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Urtica dioica agglutinin (UDA) is a very small plant lectin with anti-prostatic activity. In this study, we investigated the effect of UDA on proliferation and apoptosis induction in human acute lymphoid leukemia (ALL) cell lines. The effect of UDA on Jurkat and Raji cell proliferation was examined by MTS assay. Distribution of cell cycle phases was determined by PI staining and apoptosis was examined with annexin V/PI and western blot. Results showed UDA treatment reduced cell proliferation in cells by inducing apoptosis. PI staining was associated with a higher percentage of the cell population in sub G1. Caspase-8 and caspase-9 dependent apoptosis occurred in Jurkat cells. Generally, UDA treatment resulted in cell death in ALL cell lines and induced apoptosis in the T-ALL cell line, Jurkat, through extrinsic and intrinsic pathways. These results may be considered as a guide to working on UDA as an anti-leukemic drug in the future.

During the past two decades, tumor therapy based on monoclonal antibody has been found as a confident therapeutic approach in solid tumors and hematologic malignancies. Nanobodies are the smallest fragment of an antigen-binding domain in heavy chain-only antibody originated from the Camelidae family. Accordingly, they are being recently developed rapidly as diagnostic and therapeutic agents. In this regard, targeting of angiogenic factors like Placenta growth factor (PLGF) via nanobodies show a high effectiveness. In the current study, we developed a recombinant anti-PLGF bivalent nanobody based on the affinity enhancement mutant form of anti-PLGF nanobody to suppress the angiogenesis progression. Thereafter, the bivalent nanobody (bi-Nb) was cloned and then expressed into a bacterial system. Afterward, the purity was authorized using western blot assay and the affinity was assessed using ELISA. In this regard, proliferation, 3D capillary tube formation, and migration assays were employed as functional assays. The obtained data were analyzed using t-test and P

Blood vessel development is one of the most prominent steps in regenerative medicine due tothe restoration of blood flow to the ischemic tissues and providing the rapid vascularizationin clinical-sized tissue-engineered grafts. However, currently tissue engineering technique isrestricted because of the inadequate in vitro/in vivo tissue vascularization. Some challenges likeas transportation in large scale, distribution of the nutrients and poor oxygen diffusion limit theprogression of vessels in smaller than clinically relevant dimensions as well in vivo integration.In this regard, the scholars attempted to promote the vascularization process relied on the stemcells (SCs), growth factors as well as exosomes and interactions of biomaterials with all of themto enable the emergence of ideal microenvironment which is needed for treatment of unhealthyorgans or tissue regeneration and formation of new blood vessels. Thus, in the present reviewwe aim to describe these approaches, advances, obstacles and opportunities as well as theirapplication in regeneration of heart as a prominent angiogenesis-dependent organ.

BackgroundCurcumin is herbal compound that has been shown to have anti-cancer effects in pre-clinical and clinical studies. The anti-cancer effects of curcumin include inhibiting the carcinogenesis, inhibiting angiogenesis, and inhibiting tumour growth. This study aims to determine the Clinical effects of curcumin in different types of cancers using systematic review approach.MethodsA systematic review methodology is adopted for undertaking detailed analysis of the effects of curcumin in cancer therapy. The results presented in this paper is an outcome of extracting the findings of the studies selected from the articles published in international databases including SID, MagIran, IranMedex, IranDoc, Google Scholar, ScienceDirect, Scopus, PubMed and Web of Science (ISI). These databases were thoroughly searched, and the relevant publications were selected based on the plausible keywords, in accordance with the study aims, as follows: prevalence, curcumin, clinical features, cancer.ResultsThe results are derived based on several clinical studies on curcumin consumption with chemotherapy drugs, highlighting that curcumin increases the effectiveness of chemotherapy and radiotherapy which results in improving patient’s survival time, and increasing the expression of anti-metastatic proteins along with reducing their side effects.ConclusionThe comprehensive systematic review presented in this paper confirms that curcumin reduces the side effects of chemotherapy or radiotherapy, resulting in improving patients’ quality of life. A number of studies reported that, curcumin has increased patient survival time and decreased tumor markers’ level.

Escherichia coli is a widely-used cell factory for recombinant protein production, nevertheless, high amount of produced protein is seen in aggregated form. The purpose of this study was to improve the solubility of recombinant bovine sex-determining region Y protein (rbSRY) by exploring the effect of temperature, inducer, and water-arginine mixed solvent. Codon-optimized rbSRY expressed in Rosetta-gami B (DE3) pLysS and purified by NI–NTA His-select affinity chromatography in the native and denaturing conditions. A three-dimensional model of SRY was built and studied through molecular dynamics simulations in water and in the presence of l-arginine as co-solvent. Results indicated the significant effects of temperature and IPTG concentration (P

Background Rapamycin has been known as an anti-cancer agent that affects different malignancies such as glioblastoma and prostate cancer. However, there are few studies concerning rapamycin effects on the cervical cancer cells. In this study, it was aimed to investigate the possible effect of rapamycin on a cervical cancer cell line and explored the possible mechanism(s) and pathway(s) for this agent. Materials and methods To do so, HeLa cells as cervical cancer cell line were used and treated with different concentrations of rapamycin under both normoxic and hypoxic conditions. Then, cell viability assays, Western blot, quantitative real-time polymerase chain reaction (QR-PCR), acridine orange and acridine orange/propidium iodide staining were performed to evaluate rapamycin effect on the mentioned cell line. Results The results showed that autophagy and apoptosis-related genes increased significantly in rapamycin-treated HeLa cells compared to controls. Moreover, cervical cancer cell death by rapamycin-induced autophagy in hypoxia was greater than normoxia compared with controls. In this study, it was showed that autophagy induction by rapamycin can mediate programmed cell death of cervical cancer cells, especially in hypoxic condition. Conclusion These findings provide a new evidence that rapamycin may inhibit hypoxic HeLa cell proliferation through the trigger of programmed cell death, facilitating the development of novel anti-cancer therapy.

Background and Aims HIF-1 is an important factor that play critical roles in metabolic and metastasis activity of cancer cells. HIF-1 activity can have regulated by TSGA10. Although decreased metastatic activity of cancer cells through TSGA10 inhibitory effect on HIF-1 have already been demonstrated, changes in cancer metabolism and its impact on metastasis in breast cancer is still not determined. So, we aimed to investigate TSGA10 overexpression effect on breast cancer metabolism as well as metastasis. Methods TSGA10 vector was designed and stable transfected into MCF-7 cells. The efficiency of transfection was assessed by Real-time PCR and western blot. After HIF-1 induction at high and low glucose conditions, cell proliferation, cell cycle profile, metabolic and metastasis activity of cells were assessed. Furthermore, biomarker expressions of ER, PR, HER2, Ki67 and E-cadherin in cancer cells were measured. Results Our results showed decrease of cell proliferation and cell cycle arrest in G2/M phase. Reduce expression of GLUT1, lactate production and reactive oxygen species (ROS) below their basal level indicated decreased metabolic activity. Furthermore, metastatic activity reduction was shown by decrease expression of different involve genes in metastasis, protelytic activity of MMOLP-2/9, carbonic anhydrase (CA) IX activity and increase of wound closure. Moreover, except for E-cadherin, expression of ER, PR, HER2 and Ki67 was declined in cells. Conclusion Our findings indicated that TSGA10 overexpression could decrease the metastatic and metabolic activity of cancer cells through its inhibitory effect on HIF-1 activity. Therefore, TSGA10 could be considered in the research for therapeutic candidates in cancer.

