Histological Examination Research Articles

SPLASH: Split-Body Randomized Clinical Trial of Poly-l-Lactic Acid for Adipogenesis and Volumization of the Hip Dell.

Injectable poly-l-lactic acid (PLLA-SCA) increases extracellular matrix to improve skin quality. The hip dell is an underappreciated element of gluteal aesthetics. Adipose tissue has roles in aesthetics and skin functioning. To investigate the efficacy of PLLA-SCA treatment to induce adipogenesis and volumize the hip dell. This was a double-blinded, split-body trial of 15 women with hip dell volume deficits. Each subject was randomized to have 1 hip dell treated with 150 mg of PLLA-SCA while the contralateral hip dell received the equivalent volume of saline. Subjects received 3 treatments at 1-month intervals and were followed for 9 months. Assessments included physician global aesthetic improvement scale, ultrasonography, and histologic examination. Blinded investigators rated PLLA-SCA-treated hip dells as improved and much improved. The dermis and adipose layers increased in thickness by 26.1% and 27%. These measures, in addition to collagen and elastic fiber quality, were significantly improved compared with saline-treated hip dells, which did not change from baseline. Subject satisfaction was also significantly greater on the PLLA-SCA-treated side. No subject experienced significant adverse effects. Poly-l-lactic acid is a safe and effective method for durable volumization and aesthetic improvement of the hip dell. PLLA-SCA may promote adipogenesis and elastogenesis.

Therapeutic Effects of Pterocarpus santalinoides Stem Bark Aqueous Extract: Evidence from L-NAME-induced Hypertensive Wistar Rats

Aims: Ethnopharmacological information indicates that the stem bark of Pterocarpus santalinoides is used in traditional medicine to treat many diseases including hypertension. Thus, this study was designed to evaluate the therapeutic effects of the stem bark aqueous extract of Pterocarpus santalinoides (AEPS) in L-NAME-induced hypertensive rats (LNHR). Methodology: Hypertension was induced in normotensive rats by intraperitoneal administration of L-NAME (25 mg/kg/day) for 42 days. Forty-two animals were divided into two main groups: one group of seven rats (group 1) receiving distilled water (10 mL/kg) and another thirty-five rats receiving L-NAME (group 2). After three weeks of treatment, the hypertensive animals (group 2) were divided into five groups of seven rats each. Animals of the first group received distilled water, those of the second group were treated with captopril (20 mg/kg), and the three last groups received the AEPS (50, 100, and 200 mg/kg). These rats were daily treated per os with the above substances for three weeks. At the end of the experimental period (42 days), animals were anesthetized and the blood pressure and heart rate were recorded by invasive method. Afterward, the blood, aorta, and heart of each rat were collected for some biochemical and/or histological examination. Results: L-NAME administration induced hypertension, as associated with left ventricular hypertrophy, dyslipidemia, oxidative stress, hepatic and renal dysfunctions. Aqueous extract administration significantly improved all these metabolic disorders induced by L-NAME. Furthermore, the remodeling of the aortic media after NO deficiency-induced L-NAME has also been improved by Pterocarpus santalinoides aqueous extract. The therapeutic effect of AEPS against L-NAME-induced hypertension could probably be due to its antihypertensive, hypolipidemic, and antioxidant properties. Conclusion: Current results confirmed the empirical use of Pterocarpus santalinoides stem bark for the treatment of hypertension in traditional medicine.

Exploring the Role of Gut Vascular Barrier Proteins in HIV-Induced Mucosal Damage: A Comparative Study.

