A novel therapeutic strategy: the significance of exosomal miRNAs in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a fast-growing blood cancer that interferes with the normal growth of blood cells in the bone marrow and blood. It is characterized by its unpredictable outlook and high death rate. The main treatment for AML is chemotherapy, but this often results in drug resistance and the possibility of the disease returning. For this reason, new biomarkers are necessary to diagnose, predict, and treat this disease. Research has demonstrated that cells responsible for AML release exosomes that interact with the disease's microenvironment. These exosomes have significant roles in promoting leukemia growth, suppressing normal hematopoiesis, facilitating angiogenesis, and contributing to drug resistance in AML. Further investigations have shown that these exosomes contain miRNAs, which are transferred to target cells and have functional roles. Biomarkers are utilized to assess various aspects of tumor cell behavior, including proliferation, apoptosis, angiogenesis, changes in the microenvironment, transfer of drug resistance, and stability in serum and blood plasma. In this research, we showed that exosomal miRNAs and exosomes have the potential to be used as indicators for detecting various phases of AML and can aid in its medical treatment. Furthermore, they can be specifically targeted for therapeutic purposes in addressing this condition.

Recent advances in pre-conditioned mesenchymal stem/stromal cell (MSCs) therapy in organ failure; a comprehensive review of preclinical studies.

Mesenchymal stem/stromal cells (MSCs)-based therapy brings the reassuring capability to regenerative medicine through their self-renewal and multilineage potency. Also, they secret a diversity of mediators, which are complicated in moderation of deregulated immune responses, and yielding angiogenesis in vivo. Nonetheless, MSCs may lose biological performance after procurement and prolonged expansion in vitro. Also, following transplantation and migration to target tissue, they encounter a harsh milieu accompanied by death signals because of the lack of proper tensegrity structure between the cells and matrix. Accordingly, pre-conditioning of MSCs is strongly suggested to upgrade their performances in vivo, leading to more favored transplantation efficacy in regenerative medicine. Indeed, MSCs ex vivo pre-conditioning by hypoxia, inflammatory stimulus, or other factors/conditions may stimulate their survival, proliferation, migration, exosome secretion, and pro-angiogenic and anti-inflammatory characteristics in vivo. In this review, we deliver an overview of the pre-conditioning methods that are considered a strategy for improving the therapeutic efficacy of MSCs in organ failures, in particular, renal, heart, lung, and liver.

Early Vitrectomy: An Effective Treatment for Acute Postcataract Surgery Endophthalmitis.

Background: Endophthalmitis is a rare but a high morbid complication after cataract surgery, and a gold standard treatment is not recommended yet. In this study, we aim to evaluate the effect of early vitrectomy on the visual acuity of patients with postcataract endophthalmitis. Materials and Methods: This study was a single-arm clinical trial on 27 patients with postcataract surgery endophthalmitis. Early vitrectomy was the intervention. Visual acuity as the primary outcome was evaluated and compared at baseline, at discharge, and 1 and 3 months after the intervention. Results: From 27 patients who included in our study, six patients gain favorable visual acuity of 5/10 and above (success rate = 22%), and four of them have no improvement in their visual acuity. Retinal detachment was reported as a complication in just one case. Negative culture was a predictor for success in terms of visual acuity after the surgery. All patients who gain favorable results, presented in the first 15 days after the cataract surgery. Conclusion: The result of our study showed that, considering complete, early vitrectomy for the treatment of postcataract surgery endophthalmitis, especially for those who presented in the first 15 days of cataract surgery and for those who have negative culture is promising.

Fabrication of a microfluidic device for probiotic drug's dosage screening: Precision Medicine for Breast Cancer Treatment.

