Ezetimibe ameliorates cisplatin-induced nephrotoxicity: A novel therapeutic approach via modulating AMPK/Nrf2/TXNIP signaling.

Cisplatin (Cis) is among the most powerful antineoplastic medications, nevertheless, its serious side effects; particularly nephrotoxicity designates a major concern. Previous studies reported that ezetimibe (Eze), a well-known antihyperlipidemic drug, exerts additional trivial pharmacological effects. In this work, we displayed Eze as an intriguing protective candidate in a cisplatin-induced nephrotoxicity rat model through AMPK activation. Eze (10 mg/kg, p.o.) was administered for two weeks and Cis (10 mg/kg, i.p.) was administered on the 10th day to induce nephrotoxicity in male Wistar rats. Treatment with Eze greatly augmented the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) and the antioxidant regulator; nuclear factor erythroid 2-related factor 2 (Nrf2), thus, mitigating oxidative injury through induction of the antioxidant enzymes, such as heme oxygenase-1 (HO-1) and glutathione reductase (GR). As well, Eze relieved inflammation by reducing protein expression of thioredoxin-interacting protein (TXNIP) and nucleotide-binding domain-like receptor protein 3 (NLRP3), which led to a decrease in the release of caspase-1, in addition to, the inflammatory markers IL-18 and IL-1 ß. Besides, Eze ameliorated apoptosis in the renal cells through inhibiting the phosphorylated Apoptosis signal-regulating kinase-1(p-ASK1), caspase-3 and reducing Bax/Bcl2ratio. Correspondingly, histopathological examination corroborated the previous biochemical findings. Collectively, Eze exerts significant renal protection against Cis-induced nephrotoxicity via antioxidant, anti-inflammatory and anti-apoptotic pathways that are probably mediated, at least partly, via activating AMPK/Nrf2/HO-1 pathway and conquering both TXNIP/NLRP3 inflammasome and TXNIP/ASK1 signaling pathways. To confirm the protective effect of Eze via AMPK-activation, an AMPK-inhibitor, dorsomorphin (Dors), when co-administered with Eze abolished its protective effect.

Split body comparative clinical and radiological study of fractional CO2 laser versus carboxytherapy in treatment of striae distensae.

Striae Distensae (SD) are quite common complaint in dermatology practice. They are linear lesions of variable length and width according to the site and the causative condition. Several treatment modalities have been tried. To achieve satisfactory results, a combination therapy is often needed. To evaluate the efficacy and safety of fractional CO2 laser versus carboxytherapy in the treatment of Striae Distensae clinically and radiologically. Thirty Egyptian patients with striae distensae, received a split body therapy: the left side was treated by fractional CO2 laser and the right side was treated by carboxytherapy in the same session. Six sessions were done with 4 weeks apart. Clinical evaluation by measurement of the width of widest striae on both sides, global aesthetic improvement scale (GAIS), and Likert satisfaction scale. Radiological evaluation by measurement of cutaneous thickness of widest striae on both sides by ultrasonography. There was a highly statistically significant decrease in the median width of the widest striae distensae on both sides after the last session (P < 0.01). Regarding GAIS, satisfaction scale and ultrasound, there was highly statistically significant improvement on laser side than carboxytherapy side (P < 0.01) after last session. Both fractional CO2 laser and carboxytherapy may be considered as safe and effective lines of treatment for striae distensae, but fractional CO2 laser showed excellent improvement clinically, radiologically when compared with carboxytherapy which made it a promising module in treatment of striae distensae.

Clinicopathological characterization and prognostic implication of FOXP3 and CK19 expression in papillary thyroid carcinoma and concomitant Hashimoto's thyroiditis.

Papillary thyroid carcinoma (PTC) is considered the most prevalent thyroid malignancy. The association between Hashimoto's thyroiditis (HT) and PTC is still unclear. We aimed to examine the clinicopathological impact of immunohistochemical staining of FOXP3 and Cytokeratin 19 in PTC and concomitant HT and their correlation with patients' outcome and survival. Eighty thyroid biopsies obtained from patients with PTC were immunostained by FOXP3 and CK19.The patients were treated by radioactive iodine (I131) and followed up. FOXP3 and CK19 expression were detected in 45% and 80% studied cases of PTC respectively. 16.7% of PTC with associated HT showed FOXP3+ lymphocytes in lymphocytic infiltrate of HT, while most of PTC associated HT express cytoplasmic CK19 positive Hurtle cells. FOXP3 was more expressed in PTC female patients more than 45 years with higher stage, lymph node, and distant metastasis, extracapsular extension, number of I131doses, and cumulative radioiodine doses with a highly statistically significant difference (p < 0.001). The relation was significant between CK19 immunostaining as regard 10-year Overall Survival and death (p value = 0.027 and 0.036, respectively). HT represents a step in the process of autoimmune inflammatory disease ending by the evolution of PTC with better prognosis, therefore appropriate follow up of these cases is needed. FOXP3 tends to be more expressed in PTC cases with worse prognostic variables and is predictable to become a recent prognostic and targeted therapy for PTC. There was a significant relation between CK19 immunostaining and 10 year overall survival.