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Search Results (1,654)

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12 pages, 248 KB  
Article
Safety and Efficacy Performance of Coaxial 18G vs. 20G Needles for Pediatric Percutaneous Liver Biopsy: A Retrospective Cohort Study
by Gil N. Bachar, Shlomit Tamir, Aeonv Choen, Yael Rapson, Ahuva Grubstein and Eli Atar
J. Clin. Med. 2026, 15(9), 3497; https://doi.org/10.3390/jcm15093497 (registering DOI) - 2 May 2026
Abstract
Background: Percutaneous liver biopsy is a cornerstone in the diagnostic and therapeutic management of pediatric liver diseases. However, data on the optimal needle gauge for coaxial techniques in children remain scarce. Smaller-gauge needles may theoretically enhance safety but could potentially compromise diagnostic yield. [...] Read more.
Background: Percutaneous liver biopsy is a cornerstone in the diagnostic and therapeutic management of pediatric liver diseases. However, data on the optimal needle gauge for coaxial techniques in children remain scarce. Smaller-gauge needles may theoretically enhance safety but could potentially compromise diagnostic yield. Objectives: The primary objective of this study was to evaluate and compare the safety and diagnostic clinical adequacy of ultrasound-guided percutaneous liver biopsies performed with semi-automated 20G versus 18G coaxial needles in pediatric patients. Patients and Methods: This retrospective cohort study included consecutive patients aged ≤19 years who underwent percutaneous non-targeted liver biopsies at a tertiary medical center between 2006 and 2012. Patient demographics, biopsy technique parameters (including needle gauge, number of cores, and tract embolization), and procedure-related complications were analyzed. Procedural success was defined by diagnostic and clinical adequacy, requiring a definitive pathology report and the presence of ≥7 portal tracts (the widely accepted threshold for a reliable histologic diagnosis). Complications were classified according to the Society of Interventional Radiology guidelines. Results: A total of 320 biopsies were performed in 260 patients (44.6% female; mean age 7.4 ± 6.0 years). Common indications included post-liver transplantation surveillance (28.4%) and unexplained liver enzyme elevation (22.5%). Biopsies were performed using 18G (n = 148; 46.3%) or 20G (n = 172; 53.7%) coaxial needles. Diagnostic and clinical adequacy was achieved in 100% of the procedures, with biopsy results directly influencing clinical management in 39.7% of cases. The overall complication rate was 5.3% (3.4% minor, 1.9% major), with no procedure-related mortality. While raw complication rates were numerically higher in the 20G group (likely to reflect an operator-driven selection bias for younger or higher-risk patients), the differences between the 18G and 20G needles were not statistically significant. Notably, the use of the 20G needle was associated with a significantly reduced clinical need for post-biopsy tract embolization. Conclusions: Our findings demonstrate no statistically significant differences in complication rates or diagnostic clinical adequacy between 18G and 20G coaxial needles for pediatric percutaneous liver biopsies. When selected based on appropriate clinical judgment, the 20G needle provides a high diagnostic yield and serves as an effective option, particularly for reducing the need for tract embolization. However, both 18G and 20G needles represent acceptable clinical options within the pediatric interventional armamentarium. Ultimately, the choice of needle gauge should be meticulously tailored to individual patient characteristics, bleeding risk profiles, and specific clinical indications, rather than uniformly recommending a smaller gauge across all pediatric age groups. Full article
(This article belongs to the Section Nuclear Medicine & Radiology)
17 pages, 7806 KB  
Article
A Flexible Wearable Electronics System for Electrocardiographic Assessment of Colchicine Therapy for Post-MI Remodeling
by Weijia Huang, Xiangfeng Gong, Maoshuai Yang, Ting Huang, Qiyao Zhuang, Zhenghua Xiao, Tao Xiong and Gang Yang
Sensors 2026, 26(9), 2814; https://doi.org/10.3390/s26092814 - 30 Apr 2026
Viewed by 361
Abstract
Objective: Myocardial infarction (MI) triggers inflammation and fibrosis that drive the progressive impairment of cardiac function. Yet most pharmacological studies still depend on single-time-point histological or imaging endpoints and lack longitudinal, non-invasive assessments of treatment response. Electrocardiography (ECG) detects conduction and repolarization abnormalities [...] Read more.
