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Background: Drug discovery strongly relies on the thorough evaluation of preclinical experimental studies. In the context of pulmonary fibrosis, micro-computed tomography (µCT) and histology are well-established and complementary tools for assessing, in animal models, disease progression and response to treatment. µCT offers dynamic, real-time insights into disease evolution and the effects of therapies, while histology provides a detailed microscopic examination of lung tissue. Here, we present a semi-automatic pipeline that integrates these readouts by matching individual µCT volume slices with the corresponding histological sections, effectively linking densitometric data with Ashcroft score measurements. Methods: The tool first geometrically aligns the vertical axis of the µCT volume with the cutting plane used to prepare the histological sample. Then, focusing on the left lung, it computes the affine registration that identifies the µCT coronal slice that best matches the histological section. Finally, quantitative µCT imaging parameters are extracted from the selected slice. In a proof-of-concept test, the tool was applied to a bleomycin-induced mouse model of lung fibrosis. Results: The proposed approach demonstrated high accuracy and time effectiveness in matching µCT and histological sections minimizing manual intervention, with an overall success rate of 95%, and reduced time required to align µCT and histological data from 40 to 5 min. Significant correlations were found between quantitative data derived from µCT and histology data. Conclusions: The precise combination of microscopic ex-vivo information with 3D in-vivo data enhances the accuracy and representativeness of tissue analysis and provides a structural context for omic studies, serving as the foundation for a multi-layer platform. By facilitating a detailed and objective view of disease progression and treatment response, this approach has the potential to accelerate the development of effective therapies for lung fibrosis. [ABSTRACT FROM AUTHOR]

Determination of infarct and scar size following myocardial infarction (MI) is commonly used to evaluate the efficacy of potential cardioprotective treatments in animal models. However, histological methods to determine morphological features in the infarcted heart have barely improved since implementation while still consuming large parts of the tissue and offering little options for parallel analyses. We aim to develop a new fluorescence technology for determining infarct area and area at risk that is comparable to 2,3,5-triphenyltetrazolium chloride (TTC) staining but allows for multiple analyses on the same heart tissue. For early and late time points following MI, we compared classical histochemical approaches with fluorescence staining methods. Reperfused MI was induced in male mice, the hearts were extracted 24 h, 7-, 21-, or 28-days later and fluorescently stained by combining Hoechst and phalloidin. This approach allowed for clear visualization of the infarct area, the area at ischemic risk and the remote area not affected by MI. The combined fluorescence staining correlated with the classic TTC/Evans Blue staining 24 h after MI (r = 0.8334). In later phases (>7 d) post-MI, wheat germ agglutinin (WGA) is equally accurate as classical Sirius Red (r = 0.9752), Masson's (r = 0.9920) and Gomori's Trichrome (r = 0.8082) staining for determination of scar size. Additionally, feasibility to co-localize fluorescence-stained immune cells in specific regions of the infarcted myocardium was demonstrated with this protocol. In conclusion, this new procedure for determination of post-MI infarct size is not inferior to classical TTC staining, yet provides substantial benefits, including the option for unbiased software-assisted analysis while sparing ample residual tissue for additional analyses. Overall, this enhances the data quality and reduces the required animal numbers consistent with the 3R concept of animal experimentation. [ABSTRACT FROM AUTHOR]

Deep learning-based virtual staining has the potential to replace chemical staining in histology and to provide more sustainable, rapid, and cost-effective pipelines for histopathology. Virtual staining will allow multiple outputs of stained images from a single input image of a tissue section, hence enabling virtual multiplexing and single-cell resolution between histological assessments that currently require separate tissue sections. Deep learning-based virtual staining models require large amounts of training data, and quantitative computational and rigorous histological validation is required for each intended use. In pathology and biomedical research, histology is the cornerstone method for tissue analysis. Currently, the histological workflow consumes plenty of chemicals, water, and time for staining procedures. Deep learning is now enabling digital replacement of parts of the histological staining procedure. In virtual staining, histological stains are created by training neural networks to produce stained images from an unstained tissue image, or through transferring information from one stain to another. These technical innovations provide more sustainable, rapid, and cost-effective alternatives to traditional histological pipelines, but their development is in an early phase and requires rigorous validation. In this review we cover the basic concepts of virtual staining for histology and provide future insights into the utilization of artificial intelligence (AI)-enabled virtual histology. [ABSTRACT FROM AUTHOR]

The aim of study was to investigate the effect of avanafil, a second-generation phosphodiesterase-5 (PDE5) inhibitor, on cerebral ischemia reperfusion (CI/R) model. 32 male albino Wistar rats were used. Four groups were constituted, as I: the healthy (sham), II: the CI/R group, III: the CI/R +I 10 mg/kg avanafil group, and IV: the CI/R + 20 mg/kg avanafil group. Avanafil was administered twice via oral gavage, first shortly after ischemia reperfusion and once more after 12 h. The rats were euthanized after 24 h. Histopathological and Real Time PCR analyzes were performed on cerebral tissues. IL-1β, NLRP3 and TNF-α mRNA expressions were statistically higher in the CI/R group when compared to healthy (sham) group. Conversely, the IL-1β, NLRP3, and TNF-α mRNA expressions were significantly decreased in both of the avanafil-treated groups when compared to CI/R group. Histopathological results showed that both doses of avanafil also decreased cellular damage in cerebral tissue that occurred after CI/R. Avanafil, was found to have ameliorated inflammatory response and cellular injury caused by CI/R. The mRNA expression of IL-1β, NLRP3, and TNF-α decreased in the I/R groups and approached the control group levels with a high dose of avanafil. [ABSTRACT FROM AUTHOR]

This paper presents a technique that can potentially help to determine the receptivity stage of the endometrium from histology images by automatically measuring the stromal nuclear changes. The presented technique is composed of an image segmentation model and the statistical evolution of segmented areas in hematoxylin and eosin (HE)-stained histology images. Three different endometrium receptivity stages, namely pre-receptive, post-receptive, and receptive, were compared. An ensemble-based AI model was proposed for histology image segmentation, which is based on individual UNet++, UNet, and ResNet34-UNet segmentation models. The performance of the ensemble-based technique was assessed using the Dice score and intersection over unit (IoU) values. In comparison to alternative segmentation architectures that were applied singly, the current ensemble-based method obtained higher Dice score (0.95) and IoU (0.90) values. The statistical comparison highlighted a noticeable difference in the number of nuclei and the size of the stroma tissue. The proposed technique demonstrated the positive potential for practical implementation for automatic endometrial tissue analysis. [ABSTRACT FROM AUTHOR]

Purpose: To compare different socket sealing approaches for alveolar ridge preservation and assess the dimensional changes and histologic characteristics of soft and hard tissues in a 4- to 6-month period. Material and Methods: A total of 22 patients with indicated single-tooth extraction in the maxillary nonmolar region were eligible for this study. After CBCT scanning and minimally traumatic tooth extraction, the alveolar sockets were filled with demineralized bovine bone mineral with collagen (DBBM-C) in patients from all groups except for those in the control group. Patients were divided into groups for socket sealing as follows: unsealed/spontaneous healing (control; n = 6), collagen matrix (n = 5), collagen membrane (n = 5), and autogenous graft (n = 6). A second CBCT scan was taken 4 to 6 months after extraction, and a trephine biopsy of soft and hard tissues was collected during implant placement. Tomographic dimensional changes were compared between groups. Intragroup tomographic evaluation and histological analysis were also performed. Results: Analysis of dimensional changes did not detect differences between the socket sealing groups (P > .05). In an intragroup evaluation, the height of the buccal bone and cross-sectional area of the alveolar ridge were significantly lower 4 to 6 months after extraction for the control group (P = .031). Histological analysis revealed that the socket sealing approach had no impact on hard and soft tissue formation. Conclusion: The data from the present study suggest that socket sealing with a collagen matrix, a collagen membrane exposed to the oral cavity, or an autogenous punch graft had no difference in the effects on volumetric maintenance and tissue formation in a period of 4 to 6 months. [ABSTRACT FROM AUTHOR]