Breast cancer is the most common cancer in women; it has been affecting the lives of millions each year globally and microfluidic devices seem to be a promising method for the future advancements in this field. This research uses a dynamic cell culture condition in a microfluidic concentration gradient device, helping us to assess breast anticancer activities of probiotic strains against MCF-7 cells. It has been shown that MCF-7 cells could grow and proliferate for at least 24 h; however, a specific concentration of probiotic supernatant could induce more cell death signaling population after 48 h. One of our key findings was that our evaluated optimum dose (7.8 mg/L) was less than the conventional static cell culture treatment dose (12 mg/L). To determine the most effective dose over time and the percentage of apoptosis versus necrosis, flowcytometric assessment was performed. Exposing the MCF-7 cells to probiotic supernatant after 6, 24 and 48 h, confirmed that the apoptotic and necrotic cell death signaling were concentration and time dependent. We have shown a case that these types of microfluidics platforms performing dynamic cell culture could be beneficial in personalized medicine and cancer therapy.

SARS-CoV-2-associated gut microbiome alteration; A new contributor to colorectal cancer pathogenesis.

The emergence of a novel coronavirus, COVID-19, in December 2019 led to a global pandemic with more than 170 million confirmed infections and more than 6 million deaths (by July 2022). Studies have shown that infection with SARS-CoV-2 in cancer patients has a higher mortality rate than in people without cancer. Here, we have reviewed the evidence showing that gut microbiota plays an important role in health and is linked to colorectal cancer development. Studies have shown that SARS-CoV-2 infection leads to a change in gut microbiota, which modify intestinal inflammation and barrier permeability and affects tumor-suppressor or oncogene genes, proposing SARS-CoV-2 as a potential contributor to CRC pathogenesis.

MicroRNA-125a-3p, -4530, and -92a as a Potential Circulating MicroRNA Panel for Noninvasive Pancreatic Cancer Diagnosis.

MicroRNA (miRNA) expression dysregulations in pancreatic ductal adenocarcinoma (PDAC) have been studied widely for their diagnostic and prognostic utility. By the use of bioinformatics-based methods, in our previous study, we identified some potential miRNA panels for diagnosis of pancreatic cancer patients from noncancerous controls (the screening stage). In this report, we used 142 plasma samples from people with and without pancreatic cancer (PC) to conduct RT-qPCR differential expression analysis to assess the strength of the first previously proposed diagnostic panel (consisting of miR-125a-3p, miR-4530, and miR-92a-2-5p). As the result, we identified significant upregulation for all the three considered miRNAs in the serum of PC patients. After that, a three-miRNA panel in serum was developed. The area under the receiver operating characteristic curves (AUC) for the panel were 0.850, 0.910, and 0.86, respectively, indicating that it had a higher diagnostic value than individual miRNAs. Therefore, we detected a promising three-miRNA panel in the plasma for noninvasive PC diagnosis (miR-125a-3p, miR-4530, and miR-92a-2-5p).

Recent findings on chimeric antigen receptor (CAR)-engineered immune cell therapy in solid tumors and hematological malignancies.

Advancements in adoptive cell therapy over the last four decades have revealed various new therapeutic strategies, such as chimeric antigen receptors (CARs), which are dedicated immune cells that are engineered and administered to eliminate cancer cells. In this context, CAR T-cells have shown significant promise in the treatment of hematological malignancies. However, many obstacles limit the efficacy of CAR T-cell therapy in both solid tumors and hematological malignancies. Consequently, CAR-NK and CAR-M cell therapies have recently emerged as novel therapeutic options for addressing the challenges associated with CAR T-cell therapies. Currently, many CAR immune cell trials are underway in various human malignancies around the world to improve antitumor activity and reduce the toxicity of CAR immune cell therapy. This review will describe the comprehensive literature of recent findings on CAR immune cell therapy in a wide range of human malignancies, as well as the challenges that have emerged in recent years.

Intraosseous ancient Schwannoma: A rare case in the mandible and a literature review.

Schwannoma, otherwise known as neurilemmoma, is a benign tumor that originates from Schwann cells. Ancient Schwannoma is a long-standing Schwannoma with degenerative and xanthomatous changes. The Head and neck region is one of the most common sites for nerve sheath tumors but Involvement of the jaw is a considerably infrequent event. We report a rare case of intraosseous ancient Schwannoma of the mandible in a 24-year-old male patient which was initially misdiagnosed with carcinoma. The clinical features, radiographic findings, and treatment plan are discussed. Furthermore, a thorough literature review demonstrated nine published cases of intra-osseous ancient Schwannoma with their summarized features. Recognition of various histopathologic features of ancient Schwannoma is essential to prevent over-treatment.

