Abstract Background Previous studies has shown that nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) is expressed in Fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) patients which is stimulated by muramyl dipeptide (MDP) present in the joint environment and induces inflammation via the NF-κB pathway. Also, other studies have shown that curcumin inhibits proliferation, migration, invasion, and Inflammation and on the other hand increases the apoptosis of RA FLSs. In this study, we aim to evaluate the effect of curcumin, a natural antiinflammatory micronutrient, on the expression of NOD2 and inflammatory cytokines. Methods Synovial membranes were collected from ten patients diagnosed with RA and ten individuals with traumatic injuries scheduled for knee surgery. The FLSs were isolated and treated with 40 μM curcumin alone or in combination with 20.3 μM MDP for 24 h. mRNA was extracted, and real-time PCR was performed to quantitatively measure gene expression levels of NOD2, p65, IL-6, TNF-α, and IL-1β. Results The study findings indicate that administering MDP alone can significantly increase the mRNA expression levels of IL-6 and IL-1β in the trauma group and TNF-α in the RA group. Conversely, administering curcumin alone or in combination whit MDP can significantly reduce mRNA expression levels of P65 and IL-6 in FLSs of both groups. Moreover, in FLSs of RA patients, a single curcumin treatment leads to a significant reduction in NOD2 gene expression. Conclusion This study provides preliminary in vitro evidence of the potential benefits of curcumin as a nutritional supplement for RA patients. Despite the limitations of the study being an investigation of the FLSs of RA patients, the results demonstrate that curcumin has an anti-inflammatory effect on NOD2 and NF-κB genes. These findings suggest that curcumin could be a promising approach to relieve symptoms of RA.

SUMMARY OBJECTIVE: The phosphoinositide 3-kinase/protein kinase AKT/mammalian target of rapamycin signaling pathway is essential for proper cellular metabolism and cell growth. However, aberrant activation of this pathway has been linked to the progression and metastasis of breast cancer. Recently, the role of long non-coding RNAs in interfering with the cell signaling pathways involved in cell growth and metabolism has been identified. HOX antisense intergenic RNA is an long non-coding RNA whose abnormal expression has been associated with development, therapy resistance, and metastasis of breast cancer. The purpose of this study was to investigate whether the long non-coding RNA HOX antisense intergenic RNA is linked to the phosphoinositide 3-kinase/protein kinase AKT/mammalian target of rapamycin signaling pathway in breast cancer cells. METHODS: HOX antisense intergenic RNA was silenced in the breast cancer cell line MCF-7 using siRNAs. Subsequently, the gene expression level of HOX antisense intergenic RNA, PI3K, AKT, and mTOR was assessed using real-time RT-PCR. Also, the 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl-tetrazolium bromide) assay was used to analyze cell proliferation. RESULTS: The results revealed that HOX antisense intergenic RNA knockdown can downregulate the expression of PI3K, AKT, and mTOR RNAs compared to negative control in MCF-7 cells. In addition, the proliferation of breast cancer cells was significantly reduced following the HOX antisense intergenic RNA silencing. CONCLUSION: This study may introduce HOX antisense intergenic RNA as a molecule involved in the upregulation of the phosphoinositide 3-kinase/protein kinase AKT/mammalian target of rapamycin signaling pathway in breast cancer cells that may contribute to breast cancer cell proliferation.

Abstract Background Vitiligo is a common disease with a high burden, and its recalcitrant type is unresponsive to current medical treatments. Autologous non-cultured and trypsinized melanocyte grafting, which is a simple and experience-based procedure, has been suggested for the treatment of vitiligo. Objective To assess autologous non-cultured and trypsinised melanocyte grafting in recalcitrant vitiligo. Methods This clinical trial was done on 28 patients (20 females and 8 males). After demarcation and preparation of both donor and recipient sites, both sites were shaved by a curette. The materials harvested from the donor site were trypsinized and centrifuged. The resulting suspension was mixed with hyaluronic acid gel and was spread over the shaved recipient area. Results Twenty-eight patients with a total of 108 lesions and a mean age of 25.93 ± 7.11 years were included in the present study. Generalized vitiligo (57.1%) was the most common clinical type and the face and neck regions (38%) were the most frequent treated sites. Good to excellent repigmentation was seen in the face and neck, trunk, upper extremity, and genitals in 31 (57.4%), 11 (20.4%), 9 (16.7%) and 3 (5.5%) patients, respectively. Face and neck showed significantly better results (p < 0.05). Study limitations Low sample size and single-center study. Conclusion Autologous non-cultured and trypsinized melanocyte grafting is a safe method with satisfactory outcomes in recalcitrant vitiligo. Appropriate training of physicians and proper use of specialists’ experiences can be effective in increasing the improvement rate.

