Identification of a novel de novo mutation in the CTNNB1 gene in an Iranian patient with intellectual disability.

CTNNB1 encodes for the ß-catenin protein, a component of the cadherin adhesion complex, which regulates cell-cell adhesion and gene expression in the canonical Wnt signaling pathway. Mutations in CTNNB1 have been reported to be associated with cancer and mental disorders. Recently, loss-of-function mutations in CTNNB1 have been observed in patients with intellectual disability and some other clinical manifestations including motor and language delays, microcephaly, and mild visual defects. We report an 8-year-old Iranian girl with intellectual disability, hypotonia, impaired vision such as vitreomacular adhesion, motor delay, and speech delay. A novel, de novo nonsense mutation (c.1014G > A; p.Trp338Ter) in exon 7 of the CTNNB1 (NM_001904) gene was detected and confirmed by whole-exome sequencing and Sanger sequencing, respectively. This study helps to expand the growing list of loss-of-function mutations known in the CTNNB1 gene.

Validation of the persian version of the COVID-19 prevention, recognition and home-management self-efficacy scale.

INTRODUCTION: Adopting preventive behaviors and following the guidelines for controlling the COVID-19 epidemic depend on people's self-efficacy in carrying out these behaviors and instructions. The aim of this study was to investigate the psychometric properties of the Persian version of the COVID-19 Self-Efficacy Scale (COVID-19 SES, Hernández-Padilla et al., 2020). MATERIAL AND METHODS: This cross-sectional study was performed in a group of 400 people who were residents of the city of Asadabad in western Iran from December 2020 to January 2021. The participants were selected using a convenience sampling method. Face and content validity was assessed qualitatively based on feedback from the participants and experts, and the necessary changes were applied to the final version of the questionnaire. For construct validity, exploratory factor analysis (n=200) and confirmatory factor analysis (n=200) were performed. Internal consistency was expressed as Cronbach's alpha coefficient. Relative stability was assessed using the intraclass correlation coefficient (ICC), and absolute stability was calculated through examination of standard error of measurement (SEM). RESULTS: In exploratory factor analysis, three factors of prevention, symptom recognition, and homemanagement of COVID-19 were extracted that together explained 71.35% of the total variance. The internal consistency of the whole instrument was 0.955 and its three dimensions were 0.894, 0.916 and 0.955, respectively. In addition, an ICC of 0.986 (95% CI: 0.975-0.993, p=0.001) was found. In the confirmatory factor analysis, comparative and parsimonious fit indices were excellent, and absolute fit indices were moderate. CONCLUSIONS: The Persian version of the COVID-19 SES has good validity and reliability and can be used to measure self-efficacy in prevention, symptoms recognition, and home-management of COVID-19.

Prevalence and antibiotic resistance of Acinetobacter baumannii among patients in postcardiac surgery intensive care units of Rajaei Hospital, Tehran.

Background: Acinetobacter baumannii is an opportunistic, aerobic, nonfermentative, Gram-negative bacterium that can cause major nosocomial infections, especially in patients hospitalized in intensive care units (ICU). Recently, A. baumannii strains have been resistant to a variety of antibiotics. Thus, it was aimed to evaluate the prevalence of A. baumannii and their resistance to the antibiotics in the patients hospitalized in postcardiac surgery ICU. Methods: This retrospective cross sectional study was performed in Rajaei hospital between March 2014 and February 2016. A. baumannii strains were isolated from blood cultures, catheter cultures, sputum cultures, and wound smear cultures. Then, isolates were characterized using standard morphological, cultural, and biochemical properties according to CLSI 2016. The frequency of A. baumannii species were reported as percent. Results: Among 27 167 patients were admitted to the ICU, 113 individuals, including 55 males and 58 females, were identified as A. baumannii-infected and the prevalence rate was 0.42%. The highest rates of antibiotic sensitivity were related to Meropenem 20 (17.7%) and Colistin 16 (14.1%). The shortest length of stay (LOS) for patients with A. baumanniiin the ICU was 3 days, while the longest LOS was 98 days. Conclusion: The findings indicated that A. baumannii strains isolated from postcardiac surgery ICUs had a high prevalence and were sensitive to Meropenem and Colistin. However, new molecular-based techniques are needed to monitor nosocomial infections. Therefore, the treatment of the patients may be feasible by appropriate antibiotic therapy, and infection control policies will be improved by adopting precise disinfection strategies.