Introduction: Stimulation of liver regeneration after hepatectomy may provide important advantages, especially in cases where liver tissue is at a critical level. Some studies have reported that vascular endothelial growth factor (VEGF) might ameliorate liver regeneration in animals. In this study, we aimed to examine the effects of exogenous VEGF164 on the regeneration of liver tissue after a 70% hepatectomy in rats. Methods: Twenty Wistar Albino male rats, weighing 300-350 g, were randomly divided into four groups, each having five animals. Group 1 and Group 3 were designated as control groups, and Group 2 and Group 4 as experimental groups. All rats underwent laparotomy and 70% partial hepatectomy. Postoperatively, control groups were administered saline through the tail vein at 0 and 6 hours, and VEGF164 was administered to the experimental groups in the same manner at 0 and 6 hours. Blood samples were collected by sacrificing the rats at 24 hours for Group 1 and Group 2, and at 72 hours for Group 3 and Group 4. Subsequently, relaparotomy was performed and the remaining liver tissues were completely removed in all groups. Then, the resected liver tissues were used to determine morphological regeneration rates. The histopathological proliferation of the liver was evaluated by calculating the Ki-67 proliferative index. Results: In the histopathological evaluation, it was revealed that the liver proliferation index was significantly higher in the VEGF164 group at 72 hours (p=0.028). Although liver weights were higher in the experimental groups, no statistically significant results were obtained in terms of morphological liver regeneration rates (p>0.05). Discussion and Conclusion: Although the positive effects of exogenous VEGF on liver regeneration were not found in this rat model, statistically significant increases in the liver proliferation index are promising. [ABSTRACT FROM AUTHOR]

This article demonstrates the ability to use autologous crushed cartilage grafts in rhinoplasty with rapid recovery and optimal nasal functionality without any tissue damage and allows its rapid rejuvenation. Eligible patients underwent primary rhinoplasty using autologous crushed cartilage graft followed by microscopy imaging of the grafted tissue after recovery. Tissue and cytological analysis using optical microscopy, transmission electronic microscopy (TEM), and scanning electronic microscopy (SEM) showed complete viability of chondrocytes, formation of new collagen fibers, neo-perichondrium, neo-angiogenesis, and exhibiting optimal aesthetic outcome. The surgical approach is easy to perform, feasible, and less time-consuming, with excellent tissue rejuvenation and rapid recovery. [ABSTRACT FROM AUTHOR]

Tissue phenotyping is a fundamental step in computational pathology for the analysis of tumor micro-environment in whole slide images (WSIs). Automatic tissue phenotyping in whole slide images (WSIs) of colorectal cancer (CRC) assists pathologists in better cancer grading and prognostication. In this paper, we propose a novel algorithm for the identification of distinct tissue components in colon cancer histology images by blending a comprehensive learning system with deep features extraction in the current work. Firstly, we extracted the features from the pre-trained VGG19 network which are then transformed into mapped features space for nodes enhancement generation. Utilizing both mapped features and enhancement nodes, the proposed algorithm classifies seven distinct tissue components including stroma, tumor, complex stroma, necrotic, normal benign, lymphocytes, and smooth muscle. To validate our proposed model, the experiments are performed on two publicly available colorectal cancer histology datasets. We showcase that our approach achieves a remarkable performance boost surpassing existing state-of-the-art methods by (1.3% AvTP, 2% F1) and (7% AvTP, 6% F1) on CRCD-1, and CRCD-2, respectively. [ABSTRACT FROM AUTHOR]

The accurate management of testicular germ cell tumors (TGCTs) depends on identifying the individual histological tumor components. Currently available data on protein expression in TGCTs are limited. The human protein atlas (HPA) is a comprehensive resource presenting the expression and localization of proteins across tissue types and diseases. In this study, we have compared the data from the HPA with our in-house immunohistochemistry on core TGCT diagnostic genes to test reliability and potential biomarker genes. We have compared the protein expression of 15 genes in TGCT patients and non-neoplastic testicles with the data from the HPA. Protein expression was converted into diagnostic positivity. Our study discovered discrepancies in three of the six core TGCT diagnostic genes, POU5F1, KIT and SOX17 in HPA. DPPA3, CALCA and TDGF1 were presented as potential novel TGCT biomarkers. MGMT was confirmed while RASSF1 and PRSS21 were identified as biomarkers of healthy testicular tissue. Finally, SALL4, SOX17, RASSF1 and PRSS21 dysregulation in the surrounding testicular tissue with complete preserved spermatogenesis of TGCT patients was detected, a potential early sign of neoplastic transformation. We highlight the importance of a multidisciplinary collaborative approach to fully understand the protein landscape of human testis and its pathologies. [ABSTRACT FROM AUTHOR]

Chronic tonsillitis (CT) is a global health issue which can impair patient's quality of life and has an important socioeconomic impact due to the nonrational use of antibiotics, increased antimicrobial resistance and frequent need for surgical treatment. In order to isolate and identify the causing agents of CT, a total of 79 postoperative palatine and adenoid tissue samples were obtained from the ENT Clinic, KBC Zvezdara, Belgrade, Serbia. Culture identification was performed by MALDI-TOF MS and the Staphylococcus aureus isolates were tested for biofilm forming capability and antibiotic susceptibility. Additionally, a histological examination of palatine and adenoid tissue was performed in order to detect the presence of CT-causing bacteria. The slight majority of participants were females with median age of 28 years for adult patients (group I) and 6 years for children (group II). Analysis of the incidence of bacteria isolated from tissue samples in both groups showed the highest prevalence of S. aureus, Streptococcus oralis and Streptococcus parasanquinis. In addition to interfollicular hyperplasia, colonies of species S. aureus were detected in histological material. The presence of biofilm might be the reason for the recurrence of infection. Therefore, searching for a new treatment of CT is of great importance. [ABSTRACT FROM AUTHOR]

Sulfur mustard (HD) poses a serious threat due to its relatively simple production process. Exposure to HD in the short-term causes an inflammatory response, while long-term exposure results in DNA and RNA damage. Respiratory tract tissue models were exposed to relatively low concentrations of HD and collected at 3 and 24 h post exposure. Histology, cytokine ELISAs, and mass spectrometric-based analyses were performed. Histology and ELISA data confirmed previously seen lung damage and inflammatory markers from HD exposure. The multi-omic mass spectrometry data showed variation in proteins and metabolites associated with increased inflammation, as well as DNA and RNA damage. HD exposure causes DNA and RNA damage that results in variation of proteins and metabolites that are associated with transcription, translation and cellular energy. [ABSTRACT FROM AUTHOR]

Hepatic diseases, such as hepatonecrosis, hepatitis, and hepatocirrhosis, are associated with mitochondrial dysfunction and increased reactive oxygen species generation and inflammation, ultimately leading to liver failure. In this study, we examined if acupuncture at LR3 can affect mitochondria-related gene expression in a liver damage model of experimentally induced acute liver failure (ALF). ALF was induced by the intraperitoneal injection of D-galactosamine (D-GalN) in experimental rats, who then received either sham (ALF), manual acupuncture (MA), electroacupuncture (EA), or silymarin (PC, positive control) treatment. Liver tissues were extracted from experimental and untreated control rats for histopathological analysis and expression profiling of genes involved in mitochondrial function. Of the 168 mitochondria-related genes profiled, two genes belonging to the solute-carrier transporter family (Slc25a15 and Slc25a25) and Ndufb7 were upregulated. Gamma-glutamylcysteine synthetase was more downregulated in MA than ALF. Furthermore, MA reversed D-GalN-induced inflammatory cell infiltration, destruction of hepatic cell plates, and increase in the levels of the proinflammatory cytokine TNF-α. MA at LR3 can reduce the risk of D-GalN-induced ALF by inducing the expression of metabolic and inflammation-related genes and regulating proinflammatory factor production in hepatic mitochondria. [ABSTRACT FROM AUTHOR]

