Mutant analysis of Kcng4b reveals how the different functional states of the voltage-gated potassium channel regulate ear development.

The voltage gated (Kv) slow-inactivating delayed rectifier channel regulates the development of hollow organs of the zebrafish. The functional channel consists of the tetramer of electrically active Kcnb1 (Kv2.1) subunits and Kcng4b (Kv6.4) modulatory or electrically silent subunits. The two mutations in zebrafish kcng4b gene - kcng4b-C1 and kcng4b-C2 (Gasanov et al., 2021) - have been studied during ear development using electrophysiology, developmental biology and in silico structural modelling. kcng4b-C1 mutation causes a C-terminal truncation characterized by mild Kcng4b loss-of-function (LOF) manifested by failure of kinocilia to extend and formation of ectopic otoliths. In contrast, the kcng4b-C2-/- mutation causes the C-terminal domain to elongate and the ectopic seventh transmembrane (TM) domain to form, converting the intracellular C-terminus to an extracellular one. Kcng4b-C2 acts as a Kcng4b gain-of-function (GOF) allele. Otoliths fail to develop and kinocilia are reduced in kcng4b-C2-/-. These results show that different mutations of the silent subunit Kcng4 can affect the activity of the Kv channel and cause a wide range of developmental defects.

In vitro co-delivery of 5-fluorouracil and all-trans retinoic acid by PEGylated liposomes for colorectal cancer treatment.

BACKGROUND: Single-target inhibitors have not been successful in cancer treatment due to the development of drug resistance. Nevertheless, therapeutic agents capable of simultaneously inhibiting multiple targets have revealed encouraging results in inducing apoptosis and overcoming drug resistance in cancerous cells. Here, we designed a composite liposomal nano-carrier co-loading 5-Fluorouracil (5-FU) with all-trans retinoic acid (ATRA) to assess anticancer efficacy of the combined drugs in colorectal cancer (CRC). METHODS: A PEGylated liposomal nano-carrier with phospholipid/cholesterol/DSPE-PEG (2000) was synthesized by the thin film hydration technique for co-delivery of ATRA and 5-FU. After characterizing, the role of 5-FU and ATRA co-loaded liposomal nano-carrier in proliferation, epithelial-mesenchymal transition (EMT), apoptosis, and cancer stem cells (CSCs) were investigated by using colony forming and MTT assay, RT-qPCR and Annexin V/PI kit. RESULTS: The average size of liposomes (LPs) was < 150 nm with uniform size distribution. Drug release analyses indicated that both ATRA and 5-FU could simultaneously release from LPs in a sustained release manner. The synergistic inhibitory effects of ATRA and 5-FU loaded in LPs were verified with a combination index of 0.43. Dual drug LPs showed the highest cytotoxicity, enhanced inhibition of cell proliferation, increased apoptotic potential, decreased CSCs, and attenuated EMT-associated biomarkers. Also, dual drug LPs decreased ß-catenin gene expression more than other liposomal formulations. CONCLUSION: These findings suggest that using LPs to achieve a synergistic effect of ATRA and 5-FU is an effectual approach to increase the therapeutic effect of 5-FU toward CRC cells.

The potential role of nucleophosmin (NPM1) in the development of cancer.

Nucleophosmin (NPM1) is a well-known nucleocytoplasmic shuttling protein that performs several cellular functions such as ribosome biogenesis, chromatin remodeling, genomic stability, cell cycle progression, and apoptosis. NPM1 has been identified to be necessary for normal cellular functions, and its altered regulation by overexpression, mutation, translocation, loss of function, or sporadic deletion can lead to cancer and tumorigenesis. In this review, we focus on the gene and protein structure of NPM1 and its physiological roles. Finally, we discuss the association of NPM1 with various types of cancer including solid tumors and leukemia.

A promising effect of zerumbone with improved anti-tumor-promoting inflammation activity of miR-34a in colorectal cancer cell lines.