Objective: Myocardial infarction (MI) triggers inflammation and fibrosis that drive the progressive impairment of cardiac function. Yet most pharmacological studies still depend on single-time-point histological or imaging endpoints and lack longitudinal, non-invasive assessments of treatment response. Electrocardiography (ECG) detects conduction and repolarization abnormalities tightly associated with myocardial injury and structural remodeling. However, ECG monitoring in mice is limited by rigid or invasive hardware, which restricts its use for longitudinal assessment of cardiac structure and function. Approach: Here, we propose an ECG-based non-invasive post-MI cardiac remodeling assessment approach and develop a flexible electrocardiographic monitoring microsystem (FECMS). Using the anti-remodeling drug (colchicine) therapy in an MI mouse model (Sham n = 4, MI n = 7 survivors, Col n = 7 survivors) for validation, we longitudinally track drug-induced changes in ECG parameters and systematically evaluate their concordance with functional, structural, and molecular indicators of cardiac injury and remodeling. Results: Colchicine treatment induced progressive shortening of the QRS and QT intervals and gradual stabilization of the PR interval. These interval changes were accompanied by increased EF and FS, decreased LVESV, reduced myocardial fibrosis and inflammatory infiltration, and lower plasma troponin I levels at the endpoint. Correlation analyses revealed strong relationships between drug-induced changes in ECG parameters and functional recovery and inhibited structural remodeling. Significance: The FECMS provides a new, non-invasive tool for longitudinal cardiovascular drug evaluation. This approach has the potential to complement or reduce reliance on terminal histological endpoints and to facilitate the optimization of dosing strategies in preclinical cardiovascular pharmacology. Full article
(This article belongs to the Section Wearables)
17 pages, 3393 KB  
Article
Juvenile Doxorubicin Exposure Causes Lasting Trabecular Bone Loss in Mice: A Preclinical Model of Long-Term Skeletal Damage
by Veli Kaan Aydın, Aliye Uysal, Gülçin Abban Mete, Gergana Lengerova, Martina Bozhkova, Steliyan Petrov and Aylin Köseler
Cancers 2026, 18(9), 1438; https://doi.org/10.3390/cancers18091438 - 30 Apr 2026
Viewed by 201
Abstract
Background/Objectives: Anthracyclines such as doxorubicin (DOX) are integral to pediatric cancer protocols, yet little is known about how juvenile DOX exposure shapes the long-term trajectory of bone growth, microarchitectural connectivity, and the functional balance of bone turnover after treatment cessation. This study [...] Read more.
Background/Objectives: Anthracyclines such as doxorubicin (DOX) are integral to pediatric cancer protocols, yet little is known about how juvenile DOX exposure shapes the long-term trajectory of bone growth, microarchitectural connectivity, and the functional balance of bone turnover after treatment cessation. This study aimed to define how juvenile DOX exposure remodels trabecular architecture and bone homeostasis both acutely and after recovery. Methods: Four-week-old female BALB/c mice were treated with 6 mg/kg DOX or saline once weekly for four weeks. Bone parameters were analyzed immediately after treatment and after a 4-week drug-free recovery period. Assessments included high-resolution µCT for bone structure and connectivity, H&E and TRAP staining for histological evaluation, and ELISA for bone turnover markers (PINP, OC/BGP, TRACP-5b) in both serum and bone marrow. Results: DOX exposure significantly compromised trabecular bone mass and network connectivity, with persistent bone loss extending into the recovery period. Histologically, DOX caused marked degeneration in the epiphyseal growth plate and calcified zones, alongside a marked increase in osteoclast numbers. Functionally, an acute increase in circulating bone formation markers was observed post-treatment. However, during the recovery phase, this transitioned to a significant suppression of these systemic markers, coupled with significantly increased localized bone resorption. Conclusions: Juvenile DOX exposure produces sustained trabecular network impairment and growth plate degeneration. This durable structural deterioration is functionally associated with the establishment of a localized, pathologically uncoupled remodeling environment. Full article
(This article belongs to the Section Clinical Research of Cancer)
18 pages, 11322 KB  
Article
Effects of Different Attractants on Growth, Antioxidant Capacity, and Feeding Gene Expression of Procambarus clarkii
by Youhai Du, Silei Xia, Wuxiao Zhang, Wenping Yang, Yebing Yu, Zhaoxia Li, Bin Peng, Yude Wang, Bo Liu, Hongyan Tian and Jianhua Ming
Fishes 2026, 11(5), 267; https://doi.org/10.3390/fishes11050267 - 30 Apr 2026
Viewed by 170
Abstract
The purpose of this study was to investigate the effects of different feeding-promoting substances added to high plant protein diets on the growth, antioxidant, serum biochemical parameters, immune, and feeding-related genes of Procambarus clarkii. A total of 450 crayfish (3.94 ± 0.03 [...] Read more.
