Lysyl Oxidase Mechanisms to Mediate Gastrointestinal Cancer Progression

Background: Malignancy is a complex process resulting from different changes such as extracellular matrix (ECM) remodeling and stiffness. One of the important enzymes that contribute to ECM remodeling is lysyl oxidase (Lox) that is overexpressed in different types of human cancers. Because of the high prevalence and poor survival of gastrointestinal (GI) malignancies in this review, we discuss the association between Lox activity and the progression of GI cancers. Lox proteins are a group of extracellular enzymes that catalyzed the cross-linking of collagen and elastin, so they have important roles in the control of structure and homeostasis of ECM. Abnormal activation and expression of the Lox family of proteins lead to changes in the ECM toward increased rigidity and fibrosis. Stiffness of ECM can contribute to the pathogenesis of cancers. Summary: Dysregulation of Lox expression is a factor in both fibrotic diseases and cancer. ECM stiffness by Lox overactivity creates a physical barrier against intratumoral concentration of chemotherapeutic drugs and facilitates cancer inflammation, angiogenesis, and metastasis. Key Message: Because of the roles of Lox in GI cancers, development targeting Lox protein isotypes may be an appropriate strategy for treatment of GI cancers and improvement in survival of patients

A review of electrical and thermal conductivities of epoxy resin systems reinforced with carbon nanotubes and graphene-based nanoparticles

Epoxy (EP) resins exhibit desirable mechanical and thermal properties, low shrinkage during cuing, and high chemical resistance. Therefore, they are useful for various applications, such as coatings, adhesives, paints, etc. On the other hand, carbon nanotubes (CNT), graphene (Gr), and their derivatives have become reinforcements of choice for EP-based nanocomposites because of their extraordinary mechanical, thermal, and electrical properties. Herein, we provide an overview of the last decade's advances in research on improving the thermal and electrical conductivities of EP resin systems modified with CNT, Gr, their derivatives, and hybrids. We further report on the surface modification of these reinforcements as a means to improve the nanofiller dispersion in the EP resins, thereby enhancing the thermal and electrical conductivities of the resulting nanocomposites

Evaluation of the diagnostic value of Sentinel Lymph Node in patients with gastric adenocarcinoma

Objective(s):  Sentinel lymph node biopsy (SLNB) has been proven as a safe and efficient procedure in some cancers like breast cancer and melanoma with a reduction of complications and side effects of unnecessary lymphadenectomy in many patients. However, the diagnostic value of SLNB in gastric cancer is a point of debate. This study evaluated the diagnostic value of SLNB using radiotracer and isosulphan blue dye injection in patients with Gastric Adenocarcinomas (GA).Methods: This descriptive study was performed at Imam-Reza HOSPITAL on 39 patients diagnosed with GA with no lymphatic metastasis using two methods: the combination of radionuclide with isosulphan together (R&I) method compared with the isosulphan alone method. Lymphatic dissection was performed in all patients. The pathological results were compared between the sentinel lymph nodes (SLN) and other lymph nodes and their accordance rate was calculated.Results: In the T1 group, the sentinel lymph node biopsy detection rate was 100% for the combination of the R&I method and 60% for the isosulphan method and the false negative rate was zero. These values respectively were 88.8% and 88.8% in the T2 group with a false negative rate of 75%. In the T3 group, the values were 100% for the combination of the R&I method and 93.7% for the isosulphan method with a false negative rate of 40%. In the combination of the R&I method, the sensitivity, specificity, and positive and negative predictive values were 57.9, 100, 100, and 69.2 percent respectively.Conclusion: Based on the false negative rate (47.4%), SLNB by injection of isosulphan blue dye alone is not a diagnostic enough value for predicting lymph node metastasis in GA. Although, SLNB by combination of the R&I had better accuracy compared to the isosulphan alone, more studies with larger samples are needed to prove this result

The Potential Association between the Risk of Post-Surgical Adhesion and the Activated Local Angiotensin II Type 1 Receptors: Need for Novel Treatment Strategies