Broadening the phenotype and genotype spectrum of novel mutations in pontocerebellar hypoplasia with a comprehensive molecular literature review.

BACKGROUND: Pontocerebellar hypoplasia is an umbrella term describing a heterogeneous group of prenatal neurodegenerative disorders mostly affecting the pons and cerebellum, with 17 types associated with 25 genes. However, some types of PCH lack sufficient information, which highlights the importance of investigating and introducing more cases to further elucidate the clinical, radiological, and biochemical features of these disorders. The aim of this study is to provide an in-depth review of PCH and to identify disease genes and their inheritance patterns in 12 distinct Iranian families with clinically confirmed PCH. METHODS: Cases included in this study were selected based on their phenotypic and genetic information available at the Center for Comprehensive Genetic Services. Whole-exome sequencing (WES) was used to discover the underlying genetic etiology of participants' problems, and Sanger sequencing was utilized to confirm any suspected alterations. We also conducted a comprehensive molecular literature review to outline the genetic features of the various subtypes of PCH. RESULTS: This study classified and described the underlying etiology of PCH into three categories based on the genes involved. Twelve patients also were included, eleven of whom were from consanguineous parents. Ten different variations in 8 genes were found, all of which related to different types of PCH. Six novel variations were reported, including SEPSECS, TSEN2, TSEN54, AMPD2, TOE1, and CLP1. Almost all patients presented with developmental delay, hypotonia, seizure, and microcephaly being common features. Strabismus and elevation in lactate levels in MR spectroscopy were novel phenotypes for the first time in PCH types 7 and 9. CONCLUSIONS: This study merges previously documented phenotypes and genotypes with unique novel ones. Due to the diversity in PCH, we provided guidance for detecting and diagnosing these heterogeneous groups of disorders. Moreover, since certain critical conditions, such as spinal muscular atrophy, can be a differential diagnosis, providing cases with novel variations and clinical findings could further expand the genetic and clinical spectrum of these diseases and help in better diagnosis. Therefore, six novel genetic variants and novel clinical and paraclinical findings have been reported for the first time. Further studies are needed to elucidate the underlying mechanisms and potential therapeutic targets for PCH.

Selective detection of nitenpyram by silica-supported carbon quantum dots.

In this study, a fluorescent sensor of nitrogen-doped carbon quantum dots (N-CQDs) and silica gel hybrid was developed for the quantitative detection of nitenpyram, a toxic neonicotinoid existing in groundwater and/or surface water.The prepared N-CQDs@SiO2 sensor exhibited remarkable sensing selectivity and sensitivity towards nitenpyram among the four pesticides and six metal ions. A prominent fluorescence quenching of N-CQDs@SiO2 at 445 nm was observed in the presence of nitenpyram with a linear response range of 0-300.0 mg L-1 and an estimated limit of detection of 1.53 mg L-1. The main cause for selective sensing is that nitenpyram absorbs the excitation light of N-CQDs@SiO2, leading to fluorescence quenching of the sensor through the inner filter effect.

The role of lymph node metastasis in early gastritis Individuals following noncurative endoscopic Resection: a systematic review and meta-analysis.

BACKGROUND: Recent studies suggest that individuals who underwent noncurative endoscopic resection for gastric cancer may require additional surgery. We conducted a comprehensive systematic review and meta-analysis to investigate the risk of lymph node metastasis in these cases. METHODS: We comprehensively examined relevant literature by extensively reviewing electronic databases such as PubMed, Cochrane Library, and Google Scholar. Subsequently, we analyzed clinicopathological outcomes and calculated pooled odds ratios and 95 percent confidence intervals using diverse effects models. RESULTS: This analysis included 12 papers with 4808 individuals who underwent additional surgery after noncurative endoscopic resection for early gastric cancer. The results indicated significant associations between lymph node metastasis and submucosal invasion (Odd ratio 2.04, 95% (CI): 1.58-2.63, I 2 = 88.7%; p<0.001), vertical margin (Odd ratio 6.11, 95% (CI): 1.94-19.23, I 2 = 0%; p<0.001), lymphatic invasion (Odd ratio 10.02, 95% (CI): 7.57-13.27, I 2 = 92%; p<0.000), and vascular invasion (Odd ratio 7.11, 95% (CI): 5.49-9.22, I 2=92%; p<0.000). CONCLUSIONS: When choosing factors for surgical treatment, it is essential to thoroughly consider the invasion of lymph nodes, vascular system, submucosa, and positive vertical margin.

