Brain Tumor Classification from MRI Using Image Enhancement and Convolutional Neural Network Techniques.

The independent detection and classification of brain malignancies using magnetic resonance imaging (MRI) can present challenges and the potential for error due to the intricate nature and time-consuming process involved. The complexity of the brain tumor identification process primarily stems from the need for a comprehensive evaluation spanning multiple modules. The advancement of deep learning (DL) has facilitated the emergence of automated medical image processing and diagnostics solutions, thereby offering a potential resolution to this issue. Convolutional neural networks (CNNs) represent a prominent methodology in visual learning and image categorization. The present study introduces a novel methodology integrating image enhancement techniques, specifically, Gaussian-blur-based sharpening and Adaptive Histogram Equalization using CLAHE, with the proposed model. This approach aims to effectively classify different categories of brain tumors, including glioma, meningioma, and pituitary tumor, as well as cases without tumors. The algorithm underwent comprehensive testing using benchmarked data from the published literature, and the results were compared with pre-trained models, including VGG16, ResNet50, VGG19, InceptionV3, and MobileNetV2. The experimental findings of the proposed method demonstrated a noteworthy classification accuracy of 97.84%, a precision success rate of 97.85%, a recall rate of 97.85%, and an F1-score of 97.90%. The results presented in this study showcase the exceptional accuracy of the proposed methodology in accurately classifying the most commonly occurring brain tumor types. The technique exhibited commendable generalization properties, rendering it a valuable asset in medicine for aiding physicians in making precise and proficient brain diagnoses.

Alpha-Mangostin as a New Therapeutic Candidate for Concanavalin A-Induced Autoimmune Hepatitis: Impact on the SIRT1/Nrf2 and NF-κB Crosstalk.

Alpha-mangostin (α-MN) is a xanthone obtained from Garcinia mangostana that has diverse anti-oxidative and anti-inflammatory potentials. However, its pharmacological activity against autoimmune hepatitis (AIH) has not been investigated before. Concanavalin A (Con A) was injected into mice to induce AIH and two doses of α-MN were tested for their protective effects against Con A-induced AIH. The results demonstrated the potent hepatoprotective activity of α-MN evidenced by a remarkable decrease of serum indices of the hepatic injury and amendment of the histological lesions. α-MN significantly attenuated the level and immuno-expression of myeloperoxidase (MPO) indicating a decrease in the neutrophil infiltration into the liver. Additionally, the recruitment of the CD4+ T cell was suppressed in the α-MN pre-treated animals. α-MN showed a potent ability to repress the Con A-induced oxidative stress evident by the reduced levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and protein carbonyl (PC), as well as the enhanced levels of antioxidants as the reduced glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (TAC). The ELISA, RT-PCR, and IHC analyses revealed that α-MN enhanced the sirtuin1/nuclear factor erythroid 2 related factor-2 (SIRT1/Nrf2) signaling and its downstream cascade genes concurrently with the inhibition of the nuclear factor kappa B (NF-κB) and the inflammatory cytokines (tumor necrosis factor-alpha and interleukine-6) signaling. Taken together, these results inferred that the hepatoprotective activity of α-MN could prevent Con A-induced AIH through the modulation of the SIRT1/Nrf2/NF-κB signaling. Hence, α-MN may be considered as a promising candidate for AIH therapy.

Generation of Combinatorial Lentiviral Vectors Expressing Multiple Anti-Hepatitis C Virus shRNAs and Their Validation on a Novel HCV Replicon Double Reporter Cell Line.

Despite the introduction of directly acting antivirals (DAAs), for the treatment of hepatitis C virus (HCV) infection, their cost, patient compliance, and viral resistance are still important issues to be considered. Here, we describe the generation of a novel JFH1-based HCV subgenomic replicon double reporter cell line suitable for testing different antiviral drugs and therapeutic interventions. This cells line allowed a rapid and accurate quantification of cell growth/viability and HCV RNA replication, thus discriminating specific from unspecific antiviral effects caused by DAAs or cytotoxic compounds, respectively. By correlating cell number and virus replication, we could confirm the inhibitory effect on the latter of cell over confluency and characterize an array of lentiviral vectors expressing single, double, or triple cassettes containing different combinations of short hairpin (sh)RNAs, targeting both highly conserved viral genome sequences and cellular factors crucial for HCV replication. While all vectors were effective in reducing HCV replication, the ones targeting viral sequences displayed a stronger antiviral effect, without significant cytopathic effects. Such combinatorial platforms as well as the developed double reporter cell line might find application both in setting-up anti-HCV gene therapy approaches and in studies aimed at further dissecting the viral biology/pathogenesis of infection.

Novel scaffold hopping of potent benzothiazole and isatin analogues linked to 1,2,3-triazole fragment that mimic quinazoline epidermal growth factor receptor inhibitors: Synthesis, antitumor and mechanistic analyses.

A series of benzothiazole/isatin linked to 1,2,3-triazole moiety and terminal sulpha drugs 5a-e and 6a-e were synthesized and evaluated for cytotoxic activity against a panel of cancer cell lines. The novel compounds showed variable IC50 range of activity and some of them were potent compared to reference drug. The promising compounds were subjected as postulated the mimicry proposal for quinazoline-based EGFR inhibitors for their inhibitory profile against EGFR TK enzyme. That data obtained revealed that most of these compounds were potent EGFR TK inhibitors at nanomolar concentrations. Among these, compounds 5a and 5b showed more potent activity on EGFR compared to erlotinib (IC50 103 and 104 versus 67.6 nM). Based upon the results, molecular docking analysis was performed on EGFR receptor and proved the strong contribution of fragments; benzothiazole, isatin, and triazole to the binding ATP pocket. When these selected compounds 5a and 5b were tested in an HepG2 model, they could effectively inhibited tumor growth, strongly induced cancer cell apoptosis, and suppressed cell cycle progression leading to DNA fragmentation. Well-DMET profile of the most active derivatives was presented and compared to the reference drugs. Taken together, we introduced novel triazole-sulpha drug hybrid for the first time as EGFR inhibitors and the results of our studies indicate that the newly discovered inhibitors have significant potential for anticancer treatment.