This study aims to compare intestinal mucosal damage and the expression levels of occludin, zonula occludens-1 (ZO-1), vascular endothelial (VE)-cadherin, β-catenin, and plasmalemma vesicle-associated protein (PLVAP) in the gut vascular barrier (GVB) among people living with HIV (PLWH), asymptomatic PLWH, and healthy volunteers (non-PLWH). Three groups were selected for the study: PLWH, asymptomatic PLWH, and healthy volunteers. Colonic mucosal tissue samples were collected via colonoscopy from all participants. Histological examination of the colonic mucosa was conducted using hematoxylin and eosin staining. The expression levels of occludin, ZO-1, VE-cadherin, β-catenin, and PLVAP were assessed using RT-qPCR, immunohistochemistry, and western blot analyses. Pathological scores of colonic mucosa in PLWH and asymptomatic PLWH were significantly higher than those in non-PLWH (p < .001 and p = .0056, respectively). CD4+ T cell counts in asymptomatic PLWH and non-PLWH were significantly higher than in PLWH (p < 0.05). The CD4+/CD8+ T cell ratio in non-PLWH significantly exceeded those in PLWH and asymptomatic PLWH (p < .05). Analysis of protein and mRNA expression revealed: (1) no statistically significant differences in PLVAP-mRNA expression across all groups (p > .05); (2) higher PLVAP protein levels in PLWH compared with asymptomatic PLWH and non-PLWH (p < .05), with no significant differences between asymptomatic PLWH and non-PLWH (p = .632); (3) significantly higher PLVAP expression in the colonic mucosa of PLWH and asymptomatic PLWH compared with non-PLWH (p = .034 and p = .011, respectively), with no significant differences between PLWH and asymptomatic PLWH (p > .999). ZO-1 expression was significantly lower in PLWH than in non-PLWH (p = .012), with no notable differences between asymptomatic PLWH and other groups. PLWH, compared with healthy controls, exhibit significant inflammatory changes in the intestinal mucosa. PLVAP expression serves as a potential indicator to assess the extent of GVB damage and disease progression in PLWH.

The ameliorative potential of platelet-rich plasma and exosome on renal ischemia/reperfusion-induced uremic encephalopathy in rats.

Uremic Encephalopathy results from the elevation of toxins and blood-brain barrier (BBB) disruption. Renal Ischemia/Reperfusion (I/R) injury is the principal cause of acute kidney injury and brain tissue injury. The present study was crafted to estimate the restorative impact of platelet-rich plasma (PRP) and exosome injection before the reperfusion phase on the kidney following renal I/R injury and its influence on brain tissue by tracking the histopathological, biochemical, and Doppler ultrasonography alternations in both kidney and brain tissue. Forty mature male rats were divided into five groups as follows: control, I/R, PRP, exosome, and Exosome + PRP. Renal Doppler ultrasonography was traced for all rats. Serum kidney functions and acetylcholine esterase enzyme (AchE) were evaluated. Both Gamma-aminobutyric acid (GABA) and glutamate were assessed in brain tissues. The oxidative stress (malondialdehyde), anti-oxidative (glutathione and catalase), and pro-inflammatory (Tumor necrosis factor- α and interleukin-6) markers were estimated in renal tissues. Additionally, morphometric histological examination was performed in both renal and brain tissues. Both PRP and exosome-received rats exhibited a significant improvement in both serum kidney functions and AchE compared to I/R rats. There was a 3.39-fold increase in GABA and a 2.27-fold decrease in glutamate levels in the brain tissue of PRP rats compared to the I/R rats. A significant elevation (P ≤ 0.0001) of glutathione and catalase besides a significant reduction in the expression of TNF-α and IL-6 was observed in renal tissue compared to I/R rats. A significant severe reduction (P < 0.0001) in the number of Purkinje cells, pyramidal cells in the cerebellar cortex, and the CA1 region in the hippocampus was observed in I/R rats which was significantly alleviated by both PRP and exosome. Furthermore, there was a significant improvement in Doppler parameters. PRP exerted a significant superior impact on the restoration of kidney functions and repairing uremic-induced damage in brain tissue.

Classification of salivary gland biopsies in Sjögren's syndrome by a convolutional neural network using an auto-machine learning platform.

The histopathological analysis of minor salivary gland biopsies, particularly through the quantification of the Focus Score (FS), is pivotal in the diagnostic workflow for Sjögren's Syndrome (SS). AI-based image recognition using deep learning models has demonstrated potential in enhancing diagnostic accuracy and efficiency in preclinical research. The primary aim of this investigation was to utilize an auto-machine learning (autoML) platform for the automated segmentation and quantification of FS on histopathological slides, aiming to augment diagnostic precision and speed in SS. A cohort comprising 86 patients with sicca syndrome (37 diagnosed with SS based on the 2016 ACR/EULAR Classification Criteria and 49 non-SS) was selected for an in-depth histological examination. A repository of 172 slides (two per patient) was assembled, encompassing 74 slides meeting the classificatory thresholds for SS (FS ≥ 1, indicative of lymphocytic infiltration) and 98 slides showcasing normal salivary gland histology. The autoML platform utilized (Giotto, L2F, Lausanne Switzerland) employed a Convolutional Neural Network (CNN) architecture (ResNet-152) for the training and validation phases, using a dataset of 172 slides. The developed model exhibited a reliability score of 0.88, proficiently distinguishing SS cases, with a sensitivity of 89.47% (95% CI: 66.86% to 98.70%) and a specificity of 88.24% (95% CI: 63.56% to 98.54%). The model found histological slides of suboptimal quality (e.g., those compromised during fixation or staining processes) to be the most challenging for accurate classification. AutoML platforms offer a rapid and flexible approach to developing machine learning models, even with smaller datasets, as demonstrated in this study for SS. These platforms hold significant potential for enhancing diagnostic precision and efficiency in both clinical and research settings. Multicentric studies with larger patient cohorts are essential for thorough evaluation and validation of this innovative diagnostic approach.