Probiotics are beneficial bacteria that have a significant effect on host health and they are widely used in preventing and treating diseases. Nowadays probiotics are present in food, drug and several commercial complement products. In recent years the use of probiotics in the nanotechnology area, especially in nanoparticle synthesis, has significantly been increased. In this review, after some introduction about probiotic and their advantages, all the nanoparticles produced by probiotics are reviewed and discussed. Furthermore, biosynthetic mechanisms of nanoparticles and its applications in cancer therapy, antibacterial and photo catalytic activities, are also discussed.

Coronavirus disease 2019 (COVID-19) is still an emergency in many countries. Herein, we report treatment with human placental-derived mesenchymal stromal cells transfusion (hPD-MSCT) in a critically ill infant diagnosed with COVID-19. A 28-day-old male infant with a history of pneumonia was referred to our center with decreased SpO

Varicocele is considered the main reason for male infertility. Antioxidants are common drugs used to reduce the complications of varicocele in these patients. So, we investigated the effects of lycopene on sperm quality, testicular histology, and the expression of some genes in experimentally induced varicocele. Fifty adult male Wistar rats were divided into three groups: control (

Metabolic reprogramming is a potential hallmark of tumor cells to support continuous proliferation. Metabolic heterogeneity in breast cancer patients has been highlighted as the driving cause of tumor progression and resistance to anticancer drugs. Studying and identifying distinct metabolic alterations in breast cancer subtypes could offer new perspectives for faster diagnosis and treatment. Given cancer cell dependency on glycolysis, the primary energy source, this enzymatic pathway will play a critical role in targeting therapies. Knowledge about the specific metabolic dependencies of tumors for growth and proliferation can be promising for novel targeted and cell-based therapies. Here, the metabolic status with emphasis on glycolysis of breast cancer cell lines according to their classification was reviewed.

Cardiovascular disease (CVD) is a major concern for health with high mortality rates around the world. CVD is often associated with partial or full occlusion of the blood vessel network. Changes in lifestyle can be useful for management early-stage disease but in the advanced stage, surgical interventions or pharmacological are needed to increase the blood flow through the affected tissue or to reduce the energy requirements. Regeneration medicine is a new science that has provided many different options for treating various diseases, especially in CVD over the years. Stem cell therapy, gene therapy, and tissue engineering are some of the powerful branches of the field that have given patients great hope in improving their condition. In this review, we attempted to examine the beneficial effects, challenges, and contradictory effects of angiogenesis in vivo, and in vitro models’ studies of CVD. We hope that this information will be able to help other researchers to design new effective structures and open new avenues for the treatment of CVD with the help of angiogenesis and regeneration medicine in the future.

Background: Glioblastoma multiforme (GBM) is considered the deadliest human cancer. Temozolomide is now a part of postresection standard chemotherapy for this type of cancer. Unfortunately, resistance to temozolomide is a major obstacle to treatment success. Combination therapy with natural anticancer agents increases the activity of temozolomide against cancer cells. Objectives: This study aimed to assess the effects of temozolomide in combination with harmine against GBM cells. Methods: Cancer cells were treated with temozolomide and/or harmine. After 24, 48, 72, and 96 h, the viability of the cells was assessed by the MTT test. The combination index and dose reduction index were determined by CompuSyn software. Tumor invasion potential was investigated by evaluating cell migration, invasion, and adhesion. The real-time PCR technique was done to study the expression pattern of two genes involved in cancer cell invasion. Statistical analysis was performed using one-way analysis of variance and Tukey’s post-hoc test, and differences were considered non-significant at P > 0.05. Results: After treatment with temozolomide, cell viability showed a concentration- and time-dependent decrease, and the cells’ survival rate decreased. The combination of temozolomide and harmine had a synergistic effect. Also, temozolomide and/or harmine treatment decreased cancer cells’ migration, invasion, and adhesion potentials, as well as the expression of metalloproteinases 2 and 9 in T98G cells. Conclusions: The combination of temozolomide and harmine can be promising for the successful treatment of GBM.

Diabetes is a chronic disorder characterized by dysregulated glycemic conditions. Diabetic complications include microvascular and macrovascular abnormalities and account for high morbidity and mortality rates in patients. Current clinical approaches for diabetic complications are limited to symptomatic treatments and tight control of blood sugar levels. Extracellular vesicles (EVs) released by somatic and stem cells have recently emerged as a new class of potent cell-free therapeutic delivery packets with a great potential to treat diabetic complications. EVs contain a mixture of bioactive molecules and can affect underlying pathological processes in favor of tissue healing. In addition, EVs have low immunogenicity and high storage capacity while maintaining nearly the same regenerative and immunomodulatory effects compared to current cell-based therapies. Therefore, EVs have received increasing attention for diabetes-related complications in recent years. In this review, we provide an outlook on diabetic complications and summarizes new knowledge and advances in EV applications. Moreover, we highlight recommendations for future EV-related research.

Purpose Breast cancer is the most common cancer in women. In recent research works, the role of cytokines in development of cancer has attracted attention. Therefore, this paper intends to comprehensively assess the association between breast cancer and polymorphism A/T 251 from the IL-8 gene using meta-analysis. Methods In this study, to find articles published electronically between 2004 and 2020, national and international databases of SID, MagIran, Embase, ScienceDirect, Scopus, PubMed, and Web of Science (WoS). Results The odds ratio of AA genotype in patients with breast cancer based was obtained as 1.42 (1.11–1.82: 95% confidence interval), which shows the increasing effect of AA genotype by 0.42, the odds ratio of the AT genotype in patients with breast cancer based on a meta-analysis of studies was obtained as 1.01 (0.84–1.22: 95% confidence interval), which demonstrates the increasing effect of the AT genotype by 0.01, and the odds ratio of the TT genotype in patients with breast cancer was similarly obtained and was 0.95 (1.08–0.24: 95% confidence limit), which shows the decreasing effect of TT genotype by 0.05. Conclusion According to this meta-analysis, allele A has a significant relationship with breast cancer, which can be used as a predictor of the course of the disease and the clinical outcome of breast cancer. Identifying polymorphism A/T 251 from the IL-8 gene, as a genetic marker and predictor, can also be effective in treating breast cancer.