Cross-talk among inflammation and colorectal cancer cells is chiefly reported through a complex of cytokines, chemokines, and growth factors. MicroRNA performs strategic roles in controlling a variety of signaling cascades. miR-34a is known as a master regulator of tumor suppression. Combined application of different miRNA-based agents and chemotherapeutic drugs has been used to augment drug sensitivity and may reinforce the antitumor effect. A lot of studies specify a substantial increase in the effectiveness of combination therapies. The anti-inflammatory activity of Zerumbone (ZER) was investigated in many cancers. In this study the level of the inflammatory cytokines including CXCL-12 (SDF-1), CCL-2 (MCP-1), TGF-ß and IL-33 has been measured in pmiR-34a-5p transfected and pmiR-34a-5p +ZER treated CRC cell lines (HCT-116 and SW48) by QRT-PCR and ELISA methods, respectively. The results showed that miR-34a could significantly inhibit cytokine expression in both cell lines for 48 and 72 h except SDF-1 which no inhibition was observed in SW48 cells. ZER suppressed SDF-1 for all three time points in both cell lines, while in SW48 cells IL-33 and TGF-ß were inhibited in 72 h and in HCT-116 cells MCP-1 diminished for only 24 h and TGF-ß diminished for all three times. Combination of both miR-34a and ZER suppressed TGF-ß, SDF-1 and MCP-1 in HCT-116 cells in all time points while in SW48 cells, suppression of most cytokines was observed in 48 and 72 h. Furthermore Colony formation assay and scratch test were employed to detect changes of proliferation and migration in CRC transfected and treated cells. Generally, we found that miR-34a could considerably decrease the expression of inflammatory cytokines and the combination of ZER+ miR-34 boosted this effect. Moreover the migration and proliferation decreased in treated and transfected cells and this reduction was more severe in miR-34a +ZER treatment. It is important to note that in the case of cell resistance to each of these therapeutic agents, inhibition of cytokines can be compensated by another one.

Investigating the relationship between the severity of coronary artery disease and inflammatory factors of MHR, PHR, NHR, and IL-25.

Background: Coronary artery disease (CAD), as a most common cause of death, is mainly caused by atherosclerosis. Due to the role of inflammation in the process of atherosclerosis, in the present study, the relationship between the severity of coronary artery disease and inflammatory factors of monocyte to HDL-C ratio (MHR), platelet-to-HDL-C ratio (PHR), neutrophil to HDL-C ratio (NHR), and IL-25 was investigated. Methods: In this cross-sectional study, 64 patients with diagnosis of coronary artery disease who were undergoing angiography in Farshchian heart center in Hamadan were studied. For each patient, the count of monocytes, neutrophils, platelet, and HDL-C, and IL-25 were measured from their blood and serum samples. Also, demographic information, such as age, gender, diabetes, smoking, and history of hypertension, was collected using a checklist. Data were described using frequency, percent, mean, and standard deviation. Statistical analysis was performed using independent t test, Mann-Whitney, Wilcoxon, and Spearman rank correlation tests, and multiple linear regression by SPSS version 25.0 SPSS Inc). P <.05 was considered as significant. Results: The results of this study showed that IL-25 and MHR index has a significant correlation with coronary artery disease and Gensini score (P ˂.001). The PHR index was associated with coronary artery disease. Also, qualitative variables, such as history of hypertension, history of smoking, and gender, have a significant association with the severity of coronary artery disease (P <.05). Conclusion: Among the inflammatory markers examined, IL-25 and MHR are stronger markers for assessing the severity of coronary artery disease. Simple and available IL-25 and MHR measurements may be able to, along with common risk factors and lipid profiles, predict the amount of vascular occlusion in treatment centers as an alternative of angiography as well as screening high risk patients prone to cardiovascular disease.

Cross-Resistance of Acquired Radioresistant Colorectal Cancer Cell Line to gefitinib and regorafenib.

