone as antioxidants. Forty-eight rats were divided into six groups, which included control, MTX, cosolvent, citral, thymoquinone, and silymarin groups. At the end of the study, the rats were anesthetized (ketamine and xylazine) and killed using CO2. Their blood samples were collected to measure the enzymatic activities of creatine kinase-myoglobin binding (CK-MB), creatine phosphokinase (CPK), and lactate dehydrogenase (LDH). Also, the heart tissue was sampled to determine the antioxidant capacity and examine the histopathology. The findings revealed that the activity of CPK, CK-MB, and LDH enzymes significantly reduced in the thymoquinone treatment group compared to the MTX group (p < 0.05). On the other hand, total antioxidant capacity was significantly increased in the thymoquinone group compared to the MTX group (p < 0.05). The pathological modifications (i.e. severe congestion, edema fluid, the presence of inflammatory cells around the blood vessels, mild to moderate hemorrhaging between cardiac muscle fibers) were seen in the MTX group. The treatment groups, particularly thymoquinone, did not experience any appreciable pathological changes. The thymoquinone was found to have the strongest protective effect against the heart damage caused by MTX.

Daily Intake of Household-Produced Milk Kefir on Salmonella Typhimurium Infection in C57BL/6 Mice: Mortality, Microbiota Modulation and Immunological Implications.

Salmonellosis, a major global cause of diarrheal diseases, significantly impacts the intestinal microbiome. Probiotic-rich beverages, such as kefir, are increasingly utilized as alternative health-promoting beverages associated with various microbiota benefits. This study investigated the repercussions of daily consumption of household-produced milk kefir on Salmonella enterica serovar Typhimurium infection in C57BL-6 mice. Kefir consumption pre infection reduced the presence of inflammatory cells in the colon and altered the cytokine profile by reducing IL-10 and increasing IFN-γ. Despite reducing intestinal inflammation, kefir intake did not yield a prompt response to an acute infection caused by the aggressive pathogen Salmonella. This contributed to increased mortality in the mice, evidenced by higher fecal Salmonella counts post-infection. Metabarcoding analysis demonstrated that the use of kefir before infection increases butyric acid by the higher abundance of Lachnospiraceae and Prevotellaceae families and genus in feces, coupled with an increase in Muribaculaceae family and Bacteroides genus among infected kefir-treated mice. While kefir hinted at microbiota alterations reducing enterobacteria (Helicobacter), decrease IL-10, and increased IFN-γ, butyric acid on pre-infection, the beverage potentially facilitated the systemic translocation of pathogens, intensifying the infection's severity by altering the immune response. The use of kefir in the dosage of 10% w/v (109 CFU), for acute infections with Salmonella Typhimurium, may not be enough to combat the infection and worsen the prognosis, leaving the intestine less inflamed, favoring the replication and translocation of the pathogen. These findings underscore the importance of prudently evaluating the widespread use of probiotics and probiotic-rich beverages, especially during acute infections, given their potential association with adverse effects during these diseases.

Can Cardiovascular Risk Be Simply Estimated in Nonalcoholic Fatty Liver Disease Patients?

Backgrounds and Aims: In the pathogenesis of nonalcoholic fatty liver disease (NAFLD), inflammation plays a pivotal role. The presence of inflammatory cells is closely linked with epicardial adipose tissue (EAT). A recently identified prognostic indicator for cardiovascular disease (CVD) is the ratio of monocyte count to HDL-cholesterol (MHR). Our primary aim was to investigate the relationship between EAT and markers of inflammation in individuals with NAFLD, and to evaluate its predictability using straightforward diagnostic measures. Material-Method: This retrospective study included two hundred eighteen patients who underwent thoracic computed tomography angiography between 2014 and 2021. The patients were divided into the NAFLD group (HU48 IU) according to the liver attenuation ratio. 136 patients in the NAFLD group and 82 in the non-NAFLD group. Results: The body mass index (BMI), triglyceride levels, notably the EAT volume and MHR in the NAFLD group, exhibited higher values than non-NAFLD group. Among participants in the NAFLD group, a positive correlation was observed between EAT volume and factors such as age, MHR, c-reactive protein, BMI, urea, glucose, and alanine aminotransferase. Through linear regression analysis, it was determined that MHR stood as the sole independent predictor of EAT volume in patients with NAFLD. Conclusion: EAT volume, a risk marker for CVD, can be predicted in NAFLD patients by MHR without radiological methods. Thus, easier and earlier detection of NAFLD patients in the high-risk group for CVD will be possible.

