Combination of IFN-gamma with STING agonist and PD-1 immune checkpoint blockade: a potential immunotherapy for gastric cancer.

Suppression of the cGAS-STING pathway is an immune escape mechanism in cancer cells. The critical role of this pathway in gastric cancer (GC) is not fully understood. Herein, we evaluated the effect of the interferon-gamma (IFN-gamma), STING agonist, PD-1 immune checkpoint blockade, and their combination on the cGAS-STING pathway in GC. Expression of cGAS and STING in tumor tissue samples and adjacent normal tissue (ANT) biopsies of fifty new GC patients was evaluated by quantitative real-time PCR (qRT-PCR). Moreover, cGAS and STING expression levels were examined in Peripheral Blood Mononuclear Cells (PBMC) samples of forty GC patients and twenty-five healthy subjects. The apoptosis rate of cancer cells was analyzed by Annexin V-FITC/PI. Cell proliferation was measured by the BrdU assay. Also, IFN-ß levels were evaluated in the supernatants of the treated groups. The cGAS expression was decreased in patients with distant metastasis. Co-cultures treated with IFN-gamma showed an elevated level of cGAS and STING expressions in PBMC and cancer cells. The rate of apoptosis increased in all the treatment groups. In addition, the rate of proliferation in PBMCs increased in different treated groups. The main role of PBMCs in cytotoxicity was determined by a comparative analysis of the viability of cells treated with all treatments, both with and without PBMCs. The production of IFN-ß was elevated in all treated groups. The current study suggests that a combination therapy using IFN-gamma, STING agonist, and anti-PD-1 antibody can provide a promising approach to the treatment of GC.

Evaluation of HLA-DR and HLA-DQ expression in gastric cancer tissues.

BACKGROUND AND OBJECTIVES: Despite recent advances in understanding the gastric cancer (GC) biology, the precise molecular mechanism of gastric carcinogenesis and role of deregulated immune responses in GC progression are still not well understood. In this study, mRNA levels of human leukocyte antigen (HLA)-DRA and -DQA1 were assessed in GC patients to find a potential association between expression of these HLA-II molecules and gastric carcinogenesis. METHODS: Using quantitative real-time (qRT)-PCR, mRNA levels of HLA-DRA and -DQA1 were assessed in 20 pairs of matched GC and normal tissues. RESULTS: Our results showed that overall mRNA level of HLA-DRA was decreased in the tumor samples relative to control tissues (median fold change [FC] = 0.693; P = 0.445). Overall HLA-DQA1 level was increased in the tumor samples relative to control tissues (median FC = 1.659; P = 0.5117). However, the mentioned data were not statistically significant. Meanwhile, using a ≥ 2.5 FC as the cutoff to determine upregulation or downregulation, 35% of patients showed a downregulated expression of HLA-DRA, while 10% of those showed upregulation in HLA-DRA expression. Upregulation and downregulation of HLA-DQA1 expression were detected, respectively, in 35% and 25% of samples. A strong positive correlation was determined between HLA-DRA and HLA-DQA1 levels in tumor tissues (r = 0.7298; P = 0.0003). CONCLUSION: The results reported here along with future studies can be useful to understand the interplay between immune system and GC, therefore, may be helpful to design an effective immune-based therapy.

Effects of a multi-component virtual reality program on motor skills and functional postural control in children with hemiplegic cerebral palsy.

Background: Pediatric neurorehabilitation has recently employed virtual reality (VR) technologies as a platform to design and implement novel modalities. Aims: To evaluate the feasibility of a multi-component VR-based program on motor skills and functional postural control for children with hemiplegic cerebral palsy (HCP). Methods: A single-case-experimental design was conducted on eight children with HCP (12.33 ± 4.71 years and GMFCS= II, I). The VR-based program consisted of 3 sessions per week for four weeks. Timed Up and Go (TUG) test, Functional Reach Test (FRT), Pediatric Balance Scale (PBS), Activities Scale for Kids (ASK), ABILHAND-Kids, and Box and Block Test (BBT) were used to evaluate functional changes. Outcomes and results: Statistical analysis showed that improvements in functional postural control were significant on at least one balance measure for seven out of eight participants during the intervention phase. For all participants, a significant increase was observed in the BBT scores. Before-after intervention analysis revealed statistically significant improvements in PBS (z = -2.52, p ≤ 0.01), ABILHAND-Kids (z = -2.25, p ≤ 0.01), and ASK (z = -2.38, p ≤ 0.01). Conclusions and implications: This study provided early evidence of the effectiveness of the multi-component VR-based program in children with HCP. However, future studies with randomized controlled trial design are needed to evaluate the long-term effects and compare them with conventional rehabilitation practice.