Today, nanoscience has grown and developed in various fields of medicine and treatment, including cancer treatment. Currently, the existing treatments, including chemotherapy and radiotherapy, cause side effects that are unpleasant to the patient. Due to the fact that anticancer drugs cause severe and widespread side effects, liposomes are considered as new drug carriers to minimize the untimely destruction of the drug when it is delivered to the target tissue and to prevent the side effects of toxic drugs. This systematic review study examined the importance of using liposomes as new drug carriers for the delivery of genes and anticancer drugs. The articles published in English in the databases of Google scholar, WoS, PubMed, Embase, Scopus and science direct were reviewed. According to the results of this study, a new targeted nanosystem has been used for loading and delivering anticancer drugs, genes and controlled drug release which has a significant therapeutic effect compared to the same amount of free drug. In general, liposomal systems have been considered because of their capability in preserving the effect of the drug along with reducing the side effects and toxicity of the drug, especially in the case of anticancer drugs. Accumulation of the drug in a target tissue which results in a reduction of the drug entry into other tissues is the main reason for reducing the side effects of these drugs.

Cancer is one of the leading causes of death in humans because of the lack of early diagnosis, distant metastases, and the resistance to adjuvant therapies, including chemotherapy and radiotherapy. In addition to playing an essential role in tumor progression and development, microRNAs (miRNAs) can be used as a robust biomarker in the early detection of cancer. MiR-1290 was discovered for the first time in human embryonic stem cells, and under typical physiological situations, plays an essential role in neuronal differentiation and neural stem cell proliferation. Its coding sequence is located at the 1p36.13 regions in the first intron of the aldehyde dehydrogenase 4 gene member A1. miR-1290 is out of control in many cancers such as breast cancer, colorectal cancer, esophageal squamous cell carcinoma, gastric cancer, lung cancer, pancreatic cancer, and plays a vital role in their development. Therefore, it is suggested that miR-1290 can be considered as a potential diagnostic and therapeutic target in many cancers. In addition to the importance of miR-1290 in the noninvasive diagnosis of various cancers, this systematic review study discussed the role of miR-1290 in altering the expression of different genes involved in cancer development and chemo-radiation resistance. Moreover, it considered the regulatory effect of natural products on miR-1290 expression and the interaction of lncRNAs by miR-1290.

Human endometriosis can lead to many complications, including permanent infertility. Rodent model of endometriosis is complicated due to the impractical isolation of myometrium. In this method, we defined a new model of endometriosis with some modifications. 40 female mice were grouped as; 1st sham, 2nd mice-mice allograft uterus transplantation of mice to anterior abdominal wall of mice, 3rd mice-mice allograft uterus transplantation of mice to mesentery of mice, 4th rat-mice xenograft endometrial transplantation of rat to anterior abdominal wall of mice, 5th rat-mice xenograft endometrial transplantation of rat to mesentery of mice. In recipient animals, estrous cycle was synchronized. Endometrium was dissected in rats and transplanted in abdominal wall or mesentery layer. Angiogenetic and inflammatory factors, serum levels of CA125, oxidative stress in peritoneal fluid, physical and histopathological features, and genes expression in uterus were assessed. Peritoneal concentrations of VEGF-A, TNF-α, NO, MDA, and serum levels of CA125, IL-37 were increased significantly (P 0.05). Genes expression of HOXA10 and HOXA11 were decreased in endometrium of uterus. Finally, histopathological features of endometrial lesions were confirmed by H&E and Perl staining. Xenograft transplantation of endometrium from rat to anterior abdominal wall of mice can potentially mimic the human endometriosis morphologically, histologically and genetically.

BACKGROUND: The association of 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) and its receptor, vitamin D receptor (VDR), with cancer types have been studied. However, there are controversial findings regarding the association of specific VDR polymorphisms with different kinds of cancers. In the current study, we investigated the association of VDR polymorphisms (Fok1 (rs2228570), ApaI (rs7975232), BsmI (rs1544410), and TaqI (rs731236)) with the risk of gastric cancer in a Kurdish population of Kermanshah in Iran for the first time. METHODS: In this case-control study, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used in 99 gastric cancer patients and 100 healthy subjects as controls. RESULTS: The frequencies of f (FokI), b (BsmI), t (TaqI), and a (ApaI) alleles were: 55.6%, 27.3%, 62.1%, and 44.95% in the patient group, respectively and 42%, 29.5%, 54.5%, and 46.0% in the control group, respectively. Analysis of the results indicated that there was a positive association between the frequency of FokI genotypes with gastric cancer risk (p= 0.021). However, no statistically significant association of BsmI, Taq1, and ApaI polymorphisms of VDR was detected in gastric patients when compared with healthy individuals. CONCLUSION: VDR-FokI polymorphism could increase the risk of GC development and predispose to the disease by mechanisms.

In this study, an efficient drug delivery system composed of Fe3O4, CaAl layered double hydroxide (LDH) and l -Dopa has been synthesized through hydrogen bonds between l -Dopa and CaAl-LDH encapsulated Fe3O4 nanoparticles (Fe3O4@CaAl-LDH@ l -Dopa). The structural features of Fe3O4@CaAl-LDH@ l -Dopa were characterized using XRD, SEM, TEM, EDX, FT-IR, VSM, TGA, XPS, zeta potential analysis and BET. All of the characterization techniques show the uniform high surface area core-shell structure with about 120 nm in average size. Also, the obtained results clearly indicate that this drug delivery system possess high potent for adsorption of l -Dopa (52 wt%) and high drug encapsulation efficiency (71%). The amount of l -Dopa release in low pHs (53.8%) which simulates the environment of cancer cells is greater than higher pHs. The in vitro cytotoxic and anticancer activities of Fe3O4@CaAl-LDH@ l -Dopa were investigated against Mel-Rm Cells Melanoma (NCIt: C3224) using LDH colorimetric assay and differential staining cell death assay. The results showed Fe3O4@CaAl-LDH@ l -Dopa with a lower concentration of l -Dopa, illustrate a higher cytotoxicity and anticancer activity.

Dopants strongly affect properties and optical behaviors of quantum dots, therefore doped-QDs considered as a novel class of luminescent materials. Following development doping approach and using Pd2+ ions as a dopant, for the first time, in this study, a facile preparation of Pd-doped CdTe QDs was reported with thioglycolic acid as a stabilizer. The essential parameters of the synthesis conditions such as dopant concentration, reaction time and optical properties of the Pd: CdTe QDs was studied. The Pd: CdTe QDs with excellent photostability and biocompatibility, exhibited a greenish emission at 529 nm. Interestingly, these nanoparticles display high fluorescence sensitivity to diazinon (DZN). Under optimal conditions, a proposed sensor was designed based on Pd: CdTe QDs which represented a wide range of linear response (2.3–100 µM), low detection limit [3.3 nM, (S/N = 3)], high stability, and selectivity. Additionally, the newly sensing nanoprobe was used for the determination of DZN in environmental water samples with satisfactory results.