Radiation-induced Testicular Damage in Mice: Protective Effects of Apigenin Revealed by Histopathological Evaluation.

Radiation exposure poses a significant threat to reproductive health, particularly the male reproductive system. The testes, being highly sensitive to radiation, are susceptible to damage that can impair fertility and overall reproductive function. The study aims to investigate the radioprotective effects of apigenin on the testis through histopathological evaluation. This research involved utilizing a total of 40 mice, which were randomly divided into eight groups of five mice each. The groups were categorized as follows: A) negative control group, B, C, and D) administration of apigenin at three different doses (0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg) respectively, E) irradiation group, and F, H, and I) administration of apigenin at three different doses (0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg) in combination with irradiation. The irradiation procedure involved exposing the mice to a 2Gy X-ray throughout their entire bodies. Subsequently, histopathological assessments were conducted seven days after the irradiation process. The findings indicated that radiation exposure significantly impacted the spermatogenesis system. This research provides evidence that administering apigenin to mice before ionizing radiation effectively mitigated the harmful effects on the testes. Apigenin demonstrated radioprotective properties, positively influencing various parameters, including the spermatogenesis process and the presence of inflammatory cells within the tubular spaces. Apigenin can provide effective protection for spermatogenesis, minimize the adverse effects of ionizing radiation, and safeguard normal tissues.

Cardiac Histopathology Alterations Induced by Subchronic Mangosteen Rind Extract in Wistar Rats

Mangosteen (Garcinia mangostana L.) is renowned for its potent antioxidant characteristics, including free radical scavenging, and its antibacterial, antifungal, anti-inflammatory, and antidiabetic properties. This study aims to assess the subchronic toxicity effects of ethanol extract from mangosteen rind on the cardiac histopathology of male and female Wistar rats. This research was a posttest-only control group design. Forty biological specimens from 40 Wistar rats were divided into four groups, a control group, and three treatment groups, which were given ethanol extract of mangosteen rind with doses of 250 mg/kg, 500 mg/kg, and 1,000 mg/kg for 28 days. Cardiac specimens were prepared and examined using hematoxylin-eosin (HE) staining at the Anatomical Pathology Laboratory of Universitas Jenderal Achmad Yani in December 2021. The findings indicated that prolonged ingestion of large amounts of ethanol extract from mangosteen rind can cause toxic effects characterized by an inflammatory response in cardiac tissue. No fibrosis or hypertrophy was detected; however, inflammatory changes such as the presence of inflammatory cells, vacuolar changes, and neovascularization were observed. The inflammation observed might be due to excessive antioxidant administration leading to oxidative stress. Inflammatory cells may trigger fibrotic remodeling in the heart. The difference in the quantity of inflammatory cells between male and female rats suggests that gender influences the inflammatory response. Overall, administration of ethanol extract from mangosteen rind at doses of 250 mg/kg, 500 mg/kg, and 1,000 mg/kg cause subchronic toxicity effects on the heart histopathology of Wistar rats, marked by inflammation.

Cannabinoid receptor-2 agonist AM1241 attenuates myocardial ischemia-reperfusion-induced oxidative stress in rats via Nrf2/HO-1 pathway.