GC-MS determination of the content of polycyclic aromatic hydrocarbons in bread and potato Tahdig prepared with the common edible oil.

The polycyclic aromatic hydrocarbon (PAH) content of the Tahdig of the breads and potatoes prepared with edible oil was determined by GC-MS. The Tahdigs of bread and potato were baked under the same condition (volume of any oil 40 cc, temperature 180 °C, time 30 min). Polycyclic aromatic hydrocarbon determination was performed by an Agilent 6890 N Gas chromatography with mass selective detector, equipped with a capillary column. The highest contents of PAHs in Tahdig of bread and Tahdig of potato were observed in canola with 550 ± 3.9 ng/kg and sesame with 408.3 ± 41 ng/kg. The mean of PAH content was significantly higher in the Tahdig of bread compared to the Tahdig of potato (p < 0.05). Among the 16 PAHs examined by GC/MS, 10 PAHs were detected. The amount of high molecular weight (HMW) PAHs were significantly more than low molecular weight (LMW) PAHs (p < 0.05). Benzo [b]fluoranthene and benz[a]anthracene concentrations were significantly more than the other detected compounds (p < 0.05). Due to high PAH contamination of both Tahdig groups, the consumption of Tahdig (any type) was not recommended.

Cabbage-derived three-dimensional cellulose scaffold-induced osteogenic differentiation of stem cells.

Herbal-derived three-dimensional scaffolds have a unique structure that represents the natural cellular microenvironment and can be potentially used for tissue engineering applications. In the present study, cabbage (Cb) leaves were decellularized and then their characteristics, such as surface roughness, wettability, porosity, mechanical properties, and specific surface area, were investigated. After that, scaffold osteoinductivity was studied by bone-marrow-derived mesenchymal stem cells (BM-MSCs) osteogenic differentiation while growing on the decellularized Cb leaves. Cells mineralization, calcium secretion, alkaline phosphatase (ALP) activity, and expression levels of bone-related genes were determined during the differentiation process. Our results from the structural characterization of the scaffolds demonstrated that decellularized Cb leaves are good candidates for bone differentiation in terms of surface roughness, mechanical properties, and interconnected pores. Osteogenic differentiation evaluation of the BM-MSCs determined that the cell's ALP activity and mineralization were increased significantly while cultured on the decellularized Cb leaves compared to the cells cultured on the culture plate as a control. Besides, Runx2, ALP, collagen-1 (Col-I), and osteocalcin genes were expressed in cells cultured on decellularized Cb leaves significantly higher than cells cultured on the culture plate. Based on these results, it can be concluded that the decellularized Cb scaffold has great potential for promoting BM-MSCs proliferation and osteogenic differentiation.

Efficient mineralization and osteogenic gene overexpression of mesenchymal stem cells on decellularized spinach leaf scaffold.

Until now, various methods have been introduced to fabricate 3D scaffolds to provide a suitable substrate for cell growth and proliferation and subsequent use in tissue engineering to repair damaged tissues. The 3D scaffolds can simulate the natural cellular microenvironment well. Herein, the decellularized leaf spinach has been used which not only have no problems associated with artificial scaffolds, but they also do not cost significantly. Decellularized scaffolds surface properties were characterized by the investigation of scaffolds surface roughness, hydrophilicity, mechanical properties, size and shape of porosities and specific surface area. In the next step, osteogenic differentiation potential of bone marrow derived mesenchymal stem cells cultured on the scaffold and culture plate (as a control) was evaluated using alizarin staining and calcium content, alkaline phosphatase activity and bone related genes expression assays. The results indicated that the surface properties and shape of scaffold pores were effective in the stem cells binding, growth and proliferation. This higher biocompatibility due to the ideal surface hydrophilicity as well as high specific surface area due to the presence of a rough grid surface ultimately increased the efficiency of stem cell's bone differentiation. Taken together, it can be concluded that the decellularized spinach leaf scaffold, due to its easy availability, low prices and high efficiency, can be considered as a promising potential candidate for use as a proper substrate for stem cell growth and differentiation in bone tissue engineering.