Given the increase in global mortality rate due to various types of cancer, the present study aimed to develop optimal conditions for the synthesis of cellulose-magnesium oxide nanocomposite with favorable anticancer activity. For this purpose, the Taguchi method was used to design nine experiments with varied ratios of cellulose biopolymer, magnesium oxide nanoparticles and different stirring times. The scanning electron microscopy (SEM) images confirmed the formation of cellulose-magnesium oxide nanocomposite. The anticancer activity level of nine nanocomposites studied was evaluated using MTT assay on Michigan Cancer Foundation-7 (MCF-7) cell line. The nanocomposite synthesized in experiment 9 (8 mg/ml of magnesium oxide, 2 mg/ml of cellulose and stirring time of 60 min) showed the highest growth inhibitory activity on the cancer cells. Based on the attained results,e cellulose-magnesium oxide nanocomposite synthesized in optimal conditions can be used as an eligible anticancer agent.

Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are pivotal regulators of angiogenesis. The VEGF–VEGFR system is therefore an important target of anti-angiogenesis therapy. Based on the X-ray structure of VEGF-B/VEGFR-1 D2, we designed a cyclic peptide (known as VGB1) reproducing the α1 helix and its adjacent region to interfere with signaling through VEGFR-1. Unexpectedly, VGB1 bound VEGFR-2 in addition to VEGFR-1, leading to inhibition of VEGF-stimulated proliferation of human umbilical vein endothelial cells and 4T1 murine mammary carcinoma cells, which express VGEFR-1 and VEGFR-2, and U87 glioblastoma cells that mostly express VEGFR-2. VGB1 inhibited different aspects of angiogenesis, including proliferation, migration and tube formation of endothelial cells stimulated by VEGF-A through suppression of extracellular signal-regulated kinase 1/2 and AKT (Protein Kinase B) phosphorylation. In a murine 4T1 mammary carcinoma model, VGB1 caused regression of tumors without causing weight loss in association with impaired cell proliferation (decreased Ki67 expression) and angiogenesis (decreased CD31 and CD34 expression), and apoptosis induction (increased TUNEL staining and p53 expression, and decreased Bcl-2 expression). According to far-UV circular dichroism (CD) and molecular dynamic simulation data, VGB1 can adopt a helical structure. These results, for the first time, demonstrate that α1 helix region of VEGF-B recognizes both VEGFR-1 and VEGFR-2.

CD147 plays an important role in germ cells migration and survival/apoptosis during the spermatogenesis process. However, to best of our knowledge, there is no report on the exact role of CD147 gene in the regulation of germ cells apoptosis through matrix metalloproteinases (MMPs). So, the current study aims to evaluate the role of CD147 gene expression in the regulation of germ cells apoptosis in conjunction with MMPs. Real-Time PCR was applied to investigate the expression of CD147, MMP2, MMP7, and MMP9 genes in the azoospermic patients and fertile males. Receiver-operating characteristic curve was used to interpret gene expression data. According to our results, a significant decrease in the expression of CD147 gene and an increase in MMPs genes expression were observed in infertile patients compared to fertile males. These results proved this fact that the CD147 gene has an important role in the regulation of germ cells apoptosis via a MMPs-dependent pathway.

The compound "2-methylpyridine-1-ium-1-sulfonate" (MPS) is the active constituent of Allium hirtifolium Boiss. bulbs with potent anti-angiogenic and anti-cancer activities. Tumor microenvironment (TME) plays a key role in tumor progression via tumor derived exosome (TEX) mediated polarization of M2 type tumor associated macrophages (TAMs). In this study, we explored direct and colorectal cancer (CRC) exosome-mediated impacts of MPS on macrophage polarization to find out whether MPS could modify TEX in favor of anti-tumor M1-like macrophage polarization. After MPS isolation and characterization, first its direct anti-cancer effects were evaluated on HT-29 cells. Then, TEX were isolated from untreated (C-TEX) and MPS-treated (MPS-TEX) HT-29 cells. THP-1 M0 macrophages were incubated with MPS, C-TEX and MPS-TEX. Macrophage polarization was evaluated by flow cytometry, ELISA and gene expression analysis of several M1- and M2-related markers. MPS induced apoptosis and cell cycle arrest and reduced the migration ability of HT-29 cells. C-TEX polarized M0 macrophages toward a mixed M1-/M2-like phenotype with a high predominance of M2-like cells. Macrophage treatment with MPS was associated with the induction of M1-like phenotype. Also, MPS was demonstrated to ameliorate TEX-mediated effects in favor of M1-like polarization. In conclusion, our study addresses for the first time, the potential capability of MPS in skewing macrophages toward an anti-cancer M1-like phenotype both directly and in a TEX-dependent manner. Thus, in addition to its direct anti-cancer effects, this compound could also modify TME in favor of tumor eradication via its direct and TEX-mediated effects on macrophage polarization as a novel anti-cancer mechanism.

Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) involve in the degradation of the extracellular matrix (ECM) that imbalances their activity and may lead to various diseases. The present study aims to evaluate the association between MMP9-1562C/T and TIMP2-418G/C variants and synergistic effects of both variants on male infertility in an Iranian population. We analyzed these polymorphisms in 101 infertile men and 106 fertile men as a control group using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Based on the obtained results, no considerable association was observed in MMP9-1562C/T polymorphism frequency between infertile men and controls while frequencies of TIMP2-418G/C variant were significantly different in infertile and control groups (P = 0.028). Men with CC, GC and CC + GC genotypes for TIMP2-418G/C polymorphism had an increased risk of infertility compared to men with GG genotype [OR = 1.85, 95% CI (0.917-3.734, P = 0.086), OR = 1.94, 95% CI (1.098-3.437, P = 0.023) and OR = 2.053 95% CI (1.179-3.577, P = 0.011), respectively]. Also, in the presence of both TIMP2-418C and MMP9-1562T alleles the male infertility risk was significantly increased (P = 0.032). The current study suggests that the variation of TIMP2 gene and its interaction with MMP9 gene might be associated with male infertility. However, to confirm these findings, further studies are required in different ethnicities and with a larger sample size.

Interfering with interactions of vascular endothelial growth factors (VEGFs) with their receptors (VEGFRs) effectively inhibits angiogenesis and tumor growth. We designed an antagonist peptide of VEGF-A and VEGF-B reproducing two discontinuous receptor binding regions of VEGF-B (loop 1 and loop3) covalently linked together by a receptor binding region of VEGF-A (loop3). The designed peptide (referred to as VGB4) was able to bind to both VEGFR1 and VEGFR2 on the Human Umbilical Vein Endothelial Cells (HUVECs) surface and inhibited VEGF-A driven proliferation, migration and tube formation in HUVECs through suppression of ERK1/2 and AKT phosphorylation. The whole-animal fluorescence imaging demonstrated that fluorescein isothiocyanate (FITC)-VGB4 accumulated in the mammary carcinoma tumors (MCTs). Administration of VGB4 led to the regression of 4T1 murine MCT growth through decreased expression of p-VEGFR1 and p-VEGFR2 and abrogation of ERK1/2 and AKT activation followed by considerable decrease of tumor cell proliferation (Ki67 expression) and angiogenesis (CD31 and CD34 expression), induction of apoptosis (increased p53 expression, TUNEL staining and decreased Bcl2 expression), and suppression of metastasis (increased E-cadherin and decreased N-cadherin, NF-κB and MMP-9 expression). These findings indicate that VGB4 may be applicable for antiangiogenic and antitumor therapy.