Genetically Engineered Mesenchymal Stem Cell Therapy Against Murine Experimental Autoimmune Encephalomyelitis.

We used recombinant interleukin 23 receptor (RIL-23R)-engineered mesenchymal stem cells (MSCs) to study its therapeutic role in enhancing inflammation of nervous tissue in the mouse model (EAE) of multiple sclerosis (MS). Recombinant IL-23 receptor construct was designed to enter MSCs. The bioactivity of the constructs was assessed by the co-culture of MSCs/CD4 + T cells. The EAE model was induced in mice. After cell transplantation, clinical scores were evaluated, and tissue demyelination was measured by Luxol fast blue staining. The transfection of RIL-23R mRNA improved MSC properties significantly to the inflamed regions of EAE mice, and it performed an increased suppressive function on the T lymphocyte proliferation. Furthermore, in vivo therapy with RIL-23R MSCs in EAE mice showed an enhanced therapeutic action than MSCs, proven by improved myelination and a reduction in the penetration of inflammatory cells into the white matter. Our targeted transplantation procedure of modified MSC can be applied to improve the effectiveness of cellular therapy for multiple sclerosis and other autoimmune disorders.

Carbon Quantum Dot-Incorporated Chitosan Hydrogel for Selective Sensing of Hg2+ Ions: Synthesis, Characterization, and Density Functional Theory Calculation.

A carbon quantum dot-based chitosan hydrogel was prepared in this work as a fluorescence sensor for the selective sensing of Hg2+ ions. Among the eight tested metal ions, the prepared hydrogel exhibited remarkable sensing selectivity and sensitivity toward Hg2+. The results demonstrated that a prominent fluorescence quenching at 450 nm was observed in the presence of Hg2+ with a linear response range of 0-100.0 nM and an estimated limit of detection of 9.07 nM. The as-prepared hydrogel demonstrates pH-dependent fluorescence intensity and sensitivity. The highest fluorescence intensity and sensitivity were obtained under pH 5.0. The excellent sensing selectivity could be attributed to a strong interaction between the hydrogel film and Hg2+ ions to form complexes, which provokes an effective electron transfer for fluorescence quenching. Results from density functional theory (DFT) calculation confirm that the interaction energies (ΔIE) of the hydrogel with three toxic metal ions (Hg2+, Cd2+, and Pb2+) are in the following order: Hg2+ > Cd2+ > Pb2+.

Access-dispersion-recovery strategy for enhanced mitigation of heavy crude oil pollution using magnetic nanoparticles decorated bacteria.

Heavy crude oil (HCO) pollution has gained global attention, but traditional bioremediating practices demonstrate limited effectiveness. This study developed magnetic nanoparticles decorated bacteria (MNPB) using an oil-degrading and biosurfactant-producing Rhodococcus erythropolis species and identified a novel access-dispersion-recovery strategy for enhanced HCO pollution mitigation. The strategy entails (1) magnetic navigation of the MNPB towards HCO layer, (2) enhanced oil dispersion and formation of suspended oil-bacteria aggregates, and (3) magnetic recovery of these aggregates. The UV-spectrophotometer analysis showed that this strategy can enable up to 62% removal of HCO. The GC-MS analysis demonstrated that the MNPB enhanced the degradation of low-molecular-weight aromatics comparing with the pure bacteria, and the recovery process further removed oil-bacteria aggregates and entrained high-molecular-weight aromatics. The feasibility of using MNPB to mitigate HCO pollution could shed light on the emerging bioremediation applications.

Mutations in the VPS13B Gene in Iranian Patients with Different Phenotypes of Cohen Syndrome.