Introducing GATA3 as a prominent player in Crohn's disease.

AIM: This study was aimed at gene assessment of Crohn's disease (CD) through protein-protein interaction (PPI) network analysis to find crucial genes. BACKGROUND: CD is a major subtype of inflammatory bowel diseases (IBD), which affects gastrointestinal tract. PPI network analysis is a suitable tool to clarify a critical gene as a drug target or diagnostic biomarker for these types of diseases. METHODS: Gene expression profile GSE126124 of 20 CD patients and 20 healthy controls was obtained from the Gene Expression Omnibus (GEO) database. RNA profile of peripheral blood mononuclear cells (PBMCs) and colon biopsy samples of the studied groups was investigated. Crucial genes were selected and analyzed via the PPI network by Cytoscape software. Gene ontology enrichment for the hubs, bottlenecks, and hub-bottlenecks was performed via CluGO plugin of Cytoscape software. RESULTS: Eighty-one differentially expressed genes (DEGs) among 250 initial DEGs were highlighted as significant by FC>2 and p-value ≤ 0.05, and 69 significant DEGs were used for PPI network construction. The network was characterized by poor connections, so 20 top neighbors were added to form a scale-free network. The main connected component included 39 query DEGs and 20 added first neighbors. Three clusters of biological processes associated with crucial genes were identified and discussed. CONCLUSION: The results of this study indicated that GATA3 has a key role in CD pathogenesis and could be a possible drug target or diagnostic biomarker for Crohn's disease.

Possible dual contribution of a novel GUCY2D mutation in the development of retinal degeneration in a consanguineous population.

Molecular characterization of novel mutations in Leber Congenital Amaurosis (LCA) disease improves the disease diagnosis and contributes to the development of preventive and therapeutic approaches. We studied an isolated inbred population in Iran with a high prevalence of retinal degeneration with clinical variability. The clinical examinations were performed on eight patients belonging to three consanguineous families. The identical-by-descent (IBD) mapping technique was employed to identify the shared loci in patients. Subsequently, Sanger sequencing of the GUCY2D gene, in silico analysis, as well as segregation study were conducted. The whole-exome sequencing method was applied for negative cases of GUCY2D mutation, followed by segregation study in suspected variants among families. A novel deletion mutation in the GUCY2D gene can explain the emergence of LCA-1 in most patients but not all. Besides, a heterozygous variant of uncertain significance (VUS) was observed in the BEST1 gene in some healthy and participant patients. These results further support inter/intra-familial clinical heterogeneity in retinal dystrophy and suggest that screening the GUCY2D gene would be needed for the diagnosis of LCA in Iranian people living in the central regions. The variant in the BEST1 gene might be considered a benign heterozygous variant; however, we hypothesized a possible double heterozygosity in both GUCY2D and BEST1 genes that may cause the pathogenesis of cone-rod dystrophy-6 (CRD-6) disease. This would propose a new scenario for the pathogenesis of a monogenic disorder such as CRD-6 disease in which other genetic elements may be involved in the development of the disease.

Comparison of the Sedation Quality of Etomidate, Propofol, and Midazolam in Combination with Fentanyl During Phacoemulsification Cataract Surgery: A Double-Blind, Randomized, Controlled, Clinical Trial.