Introduction: There are controversial reports about association between sleep and Hypothalamic-Pituitary-Adrenal (HPA) activity. Studies have reported the influence of insomnia on HPA hormones. However, they usually ignored the heterogeneity of insomnia symptoms, so subtypes of the disorder have not been considered in the reports. The present study aimed to investigate the final and intermediate products of HPA system among a group of psychophysiological and paradoxical insomniac patients in comparison to a group of normal sleepers. Methods: We investigated the awakening serum level of Adrenocorticotropic Hormone (ACTH) and cortisol after one night Polysomnography (PSG) in 17 subjects with psychophysiological insomnia, 19 subjects with paradoxical insomnia and 17 subjects with normal sleep profile. Groups were matched for age and Body Mass Index (BMI). Serum levels of ACTH and cortisol were measured by Enzyme-Linked Immunosorbent Assay (ELISA) method. Results: Although, a tendency toward elevation of both ACTH and cortisol was observed among patients with paradoxical insomnia compared to both control and psychophysiological insomnia, the differences were not significant comparing three groups. According to regression analysis, higher Non-Rapid Eye Movement sleep (NREM) arousal and Pulse Transit Time (PTT) significantly predicted higher level of ACTH. Conclusion: These findings could suggest the personality traits hypothesis for paradoxical insomnia. Both cortical and subcortical arousal could lead to more HPA activity and higher ACTH level. Further studies are recommended to confirm the hypothesis.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been led to a pandemic emergency. So far, different pathological pathways for SARS-CoV-2 infection have been introduced in which the excess release of pro-inflammatory cytokines (such as interleukin 1 β [IL-1β], IL-6, and tumor necrosis factor α [TNFα]) has earned most of the attentions. However, recent studies have identified new pathways with at least the same level of importance as cytokine storm in which endothelial cell (EC) dysfunction is one of them. In COVID-19, two main pathologic phenomena have been seen as a result of EC dysfunction: hyper-coagulation state and pathologic angiogenesis. The EC dysfunction-induced hypercoagulation state seems to be caused by alteration in the levels of different factors such as plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor (vWF) antigen, soluble thrombomodulin, and tissue factor pathway inhibitor (TFPI). As data have shown, these thromboembolic events are associated with severity of disease severity or even death in COVID-19 patients. Other than thromboembolic events, pathologic angiogenesis is among the recent findings. Furthermore, over-expression/higher levels of different proangiogenic factors such as vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1 α (HIF-1α), IL-6, TNF receptor super family 1A and 12, and angiotensin-converting enzyme 2 (ACE2) have been found in the lung biopsies/sera of both survived and non-survived COVID-19 patients. Also, there are some hypotheses regarding the role of nitric oxide in EC dysfunction and acute respiratory distress syndrome (ARDS) in SARS-CoV-2 infection. It has been demonstrated that different pathways involved in inflammation are generally common with EC dysfunction and angiogenesis. Altogether, considering the common possible upstream pathways in cytokine storm, pathologic angiogenesis, and EC dysfunction, it seems that targeting these molecules (such as nuclear factor κB) could be more effective in the management of patients with COVID-19., Graphical abstract Unlabelled Image

Hypoxia has been suggested as an important pathophysiological feature in varicocele disease. On the other hand, the expression of hypoxia-inducible factor 1-alpha (HIF1-α) is associated with the incidence of hypoxia. In this study, we investigated the expression of HIF1-α in varicocele disease through a comprehensive systematic review. We searched PubMed, Scopus, Web of Science, and Embase databases to identify the related studies published up to February 2021. Human studies have demonstrated an increase in the HIF-1α protein expression in the internal spermatic vein (ISV) of the varicocele testicle. HIF-1α mRNA expression in the seminal plasma was significantly higher in infertile varicocele patient compared with fertile ones. Similarly, most animal studies demonstrated a significant increase in HIF-1α gene and protein expression in varicocele testicular tissue compared with control groups. The studies illustrated that hypoxia followed by increased expression of hypoxia-inducible factor 1-alpha (HIF1-α) mRNA and protein occurs in varicocele disease. Expression of HIF-1α regulates the expression of many genes, including VEGF, p53, GLUT, Bax, and Caspase-3, that could be involved in many of the varicocele pathophysiological effects such as DNA fragmentation and apoptosis of sperm cells. Further studies with a large number of patients are necessary and can provide more definitive evidence.

In recent years, nanotechnology has attracted attention for its capability to diagnose and remedy diverse tumors successfully. Protein nanocarriers as a platform of targeted drug delivery can be used to reduce toxicity and improve the effect of anticancer drugs. Idarubicin (IDR) is a chemotherapy drug that is classified as an anthracycline antitumor. In this study, IDR was encapsulated within horse spleen apoferritin (HsAFr) nanocarriers. Encapsulation was obtained through disassembling apoferritin into subunits at pH 2 and subsequently reassembling it at pH 7.4 in the presence of IDR. Transmission electron microscopy, UV-vis, and fluorescence spectroscopy techniques showed that drug molecules are loaded within apoferritin. Intrinsic fluorescence information exhibited that the encapsulation does not have any effects on the tertiary structure of the protein. Drug loading and entrapment efficiency were found to be 7.15% and 84.75%, respectively. Comparison of anticancer activities in HsAFr-IDR and free drug IDR was made via the MTT viability technique in a human breast cancer cell line (MCF-7).

BACKGROUND: Human serum paraoxonase (PON) is an enzyme that is synthesized by the liver and enters the bloodstream, and it is transmitted by high-density lipoproteins (HDL). Paraoxonase 1 (PON1) is a hydrolytic enzyme with a wide range of substrates and the ability to protect against lipid oxidation. In this study, due to the activity of PON1 in the brain and its antioxidant effects on the reduction of neurological disorders in the central nervous system, the role of PON1 and its polymorphisms related to multiple sclerosis has been examined to enhance treatment methods. METHODS: This article is a systematic review. In this study, the role of PON1 and its polymorphisms in multiple sclerosis (MS) has been investigated. Articles published in Persian and international databases of SID, Google Scholar, ISI (WoS), Magiran, PubMed, Scopus, IranDoc, Science Direct, and Iran Medix were examined, using the search keywords of Paraoxonase 1, polymorphism, multiple sclerosis, and PON1. RESULTS: PON1 is undoubtedly a potential factor in the pathogenesis of multiple sclerosis, and it plays an important role in protecting antioxidants in the blood. Oxidative stress and lipid peroxidation are factors in the pathogenesis of MS. Both inflammatory cytokines and oxidative stress have a detrimental effect on PON1. However, reducing the activity of PON1 may help to restore the pathogenesis of the disease. CONCLUSION: Decreased PON1 activity and PON1 polymorphism are associated with several neurological diseases, including ischemic stroke, white matter lesions (WMLs), amyotrophic lateral sclerosis (ALS), dementia, and Parkinson's disease. PON1-55M alleles in Italians and PON1-192Q alleles in Poles were associated with a high risk of MS. Moreover, PON1-55 and PON1-192 polymorphisms were not associated with MS onset age, nor its evolutionary type.