Cohen syndrome is a rare autosomal recessive disorder characterized by hypotonia, obesity, developmental delay, mental retardation, and facial, oral, ophthalmic, and limb deformities. Mutations in VPS13B have been found to be responsible for this disorder. In the current report, we have assessed three Iranian families with developmental delay and skeletal deformities. Whole exome sequencing of the affected probands led to identification of the underlying genetic cause in these families. Three mutations were found in VPS13B gene. The detected mutations were c.4608_4609del (p.E1537Rfs*7), c.11486dupG (p.L3830Tfs*13), and c.10360dupC (p.L3454fs*7). The current study broadens the mutation spectrum of VPS13B gene and demonstrates different phenotypic features from classic Cohen syndrome. Moreover, the provided data can be used in genetic counseling and prenatal diagnosis of Iranian patients.

Genetically Engineered Adipose Mesenchymal Stem Cells Using HIV-Based Lentiviral Vectors as Gene Therapy for Autoimmune Diseases.

The immunomodulatory and self-renewable features of human adipose-derived mesenchymal stem cells (hAD-MSCs) mark their importance in regenerative medicine. Interleukin (IL)-23 as a proinflammatory cytokine suppresses T regulatory cells and promotes the response of T helper 17 and T helper 1 cells. This pathway initiates inflammation and immunosuppression in several autoimmune diseases. The current study aimed at producing recombinant IL-23 decoy receptor (RIL-23R) using hAD-MSCs as a good candidate for ex vivo cell-based gene therapy purposes to reduce inflammation in autoimmune diseases. hAD-MSCs was isolated from lipoaspirate and then characterized by differentiation. RIL-23R was designed and cloned into a pCDH813A-1 lentiviral vector. The transduction of hAD-MSCs was performed at multiplicity of infection = 50 with pCDH-EFI α-RIL-23R-PGK copGFP. Expressions of RIL-23R and octamer-binding transcription factor 4 (OCT-4) were determined by real-time polymerase chain reaction. Self-renewing properties were assayed with OCT-4. Bioactivity of the designed RIL-23R was evaluated by IL-17 and IL-10 expression of mouse splenocytes. The results showed that the transducted hAD-MSCs/RIL-23R, expressing IL-23 decoy receptor, can provide a useful approach for a basic research on cell-based gene therapy for autoimmune disorders.

The Human IL-23 Decoy Receptor Inhibits T-Cells Producing IL-17 by Genetically Engineered Mesenchymal Stem Cells.

The immunomodulatory and self-renewable features of human adipose mesenchymal stem cells (hAD-MSCs) mark their importance in regenerative medicine. Interleukin 23 (IL- 23) as a proinflammatory cytokine suppresses T regulatory cells (Treg) and promotes the response of T helper 17 (Th17) and T helper 1 (Th1) cells. This pathway starts inflammation and immunosuppression in several autoimmune diseases. The current study for producing recombinant IL- 23 decoy receptor (RIL- 23R) using hAD-MSCs as a good candidate for ex vivo cell-based gene therapy purposes reducing inflammation in autoimmune diseases. hAD-MSCs was isolated from lipoaspirate and then characterized by differentiation. RIL- 23R was designed and cloned into a pCDH-813A- 1 lentiviral vector. The transduction of hAD-MSCs was performed at MOI (multiplicity of infection) = 50 with pCDH- EFI α- RIL- 23R- PGK copGFP. Expressions of RIL- 23R and octamer-binding transcription factor 4 (OCT- 4) were determined by real-time polymerase chain reaction (real time-PCR). Self-renewing properties were assayed with OCT- 4. Bioactivity of the designed RIL- 23R was evaluated by IL- 17 and IL- 10 expression of mouse splenocytes. Cell differentiation confirmed the true isolation of hAD-MSCs from lipoaspirate. Restriction of the enzyme digestion and sequencing verified the successful cloning of RIL- 23R in the CD813A-1 lentiviral vector. The green fluorescent protein (GFP) positive transduction rate was up to 90%, and real-time PCR showed the expression level of RIL-23R. Oct-4 had a similar expression pattern with nontransduced hAD-MSCs and transduced hAD-MSCs/ RIL-23R indicating that lentiviral vector did not affect hAD-MSCs characteristics. Downregulation of IL-17 and upregulation of IL-10 showed the correct activity of the engineered hAD-MSCs. The results showed that the transduced hAD-MSCs/ RIL- 23R, expressing IL-23 decoy receptor, can give a useful approach for a basic research on cell-based gene therapy for autoimmune disorders.

Evaluation of antagonistic effects of metformin with Cisplatin in gastric cancer cells.