Comparing Pregabalin and Sodium Valproate in Pediatric Migraine Prophylaxis: A Randomized Clinical Trial.

Objectives: Migraine is a common disorder in children, and its prophylaxis with minimal side effects is momentous. This study aimed to compare the efficacy of Pregabalin and Sodium Valproate in preventing migraine attacks. Material & methods: Sixty-four children (aged 6-18) with migraines were recruited, as defined by Internation Headache Criteria (ICHD-III). They were randomly assigned to two groups: Sodium Valproate (n=32) and Pregabalin (n=32). The minimum dosage of drugs was prescribed in both groups. The patients were followed for four months. The parameters such as frequency, intensity, duration of migraine attacks, and the number of painkillers that the patients used monthly were recorded. The Spence Children's anxiety scale was also used to evaluate medications' effect on patients' anxiety levels. Results: Two medications were equally effective in reducing the intensity and duration of attacks. Additionally, their effect on reducing the anxiety level of patients was equal. There was a significant difference between the effect of drugs on the frequency of migraine attacks at the end of the first and fourth months and the number of painkillers used at the end of the fourth month. The frequency of attacks was decreased by more than 50% in twenty-eight patients (90%) of Pregabalin recipients and twenty-one patients (84%) of Sodium Valproate recipients. Conclusion: Considering the better effect of Pregabalin in the reduction of frequency of migraine attacks and pain-reducing medications consumption, Pregabalin could be a proper substitute for Sodium Valproate for prophylactic migraine treatment in children.

The Upregulation of HLA-G1 and miRNA-34a in Lens Epithelial Cells of Diabetic Retinopathy Patients.

Background: Retinopathy of diabetes is a chronic diabetes mellitus complication affecting retinal vessels, and some ocular complications' molecular mechanisms remain obscure. Objective: To evaluate the expression of HLA-G1, HLA-G5, miRNA-181a, and miRNA-34a in the lens epithelial cells of patients with retinopathy of diabetes. Methods: In a case-control study, 30 diabetic patients with retinopathy, 30 diabetic patients without retinopathy, and 30 cataract patients without diabetes mellitus as the control group were enrolled after a full description with details about the study methods and objectives. The expression of HLA G1, HLA G5, miRNA-181a, and miRNA-34a in lens epithelial cells was assessed by quantitative RT PCR. Moreover, the levels of HLA-G protein in aqueous humor were evaluated by the ELISA method. Results: HLA-G1 expression was significantly upregulated in the retinopathy group (P=0.003). The aqueous humor of diabetic retinopathy patients contained significantly higher levels of HLA-G protein compared with the non-diabetic patients (P=0.001). miRNA-181a was significantly downregulated in the diabetic retinopathy group compared with the patients without diabetes (P=0.001). In addition, miRNA-34a was upregulated in the retinopathy group (P=0.009). Conclusion: Taken together, the present results showed that HLA-G1 and miRNA-34a can be valuable markers for diabetic retinopathy. Our data offers new perspectives for improving the control of inflammation in the lens epithelial cells by considering HLA-G and miRNA.

Efficacy of Addition of Atomoxetine to Speech Therapy in Stuttering Severity of Children Aged 4-12 Years: A Double-Blind Randomized Controlled Trial.

