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This investigation looked at the ameliorative role of camel whey protein hydrolysates-diet (PH) in Oreochromis niloticus stocked under alkaline conditions. One hundred sixty fish (16.02 ± 0.14 g) were allocated equally into four groups with four replications for 30 days. The first (control) and second (alkaline) groups were fed basal diets and maintained in fresh and alkaline water, respectively. The third and fourth groups were fed on a PH diet (basal diet containing 75 g PH/kg) and maintained in fresh water and alkaline water, respectively. The hematology, immune-antioxidant indices, immune-regulatory genes, histopathological investigation of the spleen, and resistance to Aeromonas sobria were investigated. The results showed that the alkaline condition induced hematological disorders (lowered red blood cells, hemoglobin, packed cell volume, and white blood cell count) and immunosuppression (lowered phagocytic activity and index, lysozyme, nitric oxide, and complement 3) in the exposed fish. Alkaline exposure induced oxidative stress through elevation of the malondialdehyde and reduction in the antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, glutathione S-reductase, and reduced glutathione). The immune modulatory genes (tolls like receptor-5, interleukin-1beta, interleukin-6, interleukin-8, interleukin-10, interleukin-17, nuclear factor kappa beta, and tumor necrosis factor-alpha) were down-regulated by exposure to alkaline conditions. The microscopic section of the spleen of the fish subjected to alkaline conditions showed notable hyperplasia of the melanomacrophage centers, besides vascular congestion, endothelial cell hypertrophy, and mild hypercellularity in the erythroid and lymphoid elements. In addition, few sections manifested more pronounced erythroid hyperplasia than the lymphoid one. The survival of the fish subjected to alkaline conditions was reduced during the A. sobria challenge. Feeding on a PH diet, the hematology was restored and the immune-antioxidant functions were modulated. Modulation of the immune-regulatory genes and increased survivability of the alkaline-exposed fish were noticed when fed on the PH diet. Consequently, we can recommend enriching the Nile tilapia diet with a 75 g PH/kg diet especially when reared under alkaline conditions to support the immune functions of the fish., Competing Interests: Declarations. Ethics approval: This study has been authorized by the Zagazig University Authority for Animal Use in Research (ZU-IACUC/2/F/393/2023), and all applicable institutional standards were followed when caring for and using animals in this study. Consent to participate: All authors have participated in this work. Consent for publication: All authors review and approve the manuscript for publication. Conflict of interest: The authors declare that they have no conflict. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature B.V.)

Background/objectives: Carcinoembryonic antigen (CEA) is a cell-surface glycoprotein serving as a drug target, diagnostic marker, and serum marker for cancer monitoring. However, prevalence data on CEA expression in cancer tissues vary considerably. This study was designed to determine CEA expression in normal and neoplastic tissues., Methods: A tissue microarray containing 13,725 samples from 120 different tumor types, as well as 76 different normal tissue types, was analyzed by immunohistochemistry (IHC)., Results: CEA was detectable in 65 (54.2%) of 120 tumor categories, including 49 (40.8%) tumor types with at least one strongly positive case. CEA positivity was most common in colorectal adenomas (100%) and carcinomas (98.7%), other gastrointestinal adenocarcinomas (61.1-80.3%), medullary carcinomas of the thyroid (96.3%), pulmonary adenocarcinoma (73.7%), mucinous carcinomas of the ovary (79.8%) and the breast (43.2%), small-cell carcinomas of the lung (64.3%), and urinary bladder (38.9%). CEA overexpression was linked to high tumor grade and invasive growth ( p < 0.0001 each) in urinary bladder cancer, and estrogen and HER2 receptor positivity ( p ≤ 0.0158) in invasive breast cancer of no special type. In colorectal adenocarcinomas, reduced CEA expression was associated with mismatch repair deficiency ( p < 0.0001)., Conclusions: The comprehensive list of CEA-positive human tumor types demonstrates that CEA is expressed in a broad range of epithelial neoplasms, many of which might benefit from CEA serum monitoring and anti-CEA therapies.

