Mcgrathfrom0024

To further validate the neuroprotective effect of α-syn inhibition, we used a lentiviral Snca-shRNA (Lv-shSnca) to knockdown Snca. Of note, Lv-shSnca transfection significantly inhibited neuronal apoptosis mediated by the mitochondrial apoptosis pathway in neurons exposed to lipopolysaccharide. This α-syn inhibition improved the disruption to mitochondrial morphology and function, as well as decreased levels of apoptosis. Our results suggest that targeting pathological α-syn may achieve neuroprotection through regulation of mitochondrial homeostasis and suppression of apoptosis in the aged hippocampus, further strengthening the therapeutic potential of targeting α-syn for dNCR.Breast cancer is one of the most common type of tumor and the leading cause of death in the world's female population. Various therapeutic approaches have been used to treat tumors but have not led to complete recovery and have even damaged normal cells in the body. Moreover, metastatic tumors such as breast cancer are much more resistant to treatment, and current treatments have not been very successful in treating them and remain a challenge. Therefore, new approaches should be applied to overcome this problem. Given the importance of hypoxia in tumor survival, we aimed to test the antitumor effects of oxygenated water to decrease hypoxia along with tumor-derived exosomes to target tumor. The purpose of administering oxygenated water and tumor exosomes was to reduce hypoxia and establish an effective immune response against tumor antigens, respectively. For this purpose, the breast cancer mice model was induced using the 4T1 cell line in Balb/c mice and treated with oxygenated water via an intratumoral (IT) and/or intraperitoneal (IP) route and/or exosome (TEX). Oxygenation via the IT+IP route was more efficient than oxygenation via the IT or IP route. The efficiency of oxygenation via the two routes along with TEX led to the best therapeutic outcome. Antitumor immune responses directed by TEX became optimized when systemic (IP) and local (IT) oxygenation was applied compared to administration of TEX alone. Results demonstrated a significant reduction in tumor size and the highest levels of IFN-γ and IL-17 and the lowest levels of IL-4 FoxP3, HIF-1α, VEGF, MMP-2, and MMP-9 in the IT+IP+TEX-treated group. Oxygenated water on the one hand could reduce tumor size, hypoxia, angiogenesis, and metastasis in the tumor microenvironment and on the other hand increases the effective immune response against the tumor systemically. This therapeutic approach is proposed as a new strategy for devising vaccines in a personalized approach.Carbon monoxide releasing molecule-3 (CORM-3) has been shown to protect inflammatory diseases via the upregulation of heme oxygenases-1 (HO-1). However, in rat brain astrocytes (RBA-1), the mechanisms underlying CORM-3-induced HO-1 remain poorly defined. This study used western blot, real-time PCR, and promoter activity assays to determine the levels of HO-1 expression and 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) and dihydroethidium (DHE) to measure reactive oxygen species (ROS). SHP099 We found that CORM-3-induced HO-1 expression was mediated through ROS generation by Nox or mitochondria. The signaling components were differentiated by pharmacological inhibitors and small interfering RNA (siRNA). Subcellular fractions, immunofluorescent staining, and chromatin immunoprecipitation assay were used to evaluate the nuclear translocation and promoter binding activity of Nrf2 induced by CORM-3. The roles of mTOR and FoxO1 in CORM-3-stimulated responses are still unknown in RBA-1 cells. Our results demonstrated that transfection with siRNAs or pretreatment with pharmacological inhibitors attenuated the levels of HO-1 and phosphorylation of signaling components including Akt, mTOR, FoxO1, and Nrf2 stimulated by CORM-3. Moreover, pretreatment with N-acetyl-L-cysteine, diphenyleneiodonium chloride, apocynin, or rotenone blocked nuclear translocation and promoter binding activity of Nrf2 induced by CORM-3. The present study concluded that in RBA-1 cells, CORM-3-induced HO-1 expression is, at least partially, mediated through Nox and mitochondria/ROS-dependent PI3K/Akt/mTOR cascade to activate FoxO1 or ROS leading to activation of Nrf2 activity.Antioxidant and hepatoprotective activities in vitro of saffron petals were examined in this study for better utilizing saffron (Crocus sativus L.) biowaste. Using the DPPH and ABTS radical scavenging method, we compared the antioxidant activity and the content of total flavonoid extracts from petals (TFESP), stamens (TFESS), and both saffron petals and stamens (TFEMS). The results showed that the antioxidant capacity and the flavonoid content of TFESP were higher than those of TFESS and TFEMS. Then, the hepatoprotective activity of TFESP was determined, and the silymarin was used as a positive control. The main components of TFESP were analysed by ultrahigh performance liquid chromatography (UPLC) photodiode array (PDA)/mass spectrometry (MS) and nuclear magnetic resonance (NMR). The result showed that (1) TFESP could release oxidative liver injury induced by tert-butyl hydroperoxide (t-BHP). (2) TFESP could reduce the accumulation of reactive oxygen species (ROS); enhance the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH); and then improve the total antioxidant capacity (T-AOC) in BRL-3A cells. (3) TFESP could enhance the expression of B-cell lymphoma-2 (BCL-2) and decrease the expression of caspase-3 and caspase-9; increase the expression of Kelch-like ECH-associated protein-1 (Keap-1), nuclear factor, erythroid 2-related factor 2 (Nrf2), superoxide dismutase, and heme oxygenase 1 (HO-1); and downregulate inducible nitric oxide synthase (INOS), interleukin-6 (IL-6), and nuclear factor kappa B-9 (NF-κB-9). (4) The main hepatoprotective component of TFESP was identified as kaempferol-3-o-sophoroside. The mechanism may be that kaempferol-3-o-sophoroside can protect t-BHP-induced cell injury by regulating the expression of antioxidant, antiapoptotic, and anti-inflammatory genes. Thus, saffron petals are a potential hepatoprotective resource worthy of development.Visceral artery pseudoaneurysms are rare and potentially fatal unless recognized and treated immediately. Here we present to our mind the first documented case of a ruptured pseudoaneurysm involving the left gastric artery giving rise to Michels' Type II replaced left hepatic artery. An 84-year-old female presented with an acute rupture of such an aneurysm post radical cystectomy. CT Angiogram prior to intervention was key for appropriate catheter selection. Endovascular embolization proved effective, and the patient recovered unremarkably. The case report includes a brief discussion regarding the investigation and management of such ruptures, as well as the rarity of the variant anatomy described.Renal angiomyolipomas are uncommon benign tumors containing fatty tissue. Only a few cases of infiltrating angiomyolipomas have been reported. We aimed to describe a case of a 65-year-old woman presenting a peripheral angiomyolipoma of the left kidney with CT evidence of involvement of the renal vein. The lesion has been found incidentally during abdominal CT for an unrelated reason. The patient underwent surgical treatment considering the vascular extension of the lesion and the risk of thromboembolic complications. The pathological analysis confirmed the diagnosis of renal AML in the upper pole of the left kidney invading the renal vein without malignancy.No post-operative complications and the evolution was favorable.Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare congenital malformation characterized by uterus didelphys, unilateral blind hemivagina, and ipsilateral renal agenesis. link2 The obstructed vagina affects menstrual flow, leading to related clinical symptoms after menarche. However, the age of onset, initial symptoms, and clinical complications differ among patients owing to the different types of vaginal septum. Herein, we report 2 cases. The first case is of a 20-year-old woman who presented with fever; she was diagnosed with vaginitis and pelvic inflammation due to the vaginal septum with ostiole. The second case is of a 12-year-old girl who complained of abdominal pain; she was diagnosed as having pelvic inflammation, omentitis, and suppurative appendicitis due to the atretic vaginal septum.We report a rare case of KIT-negative extra-gastrointestinal stromal tumor, in a 40-year-old woman. Contrast-enhanced computed tomography and magnetic resonance imaging revealed a >15-cm mass of multiple cystic lesions in the greater omentum. link3 Histopathological findings after surgery showed a sheet-like growth of stellate tumor cells from epithelial cells, cystic degeneration, and mucus-like stroma. Immunohistochemistry was positive for discovered on GIST-1 (DOG1) but negative for CD117 (c-kit).Acute renal failure due to primary renal Burkitt lymphoma in children is extremely rare. We report a case with acute secondary renal failure in a 4-year-old boy who presented with abdominal pain, anorexia, and vomiting. Abdominal computed tomography scans showed bilateral nephromegaly with multiple hypoenhancing regions. Renal biopsy confirmed Burkitt lymphoma. There was no lymphadenopathy or evidence of other solid organ involvement. The patient was responsive to treatment using the EPOCH-R protocol (etoposide, prednisone, vincristine, cyclophosphamide , doxorubicin, and rituximab). Here, we describe the clinical and imaging features associated with this rare entity.Chordomas are relatively rare malignant tumors derived from embryonic notochord remnants. Most intracranial chordomas show extradural extension and cause bone erosion. However, a small percentage of these tumors are exclusively intradural and tend to show less aggressive features, although local recurrence and metastatic spread have been described. Intradural chordomas with imaging features similar to epidermoid cysts are exceedingly rare. We describe the case of a nonenhancing and nondestructive intradural prepontine chordoma showing restricted diffusion on magnetic resonance imaging on a 44-year-old man who presented with acute-onset vertigo and vomiting. Subtotal resection of the lesion was performed followed by adjuvant radiation therapy. Histopathological examination revealed a chordoma. This case report highlights the need to include intradural chordomas in the differential diagnosis of a nonenhancing and nondestructive prepontine intradural lesion demonstrating restricted diffusion. Gross total resection, adjuvant radiation therapy in cases of macro/microscopical residual disease and regular follow-up imaging assessment are warranted due to the possibility of local recurrence and metastatic dissemination.Ollier disease is a rare condition presenting with enchondromas in an irregular distribution within the medullary cavity of bones. The disease is well known for sarcomatous transformation to chondrosarcomas. It also increases the risk of other malignancies like leukemia, ovarian tumors, and glial tumors. Central nervous system malignancies associated with Ollier disease are thought to arise by somatic IDH mosaicism with their atypical features of distribution, multifocality, and age of onset. We present a case with imaging consistent with diffuse midline glioma in a patient with Ollier disease. We conclude with a brief review of the literature on Ollier Disease with a focus on central nervous system malignancies, tumorigenesis and pathophysiology.