Objectives: Stuttering is a common problem at all ages that is required to be treated since childhood. Atomoxetine is currently used for the treatment of attention deficit hyperactivity disorder (ADHD). It can be effective for the treatment of stuttering due to its selective inhibition of norepinephrine reuptake and dopaminergic properties. Therefore, this randomized controlled trial aimed to evaluate the effect of atomoxetine on children's stuttering. Materials & Methods: The children aged 4-12 years and diagnosed with stuttering, referred to Pediatric Neurology and Psychology clinics , were randomly divided into experimental (n=50) and control (n=50) groups. One group received atomoxetine plus speech therapy, and the other group received only speech therapy. Both groups completed the Stuttering Severity Instrument-Fourth Edition at the baseline (on the first visit) and 3 months after the intervention. The results were compared between the two groups using SPSS software (version 21). Results: Most of the children (67%) were male. Moreover, 24%, 46%, and 30% of the subjects were within the age ranges of < 60, 60-95, and > 95 months, respectively. Nearly half of the patients (52%) had a positive family history of stuttering. Stuttering severity was the highest within the age range of 60-95 months, in left-handed children, in those who used formula, and in those who felt insecure in the family; however, there was no difference in stuttering severity based on child's gender, concomitant ADHD, multilingualism, facial or movement tics, sleeping hours, and using teats. The mean stuttering severity reduced in both groups (P<0.001), with a greater decrease in the experimental group, compared to that of the control group (P=0.011). Conclusion: Atomoxetine plus speech therapy is effective for the treatment of children's stuttering and can be used as a complementary treatment strategy in such patients.

Vascular Brain Damage in Thalassemia Syndrome: An Emerging Challenge.

Thalassemia syndromes are the most prevalent monogenic hemoglobinopathy in the world. In Iran, thalassemia is a public health problem because this country has been located on the thalassemia belt. In recent decades, considering that the life expectancy of patients with thalassemia has dramatically improved, some unrecognized complications have emerged in these individuals. One of these complications is a hypercoagulable state that may lead to thromboembolic events (TEE). The TEE may involve any organ in the body, including the central nervous system. Ischemic cerebrovascular events in thalassemic patients have been divided into two categories, namely overt stroke and silent cerebral infarcts (SCI). Overt stroke often develops in patients with beta-thalassemia major; however, patients with thalassemia intermedia usually suffer from SCI. This review article discusses brain vascular involvement.

miR-34a mimic or pre-mir-34a, which is the better option for cancer therapy? KatoIII as a model to study miRNA action in human gastric cancer cells.

BACKGROUND: Aberrantly expressed microRNAs play important roles in gastric tumorigenesis. However, use of miRNAs as a therapeutic option in gastric cancer still remains as a challenging problem. METHODS: We performed transient transfection of miR-34a-5p mimic and stable transfection of pre-mir-34a into KatoIII cells. Then, we evaluated the effect of transfected miRNAs on numerous cellular and molecular processes. RESULTS: Following transient transfection of miR-34a-5p mimic at 25 nM-a commonly used concentration-into KatoIII cells, inhibition of two target genes expression, namely Notch1 and ß-catenin, was not observed, but a non-significant marginal increase of these genes was detected. No changes were detected in the percentage of apoptotic cells as well as in CD44 + and EpCAM + cells after 25 nM miR-34a-5p mimic transfection. Interestingly, stable transfection of pre-mir-34a into KatoIII cells (named as KatoIII-pGFPC1-34a cells) caused a significant repression in ß-catenin protein and Notch1 mRNA levels (p < 0.05 and p < 0.01, respectively) relative to equivalent control (KatoIII- pGFPC1-empty cells). The percentage of CD44 + cells in the KatoIII-pGFPC1-34a cells (< 40%) was significantly lower than that in control cells (~ 95%) (p < 0.05). An increase of ~ 3.5% in apoptotic cells and a slower proliferation rate were detected in KatoIII-pGFPC1-34a cells. CONCLUSIONS: Our study revealed that the effect of miR mimic in target gene repression can be dependent to its concentration as well as to the cell type. Meanwhile, our findings further support a regulatory function for pre-miRNAs in target repression and will help to develop effective therapeutic strategies in cancer treatment.

PD-L1 overexpression conveys tolerance of mesenchymal stem cell-derived cardiomyocyte-like cells in an allogeneic mouse model.