Background. Sepsis is defined as a host inflammatory response to infection that can result in end-organ dysfunction. One of the most common consequences of sepsis is acute kidney injury (AKI). Panax notoginseng powder (PNP) has been previously reported to protect against overactive inflammation process. However, the potential effect of PNP on septic AKI is poorly described. The current study was conducted to investigate the protective effects of PNP in septic AKI rats. Methods. A model of septic AKI was established on male SD rats by using the cecal ligation and puncture procedure. PNP was administrated by gavage after the cecal ligation and puncture (CLP) procedure, and the mice were sacrificed at 6, 12, and 72 h after induction of sepsis. The serum and kidney samples were collected and assayed for biochemical tests, histopathological staining, inflammation, and apoptosis-related gene/protein expression. In addition, 15 rats in each group were used to calculate the 7-day survival rate. Results. CLP-induced kidney injury was observed by the histopathological score, which markedly was attenuated by PNP treatment. Consistently, PNP intervention significantly alleviated the elevated levels of serum creatinine and blood urea nitrogen in CLP-induced sepsis rats. The CLP procedure also triggered proinflammatory cytokine production and increased the expression of various inflammation-related proteins in the kidneys. However, PNP inhibited the renal expression of IL-18, IL-1β, TNF-α, and IL-6 to substantially improve inflammatory response. Mechanistically, CLP induced the increase of the NF-κB p65 level in the injured kidneys, while PNP notably inhibited the corresponding protein expression. Conclusion. PNP attenuated kidney inflammation to protect against CLP-induced septic AKI in rats via inhibiting the NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

* Context.--Gender-affirming surgery is part of a multidisciplinary approach in gender transitioning. Deeper histologic examination may strengthen care for transmasculine individuals and increase the understanding of the influence of hormonal therapy in specific organs. Objective.--To evaluate and catalogue histologic findings of tissue obtained from gender-affirming gynecologic surgery and cervical cytology specimens. Design.--This is an institutional review board-approved retrospective study that included transmasculine individuals who underwent gender-affirming gynecologic surgery from January 2015 to June 2020. All surgical gynecologic pathology and cervical cytology slides were reviewed by 2 pathologists. Results.--Fifty-five patients were included, which represented 40 uteri, 35 bilateral ovaries, 15 vaginectomy specimens, and 24 cervical cytology results. The median age was 27 years (range, 18-56), and 94% (50 of 53) of patients were receiving testosterone for at least 1 year. Seventy-five percent (30 of 40) of endometria were inactive, while 25% (10 of 40) showed evidence of cycling. Transitional cell metaplasia was the most common finding in the cervix (17 of 40) and vagina (15 of 15), reflecting a high percentage (4 of 24) of unsatisfactory or ASC-US (atypical squamous cells of undetermined significance) cervical cytologies. Prostatic-type glands were identified in 20% (8 of 40) of cervices and 67% (10 of 15) of vaginectomy specimens. Multiple bilateral cystic follicles and evidence of follicular maturation were present in 57% (20 of 35) of cases. Four cases showed paratubal epididymis-like mesonephric remnant hypertrophy. Conclusions.--A comprehensive evaluation of tissue from gender-affirming surgery increases knowledge of the changes following androgen therapy in transmasculine individuals and may contribute to optimal patient care by raising awareness of normal histologic variations in this population. [ABSTRACT FROM AUTHOR]

Introduction: Electroporation ablation creates deep and wide myocardial lesions. No data are available on time course and characteristics of acute lesion formation. Methods: For the acute phase of myocardial lesion development, seven pigs were investigated. Single 200 J applications were delivered at four different epicardial right ventricular sites using a linear suction device, yielding a total of 28 lesions. Timing of applications was designed to yield lesions at seven time points: 0, 10, 20, 30, 40, 50, and 60 min, with four lesions per time point. After killing, lesion characteristics were histologically investigated. For the chronic phase of myocardial lesion development, tissue samples were used from previously conducted studies where tissue was obtained at 3 weeks and 3 months after electroporation ablation. Results: Acute myocardial lesions induce a necrosis pattern with contraction band necrosis and interstitial edema, immediately present after electroporation ablation. No further histological changes such as hemorrhage or influx of inflammatory cells occurred in the first hour. After 3 weeks, the lesions consisted of sharply demarcated loose connective tissue that further developed to more fibrotic scar tissue after 3 months without additional changes. Within the scar tissue, arteries and nerves were unaffected. Conclusion: Electroporation ablation immediately induces contraction band necrosis and edema without additional tissue changes in the first hour. After 3 weeks, a sharply demarked scar has been developed that remains stable during follow‐up of 3 months. This is highly relevant for clinical application of electroporation ablation in terms of the electrophysiological endpoint and waiting period after ablation. [ABSTRACT FROM AUTHOR]

Acquiring comprehensive knowledge about the uptake of pollutants, impact on tissue integrity and the effects at the molecular level in organisms is of increasing interest due to the environmental exposure to numerous contaminants. The analysis of tissues can be performed by histological examination, which is still time-consuming and restricted to target-specific staining methods. The histological approaches can be complemented with chemical imaging analysis. Chemical imaging of tissue sections is typically performed using a single imaging approach. However, for toxicological testing of environmental pollutants, a multimodal approach combined with improved data acquisition and evaluation is desirable, since it may allow for more rapid tissue characterization and give further information on ecotoxicological effects at the tissue level. Therefore, using the soil model organism Eisenia fetida as a model, we developed a sequential workflow combining Fourier transform infrared spectroscopy (FTIR) and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) for chemical analysis of the same tissue sections. Data analysis of the FTIR spectra via random decision forest (RDF) classification enabled the rapid identification of target tissues (e.g., digestive tissue), which are relevant from an ecotoxicological point of view. MALDI imaging analysis provided specific lipid species which are sensitive to metabolic changes and environmental stressors. Taken together, our approach provides a fast and reproducible workflow for label-free histochemical tissue analyses in E. fetida, which can be applied to other model organisms as well. [ABSTRACT FROM AUTHOR]

Background: The navicular syndrome may be associated with alterations in other podotrochlear apparatus components, such as the deep digital flexor tendon, collareral sesamoid and distal sesamoid ligaments, podotrochlear bursa and distal sesamoid bone. However, the clinical significance and nature of these changes are not well understood, many of descriptive reports about distal sesamoid bone lesions are rarely accompanied by a complete and comprehensive comparison with animals of the control group. The aim of this study was to described histologically findings of the podrotrochlear apparatus components, allowing the understanding of the inserts and their microscopic appearance, thus providing the future recognize of their alterations. Materials, Methods & Results: Fourteen samples of the podotrochlear apparatus were taken out of 44 equine thoracic limbs specimens, separated at the radiocarpal joint of Crioulo and Thoroughbred horses, with an average age of 6.0-year-old, coming from a private clinic in southern Brazil. The thoracic limbs specimens were refrigerated at 4ºC at the clinic and then they were sent to the University Federal of Santa Maria (UFSM). Once at the University laboratory, the specimens were dissected to isolate the podotrochlear apparatus from each one. Subsequently, transversal and longitudinal samples from the distal sesamoid bone, deep digital flexor tendo, distal sesamoid ligament, colateral sesamoid ligament, were collected and podotrochlear bursa which were processed at the Veterinary Pathology Laboratory of the UFSM and University Federal of Santa Catarina (UFSC). The tissues samples were fixed in a 10% formaldehyde solution for 14 days and routinely processed for histology. The samples were sectioned at 3 µm and stained using the hematoxylin-eosin (H-E) routine method. The bone samples, after fixation, underwent a decalcified process in a formic acid-sodium citrate aqueous solution and routinely processed for histopathology. Histologic tendons evaluation showed that it is arranged in honeycombs fascicles in a transverse section observation. The tendinous fibers have a more compact and aligned collagen fibers arrangement due to the dense connective tissue. The synovial membrane of the podotrochlear bursa is composed of a cubic pseudo conjunctival epithelium arranged with a layer of synoviocytes forming villi towards the lumen. This characterization is very similar to that of the synovial joint membrane. The collateral sesamoid ligament fibers are not perfectly aligned, occurring at their confluence in some areas accompanied by the dissection of adipose tissue. The distal sesamoide ligament fibers, composed by of loose connective tissue associated with synoviocytes and vascular stroma. The articular surface of the distal sesamoid bone is arranged in 3 layers of chondrocytes embedded in a hyaline matrix. There was a clear differentiation between the subchondral bone area and the fibrocartilage tissue in the palmar aspect of the distal sesamoid bone. Discussion: The morphophysiological characterization of the podotrochlear structures inside the hoof capsule it is important for the future recognition of abnormalities and the possible hypothesis that originates the podotrochlear syndrome. These changes have great clinical relevance and very often associated of distal limb lameness in horses. The normal macroscopic, ultrasonographic and radiographic images along with the histomorphometric study of the podotrochlear structures have contributed for the morphophysiological comprehension and consequently future interpretation of the podotrochlear structures diseases. [ABSTRACT FROM AUTHOR]