The purpose of this study was to investigate the effects of different feeding-promoting substances added to high plant protein diets on the growth, antioxidant, serum biochemical parameters, immune, and feeding-related genes of Procambarus clarkii. A total of 450 crayfish (3.94 ± 0.03 g) were selected and randomly divided into six groups, with each group consisting of three replicates and 25 crayfish per replicate. The crayfish were fed a basal diet without attractant (control group) and five experimental diets supplemented with 0.4% betaine (BET), 0.4% trimetlylamine oxide (TMAO), 0.4% squid paste (SQU), 0.4% dimethyl-β-propiothetin (DMPT), and 0.4% taurine (TAU). The feeding trial lasted for 6 weeks. The results showed that compared with the control group, the BET, SQU, DMPT, and TAU groups significantly improved in growth performance, weight gain rate, and specific growth rate of crayfish. Compared with the control group, the BET, MTAO, and SQU groups significantly increased hepatopancreas SOD, CAT, and T-AOC. Histological results showed that compared with the control group, all feeding attractant groups could alleviate hepatopancreas tissue damage. Compared with the control group, the TMAO and SQU groups significantly reduced serum GLU content as well as ACP and AKP activities. The results of gene quantitative analysis showed that, compared with the control, TMAO significantly upregulated the expression of tlr, nf-kb, propo, hsp70, and tgf-β, while TAU significantly increased the expression of hsp70, hsp90 and nf-kb genes. Compared with the control group, the expression levels of tor, 4ebp1, and s6k1 in the TMAO group were significantly increased. Compared with the control group, the expression levels of leptin and npy genes in the DMPT group were significantly increased. In summary, the addition of attractants to high plant protein feed has the effects of promoting growth, enhancing antioxidant capacity, improving digestive enzyme activity, alleviating hepatopancreas injury, improving immunity, and promoting feeding. Full article
(This article belongs to the Special Issue Recent Advances in Crayfish)
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14 pages, 260 KB  
Article
Serum CD93 as a Potential Diagnostic Biomarker for Endometrial Cancer: A Case–Control Study
by İsmail Bağlar, Fatih Şanlıkan, Esra Keles, Sahra Sultan Kara, Cansu Ergenç Özdaş, Yeliz Çeçen Dönmez and Hafize Uzun
J. Clin. Med. 2026, 15(9), 3409; https://doi.org/10.3390/jcm15093409 - 29 Apr 2026
Viewed by 167
Abstract
Objectives: CD93, an angiogenesis-related transmembrane glycoprotein, is transcriptomically downregulated in uterine corpus endometrial carcinoma, yet circulating protein levels have not been clinically evaluated. This study aimed to evaluate serum CD93 as a diagnostic biomarker for EC and to examine its association with clinicopathological [...] Read more.
Objectives: CD93, an angiogenesis-related transmembrane glycoprotein, is transcriptomically downregulated in uterine corpus endometrial carcinoma, yet circulating protein levels have not been clinically evaluated. This study aimed to evaluate serum CD93 as a diagnostic biomarker for EC and to examine its association with clinicopathological parameters. Methods: In this single-center case–control study, serum CD93 concentrations were measured by enzyme-linked immunosorbent assay in 46 patients with histologically confirmed primary EC and 35 controls with histologically verified benign gynecological pathology. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed. Results: Serum CD93 was significantly lower in EC patients than controls (median 4.55 [IQR 3.51–6.97] vs. 10.24 [7.18–12.14] ng/mL; p < 0.001). In multivariable analysis adjusted for age and body mass index, lower CD93 remained independently associated with EC (OR = 0.521; 95% CI 0.061–0.720; p < 0.001). ROC analysis yielded an area under the curve of 0.845 (95% CI 0.759–0.921), with 82.6% sensitivity and 74.3% specificity at a cut-off of 7.338 ng/mL. CD93 levels showed no significant association with histological subtype, grade, lymphovascular space invasion, nodal metastasis, or recurrence. Conclusions: Serum CD93 is significantly reduced in EC and demonstrates independent diagnostic performance, supporting its prospective validation as a non-invasive biomarker in larger multicenter cohorts. Full article
(This article belongs to the Section Obstetrics & Gynecology)
12 pages, 1035 KB  
Article
Is the Lactate/Albumin Ratio Associated with 28-Day Mortality in Critically Ill Patients That Underwent Open Gastric Cancer Surgery? A Retrospective Single-Center Study
by Yavuz Selim Kahraman, Veysel Garani Soylu and Öztürk Taşkın
J. Clin. Med. 2026, 15(9), 3345; https://doi.org/10.3390/jcm15093345 - 28 Apr 2026
Viewed by 117
Abstract
Objectives: The aim of this study is to investigate the relationship between the lactate/albumin ratio (LAR) and 28-day mortality in gastric cancer patients undergoing monitoring in a postoperative intensive care unit due to reasons such as haemodynamic instability, need for vasopressor support, or [...] Read more.
