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Background: In many studies, chemicals and natural materials were tested to reduce the harmful effects of radiation. It is known that Famotidine and vitamin C reduce DNA damage. Objective: The aim of this study was to evaluate the radioprotective effect of vitamin C, Cimetidine and Famotidine on gamma-radiation-induced damage on mouse bone marrow. Methods: Six-to-seven week male NMRI mice (28 g ±3) were randomly divided into fourteen groups: control, 2Gy irradiation, six group drugs without irradition (Famotidine, Cimetidine, vitaminC, Fam-Cim, Fam-Vit, Cim-Vit), six groups received drugs and 2Gy radiation with a 60Co |γ|-ray source at room temperature 22 ± 2 °C. The mice were killed 48 hours after irradiation by cervical dislocation. Slides were prepared from bone marrow cells and stained in May-Granwald and Giemsa. Finally, the cells were counted with microscope, frequencies of polychromatic erythrocyte (PCE), normochoromatic erythrocyte (NCE) and their micronuclated cell were recorded. PCE / PCE + NCE were calculated. Results: There were significant differences of MNPCE/1000PCE, MNNCE/1000NCE and PCE/PCE+NCE among different groups with similar radiation doses (p≤0.01). Moreover, there were significant differences of MNPCE/1000PCE and PCE/PCE+NCE among different doses of radiation (p≤0.01). While considering MNNCE/1000NCE, there were no significant differences among silimar groups with radiation dose (p˃0.05). Conclusion: Oral administration of Famotidine, vitamin C and Cimetidine demonstrate reliable and similar radioprotective effects. Additionally, the protective effect of single use of these drugs was similar to the combination form. Thus, the oral use of combination, 48 hours after irradiation cannot induce more radioprotective effect.

Mehdi Hajmohammadi,1 Seyed Davar Siadat,2 Masoud Ghorbani,3,4,* Mehdi Shafiee Ardestani,5,* Shahram Teimourian,6 Vahid Asgari,3 Reza Ahangari Cohan,3 Mostafa Hajmohammadi,5 Akram Hajmohammadi,7 Ramezan Behzadi,8 Saied Rajab Nezhad,9 Nabiollah Namvar Asl10 1Department of Research and Biotechnology, 2Department of Microbiology, 3Department of Virology, Pasteur Institute of Iran, Tehran Iran; 4Department of Virology, University of Ottawa, Ottawa, ON, Canada; 5Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 6Department of Medical Genetics, Iran University of Medical Sciences, Tehran, 7Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, 8Laboratory Animal Management of North Research Center, Pasteur Institute of Iran, 9Department of Research and Development, Alhavi Pharmaceutical, Tehran, 10Pasteur Institute of Iran, Department of Animal Sciences, Karaj, Iran *These authors contributed equally to this work Abstract: In recent years, many experiments have been conducted for the production and evaluation of anticancer glycoconjugated vaccines in developed countries and many achievements have been accomplished with Globo H derivatives. In the current experiment, a new chemically designed triplicate version of (Globo H)3–diethylenetriamine pentaacetic acid (DTPA)–KLH antigen was synthesized and characterized. Immunization with (Globo H)3-DTPA-KLH, a hexasaccharide that is a member of a family of antigenic carbohydrates that are highly expressed in various types of cancers conjugated with DTPA and KLH protein, induced a high level of antibody titer along with an elevated level of IL-4 in mice. Treatment of tumors with the collected sera from immunized mice decreased the tumor size in nude mice as well. None of the immunized mice illustrated any sign of tumor growth after injection of MCF-7 cells compared to the control animals. These findings, based on the newly presented structure of the Globo H antigen, lend exciting and promising evidence for clinical advancement in the development of a therapeutic vaccine in the future. Keywords: (Globo H)3-DTPA-KLH, glycoconjugate vaccines, breast cancer

Objective: Pigmentation is one of the most obvious phenotypical characteristics in the natural world. Of the pigments, melanin is one of the most widely distributed and is found in bacteria, fungi, plants and animals. Melanins are heterogeneous polyphenol-like biopolymers with a complex structure and color varying from yellow to black. In the melanin formation pathway, tyrosinase is the rate-limiting enzyme that catalyzes tyrosine to 3,4-dihydroxyphenylalanine (DOPA) and oxidizes DOPA to dopaquinone. Tyrosinases belong to type 3 copper proteins. The binuclear active site of tyrosinase consists of two copper ions, coordinated each by three highly conserved histidines. It has been shown that melanin biosynthesis pathway can be feasibly induced using recombinant tyrosinase. Our main aim to evaluate the activity of native tyrosinase and its two mutational variants in HEK-293 cells. Materials and Methods: Two mutants of human tyrosinase enzyme have been previously constructed in our lab anticipated to possess higher catalytic activity in HEK- 293 cells in comparison with the native protein. Native enzyme and the mutational variants have already been cloned in pET-28b(+) for evaluation of protein expression in Escherichia coli BL21. In this approach, coding sequences of native and mutant proteins have been subcloned into pcDNA3.1(+) expression vector followed by subsequent transfection of HEK-293 cells with three constructed pcDNA3.1(+)-hTyr vectors. Results: Digestion and sequencing results of constructed vectors all together showing that fragments have been cloned correctly. transfection's positive control also confirms transformation accuracy. Activity studies of native tyrosinase and two mutational variants have been performed and will be presented in congress. Conclusion: Human native tyrosinase and two mutational variants have been subcloned from a prokaryotic vector pET-28b(+) into pcDNA3.1+ for activity evaluation in eukaryotic cells [ABSTRACT FROM AUTHOR]