Three-dimensional semiquantitative evaluation of reactive emphysema in magnesium implant models

Background Magnesium alloys have great potentials as bioabsorbable implants, whereas the difficulty in evaluating hydrogen gas produced in the degradation process has hindered their research and development. In this study, we investigated the possibility of industrial microfocus X-ray computed tomography (micro-CT) for the precise evaluation of subcutaneous emphysematous changes in a rabbit implantation model. Methods Magnesium plates with/without porous venting were implanted under skin defects on the backs of rabbits. The graft sites were examined by industrial micro-CT after sacrificing. The captured images were reconstructed three-dimensionally for volumetric analyses. The tissues of the graft site were also examined in the traditional histological investigation. Results We were able to image and numerate the shape and volume of subcutaneous emphysema using industrial micro-CT. The volume of emphysema was suppressed by pores punched in samples, and this trend increased as the number of pores increased. In the traditional histological examination, inflammatory changes were observed, but the emphysema could not be measured quantitatively. Conclusions Industrial micro-CT imaging makes it possible to visualize and evaluate magnesium-induced subcutaneous emphysema in animal experiment. This cross-border technology has the potential to be widely applied to other life science fields.

What can be observed in intervertebral cartilage endplate with aging? An animal model study of excessive axial mechanical loading

IntroductionThe cartilage endplate (CEP) plays a crucial role as both a mechanical barrier and nutrient channel for the intervertebral disc, but it is vulnerable to excessive axial loading. We modified the Ilizarov external fixator and applied it to the CEP of the rat tail to impose diurnal, controllable excess axial loading. The objective was to measure morphological changes in the CEP when subjected to loading during the aging process.MethodsTwo Kirschner wires were, respectively, inserted into the center of the eighth and ninth coccygeal vertebrae (Co8/9) of rat (n = 54) to apply axial loading to the CEP. A remote control device was used to establish the diurnal loading schedule. At the end of 4, 8, and 12-week periods, the Co8/9 CEPs in each group were analyzed using MRI, histological staining, and immunohistochemical staining techniques.ResultsThe novel Ilizarov model that we modified successfully induced degeneration of the rat coccygeal CEP. MRI analysis revealed significant degenerative changes in the loaded Co8/9 CEP, including decreased signal intensity and the formation of Schmorl’s nodes at 8 and 12 weeks. Histological examination showed progressive CEP degeneration (CEPD), characterized by decreased microporosity, thinning, and structural irregularities. Immunohistochemical analysis demonstrated a significant reduction in Aggrecan and Collagen II expression in the CEP and nucleus pulposus over time. Control and sham groups maintained normal CEP structure and composition throughout the study period.ConclusionExcessive axial loading induced CEPD in the rat tail, primarily characterized by the formation of Schmorl’s nodes and a reduction in CEP microporosity in this study. Our modified Ilizarov rat tail compression model, featuring stable and controllable axial loading capabilities, provided an alternative experimental paradigm for further investigation into CEPD.