BACKGROUND: Usually, chemoradiotherapy can be used for the treatment of locally advanced colorectal cancer (CRC) before surgery. On the other hand, some studies have shown that fractional radiation of tumor cells leads to chemoresistance. The aim of this study was to evaluate the chemoresistance of radioresistant sub-line (RR sub-line). METHODS: This study was done in Hamadan University of Medical Sciences in 2017-2018. MTT assay and sub-G1 fraction analysis by flow cytometry were used to evaluate cross-resistance of RR sub-line to gefitinib and regorafenib. Real-time PCR was used to investigate the role of four miRNAs and their target genes in the cross-resistance of RR sub-line. The t test and repeated measures test were used for the assessment of statistical significance between groups. RESULTS: The IC50 of gefitinib and regorafenib for RR sub-line were significantly higher than those of the parental cell line. On the other hand, the resistance index of RR sub-line for gefitinib and regorafenib were 1.92 and 1.44, respectively. The sub-G1 fraction of RR sub-line following treatment with gefitinib and regorafenib was significantly lower than that of the parental cell line (P=0.012 and P=0.038, respectively). The expression of miR-9, Let-7e, and Let-7b in RRsub-line was significantly lower than that of the parental cell line. However, NRAS, IGF1R, NFKB1, and CCND1 found to be upregulated in RR sub-line in comparison with the parental cell line. CONCLUSION: We can conclude that the acquired RR sub-line was cross-resistance to gefitinib and regorafenib. Furthermore, miR-9/NFKB1, let-7b/CCND1, let-7e/NRAS, and IGF1R played essential roles in the chemoradioresistance of CRC.

Let-7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin-like growth factor 1 receptor.

Abnormal expression of various microRNAs (miRNAs), as regulators of biological signaling pathways, has a strong association with cancer resistance to chemotherapy and radiotherapy. The let-7 family of miRNAs as tumor suppressors have shown to be downregulated in different types of human malignancies including colorectal cancer (CRC). However, the biological function of let-7 members in the processes of resistance to radiation in CRC has not yet been completely elucidated. Insulin-like growth factor 1 receptor (IGF-1R) signaling pathway is amplified in CRC and leads to its progression, development, and also radiation resistance. So, it seems like an attractive target for anticancer therapy. In this study, by using bioinformatics analysis, it has been revealed that IGF-1R is a direct target of the let-7e member. Consistent with this, we identified that increased levels of let-7e in CRC cells reduced IGF-1R protein level and subsequently its downstream signaling pathways, which resulted in the G1 cell cycle arrest and a significant reduction in the proliferation, survival and also resistance to radiation of CRC cells. Altogether, these results suggested that let-7e by targeting the IGF-1R signaling pathway might serve as therapeutics in anticancer therapy.

Zerumbone Suppresses Human Colorectal Cancer Invasion and Metastasis via Modulation of FAk/PI3k/NFκB-uPA Pathway.

The current study explored the basic molecular mechanisms of zerumbone (ZER), an herbal compound, in inhibiting the migration and invasion of colorectal cancer (CRC) cells in vitro. Two types of CRC cells, namely HCT-116 and SW48, were treated with various concentrations of ZER (8, 16, and 24 µM) for 24, 48, and 72 h, respectively. In vitro assays were performed to determine alterations in proliferation ability, mRNA expression and protein levels, and migration and invasion potential of CRC cells. An SYBR Green-based quantitative polymerase chain reaction (PCR) was utilized to detect the gene expression of focal adhesion kinase (FAK), nuclear factor (NF)-κB, and urokinase-type plasminogen activator (uPA) followed by the evaluation of the level of proteins by western blotting. Migration and invasion potentials of HCT-116 and SW48 cells treated by ZER were examined using migration and invasion assay kits, respectively. We compared the results of all experiments with control groups, including FAK inhibitor, ZER + FAK inhibitor-treated cells, NF-ß inhibitor, ZER + NF-ß inhibitor, and untreated cells. The data in the present study suggest that ZER may exert its antimetastatic effects through inhibition of FAk/PI3k/NF-κB-uPA signaling pathway, thereby possibly representing a novel class of FAK inhibitors.

Remarkable apoptotic pathway of Hemiscorpius lepturus scorpion venom on CT26 cell line.