Objectives: The aim of this study is to investigate the relationship between the lactate/albumin ratio (LAR) and 28-day mortality in gastric cancer patients undergoing monitoring in a postoperative intensive care unit due to reasons such as haemodynamic instability, need for vasopressor support, or intraoperative bleeding. Methods: This retrospective study included patients followed up at the tertiary surgical intensive care unit of Kastamonu University Faculty of Medicine between January 2020 and October 2025 who were diagnosed with histologically confirmed gastric adenocarcinoma and underwent total open surgery or subtotal gastrectomy + D2 lymphadenectomy. The patients were categorized into two groups: non-survivors within 28 days (n: 45) and survivors within 28 days (n: 139). Results: A total of 184 critically ill patients (110 males, 74 females) who underwent gastric adenocarcinoma surgery and were followed up in the surgical intensive care unit were included in this study. The mean age of the patients was 72.2 ± 11.3 years. Of these patients, 139 (75.5%) were survivors, and 45 (24.5%) were non-survivors. Albumin, the C-reactive protein (CRP)/albumin ratio, lactate, and the lactate/albumin ratio were associated with 28-day mortality. Receiver operating characteristic (ROC) analysis showed that the LAR (area under the curve (AUC): 0.839) was superior to the serum albumin (AUC: 0.736) and lactate levels (AUC: 0.796) for predicting 28-day mortality. The optimal cut-off value of the LAR was 0.82, and an LAR of ≥ 0.82 was shown to be a significant and independent prognostic factor for 28-day mortality in patients with stomach cancer in a critical postoperative condition (odds ratio (OR): 4.78, confidence interval (CI): 1.09–21.08, p = 0.0386). Conclusions: The lactate/albumin ratio is a prognostic parameter for 28-day mortality in critically ill postoperative gastric cancer patients. The optimal cut-off value for the lactate/albumin ratio is 0.82. Full article
(This article belongs to the Section Oncology)
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22 pages, 6012 KB  
Proceeding Paper
Histology-Based Circulatory System Reconstruction of Sepiolidae (Bobtail Squids) and Renal Parasite Documentation
by Fahima Tabassum
Biol. Life Sci. Forum 2026, 62(1), 1; https://doi.org/10.3390/blsf2026062001 - 27 Apr 2026
Viewed by 124
Abstract
The circulatory system of cuttlefish (family Sepiidae) has been extensively studied; however, a comprehensive anatomical reconstruction of bobtail squids (family Sepiolidae) remains limited despite their ecological and evolutionary importance within Decapodiformes. This study reconstructs the circulatory architecture of sepiolids through comparative histological analysis [...] Read more.
The circulatory system of cuttlefish (family Sepiidae) has been extensively studied; however, a comprehensive anatomical reconstruction of bobtail squids (family Sepiolidae) remains limited despite their ecological and evolutionary importance within Decapodiformes. This study reconstructs the circulatory architecture of sepiolids through comparative histological analysis and documents microorganisms or parasites associated with renal tissues. Two bobtail squid species, Rossia bipapillata and Sepiolina nipponensis, were examined using serial histological sections, while four cuttlefish species—Sepia lycidas, Sepia esculenta, Sepia japonica, and Sepia tenuipes—were analyzed for comparative purposes. Morphometric parameters, including sex, total length, and mantle length, were recorded prior to histological processing. Branchial hearts and renal appendages were sectioned using serial microtomy (~120 sections per specimen) and stained with hematoxylin and eosin, periodic acid–Schiff, Masson’s trichrome, and Giemsa to visualize vascular continuity and tissue organization. Histological observations confirmed vascular connections between the gills, branchial hearts, the systemic heart, and renal appendages, enabling reconstruction of the sepiolid circulatory pathway. In addition, the light organ characteristic of Sepiolidae was identified as a tissue receiving oxygenated blood within the circulatory network. Renal tissues revealed the presence of parasitic organisms, including Dicyema in cuttlefish and ciliates of the genus Chromidina in bobtail squids. Morphological observations revealed structural diversity in Chromidina, including characteristic spiral anterior features and variation in body form, as well as developmental variation in nuclear number relative to body length in dicyemids. These findings provide new insights into cephalopod circulatory organization, parasite diversity, and host–parasite interactions. Full article
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15 pages, 5228 KB  
Article
Historical Anatomy of the Devotional Sculpture of Our Lady of Grace: Scientific and Patrimonial Contributions to the History of Southern Brazil
by Marylene Santos Rodrigues and João Carlos Ferreira de Melo Júnior
Histories 2026, 6(2), 30; https://doi.org/10.3390/histories6020030 - 27 Apr 2026
Viewed by 231
Abstract
The history of ancient cities is often associated with devotional sculptures that accompanied the founding process of settlements. In southern Brazil, an old city founded in 1553 has its history linked to the image of Our Lady of Grace. However, the definition of [...] Read more.
The history of ancient cities is often associated with devotional sculptures that accompanied the founding process of settlements. In southern Brazil, an old city founded in 1553 has its history linked to the image of Our Lady of Grace. However, the definition of its origin presents gaps, especially regarding its historical authenticity. This study aimed to identify the botanical species associated with this sculpture using the principles of historical anatomy. The sculpture underwent X-ray and CT scan examinations. Wood samples were extracted with a Pressler borer for histology and C14 dating. The identification was based on comparative anatomy. The artifact is carved from a single wood block, exhibiting wood integrity and absence of degrading agents. The species was identified as Cedrela sp. (Meliaceae), popularly known as cedar. C14 dated the wood around 1620 AD (330 ± 30 BP), offering new parameters for reflection on the origin of the piece and its relationship with the foundation of the city, traditionally associated with the year 1553. Cedar presents physical–structural characteristics of light density, is resistant to degrading agents, and possesses a pleasant aroma and dimensional stability, favoring its cultural use by master craftsmen and highlighting the richness in the carvings of religious images. The information contained within the wood was able to elucidate historical aspects regarding the founding of the city. Full article
(This article belongs to the Section Environmental History)
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14 pages, 2488 KB  
Article
Exploratory Changes in Surfactant Protein D During Intermittent Hypoxia and Modulation by Galectin-3 Inhibition
by Saad Al-Anazi, Yasser A. Alshawakir, Syed Shahid Habib, Hayam Gad, Asma F. Alotaibi, Alanoud T. Aljasham, Wajd Ahmed Althakfi, Mohamed A. Mekhtiche and Abeer Abdulmoati Al-Masri
Adv. Respir. Med. 2026, 94(3), 27; https://doi.org/10.3390/arm94030027 - 24 Apr 2026
Viewed by 144
Abstract
Background: Surfactant Protein D (SP-D) is a critical immunomodulatory collectin maintaining alveolar homeostasis. Obstructive sleep apnea (OSA)-related intermittent hypoxia (IH) disrupts pulmonary surfactant integrity; however, severity-dependent SP-D dynamics remain incompletely characterized. This study explores SP-D as a potential indicator of IH-induced alveolar stress [...] Read more.
