Dapagliflozin/Hesperidin Combination Mitigates Lipopolysaccharide-Induced Alzheimer's Disease in Rats.

Alzheimer's disease (AD) is the most common form of neurodegenerative disorders worldwide. Its pathologic features include massive neuroinflammation with abnormal deposition of ß-amyloid peptide in the cerebral tissues leading to degeneration of the brain neurons. Adverse effects associated with the traditional drugs used for the treatment of this pathological condition have directed the research efforts towards searching for alternative effective agents with minimal adverse effects. The aim of this study was to elucidate the potential ameliorative effects of dapagliflozin and/or hesperidin on Alzheimer's disease (AD) induced by lipopolysaccharide (LPS) injection in rats. In a rodent model of AD, the effect of dapagliflozin with or without hesperidin on the biochemical parameters and the behavioral tests as well as the histopathological parameters was determined. Each of dapagliflozin and hesperidin restored the behavioral tests to the reference values, augmented the antioxidant defense mechanisms, ameliorated the neuronal inflammatory responses, combatted the changes in Toll-like receptor-4 (TLR-4)/High-mobility group box 1 (HMGB1) protein signaling and receptors of advanced glycation end products (RAGE) levels, and restored the balance between the apoptotic signals and autophagy in the hippocampal tissues. Additionally, both agents exhibited an outstanding ability to combat LPS-induced perturbations in the histopathological and electron microscopic image of the brain tissues. These favorable effects were significantly encountered in the group treated with dapagliflozin/hesperidin combination when compared versus animals treated with either dapagliflozin or hesperidin. In conclusion, inhibition of the hippocampal HMGB1/TLR4/RAGE signaling, the pro-inflammatory axis, and apoptosis alongside augmentation of the antioxidant defenses and autophagy can be regarded as beneficial effects by which dapagliflozin/hesperidin combination may combat LPS-triggered AD.

The Significance of FDG PET/CT-Derived Parameters in Determining Prognosis of Cases with Pancreatic Adenocarcinoma: A Prospective Study.

Background and objectives: Pancreatic adenocarcinoma represents one of the common malignancies with a relatively poor prognosis. However, early detection of this type of cancer may prove to be curable. Recent advancements in the radiological techniques might represent a hope for the early diagnosis and prediction of prognosis of pancreatic adenocarcinoma. This study aimed to assess the prognostic value of the primary tumor volumetric parameters obtained from FDG PET/CT first stage for the overall survival (OS) and progression-free survival (PFS) of patients with pancreatic adenocarcinoma and to explore the possible correlation between serum matrix metalloproteinase-2 (MMP-2) and the patients' characteristics. Methods: Fifty patients with pancreatic adenocarcinoma were subjected to FDG PET/CT scan. The SUVpeak, SUVmax, and the metabolic tumor volume (MTV) were determined, as well as the SUVmean of the liver. Moreover, serum levels of MMP-2 were assessed. Follow-up of the patients was carried out for sixty months with determination of PFS and OS. Results: Peak SUV ≥ 3.9 was significantly correlated with the primary pancreatic lesions' mean total glycolytic activity of >92 g, and MTV and was directly correlated with mortality. There was a positive correlation between peak SUV ≥ 3.9 and 50% SUVmax threshold > 82. Moreover, there was significant correlation between the total glycolytic activity and the studied clinicopathologic factors, except the age and sex of the patients and ECOG performance status. In addition, FDG uptake and the tumor glycolytic activity were substantially linked with a shorter PFS. Similarly, a strong correlation was found between MTV and PFS. Serum MMP-2 levels showed a significant relationship with the performance status, tumor stage, SUVmax threshold, and the glycolytic activity. Conclusions: Peak SUV, main lesion SUVmax, serum MMP-2, and the tumor glycolytic activity are good predictors of PFS of patients with pancreatic adenocarcinoma.

Ameliorative Potential of L-Alanyl L-Glutamine Dipeptide in Colon Cancer Patients Receiving Modified FOLFOX-6 Regarding the Incidence of Diarrhea, the Treatment Response, and Patients' Survival: A Randomized Controlled Trial.

Background and Objectives: Diarrhea induced by chemotherapy may represent a life-threatening adverse effect in cancer patients receiving chemotherapy. FOLFOX, an effective treatment for colon cancer, has been associated with diarrhea with high severity, particularly with higher doses. Management of diarrhea is crucial to increase the survival of cancer patients and to improve the quality of life. Glutamine is an abundant protein peptide found in blood and has a crucial role in boosting immunity, increasing protein anabolism, and decreasing the inflammatory effects of chemotherapy on the mucosal membranes, including diarrhea. This study aimed to provide evidence that parenteral L-alanyl L-glutamine dipeptide may have a positive influence on the incidence of diarrhea, treatment response, and the overall survival in colon cancer patients treated with modified FOLFOX-6 (mFOLFOX-6). Materials and Methods: Forty-four stage II and III colon cancer patients were included in this study where they were treated with the standard colon cancer chemotherapy mFOLFOX-6 and were randomly allocated into glutamine group and placebo group, each of 22 patients. Results: L-alanyl L-glutamine dipeptide was found to be significantly effective in decreasing the frequency and severity of diarrhea when compared to the placebo group, particularly after four and six cycles of mFOLFOX-6. There was no significant difference between the studied groups regarding to the overall survival. Conclusion: L-alanyl L-glutamine dipeptide can be considered as an add-on with chemotherapy to improve the quality of life and the overall survival of colon cancer patients.