In preclinical research, histological analysis of tissue samples is often limited to qualitative or semiquantitative scoring assessments. The reliability of this analysis can be impaired by the subjectivity of these approaches, even when read by experienced pathologists. Furthermore, the laborious nature of manual image assessments often leads to the analysis being restricted to a relatively small number of images that may not accurately represent the whole sample. Thus, there is a clear need for automated image analysis tools that can provide robust and rapid quantification of histologic samples from paraffin‐embedded or cryopreserved tissues. To address this need, we have developed a color image analysis algorithm (DigiPath) to quantify distinct color features in histologic sections. We demonstrate the utility of this tool across multiple types of tissue samples and pathologic features, and compare results from our program to other quantitative approaches such as color thresholding and hand tracing. We believe this tool will enable more thorough and reliable characterization of histological samples to facilitate better rigor and reproducibility in tissue‐based analyses. [ABSTRACT FROM AUTHOR]

Histological changes in tissue are of primary importance in pathological research and diagnosis. Automated histological analysis requires ability to computationally separate pathological alterations from normal tissue. Conventional histopathological assessments are performed from individual tissue sections, leading to the loss of three-dimensional context of the tissue. Yet, the tissue context and spatial determinants are critical in several pathologies, such as in understanding growth patterns of cancer in its local environment. Here, we develop computational methods for visualization and quantitative assessment of histopathological alterations in three dimensions. First, we reconstruct the 3D representation of the whole organ from serial sectioned tissue. Then, we proceed to analyze the histological characteristics and regions of interest in 3D. As our example cases, we use whole slide images representing hematoxylin-eosin stained whole mouse prostates in a Pten+/- mouse prostate tumor model. We show that quantitative assessment of tumor sizes, shapes, and separation between spatial locations within the organ enable characterizing and grouping tumors. Further, we show that 3D visualization of tissue with computationally quantified features provides an intuitive way to observe tissue pathology. Our results underline the heterogeneity in composition and cellular organization within individual tumors. As an example, we show how prostate tumors have nuclear density gradients indicating areas of tumor growth directions and reflecting varying pressure from the surrounding tissue. The methods presented here are applicable to any tissue and different types of pathologies. This work provides a proof-of-principle for gaining a comprehensive view from histology by studying it quantitatively in 3D.

Background Complete diagnostic autopsy (CDA) is considered to be the gold-standard procedure that aids in determination of cause of death in stillbirths and neonatal deaths. However, CDA is not routinely practiced in South Asian countries due to religious beliefs, lack of expertise, and lack of resources. Minimally invasive tissue sampling (MITS) has been recommended as a less mutilating and less expensive alternative to CDA for obtaining tissues for analysis. The present study aims to evaluate the yield of lung tissue and histological findings using MITS as part of a cause of death analysis for stillborns and preterm neonatal deaths. Methods Data were collected during an observational multicenter prospective study called the Project to Understand and Research Preterm birth and Stillbirth (PURPOSe) conducted in India and Pakistan. After obtaining written informed consent from parents, the eligible stillbirths and neonatal deaths were subjected to MITS using a standard protocol. The tissues were obtained from both lungs for histological and microbiological analysis. Results At both sites, a total of 453 stillbirths and 352 neonatal deaths underwent MITS. For stillbirths and neonatal deaths, the yield of lung tissue using MITS was high (92%). Intrauterine fetal distress and respiratory distress syndrome were the leading lung pathologies reported in stillbirths and neonatal deaths, respectively. Conclusions MITS appears to be a reasonable alternative to CDA in obtaining and evaluating lung tissue to inform accurate cause of death analysis in stillbirth and preterm deaths. [ABSTRACT FROM AUTHOR]

Background Minimally invasive tissue sampling (MITS), a postmortem procedure that uses core needle biopsy samples and does not require opening the body, may be a valid alternative to complete autopsy (CA) in highly infectious diseases such as coronavirus disease-19 (COVID-19). This study aimed to (1) compare the performance of MITS and CA in a series of COVID-19 deaths and (2) evaluate the safety of the procedure. Methods From October 2020 to February 2021, MITS was conducted in 12 adults who tested positive before death for COVID-19, in a standard, well-ventilated autopsy room, where personnel used reinforced personal protective equipment. In 9 cases, a CA was performed after MITS. A thorough histological evaluation was conducted, and the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated by real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Results The diagnoses provided by MITS and CA matched almost perfectly. In 9 patients, COVID-19 was in the chain of events leading to death, being responsible for diffuse alveolar damage and mononuclear T-cell inflammatory response in the lungs. No specific COVID-19 features were identified. Three deaths were not related to COVID-19. All personnel involved in MITS repeatedly tested negative for COVID-19. SARS-CoV-2 was identified by RT-PCR and immunohistochemistry in the MITS samples, particularly in the lungs. Conclusions MITS is useful for evaluating COVID-19–related deaths in settings where a CA is not feasible. The results of this simplified and safer technique are comparable to those of CA. [ABSTRACT FROM AUTHOR]

Pi-pa-run-fei-tang (PPRFT), a traditional Chinese medicine formula with long-standing history, demonstrated beneficial effect on chronic cough. However, the mechanism underlying efficacy unclear. In current research, we explored the impact and molecular mechanism of chronic cough mouse stimulating with capsaicin combined with ammonia. To investigate the metabolic modulating effects, and potential mechanisms underlying the therapeutic effect of PPRFT in chronic cough. Chronic cough mouse models were created by stimulating mice by capsaicin combined with ammonia. Number of coughs and cough latency within 2 min were recorded. With lung tissue and serum samples collected for histopathology, metabolomics, RT-qPCR, immunohistochemistry, and WB analysis. Lymphocytes were isolated and flow cytometric assays were conducted to evaluate the differentiation between Th17 and Treg cell among CD4+ cells. Results indicated that PPRFT obviously reduced the number of coughs, prolonged cough latency, reduced inflammatory cell infiltration and lung tissues damage, and decreased the serum level of IL-6, IL-1β, TNF-α, and IL-17 while increasing IL-10 levels. Notably, PPRFT suppressed Th17 cell divergence and promoted Treg cell divergence. Furthermore, serum metabolomic assays showed that 46 metabolites differed significantly between group, with 35 pathways involved. Moreover, mRNA levels of IL-6, NF-κB, IL-17, RORγT, JAK2, STAT3, PI3K and AKT in lung tissues remarkably reduced and mRNA levels of IL-10 and FOXP3 were elevated after PPRFT pretreatment. Additionally, PPRFT treatments decreased the protein levels of IL-6, NF-κB, IL-17, RORγT, p-JAK2, p-STAT3, p-PI3K, and p-AKT and increased the protein levels of IL-10 and FOXP3, but no significantly effects to the levels on JAK2, STAT3, PI3K, and AKT in the lungs. Conclusively, our result suggested the effect with PPRFT on chronic cough may be mediated through IL-6/JAK2/STAT3 and PI3K/AKT/NF-κB pathway, which regulate the differentiation between Th17 and Treg cell. This beneficial effect of PPRFT in capsaicin and ammonia-stimulated chronic cough mice indicates its potential application in treating chronic cough. [Display omitted] • PPRFT significantly reduces capsaicin combined with ammonia induced chronic cough. • PPRFT regulates the levels of serum metabolites with ammonia induced chronic cough. • PPRFT inhibit IL-6/JAK2/STAT3/IL-17 and PI3K/AKT/NF-κB pathway to relieve chronic cough. [ABSTRACT FROM AUTHOR]