Although the autologously transplanted cells are immunologically durable, allogeneic cell transplantation is inevitable in a series of cases. Mesenchymal stem cells (MSCs) are one of the suitable candidates for cardiac tissue regeneration that have been shown to acquire immunogenicity concurrent with cardiomyogenic differentiation. The present study aimed to exploit PD-L1, as a key immunomodulatory checkpoint ligand to protect the MSCs-derived cardiomyocyte-like cells (CLCs) against the detrimental alloimmunity. Mouse bone marrow-derived MSCs were stably transduced to overexpress PD-L1. MSCs were in vitro differentiated into CLCs and the expressions of immunologic molecules were compared between MSCs and CLCs. The in vitro and in vivo allogeneic immune responses were also examined. The differentiated CLCs had higher expressions of MHC-I and CD80. Upon in vitro coculture with allogeneic splenocytes, CLCs caused more CD4+ and CD8+ T cell activation, lymphocyte proliferation, and interferon-γ (IFN-γ) release in comparison to MSCs. PD-L1 overexpression on CLCs decreased the activation of CD8+ T cells, proliferation of lymphocytes, and release of IFN-γ. The PD-L1-overexpressing CLCs elicited lower in vivo CD4+ and CD8+ T cell activation and reduced the anti-donor antibody response accompanied by increased durability and reduced T cell infiltration. The present study verified the potential of PD-L1 overexpression as a preparative strategy for the protection of allogeneic MSCs-derived CLCs against the detrimental alloreaction.

Expression patterns of seven key genes, including ß-catenin, Notch1, GATA6, CDX2, miR-34a, miR-181a and miR-93 in gastric cancer.

Gastric cancer (GC) is one of the most prevalent cancers and a major cause of cancer related mortality worldwide. Incidence of GC is affected by various factors, including genetic and environmental factors. Despite extensive research has been done for molecular characterization of GC, it remains largely unknown. Therefore, further studies specially conducted among various ethnicities in different geographic locations, are required to know the precise molecular mechanisms leading to tumorigenesis and progression of GC. The expression patterns of seven candidate genes, including ß-catenin, Notch1, GATA6, CDX2, miR-34a, miR-181a, and miR-93 were determined in 24 paired GC tissues and corresponding non-cancerous tissues by quantitative Real-Time PCR. The association between the expression of these genes and clinicopathologic factors were also investigated. Our results demonstrated that overall mRNA levels of GATA6 were significantly decreased in the tumor samples in comparison with the non-cancerous tissues (median fold change (FC) = 0.3143; P = 0.0003). Overall miR-93 levels were significantly increased in the tumor samples relative to the non-cancerous gastric tissues (FC = 2.441; P = 0.0002). ß-catenin mRNA expression showed a strong positive correlation with miR-34a (r = 0.5784; P = 0.0031), and miR-181a (r = 0.5652; P = 0.004) expression. miR-34a and miR-181a expression showed a significant positive correlation (r = 0.4862; P = 0.016). Moreover, lower expression of Notch1 was related to distant metastasis in GC patients with a borderline statistical significance (p = 0.0549). These data may advance our understanding of the molecular biology that drives GC as well as provide potential targets for defining novel therapeutic strategies for GC treatment.

Three Cases of Acute Necrotizing Encephalopathy: Is It an Epidemic or Only Incidental?

Acute necrotizing encephalopathy of childhood (ANEC) is a disease, characterized by a respiratory or gastrointestinal infection, accompanied with fever, rapid alteration of consciousness, and seizures. The clinical characteristics of ANEC include acute encephalopathy following a viral infection, seizure, altered consciousness, and absence of cerebrospinal fluid (CSF) pleocytosis, with an occasional increase in the level of proteins. This disease is almost exclusively seen in previously healthy infants and children from East Asia. Serial magnetic resonance imaging (MRI) examinations have demonstrated symmetric lesions involving the thalami, brainstem, cerebellum, and white matter. ANEC has a poor prognosis with high morbidity and mortality rates. Herein, we present three cases of ANEC, who were referred to Bu-Ali Hospital of Ardabil, Iran during two weeks. Report of these three cases promoted the idea of an epidemic. The purpose of this case series was to raise the issue that ANEC may occur as an epidemic.