Metformin has recently been introduced as an anti-cancer agent. In this study, we evaluated the effect of metformin and metformin/cisplatin on human gastric MKN-45 cell line. When we used metformin alone, it could inhibit proliferation and induce apoptosis, but it diminish anti-proliferative effects of cisplatin when they are used in combination. Further, we checked mRNA levels of survivin, mTOR, and Akt by real-time PCR. When MKN-45 cells were treated with metformin/cisplatin, the expression of survivin and mTOR were increased. The antagonistic effect of metformin on cisplatin could be through survivin and mTOR signaling pathways. Our results also suggest that interfering effect of metformin on cisplatin may be also through upregulation of Akt. Regarding the pivotal role of Akt in drug resistance, it may be reasonable to conclude that the antagonistic effect of metformin on cisplatin effect may be through this central mediator of drug resistance. Taken together, it seems that metformin is not a good option for sensitizing MKN-45 cell line to cisplatin, and in co-prescription of metformin and cisplatin in gastric cancer patients who suffer diabetes type 2, it should be highly cared.

Study on association between H-ras gene polymorphism and gastric adenocarcinoma risk.

AIM: The aim of this study was to investigate relation between H-ras T81C polymorphism and some of the important risk factors in gastric adenocarcinoma (GA). BACKGROUND: GA is one of the leading causes of cancer death in most countries. RAS gene is an important member in the PI3K-AKT signaling and the single nucleotide polymorphism at H-rasc DNA position 81 has been demonstrated has an important role in tumor genesis. PATIENTS AND METHODS: In this study, we carried out single-nucleotide polymorphism analysis in an Iranian population. A total of 100 patients with gastric adenocarcinoma and 100 controls were examined for the presence of T81C H-ras polymorphism using PCR- RFLP assay. RESULTS: Statistical analysis revealed no relationship significant between TT, TC, CC and risk of GA, but, there was a poorly relation between male patient with C-carrier genotype and increasing risk of GA (P=0.07). Also, we investigate effect of four important risk factors for GA. There was a statistically significant difference between increasing of age and susceptibility for GA (OR=1.106, 95%CI=1.073-1.139, P < 0.001). We observed a statistically significant between smoking and T81C polymorphism C-carrier genotypes (OR=3.98, 95%CI=1.831-8.68, P < 0.001) as this individual had three-time risk for GA. We did not show a significant association between three main genotypes and H. pylori infection for risk of GA. CONCLUSION: These results suggested that there is no relationship between T81C-HRAS polymorphism and gastric cancer risk in Iranian patients. But, gender (male in our study) and the other risk factor described above have an important role in developing of GA.

Differential sensitivity of p44/p42-MAPK- and PI3K/Akt-targeted neuroblastoma subtypes to arsenic trioxide.

PI3K/Akt and MAPK/ERK pathways are differentially activated in neuroblastoma (NB) cell types. In an effort to enhance the effectiveness of the NB treatment, we designed experiments to evaluate the effects of ATO in combination with PI3K and MEK1/2 specific inhibitors, LY29004 and U0126, respectively, in SK-N-MC and SK-N-BE(2) cell lines. The results indicated that specific inhibition of PI3K and MEK1/2 significantly enhanced antiproliferative and proapoptotic effects of ATO in SK-N-BE(2), but not in SK-N-MC. Furthermore, in SK-N-BE(2), NF-κB activation was significantly suppressed by LY29004+ATO treatments as compared with ATO alone, indicating that inhibition of PI3K may enhance anti-neoplastic properties of ATO in I-type NB cells through suppression of NF-κB. Moreover, expressions of c-Myc, Bad, Bax and ATM in SK-N-BE(2) cell line were significantly increased by U0126+ATO treatment as compared to treatment with ATO alone. Expression of telomerase hTERT was almost depleted by U0126+ATO treatment. Regarding the fact that activation of PI3K and MAPK in SK-N-BE(2) is higher than in other NB subtypes, we hypothesize that growth of SK-N-BE(2) cell line is highly dependent on these pathways and inhibition of these pathways may has promise for the treatment of multi-drug resistant I-type NB cells by ATO. However, for successful strategies for the treatment of this heterogeneous tumor, other combinations approaches need to be considered to simultaneously target other NB cells.