OBJECTIVE: Scorpion venom, considered as a treasure trove of various bioactive molecules, is a new approach to induce cancer cell death via apoptosis pathways. In the present study, we evaluated for first time the anti-proliferative efficacy of Hemiscorpius lepturus scorpion venom and its pathway on a colon carcinoma cell. MATERIALS AND METHODS: The CT26 and VERO cell lines were treated with various concentrations of the venom. The IC50 values were estimated by MTT assay test, and the apoptosis was evaluated by flow cytometry. Moreover, RT-PCR analysis was used to investigate the levels of Bax, Bcl2, Trp53, and Casp3 mRNA expression. The mice xenograft model was established to evaluate the therapy efficiency of venom. Some valuable exponential growth parameters were evaluated in treated mice. RESULT: The scorpion venom inhibited the growth of CT26 cells with an IC50 value about 120 µg/ml. However, VERO cells increased to 896 µg/ml under the same condition. A remarkable apoptotic cells in CT26 cells were revealed by flow cytometry assay. A significant over-expression was observed in Bax, Casp3, and Trp53 and downregulated in Bcl2 mRNA level in tumor tissue after treatment with scorpion venom (p < 0.05). All changes of valuable exponential growth parameters showed a shrinking tumor size. CONCLUSION: Our findings indicated that Hemiscorpius lepturus venom has a special anti-proliferative effect on CT26 cells via Trp53/Bcl2/Casp3 pathway. Considering its powerful cytotoxic vigor against a colon cancer cell (CT26) and low toxicity to non-tumorigenic cell (VERO), we propose that this venom probably has a specific effect on other colon cancer cells and may turn out to be a novel therapeutic strategy in treating colon cancer.

Zerumbone inhibits epithelial-mesenchymal transition and cancer stem cells properties by inhibiting the ß-catenin pathway through miR-200c.

Colorectal cancer (CRC) is one of the most lethal and rampant human malignancies in the world. Zerumbone, a sesquiterpene isolated from subtropical ginger, has been found to exhibit an antitumor effect in various cancer types. However, the effect of Zerumbone on the biological properties of CRC, including epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) has not been fully elucidated. Here, we investigated the inhibitory action of Zerumbone on the EMT process, CSC markers, and the ß-catenin signaling pathway in the presence or absence of miR-200c. The effect of Zerumbone on HCT-116 and SW-48 cells viability was examined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effects of Zerumbone on EMT-related genes, CSCs markers, cell migration, invasion, sphere-forming, and ß-catenin signaling pathway were explored. To evaluate the role of miR-200c in anticancer effects by Zerumbone, miR-200c was downregulated by LNA-anti-miR-200c. Zerumbone significantly inhibited cell viability, migration, invasion, and sphere-forming potential in HCT-116 and SW-48 cell lines. Zerumbone significantly suppressed the EMT and CSC properties as well as downregulated the ß-catenin. Silencing of miR200c reduced the inhibitory effects of Zerumbone on EMT and CSCs in CRC cells. These data indicated that Zerumbone may be a promising candidate for reducing the risk of CRC progression by suppressing the ß-catenin pathway via miR-200c.

miR-200c, a tumor suppressor that modulate the expression of cancer stem cells markers and epithelial-mesenchymal transition in colorectal cancer.

Colorectal cancer (CRC) is the most frequently diagnosed cancer and the most common gastrointestinal cancer worldwide. Due to the presence of populations of cancer stem cells (CSCs) that cause recurrence, the possibility of cancer treatment is very low. The aim of current study was to evaluate the inhibitory role of miR-200c on EMT, CSCs markers and ß-catenin in HCT-116 and SW48 cell lines. The expression of miR-200c, EMT-related genes, CSCs markers, and ß-catenin were quantified by qRT-PCR. Further, expression of ß-catenin and EMT-related proteins, and migration were analyzed by Western blot, and migration assay kit, respectively. Spheroid formation assay was used to enrich colorectal CSCs from colorectal cancer cell lines. LNA-anti-miR-200c suppressed the endogenous miR-200c in transfected cells compared with the control. qRT PCR and Western blot analysis of LNA-anti-miR-200c transfected cells revealed a considerable increase in CSCs markers, vimentin, ZEB-1, N-cadherin, and ß-catenin expression, with a concomitant reduction in E-cadherin expression level. Migration and sphere forming ability of HCT-116 and SW48 cells increased in transfected cells. The results of current study revealed that downregulation of miR-200c may be an important factor for the overexpression of CSCs markers and EMT related genes via ß-catenin upregulation in CRC.