Background: Post-surgical adhesion bands (PSABs) are a common complication after abdominal or pelvic surgeries for different reasons like cancer treatment. Despite improvements in surgical techniques and the administration of drugs or the use of physical barriers, there has only been limited improvement in the frequency of postoperative adhesions. Complications of PSAB are pain, infertility, intestinal obstruction, and increased mortality. The most important molecular mechanisms for the development of PSAB are inflammatory response, oxidative stress, and overexpression of pro-fibrotic molecules such as transforming growth factor beta. However, questions remain about the pathogenesis of this problem, for example, the causes for individual differences or why certain tissue sites are more prone to post-surgical adhesions. Summary: Addressing the pathological causes of PSAB, the potential role of local angiotensin II/angiotensin II type 1 receptors (AngII/AT1R), may help to prevent this problem. Key Message: The objective of this article was to explore the role of the AngII/AT1R axis potential to induce PSAB and the therapeutic potential of angiotensin receptor blockers in the prevention and treatment of PSAB

An overview of the innate and adaptive immune system in atherosclerosis

Cardiovascular disease is the leading cause of death globally. Coronary artery disease (CAD) is a chronic inflammatory disease usually caused by atherosclerosis, in which the coronary arteries become narrowed by atheromatous plaque. Plaques in atherosclerosis are formed through the accumulation of lipids and various immune cells. Both adaptive and innate immune systems are involved in the pathogenesis of atherosclerosis and facilitate plaque formation and disease progression. Almost all immune system cells, including neutrophils, B cells, T cells monocytes, macrophages, foam cells, and dendritic cells (DCs), play a vital role in atherosclerotic plaque. Atherogenesis, the normal function of the endothelium, is initially disrupted and, then, cells of the immune system are recruited to the endothelium following increased expression of cell adhesion molecules. Accumulation of immune cells and lipids leads to the formation of a necrotic nucleus. As the disease progresses, smooth muscle cells form fibrous layers, whose rupture results in exposing the necrotic nucleus and thrombosis. Accordingly, the present review was conducted to determine the role of different cells in innate and adaptive immune systems in inhibition and progression of atherosclerosis

Metformin inhibits polyphosphate-induced hyper-permeability and inflammation

Circulating inflammatory factor inorganic polyphosphate (polyP) released from activated platelets could enhance factor XII and bradykinin resulted in increased capillary leakage and vascular permeability. PolyP induce inflammatory responses through mTOR pathway in endothelial cells, which is being reported in several diseases including atherosclerosis, thrombosis, sepsis, and cancer. Systems and molecular biology approaches were used to explore the regulatory role of the AMPK activator, metformin, on polyP-induced hyper-permeability in different organs in three different models of polyP-induced hyper-permeability including local, systemic shortand systemic long-term approaches in murine models. Our results showed that polyP disrupts endothelial barrier integrity in skin, liver, kidney, brain, heart, and lung in all three study models and metformin abrogates the disruptive effect of polyP. We also showed that activation of AMPK signaling pathway, regulation of oxidant/ anti-oxidant balance, as well as decrease in inflammatory cell infiltration constitute a set of molecular mechanisms through which metformin elicits it's protective responses against polyP-induced hyper-permeability. These results support the clinical values of AMPK activators including the FDA-approved metformin in attenuating vascular damage in polyP-associated inflammatory diseases.Peer reviewe

Exploring SARS-COV-2 structural proteins to design a multi-epitope vaccine using immunoinformatics approach: An in silico study

In December 2019, a new virus called SARS-CoV-2 was reported in China and quickly spread to other parts of the world. The development of SARS-COV-2 vaccines has recently received much attention from numerous researchers. The present study aims to design an effective multi-epitope vaccine against SARS-COV-2 using the reverse vaccinology method. In this regard, structural proteins from SARS-COV-2, including the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins, were selected as target antigens for epitope prediction. A total of five helper T lymphocytes (HTL) and five cytotoxic T lymphocytes (CTL) epitopes were selected after screening the predicted epitopes for antigenicity, allergenicity, and toxicity. Subsequently, the selected HTL and CTL epitopes were fused via flexible linkers. Next, the cholera toxin B-subunit (CTxB) as an adjuvant was linked to the N-terminal of the chimeric structure. The proposed vaccine was analyzed for the properties of physicochemical, antigenicity, and allergenicity. The 3D model of the vaccine construct was predicted and docked with the Toll-like receptor 4 (TLR4). The molecular dynamics (MD) simulation was performed to evaluate the stable interactions between the vaccine construct and TLR4. The immune simulation was also conducted to explore the immune responses induced by the vaccine. Finally, in silico cloning of the vaccine construct into the pET-28 (+) vector was conducted. The results obtained from all bioinformatics analysis stages were satisfactory; however, in vitro and in vivo tests are essential to validate these results