Background: Surfactant Protein D (SP-D) is a critical immunomodulatory collectin maintaining alveolar homeostasis. Obstructive sleep apnea (OSA)-related intermittent hypoxia (IH) disrupts pulmonary surfactant integrity; however, severity-dependent SP-D dynamics remain incompletely characterized. This study explores SP-D as a potential indicator of IH-induced alveolar stress and evaluates whether Galectin-3 (Gal-3) inhibition modulates surfactant homeostasis. Methods: Forty adult male Sprague-Dawley rats (8 per group) were randomized to Control (normoxia), Moderate IH (MIH; 15–30 events/hour), Severe IH (SIH; 30–60 events/hour), MIH + Gal-3 inhibitor (Modified Citrus Pectin, 800 mg/kg/day), or SIH + Gal-3 inhibitor. IH exposure lasted 8 h/day for 10 days. Outcomes included circulating SP-D, Surfactant Protein B (SP-B), inflammatory markers, physiological parameters, and histopathological lung injury scores assessed via American Thoracic Society guidelines. Results: SP-D levels showed numerical reductions with increasing IH severity (Control: 1969.07 pg/mL [IQR: 262.15]; SIH: 1404.30 pg/mL [IQR: 351.88]), representing a 28.6% decrease. However, between-group variability resulted in non-significant omnibus testing (Kruskal–Wallis p = 0.187). Gal-3 inhibition elevated SP-D levels, particularly in severe IH (2133.95 pg/mL [IQR: 1240.70]), though high inter-individual variability was observed (CV = 58.1%). SP-B showed significant suppression under moderate IH (p = 0.019) with restoration by treatment. Exploratory correlation analysis revealed moderate positive associations between SP-D and heart rate (r = 0.587) and respiratory rate (r = 0.419) in severe IH, though these did not reach statistical significance (p = 0.126 and p = 0.301, respectively). Histologically, severe IH induced diffuse alveolar damage (total lung score: 19.67 ± 0.82). Gal-3 inhibition produced context-dependent effects: protective in severe IH but paradoxically exacerbating inflammation under moderate IH (29.20 ± 4.64 vs. 20.00 ± 4.34; p < 0.05). Gal-3 inhibition significantly attenuated cardiac injury (injury score: 0.00 ± 0.00 vs. 7.17 ± 0.75 in severe IH; p < 0.001, η2 = 0.859). Conclusions: SP-D demonstrates severity-associated alterations consistent with alveolar epithelial stress during IH, though high variability limits definitive biomarker validation in this sample. Gal-3 inhibition modulates surfactant homeostasis and attenuates cardiopulmonary injury in a context-dependent manner. These findings support further investigation into SP-D as a component of multimodal severity stratification in OSA and highlight Gal-3 inhibition as a context-dependent anti-inflammatory strategy, pending validation in larger cohorts with tissue-level confirmation. Full article
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15 pages, 5264 KB  
Article
Pilose Antler Protein Extract Alleviates Osteoporosis and Is Associated with Activation of the Wnt/β-Catenin Signaling Pathway
by Junxiao Gong, Yuman Ma, Jun Huang, Wenyu Yang, Yi Wang and Yanan Sun
Pharmaceuticals 2026, 19(5), 665; https://doi.org/10.3390/ph19050665 - 24 Apr 2026
Viewed by 347
Abstract
Objectives: Pilose antler protein extract (PAE) was investigated for its therapeutic efficacy against ovariectomy (OVX)-induced osteoporosis and its underlying molecular mechanism. Methods: An OVX rat model was established to evaluate the effects of PAE on bone microarchitecture, histopathological changes, and bone [...] Read more.