Utility of Seizure Pattern and Related Clinical Features in the Diagnosis of Neurometabolic Disorders.

OBJECTIVES: The current study aimed at identifying the role of seizure types and related clinical features in differentiation between neurometabolic disorders and other causes of seizure. MATERIALS & METHODS: The current cross sectional study was conducted at two referral children hospitals in Tehran, Iran, from 2011 to 2018. The study population included 120 patients presenting with seizure due to neurometabolic disorders and 120 cases due to other causes. The types of seizure and related clinical findings were assessed in both groups. RESULTS: There was a significant difference in the frequency of seizure types in the two groups. Tonic and myoclonic seizures as well as infantile spasm were observed more commonly in the patients with neurometabolic disorders, while atonic, partial and generalized tonic-clonic seizures were more common in the control group. In addition, frequency of refractory seizure, age at onset of seizure, and pattern of involvement in brain imaging were helpful for differentiation. CONCLUSION: The pattern of seizure and related findings varied in patients with metabolic disorders, and was helpful for diagnosis. Thus, these factors can contribute to early diagnosis and treatment.

Epigallocatechin-3-gallate Enhances the Efficacy of MicroRNA-34a Mimic and MicroRNA-93 Inhibitor Co-transfection in Prostate Cancer Cell Line.

The potential role of microRNAs (miRNA or MIR) as therapeutic molecules has moved them from basic research to the field of cancer therapy. High expression of miR-93 and low expression of miR-34a have previously been indicated in prostate cancer (PC), which is the second leading cause of cancer-related death in men. Androgen receptor (AR) and prostate-specific antigen (PSA) play key roles in the initiation and progression of this cancer. Therefore, this study aimed to investigate the effects of the transfection and co-transfection of miR-34a mimic and miR-93 inhibitor with or without epigallocatechin-3-gallate (EGCG) on prostate cancer cell line and also to evaluate their effects on the expression of AR, PSA. Human lymph node carcinoma of the prostate (LNCaP) cells were treated with miR-34a mimic or/and miR-93 inhibitor with or without EGCG. Gene or protein expressions were assessed by real-time PCR or western blotting of lysates. The transfection with miR-34a mimics significantly reduced the mRNA expression of AR (p=0.0016), and PSA (p=0.038) compared to the control. Also, the miR-93 inhibitor led to a decrease in the mRNA expression of AR (p=0.0057) and PSA (p>0.05) compared to the control group. Furthermore, the co-transfection, along with EGCG, caused more decrease in both the AR (p<0.001) and the PSA (p=0.003) expression compared with the co-transfection without EGCG. Our study indicates that the reduced expression of AR and PSA in PC cells followed by treatment with miR-34a mimic and miR-93 inhibitor and their combination with EGCG as a natural substance may be a promising therapeutic way for controlling the growth of these malignant cells.

Gaucher Disease: New Expanded Classification Emphasizing Neurological Features.

Gaucher disease (GD) is a rare inherited metabolic disorder and the most common lysosomal storage disorder, caused by a deficiency in glucocerebrosidase enzyme activity. It has been classified according to the neurological manifestations into three types: type 1, without neuropathic findings, type 2 with acute infantile neuropathic signs and type 3 or chronic neuropathic form. However, report of new variants has led to the expansion of phenotype as a clinical phenotype of GD considered as a continuum of phenotypes. Therefore, it seems that a new classification is needed to cover new forms of the disease.

SDF-1α Reduces Human Natural Killer Cell Cytotoxicity against Chronic Myelogenous Leukemia K562 Cells.

