Compatibility of Lecanicillium longisporum with acetamipride and imidaclopride under laboratory conditions

Lecanicillium longisporum is one of the facultative insect pathogens with significant host range and host specificity. The conidia survival may be affected by environmental factors or by bio-pesticides and chemical products used to protect crop plants. In this research, the compatibility of the mentioned fungi with acetamipride and imidaclopride and the effect of these insecticides on conidial germination and vegetative growth were studied. The formulations of insecticides were tested in three concentrations (mean concentration (MC), half MC and twice the MC). The study was conducted in completely randomised design (CRD) with four replications. The results indicated that acetamipride and imidaclopride in half MC were compatible with L. longisporum (isolate LRC195). However, based on the results, imidacloprid compared to acetamipride is adaptable with L. longisporum. These insecticides could be used simultaneously in low concentration with this entomopathogenic fungus in integrated pest management.     

PD-1/PD-L1-dependent immune response in colorectal cancer

Colorectal cancer (CRC) is still considered as the third most frequent cancer in the world. Microsatellite instability (MSI), inflammation, and microRNAs have been demonstrated as the main contributing factors in CRC. Subtype 1 CRC is defined by NK cells infiltration, induction of Th1 lymphocyte and cytotoxic T cell responses as well as upregulation of immune checkpoint proteins including programmed cell death-1 (PD-1). Based on the diverse features of CRC, such as the stage and localization of the tumor, several treatment approaches are available. However, the efficiency of these treatments may be decreased due to the development of diverse resistance mechanisms. It has been proven that monoclonal antibodies (mAbs) can increase the effectiveness of CRC treatments. Nowadays, several mAbs including nivolumab and pembrolizumab have been approved for the treatment of CRC. Immune checkpoint receptors including PD-1 can be inhibited by these antibodies. Combination therapy gives an opportunity for advanced treatment for CRC patients. In this review, an update has been provided on the molecular mechanisms involved in MSI colorectal cancer immune microenvironment by focusing on PD-ligand 1 (PD-L1) and treatment of patients with advanced immunotherapy, which were examined in the different clinical trial phases. Considering induced expression of PD-L1 by conventional chemotherapeutics, we have summarized the role of PD-L1 in CRC, the chemotherapy effects on the PD-1/PD-L1 axis and novel combined approaches to enhance immunotherapy of CRC by focusing on PD-L1.     

Berberine as a potential autophagy modulator

Today, pharmacognosy is considered a valuable science in the prevention and treatment of diseases. Among herbals, Berberine is an isoquinoline alkaloid found in the Berberis species. Surprisingly, it shows antimicrobial, antiviral, antidiarrheal, antipyretic, and anti-inflammatory potential. Furthermore, it diminishes drug resistance in cancer therapy and enhances tumor suppression in part through autophagy and cell cycle arrest mechanisms. In the present review, we discuss the effect of berberine on diverse cellular pathways and describe how berberine acts as an autophagy modulator to adjust physiologic and pathologic conditions and diminishes drug resistance in cancer therapy.     

Role of MDM2 309T>G (rs2279744) and I/D (rs3730485) polymorphisms and haplotypes in risk of papillary thyroid carcinoma,tumor stage,tumor size,and early onset of tumor: A case control study

Murine double minute clone 2 (MDM2) protein plays an important role in the regulation of p53 tumor suppressor. Genetic polymorphisms of the MDM2 gene are the candidate variants in susceptibility to various cancers. In the present study, we aimed to investigate the possible effects of MDM2 309T>G (rs2279744) and I/D (rs3730485) polymorphisms on papillary thyroid carcinoma (PTC) susceptibility and clinical or pathological features of the disease. A case control study was carried out involving in a total of 131 patients with PTC and 144 healthy controls. Both cases and controls were genotyped for MDM2 309T>G and I/D polymorphisms. There was no significant difference regarding MDM2 309T>G and I/D genotypes between patients with PTC and controls in neither dominant nor recessive and allelic models. The frequency of G-D haplotype was higher in patients with PTC and this haplotype was associated with a 1.7-fold increased risk of PTC. The MDM2 309T>G polymorphism was associated with a higher risk of III–IV stages in patients with PTC. The MDM2 ID genotype was significantly higher in patients with PTC less than 40 years and associated with larger tumor size (≥1 cm). In conclusion, the G-D haplotype but not MDM2 309T>G and I/D polymorphisms were associated with higher risk of PTC. MDM2 309T>G polymorphism was associated with a higher incidence of III–IV stages, however, I/D polymorphism was associated with larger tumor size and a lower age of disease occurrence.     