Neurochemical, neurobehavioral and histochemical effects of therapeutic dose of l-dopa on striatal neurons in rats: Protective effect of virgin coconut oil.

Despite the fact that levodopa has proven its effectiveness in treating the symptoms of Parkinson's disease (PD), increasing concerns have emerged about its possible long-term toxic effects on dopamine (DA) neurons. The study investigated the possible ameliorative effect of virgin coconut oil against l-dopa- induced neurotoxicity in adult rats. A total number of 40 rats were divided into four groups. Briefly, the first served as control, the second was orally administered virgin coconut oil (1.42 mL/kg), the third group was administered a single daily dose of l-dopa/carbidopa (100/10 mg/kg/day, p.o) and the fourth group pre-treated with virgin coconut oil then administered a single daily dose of l-dopa/carbidopa. The different treatments were extended for 30 days. l-dopa treated group exhibited aggressive behavior and behavioral abnormalities in open field test compared to control group. In addition, l-dopa treatment caused significant increase in the levels of striatal dopamine and norepinephrine and their metabolites with concomitant decrease of serotonin and its metabolite. Moreover, l-dopa treatment increased histamine and GABA levels. In addition, l-dopa treatment induced oxidative stress and energy crisis. The histological and immunohistochemical studies showed that l-dopa caused a remarkable neurodegeneration and increased glial fibrillary acidic protein (GFAP) immunoexpression in the striatal area. Virgin coconut oil co-treatment significantly minimized the harmful effects of l-dopa. In conclusion, the present study revealed that virgin coconut oil provided a notable protection against l-dopa's untoward effects.

Antioxidant, anti-inflammatory and anti-fibrotic effects of Boswellia serrate gum resin in CCl4-induced hepatotoxicity.

The present study aims to investigate the potential antioxidant, anti-inflammatory and anti-fibrotic effects of Boswellia serrate (BS) gum resin against carbon tetrachloride (CCl4)-induced liver damage. Four groups consisting of eight rats each were designated: Group I, normal healthy control; group II, CCl4-induced liver fibrosis; group III, CCl4-induced liver fibrosis followed by BS treatment daily for two weeks; and group IV, CCl4-induced liver fibrosis followed by silymarin treatment daily for two weeks. Expression of tumor necrosis factor-α (TNF-α) and nuclear factor κB (NF-κB), interleukin-6 (IL-6), transforming growth factor-ß (TGF-ß) and cyclooxygenase-2 (COX-2) were assessed, in addition to histopathological and fibrotic changes in liver tissues isolated from the rats. BS significantly ameliorated CCl4-induced increases in serum aspartate (AST) and alanine transaminase (ALT) levels, reduced lactate dehydrogenase (LDH) activities in addition to restoring total bilirubin, triglyceride and albumin levels. BS treatment also alleviated oxidative stress and improved total antioxidant capacity in the liver, and reduced the expression of TNF-α, NF-κB, TGF-ß, IL-6 and COX-2. On a histopathological level, BS treatment also exhibited antifibrotic activity. In conclusion, these findings suggest that BS contains potentially hepatoprotective effects against CCl4-induced liver injury via its antioxidant, anti-inflammatory and antifibrotic characteristics.

Design, synthesis, molecular docking of new lipophilic acetamide derivatives affording potential anticancer and antimicrobial agents.

Fifteen new substituted N-2-(2-oxo-3-phenylquinoxalin-1(2H)-yl) acetamides 5a-f, 6a-f, and 8a-c were synthesized by reacting ethyl 2-(2-oxo-3-phenylquinoxalin-1(2H)-yl)acetate with various primary amines including benzylamines, sulfonamides, and amino acids. The in vitro antimicrobial screening of the target compounds was screened to assess their antibacterial and antifungal activity. As a result, seven compounds namely; 5a, 5c, 5d, 6a, 6c, 8b and 8c showed a promising broad spectrum antibacterial activity against both Gram-positive and Gram-negative strains. Among these, the analogs 5c and 6d were nearly as equiactive as ciprofloxacin drug. Meanwhile, four compounds namely; 5c, 6a, 6f and 8c exhibited appreciable antifungal activity with MIC values range 33-40 mg/mL comparable with clotrimazole (MIC 25 mg/mL). In addition, the anticancer effects of the synthesized compounds were evaluated against three cancer lines. The data obtained revealed the benzylamines and sulpha derivatives were the most active compounds especially 5f and 6f ones. Further EGFR enzymatic investigation was carried out for these most active compounds 5f and 6f resulting in inhibitory activity by 1.89 and 2.05 µM respectively. Docking simulation was performed as a trial to study the mechanisms and binding modes of these compounds toward the enzyme target, EGFR protein kinase enzyme. The results revealed good compounds placement in the active sites and stable interactions similar to the co-crystallized reference ligand. Collectively, the analogs 5f and 6f could be further utilized and optimized as good cytotoxic agents.