Abstract: Background: Psoriasis is a chronic inflammatory disorder, characterized by increased keratinocyte proliferation due to abnormal differentiation of basal keratinocytes. The etiology of the disease is unclear, and according to the survey results, it is hypothesized that a combination of genetic and environmental factors prompts an abnormal immune response in patients with psoriasis. CD4+ Th cells play a multifaceted role in both immune defense and pathogenesis of certain diseases such as psoriasis. Nonetheless, the exact contribution of different subpopulations of Th cells in psoriasis is still not clear. Objective: The aim of present study was to determine the mRNA expression level of RORC as potential inducer of Th17 cell differentiation and expression pattern of Th17-signature cytokines (IL-17A and IL-22). Methods: Twenty patients with psoriasis and twenty-one healthy subjects were included in the study. Peripheral blood mononuclear cells (PBMCs) were separated and expression of three genes were determined by quantitative real-time reverse transcriptase PCR (qRT-PCR). Plasma levels of IL-17 and IL-22 were also evaluated by ELISA. Results: RORC, IL-17A and IL-22 gene expression was significantly higher in patients with psoriasis compared with healthy controls (P<0.05). In addition, a marked increase in plasma IL-17A and IL-22 levels was observed in patient group compared to controls (P<0.001). Study limitations: small number of patients. Conclusion: These data suggest that Th17 response may contribute to the pathogenesis of psoriasis.

Surgical techniques for treatment of sensory neural hearing loss (SNHL) have unpredictable outcomes and in recent years cell therapy investigated for treatment of SNHL. Olfactory epithelium proceed neurogenesis during life time and provide an easily accessible source of neural stem cells. So the aim of this study was isolating neural stem cells from olfactory epithelium of rat and differentiation of these cells into hair cells of inner ear in vitro. The epithelium tissue of olfactory mucosa of rats were removed and digested by collagenase H. The digested tissue was cultured in flasks in suspension forms to create spheres. Spheres were passaged and from passage 2 spheres selected for differentiation. At this stage cells of spheres isolated from each other and placed in flask containing defined differentiation medium. Cells at this stage cultured in adhesive form. Immunohistochemistry and RT-PCR were used for neural stem cells and hair cells identification. Spheres formed from olfactory epithelium culture and immunohistochemistry revealed that cells of spheres from passage one and two expressed the neural stem cells markers. After culture of isolated cells in differentiation medium, the morphology of cells begun to change. The cells presented neural cells projections and after 10 days the projections elongated more and interact to each other in multi layers. RT-PCR and immunohistochemistry revealed that differentiated cells expressed hair cells specific genes. In this study we showed that neural stem cells of olfactory epithelium can differentiate into hair cells of inner ear and therefore can be used for treatment of SNHL.

Las técnicas quirúrgicas para el tratamiento de la pérdida auditiva neural sensorial (PANS) tienen resultados impredecibles y en los últimos años la terapia celular ha sido investigada para su tratamiento. El epitelio olfatorio se forma durante la neurogénesis y proporciona una fuente fácilmente accesible de células madre neurales. El objetivo de este estudio fue aislar las células madre neurales del epitelio olfativo de la rata y la diferenciación de estas células en vestibulocitos del oído interno in vitro. Se retiró el tejido del epitelio de la mucosa olfatoria de ratas y fue digerido con colagenasa H. El tejido se cultivó en forma de suspensión para crear esferas. Se seleccionaron dos esferas para la diferenciación. En esta fase, las células de esferas fueron aisladas unas de otras y colocadas en un medio de diferenciación definido. Células en esta etapa fueron cultivadas en forma adhesiva. Inmunohistoquímica y RT-PCR se utilizó para las células madre neurales y la identificación de células ciliadas. Las esferas formadas a partir del cultivo del epitelio olfatorio y la inmunohistoquímica revelaron que las células de esferas en etapas uno y dos expresaban los marcadores de células madre neurales. Se observaron cambios en la morfología de las células después del cultivo de células aisladas. RT-PCR e inmunohistoquímica revelaron que las células diferenciadas expresaron células específicas de gen de vestibulocitos. Se observó que las células madre neuronales de epitelio olfatorio puede diferenciarse en células en forma de cabello del oído interno y por lo tanto puede ser utilizado para el tratamiento de PANS.

Abstract This paper investigates the numerical modeling of the flexural wave propagation in Euler-Bernoulli beams using the Hermite-type radial point interpolation method (HRPIM) under the damage quantification approach. HRPIM employs radial basis functions (RBFs) and their derivatives for shape function construction as a meshfree technique. The performance of Multiquadric(MQ) RBF to the assessment of the reflection ratio was evaluated. HRPIM signals were compared with the theoretical and finite element responses. Results represent that MQ is a suitable RBF for HRPIM and wave propagation. However, the range of the proper shape parameters is notable. The number of field nodes is the main parameter for accurate wave propagation modeling using HRPIM. The size of support domain should be less thanan upper bound in order to prevent high error. With regard to the number of quadrature points, providing the minimum numbers of points are adequate for the stable solution, but the existence of more points in damage region does not leads to necessarily the accurate responses. It is concluded that the pure HRPIM, without any polynomial terms, is acceptable but considering a few terms will improve the accuracy; even though more terms make the problem unstable and inaccurate.

