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Mesoaxial synostotic syndactyly with phalangeal reduction (MSSD) represents a rare non-syndromic defect with an autosomal recessive pattern of inheritance. Sequence variants in the BHLHA9 gene cause MSSD and to date only a few mutations in this gene have been reported. In the present report, we have described a consanguineous Iranian family segregating MSSD in an autosomal recessive manner. The family had two affected siblings showing evidence of camptodactyly in some fingers, complete syndactyly of the 3rd and 4th fingers with synostoses of the corresponding metacarpals, and associated single phalanx in both right and left hand. Whole exome sequencing (WES) followed by segregation analysis using Sanger sequencing identified a novel homozygous frameshift variation [c.74_74delG p.(G25Afs*55)] in the BHLHA9 gene. This has expanded the spectrum of mutations in the BHLHA9 and will facilitate genetic counseling in Iranian families segregating MSSD-related phenotypes. This article is protected by copyright. All rights reserved.

Congenital disorder of glycosylation (CDG) and Glycogen storage diseases (GSDs) are inborn metabolic disorders caused by defects in some metabolic pathways. These disorders are a heterogeneous group of diseases caused by impaired O- as well as N-glycosylation pathways. CDG patients show a broad spectrum of clinical presentations; many GSD types (PGM1-CDG) have muscle involvement and hypoglycemia.We applied WES for all seven patients presenting GSD and CDG symptoms. Then we analyzed the data using various tools to predict pathogenic variants in genes related to the patients' diseases.In the present study, we identified pathogenic variants in Iranian patients suffering from GSD and CDG, which can be helpful for patient management, and family counseling. We detected seven pathogenic variants using whole exome sequencing (WES) in known AGL (c.1998AG, c.3635TC, c.3682CT), PGM1 (c.779GA), DPM1 (c.742TC), RFT1 (c.127AG), and GAA (c.1314CA) genes.The suspected clinical diagnosis of CDG and GSD patients was confirmed by identifying missense and or nonsense mutations in PGM1, DPM1, RFT1, GAA, and AGL genes by WES of all 7 cases. This study helps us understand the scenario of the disorder causes and consider the variants for quick disease diagnosis.

Lung cancer is the deadliest malignancy worldwide. An inflammatory microenvironment is a key factor contributing to lung tumor progression. Tumor-Associated Macrophages (TAMs) are prominent components of the cancer immune microenvironment with diverse supportive and inhibitory effects on growth, progression, and metastasis of lung tumors. Two main macrophage phenotypes with different functions have been identified. They include inflammatory or classically activated (M1) and anti-inflammatory or alternatively activated (M2) macrophages. The contrasting functions of TAMs in relation to lung neoplasm progression stem from the presence of TAMs with varying tumor-promoting or anti-tumor activities. This wide spectrum of functions is governed by a network of cytokines and chemokines, cell-cell interactions, and signaling pathways. TAMs are promising therapeutic targets for non-small cell lung cancer (NSCLC) treatment. There are several strategies for TAM targeting and utilizing them for therapeutic purposes including limiting monocyte recruitment and localization through various pathways such as CCL2-CCR2, CSF1-CSF1R, and CXCL12-CXCR4, targeting the activation of TAMs, genetic and epigenetic reprogramming of TAMs to antitumor phenotype, and utilizing TAMs as the carrier for anti-cancer drugs. In this review, we will outline the role of macrophages in the lung cancer initiation and progression, pathways regulating their function in lung cancer microenvironment as well as the role of these immune cells in the development of future therapeutic strategies.