Objectives: Pilose antler protein extract (PAE) was investigated for its therapeutic efficacy against ovariectomy (OVX)-induced osteoporosis and its underlying molecular mechanism. Methods: An OVX rat model was established to evaluate the effects of PAE on bone microarchitecture, histopathological changes, and bone metabolism-related parameters. Bone structure was assessed using Micro-CT and histological analysis, and biochemical and bone turnover markers were quantified. In vitro, Mouse calvarial pre-osteoblast subclone 14 (MC3T3-E1) Subclone 14 cells were used to examine the effects of PAE on cell viability, proliferation, osteogenic differentiation, and osteogenesis-related protein expression. Results: High-dose PAE markedly improved trabecular bone microarchitecture in OVX rats, as reflected by increased bone surface area and bone volume fraction and reduced trabecular separation. PAE significantly enhanced bone calcium content and elevated serum Bone Morphogenetic Protein 2 (BMP-2) and Procollagen Type I N-Terminal Propeptide (PINP) levels, while decreasing serum Alkaline Phosphatase (ALP) activity and C-Terminal Telopeptide of Type I Collagen (CTX-I) levels, indicating a shift toward bone formation. Mechanistically, PAE activated the Wnt-3a/β-Catenin signaling pathway in bone tissue and MC3T3-E1 cells, as evidenced by increased expression of Wnt-3a and β-Catenin proteins. In vitro experiments further demonstrated that PAE promoted MC3T3-E1 cell proliferation and upregulated osteogenic markers, i.e., Runt-related transcription factor 2 (RUNX2) and Osteocalcin (OCN). Conclusions: Collectively, these findings suggest that PAE exerts pronounced anti-osteoporotic effects and is associated with activation of the Wnt/β-Catenin signaling pathway. Full article
(This article belongs to the Section Natural Products)
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22 pages, 6673 KB  
Article
Expression of HSP70, IGF-1, OCT4, and AIF in Clear Cell Renal Cell Carcinoma
by Matea Buljubašić Franić, Petar Todorović, Ivana Tica Sedlar, Natalija Filipović, Nela Kelam, Anita Racetin, Andrea Kopilaš, Ana Dunatov Huljev and Katarina Vukojević
Biomedicines 2026, 14(5), 974; https://doi.org/10.3390/biomedicines14050974 - 23 Apr 2026
Viewed by 467
Abstract
Background/Objectives: Clear cell renal cell carcinoma is the most common subtype of kidney cancer and exhibits marked biological heterogeneity, even among tumors of the same histological grade. Although tumor grade remains a key prognostic parameter, the molecular alterations associated with tumor differentiation [...] Read more.
Background/Objectives: Clear cell renal cell carcinoma is the most common subtype of kidney cancer and exhibits marked biological heterogeneity, even among tumors of the same histological grade. Although tumor grade remains a key prognostic parameter, the molecular alterations associated with tumor differentiation are not fully understood. This study aimed to evaluate grade-dependent tissue-level expression patterns of proteins involved in cellular stress response, growth regulation, stemness, and apoptosis in clear cell renal cell carcinoma. Methods: Protein expression of heat shock protein 70, insulin-like growth factor 1, octamer-binding transcription factor 4, and apoptosis-inducing factor were analyzed in human clear cell renal cell carcinoma samples and normal renal cortex. Low-grade and high-grade tumors were compared using immunofluorescence staining combined with semi-quantitative and quantitative image analysis. The proportion of positive signals and the number of positive cells were assessed across tissue compartments. In addition, publicly available transcriptomic data from The Cancer Genome Atlas kidney renal clear cell carcinoma cohort were analyzed to explore associations between gene expression levels and overall survival. Results: Distinct grade-dependent expression patterns were observed for all investigated proteins. Heat shock protein 70, insulin-like growth factor 1, and octamer-binding transcription factor 4 showed a higher expression in normal renal tissue with a progressive reduction across tumor grades. In contrast, apoptosis-inducing factor exhibited increased expression in tumor tissue, particularly in low-grade tumors, with a relative decrease in high-grade carcinomas. Stromal compartments of tumor tissue showed minimal or no expression for most markers. Transcriptomic survival analysis did not reveal significant differences in overall survival between high- and low-expression groups for any of the investigated genes. Grade-stratified transcriptomic analysis of the TCGA KIRC cohort revealed consistent patterns for HSP70 family members and OCT4, with progressive grade-dependent mRNA reduction toward higher grades, while IGF1 showed an inverse mRNA trend and AIFM1 showed a uniform reduction across all tumor grades without a clear inter-grade pattern. Conclusions: The findings demonstrate that stress response, growth-related, stemness-associated, and apoptotic proteins display distinct grade-dependent tissue-level expression patterns in clear cell renal cell carcinoma, with the expression profiles of high-grade tumors being of particular translational interest given the aggressive clinical behavior and therapeutic resistance characteristic of this disease stage. These alterations appear to reflect tumor differentiation and biological behavior rather than independent prognostic value, highlighting the complexity of molecular regulation in renal tumorigenesis. Full article
(This article belongs to the Section Cancer Biology and Oncology)
14 pages, 915 KB  
Article
Diagnostic Accuracy of Prognostic Nutritional Index and Systemic Immune–Inflammatory Index in Predicting Fibrosis and Histological Activity in Chronic Hepatitis B
by Ali Can Uguz, Mehmet Bayram, Hafize Uzun and Omur Tabak
Nutrients 2026, 18(9), 1332; https://doi.org/10.3390/nu18091332 - 23 Apr 2026
Viewed by 199
Abstract
Background: Liver biopsy remains the gold standard for staging chronic hepatitis B (CHB), yet it is invasive, costly, and associated with potential complications. There is a critical need for non-invasive, cost-effective biomarkers to monitor disease progression. This study aimed to evaluate the correlation [...] Read more.