O objetivo do presente estudo foi investigar o efeito protetor da crocina em lesões da mucosa gástrica causadas por isquemia-reperfusão (I/R) em ratos. Trinta e dois ratos machos aleatoriamente divididos em grupos de ratos normais, operados como controle, I/R. I/R + pré-tratamento com crocina e crocina sozinha. Para induzir lesões I/R, a artéria celíaca foi grampeada durante 30 minutos e, em seguida, o grampo foi removido para permitir a reperfusão por 3 h. Ratos com pré-tratamento com crocina receberam crocina (15 mg/kg, ip) 30 minutos antes da indução do dano I/R. Amostras de mucosa gástrica foram coletadas para qiuantificar a expressão da proteína da caspase-3, o fator apoptótico, e óxido nítrico sintase induzível (iNOS), uma proteína anti-inflamatória, pela técnica de Western Blot. O pré-tratamento com crocina diminuiu a área total de lesões gástricas e a expressão de níveis de caspase-3 e iNOS induzidas pelo dano I/R. Nossos resultados mostraram o efeito protetor da crocina na mucosa gástrica contra o dano I/R. Este efeito foi mediado, principalmente, por diminuição da expressão das proteínas iNOS e caspase-3.

The aim of the present study was to investigate the protective effect of crocin on gastric mucosal lesions caused by ischemia-reperfusion (I/R) injury in rats. Thirty-two male rats were randomly divided into sham, I/R, I/R + crocin pretreatment and crocin alone groups. To induce I/R lesions, the celiac artery was clamped for 30 min, and the clamp was then removed to allow reperfusion for 3 h. Crocin-pretreated rats received crocin (15 mg/kg, i.p.) 30 min prior to the induction of I/R injury. Samples of gastric mucosa were collected to quantify the protein expression of caspase-3, an apoptotic factor, and inducible nitric oxide synthase (iNOS), a pro-inflammatory protein, by Western blot. Pretreatment with crocin decreased the total area of gastric lesions and decreased the protein expression levels of caspase-3 and iNOS induced by I/R injury. Our findings showed a protective effect of crocin in gastric mucosa against I/R injury. This effect of crocin was mainly mediated by reducing the protein expression of iNOS and caspase-3.

Nuclear transfer embryonic stem cells (ntESCs) show stem cell characteristics such as pluripotency but cause no immunological disorders. Although ntESCs are able to differentiate into somatic cells, the ability of ntESCs to differentiate into primordial germ cells (PGCs) has not been examined. In this work, we examined the capacity of mouse ntESCs to differentiate into PGCs in vitro. ntESCs aggregated to form embryoid bodies (EB) in EB culture medium supplemented with bone morphogenetic protein 4(BMP4) as the differentiation factor. The expression level of specific PGC genes was compared at days 4 and 8 using real time PCR. Flow cytometry and immunocytochemical staining were used to detect Mvh as a specific PGC marker. ntESCs expressed particular genes related to different stages of PGC development. Flow cytometry and immunocytochemical staining confirmed the presence of Mvh protein in a small number of cells. There were significant differences between cells that differentiated into PGCs in the group treated with Bmp4 compared to non-treated cells. These findings indicate that ntESCs can differentiate into putative PGCs. Improvement of ntESC differentiation into PGCs may be a reliable means of producing mature germ cells.

Background:This study performed at the National Research Institute of Tuberculosis and Lung Disease, Tehran, Iran, aimed to evaluate the effect of concomitant pulmonary hypertension on the outcome of pulmonary tuberculosis.Methods:New cases of pulmonary tuberculosis were recruited for the study. Pulmonary hypertension was defined as systolic pulmonary arterial pressure ≥35 mm Hg estimated by transthoracic Doppler echocardiography. We assessed the relationship between pulmonary hypertension and mortality during the six-month treatment of tuberculosis.Results:Of 777 new cases of pulmonary tuberculosis, 74 (9.5%) had systolic pulmonary arterial pressure ≥35 mm Hg. Ten of them (13.5%) died during treatment compared to 5% of cases with pulmonary arterial pressure less than 35 mm Hg (p = 0.007). Logistic regression analysis showed that pulmonary hypertension and drug abuse remained independently associated with mortality (OR = 3.1; 95% CI: 1.44–6.75 and OR = 4.4; 95% CI: 2.35–8.17, respectively).Conclusion:A significant association was found between mortality and presence of pulmonary hypertension and drug abuse among new cases of pulmonary tuberculosis.