Stromal cell-derived factor-1 alpha (SDF-1α) has been shown to be up-regulated in a variety of malignancies. So that, its expression is associated with poor prognosis and invasiveness. Natural killer (NK) cells are important effector cells against virus-infected and transformed cells. Especially they play a key role in tumor immune surveillance. Whereas it was not well understood whether SDF-1α modulates anti-tumor immune response or not, the purpose of the present study was to investigate the effect of SDF-1α on the cytotoxic properties of peripheral blood NK cells. Human peripheral blood NK cells were freshly isolated using MACSxpess system and cultured in the presence or absence of recombinant human SDF-1α or SDF-1α plus CXCR4 antagonist, AMD3100. CD107a degranulation assay was conducted through the co-culture of NK cells with K562 cells. The percentage of CD107a positive cells was assessed by flowcytometry. Effect of SDF-1α was also examined on the mRNA levels of NKG2A and NKG2D as indicator examples of NK cell inhibitory and activating receptors, respectively. SDF-1α significantly decreased the degranulation activity of NK cells (p=0.04). The mRNA content of NKG2D was down-regulated under the influence of SDF-1α (p=0.03). Moreover, AMD3100 exhibited a trend in recovering the NKG2D mRNA level to its un-treated state (p=0.05).  The present study reveals that SDF-1α has a negative impact on NK cell activity and might is involved in tumor immune-suppression. Thus, it can be concluded that microenvironment manipulations targeting SDF-1α may reinforce current cancer therapies by disturbing one of the immune-suppressive axes in the cancerous milieu.

Prediction of Response to Treatment in Children with Epilepsy.

OBJECTIVE: This study was conducted to predict the response to treatment in patients treated with anti-epilepsy drugs. MATERIAL AND METHODS: This analytical questionnaire-based study was conducted in 2014 among 128 patients with epilepsy admitted to Mofid Children's Hospital, Tehran, Iran. The inclusion criteria were children 2 months to 12 yr of age with epilepsy and patients who experienced fever and seizure attacks at least once were excluded from the study. Patients were followed up for 6 months and the response to their treatment was recorded. The good response to treatment was defined as the absence of seizure with two drugs during follow up. RESULTS: Seventy-two patients (56.3%) were boys. The age of the first seizure was under 2 yr old in 90 patients (70.3%). History of febrile convulsion, family history of epilepsy and history of asphyxia was found in 16 (12.5%), 41 (32%), and 27 (21.1%) patients, respectively. Seizure etiology was idiopathic in 90 patients (70.3%), and the number of seizures was 1-2 in 36 patients (28.1%). Overall, 57 patients (44.5%) had cerebral lesion according to CT scan or MRI, and EEG was abnormal in 101 patients (78.9%). In 6-month follow-up, 40 patients (31.3%) responded well to the treatment and 88 patients (68.8%) responded poorly to the treatment. History of asphyxia (OR = 6.82), neonatal jaundice (OR = 2.81) and abnormal EEG (OR = 0.19) were effective factors in response to treatment. CONCLUSION: Abnormal EEG is an effective factor in treatment response in the children studied.

miR-20a inhibition using locked nucleic acid (LNA) technology and its effects on apoptosis of human macrophages infected by Toxoplasma gondii RH strain.

Toxoplasma gondii is a ubiquitous and infectious parasite that multiplies in any nucleated cell of warm-blooded animals and humans worldwide. This parasite has intricate mechanisms to reciprocate host-cell apoptosis to exist in the host cell. So far, the details of the parasite interactions with host cells are not well known. MicroRNAs (miRNAs) are one of the small noncoding RNAs that are now considered as a key mechanism of gene regulation. They are important in physiological and pathological processes such as apoptosis. In this study a Real Time quantitative PCR technique was used to evaluate the levels of miR-20a of miRNAs family in human macrophage during T. gondii infection to determine the role of miR-20a in apoptosis. Then, the inhibition of miR-20a function through interaction with transfection of Locked Nucleic Acid (LNA) antisense oligomer was studied. Furthermore, it was examined whether miR-20a is involved in apoptosis of human macrophages with T. gondii infected cells using flow cytometry. We found that miR-20a expression is up-regulated in human macrophages following T. gondii infection. After LNA anti miR-20a oligomer transfection, miR-20a inhibition was evaluated by quantitative reverse transcriptase polymerase chain reaction. Flow cytometry results showed that LNA anti-miR20a oligomer increased apoptosis. In agreement with this result, we found that specific LNA oligonucleotides prevent the functional activity of miR-20a and promotion of human macrophages apoptosis with T. gondii infection by inhibition of this miRNAs gene. Also, the results support the concept that LNA oligomer antisense may be used as a therapeutic implement for blocking detrimental miRNAs overexpressed in infections.