Background: Liver biopsy remains the gold standard for staging chronic hepatitis B (CHB), yet it is invasive, costly, and associated with potential complications. There is a critical need for non-invasive, cost-effective biomarkers to monitor disease progression. This study aimed to evaluate the correlation between the Prognostic Nutritional Index (PNI) and Systemic Immune–Inflammatory Index (SII) with histological fibrosis stages and the Histological Activity Index (HAI) in patients with CHB. Methods: This retrospective study analyzed 274 patients diagnosed with CHB (HBsAg positivity > 6 months) who underwent liver biopsy at the University of Health Sciences, Kanuni Sultan Süleyman Training and Research Hospital between February 2016 and February 2022. Histopathological findings were staged using the Ishak fibrosis score and HAI. PNI and SII were calculated from peripheral blood parameters. Statistical discrimination power was assessed using Area Under the Receiver Operating Characteristic (AUROC) curves. Results: The cohort comprised 119 females (43.4%) and 155 males (56.6%), with a mean age of 45.25 ± 11.2 years. Mean values were 55.83 ± 5.33 for PNI and 494.37 ± 336.86 for SII. Fibrosis distribution showed 56.2% at stages F0–F1 and 43.8% at ≥F2. For fibrosis staging, SII demonstrated statistically significant but limited predictive ability for Ishak scores ≥F2, while PNI was significant for identifying advanced fibrosis (≥F4) (p < 0.05). SII showed moderate diagnostic performance for severe inflammation (HAI ≥12; AUROC = 0.848), although this finding should be interpreted cautiously. For lower HAI thresholds (≥6), both PNI and SII demonstrated poor discriminative ability (AUROC 0.5–0.6). Conclusions: Both indices were associated with histological parameters but showed limited overall diagnostic performance. SII appeared relatively better; however, this was descriptively observed without formal statistical comparison. These markers may provide complementary information but should not be used as standalone diagnostic tools. Full article
(This article belongs to the Section Nutritional Epidemiology)
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12 pages, 830 KB  
Article
Immunohistological Characterization of Actinic Keratoses with Varying Degrees of Proliferation
by Vasileios Dervenis, Conrad Falkenberg, Alexandra Knebel, Lutz Schmitz and Thomas Dirschka
Cancers 2026, 18(9), 1340; https://doi.org/10.3390/cancers18091340 - 23 Apr 2026
Viewed by 342
Abstract
Background: Actinic keratoses (AKs) are considered early in situ forms of cutaneous squamous cell carcinoma (cSCC). However reliable histopathological or molecular markers for predicting the risk of progression are still lacking. The aim of this study was to investigate the relationship between immunohistochemical [...] Read more.
Background: Actinic keratoses (AKs) are considered early in situ forms of cutaneous squamous cell carcinoma (cSCC). However reliable histopathological or molecular markers for predicting the risk of progression are still lacking. The aim of this study was to investigate the relationship between immunohistochemical markers and basal proliferation patterns of AKs in order to identify histopathological associations that may be relevant for malignant transformation. Methods: A total of 97 AK samples from facial and scalp areas were retrospectively analyzed and classified according to their basal proliferation pattern (Pro I: non-proliferative and Pro III: proliferative). Immunohistochemical staining was performed for Ki-67, p53, p16 and podoplanin. In addition, histopathological parameters such as Röwert-Huber grade, inflammatory infiltrate, parakeratosis, elastosis and the presence of acantholysis were evaluated. Results: Pro III lesions were significantly more frequently associated with higher Röwert-Huber grades (AK III: 47.9% vs. 14.3%; p = 0.0004) and with acantholysis (p = 0.0004). No significant differences between the groups were found for Ki-67, p53 and p16. Podoplanin expression, however, was significantly higher in Pro III lesions (93.7% vs. 57.1%, p < 0.0001) and was predominantly localized basally. The combination of a PRO III pattern and podoplanin positivity identified a distinct histopathological subgroup associated with features linked to progression. Conclusions: Podoplanin expression, especially in combination with PRO III pattern and acantholysis, characterizes a histologically and biologically distinct AK subgroup. In contrast, Ki-67, p53 and p16 showed no additional discriminative value in this cohort. Podoplanin could therefore be a useful addition to existing classification systems and in the future support risk-adapted treatment decision. However, prospective longitudinal studies are required to determine its prognostic value. Full article
(This article belongs to the Special Issue Risk of Skin Cancer: Non-Melanoma/Melanoma)
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20 pages, 2083 KB  
Article
Intraperitoneal Polypropylene Mesh in Clean, Potentially Septic, and Controlled Contamination Fields: An Experimental Rat Study
by Apostolos Makrantonakis, Ioannis Mantzoros, Orestis Ioannidis, Konstantinos Zapsalis, Elissavet Anestiadou, Styliani Parpoudi, Dimitrios Kyziridis, Ekaterini Klonou, Savvas Simeonidis, Stefanos Bitsianis, Manousos George Pramateftakis, Efstathios Kotidis and Stamatios Angelopoulos
Medicina 2026, 62(5), 803; https://doi.org/10.3390/medicina62050803 - 22 Apr 2026
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Abstract
Background and Objectives: Intraperitoneal onlay mesh (IPOM) reduces ventral/incisional hernia recurrence but raises concern for adhesions and infection, particularly when the operative field is not strictly clean. We aimed to determine how contamination severity modulates the peritoneal response to intraperitoneal polypropylene mesh. [...] Read more.