BACKGROUND: According to the favorable effects of combination therapy to provide better sedation during phacoemulsification and lack of any studies investigating the sedative effect of etomidate, propofol, and midazolam in combination with fentanyl during the procedure. OBJECTIVES: The current study aimed at comparing the sedative properties of the mentioned three combination therapies in this field. METHODS: The current double-blind, randomized, controlled clinical trial was conducted on patients referred for elective phacoemulsification surgery under sedation. They were randomly allocated to the three groups to receive fentanyl plus one of the following medications: Propofol, midazolam, and etomidate. Demographic characteristics, medical condition, and hemodynamic parameters before, during, and after surgery, sedation level, anesthetic complications, sedation-related adverse events, and patients' and surgeons' satisfaction were evaluated and recorded by the anesthesiologist and compared in the three studied groups. RESULTS: In the current study, out of 150 enrolled patients, 98 completed the study. Frequency of different levels of Ramsay scores was not significantly different between the groups (P = 0.41). Frequency of Ramsay scores 3 and 4 was 92%, 79.4%, and 88.2% in etomidate, midazolam and propofol groups, respectively (P = 0.32). The median recovery time was significantly higher in the midazolam group than the propofol group (P = 0.04); intergroup comparisons indicated that the patients' mean score of satisfaction in the propofol group was significantly higher than that of the etomidate group (P = 0.006). CONCLUSIONS: The current study findings indicated that though the quality of sedation during phacoemulsification cataract surgery was acceptable in the three agents and the results had no significantly differences among the groups, and considering other factors including recovery time, hemodynamic evaluation, sedation-related complications, and patients' satisfication scores, it is suggested that propofol was superior to the other two agents.

The effect of banana leaf package on the shelf life of rainbow trout fillet in comparison with plastic bag s / O efeito da embalagem de folha de bananeira na vida de prateleira do filé de truta arco-íris em comparação com sacos de plástico

The aim of this study was to evaluate the effect of banana leaf extract on the quality and shelf life of rainbow trout compared to plastic bags at freezing temperature for 40 days. For evaluating this propose, the antioxidant activity of banana leaf extract was assessed. In addition, the shelf life of fish filets was determined by measuring thiobarbituric acid (TBA) and pHof fish. The banana leaves extract showed the highest content of vitamin E (5.8 ± 0.61 mg /g) and carotenoids (12.8 ± 0.1 mg /g). The potential of Cu (II) reduction the extract was 1.76 ± 0.09. The magnitude of modification in TBA and pH of the packed fish with banana leaves were less than the control samples. The present study demonstrated that the use of banana leaf extract will retard lipid oxidation in fish. fillet during freezing storage that may due to its strong antioxidant properties.

O objetivo deste estudo foi avaliar o efeito do extrato de folhas de bananeira sobre a qualidade e vida de prateleira da truta arco-íris comparada a sacolas plásticas na temperatura de congelamento por 40 dias. Para avaliar essa proposta, foi determinada a atividade antioxidante do extrato de folhas de bananeira. Além disso, a vida de prateleira dos filés de peixe foi determinada medindo o ácido tiobarbitúrico (TBA) e o pH do peixe. O extrato de folhas de bananeira apresentou o maior teor de vitamina E (5,8 ± 0,61 mg/g) e carotenóides (12,8 ± 0,1 mg/g). O potencial de redução de Cu (II) no extrato foi de 1,76 ± 0,09. A magnitude da modificação no TBA e pH do peixe embalado com folhas de bananeira foi menor que as amostras controle. O presente estudo demonstrou que o uso de extrato de folhas de bananeira é capaz de retardar a oxidação lipídica no filé de peixe durante o armazenamento de congelamento, devido às suas fortes propriedades antioxidantes.

Simultaneous Unilateral Presentation of Three Different Ocular Manifestations of Granulomatosis with Polyangiitis.

PURPOSE: To report the simultaneous presentation of three ocular manifestations of granulomatosis with polyangiitis in one eye. CASE REPORT: A 42-year-old man with a confirmed diagnosis of granulomatosis with polyangiitis was referred to the emergency room with sudden blurred vision. Eye examination showed hyperemic conjunctiva due to necrotizing scleritis in the superior nasal quadrant of the left eye, a mass in the left superior lid, as well as central retinal artery occlusion in the same eye. CONCLUSION: This case suggests that unilateral eye involvement may be a manifestation of underlying granulomatosis with polyangiitis.

Blockade of nuclear factor-κB (NF-κB) pathway inhibits growth and induces apoptosis in chemoresistant ovarian carcinoma cells.