Pathological Changes and CYP1A1 Expression as Biomarkers of Pollution in Sarpa Salpa and Diplodus Sargus

In a marine ecosystem, the most sensitive organisms to environmental changes, mainly to anthropic pressures, are fishes and invertebrates. Therefore, they are considered the ideal targets to indirectly evaluate the health of an entire ecosystem. Teleost fishes, particularly those that occupy the highest trophic levels, can accumulate toxic substances through their diet. In this study, we used two fish species with sedentary behavior and trophic habits, Diplodus sargus and Sarpa salpa, caught in two areas at different anthropic pressures divided into the Gulf of Naples (Na) and the Gulf of Salerno (Sa). This study aimed to correlate the pathological alterations in target organs in both species with known concentrations of polychlorinated biphenyls (PCBs) and heavy metals (lead and cadmium) to the expression of CYP1A1. Histological examination took into consideration circulatory disorders, increase in melanomacrophages (MMs) number, inflammation in kidney and hepatopancreas and gonadal stage maturation. Next, the pathological and morphological changes found were compared to immunohistochemical expression of CYP1A1 in the same samples. Chemical analysis of PCBs, based on 28, 52, 101, 138, 153, and 180 congeners, and heavy metals, were performed on hepatopancreas and muscle samples. Higher median values of PCBs concentration were detected in both species in the Salerno area (8.1 ng/g in Diplodus sargus muscles and 51.1 ng/g in Sarpa salpa hepatopancreas, respectively), although the values were consistently below the legal limits. No critical values were found for lead and cadmium. Therefore, we hypothesized that CYP1A1 and pathological alterations were more expressed in fish from Salerno area. The pathological changes showed a statistically significant difference in inflammation of the kidneys (p &lt; 0.0001) between S. salpa of both Gulfs. In addition, we found a statistically significant difference in the assessment of the increase in MMs/MMCs (p = 0.0384) and circulation disorders (p = 0.0325) of hepatopancreas in D. sargus of both Gulfs. As not all the variables considered showed statistical significance, the analysis of the results does not fully support the correlation between the highest levels of contaminants found in the Salerno area and the expression of CYP1A1. Our data could be a starting point for future studies to better correlate the role of CYP1A1 to pollutants, considering this is the first study involving two of the most common species in the Mediterranean Sea. Thus, future studies could include other species to improve and increase records.

Cardioprotective effects of liposomal resveratrol in diabetic rats: unveiling antioxidant and anti-inflammatory benefits

ABSTRACT As a consequence of chronic hyperglycemia, diabetes complications and tissue damage are exacerbated. There is evidence that natural phytochemicals, including resveratrol, a bioactive polyphenol, may be able to reduce oxidative stress and improve insulin sensitivity. However, resveratrol's limited bioavailability hampers its therapeutic effectiveness. By using liposomes, resveratrol may be better delivered into the body and be more bioavailable. The objective of this study was to assess the cardioprotective potential of liposome-encapsulated resveratrol (LR) in a streptozotocin-induced (STZ) diabetic rat model. Adult male Wistar rats were categorized into five groups: control, diabetic, resveratrol-treated (40 mg/kg), liposomal resveratrol (LR)-treated (20 mg/kg) and liposomal resveratrol (LR)-treated (40 mg/kg) for a five-week study period. We compared the effects of LR to those of resveratrol (40 mg/kg) on various parameters, including serum levels of cardiac markers, tissue levels of pro-inflammatory cytokines, nuclear transcription factor, oxidative stress markers, and apoptotic markers. LR treatment in STZ-diabetic rats resulted in notable physiological improvements, including blood glucose regulation, inflammation reduction, oxidative stress mitigation, and apoptosis inhibition. LR effectively lowered oxidative stress and enhanced cardiovascular function. It also demonstrated a remarkable ability to suppress NF-kB-mediated inflammation by inhibiting the pro-inflammatory cytokines TNF-α and IL-6. Additionally, LR restored the antioxidant enzymes, catalase and glutathione peroxidase, thereby effectively counteracting oxidative stress. Notably, LR modulated apoptotic regulators, including caspase, Bcl2, and Bax, suggesting a role in regulating programmed cell death. These biochemical alterations were consistent with improved structural integrity of cardiac tissue as revealed by histological examination. In comparison, resveratrol exhibited lower efficacy at an equivalent dosage. Liposomal resveratrol shows promise in alleviating hyperglycemia-induced cardiac damage in diabetes. Further research is warranted to explore its potential as a therapeutic agent for diabetic cardiovascular complications and possible cardioprotective effects.

A unique presentation of trigeminal neuralgia related to a central nervous tissue choristoma along the trigeminal nerve root: illustrative case.