Anticancer effects of miR-200c in colorectal cancer through BMI1.

Colorectal cancer (CRC) is one of the most leading cancer deaths throughout the world. MiR-200c has been shown to have a critical role in cancer initiation and progression. In this study, we investigated the miR-200c expression in CRC tissues and its effects on CRC cell lines which were mediated by polycomb complex protein (BMI1). Quantitative reverse transcription polymerase chain reaction (QRT-PCR) and immunohistochemistry were used to detect miR-200c and BMI1 expression in tumor tissues from 38 patients with CRC and 38 normal colon tissues. HCT-116 and SW-48 cells were transfected by locked nucleic acid (LNA)-anti-miR-200c. Western blot analysis and real-time PCR were applied to determine the BMI1 protein and microRNA (miRNA) levels. The apoptosis was analyzed via annexin/propidium iodide staining, and cell invasion was evaluated by transwell assay. MiR-200c was markedly downregulated in CRC tissues, whereas the protein expression of BMI1 in CRC tissues was upregulated compared with normal colon tissues. In the colon cancer cell lines, transfection of LNA-anti-miR-200c increased BMI1 gene and protein expression as well as the cell invasion. Downregulation of miR-200c by LNA decreased the apoptotic cells. The results from this study revealed that miR-200c may have antitumor effects through inhibition of BMI1 expression.

The Effect of the MicroRNA-183 Family on Hair Cell-Specific Markers of Human Bone Marrow-Derived Mesenchymal Stem Cells.

Hearing loss is considered the most common sensory disorder across the world. Nowadays, a cochlear implant can be an effective treatment for patients. Moreover, it is often believed that sensorineural hearing loss in humans is caused by loss or disruption of the function of hair cells in the cochlea. In this respect, mesenchymal cells can be a good candidate for cell-based therapeutic approaches. To this end, the potential of human bone marrow-derived mesenchymal stem cells to differentiate into hair cells with the help of transfection of microRNA in vitro was investigated. MicroRNA mimics (miRNA-96, 182, and 183) were transfected to human bone marrow-derived mesenchymal stem cells using Lipofec-tamine as a common transfection reagent following the manufacturer's instructions at 50 nM for microRNA mimics and 50 nM for the scramble. The changes in cell morphology were also observed under an inverted microscope. Then, the relative expression levels of SOX2, POU4F3, MYO7A, and calretinin were assayed using real-time polymerase chain reaction according to the ΔΔCt method. The ATOH1 level was similarly measured via real-time polymerase chain reaction and Western blotting. The results showed that increased expression of miRNA-182, but neither miRNA-96 nor miRNA-183, could lead to higher expression levels in some hair cell markers. The morphology of the cells also did not change in this respect, but the evaluation of gene expression at the levels of mRNA could promote the expression of the ATOH1, SOX2, and POU4F3 markers. Furthermore, miRNA-182 could enhance the expression of ATOH1 at the protein level. According to the results of this study, it was concluded that miRNA-182 could serve as a crucial function in hair cell differentiation by the upregulation of SOX2, POU4F3, and ATOH1 to promote a hair cell's fate.

Resveratrol Inhibits Proliferation, Invasion, and Epithelial-Mesenchymal Transition by Increasing miR-200c Expression in HCT-116 Colorectal Cancer Cells.

