Comprehensive Chemical Profiling and Mechanistic Insight into Anticancer Activity of Annona muricata Leaves Extract.

The aqueous extract of Annona muricata L. leaves was thoroughly analyzed using the UPLC-MS/MS, in addition to a new approach of examination of the extract's impact on cancer of EAC(Ehrlich ascites carcinoma) in albino male mice. The aim was to investigate the diversity of the phytochemical constituents of the aqueous leaf capsule extract and their impacts on EAC as anticancer agents. The UPLC-ESI-MS/MS screening resulted in 410 tentatively identified metabolites. Among them, 384 compounds were tentatively identified in a previous study, besides a number of 26 compounds belonging to acetogenins, phenolics, flavonoids, alkaloids, and other miscellaneous compounds, which were exclusively identified in the aqueous extract of the leaf capsule. Interestingly, a new compound was tentatively characterized as galloyl-quinic acid-rutinoside. This study also demonstrated that treating EAC mice with an extract from A. muricata leaves significantly improved the abnormalities in the expression of pro-apoptotic (Bax and caspase-3) and anti-apoptotic (Bcl-2) genes. Furthermore, the extract showed good protection against induced Ehrlich hepatocarcinoma, according to the microscopical, histological, and immune-histochemical analyses of the liver tissues and tumor mass.

Pathological, histochemical, and immune-histochemical studies on some canine-skin neoplasm at Sharkia province, Egypt.

Background: Cutaneous neoplastic disorders are often observed in small mammal pets, such as dogs, regardless of their gender. Aim: An important objective of this work was to give a full account of the clinical, pathological, and immune-histochemical features of several skin tumors in dogs. Methods: This study was a case series in the hospital clinic, Faculty of Veterinary Medicine, Zagazig University, Egypt. Twenty-five dogs (14 males and 11 females) were examined clinically during the period from March 2022 to October 2023. The skin swelling was collected from affected animals and then subjected to a detailed histopathological study to record the different gross and microscopic findings and confirm the diagnosis by immunohistochemistry. Results: Skin neoplasia in dogs was exposed to various clinical signs, and the dogs' ages ranged between 3 and 11 years. Concerning tumor features, the majority of neoplasms were malignant (65.52%) more than benign (34.48%). The study revealed the presence of 29 cases of dogs showed neoplasia with different prevalence rates including squamous cell carcinoma (13.79%), mast cell tumor (6.89%), basal cell tumors (10.34%), histiocytoma (6.89%), trichoepithelioma (10.34%), transmissible venereal tumor (10.34%), trichilemmoma (3.44%), scalp paraganglioma (3.44%), pilomatricoma (10.34%), malignant melanomas (17.24%), and miscellaneous cases as fat necrosis (6.89%), in males and females dogs with different histopathological lesions and immunohistochemistry expressions for pan-cytokeratin (CK), melanocyte-differentiation antigens (S100 protein), and synaptophysin. Conclusion: Malignant melanomas (17.24%) are the extremely common cutaneous tumors diagnosed in this study. Meanwhile, benign tumors such as trichilemmoma, trichoepithelioma, pilomatricoma, and paraganglioma are less frequent in dogs.

The classification of the bladder cancer based on Vision Transformers (ViT).

Bladder cancer is a prevalent malignancy with diverse subtypes, including invasive and non-invasive tissue. Accurate classification of these subtypes is crucial for personalized treatment and prognosis. In this paper, we present a comprehensive study on the classification of bladder cancer into into three classes, two of them are the malignant set as non invasive type and invasive type and one set is the normal bladder mucosa to be used as stander measurement for computer deep learning. We utilized a dataset containing histopathological images of bladder tissue samples, split into a training set (70%), a validation set (15%), and a test set (15%). Four different deep-learning architectures were evaluated for their performance in classifying bladder cancer, EfficientNetB2, InceptionResNetV2, InceptionV3, and ResNet50V2. Additionally, we explored the potential of Vision Transformers with two different configurations, ViT_B32 and ViT_B16, for this classification task. Our experimental results revealed significant variations in the models' accuracies for classifying bladder cancer. The highest accuracy was achieved using the InceptionResNetV2 model, with an impressive accuracy of 98.73%. Vision Transformers also showed promising results, with ViT_B32 achieving an accuracy of 99.49%, and ViT_B16 achieving an accuracy of 99.23%. EfficientNetB2 and ResNet50V2 also exhibited competitive performances, achieving accuracies of 95.43% and 93%, respectively. In conclusion, our study demonstrates that deep learning models, particularly Vision Transformers (ViT_B32 and ViT_B16), can effectively classify bladder cancer into its three classes with high accuracy. These findings have potential implications for aiding clinical decision-making and improving patient outcomes in the field of oncology.

LCMS/MS Phytochemical Profiling, Molecular, Pathological, and Immune-Histochemical Studies on the Anticancer Properties of Annona muricata.

