Small molecule inhibitor of TLR4 inhibits ovarian cancer cell proliferation: new insight into the anticancer effect of TAK-242 (Resatorvid)

Cancer Chemotherapy and Pharmacology - Despite all advances in the treatment of ovarian cancer (OC), it remains the most lethal gynecological malignancy worldwide. There are growing amounts of...     

RAR‐related orphan receptor A: One gene with multiple functions related to migraine

AimsRAR‐related orphan receptor (RORA) involves in regulation of several biological processes including inflammation and circadian rhythm that probably are involved in migraine pathophysiology. In the current study, the association between RORA rs11639084 and rs4774388 variants and susceptibility to migraine were investigated in a sample of Iranian migraine patients for the first time.MethodsIn a case‐control study including 400 participants, 200 migraineurs and 200 healthy controls, genotyping of RORA rs4774388 and rs11639084 polymorphisms was performed using tetra‐primer amplification refractory mutation system–polymerase chain reaction (TP‐ARMS‐PCR).ResultsThe distribution of rs4774388 C/T and T/T genotypes differed significantly between the studied groups. Moreover, an association was observed between rs4774388 and migraine under the recessive mode of inheritance (P = 0.002; OR = 1.89.; CI = 1.25‐2.87). The distribution of rs11639084 alleles and genotypes was not significantly different between migraineurs and healthy controls.ConclusionCurrent results suggest RORA, as a molecular link, may explain inflammation and circadian rhythm dysfunction in migraine. Further studies in different ethnicities are required to confirm the function of RORA in migraine development.     

Aquaporin3 expression and the potential role of aquaporins in motility and mitochondrial membrane potential in human spermatozoa

Aquaporins are water selective channels which play important roles in cell volume regulation during the transmission of spermatozoa to female tract. This study investigated the expression of aquaporin3 and determined the role of aquaporins in human sperm motility and mitochondrial membrane potential (MMP). RT-PCR and flow cytometry analysis were done to investigate aquaporin3 expression levels, and immunolocalisation of aquaporin3 in the spermatozoa was detected using immunocytochemical analysis. The sperm suspension was divided into four groups of spermatozoa: (a) Spermatozoa at 0 hr, (b) spermatozoa in control group, (c) spermatozoa treated with HgCl₂ (as an aquaporin inhibitor) and (d) spermatozoa treated with HgCl₂+ and 2-mercaptoethanol. The sperm samples were examined in terms of sperm motility and mitochondrial membrane potential. Results confirmed aquaporin3 expression in human spermatozoa and immunocytochemistry results showed an intense immunoreactivity in whole sperm tail. After 60 min, HgCl₂ showed a significant decrease in motility and MMP compared to the control group. At this time point, 2-mercaptoethanol in the HgCl₂+ 2-mercaptoethanol group reversed the effects of HgCl₂ as compared to the HgCl₂ group. Present study showed the expression and immunolocalisation of AQP3 in human spermatozoa and the potential role of AQPs in the sperm motility and MMP.     

An in vitro evaluation of the responses of human osteoblast-like SaOs-2 cells to SLA titanium surfaces irradiated by erbium:yttrium–aluminum–garnet (Er:YAG) lasers

Erbium:yttrium–aluminum–garnet (Er:YAG) laser treatment is an effective option for the removal of bacterial plaques. Many studies have shown that Er:YAG lasers cannot re-establish the biocompatibility of titanium surfaces. The aim of this study was to evaluate the responses of the human osteoblast-like cell line, SaOs-2, to sand-blasted and acid-etched (SLA) titanium surface irradiation using different energy settings of an Er:YAG laser by examining cell viability and morphology. Forty SLA titanium disks were irradiated with an Er:YAG laser at a pulse energy of either 60 or 100 mJ with a pulse frequency of 10 Hz under water irrigation and placed in a 24-well plate. Human osteoblast-like SaOs-2 cells were seeded onto the disks in culture media. Cells were then kept in an incubator with 5 % carbon dioxide at 37 °C. Each experimental group was divided into two smaller groups to evaluate cell morphology by scanning electron microscope and cell viability using 3-4,5-dimethylthiazol 2,5-diphenyltetrazolium bromide test. In both the 60 and the 100 mJ experimental groups, spreading morphologies, with numerous cytoplasmic extensions, were observed prominently. Similarly, a majority of cells in the control group exhibited spreading morphologies with abundant cytoplasmic extensions. There were no significant differences among the laser and control groups. The highest cell viability rate was observed in the 100 mJ laser group. No significant differences were observed between the cell viability rates of the two experimental groups (p?=?1.00). In contrast, the control group was characterized by a significantly lower cell viability rate (p?<?0.001). Treatments with an Er:YAG laser at a pulse energy of either 60 or 100 mJ do not reduce the biocompatibility of SLA titanium surfaces. In fact, modifying SLA surfaces with Er:YAG lasers improved the biocompatibility of these surfaces.     