Trigeminal neuralgia (TNa), or tic douloureux, is characterized by severe facial pain triggered by everyday activities. Recurring and intense TNa pain results from localized demyelination within the affected nerve segment. The primary cause of TNa is typically vascular compression, with the superior cerebellar artery being the most common vessel. Tumors, multiple sclerosis, and infectious diseases such as herpes are less frequent causes of TNa. The authors present a unique case in which TNa was caused by an aberrant mass resembling a schwannoma during surgery. However, histological examination revealed heterotopic benign central nervous neurons and myelinated axons, which could represent a choristoma in the cisternal segment of the portio major of the trigeminal nerve. Following surgery, the patient's TNa was completely resolved. To the best of the authors' knowledge, this is the first documented case of a central nervous tissue choristoma causing TNa and responding positively to surgical intervention, aside from one previous report that did not specifically use the term "choristoma" in identifying the lesion. This case highlights the challenges involved in diagnosing and managing a rare TNa presentation, with a particular focus on pathology findings. It underscores the potential role of surgery for patients whose condition is resistant to medical intervention. https://thejns.org/doi/10.3171/CASE24384.

A case of indeterminate cell histiocytosis with ETV3-NCOA2 translocation.

Indeterminate cell histiocytosis (ICH) is a rare histiocytic disorder characterized by a proliferation of CD1a+ and CD207/langerin- cells. Recent molecular analyses have identified ETV3-NCOA2 translocation as a possible aetiopathogenesis of ICH. Herein, we describe the first Japanese case of ICH with ETV3-NCOA2 translocation. A 79-year-old Japanese man presented with a 1-year history of pruritic erythematous papules and nodules on his trunk and extremities. Histological examination revealed a dense and diffuse sheets-like infiltration of medium-sized histiocyte-like cells from the epidermis to the deep dermis. Immunohistochemically, the atypical cells were positive for CD1a but negative for CD207/langerin. Fluorescence insitu hybridization using NCOA2 break-apart probes confirmed a chromosomal break occurring on NCOA2 monoallele in the tumor cells. Furthermore, ETV3 exon 4-NCOA2 exon 14 translocation was identified in formalin-fixed paraffin-embedded skin samples using reverse transcription polymerase chain reaction and subsequent direct DNA sequencing. He also presented with interspersed eczematous plaques on his trunk and reactive dermatopathic lymphoadenopathy without any infiltration of ICH. He was treated with topical corticosteroids and narrowband UVB phototherapy. Four months later, his ICH skin eruptions, eczematous plaques, and lymphoadenopathy gradually regressed. Our case supports the notion that the detection of ETV3-NCOA2 translocation can be useful for diagnosis of ICH.

Pathomorphological examination of specimen after vacuum-assisted biopsy in patients with breast cancer after neoadjuvant systemic therapy

Introduction. Vacuum-assisted biopsy (VAB) of the tumor bed in the breast has shown promising results as a minimally invasive method for determining pCR. A significant disadvantage of VAB is the fragmentation of the obtained material and the lack of methods for determining generally accepted predictive and prognostic factors.The objective was to provide a description of the accumulated experience of histological examination of specimens obtained using VAB in patients with breast cancer after neoadjuvant systemic therapy.Methods and materials. A single-center, prospective, non-randomized study included patients with unifocal breast cancer (cT1–2N0–1M0). Patients who achieved a complete clinical response (cCR) underwent VAB. Based on the results of histological examination, patients without signs of residual tumor (pCR, ypT0N0) did not undergo further surgical intervention. When residual tumor cells (ypTisN0-1, ypT1-2N0-1) were detected, standard breast surgery was performed.Results. 35 patients with a mean age of 48.3 (31–67) years were included in the analysis. The examination of VAB samples showed that 11 (31.4 %) patients had a residual tumor, and in 24 (68.6 %) patients, no tumor cells were detected (ypT0N0). According to the Miller-Payne system, 28 patients had a complete pathological response, which corresponds to Miller-Payne=5 and pathological stage ypT0/ypTis (24 patients ypT0N0, 3 patients ypTisN0 and 1 patient ypT0N1). In 3 patients with residual invasive tumor, the tumor response according to the Miller-Payne scale corresponded to grade 3. There was a statistically significant correlation between presence of residual tumor cells in the outer counter after VAB and presence of residual tumor cells in the postoperative histology after standard surgery (Х2 p=0.01, Fisher exact test p=0.048). In addition, there was a statistically significant correlation between hormone receptor status and the degree of tumor response when evaluated using the Pearson criterion (p=0.046). We observed the smallest discordance between the data of the control examination and the data of the histological conclusion when interpreting the results of mammolymphoscintigraphy (25 %) and if 3 out of 3 studies described a complete clinical regression (16.7%).Conclusions. The method used to evaluate histological material allows to obtain predictive and prognostic information necessary to clarify further treatment tactics in accordance with modern standards. It is necessary to conduct more largescale studies in this area to answer the question if this method can be used in routine clinical practice.