Background and Objectives: Intraperitoneal onlay mesh (IPOM) reduces ventral/incisional hernia recurrence but raises concern for adhesions and infection, particularly when the operative field is not strictly clean. We aimed to determine how contamination severity modulates the peritoneal response to intraperitoneal polypropylene mesh. Materials and Methods: In a prospective, randomized, blinded rat study, 60 male Wistar rats were allocated to three groups (n = 20/group) and evaluated at postoperative day (POD) 4 and POD 8 (n = 10/timepoint): A, clean mesh placement; B, small-bowel resection with end-to-end anastomosis without spillage (“potentially septic”); and C, mesh placement followed by intraperitoneal inoculation with Escherichia coli and Staphylococcus aureus (“controlled contamination”). The primary outcome was adhesion severity (Van der Ham scale, 0–3). Secondary outcomes included semi-quantitative histological scores (0–4) for neutrophil infiltration, fibroblast proliferation, neoangiogenesis, and collagen deposition. Prespecified non-parametric analyses were applied. Results: All animals completed follow-up; no pre-sacrifice deaths occurred. Adhesion severity showed no statistically significant differences between Groups A and B at either timepoint (mean POD4: 0.3 vs. 0.6; POD8: 0.4 vs. 0.8; p > 0.05). In contrast, Group C demonstrated markedly higher adhesion scores (mean POD4: 2.3; POD8: 2.4; both p < 0.001 vs. Groups A and B), with a substantially greater proportion of grade 2–3 adhesions. Histological parameters paralleled these findings: at both POD4 and POD8, Group C showed significantly higher neutrophil, fibroblast, neoangiogenesis, and collagen scores compared with Groups A and B (all p < 0.001). No statistically significant within-group temporal differences were observed between POD4 and POD8. Conclusions: In this experimental model, intraperitoneal polypropylene mesh demonstrated similar early biological response patterns in clean and controlled contamination settings, whereas established intra-abdominal sepsis was associated with a marked escalation of inflammation, fibroproliferation, and adhesion formation. These findings suggest that selective use of synthetic intraperitoneal mesh may be considered when contamination is controlled, while caution is warranted in frankly septic environments. Full article
(This article belongs to the Special Issue Hernia Repair: Current Advances and Challenges)
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23 pages, 14922 KB  
Article
Pneumocystis Colonization Is Associated with Enhanced Pulmonary Remodeling and Activation of Redox-Responsive Pathways in a COPD Experimental Model
by Andrea Méndez, Krishna Coronado and Diego A. Rojas
Antioxidants 2026, 15(5), 526; https://doi.org/10.3390/antiox15050526 - 22 Apr 2026
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Abstract
Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent inflammation and structural alterations in the lung triggered mainly by oxidative stress. Colonization by the opportunistic fungus Pneumocystis has been associated with worse clinical outcomes in COPD, yet its role in airway remodeling remains [...] Read more.
Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent inflammation and structural alterations in the lung triggered mainly by oxidative stress. Colonization by the opportunistic fungus Pneumocystis has been associated with worse clinical outcomes in COPD, yet its role in airway remodeling remains unclear. To this end, an elastase-induced COPD model was established, followed by colonization with Pneumocystis. Lung tissue was analyzed histologically and molecularly to assess epithelial thickness, alveolar morphometric parameters (mean linear intercept [MLI], D0, D1, D2), inflammation, collagen deposition, and the expression of remodeling and oxidative stress markers. Emphysematous damage parameters MLI, D0, D1, and D2 were markedly elevated in co-exposed animals, indicating enhanced alveolar enlargement. Animals with COPD and Pneumocystis colonization showed a significant increase in airway inflammation compared with control, COPD, and Pneumocystis groups. Airway epithelial thickness, mucus metaplasia, and collagen deposition exhibited a summative increase in the COPD/Pneumocystis group. Redox-responsive markers, such as superoxide dismutase (SOD) and catalase, were upregulated. Moreover, protein and mRNA levels of nuclear factor erythroid 2–related factor 2 (Nrf2) and its downstream gene heme oxygenase-1 (Hmox1) were significantly increased, with the strongest activation observed in co-exposed animals. Integrative correlation analysis showed that Pneumocystis burden positively correlated with lung damage, inflammation, and epithelial remodeling. These structural alterations were accompanied by coordinated activation of the antioxidant pathway Nrf2. Taken together, Pneumocystis colonization is associated with enhanced pulmonary remodeling and modulation of antioxidant signaling in experimental COPD, promoting structural and molecular changes that may contribute to disease progression. These findings suggest that Pneumocystis acts as an amplifying factor in COPD-associated lung damage. Full article
(This article belongs to the Special Issue Oxidative Stress and Airway Diseases)
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