Background Non-alcoholic fatty liver disease (NAFLD) is a common disorder that is known to be the leading cause of chronic liver disease worldwide. This study aims to systematically review and meta-analyze the association between PNPLA3 rs738409 polymorphism and non-alcoholic fatty liver. Methods Following a systematic review and meta-analysis method, articles without any time limitation, were extracted from SID, MagIran, IranDoc, Scopus, Embase, Web of Science (WoS), PubMed and ScienceDirect international databases. Random effects model was used for analysis, and heterogeneity of studies was investigated considering the I2 index and using Comprehensive Meta-Analysis software. Results The odds ratio of CC genotype in patients with non-alcoholic fatty liver demonstrates the protective effect of CC genotype with the ratio of 0.52, whereas CG genotype presents an increasing effect of CG genotype with the ratio of 0.19, and GG genotype also showed an increasing effect of GG genotype with the ratio of 1.05. Moreover, CG + GG genotypes as a single group demostrated an odds rartio of 0.88. Conclusion This meta-analysis highlights that people with CC genotype has 52% lower chance of developing non-alcoholic fatty liver disease, and those with CG genotype had 19% higher risk of developing non-alcoholic fatty liver. Those with GG genotype were 105% more likely to develop non-alcoholic fatty liver than others. Moreover, those present in a population with CG + GG genotypes were 88% more likely to have non-alcoholic fatty liver disease.

Targeted therapy is an effective and appropriate approach with low side effects in cancer therapy compared with other treatment approaches. Epidermal growth factor receptor, EGFR, is a favorable biomarker as targeted therapy because it overexpresses in several cancers. Monoclonal antibodies are common agents for targeted therapy. Nanobody is the smallest format of monoclonal antibodies with unique properties that include hiding epitope targeting, high stability, low production cost, and ease of connection to other components. The main challenge in targeted therapy by monoclonal antibodies is their immunogenicity due to their non-human nature. In this study, we designed, constructed, and evaluated a novel humanized anti- EGFR biparatopic nanobody, hu7CG2. The hu7CG2 was designed by grafting the complementarity-determining regions of two camelid anti- EGFR nanobodies known as 7C12 and EG2 to a universal scaffold and then connected with a glycine-serine linker. The results of antigen-binding activity and cell viability assays showed that the hu7CG2 inhibited the growth of EGFR overexpression tumor cells. The data showed that hu7CG2 might be a useful tool in the targeting and treatment of tumor cells.

Testis-specific gene antigen 10 (TSGA10) plays an important role in spermatogenesis. However, the exact TSGA10 role and its relationship with the autophagy pathway in the process of spermatids differentiation/maturation is still not clear. Therefore, the present study evaluates the role of TSGA10 gene in the spermatid differentiation/maturation through its effect on autophagy and explores possible underlying pathway(s). Sperm samples from patients with teratospermia were collected. The mRNA and protein level of TSGA10 in these samples were assessed by real-time PCR and western blotting. Using the ingenuity pathway analysis (IPA) software, the gene network and interactions of TSGA10 involved in sperm maturation and autophagy were investigated. Based on these analyses, the expression levels of identified genes in patient's samples and healthy controls were further evaluated. Moreover, using flow cytometry analysis, the levels of reactive oxygen species (ROS( production in teratospermic sperm samples were evaluated. The results showed that the expression levels of TSGA10 mRNA and protein decreased significantly in the teratospermic patients compared to controls (P < 0.05). Moreover, a significant reduction in the expression of the important genes involved in sperm maturation and autophagy was observed (P < 0.05). Also, the levels of ROS production in teratospermic sperm samples were shown to be significantly higher compared to those in normal sperms (P < 0.05). Our findings provide new evidence that simultaneous decrease in TSGA10 and autophagy beside the increased level of ROS production in sperm cells might be associated with the abnormalities in the spermatids differentiation/maturation and the formation of sperms with abnormal morphology.

Graphical abstract, Highlights • SARS-CoV-2 replication demands an upregulated cellular lipogenesis to support viral packaging. • SARS-CoV-2-induced ARDS in the alveoli is the main culprit for COVID-19 fatality. • Increased oxidative stress, as one of the key features of ARDS, could be overcome by high-dose vitamin C. • A combination of metformin plus azythromycin/doxicycline could target viral replication by downregulating lipogenesis. • We propose the combination of vitamin C plus metformin and azythromycin/doxicycline for the treatment of fatal SARS-CoV-2 attacks., As a process entailing a high turnover of the host cell molecules, viral replication is required for a successful viral infection and requests virus capacity to acquire the macromolecules required for its propagation. To this end, viruses have adopted several strategies to harness cellular metabolism in accordance with their specific demands. Most viruses upregulate specific cellular anabolic pathways and are largely dependent on such alterations. RNA viruses, for example, upregulate both glycolysisand glycogenolysis providing TCA cycle intermediates essential for anabolic lipogenesis. Also, these infections usually induce the PPP, leading to increased nucleotide levels supporting viral replication. SARS-CoV-2 (the cause of COVID-19)that has so far spread from China throughout the world is also an RNA virus. Owing to the more metabolic plasticity of uninfected cells, a promising approach for specific antiviral therapy, which has drawn a lot of attention in the recent years, would be the targeting of metabolic changes induced by viruses. In the current review, we first summarize some of virus-induced metabolic adaptations and then based on these information as well as SARS-CoV-2 pathogenesis, propose a potential therapeutic modality for this calamitous world-spreading virus with the hope of employing this strategy for near-future clinical application.

COVID-19, disease caused by the new coronavirus, SARS-CoV-2, appeared in the end of 2019 and was rapidly spread in most countries. This respiratory virus has different symptoms from moderate to severe, and results in lung pneumonia following acute respiratory distress syndrome (ARDS) and patient’s death in severe cases. ARDS is a severe form of acute lung injury that is caused by high inflammatory response of the innate immunity cells. Hypoxia is the common feature in the inflammatory sites with having various impacts on this condition by induction of some factors such as hypoxia inducible factor-1α (HIF-1α). HIF-1α regulates some important cellular processes including cell proliferation, metabolism and angiogenesis. Furthermore, this factor is activated during the immune responses and plays important roles in the inflammation site by inducing pro-inflammatory cytokines production through immune cells. So, in this study the possible effect of the HIF-1α on the COVID-19 pathogenesis with emphasizes on its role on innate immunity response has been discussed.