Purpose: A histological study of a structure between the posterior horn of the lateral meniscus and the anterior cruciate ligament. Methods: Bilateral fresh-frozen cadaveric knees of two male donors (age 71 and 76 years) with no history of prior knee injury were examined. All dissections were performed by one experienced orthopaedic surgeon. Haematoxylin and Eosin staining was used to reveal tissue morphology. Goldner trichrome staining was used to evaluate the connective tissue. S100 and PGP 9.5 labelling were used for immunohistochemical analysis. Results: In all cadaveric knees, a structure between the posterior horn of the lateral meniscus and the anterior cruciate ligament was identified. Histological analysis confirmed the ligamentous nature of this structure. Furthermore, Golgi tendon organs were observed within the ligamentous structure. Conclusion: This is the first study showing the presence of mechanoreceptors within the ligamentous structure between the posterior horn of the lateral meniscus and the anterior cruciate ligament. The ligamentous structure could contribute to stability of the knee by providing proprioceptive input, while preservation of the ligamentous structure might ensure a better functional outcome after surgery. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of data on the role of molecular methods in the diagnosis of osteoarticular tuberculosis. The present study was conducted to define the role of molecular (CBNAAT, LPA), phenotypic (AFB smear and culture) and histopathological evaluation in the diagnosis of osteoarticular TB. Methods: Seventy-seven consecutive cases of osteoarticular tuberculosis were grouped into presumptive TB cases (group A) and presumptive drug-resistant cases (group B). Tissue samples obtained were submitted for CBNAAT, LPA, AFB smear, liquid culture and histological examinations. The diagnostic accuracy of each test was reported against histologically diagnosed cases and in all tests in tandem. Results: Group A and group B had 65 and 12 cases, respectively. The diagnostic accuracy for tuberculosis was 84.62% by CBNAAT, 70.77% by LPA, 86.15% by molecular tests (combined), 47.69% by AFB smear, 50.77% by liquid culture and 87.69% by histology in group A, and 91.67% for CBNAAT, 83.33% for LPA, 91.67% for molecular tests (combined), 25% for AFB smear, 16.67% for liquid culture and 83.33% for histology in group B. The drug resistance detection rate was 4.62% on CBNAAT, 3.08% on LPA, 6.15% on molecular tests (combined) and 1.54% on DST in group A, while it was 33.33% on CBNAAT, 58.33% on LPA, 58.33% on molecular tests (combined) and 16.67% on DST among group B cases. Similar sensitivity rates for the various tests were obtained among both the groups on comparison with histology (taken as denominator). The addition of molecular methods increased the overall diagnostic accuracy (all tests in tandem) from 93.8 to 100% in group A and from 83.3 to 100% in group B cases. Conclusion: No single tests could diagnose tuberculosis in all cases; hence, samples should be evaluated by molecular tests (CBNAAT and LPA), AFB smear, culture and histological examinations simultaneously. The molecular tests have better demonstration of drug resistance from mycobacterial culture. [ABSTRACT FROM AUTHOR]

Osseointegration is a well-established concept used in applications including the percutaneous Bone-Anchored Hearing System (BAHS) and auricular rehabilitation. To date, few retrieved implants have been described. A systematic review including cases where percutaneous bone-anchored implants inserted in the temporal bone were retrieved and analyzed was performed. We also present the case of a patient who received a BAHS for mixed hearing loss. After the initial surgery, several episodes of soft tissue inflammation accompanied by pain were observed, leading to elective abutment removal 14 months post-surgery. Two years post-implantation, the implant was removed due to pain and subjected to a multiscale and multimodal analysis: microbial DNA using molecular fingerprinting, gene expression using quantitative real-time polymerase chain reaction (qPCR), X-ray microcomputed tomography (micro-CT), histology, histomorphometry, backscattered scanning electron microscopy (BSE-SEM), Raman spectroscopy, and fluorescence in situ hybridization (FISH). Evidence of osseointegration was provided via micro-CT, histology, BSE-SEM, and Raman spectroscopy. Polymicrobial colonization in the periabutment area and on the implant, including that with Staphylococcus aureus and Staphylococcus epidermidis , was determined using a molecular analysis via a 16S-23S rDNA interspace [IS]-region-based profiling method (IS-Pro). The histology suggested bacterial colonization in the skin and in the peri-implant bone. FISH confirmed the localization of S. aureus and coagulase-negative staphylococci in the skin. Ten articles (54 implants, 47 patients) met the inclusion criteria for the literature search. The analyzed samples were either BAHS (35 implants) or bone-anchored aural epitheses (19 implants) in situ between 2 weeks and 8 years. The main reasons for elective removal were nonuse/changes in treatment, pain, or skin reactions. Most samples were evaluated using histology, demonstrating osseointegration, but with the absence of bone under the implants' proximal flange. Taken together, the literature and this case report show clear evidence of osseointegration, despite prominent complications. Nevertheless, despite implant osseointegration, chronic pain related to the BAHS may be associated with a chronic bacterial infection and raised inflammatory response in the absence of macroscopic signs of infection. It is suggested that a multimodal analysis of peri-implant health provides possibilities for device improvements and to guide diagnostic and therapeutic strategies to alleviate the impact of complications. [ABSTRACT FROM AUTHOR]

From a general structural perspective, a mucosal tissue is constituted by two main matrices: the tissue and the secreted mucus. Jointly, they fulfill a wide range of functions including the protection of the epithelial layer. In this study, we simultaneously analyzed the epithelial tissue and the secreted mucus response using a holistic interactome-based multi-omics approach. The effect of the gilthead sea bream (Sparus aurata) skin mucosa to a dietary inclusion of spray-dried porcine plasma (SDPP) was evaluated. The epithelial skin microarrays-based transcriptome data showed 194 differentially expressed genes, meanwhile the exuded mucus proteome analysis 35 differentially synthesized proteins. Separately, the skin transcripteractome revealed an expression profile that favored biological mechanisms associated to gene expression, biogenesis, vesicle function, protein transport and localization to the membrane. Mucus proteome showed an enhanced protective role with putatively higher antioxidant and antimicrobial properties. The integrated skin mucosa multi-interactome analysis evidenced the interrelationship and synergy between the metabolism and the exuded mucus functions improving specifically the tissue development, innate defenses, and environment recognition. Histologically, the skin increased in thickness and in number of mucous cells. A positive impact on animal performance, growth and feed efficiency was also registered. Collectively, the results suggest an intimate crosstalk between skin tissue and its exuded mucus in response to the nutritional stimulus (SDPP supplementation) that favors the stimulation of cell protein turnover and the activation of the exudation machinery in the skin mucosa. Thus, the multi-omics-based interactome analysis provides a comprehensive understanding of the biological context of response that takes place in a mucosal tissue. In perspective, this strategy is applicable for evaluating the effect of any experimental variable on any mucosal tissue functionality, including the benefits this assessment may provide on the study of the mammalian mucosa. [ABSTRACT FROM AUTHOR]

In surgical and anatomical training, use of cadaver remains the most ideal technique. Standard formaldehyde solution preserves cadaveric tissues for an extended period comparing to the unfixed tissues. However, it fails to retain the natural texture, color, and biomechanical features. Phenol based soft embalming methods were developed to maintain these properties, while simultaneously decreasing the biohazard risk. Soft embalming techniques have made the bodies more 'lifelike' and wellfitted for training. Though phenol fixation displays rewarding morphological maintenance, we have scanty evidences on the histological preservation. This mini review primarily discussed the latest reports regarding the effect of phenol-based fixation on the tissue histology. Published literatures revealed phenol-based fixation displayed comparable histological preservation to that ofgold standard paraformaldehyde-based solution. It was concluded that phenol-based solution is an excellent fixative used to preserve tissues for microscopic analysis. [ABSTRACT FROM AUTHOR]