OBJECTIVE: colorectal cancer (CRC) is one of the most common malignancies, associated with high rates of relapse. A notable challenge in treatment is low response rate to current therapies for advanced CRC. The miR-200c plays an essential role in tumor suppression by inhibiting epithelial-mesenchymal transition (EMT). Resveratrol, a natural compound found in red wine, reveals anti-cancer properties in several types of cancers such as CRC. The aim of current study was to evaluate the effects of resveratrol on proliferation, apoptosis, and invasion of HCT-116 cells and also expression of EMT-related genes in presences or absence of miR-200c. METHODS: the effect of resveratrol on viability was examined by MTT assay. LNA-anti-miR-200c transfection of HCT-116 cells was carried out in a time dependent manner. Then, the expression of miR-200c and EMT-related genes were quantified by qRT-PCR. Further, expression of EMT-related proteins, apoptosis, and invasion were analyzed by Western blot, Annexin V/PI staining and scratch test, respectively. RESULTS: resveratrol could significantly inhibit viability of HCT-116 cells. LNA-anti-miR-200c suppressed the endogenous miR-200c in transfected cells compared with the control. qRT-PCR and Western blot analysis of LNA-anti-miR-200c transfected cells revealed a considerable increase in vimentin and ZEB-1 expression, with a concomitant reduction in E-cadherin expression level. Migration of HCT-116 cells increased, and apoptosis significantly reduced in transfected cells. While, resveratrol could entirely reverse these changes by modulation of miR-200c expression. CONCLUSION: our findings revealed a major role of resveratrol in apoptosis, invasion, and switching of EMT to MET phenotype through upregulation of miR-200c in CRC. J. Cell. Biochem. 118: 1547-1555, 2017. © 2016 Wiley Periodicals, Inc.

The Frequency of HBB Mutations Among ß-Thalassemia Patients in Hamadan Province, Iran.

ß-Thalassemia (ß-thal) caused by mutations on the HBB gene is the most common single-gene disorder in the world. In this study, the HBB gene mutation was investigated in Hamadan province, Iran. Forty-one patients referred to a referral hospital were admitted to the study. DNA samples were extracted from peripheral blood. The HBB gene was sequenced in all recruited patients. Eleven mutations and eight polymorphisms were found in the studied patients. IVS-II-1 (G>A) (HBB: c.315+1 G>A) was the most common mutation, accounting for 25.61% of mutant alleles. Other mutations included codon 8 (-AA) (HBB: c.25-26delAA); IVS-I-110 (G>A) (HBB: c.93-21 G>A); codons 8/9 (+G) (HBB: c.27-28insG); IVS-I-1 (G>A) (HBB: c.92 G>A); codon 44 (-C) (HBB: c.135delC); codons 25/26 (+T) (HBB: c.78-79insT); IVS-I-130 (G>C) (HBB: c.93-1 G>C); -28 (A>C) (HBB: c.-78 A>C); codons 36/37 (-T) (HBB: c.112delT) and IVS-I-6 (T>C) (HBB: c.92+6 T>C). According to our findings, the IVS-II-1 mutation has the highest prevalence in Hamadan Province. It was found that the total frequency of the IVS-II-1, codons 25/26 (+T), codons 8/9 (+G), IVS-I-110 and IVS-I-1 mutations was 82.92%. Therefore, given these findings, it is recommended that these five mutations are screened for as a first step in laboratories without sequencing instruments, and that the rest of the gene is subsequently examined.

Sewage as a rich source of phage study against Pseudomonas aeruginosa PAO.

Pseudomonas aeruginosa is a ubiquitous organism which has emerged as a major public health threat in hospital environments. Overuse of antibiotics has significantly exacerbated the emergence of multi-drug resistant bacteria such as P. aeruginosa. Phages are currently being utilized successfully for aquaculture, agriculture and veterinary applications. The aim of this study was to isolate and characterize of lytic P. aeruginosa phage from sewage of Ilam, Iran. Phage was isolated from sewage that was added to the enrichment along with the host and subsequently filtered. Plaque assay was done by using an overlay method (also called the double agar layer method). Purified plaques were then amplified for characterization. Finally, RAPD-PCR method was conducted for genotyping and Transition electron micrograph (TEM) recruited to determine the morphology and phage family. The phage had high concentration and tremendous effects against a variety of clinical and general laboratory strains (ATCC15693) of P. aeruginosa. Among a set of primers in RAPD panel, only P2 and RAPD5 primers, were useful in differentiating the phages. TEM images revealed that the isolated phages were members of the Siphoviridae family. The phage effectiveness and specificity towards target bacteria and potential to control biofilm formations will be investigate in our further studies.