Electrical stimulation promotes the proliferation of human keratinocytes,increases the production of keratin 5 and 14, and increases the phosphorylation of ERK1/2 and p38 MAP kinases

Effective wound healing remains a significant clinical challenge in reducing patient morbidity and improving quality of life. Wound healing is a complex process involving the endogenous electrical field. The electrical field can contribute to wound healing by activating keratinocytes to promote reepithelialization. The objective of this study was to determine the effects of exogenous electrical stimulation (ES) on human keratinocyte viability and proliferation and on production of IL‐6, IL‐8, and keratins (K5 and K14) and to investigate the activated signalling pathways in keratinocytes exposed to ES. Keratinocytes were cultured under ES at different intensities for 6 or 24 hr. Cell proliferation, cytokines and growth factors, K5 and K14, as well as phosphorylated ERK1/2 and p38 MAP kinases, were evaluated. The results showed that the keratinocytes exposed to ES between 100 and 150 mV/mm for 6 or 24 hr showed a significantly increased proliferation rate. However, a 24 hr exposure to 200 mV/mm revealed no significant effect in cell growth. ES at 100 and 200 mV/mm for 6 hr increased the secretion of epidermal growth factor and vascular endothelial growth factor, and the production of K5 and K14. K14 was more sensitive than K5 to ES. However, ES down‐regulated the secretions of IL‐6 and IL‐8. Finally, ES increased the phosphorylation of ERK1/2 and p38 MAP kinases. Overall results suggested that ES can be useful in supporting skin wound healing by activating keratinocytes.     

The serotonin-1A agonist ipsapirone prevents ethanol-associated death of total rhombencephalic neurons and prevents the reduction of fetal serotonin neurons

Previously, this laboratory showed that in utero and in vitro ethanol exposure significantly reduces developing serotonin (5-HT) neurons and that treatment with a 5-HT1A agonist such as buspirone or ipsapirone prevents the ethanol-associated loss. The present study investigated whether ethanol decreases fetal rhombencephalic neurons, including 5-HT neurons, by causing apoptosis. We also investigated whether ipsapirone prevents the ethanol-associated deficit of fetal rhombencephalic neurons by reducing apoptosis. The results of these studies strongly suggest that the ethanol-associated reduction in fetal rhombencephalic neurons that accompanies both in utero and in vitro exposure to physiological concentrations of ethanol is associated with increased apoptosis in these neurons. A physiological concentration of ethanol (i.e., 50 mM) increases apoptosis in fetal rhombencephalic neurons and decreases the number 5-HT neurons. It also appears that the 5-HT1A agonist ipsapirone provides neuroprotection to these neurons by reducing apoptosis. Another mechanism by which ethanol-associated apoptosis can be blocked is by including serum proteins in the media at a concentration of 1% or higher; this concentration of serum proteins is high in comparison to the protein concentration in cerebrospinal fluid.     

Comparison of Short-Term Effectiveness and Postoperative Complications: Laparoscopic Gastric Plication vs Laparoscopic Sleeve Gastrectomy

Introduction

Bariatric surgeries are the only effective long-term treatment in obese patients. The innovation of laparoscopic gastric plication (LGP) raised some questions about its effectiveness compared to traditionally used techniques such as laparoscopic sleeve gastrectomy (LSG). We tried to answer some of these questions.

Materials and Methods

We investigated 70 patients in a randomized clinical trial (IRCT2013123012294N5) from 2012 to 2015. Thirty-five patients were randomly assigned to each LSG or LGP group, using sealed envelope method. The body mass index (BMI) reduction and the percentage of excess weight loss (%EWL) along with %total body weight loss (%TWL) were primary endpoint and were assessed at follow-up periods. We recorded postoperative complications, as well.

Results

Two-year follow-up rate was 100%. There were no statistically significant differences between the two groups in means of preoperative BMI. Also, postoperative follow-ups were not suggestive for a significant difference in BMI (all p values > 0.05). The mean %EWL at follow-ups showed no significant difference at any point, except for 3 and 6 months after surgery (p value = 0.002 and 0.017, respectively). This finding was confirmed by %TWL trend in 12 months after surgery. LSG patients were readmitted more than LGP patients (seven cases vs one case, p value = 0.024). Postoperative complications such as nausea and vomiting, hair loss, iron deficiency, vitamin D deficiency, and cholelithiasis were not different between the two groups. There was one death in the LGP group due to pulmonary thromboembolism.

Conclusions

LGP showed to be efficient regarding %EWL and %TWL reduction in short-term follow-ups with comparable postoperative complications to LSG.

     

Kaposi’s sarcoma following living donor kidney transplantation: review of 7,939 recipients

Introduction  Kaposi’s sarcoma (KS) is one of the most common tumors to occur in kidney recipients, especially in the Middle East countries. Limited data with adequate sample size exist about the development of KS in living kidney recipients. Methods  Therefore, we made a plan for a multicenter study, accounting for up to 36% (n = 7,939) of all kidney transplantation in Iran, to determine the incidence of KS after kidney transplantation between 1984 and 2007. Results  Fifty-five (0.69%) recipients who developed KS after kidney transplantation were retrospectively evaluated with a median follow-up of 24 (1–180) months. KS occurred more often in older age when compared to patients without KS (49 ± 12 vs. 38 ± 15 years, P = 0.000). KS was frequently found during the first 2 years after transplantation (72.7%). Skin involvement was universal. Furthermore, overall mortality rate was 18%, and it was higher in patients with visceral involvement compared to those with mucocutaneous lesions (P = 0.01). However, KS had no adverse affect on patient and graft survival rates compared to those without KS. Forty-four patients with limited mucocutaneous disease and four with visceral disease responded to withdrawal or reduction of immunosuppression with or without other treatment modalities. Renal function was preserved when immunosuppression was reduced instead of withdrawn in patients with and without visceral involvement (P = 0.001 and 0.008, respectively). Conclusion  The high incidence of KS in this large population studied, as compared to that reported in other transplant patient groups, suggests that genetic predisposition may play a pathogenetic role.