Suppressing Glucose Transporter Gene Expression in Schistosomes Impairs Parasite Feeding and Decreases Survival in the Mammalian Host

Adult schistosomes live in the host''s bloodstream where they import nutrients such as glucose across their body surface (the tegument). The parasite tegument is an unusual structure since it is enclosed not by the typical one but by two closely apposed lipid bilayers. Within the tegument two glucose importing proteins have been identified; these are schistosome glucose transporter (SGTP) 1 and 4. SGTP4 is present in the host interactive, apical tegumental membranes, while SGTP1 is found in the tegumental basal membrane (as well as in internal tissues). The SGTPs act by facilitated diffusion. To examine the importance of these proteins for the parasites, RNAi was employed to knock down expression of both SGTP genes in the schistosomula and adult worm life stages. Both qRT-PCR and western blotting analysis confirmed successful gene suppression. It was found that SGTP1 or SGTP4-suppressed parasites exhibit an impaired ability to import glucose compared to control worms. In addition, parasites with both SGTP1 and SGTP4 simultaneously suppressed showed a further reduction in capacity to import glucose compared to parasites with a single suppressed SGTP gene. Despite this debility, all suppressed parasites exhibited no phenotypic distinction compared to controls when cultured in rich medium. Following prolonged incubation in glucose-depleted medium however, significantly fewer SGTP-suppressed parasites survived. Finally, SGTP-suppressed parasites showed decreased viability in vivo following infection of experimental animals. These findings provide direct evidence for the importance of SGTP1 and SGTP4 for schistosomes in importing exogenous glucose and show that these proteins are important for normal parasite development in the mammalian host.     

MAPK14 cooperates with MAPK3/1 to regulate endothelin-1-mediated prostaglandin synthase 2 induction and survival in leiomyoma but not in normal myometrial cells

We recently reported that in ELT3 uterine leiomyoma cells, but not in normal myometrial cells, endothelin (ET)-1 exerts a survival effect insensitive to MAPK3/1(ERK1/2) inhibition. In the present work, we investigated the potential role of MAPK14 (p38) in this ET-1-mediated effect. We demonstrated that, in ELT3, but not in normal myometrial cells, ET-1 activated MAPK14. Data based on pharmacological and siRNA approaches indicate that ETA and ETB receptors contributed to the activation of MAPK14 by ET-1 through a mechanism involving Gi protein, but not PI3-kinase. The inhibition of MAPK3/1 by U0126 did not affect the activation of MAPK14 by ET-1. Conversely, the inhibition of MAPK14 by SB203580 and the down-regulation of MAP2K3/MAP2K6 (kinases upstream of MAPK14) by specific siRNA did not alter the activation of MAPK3/1. These data indicate that MAPK14 was activated by ET-1 independently from MAPK3/1. Furthermore, ET-1 increased protein expression of prostaglandin synthase 2 (PTGS2 or COX2), prostaglandin E2 (PGE2) production, and subsequent ELT3 cell survival. The inhibition of PTGS2 induction and subsequent survival induced by ET-1 required the coinhibition of MAPK14 and MAPK3/1. Our findings provide evidence that ET-1 activated MAPK14 only in ELT3 cells, but not in normal myometrial cells. This MAPK14 activation was required, in addition to MAPK3/1 in ET-1-mediated survival through the COX2/prostaglandin axis, and may explain the absence of ET-1 antiapoptotic effect in normal myometrial cells. Our data reinforce the role of ET-1 and associated signaling pathways in leiomyoma pathology.