Ultrasound-guided percutaneous biopsy for challenging perihilar focal liver lesions: diagnostic accuracy and safety assessment.

In cases of perihilar focal liver lesions, distinguishing between benign strictures and malignancies is critical to prevent unnecessary surgery. Although the use of contrast-enhanced CT or MRI in combination with clinical and laboratory findings can aid in diagnosis, histologic examination is often necessary. Histologic specimens can be obtained through various techniques, including ERCP-guided brush cytology or intraductal biopsy, cholangioscopy-directed biopsy or endoscopic ultrasound (EUS). However, these methods have been associated with suboptimal sensitivity and specificity, sometimes leading to inconclusive results. Therefore, ultrasound-guided percutaneous biopsy (US-guided PB) may play a crucial role, but data is lacking for perihilar lesions. The objective of our study was to assess the technical feasibility and safety of US-guided PB for perihilar lesions. We included 20 consecutive patients who underwent US-guided PB of perihilar liver lesions that were not suitable for surgery between June 2018 and October 2023. All samples were obtained using a Menghini needle 20G and were adequate for histological examination, with a mean diameter of 12.3 mm (range 3-40 mm). Out of the 20 patients, 11 were diagnosed with malignancy while the remaining 9 had inflammatory or fibrotic tissue samples. No adverse events related to the procedure were reported. US-guided PB of perihilar liver lesions is a valuable and safe diagnostic approach to consider for patients who are not suitable for surgery.

Comparative histological assessment of the effect of retinol palmitate preparations on aging skin

Background: Most often, the natural form of vitamin A (retinol palmitate) is used to prevent skin aging. There are two topical drugs on the Russian market that contain a high concentration of retinоl palmitate. This is the ointment "Videstim", which contains 0.5% retinol palmitate and ointment "RadevitАctive", which in addition to 1% retinol palmitate also includes cholecalciferol (0.005%) and tocopherol acetate (0.5%). The specific effects of these drugs on the structure of aging skin have not yet been fully studied. Aims: Comparative histological assessment of the effects of "Videstim" ointment and "RadevitАctive" ointmenton the epidermis and dermis of woman aged 40-55 years old. Materials and methods: The clinical study included 18 women aged 40 to 55 years old. Group I included 6 women who used "Videstim" ointment 2 times a day on the skin of the face. Group II consisted of 6 women who used "RadevitАctive" ointment 2 times a day on the skin of the face. Group III consisted of 6 women and was an intact comparison group. The observation period is 90 days. Patients underwent a punch biopsy with with histological examination of the skin before and after 90 days of using of the aforementioned drugs. Results: According to the results of the study, it was revealed that "Videstim" and "RadevitАctive" ointments they have a stimulating effect on the proliferation of keratinocytes of the epidermis, which manifested itself in an in increasing the number of rows of cells of the prickly layer. In addition, under the action of these drugs, the synthetic activity of keratinocytes of the granular layer increases, which contributes to the proper formation of the stratum corneum of the epidermis.. The use of ointments leads to a significant increase in the thickness of both the granular and prickly layers of the epidermis and the dermis. Conclusions: Ointments with a high concentration of retinol palmitate improve the structure of aging skin.

Impact of aortic and pulmonary artery wall histology on radicular dilatation during the Ross procedure

ObjectiveIn our study, we aim to explore the structural differences between the aortic root and the pulmonary artery to better understand the process of pulmonary autograft dilatation during the Ross procedure.Materials and methodsWe studied twenty human fetuses (aged 14–36 weeks of gestation) and four adults (one female and three males, aged 30–45 years, mean age = 37 ± 16 years). Samples of aortic root and pulmonary artery were obtained through dissection. Histological examinations, including hematoxylin–eosin, Masson’s trichrome, and orcein staining, as well as immunohistochemical technique with caldesmon staining, were performed. Microscopic counting was conducted to assess the number of elastic laminae and smooth muscle cells in each arterial wall. Statistical analyses were performed using R software. Means and standard deviations were used to present central tendencies and data dispersion for elastic laminae and smooth muscle.ResultsSignificant histological differences were observed between the aortic root and pulmonary artery in both adults and fetuses. In fetuses, no difference was found between the two vessels in terms of elastic laminae (p = 0.26) and smooth muscle cells (p = 0.69). However, in adults, significant differences were found for elastic laminae (p < 0.001) and smooth muscle cells (p < 0.001) between the aorta and pulmonary artery.ConclusionsThe microscopic vascular structure impacts the mechanical properties of the pulmonary autograft wall and explains its observed dilatation remote from the Ross procedure due to wall stresses related to systemic pressure.