The cannabinoid receptor-2 agonist AM1241 exhibits notable cardioprotective effects against myocardial infarction, positioning it as a promising therapeutic candidate for cardiovascular disease. This study explores AM1241's protective role in myocardial ischemia-reperfusion (IR) injury and its association with the Nrf2/HO-1 pathway. In an established SD rat IR model, AM1241's impact on cardiac injury was assessed through echocardiography, 2,3,5-triphenyl tetrazolium chloride staining, and histological analysis. H9c2 cells underwent hypoxia-reoxygenation, with AM1241's influence on cell viability determined by the CCK-8 assay. Reactive oxygen species (ROS) production was measured using the DCFH-DA assay, and Nrf2 and HO-1 protein expressions were evaluated through immunofluorescence and Western blot. Myocardial ischemia-reperfusion injury (MIRI) increased infarct size, inflammatory cell presence, oxidative and nitrosative stress, impaired cardiac function, and elevated apoptosis rates. AM1241 mitigated these effects, enhancing cell viability, reducing ROS production, and upregulating Nrf2 and HO-1 expression. The antioxidant effect of AM1241 was inhibited by ML385 intervention. AM1241 attenuates oxidative stress, alleviates MIRI, and activates the Nrf2/HO-1 signaling pathway, underscoring its potential as a therapeutic strategy for myocardial ischemia-reperfusion injury.

A novel approach to investigate severe asthma and COPD: the 3d ex vivo respiratory mucosa model

Purpose: This article illustrates the replication of asthma and COPD conditions in a laboratory setting and the potential applications of this methodology. Introduction: Biologic drugs have been shown to enhance the treatment of severe asthma and COPD. Monoclonal antibodies against specific targets have dramatically changed the management of these conditions. Although the inflammatory pathways of asthma and COPD have already been clearly outlined, alternative mechanisms of action remain mostly unexplored. They could provide additional insights into these diseases and their clinical management. Aims: In vivo or in vitro models have thus been developed to test alternative hypotheses. This study describes sophisticated ex vivo models that mimic the response of human respiratory mucosa to disease triggers, aiming to narrow the gap between laboratory studies and clinical practice. Results: These models successfully replicate crucial aspects of these diseases, such as inflammatory cell presence, cytokine production, and changes in tissue structure, offering a dynamic platform for investigating disease processes and evaluating potential treatments, such as monoclonal antibodies. The proposed models have the potential to enhance personalized medicine approaches and patient-specific treatments, helping to advance the understanding and management of respiratory diseases.

Benign prostatic hyperplasia nodules in patients treated with celecoxib and/or finasteride have reduced levels of NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, a mitochondrial protein essential for efficient function of the electron transport chain.

Benign prostatic hyperplasia (BPH) is a condition generally associated with advanced age in men that can be accompanied by bothersome lower urinary tract symptoms (LUTS) including intermittency, weak stream, straining, urgency, frequency, and incomplete bladder voiding. Pharmacotherapies for LUTS/BPH include alpha-blockers, which relax prostatic and urethral smooth muscle and 5ɑ-reductase inhibitors such as finasteride, which can block conversion of testosterone to dihydrotestosterone thereby reducing prostate volume. Celecoxib is acyclooxygenase-2inhibitor that reduces inflammation and has shown some promise in reducing prostatic inflammation and alleviating LUTS for some men with histological BPH. However, finasteride and celecoxib can reduce mitochondrial function in some contexts, potentially impacting their efficacy for alleviating BPH-associated LUTS. To determine the impact of these pharmacotherapies on mitochondrial function in prostate tissues, we performed immunostaining of mitochondrial Complex I (CI) protein NADH dehydrogenase [ubiquinone] iron-sulfur protein 3(NDUFS3) and inflammatory cells on BPH specimens from patients naïve to treatment, or who were treated with celecoxib and/or finasteride for 28 days, as well as prostate tissues from male mice treated with celecoxib or vehicle control for 28 days. Quantification and statistical correlation analyses of immunostaining were performed. NDUFS3 immunostaining was decreased in BPH compared to normal adjacent prostate. Patients treated with celecoxib and/or finasteride had significantly decreased NDUFS3 in both BPH and normal tissues, and no change in inflammatory cell infiltration compared to untreated patients. Mice treated with celecoxib also displayed a significant decrease in NDUFS3 immunostaining and no change in inflammatory cell infiltration. These findings suggest that celecoxib and/or finasteride are associated with an overall decrease in NDUFS3 levels in prostate tissues but do not impact the presence of inflammatory cells, suggesting a decline in mitochondrial CI function in the absence of enhanced inflammation. Given that BPH has recently been associated with increased prostatic mitochondrial dysfunction, celecoxib and/or finasteride may exacerbate existing mitochondrial dysfunction in some BPH patients thereby potentially limiting their overall efficacy in providing metabolic stability and symptom relief.