Annona muricate is a tropical plant that is well-known for its edible fruit of therapeutic interest. LCMS/MS analyses were applied to identify phytoconstituents of the ethanolic extract of the whole fruits and the aqueous extract of the edible fruit part, in addition to the investigation of their anticancer properties against Ehrlich ascites carcinoma (EAC) in male albino mice. LCMS/MS analyses resulted in the identification of 388 components, representing a wide array of classes of compounds, including acetogenins as the major constituents, alkaloids, flavonoids, and phenolics. Among them, four compounds were tentatively characterized as new compounds (1-4), including an acid derivative, protocatechuic-coumaroyl-quinic acid (1), and three flavonoid derivatives, dihydromyricetin galloyl hexoside (2), apigenin gallate (3), and dihydromyricetin hexouronic acid hexoside (4). Induction with EAC cells resulted in abnormalities in the gene expression of pro-apoptotic genes (Bax and caspase-3) and anti-apoptotic gene (Bcl-2) in the tumor mass. Moreover, microscopic, histopathological, and immune-histochemical examinations of the tumor mass and liver tissues exhibited extensive growth of malignant Ehrlich carcinoma cells and marked hydropic degeneration of hepatocytes and infiltration by tumor cells to liver tissue with marked inflammatory reaction. These abnormalities were markedly ameliorated aftertreatment of EAC mice with A. muricata extracts.

Mitigation of Toxoplasma gondii-induced ileitis by Trichinellaspiralis infection pinpointing immunomodulation.

The current study sought to investigate the potential role of Trichinellaspiralis infection in the treatment of T. gondii-induced ileitis. Forty male Swiss albino mice were divided into four groups:a normal control group Igiven only phosphate-buffered saline (PBS), Group II givenPBS for 28 days then infected with T. gondii cysts for the induction of gastroenteritis, Group III infected only with T. spiralis larvae, and Group IV concurrently infected with T. spiralis larvae, then 28 days post infection, enteritis was induced by oral inoculation withT. gondii cysts. Histopathologicaland immunohistochemicalassessmentswere performed to determine the levels of inflammatory markers nuclear factor- κB (NF-κB) and myeloperoxidase in the ileum samples.Theconcentrations of cytokinesIFN-γ and IL10 were measured in successive serum samples. Histological assessment revealed severe inflammatory infiltrations in ileum samples of T. gondiimonoinfected mice. In addition, the immunological assessment revealed elevated levels of IFN-γ and decreased IL10 concentrations in blood samples. Clear improvement of inflammations, besidesthe decreasedlevels of IFN-γ and increased IL10 concentrations in blood samples were detected in T. spiraliscoinfected animals.Theileal tissue revealed elevated expression of (NF-κB) and myeloperoxidase signaling, all of which were mitigated by T. spiralis coinfection. There is a possibility that regulatory T cells are immunomodulated, releasing anti-inflammatory cytokines while suppressing pro-inflammatory cytokines, causing its therapeutic impact. Trichinellaspiralis infection has the potential to be used for treatment of T. gondii-induced ileitis. As a consequence of these encouraging results, T. spiralis crude and secretory-excretory antigens coated on nanoparticles are being studied in our future research.

Ameliorative Effect of Thymoquinone-Loaded PLGA Nanoparticles on Chronic Lung Injury Induced by Repetitive Intratracheal Instillation of Lipopolysaccharide in Rats.

Thymoquinone (TQ), the active constituent of Nigella sativa, possesses several benefits in traditional and modern medicines. This study examined the effect of a single dose of Nano-TQ on chronic lung injury induced by repetitive intratracheal installation of lipopolysaccharide (LPS). Rats received LPS twice weekly for 8 weeks via intratracheal installation and a single dose of TQ-PLGA NPs on the day after the last dose of LPS. Six rats from each group were sacrificed after 8 and 10 weeks, and samples were collected for analysis. Repetitive intratracheal installation of LPS caused histopathological alterations, including partial or complete obstruction of the alveoli, interstitial edema, mild fibroblastic proliferation, fibrous strands besides lymphocytes and plasma infiltrations, suffered fetalization, bronchiectasis, hypertrophied arterioles, and others. Investigation of the ultrastructure revealed prominent necrotic pneumocytes with destructed chromatin and remnant of necrotic debris in the narrowing alveolar lumen in LPS-induced rats. TQ-PLGA NPs effectively ameliorated LPS-induced histopathological and ultrastructural alterations in the lung of rats. In addition, TQ-PLGA NPs significantly alleviated serum levels of IL-10 and TGF-ß1 in LPS-induced rats. In conclusion, TQ-PLGA NPs prevented inflammation and tissue injury in the lungs of rats challenged with repetitive intratracheal installation of LPS. Therefore, TQ-PLGA NPs represent a promising candidate for the prevention of lung injury induced by LPS, pending further studies to determine its safety and exact protective mechanism.