Vanillic acid ameliorates diethyl phthalate and bisphenol S-induced oxidative stress and neuroinflammation in the hippocampus of experimental rats.

Long-term adverse effects on human health are caused by exogenous compounds that alter the functions of biological systems, especially neuroendocrine disruptors like diethyl phthalate (DEP) and bisphenol S (BPS). Although vanillic acid (VA) has pertinent neuropharmacological characteristics, its effect against DEP + BPS-induced neurotoxicity has not been explored. This study proposed that VA may offer protection against the neurotoxicity caused by DEP + BPS. Thirty male Wistar rats were randomly distributed across five groups: a control group receiving DMSO, a group exposed to a mixture of BPS and DEP, two BPS + DEP-exposed groups treated with VA at doses of 25 mg/kg or 50 mg/kg, and a nonexposed group treated with 50 mg VA/kg. After 21 days, the hippocampal tissues were processed for biochemical analyses. Our results indicate that exposure to DEP + BPS upregulated neurosignaling mediators (NTPDase, ADA, MAO-A, and Ca2+), inhibited others (AChE and Ca2+/Mg2+-ATPase), decreased hippocampus antioxidants (GSH, GPx, CAT, and SOD), and elevated markers of oxidative stress/damage (NO, H2O2, MDA, and AOPP). AR, BAX, TNF-α, BAK1, and IL-1β expressions were upregulated, while IL-10 and BDNF expressions were downregulated. NF-κB and caspase-3/9 pathways were also upregulated. Co-treatment with vanillic acid remarkably precluded these neurotoxic outcomes by improving neurosignaling, augmenting antioxidant status, abrogating oxidative damage, inflammation (TNF-α, IL-1β), and apoptosis (BAX, BAK1, caspase-3/9). Vanillic acid also restored IL-10 and BDNF levels, thereby exhibiting neuroprotective effects, corroborated by histological examinations. We posit vanillic acid as a safe and effective therapeutic agent against neurotoxicity occasioned by exposure to neuroendocrine disruptors.

Treatment Approaches for Diffuse Cutaneous Mastocytosis in Children: Literature Review and Actual Clinical Experience

Background. Mastocytosis is a very rare disease with various manifestations, based on abnormal clonal proliferation of mast cells in organs and tissues, such as: skin, bone marrow, lymph nodes, liver, spleen, and gastrointestinal tract. The diagnosis can be established according to clinical manifestations, laboratory, and instrumental data. Darier’s sign and histological examination are crucial for mastocytosis diagnosis. The presented clinical case describes very rare cutaneous form of mastocytosis. Clinical case description. The girl, 2.5 years old, was hospitalized with multiple erythematous papules on her body, face, and limbs. Comprehensive examination, including bone marrow biopsy and positron-emission tomography, allowed us to exclude mastocytosis systemic manifestations. Conclusion. Despite the fact that mastocytosis in children is mostly represented by skin form, it is necessary to perform complex patient examination on any systemic damage. Antihistamines in combination with topical and/or systemic glucocorticoids are often effective, but complete response does not always occur. Implementation of other therapeutic options, such as targeted drugs (tyrosine kinase inhibitors), is suggested In case of no or insufficient therapeutic effect.