Background: The hallucinogenic tryptamine analog 5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT) causes social problems worldwide. There are several studies on the metabolism; however, not more studies were found in the literature on acute toxicity. Aims: To report the acute toxicity of 5-MeO-MiPT in mice, followed by quantitative toxicological analysis of blood and organs, hystotoxicological and immunohistochemical analysis of tissues and cells. Study design: Animal experiment Methods: In vivo experiments were performed using CDl adult female mice (n=26). Animals were caged in 4 groups randomly. First group was a control (n=3). Second group was vehicle control (n=3) and injected 150 µL of blank solution (50% dimethyl sulfoxide in saline /0.9% of NaCl). While for acute toxicity experiments, 5-MeO-MiPT was added to a blank solution in order to obtain a dose of 0.27 mg/kg in 150 µL injection (n=10) and the last group were injected 2.7 mg/kg 5-MeO- MiPT in a 150 µL injection (n=10). Quantitative toxicological analysis, hystotoxicological and immunohistochemical analysis were performed. Results: In the toxicological analysis, 5-MeO-MiPT was found negative in biological samples which were control, vehicle control, and 0.27 mg/kg dose mice groups. 5-MeO-MiPT was found 2.7-13.4 ng/ mL in blood, 11-29 ng/g in kidney, 15.2-108.3 ng/g in liver, and 1.540.6 ng/g in the brain in 2,7 mg/kg injected group. In a low dose of the 5-MeO-MiPT liver section, compared with normal tissues, the difference in staining was statistically significant (p<0.0001). In highdose of 5-MeO-MiPT, H-score showed that the increase in the number of Caspase-3 positive cells was significant compared to the control (p<0.05). In high-dose of 5-MeO-MiPT, intense Caspase-3 immunore-activity was observed and the increase in the number of Caspase-3 positive cells compared to the control was statistically significant (p<0.05). In brain section, the statistics of the results obtained from the H-score showed that the increase in the number of Caspase-3 positive cells was significant compared to the control (p=0.0183). In vehicle control liver section, there were few Caspase-8 positive cells characterized by a light brown appearance (p=0.0117). In the high-dose 5-MeO-MiPT group, the numbers of positive cells at low and high doses of 5-MeO-MiPT group were statistically significant compared to the control (p<0.05). In the high-dose 5-MeO-MiPT group, Caspase-8 immunoreactivity was detected in the glomerular structures. Compared to control, the increase in Caspase-8 immunoreactivity was found to be statistically significant (p<0.05). Conclusion: Low-dose 5-MeO-MiPT did not cause any serious histo-pathological effects on the liver, kidney, and brain. High doses induce apoptotic cell death through caspase activity. [ABSTRACT FROM AUTHOR]

Both preclinical in vivo experiments and clinical trials are indispensable for analysis of tissue reactions in evaluating the compatibility of biomaterials or medical devices, i.e. the cell types interacting with the material, integration or degradation behavior, implant bed vascularization and immunological response. In particular, both the histological workup (including the processes such as embedding, cutting, histochemical and immunohistochemical staining methods), as well as qualitative and quantitative analysis are crucial steps enabling the final evaluation of biocompatibility. We present a short overview of the most important steps of the different workup and analytical methods used in preclinical and clinical biopsies for both novice and experienced researchers in the field of biomaterial science. [ABSTRACT FROM AUTHOR]

The main aim of our study was to study morphological state of the autograft from the fascia of the temporal muscle in myringoplasty. Until now, there is no consensus on issue of which fabrics are more suitable for use in the eardrum. We decided to study of use of an autograft from the fascia of the temporal muscle for myringoplasty in rabbits in the experiment, and in patients with chronic dry mesotympanitis. An electron microscopic examination of the fascia taken immediately, after 10, 20 min and 1 h after sampling. It was found that there are no gross destructive changes in the fascia structure. Minor changes are detected in the form of a light disorganization of the collagen complex, granular dystrophy with an increase in cell. Inflammatory diseases of the middle ear are widespread among population of all age groups. In the experiment, a positive result was obtained in 29 (82.8%) rabbits. In our research we performed morphological features of xenograft engraftment in an experimental animal on 3, 7, 14, 21 days and 1-3 months. In period from 3 days to 3 months after operation, the animals were euthanized by an air embolism and subjected to pathological examination. Then recovered xenograft, was examined macro and microscopically. Pieces were fixed in a 10% solution of neutral formalin. After washing with water, dehydration was carried out in alcohol and chloroform, and after, waxed with paraffin. Histological sections were stained with hematoxylin-eosin. Collagen fibers were detected by method of Vann-Gieson. [ABSTRACT FROM AUTHOR]

Brain invasion (BI) is a new criterion for atypia in meningiomas and therefore potentially impacts adjuvant treatment. However, it remains unclear whether surgical practice and specimen characteristics influence histopathological analyses and the accuracy of detecting BI. Tumor location, specimen characteristics, and rates of BI were compared in meningioma samples obtained from 2938 surgeries in different neurosurgical departments but diagnosed in a single neuropathological institute. Non-skull base tumor location was associated with CNS tissue on the microscopic slides (OR 1.45; p <.001), increasing specimen weight (OR 1.01; p <.001), and remaining tissue not subjected to neuropathological analyses (OR 2.18; p <.001) but not with BI (OR 1.29; p =.199). Specimen weight, rates of residual tissue not subjected to histopathological analyses, of BI and of brain tissue, on the microscopic slides differed among the neurosurgical centers (p <.001, each). Frequency of BI was increased in one department (OR 2.07; p =.002) and tended to be lower in another (OR.61; p =.088). The same centers displayed the highest and lowest rates of brain tissue in the specimen, respectively (p <.001). Moreover, the correlation of BI with the neurosurgical center was not confirmed when only analyzing specimen with evidence of brain tissue in microscopic analyses (p =.223). Detection of BI was not correlated with the intraoperative use of CUSA in subgroup analyses. Rates of brain invasion in neuropathological analyses are not associated with tumor location but differ among some neurosurgical centers. Evidence raises that surgical nuances impact specimen characteristics and therefore the accuracy of the detection of BI. [ABSTRACT FROM AUTHOR]

Existing clinical approaches and tools to measure burn tissue destruction are limited resulting in misdiagnosis of injury depth in over 40% of cases. Thus, our objective in this study was to characterize the ability of short‐wave infrared (SWIR) imaging to detect moisture levels as a surrogate for tissue viability with resolution to differentiate between burns of various depths. To accomplish our aim, we constructed an imaging system consisting of a broad‐band Tungsten light source; 1,200‐, 1,650‐, 1,940‐, and 2,250‐nm wavelength filters; and a specialized SWIR camera. We initially used agar slabs to provide a baseline spectrum for SWIR light imaging and demonstrated the differential absorbance at the multiple wavelengths, with 1,940 nm being the highest absorbed wavelength. These spectral bands were then demonstrated to detect levels of moisture in inorganic and in vivo mice models. The multiwavelength SWIR imaging approach was used to diagnose depth of burns using an in vivo porcine burn model. Healthy and injured skin regions were imaged 72 hours after short (20 seconds) and long (60 seconds) burn application, and biopsies were extracted from those regions for histologic analysis. Burn depth analysis based on collagen coagulation histology confirmed the formation of superficial and deep burns. SWIR multispectral reflectance imaging showed enhanced intensity levels in long burned regions, which correlated with histology and distinguished between superficial and deep burns. This SWIR imaging method represents a novel, real‐time method to objectively distinguishing superficial from deep burns. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the current study is to evaluate the antihyperlipidemic and antioxidative effects of hydro-alcoholic extract of marjoram (HAEM) in rats fed with a high-fat diet (HFD). Methods: In the experimental study, the rats were randomly divided into four groups of five rats in each and fed with high-fat diet for 12 weeks as follows: One group (normal diet group) was fed with a standard diet, one group was fed with HFD, and two groups were fed with HFD and orally fed with 150 and 450 mg/kg/day HAEM. The serum samples and liver tissues were used for measuring the biochemical and oxidative parameters and histopathological studies. HFD induced hepatosteatosis in rats as evidenced by the altered liver enzymes activity, serum lipid profile and oxidative status. Results: Serum lipid profile (triglyceride, cholesterol and low-density lipoprotein) in rats fed with HFD + HAEM (150 and 450 mg/kg/day) was significantly decreased. Furthermore, the evaluation of oxidative stress showed a reduction of the malondialdehyde (MDA) level and an increase in ferric-reducing anti-oxidant power. Meanwhile, liver enzyme activities declined in response to HAEM. Conclusion: Using the HAEM could be a future therapeutic agent in treating hepatosteatosis and reducing oxidative damages of HFD in the liver. [ABSTRACT FROM AUTHOR]