Effect of ASC Injection in the Inflammatory Reaction in Silicone Implant Capsule: Animal Model.

Capsular contracture is a common complication affecting about 80% of patients who receive radiotherapy after breast reconstruction with silicone prostheses. This study examines the use of adipocyte stem cells (ASCs) to treat capsular contracture. Thirty rats were operated on to implant a minisilicone prosthesis in the dorsal region. The rats were divided into three groups: control (saline solution injection), radiotherapy (RDT), and RDT + ASC. After 3 months, the capsules were collected and submitted to histological analysis for inflammatory cell presence, vascular density, and collagen fibers, and gene expression of Tnf, Il1rap, Il10, Cd68, Mmp3, and Mmp9 by qPCR. In macroscopic analysis, the RTGO score showed a two-point reduction in RDT + ASC compared with the RDT (P = 0.003). In histological analysis, ASC exhibited less than 50% of inflammatory cells compared with RDT (P = 0.004), which was similar to control. This study demonstrated that Il1rap gene expression was identical in both RDT and RTD + ASC. Compared with control, treatment with ASC reduced Il1rap expression by 30%. Cd68 and Mmp3 expression levels were similar in both the control and RTD + ASC. This study suggests that ASC treatment decreases silicone prosthesis capsule inflammation.

Red and melanized focal changes in the white skeletal muscle of farmed rainbow trout Oncorhynchus mykiss.

Fillet discoloration by red and melanized focal changes (RFCs and MFCs) is common in farmed Atlantic salmon Salmo salar. In farmed rainbow trout Oncorhynchus mykiss, similar changes have been noted, but their prevalence and histological characteristics have not been investigated. Thus, we conducted a study encompassing 1293 rainbow trout from 3 different farm sites in Norway, all examined at the time of slaughter. Both macroscopic and histological assessments of the changes were performed. Reverse transcription (RT)-qPCR analyses and in situ hybridization (ISH) were used to detect the presence and location, respectively, of potential viruses. Only 1 RFC was detected in a single fillet, while the prevalence of MFCs ranged from 1.46 to 6.47% between populations. The changes were predominantly localized in the cranioventral region of the fillet. Histological examinations unveiled necrotic myocytes, fibrosis, and regeneration of myocytes. Melano-macrophages were found in the affected areas and in myoseptal adipose tissue. Organized granulomas were observed in only 1 fish. Notably, the presence of inflammatory cells, including melano-macrophages, appeared lower compared to what has been previously documented in Atlantic salmon MFCs. Instead, fibrosis and regeneration dominated. RT-qPCR and ISH revealed the presence of piscine orthoreovirus 1 (PRV-1) and salmonid alphavirus (SAV) in skeletal muscle. However, these viruses were not consistently associated with lesioned areas, contrasting previous findings in Atlantic salmon. In conclusion, rainbow trout develop MFCs of a different character than farmed Atlantic salmon, and we speculate whether the observed pathological differences are contributing to their reduced occurrence in farmed rainbow trout.

Comparison of Stored and Fresh Injectable Acellular Adipose Matrix in Soft Tissue Reconstruction in a Murine Model.

We previously showed comparable volume effects of injections of acellular adipose matrix (AAM), an adipose tissue-derived extracellular matrix, and conventional fat grafting in a murine model. Thus, AAM could be a novel allogenic injectable product. However, its retention rate poses a concern, as repeated AAM injections may be required in some cases. This study investigated the biological properties and therapeutic value of stored AAM and compared them with those of fresh AAM, in a murine model. AAM was manufactured from fresh human abdominoplasty fat. Fresh and stored injectable AAM was prepared within 24 h and 3 months after generation, respectively. Either fresh or stored injectable AAM was injected into the scalp of athymic nude mice (0.2 mL/sample, n = 6 per group). After 8 weeks, graft retention was assessed through weight measurement, and histological analysis was performed, including immunofluorescence staining for CD31 and perilipin. Retention rate was significantly reduced in the stored compared to the fresh injectable AAM group. Nevertheless, histological analysis revealed comparable inflammatory cell presence, with minimal capsule formation, in both groups. Adipogenesis occurred in both groups, with no significant difference in the blood vessel area (%) between groups. Although the volume effects of stored AAM for soft tissue reconstruction were limited compared to those of fresh injectable AAM, stored AAM had similar capacity for adipogenesis and angiogenesis. This promising allogeneic injectable holds the potential to serve as an effective "off-the-shelf" alternative for repeated use within a 3-month storage period. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://link.springer.com/journal/00266 .