Feasibility and Safety of Pulsed Field Ablation at the Ventricular Outflow Tract Using Focal Point Catheter

BackgroundVentricular arrhythmias commonly originate from the ventricular outflow tract (VOT). It remains unexplored whether pulsed-field ablation (PFA) can create durable lesions safely at the VOT. ObjectiveThis study aimed at evaluating the feasibility and safety of a novel PFA catheter to deliver focal ablation to the VOT, especially pulmonary and aortic sinus cusps (PSCs and ASCs). MethodsTwelve swine were divided into three groups: 24-hour, 2-week, and 4-week post-ablation. PFA was delivered to pre-defined sites of PSCs and ASCs with a focal point catheter, positioned via mapping system, fluoroscopy, and intracardiac echocardiography (ICE). Electrophysiologic assessment, coronary angiography, transesophageal echocardiogram (TEE), gross and histologic examination were performed to evaluate the impact of PFA delivery on cardiac structure and function. ResultsAll subjects survived, and no adverse events were observed. There was a significant decrease in voltage amplitude and increase in pacing thresholds at PSCs and ASCs. There were no significant differences in A-H or H-V intervals between pre- and post-ablation (A-H, P = .70; H-V, P = .90). After PFA delivery to ASCs, coronary arteries were fully perfused in each heart, without ST-segment elevation observed. No severe valvular dysfunction was observed based on ICE and TEE. Gross and histologic examination confirmed the creation of well-demarcated lesions at the targeted sites without damage to adjacent structures. ConclusionPFA delivered via the focal point catheter could create durable lesions at PSCs and ASCs without damage to coronary arteries, atrioventricular block, or valvular dysfunction, indicative of the feasibility and safety of this novel PFA catheter at the VOT.

High-throughput Bronchus-on-a-Chip system for modeling the human bronchus

Airway inflammation, a protective response in the human body, can disrupt normal organ function when chronic, as seen in chronic obstructive pulmonary disease (COPD) and asthma. Chronic bronchitis induces goblet cell hyperplasia and metaplasia, obstructing airflow. Traditional animal testing is often replaced by in vitro three-dimensional cultures of human epithelial cells to assess chronic cell responses. However, these cells are cultured horizontally, differing from the tubular structure of the human airway and failing to accurately reproduce airway stenosis. To address this, we developed the Bronchus-on-a-Chip (BoC) system. The BoC uses a novel microfluidic design in a standard laboratory plate, embedding 62 chips in one plate. Human bronchial epithelial cells were cultured against a collagen extracellular matrix for up to 35 days. Characterization included barrier integrity assays, microscopy, and histological examination. Cells successfully cultured in a tubular structure, with the apical side air-lifted. Epithelial cells differentiated into basal, ciliated, and secretory cells, mimicking human bronchial epithelium. Upon exposure to inducers of goblet cell hyperplasia and metaplasia, the BoC system showed mucus hyperproduction, replicating chronic epithelial responses. This BoC system enhances in vitro testing for bronchial inflammation, providing a more human-relevant and high-throughput method.

Heightened TPD52 linked to metabolic dysfunction and associated abnormalities in zebrafish

The tumor protein D52 (TPD52) gene encodes a proto-oncogene protein associated with various medical conditions, including breast and prostate cancers. It plays a role in multiple biological pathways such as cell growth, differentiation, and apoptosis. The function of TPD52 in lipid droplet biosynthesis has been investigated in vitro. However, its precise role in lipid metabolism in animal models is not fully understood. To investigate the functions of TPD52 in vivo, we performed a conditional TPD52 protein expression analysis using a Tet-off transgenic system to establish conditionally expressed Tpd52 transgenic zebrafish. The effect of Tpd52 on lipogenesis was assessed using various methods, including whole-mount Oil Red O staining, histological examination, and measurement of inflammatory markers and potential targets using real-time quantitative polymerase chain reaction and immunoblotting in Tpd52 fish. Zebrafish with increased Tpd52 levels exhibited notable weight gain and the enlargement of fat deposits, which were mainly attributed to an increase in the volume of adipocytes. Moreover, Tpd52 overexpression was correlated with the triggering of the adipocyte differentiation signaling pathway. During adipocytic differentiation in response to nutrient status, our observations revealed adipogenesis, nonalcoholic fatty liver disease, and metabolic cardiomyopathy (MCM) in Tpd52 transgenic zebrafish. To gain a deeper understanding of the contribution of these proteins to the regulation of cellular growth, we investigated the expression of their corresponding genes and proteins in zebrafish. In the present study, the activated protein kinase pathway was identified as the primary target of TPD52. Adult Tpd52 zebrafish showed increased lipid accumulation, resulting in the development of visceral obesity, nonalcoholic fatty liver disease, and MCM. These findings strongly suggest that TPD52 actively contributes to adipose tissue expansion and its subsequent effects. This investigation provides compelling evidence that Tpd52 facilitates adipocyte development and related metabolic comorbidities in zebrafish.