Are There Neurological Symptoms in Type 1 of Gaucher Disease?

OBJECTIVE: Gaucher disease (GD) is a rare inborn error of metabolism, classified as a lipid storage disorders. This disease is caused by a deficiency in glucocerebrosidase enzyme. It has been classified according to the presence or absence of neurological symptoms into the following types: type 1 non-neuropathic, type 2 acute infantile neuropathic and type 3 or chronic neuropathic. We evaluated neurological symptoms in patients with GD1 and GD3 and compared both of these groups. MATERIALS & METHODS: Eleven patients were identified according to their clinical presentation and the presence of disease confirmed by genetic testing, from 2006-2016, at the Mofid Children Hospital Clinic, Tehran, Iran. We included eight patients with GD 1 and three patients with GD3. Careful neurological examination was performed on these patients during treatment by pediatric neurologist. RESULTS: Patients with GD1 had some neurological symptoms including cognitive impairment, developmental disability, behavioral disorder, microcephaly and increased deep tendon reflexes (DTR). Of course, neurological signs in patients with type 3 of GD were different and were included seizures, supranuclear gaze palsy, cerebellar signs, and ataxia. CONCLUSION: The current nomenclature for 3 types of Gaucher disease does not meet all clinical symptoms. Patients with GD1 display many neurological deficits in young ages not reported adequately earlier.

Wharton's Jelly Derived-Mesenchymal Stem Cells: Isolation and Characterization.

Wharton`s jelly-derived mesenchymal stem cells (WJ-MSCs), have a high proliferation valency and they do not produce teratogen or carcinogen after subsequent transplantation. They are known as regenerative medicine. Thus more research is needed on the isolation and characterization of mesenchymal stem cells. In this experimental study, we obtained Wharton's jelly tissues from mothers during normal vaginal delivery, after obtaining their informed consent. Mesenchymal stem cells were isolated from cultured Wharton`s jelly, cultured, and were then examined for their proliferation, immunophenotypes, and differentiation capacities. The immunophenotypes of WJ-MSCs were analyzed by flow cytometry. Differentiation was performed resulting in osteogenic, chondrogenic and adipogenic cells. WJ-MSCs formed a homogenous monolayer of adherent spindle-shaped cells. Our results showed the high capacity of the proliferation of WJ-MSCs. Immunophenotyping further confirmed the purity of the isolated cells; their surface antigen expression showed the phenotypical properties like those of WJ-MSCs. The expanded cells were positive for CD 90, CD105, and CD44; they were negative for CD34 and HLA-DR surface markers. The cells had the adipocytic, osteocytic and chondrogenic differentiation capacity. The isolation and characterization of WJ-MSCs with high purity had been conducted, and the results were obtained in a short span. The present study has revealed the feasibility of the culture medium with high glucose and 15% FBS in isolation and proliferation of WJ-MSCs. When Wharton`s jelly pieces were put in the dry bottom of the flask, very effective separation of the MSCs was achieved.

Ophthalmologic Findings in Patients with Neuro-metabolic Disorders.

PURPOSE: We aimed to present the ophthalmic manifestations of neuro-metabolic disorders. METHODS: Patients who were diagnosed with neuro-metabolic disorders in the Neurology Department of Mofid Pediatric Hospital in Tehran, Iran, between 2004 and 2014 were included in this study. Disorders were confirmed using clinical findings, neuroimaging, laboratory data, and genomic analyses. All enrolled patients were assessed for ophthalmological abnormalities. RESULTS: A total of 213 patients with 34 different neuro-metabolic disorders were included. Ophthalmological abnormalities were observed in 33.5% of patients. Abnormal findings in the anterior segment included Kayser-Fleischer rings, congenital or secondary cataracts, and lens dislocation into the anterior chamber. Posterior segment (i.e., retina, vitreous body, and optic nerve) evaluation revealed retinitis pigmentosa, cherry-red spots, and optic atrophy. In addition, strabismus, nystagmus, and lack of fixation were noted during external examination. CONCLUSION: Ophthalmological examination and assessment is essential in patients that may exhibit neuro-metabolic disorders.