The kidneys have important and vital functions and provide maintenance of overall body health. Many kidney diseases are caused by single gene defects. Kidney disease is categorized in a heterogeneous group of disorders affecting the kidney, both in structure and function. The end stage of kidney disease is known as kidney failure. Kidney disease is divided into two forms: AKI and CKD (1). Among kidney diseases, polycystic kidney disease (PKD; also known as polycystic kidney syndrome) is revealed to have a genetic background (2). PKD is characterized by the presence of cysts in kidneys. The development and growth of cysts causes abnormalities in the renal tubules. PKD is a clinically and genetically heterogeneous disease (2,3). Clinical characteristics of autosomal dominant and recessive forms of PKD are variable in their penetrance. A range from neonatal death to incidence in old age was reported for PKD (2,4). Disease causing variants in three genes including PKD1 , PKD2, and PKDH1 can cause PKD. The pathogenic variations in the PKD1 and PKD2 genes can cause an autosomal dominant (ADPKD) pattern of inheritance. The pathogenic variations in PKDH1 can cause an autosomal recessive (ARPKD) pattern of inheritance (2). There are more than 500 monogenic causes of CKD (5) and numerous genes are listed in next-generation sequencing (NGS) panels for PKD, including ALG9 , ANKS6 , ATP6V0A4 , BICC1 , GANAB , GLIS3 , HNF1B , INVS , LRP5 , MUC1 , NOTCH2 , NPHP3 , OFD1 , PKD1 , PKD2 , PKHD1 , SEC61A1 , TMEM231 , TSC1 , TSC2 , UMOD , and ZNF423 , etc. (2). For classification, preprognosis, monitoring and treatment, and identification of the etiology of the disease is necessary. It helps us understand the scenario of the disorder’s causes and select the best approach for drug …

Background: Cannabinoid receptor 1 (CB1R) that located throughout the central, peripheral, and enteric nervous system can be found all over the gastrointestinal tract. Cannabinoid receptors (CBRs) play important roles in pathophysiological processes and have been identified as a therapeutic target for developing novel anticancer agents. Objectives: The purposes of this study were to evaluate the CB1R expression in human gastric cancer, mRNA and protein expression of CB1R under lipopolysaccharide (LPS)-mediated inflammation condition in human gastric cancer cells (AGS), and the effects of inflammation on cell proliferation in LPS-stimulated AGS cells. Methods: CB1R mRNA expression in human gastric cancer samples and AGS cells were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The expression level of CB1R, after inflammation induction using LPS, was evaluated by qRT-PCR and western blot techniques. Cell proliferation was evaluated using 5-bromo-2-deoxyuridine (BrdU) labeling assay. Results: CB1R mRNA was significantly higher in human gastric cancer samples compared to adjacent normal tissues. LPS induced CB1R mRNA and protein expression in stimulated cells and promoted the proliferation of AGS cells. Conclusions: Our results show the increased expression of CB1R in gastric cancer samples and reveal that LPS induction increases the expression of CB1R and promotes cell proliferation in AGS cells. Accordingly, CB1R may be suggested as a potential molecular target for diagnostic and therapeutic aims in patients with gastric cancer.

Background Various blood diseases are caused by mutations in the FANCA, FANCC, and ITGA2B genes. Exome sequencing is a suitable method for identifying single-gene disease and genetic heterogeneity complaints. Methods Among families who were referred to Narges Genetic and PND Laboratory in 2015-2017, five families with a history of blood diseases were analyzed using the whole exome sequencing (WES) method. Results We detected two novel mutations (c.190-2A>G and c.2840C>G) in the FANCA gene, c. 1429dupA mutation in the FANCC gene, and c.1392A>G mutation in the ITGA2B gene. The prediction of variant pathogenicity has been done using bioinformatics tools such as Mutation taster PhD-SNP and polyphen2 and were confirmed by Sanger sequencing. Conclusions WES could be as a precise tool for identifying the pathologic variants in affected patient and heterozygous carriers among families. This highly successful technique will remain at the forefront of platelet and blood genomic research.

Infectious bursal disease is one of the most important viral diseases in the young chickens. VP2 protein is the major host protective immunogen of the virus. A hypervariable region is present in VP2 protein (hvVP2) that contains immunodominant epitops. The high hydrophobicity of hvVP2 region causes protein aggregation in Escherichia coli (E. coli). The objective of the present study was to improve the expression and the solubility of the hvVP2 protein in E. coli. The effects of fusion partners on the solubility of hvVP2 protein were studied. The protein was expressed in forms of unfused and N-terminally fused to GST and NusA. The results showed that the unfused hvVP2 protein was expressed in very low level. But, N-terminally fused hvVP2 protein to GST (glutathione-S-transferase) and NusA (N utilization substance A) showed significantly enhanced protein expression. The fusion of GST and hvVP2 was produced in aggregated form while in the presence of NusA, the hvVP2 protein was expressed in a soluble form. The NusA-hvVP2 protein was detected by a neutralizing monoclonal antibody, 1A6, in antigen-capture ELISA. In conclusion, the NusA protein is a suitable fusion partner to improve expression and solubility of the hvVP2 protein in E. coli.