Background Breast cancer is a type of cancer with a high incidence and mortality rate worldwide. Change in epigenetic mechanisms enhances cancer cell progression. Histon deacetylase 2 (HDAC2) was found to act as a potential oncogene in different malignancies. For better understanding the mechanisms related to breast cancer development, we investigated the role of HDAC2 in breast cancer and the inhibitory effect of miR-646 on this oncogene. Methods A total of thirty cancerous tissues and 30 adjacent non-cancerous specimens and also three breast cancer cell lines were enrolled in the study. Quantitative reverse transcriptase PCR (qRT-PCR) was employed to detect the HDAC2 and miR-646 expression level in the studied samples. The biological roles of HDAC2 and miR-646 were investigated through manipulating the expression level of HDAC2 or miR-646 in breast cancer cells. Finally, we evaluated whether the HDAC2 is a direct target for miR-646. Results In this study, we found HDAC2 is significantly upregulated in cancerous specimens and cell lines compared to non-cancerous tissues and normal cell line. On the other hand, miR-646 expression was decreased in clinical specimens and breast cancer cells compared to non-cancerous samples. Knocking out of the HDAC2 and overexpression of miR-646 inhibited breast cancer cell growth but promoted cell death, while untreated groups showed inverse results. Furthermore, we showed that in the breast cancer cells, miR-646 regulates the progression and proliferation by suppressing HDAC2. Conclusion Taken together, our study identified a miR-646/HDAC2 regulatory function in the breast cancer development and introduced a therapeutically target for breast cancer.

Glucose, as the main consuming nutrient of the body, faces different destinies in cancer cells. Glycolysis, oxidative phosphorylation, and pentose phosphate pathways produce different glucose-derived metabolites and thus affect cells’ bioenergetics differently. Tumor cells’ dependency to aerobic glycolysis and other cancer-specific metabolism changes are known as the cancer hallmarks, distinct cancer cells from normal cells. Therefore, these tumor-specific characteristics receive the limelight as targets for cancer therapy. Glutamine, serine, and fatty acid oxidation together with 5-lipoxygenase are main pathways that have attracted lots of attention for cancer therapy. In this review, we not only discuss different tumor metabolism aspects but also discuss the metabolism roles in the promotion of cancer cells at different stages and their difference with normal cells. Besides, we dissect the inhibitors potential in blocking the main metabolic pathways to introduce the effective and non-effective inhibitors in the field.

Background Coronary Artery Disease (CAD) is caused by the blockage of the coronary arteries. it is argued that there has an association between the Interleukin-6 gene and the occurrence of atherosclerosis, coronary artery disease, Due to the short half-life and high variability of Interleukin-6 (IL-6), limited studies have been performed on the association of serum levels of interleukin-6 with coronary artery disease. The aim of this study is to investigate the relationship between IL-6 gene polymorphisms and coronary artery disease. Methods This study was conducted as a meta-analysis of selected articles with no lower time limit and upto March 2020. Articles related to the subject were obtained by searching several data sources,such as the SID, IranDoc, Scopus, Embase, Web of Science (ISI), PubMed, Science Direct, and Google Scholar databases. The heterogeneity of the studies was assessed using the I2 index in the Comprehensive Meta-Analysis software. Results The GG genotype of the IL-6174 G> C polymorphism with a 0.8 odds ratio tended to reduce the risk of CAD by 20%. The odds ratio of CAD in CG and GG genotypes were found to be 1.16 and 1.48 times respectively, indicating the increasing effect of these two genotypes. In the IL-6-572 C>G polymorphism, CG and GG genotypes increased the risk of CAD by 1.21 and 1.27 times respectively, and the CC genotype tended to reduce the risk of CAD by 15%, considering the odds ratio of 0.85. Conclusion This study showed a relationship between IL-6174G> C and Interleukin-6 (IL-6) 572 C>G genes and coronary artery disease. Moreover, the protective effects of GG genotype in IL-6 gene 174 G> C and CC genotype in IL-6 gene 572 C>G gene were reported. The study also confirmed that the CG and CC genotypes of the G>C IL-6174 gene have an increasing effect on coronary artery disease. Moreover, CG and GG genotypes in the IL-6 gene 572 C>G increased the risk of developing CAD. It should be noted that the increased risk of developing CAD was limited to meta-analytic studies in reported literatures.

This scenario was designed to investigate the protein corona pattern on the pillar-layer surface of a Cu-based metal–organic framework (MOF) in human plasma. The [Cu(L)(L/)].1.3DMA (MOF-1) {L = 4, 4/-bipyridine and L/ = 5-aminoisophthalic acid}, was synthesized through the sonochemical irradiation approach as well as characterized by various techniques like scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction and single-crystal X-ray diffraction. The space group was determined to be an orthorhombic space group (Pbam) by single-crystal X-ray diffraction. Single-crystal X-ray analyses on MOF-1 showed that Cu+2 ion was 6-coordinated. Besides, to study and clarify interactions between MOFs and biological milieu, human whole blood plasma was selected as a model. Fluorescence spectroscopy and SDS-PAGE techniques were employed to explore quantitative and qualitative in situ characterization of protein corona as well. Furthermore, cell viability in a cancerous cell lines was evaluated by MTT assay in the presence and absence of the corona. The results from SDS-PAGE illustrated that the most adsorbed quantity among plasma proteins belongs to fibrinogen (α, β and γ chains), and this protein showed the maximum frequency on the MOF-1s surface, so the possible interactions of MOF-1s with fibrinogen also studied using fluorescence spectroscopy and corresponding data were plotted. According to the obtained data from MTT assay, these structures have concentration-dependent toxicity. In brief, based on the obtained data in the current study, the designed MOF can be introduced as a new desirable carrier for drug/gen delivery after further prerequisite assessments.

Atherosclerosis is an inflammatory disease in which intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin (SELE) are consistently expressed in the vascular endothelium. Several evidence support the crucial role of adhesion molecules in the development of atherosclerosis and plaque instability. Due to the anti-inflammatory activity of Tribulus terrestris (TT), the present study investigated the effect of aqueous extract and saponin fraction of TT on the expression of ICAM-1, VCAM-1, and SELE genes in endothelial cells during normal and lipopolysaccharide (LPS) induced conditions. Human umbilical vein endothelial cells (HUVEC) and human bone marrow endothelial cells (HBMEC) were cultured, stimulated by LPS, and treated with aqueous extract and saponin fraction of TT. Finally, the expression of ICAM-1, VCAM-1, and SELE genes were measured using quantitative real-time polymerase chain reaction. LPS-induced HUVECs and HBMECs significantly increased the expression of ICAM-1, VCAM-1, and SELE in comparison with control groups (P

Lack of vascularization results in increased demand for oxygen and creates a defined feature of the tumor microenvironment known as tumor hypoxia. It is well established that in response to hypoxia, hypoxia-inducible factor-1 α (HIF-1α) is induced which is an important factor in angiogenesis, invasion and metastasis. In turn, HIF-1α regulates the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF). Ascribed to abnormal characteristics of tumor angiogenic networks, antiangiogenic therapy approaches can even worsen the hypoxic condition and can create cancer cells with stemness features. Hence oxygen delivery via perfluorocarbon (PFC) to hypoxic sites seems to result in unstable HIF expression and consequent inactivation of angiogenesis cascade and metastasis and therefore, inhibition of cancer cells stemness.