This study assessed the consequence of exposure to a pyrethroid insecticide, fenpropathrin (FPN), on the heart and the probable underlying mechanisms in rats. Moreover, the probable protective effect of curcumin-loaded chitosan nanoparticles (CMN-CNP) was evaluated. Forty male Sprague Dawley rats were distributed into four groups orally given corn oil, CMN-CNP (50 mg/kg b.wt), FPN (15 mg/kg b.wt), or CMN-CNP + FPN for 60 days. The results revealed that FPN exposure increased serum cardiac damage indicators. In addition, a substantial increase in the reactive oxygen species and malondialdehyde content but reduced enzymatic and non-enzymatic antioxidants and altered architecture was recorded in the cardiac tissue of FPN-exposed rats. Additionally, a significant down-regulation of expression of the mitochondrial complexes I-V, mitochondrial dynamics, and antioxidants-related genes but up-regulation of apoptosis-related genes was detected in the FPN-exposed group. Immunofluorescence analyses revealed higher amounts of the harmful protein 4-hydroxynonenal in the heart tissue of FPN-exposed rats. Nevertheless, the earlier disturbances were significantly rescued in the FPN + CMN-CNP treated group. Conclusively, our findings reported the cardiotoxic activity of FPN and the involvement of several mitochondrial imbalances as a probable underlying mechanism. Also, the study findings proved the efficacy of CMN-CNP in combating FPN cardiotoxic effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study evaluated the potential efficacy of eco-friendly biofabricated zinc oxide nanoparticles (GS-ZnONP) (10 mg/kg b.wt) to reduce the impacts of long-term oral acrylamide (ALD) exposure (20 mg/kg b.wt) on the blood cells, immune components, splenic oxidative status, and expression of CD20, CD3, CD4, CD8, TNF-α, caspase-3, microRNA-181a-5p, and microRNA-125-5p in rats in a 60-day experiment. The study findings revealed that GS-ZnONP significantly corrected the ALD-induced hematological alterations. Additionally, the ALD-induced increase in the serum C3, splenic ROS, CD4, CD8, and MDA and histological alterations were significantly repressed in the ALD + GS-ZnONP-treated rats. Instead, the depleted splenic antioxidants and Zn contents were markedly reestablished in the ALD + GS-ZnONP-treated group. Additionally, a significant upregulation of expression of splenic CD3, CD4, CD8, CD20, TNF-α, and caspase-3, but downregulation of microRNA-181a-5p and microRNA-125-5p was detected in the ALD-exposed group. Yet, the former deviations in the gene expressions were corrected in the ALD + GS-ZnONP-treated rats. Furthermore, GS-ZnONP treatment significantly minimized the increased caspase-3 and TNF-α immunoexpression in the splenic tissues of ALD-exposed rats. Conclusively, the study findings proved the efficacy of GS-ZnONP in rescuing ALD-induced disturbances in blood cell populations, immune function, splenic antioxidant status, and immune-related gene expression., Competing Interests: Declarations Ethical approval All animal experiments were approved by the Ethics Committee of Zagazig University in Egypt (approval no. ZU-IACUC/2/F/101/2022) and were per the United Kingdom’s Animals (Scientific Procedures) Act, 1986 and related recommendations, the EU Directive 2010/63/EU for animal experiments, and the National Research Council’s Guide for the Care and Use of Laboratory Animals. In addition, all techniques were described following ARRIVE principles. Consent to participate Not applicable. Consent for publication Not applicable. Competing interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Thyroid transcription factor 1 (TTF-1) immunohistochemistry (IHC) is routinely used for the distinction of primary pulmonary adenocarcinomas. However, TTF-1 can also occur in other malignancies. A tissue microarray containing 17,772 samples from 152 different tumor types was analyzed. Napsin-A, CK20, SATB2, FABP1, and Villin-1 IHC data were available from previous studies. TTF-1 staining was seen in 82 of 152 tumor categories including thyroidal cancers (19-100%), adenocarcinomas (94%), neuroendocrine tumors (67%) of the lung, small cell neuroendocrine carcinomas (71-80%), mesenchymal tumors (up to 42%), and thymomas (39%). Comparative analysis of TTF-1 and Napsin-A revealed a sensitivity/specificity of 94%/86% (TTF-1), 87%/98% (Napsin-A), and 85%/99.1% (TTF-1 and Napsin-A) for the distinction of pulmonary adenocarcinomas. Combined analysis of TTF-1 and enteric markers revealed a positivity for TTF-1 and at least one enteric marker in 22% of pulmonary adenocarcinomas but also a TTF-1 positivity in 6% of colorectal, 2% of pancreatic, and 3% of gastric adenocarcinomas. TTF-1 is a marker of high sensitivity but insufficient specificity for pulmonary adenocarcinomas. A small fraction of TTF-1-positive gastrointestinal adenocarcinomas represents a pitfall mimicking enteric-type pulmonary adenocarcinoma. Combined analysis of TTF-1 and Napsin-A improves the specificity of pulmonary adenocarcinoma diagnosis., Competing Interests: Declarations Ethics approval The usage of archived diagnostic left-over tissues for manufacturing of TMAs and their analysis for research purposes as well as patient data analysis has been approved by local laws (HmbKHG, §12,1) and by the local ethics committee (Ethics commission Hamburg, WF-049/09). All work has been carried out in compliance with the Helsinki Declaration. Conflict of interest The recombinant rabbit monoclonal TTF-1-antibody clone MSVA-312R was provided by MS Validated Antibodies GmbH, Hamburg, Germany (owned by a family member of GS)., (© 2024. The Author(s).)

Background/Objectives: Trefoil factor 1 (TFF1) plays a role in the mucus barrier. Methods: To evaluate the prevalence of TFF1 expression in cancer, a tissue microarray containing 18,878 samples from 149 tumor types and 608 samples of 76 normal tissue types was analyzed through immunohistochemistry (IHC). Results: TFF1 staining was detectable in 65 of 149 tumor categories. The highest rates of TFF1 positivity were found in mucinous ovarian carcinomas (76.2%), colorectal adenomas and adenocarcinomas (47.1-75%), breast neoplasms (up to 72.9%), bilio-pancreatic adenocarcinomas (42.1-62.5%), gastro-esophageal adenocarcinomas (40.4-50.0%), neuroendocrine neoplasms (up to 45.5%), cervical adenocarcinomas (39.1%), and urothelial neoplasms (up to 24.3%). High TFF1 expression was related to a low grade of malignancy in non-invasive urothelial carcinomas of the bladder ( p = 0.0225), low grade of malignancy ( p = 0.0003), estrogen and progesterone receptor expression ( p < 0.0001), non-triple negativity ( p = 0.0005) in invasive breast cancer of no special type, and right-sided tumor location ( p = 0.0021) in colorectal adenocarcinomas. Conclusions: TFF1 IHC has only limited utility for the discrimination of different tumor entities given its expression in many tumor entities. The link between TFF1 expression and parameters of malignancy argues for a relevant biological role of TFF1 in cancer. TFF1 may represent a suitable therapeutic target due to its expression in only a few normal cell types.