Piracetam mitigates nephrotoxicity induced by cisplatin via the AMPK-mediated PI3K/Akt and MAPK/JNK/ERK signaling pathways

AimsCisplatin (CDDP) is commonly employed as an antineoplastic agent, but its use is significantly limited by the occurrence of dose-dependent nephrotoxicity, the detailed mechanisms of which remain unclear. This research is aimed to explore the molecular mechanisms of Piracetam (PIR)’s protective effects on nephrotoxicity resulting from CDDP exposure and to elucidate the mechanisms responsible for these effects. Main methodsPIR was given in dosages of 100 and 300 mg/kg body weight for a duration of 15 days; concurrently, on the last day, a single 10 mg/kg dose of CDDP was delivered via intraperitoneal injection. Forty-eight hours post-CDDP injection, the animals were sacrificed to assess nephrotoxicity. Blood samples and renal tissues were taken for biochemical and histopathological investigations. Serum creatinine and blood urea nitrogen (BUN) were measured. AMP-activated protein kinase (AMPK), caspase-9 and nuclear factor kappa b p65 (NF-κB p65) were assessed by immunohistochemistry method. Enzyme-linked immunosorbent assay (ELISA) analysis was employed to determine cytochrome c (Cyt. c), Bcl-2-associated X-protein (BAX), caspase-3, nuclear factor erythroid 2–related factor 2 (Nrf2), Heme oxygenase-1 (HO-1), superoxide dismutase (SOD), tumor necrosis factor alpha (TNF-α), myeloperoxidase (MPO), and interleukin-1β (IL-1β) levels in renal tissue homogenates. The mRNA levels of tumor protein P53 (TP53), phosphatidylinositol-3 kinase (PI3K), protein kinase B (Akt), p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinases (ERK), and c-Jun N-terminal kinases (JNK) were tested by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, histopathological evaluations of the renal tissues and the binding affinity of PIR to AMPK by molecular docking were also performed. Key findingsPre-treatment with PIR enhanced renal function markers such as urea and creatinine, mitigated histological damage, and diminished inflammatory cell presence in renal tubules. PIR demonstrated antioxidant effects by reestablishing the equilibrium between pro-oxidants and antioxidants such as MPO, HO-1, Nrf2, as well as SOD. Furthermore, PIR inhibited the inflammatory pathways through the MAPK/NF-κB pathway. Additionally, PIR counteracted the CDDP-induced decline in PI3K/Akt activity and hindered caspase-dependent apoptotic processes. SignificanceIn summary, PIR appears to be an effective therapeutic strategy for reducing CDDP-induced nephrotoxicity, attributed to its antioxidant, anti-inflammatory, and antiapoptotic mechanisms. Consequently, PIR may serve as a complementary treatment alongside CDDP to alleviate nephrotoxicity associated with CDDP.

Dynamic Release from Acetalated Dextran Nanoparticles for Precision Therapy of Inflammation.

Polymer-based nanoparticles (NPs) that react to altered physiological characteristics have the potential to enhance the delivery of therapeutics to a specific area. These materials can utilize biochemical triggers, such as low pH, which is prone to happen locally in an inflammatory microenvironment due to increased cellular activity. This reduced pH is neutralized when inflammation subsides. For precise delivery of therapeutics to match this dynamic reaction, drug delivery systems (DDS) need to not only release the drug (ON) but also stop the release (OFF) autonomously. In this study, we use a systematic approach to optimize the composition of acetalated dextran (AcDex) NPs to start (ON) and stop (OFF) releasing model cargo, depending on local pH changes. By mixing ratios of AcDex polymers (mixed NPs), we achieved a highly sensitive material that was able to rapidly release cargo when going from pH 7.4 to pH 6.0. At the same time, the mix also offered a stable composition that enabled a rapid ON/OFF/ON/OFF switching within this narrow pH range in only 90 min. These mixed NPs were also sensitive to biological pH changes, with increased release in the presence of inflammatory cells compared to healthy cells. Such precise and controllable characteristics of a DDS position mixed NPs as a potential treatment platform to inhibit disease flare-ups, reducing both systemic and local side effects to offer a superior treatment option for inflammation compared to conventional systems.