Artemisia argyi H.Lév. & Vaniot (AA) has been extensively utilized as an important medicine and food homology in China, Japan, Korea, and eastern parts of Russia, owing to its pharmacological effects, which include anti-inflammatory, antibacterial, antitussive, and antiallergic properties. Despite the extract of AA can significantly alleviate gastric mucosal injury, its precise material basis for effectiveness is not yet clear. As one of the polymethoxy flavonoids with high content in AA, the gastroprotective activity and molecular mechanism of eupatilin (EUP) require further investigation. This study aims to investigate the gastroprotective effects and possible mechanisms of EUP by using an ethanol-induced gastric mucosal injury model in rats. EUP was isolated from 95% ethanol extract of AA using a systematic phytochemical method. The gastroprotective activity of EUP was evaluated using a male SD rat model with ethanol-induced gastric mucosa injury. Histopathology evaluation of gastric tissues was performed using hematoxylin and eosin (H&E) staining. The levels of cytokines in the plasma and tissues were tested using the ELISA kits, while western blot analysis was employed to assess the expressions of COX-2, iNOS, and NF-κB pathway proteins. A sufficient amount of EUP was obtained from AA through chromatographic methods and identified by NMR experiment. In vivo, experimental results proved that EUP could significantly alleviate pathological features, increased SOD, GSH, and IL-10 levels, and decreased the contents of MDA, TNF-α, IL-1β, and IL-6. Further in vitro and in vivo Western blot experimental results showed that EUP significantly down-regulates the expressions of the NF-κB signal pathway to relieve inflammatory responses. This study demonstrated that EUP could exert gastroprotective effects by inhibiting inflammation, enhancing gastric mucosal defense, and ameliorating oxidative stress, which is beneficial for providing scientific data for the development of gastric protection. [Display omitted] • Eupatilin is one of the most abundant polymethoxyflavone of A. argyi. • Eupatilin could alleviate the histopathological damage in gastric mucosal injury rat. • Eupatilin ameliorate oxidative stress and improve mucosal protective factor levels. • Eupatilin inhibited inflammation by NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Background Despite approximately 2.6 million stillbirths occurring annually, there is a paucity of systematic biological investigation and consequently knowledge on the causes of these deaths in low- and middle-income countries (LMICs). We investigated the utility of minimally invasive tissue sampling (MITS), placental examination, and clinical history, in attributing the causes of stillbirth in a South African LMIC setting. Methods This prospective, observational pilot study undertook sampling of brain, lung, and liver tissue using core biopsy needles, blood and cerebrospinal fluid collection, and placental examination. Testing included microbial culture and/or molecular testing and tissue histological examination. The cause of death was determined for each case by an international panel of medical specialists and categorized using the World Health Organization's International Classification of Diseases, Tenth Revision application to perinatal deaths. Results A cause of stillbirth was identifiable for 117 of 129 (90.7%) stillbirths, including an underlying maternal cause in 63.4% (n = 83) and an immediate fetal cause in 79.1% (n = 102) of cases. The leading underlying causes of stillbirth were maternal hypertensive disorders (16.3%), placental separation and hemorrhage (14.0%), and chorioamnionitis (10.9%). The leading immediate causes of fetal death were antepartum hypoxia (35.7%) and fetal infection (37.2%), including due to Escherichia coli (16.3%), Enterococcus species (3.9%), and group B Streptococcus (3.1%). Conclusions In this pilot, proof-of-concept study, focused investigation of stillbirth provided granular detail on the causes thereof in an LMIC setting, including provisionally highlighting the largely underrecognized role of fetal sepsis as a dominant cause. [ABSTRACT FROM AUTHOR]

Background: The necessity of histological analysis is increasing. A 19-gauge histology needle (PC19) in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has recently been developed and has shown high yields of tissue acquisition and histological diagnosis.Aims: To compare the histological diagnostic yield in single-pass EUS-FNA for solid lesions using PC19 and a standard 19-gauge needle (EC19).Patients and Methods: Consecutive patients with solid lesions were enrolled and underwent one pass with each of PC19 and EC19 for EUS-FNA with the randomized order of the needles. The primary endpoint was the histological diagnostic accuracy. The secondary endpoints were the feasibility, yield of histological core, cytological and overall diagnostic accuracies, and adverse events. Subgroup analysis was performed for the optimal situation with PC19.Results: Of the 115 patients, 110 underwent EUS-FNA and five were excluded. EUS-FNA was performed from the esophagus in four, stomach in 80, or duodenum in 26. The final diagnosis was malignancy in 100 and benign in 10. The feasibility was 98.2 and 97.3% with PC19 and EC19, respectively (p = 1.00). The rate of presence of a histological core and the histological, cytological, and overall diagnostic accuracies for PC19 versus EC19 were 84.6 versus 80.9% (p = 0.593), 83.6 versus 73.6% (p = 0.099), 63.6 versus 56.4% (p = 0.335), and 90.0 versus 79.1% (p = 0.039), respectively. PC19 was favored in the trans-esophageal/gastric approaches to obtain a histological diagnosis (p = 0.013). Adverse events were observed in four patients.Conclusion: Single-pass EUS-FNA with PC19 was feasible and showed significantly higher overall diagnostic accuracy and an increased tendency towards histological diagnostic accuracy, especially with trans-esophageal/gastric FNA. [ABSTRACT FROM AUTHOR]

Multimodal mass spectrometric imaging identifies bacterial and host analytes in intact tissues during invasive infection in mice. Imaging infection: There are many reagents and assays to test samples for bacterial infections, but detecting pathogens at an early stage within intact tissue is challenging. Cassat et al. developed an imaging platform that detected changes in proteins and elements within murine host tissue after infection with Staphylococcus aureus. The imaging method was based on the known competition for nutrient metal between pathogens and host. Using bioluminescent imaging, blockface imaging, and magnetic resonance imaging coupled with matrix-assisted laser desorption/ionization imaging mass spectrometry and laser ablation inductively coupled plasma mass spectrometry, the imaging platform identified regions of metal starvation within abscesses. This multimodal imaging platform could help advance our understanding of inflammatory response and host-pathogen interactions during infection. Diseases are characterized by distinct changes in tissue molecular distribution. Molecular analysis of intact tissues traditionally requires preexisting knowledge of, and reagents for, the targets of interest. Conversely, label-free discovery of disease-associated tissue analytes requires destructive processing for downstream identification platforms. Tissue-based analyses therefore sacrifice discovery to gain spatial distribution of known targets or sacrifice tissue architecture for discovery of unknown targets. To overcome these obstacles, we developed a multimodality imaging platform for discovery-based molecular histology. We apply this platform to a model of disseminated infection triggered by the pathogen Staphylococcus aureus, leading to the discovery of infection-associated alterations in the distribution and abundance of proteins and elements in tissue in mice. These data provide an unbiased, three-dimensional analysis of how disease affects the molecular architecture of complex tissues, enable culture-free diagnosis of infection through imaging-based detection of bacterial and host analytes, and reveal molecular heterogeneity at the host-pathogen interface. [ABSTRACT FROM AUTHOR]