Background: Testis-specific gene antigen (TSGA10) mainly involves in spermatogenesis and embryogenesis. In the new defined roles, being a tumor suppressor agent or a cancer/testis antigen (CTA) is still unclear for this protein. The current study aimed to examine exact role of TSGA10 as a tumor suppressor or CTA in breast cancer and evaluate the role of microenvironment on its expression. Methods: This study evaluated the expression of TSGA10 and hypoxia-inducible factor 1α (HIF-1α) in two different breast cancer cell lines (MCF-7 and MDA-MB23) as well as their control (MCF10A) using real-time PCR. Moreover, expression of the mentioned genes evaluated in samples obtained from tumoral tissues with two types of controls: paired (tumor-free margin) and unpaired (healthy individuals). Also, in order to asses TSGA10 levels in the tumoral tissues, western blotting was performed. Furthermore, to evaluate the role epigenetic changes on TSGA10 expression, breast cancer cell lines were treated with a histone deacetylase inhibitor (HDACI) as well as H2O2 for oxidative stress induction. Results: The current study evaluated 36 patients diagnosed with breast cancer as well as 10 healthy controls. According to the results, it was shown that 35 (97.7%) and 1 (2.8%) of patients were diagnosed with ductal and lobular carcinomas respectively. The TSGA10 levels in the tumoral samples showed 1.38±0.014-fold decrease and 1.41±0.127-fold increase compared with their paired (PTSGA10 expression in MCF-7 and MDA-MB23 cells had 4.9±0.283 and 4.21±0.163 folds of decrease in normoxic and 4.7±.0.283 and 7.1±0.141 folds of expression reduction in hypoxic condition respectively (all PHIF-1α expression was up-regulated in both normoxic (PTSGA10 expression increased up to 7.39±0.156 folds in MCF-7 cells after HDACI treatment (all PTSGA10 expression (all PConclusion: Results of current study showed that TSGA10 seems to be tumor suppressor, however, further studies are necessary.

Cancer is one of the main causes of death in today's world, therefore, extending fast and reliable approaches for early monitoring of cancer cells have become one of the great challenges for scientists. This work reports exploiting a fast single frequency impedance strategy coupled to a new constructed composite for the quantitative detection of the human chronic myelogenous leukemia (CML) cell lines, K562. The platform used for the fabrication of the cytosensor is based on an electrospun poly[ethersulfone] (PES) sub-layer ready for improving by the upper nanodimension layers comprised of gold nanoparticles and multiwall carbon nanotubes (AuNPs/MWCNTs). The binding of K562 cancer cells with the pre-immobilized capture ssDNA was successfully transduced by Faradaic impedance spectroscopy (FIS). To diminish the possible nonspecific impedance changes that may cause some uncertainties in FIS signal, and to considerably decrease the time of the extended method, a fast single frequency measurement (SFM) strategy was tested based on recording total impedance |Z| in different individual frequencies, the methodology that was succeeded to recognize the target cells in measurement times as low as several seconds. Under the optimum conditions, the assessed signals were proportional to the population of K562 cells from 102 to 107 cells mL−1 with a calculated detection limit of 60 cells mL−1. The proposed biosensing-device also demonstrated high stability and reproducibility, which was able to offer great promise for the quantitative assay of K562 in routine analyses. The results of real sample analyses introduced the proposed device as alternative tool for CML K562 cell detection in real biological samples.

Epidermal growth factor receptors (EGFRs) and their cytoplasmic tyrosine kinases play significant roles in cell proliferation and signaling. All the members of the EGFR/ErbB family are primary goals for cancer therapy, particularly for tumors of breast, cervix, ovaries, kidney, esophagus, prostate and non-small-cell lung carcinoma and head and neck tumors. However, the therapeutic ability of accessible anti-ErbB agents is limited. Therefore, recognizing EGF analogues or small organic molecules with high affinity for the extracellular domain of the EGFR is a critical target on cancer research. An effective EGF analogue should have a comparable binding affinity for EGFR in order to create an effective ligand competitive inhibition against circulating wild EGF while fails to transduce appropriate downstream signaling into the cancer cell. In our earlier study we have developed a mutant form of human EGF (mEGF, lacking the four critical amino acid residues; Gln43, Tyr44, Arg45 and Asp46 at the C-terminal of the protein) and its binding properties and mitogenic activity were assessed. The mEGF showed high affinity for EGFR binding domains but caused poor EGFR dimerization and phosphorylation and especially, mEGF induced EGFR internalization. However, underlying mechanism of action of EGF analogues is still unclear and thus considered to be worthwhile for further study. With regard to different effects of the EGF analogue on EGFR activating process, computational analysis of wild EGF/EGFR and mEGF/EGFR complexes (along with EGFt/EGFR complex) were done. Results of the protein dissection identified several interactions within "ligand/EGFR" that are common among EGF and EGFt/mEGF. These results disclose that while several interactions are conserved within EGF/EGFR interfaces, EGF/EGFR interactions on site III interface controls the affinity, EGFR dimerization and subsequent downstream signaling through a heterogeneous set of non-covalent interactions. These findings not only represent the EGFR dynamics complexity but also smooth the path for structure-based design of therapeutics targeting C-terminal region of EGF (and the related domain within the receptor) or EGFR-based imaging probes.

It has been reported that the antiestrogen Tamoxifen induces liver tumors in rats and genotoxic effects in vitro through DNA interaction. So, it can be proposed that its structural analogue, Clomifene, also can bind to DNA. To test this hypothesis, the DNA binding properties of Clomifene have been studied by absorption spectroscopy, fluorescence spectroscopy, cellular uptake, cell viability, cell proliferation and molecular modeling techniques. Evidences are provided that Clomifene could interact with DNA via minor groove interaction mode. The negative ΔG value implied that the interaction occurred between DNA and Clomifene spontaneously. Also, the positive ΔH and positive ΔS values indicated that the binding of Clomifene with DNA is mainly entropy driven and the enthalpy is unfavorable parameter. This also suggests that the hydrophobic interaction plays a major role in the binding with overall binding constant of K=5.645×107M-1 at 298K. From the results of docking, it can be concluded that Hydrogen bonds is also one of the most important interactions. The increase in entropy of system after binding might be due to the destruction of the DNA structure.