Effects of slit lamp-delivered retinal laser photobiomodulation in a rat model of choroidal neovascularization

Neovascular age-related macular degeneration, also known as exudative or wet age-related macular degeneration, is the leading cause of blindness in the developed world. Photobiomodulation has the potential to target the up-stream hypoxic and pro-inflammatory drivers of choroidal neovascularization. This study investigated whether photobiomodulation attenuates characteristic pathological features of choroidal neovascularization in a rodent model.Experimental choroidal neovascularization was induced in Brown Norway rats with laser photocoagulation. A custom-designed, slit-lamp-mounted, 670 nm laser was used to administer retinal photobiomodulation every 3 days, beginning 6 days prior to choroidal neovascularization induction and continuing until the animals were killed 14 days later. The effect of photobiomodulation on the size of choroidal neovascular membranes was determined using isolectin-B4 immunohistochemistry and spectral domain-optical coherence tomography. Vascular leakage was determined with fluorescein angiography. The effect of treatment on levels of vascular endothelial growth factor expression was quantified with enzyme-linked immunosorbent assay.Treatment with photobiomodulation was associated with choroidal neovascular membranes that were smaller, had less fluorescein leakage, and a diminished presence of inflammatory cells as compared to sham eyes. These effects were not associated with a statistically significant difference in the level of vascular endothelial growth factor when compared to sham eyes.The data shown herein indicate that photobiomodulation attenuates pathological features of choroidal neovascularization in a rodent model by mechanisms that may be independent of vascular endothelial growth factor.

Intranasal Glioma with Post-Endoscopic Resection in 1 Year Old Infant: Case Report and Literature Review*

Abstract Introduction Nasal gliomas - or nasal glial heterotopias - are rare congenital malformations, which correspond to 5% of the congenital nasal masses. It is a mass composed of mature glial tissue that can be located outside, inside or near the nasal region, and may or may not be connected to the brain by a fibrous pedicle. This report addresses a case of nasal glioma that suffered recurrence after endoscopic treatment. Case Report A 1-year-old boy has, since birth, a mass inside the left nostril, which obstructs and widens the bridge of the nose. Upon physical examination, it is observed that the mass does not increase in size with crying and presents negative transluminescence and Furstenberg test. Upon being biopsied, the lesion reveals malignancy and the presence of inflammatory cells. MRI ruled out communication with intracranial structures. The endoscopic resection of the heterotopia removed a mass of 3,0 × 2,5 × 1,7 cm, whose histological and immunohistochemical analysis revealed glial pattern cell proliferation in the nasal mucosa. Conclusion Considering that nasal glial heterotopy is frequently present at birth, and that newborns breathe predominantly through this route, early diagnosis of the lesion is of great importance, as it can cause signs and symptoms of respiratory distress. In addition, it is worth noting that the early approach also prevents bone deformities.

Клиническая оценка частоты и нозологической структуры патологии заднего отрезка глаза