Background: Various parts of the Moringa oleifera (M. oleifera) tree are widely accepted to have ameliorative effects against metal toxicity. In the present study, M. oleifeira oil (MO) was tested against HgCl2-induced tissue pathologies and oxidative stress. Methods: Male Wistar rats were administered MO (1.798 mg/kg p.o.) or HgCl2 (5 mg/kg body wt) alone or in combination (5 mg/kg HgCl2 + 1.798 mg/kg MO p.o.) three times per week for 21 days. After exposure and treatment periods, rats were sacrificed; blood collected and the oxidative status of the liver and kidney homogenates were evaluated. Results: In the liver, malondialdehyde (MDA) level, glutathione (GSH), and superoxide dismutase (SOD) activities were higher whereas catalase (CAT) activity was lower in the HgCl2 group than in the control group. In the kidney, MDA level, SOD, and CAT activities were higher whereas GSH activity was unchanged in the HgCl2 group compared to the control group. In the liver, MDA level, SOD, and CAT activities were lower in the HgCl2 + MO group than in the HgCl2 group. In the kidney, MDA level, SOD and CAT activities were lower in the HgCl2 + MO than in the HgCl2 group. Furthermore, Hg-induced increases in creatinine and bilirubin levels as well as the increase in γ-glutamyl transferase, lactate dehydrogenase, and alkaline phosphatase activities were attenuated in the combine exposure group and the animals showed improvement in the histology of the liver and kidney. Conclusions: MO decreased the negative effects of Hginduced oxidative stress in rats. [ABSTRACT FROM AUTHOR]

Study Design: Serial histological investigation was performed on 10 cadaveric specimens and biomechanical tests were performed on five specimens, both focused on the tissue connexion between the rectus capitis posterior minor (RCPMi) and the spinal dura.Objective: This study had two components: to clarify the microscopic structure of the tissue link between RCPMi and the dura mater, and to evaluate the mechanical role of this tissue complex.Summary Of Background Data: Dissection-based and imaging-based reports have suggested a connective tissue link between the RCPMi and the dura mater at the posterior-atlanto-occipital (PAO) level. Existence of this link, and properties, remain unclear.Methods: Histological investigation: RCPMi muscles, their bony attachments, PAO space, and adjacent spinal dura mater were resected from 10 cadavers. Tissues were subdivided into medial and lateral parts. Serial histological sections were prepared to cover maximum surface area; Masson trichrome stain was used to evaluate the tissue connection. Biomechanical investigation: individualized RCPMi muscles from five cadavers were detached from their origin. Each muscle was loaded incrementally up to 2 kg, with the cervical spine hyperextended. Using a structured light scanner, the dura mater was scanned for each loaded state. Comparison between unloaded and each loaded scanned surface quantified the displacement of the dura mater.Results: Histological investigation confirmed the existence of a connective tissue link between the RCPMi and the dura mater. The biomechanical testing suggests that this tissue link complex can reduce the bulging of the dura mater into the spinal canal, caused during hyperextension, by 53.4% ± 6.9% under RCPMi loading.Conclusion: This histological investigation clarified the structure of the tissue link between the RCPMi and the dura mater. The biomechanical testing indicated a potential mechanical function of the RCPMi in regards to the spinal dura mater, which may include a stabilizing role of the dura mater during neck extension.Level Of Evidence: N/A. [ABSTRACT FROM AUTHOR]

Background: In vitro studies suggest that the multiple functions of decorin are related to both its core protein and its dermatan sulfate chain. To determine the contribution of the dermatan sulfate chain to the functional properties of decorin in vivo, a mutant mouse whose decorin lacked a dermatan sulfate chain was generated. Results: Homozygous mice expressing only the decorin core protein developed and grew in a similar manner to wild type mice. In both embryonic and postnatal mice, all connective tissues studied, including cartilage, skin and cornea, appeared to be normal upon histological examination, and their collagen fibrils were of normal diameter and organization. In addition, abdominal skin wounds healed in an identical manner in the mutant and wild type mice. Conclusions: The absence of a dermatan sulfate chain on decorin does not appear to overtly influence its functional properties in vivo. [ABSTRACT FROM AUTHOR]

Conclusion: Mesenchymal stem-cells are good candidates for cell-therapy of chronic tympanic membranes perforations. Objectives: To determine the effects of cell-based therapy in tympanic membrane perforations. Methods: Young C57BL/6 mice were anesthetized with intraperitoneal administration of ketamine and xylazine and randomly divided into three groups (n = 4 ears/group) that underwent bilateral sub-total pars tensa perforations of equal sizes using a sterile 27-gauge needle under a surgical microscope. Six-to-eight hours after injury, one group of mice did not receive treatment (acute perforation control), and the last two groups were treated with BM-MSCs embedded within HA scaffolds previously soaked in PBS to rinse culture media residues to avoid confounders and were euthanized 1 or 2 weeks after treatment. Results: Untreated tympanic membrane perforations developed a hyper-cellular infiltrate surrounding the injury site, while BM-MSC treated eardrums showed a reduced inflammatory response after the first week and a restoration of the trilaminar configuration 2 weeks after treatment, mimicking a normal tympanic membrane. [ABSTRACT FROM AUTHOR]

The estimation of age at death is one of the most fundamental biological parameters, determined on skeletal remains in anthropological context. That is why, there is a constant need to improve applied methods. Histomorphometry, which uses microscopic analysis of bone tissue is suggested to be one alternative method. In general, this technique is based on measurements and the determination of the number and density of basic bone structural units, osteons. Osteon density is found to be related with age of the individual. The main goal of this research was to compare results of determined age at death, on the basis of ribs histology, comes from methods proposed by different authors. We analyzed ground cross sections of ribs from archeological origin. The presented methodology is simple in use and effective. Four different methods were tested (Stout and Paine 1992; Cho et al. 2002; Kim et al. 2007; Bednarek et al. 2009). The obtained age results were compared with each other as well as related to the age estimated by standard macroscopic method used in anthropology. Bednarek's method is recognized to be the most supportive for anthropological analyzes. Methodological issues connected with grinding methodology and results interpretation are also presented. Hypothesis about interpopulation as well as histological and dimorphic differences were confirmed. [ABSTRACT FROM AUTHOR]

University anatomical-pathological collections represent huge sources of human tissues and preparations from a variety of different diseases. With the help of modern genetic and histological methods, preserved fixed tissues from pathological collections can be used to re-evaluate former diagnoses. We analysed 25 specimens from our pathological collection with ages ranging from 78 to 112 years. The tissues originated from the oral cavity, lip, tongue, lung, bone, kidney, spleen, thymus, larynx, lymph node, penis and uterine cervix with an original diagnosis of epithelial cancers or tuberculosis. Amplifiable DNA was extracted and in epithelial cancers, potential HPV infection was investigated. Specimens with an original diagnosis of tuberculosis were examined for mycobacterial infection. The tissues were also examined using modern histological methods. Our data showed that in 24/25 specimens the histological structure was preserved and in 10/11 specimens the diagnosis of squamous cell carcinoma could be confirmed. Additionally, HPV type 16 was detected in 8 specimens. The histological pattern of tuberculosis was found in 11/14 specimens and the Mycobacterium tuberculosis complex was ascertained in four specimens. Our study showed that pathogens such as HPV or Mycobacterium tuberculosis can be detected in historical pathological preparations, and that these collections are suitable for further epidemiological research. [ABSTRACT FROM AUTHOR]

The issue of an automated approach for detecting cervical cancer is proposed to improve the accuracy of recognition. Firstly, the cervical cancer histology source images are needed to use image preprocessing for reducing the impact brought by noise of images as well as the impact on subsequent precise feature extraction brought by irrelevant background. Secondly, the images are grouped into ten vertical images and the information of texture feature is extracted by Grey Level Co-occurrence Matrix (GLCM). GLCM is an effective tool to analyze the features of texture. The textures of different diseases in the source image of Cervical Cancer Histology (such as contrast, correlation, entropy, uniformity and energy, etc.) can all be obtained in this way. Thirdly, the image is segmented by using K-means clustering and Marker-controlled watershed Algorithm. And each vertical image is divided into three layers to calculate the areas of different layers. Based on GLCM and lesion area features, the tissues are investigated with segmentation by using Support Vector Machine (SVM) method. Finally, the results show that it is effective and feasible to recognize cervical cancer by automated approach and verified by experiment. [ABSTRACT FROM PUBLISHER]