Glia Maturation Factor Beta: A Novel Neuro-Impairment Prediction Factor in Toxoplasmosis.

Background: Toxoplasma gondii, a neurotropic protozoan, infects up one to third of the world population. The parasite can invade a wide variety of nucleated cells but preferably glial cells. Glia maturation factor ß (GMFß), a 17KD protein expressed at high levels in the central nervous system is predominantly related to neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Multiple sclerosis. We aimed to determine the expression level of GMFß and its relation to other pro-inflammatory factors (IL33, SDF1, and CCL2) on T. gondii infected human neuroblastoma cell line. Methods: The human neuroblastoma (SK_NMC C535) cell line was infected by 5×106 (1:1 ratio). The supernatant was collected after cell lysis and centrifugation. Total RNA was extracted using the Yekta Tajhiz RNA extraction kit. cDNA was synthesized based on RevertAid First Strand cDNA Synthesis Kit manufacturer's protocol (Parstous, cDNA synthesis kit, Iran). The specificity of each primer pair (GMFß, IL33, SDF1, and CCL2) was provided by NCBI BLAST. Gene expression level was measured using Real-Time PCR. All experiments were conducted at the Hamadan University of Medical Sciences, western Iran in 2022. Results: The GMFß increased significantly up to 1.35-fold (P=0.007). The increase in GMFß expression in neuroblastoma cells was consistent with the increase in pro-inflammatory factors (CCL2 (0.47), IL33 (0.152) and, SDF1 (1.33)). Conclusion: GMFß upregulation can be a novel indicator of the destruction of nerve cells.

BACE1 Inhibition Utilizing Organic Compounds Holds Promise as a Potential Treatment for Alzheimer's and Parkinson's Diseases.

Background: Neurological disorders like Alzheimer's disease (AD) and Parkinson's disease (PD) manifest through gradually deteriorating cognitive functions. An encouraging strategy for addressing these disorders involves the inhibition of precursor-cleaving enzyme 1 (BACE1). Objectives: In the current research, a virtual screening technique was employed to identify potential BACE1 inhibitors among selected herbal isolates. Methods: This study evaluated 79 flavonoids, anthraquinones (AQs), and cinnamic acid derivatives for their potential blood-brain barrier (BBB) permeability. Using the AutoDock 4.0 tool, molecular docking analysis was conducted to determine the binding affinity of BBB permeable compounds to the BACE1 active site. Molecular dynamics (MD) simulations were performed to assess the stability of the docked poses of the most potent inhibitors. The interactions between the most effective plant-based inhibitors and the residues within the BACE1 catalytic site were examined before and after MD simulations. Results: Ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine were among the highest-ranking BACE1 inhibitors, with inhibition constant values calculated in the nanomolar range. Furthermore, during 10 ns simulations, the docked poses of these ligands were observed to be stable. Conclusion: The findings propose that ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine might serve as potential choices for the treatment of AD and PD, laying the groundwork for the creation of innovative BACE1 inhibitors.

Global investigation of the presence of adenovirus in different types of water resources: a systematic review.

Waterborne viruses such as adenoviruses cause major health problems in the world. Human adenoviruses are the second leading cause of childhood gastroenteritis worldwide. In recent years, the presence of the virus in aquatic resources has been shown in several studies. In this paper, the global presence of adenovirus in different types of water resources are reviewed through studying several surveys conducted in different countries worldwide. We designed one search study to collect the maximum number of related articles to this subject in international databases search engine via relevant keywords. After reviewing the articles, the most relevant ones were selected, and after classification and extracting the required information, they were reported in the tables presented in this study. In general, it was found that the highest rate of the presence of adenoviruses has been reported in sewage water, inlet, and outlet of the treatment plant while the lowest rate of the presence of adenovirus in the dam water. These findings demonstrate that treatment plant system has weakness in removing the adenovirus and are strongly recommended for treatment plants to use new and better protocols to remove this virus. In addition, appropriate diagnostic methods that combines molecular biological technique with infectivity assay should be implemented for detection of adenoviruses in water resources.