Background: Chronic endometritis (CE) is a persistent inflammation of the uterine lining. Although it has a minimal clinical presentation, CE adversely affects the reproductive ability of women. The aims of this study were to detect pathological endometrial patterns in D&C biopsies and to evaluate chronic endometritis in patients living in a high-altitude area (1800 m above sea level) in order to determine the clinical pathological features and prevalence., Materials and Methods: A cross-sectional study conducted at King Faisal Maternity Hospital included 100 samples of D&C biopsies from women complaining of various gynecological symptoms not due to gestational causes. The biopsies underwent tissue processing, H&E staining, and CD138 detection. Blood samples were taken for serological detection of infectious diseases, complete blood count, and chemical parameters., Results: The mean age of women in the study with CE was 48.5 ± 8.5 years, and that of those without CE was 46.9 ± 9.7 years. The most common complaints were abnormal uterine bleeding, accounting for 83%. CE was present in 8% of cases, and there was a nonsignificant difference in hematological parameters between women with CE and those with other pathological diagnoses. There were also nonsignificant differences in chemical parameters, except for FSH and LH levels, which showed a significant difference, with p -values of 0.05 and 0.02, respectively. It can be concluded that the most common gynecological complaint of women in this study was abnormal uterine bleeding., Conclusions: The most commonly diagnosed pathological endometrial disorder in D&C biopsies was disordered proliferative endometrium, followed by endometrial polyps and endometrial hyperplasia. All of these are usually associated with hormonal disturbance, which appeared to be very common in the women in this study. The prevalence of chronic endometritis detected in our study was 8%, which is relatively high.

The Melan-A (melanocyte antigen) protein, also termed 'melanoma antigen recognized by T cells 1' (MART-1) is a protein with unknown function whose expression is specific for the melanocyte lineage. Antibodies against Melan-A are thus used for identifying melanocytic tumors, but some Melan-A antibodies show an additional - diagnostically useful - cross-reactivity against an unspecified protein involved in corticosteroid hormone synthesis. To comprehensively compare the staining patterns of a specific and a cross-reactive Melan-A antibody in normal and neoplastic tissues, tissue microarrays containing 15,840 samples from 133 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. For the Melan-A-specific antibody 'Melan-A specific' (MSVA-900M), Melan-A positivity was seen in 96.0% of 25 benign nevi, 93.0% of 40 primary and 86.7% of 75 metastatic melanomas, 82.4% of 85 renal angiomyolipomas as well as 96.4% of 84 neurofibromas, 2.2% of 46 granular cell tumors, 1.0% of 104 schwannomas, and 1.1% of 87 leiomyosarcomas. The cross-reactive antibody 'Melan-A+' (MSVA-901M+) stained 98.1% of the tumors stained by 'Melan-A specific'. In addition, high positivity rates were seen in sex-cord-stroma tumors of the ovary (35.3%-100%) and the testis (86.7%) as well as for adrenocortical neoplasms (76.3%-83.0%). Only nine further tumor groups showed Melan-A+ staining, including five different categories of urothelial carcinomas. Our data provide a comprehensive overview on the staining patterns of specific and cross-reactive Melan-A antibodies. The data demonstrate that both antibodies are highly useful for their specific purpose. It is important for pathologists to distinguish these two Melan-A antibody subtypes for their daily work., (© 2024 The Author(s). APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Stimulator of interferon genes protein (STING) activates the immune response in inflammatory cells. STING expression in cancer cells is less well characterized, but STING agonists are currently being evaluated as anticancer drugs. A tissue microarray containing 18,001 samples from 139 different tumor types was analyzed for STING by immunohistochemistry. STING-positive tumor cells were found in 130 (93.5%) of 139 tumor entities. The highest STING positivity rates occurred in squamous cell carcinomas (up to 96%); malignant mesothelioma (88.5%-95.7%); adenocarcinoma of the pancreas (94.9%), lung (90.3%), cervix (90.0%), colorectum (75.2%), and gallbladder (68.8%); and serous high-grade ovarian cancer (86.0%). High STING expression was linked to adverse phenotypes in breast cancer, clear cell renal cell carcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, and papillary carcinoma of the thyroid ( p < 0.05). In pTa urothelial carcinomas, STING expression was associated with low-grade carcinoma ( p = 0.0002). Across all tumors, STING expression paralleled PD-L1 positivity of tumor and inflammatory cells ( p < 0.0001 each) but was unrelated to the density of CD8+ lymphocytes. STING expression is variable across tumor types and may be related to aggressive tumor phenotype and PD-L1 positivity. The lack of relationship with tumor-infiltrating CD8+ lymphocytes argues against a significant IFN production by STING positive tumor cells.