Cannabinoid receptor agonism suppresses tremor, cognition disturbances and anxiety-like behaviors in a rat model of essential tremor

Cognitive and motor disturbances are serious consequences of tremor induced by motor disorders. Despite a lack of effective clinical treatment, some potential therapeutic agents have been used to alleviate the cognitive symptoms in the animal models of tremor. In the current study, the effects of WIN55, 212-2 (WIN), a cannabinoid receptor (CBR) agonist, on harmaline-induced motor and cognitive impairments were studied. Adult rats were treated with WIN (0.5 mg/kg; i.p.) 15 min before harmaline administration (10 mg/kg; ip) after which exploratory and anxiety related behaviors, and cognitive function were assessed using open-field behavior and shuttle box tests. Rats that received harmaline only exhibited a markedly reduced number of central square entries when compared to harmaline vehicle-treated controls, whereas those treated with WIN and harmaline showed a significant increase in central square entries, compared to harmaline only treated. The passive avoidance memory impairments observed in harmaline treated rats, was reversed somewhat by administration of WIN. The neuroprotective and anxiolytic effects of WIN demonstrated in the current study can be offered cannabinoid receptor (CBR) agonism as a potential neuroprotective agent in the treatment of patients with tremor that manifest mental dysfunctions

Intraperitoneal administration of Telmisartan prevents postsurgical adhesion band formation

Background Angiotensin II receptor blockers (ARBs) have a potential role in reducing inflammation and fibrosis. We have integrated systems and molecular biology approaches to investigate the therapeutic potential of ARBs in preventing postsurgical adhesion band formation. Material and methods we have followed the ARRIVE guidelines point by point during experimental studies. Telmisartan (1 and 9 mg/kg), valsartan (1 and 9 mg/kg), and losartan (1 and 10 mg/kg) were administered intraperitoneally in different groups of male albino Wistar rat. After 7 d of treatment, macroscopic evidence and score of fibrotic bands based on scaling methods was performed. Moreover, the anti-inflammatory and antifibrosis effects of telmisartan on reduction of fibrotic bands were investigated by using histopathology, ELISA, and real-time polymerase chain reaction methods. Results Telmisartan, but not losartan or valsartan, prevented the frequency as well as the stability of adhesion bands. Telmisartan appears to elicit anti-inflammatory responses by attenuating submucosal edema, suppressing proinflammatory cytokines, decreasing proinflammatory cell infiltration, and inhibiting oxidative stress at the site of peritoneal surgery. We also showed that telmisartan prevents fibrotic adhesion band formation by reducing excessive collagen deposition and suppression of profibrotic genes expression at the peritoneum adhesion tissues. Conclusions These results support the potential application of telmisartan in preventing postsurgical adhesion band formation by inhibiting key pathologic responses of inflammation and fibrosis in postsurgery patients

The association between visceral adiposity with systemic inflammation, oxidative stress, and risk of post-surgical adhesion

Abdominal and pelvic adhesions are common post-operative complications. Despite new medical technologies, these adhesions are appearing to be unavoidable and little is known about their causation; for example, why certain patients/or tissues are more prone to adhesions. There have been no clinical studies about increasing the risk adhesions in obese patients, but there is some evidence about the molecular mechanisms involving visceral fat (VF) that may lead to profibrotic conditions. VF is an endocrine/inflammatory organ which produces many biologically active molecules such as adipokines and inflammatory cytokines. Inflammatory conditions, oxidative stress, and the expression some fibrotic molecules in the VF may induce pathological conditions in the abdominal cavity that predispose to the formation of fibrotic bands