Atherosclerosis and Toll-Like Receptor4 (TLR4), Lectin-Like Oxidized Low-Density Lipoprotein-1 (LOX-1), and Proprotein Convertase Subtilisin/Kexin Type9 (PCSK9).

Atherosclerosis is a leading cause of death in the world. A significant body of evidence suggests that inflammation and various players are implicated and have pivotal roles in the formation of atherosclerotic plaques. Toll-like receptor 4 (TLR4) is linked with different stages of atherosclerosis. This receptor is highly expressed in the endothelial cells (ECs) and atherosclerotic plaques. TLR4 activation can lead to the production of inflammatory cytokines and related responses. Lectin-like oxidized low-density lipoprotein-1 (LOX-1), an integral membrane glycoprotein with widespread expression on the ECs, is involved in atherosclerosis and has some common pathways with TLR4 in atherosclerotic lesions. In addition, proprotein convertase subtilisin/kexin type9 (PCSK9), which is a regulatory enzyme with different roles in cholesterol uptake, is implicated in atherosclerosis. At present, TLR4, PCSK9, and LOX-1 are increasingly acknowledged as key players in the pathogenesis of atherosclerotic cardiovascular diseases. Herein, we presented the current evidence on the structure, functions, and roles of TLR4, PCSK9, and LOX-1 in atherosclerosis.

Therapeutic properties of botulinum toxin on chronic anal fissure treatment and the patient factors role.

BACKGROUND: One of the most frequent distressing diseases which causes anal pain and bleeding after defecation is anal fissure. Despite a poorly understood pathogenesis, the internal anal sphincter spasm has been identified to play a central role in pathogenesis. Recently, botulinum toxin is being used increasingly for the treatment of chronic anal fissure to achieve chemical sphincterotomy and reduce internal sphincter tonicity. Based on the heterogeneity among the published studies, we aimed this study to evaluate its healing rate and for recognizing the factors of patients which may affect the outcome. SUBJECTS AND METHODS: In a prospective case series medical research, 106 patients who suffer from chronic anal fissure were treated by botulinum toxin injections. All patients received 30 units of botulinum toxin and were physically examined every week for 2 months. They were evaluated for bleeding, pain, hematoma, thrombosis, infection, incontinence, and healing of the fissure. At the end of the follow-up period, the fissure healing rate and its relation to age, gender, prior topical therapy, duration of symptoms, and the position of the fissure were assessed. RESULTS: At the end of the study (8 weeks), the healing rate was 84.9% (90 patients responded to injections). Healing rate was higher in females and in patients who experienced a shorter duration of symptoms before injection. The mean healing time was 4.68 weeks. In addition, patients with one fissure (anterior or posterior) demonstrated higher healing rate and shorter healing time compared to patients with two fissures (anterior and posterior). CONCLUSION: This study demonstrated that botulinum toxin injection is safe and effective for the treatment of chronic anal fissures, with a low complication rate. In addition, the healing rate was higher in females, patients with shorter duration of symptoms, and those with one fissure.

PTPN22 Silencing in Human Acute T-Cell Leukemia Cell Line (Jurkat Cell) and its Effect on the Expression of miR-181a and miR-181b.

Purpose: T-cell acute lymphoblastic leukemia (T-ALL) is one of the most common malignancies associated with T-lymphocytes, accounting for 10 to 15 percent of ALL cases in children and 25 percent in adults. Innovative therapeutic approaches that overcome ineffective treatments on tumor cells may be a potential source of improvement in therapeutic approaches. Suppression of gene expression at transfusion level is one of the important strategies in gene therapy. The expression of PTPN22 and miR-181 genes in all types of hematologic malignancies increases and is likely to contribute to the survival and death of cells by affecting a variety of signaling pathways. The purpose of this study was to determine the role of PTPN22 inhibition by siRNA, and alteration in miR-181a and miR-181b in Jurkat cell line. Methods: Jurkat cells were transfected with 80 pmol of siRNA to inhibit PTPN22. After that, expression of PTPN22 mRNA and transcript levels of miR-181a and miR-181b were measured with Real-time PCR after 48hrs. Results: Experiments demonstrated that siRNA transfection resulted in significant downregulation of PTPN22 mRNA after 48 hrs in 80 pmol dose of siRNA. Moreover, transcript levels of both miR-181a and miR-181b was decreased after transfection. Conclusion: PTPN22, miR-181a and miR-181b might be involved in progression of Jurkat cells and targeting these molecules by RNAi might confer promising tool in treatment of T-ALL.