Mucin 6 (MUC6) is a secreted gel-forming mucin covering the surfaces of gastrointestinal and other tissues. Published work demonstrates that MUC6 can also be expressed in several cancer types and can aid in the distinction of different tumor entities. To systematically analyze MUC6 expression in normal and cancerous tissues, a tissue microarray containing 15 412 samples from 119 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. At least a weak MUC6 positivity was seen in 50 of 119 (42%) tumor entities. Thirty-three tumor entities included tumors with strong positivity. MUC6 immunostaining was most frequent in mucinous carcinomas of the breast (44%), adenocarcinomas of the stomach (30%-40%) and esophagus (35%), and neuroendocrine carcinomas of the colon. Strong MUC6 staining was linked to advanced pT stage (p = 0.0464), defective mismatch repair status and right-sided tumor location (p < 0.0001 each) in colorectal cancer, as well as to high tumor grade (p = 0.0291), nodal metastasis (p = 0.0485), erb-b2 receptor tyrosine kinase 2 positivity (p < 0.0001) and negative estrogen receptor (p = 0.0332)/progesterone receptor (p = 0.0257) status in breast carcinomas of no special type. The broad range of tumor types with MUC6 expression limits the utility of MUC6 immunohistochemistry for the distinction of different tumor types., (© 2023 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

As a result of its expression in corresponding normal cell types, inhibin alpha (INHA) is used as an immunohistochemical marker for adrenocortical neoplasms and testicular or ovarian sex cord stromal tumors. However, other tumors can also express INHA. To comprehensively determine INHA expression in cancer, a tissue microarray containing 15,012 samples from 134 different tumor types and subtypes was analyzed by immunohistochemistry. INHA positivity was found in 72 of 134 tumor categories, including 26 categories with ≥1 strongly positive case. A moderate to strong INHA positivity was found in 100% of 37 granulosa cell tumors of the ovary, 100% of 43 other sex cord stromal tumors of the ovary/testis, 100% of 31 granular cell tumors, 78.5% of 28 adenomas, 44% of 25 carcinomas of the adrenal cortex, and 46.7% of 15 pancreatic acinar cell carcinomas. At least a weak INHA positivity was seen in <33% of cases of 46 additional tumor entities. In summary, these data support the use of INHA antibodies for detecting sex cord stromal tumors, granular cell tumors, and adrenocortical neoplasms. Since INHA can also be found in other tumor entities, INHA immunohistochemistry should only be considered as a part of any panel for the distinction of tumor entities.

Syndecan-1 (CD138) is a transmembrane proteoglycan known to be expressed in various normal and malignant tissues. It is of interest because of a possible prognostic role of differential expression in tumors and its role as a target for indatuximab, a monoclonal antibody coupled with a cytotoxic agent. To comprehensively analyze CD138 in normal and neoplastic tissues, we used tissue microarrays (TMAs) for analyzing immunohistochemically detectable CD138 expression in 2,518 tissue samples from 85 different tumor entities and 76 different normal tissue types. The data showed that CD138 expression is abundant in tumors. At least an occasional weak CD138 immunostaining could be detected in 71 of 82 (87%) different tumor types, and 58 entities (71%) had at least one tumor with a strong positivity. In normal tissues, a particularly strong expression was found in normal squamous epithelium of various organs, goblet and columnar cells of the gastrointestinal tract, and in hepatocytes. The highly standardized analysis of most human cancer types resulted in a ranking order of tumors according to the frequency and levels of CD138 expression. CD138 immunostaining was highest in squamous cell carcinomas such as from the esophagus (100%), cervix uteri (79.5%), lung (85.7%), vagina (89.7%) or vulva (73.3%), and in invasive urothelial cancer (76.2%). In adenocarcinomas, CD138 was also high in lung (82.9%) and colorectal cancer (85.3%) but often lower in pancreas (73.3%), stomach (54.2% in intestinal type), or prostate carcinomas (16.3%). CD138 expression was usually low or absent in germ cell tumors, sarcomas, endocrine tumors including thyroid cancer, and neuroendocrine tumors. In summary, the preferential expression in squamous cell carcinomas of various sites makes these cancers prime targets for anti-CD138 treatments once these might become available. Abundant expression in many different normal tissues might pose obstacles to exploiting CD138 as a therapeutic target, however., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2019 Simon Kind et al.)

