Mycotic Aortic Aneurysm Secondary to Salmonella enterica Infection: A Case Report and Treatment Approach.

Mycotic (infected) aortic aneurysm is a severe clinical condition with high morbidity and mortality. Salmonella spp. is a Gram-negative, rod-shaped bacteria that is typically limited to the gastrointestinal tract and resolves spontaneously but can progress to invasive infections such as bacteremia. Serious complications may arise, particularly in debilitated, elderly, and neonatal patients. We describe the case of a 74-year-old female with a history of diabetes and hypertension who presented with shortness of breath, fever, chills, abdominal pain, vomiting, and diarrhea. The patient's blood culture tested positive for Salmonella enterica, and she was given ceftriaxone based on the results, but he remained symptomatic. A computed tomography scan of the chest with contrast revealed a mycotic aneurysm of the thoracic aorta. The patient was urgently transferred to a higher level of care and underwent emergency thoracic endovascular aortic repair with stenting and intravenous antibiotics. The presence of an infected aneurysm and associated abscess formation in such high-risk patients makes the endovascular approach more suitable than other options such as open surgery, aneurysmal excision and ligation without arterial reconstruction, excision with immediate reconstruction, and excision with interval reconstruction.

The prospective effect of fucoidan on splenic dysfunction caused by oxaliplatin in male rats through endoplasmic stress dynamics.

Fucoidans (FUCs) are highly sulfated polysaccharides demonstrating multiple actions in different systems. Oxaliplatin (OXA) is a platinum-containing chemotherapeutic agent with several side effects that restrict its usage. The current study aimed to determine the potential effect of FUC in male rats with splenic dysfunction induced by OXA. Eighty adult male rats aged (8-9 weeks) weighing (190-230 g) were divided into four groups: (Group I: the control group): Rats were administrated normal saline; (Group II: controls treated by FUC): Rats were treated with FUC; (Group III: Splenic dysfunction group): Rats were treated with 8 mg/kg OXA. (IV: Splenic dysfunction treated by FUC): Rats were treated by OXA as Group III, then fucoidan was given. At the end of the experiment, blood was collected to determine red blood cells and white blood cells. Splenic tissues were divided into one part for biochemical assays, oxidative stress markers as MDA and catalase, inflammatory markers (TNF-alpha, IL6), and apoptotic markers (caspase 3) and gene expression of Nrf2, Mapk1 gene expression, and endoplasmic stress parameters and the other part was used for immunohistochemical and histopathological analysis. Compared to the OXA-induced splenic dysfunction group, FUC significantly decreased high levels of MDA, TNF- alpha, IL6, caspase-3, Mapk1, endoplasmic stress induced by OXA, and increased the level of catalase and Nrf2. Fucoidan has corrected the histopathological and immunohistochemical changes compared to the OXA-induced splenic dysfunction group. In conclusion, our findings suggest that fucoidan has a significant role in the treatment of splenic dysfunction induced by OXA.

Linking mitochondrial dynamics and fertility: promoting fertility by phoenixin through modulation of ovarian expression of GnRH receptor and mitochondrial dynamics proteins DRP-1 and Mfn-2.

Obesity is linked to reproductive disorders. Novel neuropeptide phoenixin demonstrated many therapeutic actions. In this study, we aim to evaluate phoenixin's potential effect in obesity-induced infertility through modulating mitochondrial dynamics. Ninety adult female rats were divided to 4 groups: (I), fed with normal pellet diet; (II), given phoenixin; (III), fed with high-fat diet. Rats that developed obesity and infertility were divided to 2 groups: (III-A), received no further treatment; (III-B), given phoenixin. Our results showed that phoenixin treatment in obese infertile rats significantly decreased serum levels of insulin and testosterone and ovarian levels of dynamin-related protein1(Drp1),reactive oxygen species ROS, TNF-α, MDA, and caspase-3. Phoenixin treatment also significantly increased serum estrogen progesterone, LH, and FSH together with ovarian levels of GnRH receptor (GnRHR), mitofusin2(Mfn2), mitochondrial transmembrane potential (ΔΨm), and electron transport chain (ETC) complex-I significantly when compared with obese group. Ovarian histopathological changes were similarly improved by phoenixin. Our data demonstrate phoenixin's role in improving obesity-induced infertility.

The Ameliorative Effect of Empagliflozin in Vigabatrin-Induced Cerebellar/Neurobehavioral Deficits: Targeting mTOR/AMPK/SIRT-1 Signaling Pathways.

