LC-qTOF-MS/MS phytochemical profiling of Tabebuia impetiginosa (Mart. Ex DC.) Standl. leaf and assessment of its neuroprotective potential in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tabebuia impetiginosa (Bignoniaceae) was traditionally used for memory enhancement and central nervous system (CNS) stimulation. AIM OF THE STUDY: This study aims to create a metabolic profile of the ethyl acetate fraction of T. impetiginosa (TEF) and investigate for the first time its neuroprotective potential on cyclophosphamide (CP)-induced chemobrain, validating its traditional use. MATERIALS AND METHODS: Metabolite profiling of TEF was performed using Liquid Chromatography coupled with Quadrupole Time of Flight-Mass/Mass Spectrometry (LC-qTOF-MS/MS). For the in vivo study, CP (200 mg/kg, i.p.) was administered to induce cognitive impairment in rats; TEF (30 mg/kg, p.o.) was administered throughout the 14 days of the experiment to assess its role in mitigating CP-induced neuronal deficits. Behavioral tests including locomotor, Y-maze, and passive avoidance tests were conducted. Additionally, biochemical markers such as reduced glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and caspase-3 immunoexpression were assessed in the hippocampus area. RESULTS: Forty-four phytoconstituents were tentatively identified in TEF, mainly iridoids and organic acids. TEF showed significant memory enhancement as evidenced by the increase in step-through latency in the passive avoidance test by 1.5 folds and the increase in sequence alternation percentage (SAP) in the Y-maze test by 67.3%, as compared to CP-group. Moreover, it showed pronounced antioxidant and anti-inflammatory potentials evidenced by the significant elevation in reduced glutathione (GSH) levels by 80% and a pronounced decline in MDA and TNF-α levels by 24% and 45%, respectively relative to the CP group. TEF treatment restored normal hippocampal histological features and attenuated apoptotic caspase-3 expression by 70% compared to the CP group. CONCLUSIONS: TEF can act as a promising natural scaffold in managing the chemobrain induced by CP in cancer patients.

Cytotoxic and antimicrobial mycophenolic acid derivatives from an endophytic fungus Penicillium sp. MNP-HS-2 associated with Macrozamia communis.

Macrozamia communis and its associated endophytic fungi are untapped sources of bioactive metabolites with great potential for medicinal exploitation. Chemical investigation of the mycelial extract derived from an endophytic fungus Penicillium sp. MNP-HS-2 associated with M. communis fruit afforded four mycophenolic acid derivatives recognized as previously undescribed natural products (1-4), together with nine known metabolites (5-13). Chemical structures of isolated compounds were determined based on extensive spectroscopic analyses, including 1D/2D NMR and HRESIMS. The absolute stereochemistry of alternatain E (1) was unambiguously established by comparing its experimental and calculated time-dependent density functional theory electronic circular dichroism spectra (TDDFT-ECD). All isolated compounds were assessed for their antimicrobial and cytotoxic activities, where mycophenolic acid methyl ester (7), displayed significant cytotoxic activity against seven different cell lines with IC50 values in the low micromolar to nanomolar range. Mycophenolene A (3) exhibited significant antibacterial activity against Staphylococcus aureus (MIC = 2.1 µg/mL).

Use of radiographic and histologic scores to evaluate cats with idiopathic megacolon grouped based on the duration of their clinical signs.

Since the duration of clinical signs could be used to identify cases of chronic constipation, in addition, prolonged duration is often associated with irreversible changes. Thus, the main objective of this study was to determine whether the duration of clinical signs of idiopathic megacolon in cats affected their diagnosis and prognosis after treatment. Medical records of cats that either had confirmed megacolon for an unknown cause (cat patients) or with normal bowels (control cats) were reviewed. Cat patients were grouped based on the duration of their clinical signs (constipation/obstipation) to cats <6 months and ≥6 months. For all feline patients, abdominal radiographs (for colonic indexes) and resected colon specimens (for histology) were assessed vs. control cats. Treatment applied to cat patients was also evaluated. Cat patients were older (p = 0.0138) and had a higher maximum colon diameter (MCD; mean 41.25 vs. 21.67 mm, p < 0.0001) and MCD/L5L ratio (1.77 vs. 0.98, p < 0.0001) than controls. Compared to cats with <6 months, cats ≥6 months showed a higher MCD (43.78 vs. 37.12 mm, p < 0.0001) and MCD/L5L ratio (1.98 vs. 1.67, p < 0.0001). Histologically, increased thickness of the smooth muscularis mucosa (54.1 vs. 22.33 µm, p < 0.05), and inner circular (743.65 vs. 482.67 µm, p < 0.05) and outer longitudinal (570.68 vs. 330.33 µm, p < 0.05) smooth muscular layers of the muscularis externa was noted only in cat patients with ≥6 months compared to controls. Similarly, fewer ganglion cells (0.93 vs. 2.87, p < 0.005) and more necrotized myocytes (2.25 vs. 0.07, p < 0.005) were observed in cats with ≥6 months. In contrast to <6 months, the majority of cats (94.4%) with ≥6 months duration did not show any response to medical treatment and therefore underwent surgery with favorable results. In conclusion, this study suggests that the duration of clinical signs should be considered in conjunction with maximal colon scores to evaluate cats for idiopathic megacolon and determine the level of treatment. Functional abnormalities of the colonic smooth muscles may be a possible cause of idiopathic megacolon in cats.

A pilot study of Livin gene and Yes-associated protein 1 expression in hepatocellular carcinoma patients.

BACKGROUND: Livin gene and Yes-Associated Protein 1 (YAP1 (play a pivotal role in organ size control and tumorigenesis. AIM: In the present pilot study, we investigate the expression of Livin gene and YAP1 in hepatitis C virus (HCV) associated hepatocellular carcinoma (HCC) compared to other HCV patients and controls.Methods: the studied patients were divided into three groups 30 patients in each group in addition to 30 healthy subjects as a control group. Relative quantification of Livin gene and YAP-1 were assessed by quantitative Real Time RT-PCR (qPCR) in all studied patients and healthy controls. other laboratory investigations were done including complete blood count (CBC),international normalized ratio (INR) as well as liver function tests and tumor markers. RESULTS: Significant overexpression of Livin gene and YAP-1 was detected in HCC group followed by Hepatitis C Virus (HCV) untreated group then HCV treated group. The relative quantitation (RQ) of both genes showed positive correlation to the carcinoembryonic antigen (CEA) level and a significant relation was found between higher level of Livin and YAP1 genes and tumor size. The overall survival rate was low in those patients with high levels of Livin and YAP 1 genes so they were considered as indicators of a bad prognosis. CONCLUSION: There is overexpression of Livin gene and YAP1 in hepatocellular carcinoma patients. They can be used as indicators of bad prognosis of the disease pathway together with low survival rate.