Syndecan-1 (CD138) is a transmembrane proteoglycan expressed in normal and malignant tissues. It is of interest because of a possible prognostic effect in tumors and as a target for Indatuximab, a monoclonal antibody coupled to a cytotoxic agent. To assess the prognostic role of CD138 expression in breast cancer (BCa), a tissue microarray containing 1535 BCa specimens was analyzed by immunohistochemistry. Cytoplasmic, membranous, and stromal CD138 staining was separately analyzed. In normal breast tissue, CD138 staining was limited to epithelial cell membranes. In cancers, membranous staining tended to become weaker or even disappeared (38.3% of cancers with absence of membranous staining) but cytoplasmic and stromal staining newly appeared in 29.7% and 58.1% of cancers. Loss of membranous epithelial CD138 staining as well as presence of cytoplasmic and stromal CD138 positivity were-to a variable degree-associated with high pT, high grade, nodal metastasis, estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor 2+, and poor overall patient survival. A combined analysis of epithelial and stromal CD138 expression revealed a link to overall patient survival (P < .0001) with best prognosis for patients with stromal positivity and absence of cytoplasmic staining, the worst prognosis for cancers with cytoplasmic staining and stromal negativity and intermediate prognosis for patients having either cytoplasmic staining or stromal negativity. In multivariate analyses, CD138 was not independent of established prognostic features. In summary, these data reveal a compartment depending prognostic effect of CD138 expression in BCa with cytoplasmic positivity being linked to aggressive cancer and stromal CD138 being linked to a more favorable prognosis., (© 2019 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.)

Background: Nodal metastasis (N1) is a strong prognostic parameter in prostate cancer; however, lymph node evaluation is always incomplete., Objective: To study the prognostic value of lymphatic invasion (L1) and whether it might complement or even replace lymph node analysis in clinical practice., Design, Setting, and Participants: Retrospective analysis of pathological and clinical data from 14 528 consecutive patients., Intervention: Radical prostatectomy., Outcome Measurements and Statistical Analysis: The impact of L1 and N1 on patient prognosis was measured with time to biochemical recurrence as the primary endpoint., Results and Limitations: Nodal metastases were found in 1602 (12%) of 13 070 patients with lymph node dissection. L1 was seen in 2027 of 14 528 patients (14%) for whom lymphatic vessels had been visualized by immunohistochemistry. N1 and L1 continuously increased with unfavorable Gleason grade, advanced pT stage, and preoperative prostate-specific antigen (PSA) values (p<0.0001 each). N1 was found in 4.3% of 12 501 L0 and in 41% of 2027 L1 carcinomas (p<0.0001). L1 was seen in 11% of 9868 N0 and in 61% of 1360 N1 carcinomas (p<0.0001). Both N1 and L1 were linked to PSA recurrence (p<0.0001 each). This was also true for 17 patients with isolated tumor cells (ie, <200 unequivocal cancer cells without invasive growth) and 193 metastases ≤1mm. Combined analysis of N and L status showed that L1 had no prognostic effect in N1 patients but L1 was strikingly linked to PSA recurrence in N0 patients. N0L1 patients showed a similar outcome as N1 patients., Conclusions: Analysis of lymphatic invasion provides comparable prognostic information than lymph node analysis. Even minimal involvement of the lymphatic system has pivotal prognostic impact in prostate cancer. Thus, a thorough search for lymphatic involvement helps to identify more patients with an increased risk for disease recurrence., Patient Summary: Already minimal amounts of tumor cells inside the lymph nodes or intraprostatic lymphatic vessels have a severe impact on patient prognosis., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)