Introduction. Vigabatrin (VGB) is an antiepileptic drug that acts to irreversibly inhibit the γ-aminobutyric acid (GABA) transaminase enzyme, elevating GABA levels. Broad studies have established that long-term treatment and/or high doses of VGB lead to variable visual defects. However, little attention has been paid to its other side effects, especially those demonstrating cerebellar involvement. Sodium glucose-linked co-transporter 2 (SGLT2) inhibitors are antidiabetic agents with protective effects far greater than expected based on their anti-hyperglycemic effect. Method. Our study herein was designed to investigate the possible ameliorative effect of empagliflozin, the SGLT2 inhibitors, in VGB-induced cerebellar toxicity. A total of 40 male Wistar rats were allocated equally into 4 groups: Group I: control group; Group II: VGB group; Group III empagliflozin treated VGB group; and Group IV: empagliflozin treated group. All groups were subjected to the detection of cerebellar messenger RNA gene expression of silent mating type information regulation 2 homolog 1 (SIRT1) and Nucleoporin p62 (P62). Mammalian target of rapamycin (mTOR), adenosine monophosphate-activated protein kinase (AMPK), and beclin1 levels were assessed by the ELISA technique while malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected spectrophotometrically. Immuno-histochemical studies, focusing on glial fibrillary acidic protein (GFAP) and S100 were performed, and the optical color density and the mean area percentage of GFAP positive astrocytes and the number of S 100 positive cells were also counted. Results. Following empagliflozin treatment, we documented significant upregulation of both SIRT1 and P62 mRNA gene expression. Additionally, AMPK, Beclin1 levels, and SOD activity were significantly improved, while both mTOR and MDA levels were significantly reduced. Conclusions. We concluded for the first time that empagliflozin efficiently ameliorated the VGB-induced disrupted mTOR/AMPK/SIRT-1 signaling axis with subsequent improvement of the autophagy machinery and mitigation of the oxidative and inflammatory cellular environment, paving the way for an innovative therapeutic potential in managing VGB-induced neurotoxicity.

Cdc48/VCP and Endocytosis Regulate TDP-43 and FUS Toxicity and Turnover.

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron degenerative disease. TDP-43 (TAR DNA-binding protein 43) and FUS (fused in sarcoma) are aggregation-prone RNA-binding proteins that in ALS can mislocalize to the cytoplasm of affected motor neuron cells, often forming cytoplasmic aggregates in the process. Such mislocalization and aggregation are implicated in ALS pathology, though the mechanism(s) of TDP-43 and FUS cytoplasmic toxicity remains unclear. Recently, we determined that the endocytic function aids the turnover (i.e., protein degradation) of TDP-43 and reduces TDP-43 toxicity. Here, we identified that Cdc48 and Ubx3, a Cdc48 cofactor implicated in endocytic function, regulates the turnover and toxicity of TDP-43 and FUS expressed in Saccharomyces cerevisiae Cdc48 physically interacts and colocalizes with TDP-43, as does VCP, in ALS patient tissue. In yeast, FUS toxicity also depends strongly on endocytic function but not on autophagy under normal conditions. FUS expression also impairs endocytic function, as previously observed with TDP-43. Taken together, our data identify a role for Cdc48/VCP and endocytic function in regulating TDP-43 and FUS toxicity and turnover. Furthermore, endocytic dysfunction may be a common defect affecting the cytoplasmic clearance of ALS aggregation-prone proteins and may represent a novel therapeutic target of promise.

Diagnostic Value of Glypican-3 for Hepatocellular Carcinomas

Background: Hepatocellular carcinoma (HCC) is a common and dangerous malignancy in many parts of the world, and especially in Egypt. Early diagnosis is the most important step in successful HCC management. However most cases are detected at late stage making effective intervention impossible. Aim: The aim of this study was to evaluate the potential of Glypican-3 (GPC-3) to aid in diagnosis of HCC, especially in patients with low serum alpha-fetoprotein (AFP). Subjects and methods: Serum GPC-3 was assessed by flow-cytometry and serum AFP by enzyme-linked immunosorbent assay (ELISA) in 40 HCC patients with AFP< 400ug\l. (GI), 40 HCC patients with AFP> 400ug\l. (GII) and 20 healthy controls (GIII). Results: GPC-3 was found to be significantly elevated in HCC as compared to healthy subjects (GI 38.2±22. 5, GII 50.2±22.6, and GIII 2.24±1.19), with sensitivities of 85% for GI and 84% for GII and specificities of 95% for GI and 92% for GII. AFP showed respective sensitivities of 50% and 79%, and specificities of 80% and 90%, for HCC diagnosis. The combination of GPC-3 with AFP achieved the highest sensitivity (98.5%) and specificity (97.8%). Conclusion: Serum GPC-3 has a better sensitivity than AFP for the diagnosis of HCC. Combination of two markers appears warranted for greatest accuracy.

The identity of proteins associated with a small heat shock protein during heat stress in vivo indicates that these chaperones protect a wide range of cellular functions.

The small heat shock proteins (sHSPs) are a ubiquitous class of ATP-independent chaperones believed to prevent irreversible protein aggregation and to facilitate subsequent protein renaturation in cooperation with ATP-dependent chaperones. Although sHSP chaperone activity has been studied extensively in vitro, understanding the mechanism of sHSP function requires identification of proteins that are sHSP substrates in vivo. We have used both immunoprecipitation and affinity chromatography to recover 42 proteins that specifically interact with Synechocystis Hsp16.6 in vivo during heat treatment. These proteins can all be released from Hsp16.6 by the ATP-dependent activity of DnaK and co-chaperones and are heat-labile. Thirteen of the putative substrate proteins were identified by mass spectrometry and reveal the potential for sHSPs to protect cellular functions as diverse as transcription, translation, cell signaling, and secondary metabolism. One of the putative substrates, serine esterase, was purified and tested directly for interaction with purified Hsp16.6. Hsp16.6 effectively formed soluble complexes with serine esterase in a heat-dependent fashion, thereby preventing formation of insoluble serine esterase aggregates. These data offer critical insights into the characteristics of native sHSP substrates and extend and provide in vivo support for the chaperone model of sHSP function.