Epithelial ovarian cancer (EOC) has exhibited marginal improvement in survival rate, despite advances in surgical debulking and chemotherapy regimens. Although the majority of EOC patients achieve a clinical remission after induction therapy, over 80% relapse and succumb to chemoresistant disease. In this regard, it is of paramount importance to elucidate molecular mechanisms and signaling pathways which promote therapy resistance in EOC in order to devise novel and more effective treatment strategies. In this study, we showed that activation of nuclear factor-κB (NF-κB) is significantly higher in therapy-resistant EOC cells compared to chemosensitive counterparts, which was positively associated with resistance to cisplatin, carboplatin, paclitaxel and erlotinib. Bay 11-7082, a highly selective NF-κB inhibitor, reduced cell proliferation, clonogenicity and anoikis resistance in the therapy-resistant EOC cells and induced apoptotic cell death. Moreover, Bay 11-7082 decreased the expression of pro-survival, inflammatory and metastatic genes and synergistically increased anti-proliferative efficacy of cisplatin, carboplatin, paclitaxel and erlotinib. Altogether, these findings suggest that NF-κB is an attractive therapeutic target in EOC to be exploited in translational oncology and Bay 11-7082 is a potential anti-cancer drug to overcome chemoresistance and inhibit proliferation of the EOC cells.

The effects of smoking on corneal endothelial cells: a cross-sectional study on a population from Isfahan, Iran.

PURPOSE: The aim of this study is to compare the effect of smoking in corneal endothelial cell number and morphology by specular microscopy on a non-smoker population. METHODS: Our cross-sectional study was performed on 150 participants from a non-smoker population. Non-contact specular microscopy (Tomey Corporation Inc., Nagoya, Japan) was performed in the center of the cornea of all subjects. The cell density (CD), average cell size (AVG), percent of hexagonality (HEX%) and central corneal thickness (CCT) were calculated and compared in both groups. RESULTS: Totally, 76 eyes of 76 smokers and 74 eyes of 74 non-smokers were enrolled in the study from 2015 to 2016. The mean age of smokers and non-smokers were 48.61 ± 17.04 and 46.39 ± 13.02, respectively. The mean number of pack/year among the smokers was 17.36 ± 14.68. Also, the mean values of AVG and CD were significantly different for these two groups (p = 0.011 and p = 0.039, respectively). Other corneal endothelial variables did not show a significant difference between smokers and non-smokers (p > 0.05). However, smokers with severe nicotine dependency had significantly greater AVG and lower CD in comparison with the non-smokers (p = 0.004 and p = 0.013, respectively). CONCLUSION: Our study showed that smoking can cause significant changes in some of the corneal endothelial variables, but not all of them.

Ruptured Papillary Muscles After Chordae-Preserving Bioprosthetic Mitral Valve Replacement.

Bioprosthetic valve-associated masses in the perioperative period are rare. This report describes the case of a 68-year-old man with perivalvular masses that were initially discovered on a routine postoperative transthoracic echocardiogram 7 days after chordae-preserving mitral valve replacement and coronary artery bypass grafting. An intraoperative transesophageal echocardiogram demonstrated ruptured papillary muscles. This case report describes the differential diagnosis and surgical management of this rare finding.

Radioactivity levels in the mostly local foodstuff consumed by residents of the high level natural radiation areas of Ramsar, Iran.

Among High Level Natural Radiation Areas (HLNRAs) all over the world, the northern coastal city of Ramsar has been considered enormously important. Many studies have measured environmental radioactivity in Ramsar, however, no survey has been undertaken to measure concentrations in the diets of residents. This study determined the 226Ra activity concentration in the daily diet of people of Ramsar. The samples were chosen from both normal and high level natural radiation areas and based on the daily consumption patterns of residents. About 150 different samples, which all are local and have the highest consumption, were collected during the four seasons. In these samples, after washing and drying and pretreatment, the radionuclide was determined by α-spectrometry. The mean radioactivity concentration of 226Ra ranged between 5 ± 1 mBq kg-1 wet weight (chino and meat) to 725 ± 480 mBq kg-1 for tea dry leaves. The 226Ra activity concentrations compared with the reference values of UNSCEAR appear to be higher in leafy vegetables, milk and meat product. Of the total daily dietary 226Ra exposure for adults in Ramsar, the largest percentage was from eggs. The residents consuming eggs from household chickens may receive an elevated dose in the diet.