Purpose. Clinical assessment of frequency and nosological structure of the posterior eye segment’s pathology. Material and methods. Using a continuous sampling method, 235 patients with posterior eye segment’s pathology were selected, who underwent examinations and courses of treatment in our clinic in the period from 2021 to 2023. Results. In 47 patients with uveitis, the presence of concomitant diseases was revealed: ankylosing spondylitis, rheumatoid arthritis, and toxoplasmosis. Biomicroscopy of the posterior eye segment of patients with posterior uveitis revealed the presence of inflammatory cells and protein in the vitreous cavity, grayish-yellow prominence foci in the macular zone of various sizes and configurations, hyperemia of the optic disc (OD), and newly formed vessels on OD in 5 patients, macular edema. In 45 patients with anterior ischemic optic neuropathy (AION), the following concomitant diseases were identified: coronary heart disease in 22 people (49 %), hypertension in 20 people (44 %), sickle cell anemia in 2 people (4.5 %), giant cell arteritis in 1 person (2.5 %). Conclusions. 1. The structure of the posterior eye segment’s pathology of patients undergoing treatment in the conservative treatment department included uveitis of various localizations and AION. 2. In almost 93 % of patients with AION, the presence of concomitant diseases of the cardiovascular system is confirmed, which corresponds to literature data. Keywords: posterior eye segment’s pathology, uveitis, anterior ischemic optic neuropathy

Effect of Injectable Acellular Adipose Matrix on Soft Tissue Reconstruction in a Murine Model

BackgroundThe extracellular matrix isolated from adipose tissue, known as acellular adipose matrix (AAM), represents a novel biomaterial. AAM functions as a scaffold that not only supports stem cell proliferation and differentiation but also induces adipogenesis and angiogenesis. This study aims to investigate the volumetric effects and microenvironmental changes associated with injectable AAM in comparison to conventional fat grafting.MethodsAAM was manufactured from fresh human abdominoplasty fat using a mechanically modified method and then transformed into an injectable form. Lipoaspirate was harvested employing the Coleman technique. A weight and volume study was conducted on athymic nude mice by injecting either injectable AAM or lipoaspirate into the scalp (n=6 per group). After eight weeks, graft retention was assessed through weight measurement and volumetric analysis using micro-computed tomography (micro-CT) scanning. Histological analysis was performed using immunofluorescence staining for perilipin and CD31.ResultsInjectable AAM exhibited similar weight and volume effects in murine models. Histological analysis revealed comparable inflammatory cell presence with minimal capsule formation when compared to conventional fat grafts. Adipogenesis occurred in both AAM-injected and conventional fat graft models, with no significant difference in the blood vessel area (%) between the two.ConclusionsIn summary, injectable AAM demonstrates effectiveness comparable to conventional fat grafting concerning volume effects and tissue regeneration in soft tissue reconstruction. This promising allogeneic injectable holds the potential to serve as a safe and effective “Off-the-Shelf” alternative in both aesthetic and reconstructive clinical practices.No Level AssignedThis journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Avenanthramide and β-Glucan Therapeutics Accelerate Wound Healing Via Distinct and Nonoverlapping Mechanisms.

Objective: Given the significant economic, health care, and personal burden of acute and chronic wounds, we investigated the dose dependent wound healing mechanisms of two Avena sativa derived compounds: avenanthramide (AVN) and β-Glucan. Approach: We utilized a splinted excisional wound model that mimics human-like wound healing and performed subcutaneous AVN and β-Glucan injections in 15-week-old C57BL/6 mice. Histologic and immunohistochemical analysis was performed on the explanted scar tissue to assess changes in collagen architecture and cellular responses. Results: AVN and β-Glucan treatment provided therapeutic benefits at a 1% dose by weight in a phosphate-buffered saline vehicle, including accelerated healing time, beneficial cellular recruitment, and improved tissue architecture of healed scars. One percent AVN treatment promoted an extracellular matrix (ECM) architecture similar to unwounded skin, with shorter, more randomly aligned collagen fibers and reduced inflammatory cell presence in the healed tissue. One percent β-Glucan treatment promoted a tissue architecture characterized by long, thick bundles of collagen with increased blood vessel density. Innovation: AVN and β-Glucan have previously shown promise in promoting wound healing, although the therapeutic efficacies and mechanisms of these bioactive compounds remain incompletely understood. Furthermore, the healed ECM architecture of these wounds has not been characterized. Conclusions: AVN and β-Glucan accelerated wound closure compared to controls through distinct mechanisms. AVN-treated scars displayed a more regenerative tissue architecture with reduced inflammatory cell recruitment, while β-Glucan demonstrated increased angiogenesis with more highly aligned tissue architecture more indicative of fibrosis. A deeper understanding of the mechanisms driving healing in these two naturally derived therapeutics will be important for translation to human use.