The article has been withdrawn at the request of the Corresponding author., Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused., The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php, Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net)

The rabies virus, which belongs to the genus Lyssavirus , the family Rhabdoviridae , is the causative agent of rabies, a contagious, deadly, and progressive neurological infection. This illness is commonly distributed worldwide and affects all warm-blooded animals. Regarding the zoonotic aspects of rabies, the prevalence of rabies was investigated in this study. Over 2 years, 188 samples were examined via the direct fluorescent antibody test (DFAT) and mouse inoculation test (MIT) techniques by using brain tissue samples. Our findings showed that 73.94% of samples were rabies positive. The highest number of samples belonged to cows and dogs, respectively. The positivity rate in cows was 71.88%, followed by dogs with a 57.78% infection rate. These findings suggested that despite the heavy monitoring protocols in Iran, rabies is still a prevalent disease, and it is advised that vaccinations and screening programs should be carried out more frequently with heavier observation., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2023 Saeid Kavoosian et al.)

Background: Xenografts of various human cancers in nude mice provide a helpful model in cancer research. This study aimed to develop a xenograft mouse model of MCF-7 breast cancer using injectable estradiol valerate., Methods: Thirty healthy female C57 nu/nu mice were engrafted with three protocols to establish an MCF-7 tumor. Injectable estradiol valerate (10 mg/ml) was used as a substitute for estradiol pellets. The development of tumors was recorded daily, and data were statistically analyzed. Histology of bladder, kidney, and tumors was used to estimate tumor establishment and probable urinary adverse effects., Results: According to the findings, the duration of MCF-7 tumor growth was the lowest for protocol B (tumor tissue). Also, this protocol had the highest xenograft yield within the shortest time duration (37 days for protocol B vs. 73 days for protocol A) without causing urinary adverse effects., Conclusion: Our findings revealed that estradiol valerate, which is way less expensive than estradiol pellets, can be used as a tumor proliferator to establish MCF-7 tumors with the highest yield when MCF-7 tumors have been used for xenograft., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Tumor vascular targeting appeared as an appealing approach to fight cancer, though, the results from the clinical trials and drugs in the market were proved otherwise. The promise of anti-angiogenic therapy as the leading tumor vascular targeting strategy was negatively affected with the discovery that tumor vascularization can occur non-angiogenic mechanisms such as co-option. An additional strategy is induction of tumor vascular infarction and ischemia. Methods: Such that we used truncated coagulase (tCoa) coupled to tumor endothelial targeting moieties to produce tCoa-NGR fusion proteins. We showed that tCoa-NGR can bypass coagulation cascade to induce selective vascular thrombosis and infarction of mild and highly proliferative solid tumors in mice. Moreover, combination therapy can be used to improve the potential of cancer vascular targeting modalities. Herein, we report combination of tCoa-NGR with vascular disrupting agent (VDA), vadimezan. Results: Our results show that synergistic work of these two agents can significantly suppress growth of B16-F10 melanoma tumors in C57/BL6 mice. Conclusion: For the first time, we used the simultaneous benefits of two strategies for inducing thrombosis and destruction of tumor vasculature as spatial co-operation. The tCoa-NGR induce thrombosis which reduces blood flow in the peripheral tumor region. And combined with the action of DMXAA, which target inner tumor mass, growth and proliferation of melanoma tumors can be significantly suppressed., (© 2021 The Authors.)

Background: The anti-cancer activity of some lactic acid bacterial strains is well documented in several kinds of literatures. Lactobacillus strains have received considerable attention as a beneficial microbiota. The aim of this study is to evaluate the effects of anti-tumor activities of L. acidophilus ATCC4356 culture supernatants on the MCF-7 human breast cancer cells., Materials and Methods: The anti-cancer effects of 24h and 48h culture supernatants at various concentrations (1.25, 2.5, 5, 10 and 20 μg/ml) were determined by various in vitro and in vivo assays including MTT, tumor volume measurement as well as 99m Tc-MIBI biodistribution in MCF-7 tumor bearing nude mice and histopathology test. For evaluation of the related mechanism of action, quantitative PCR was conducted., Results: The 48h culture supernatants at 10 and 20 μg/ml exhibited significant in vitro inhibition of MCF-7 cell proliferation. However, this inhibition was not observed for HUVEC human endothelial normal cells. Q-PCR indicated that treatment by the supernatant led to a significant downregulation of VEGFR (~ 0.009 fold) and Bcl- 2 (~ 0.5 fold) and upregulation of p53 (~ 1.3 fold). In vivo study using MCF-7 xenograft mouse models demonstrated a reduction in tumor weight and volume by both 24h and 48h supernatants (2 mg/kg) after 15 days. According to the 99m Tc-MIBI biodistribution result, treatment of MCF-7 bearing nude mice with both 24h and 48h supernatant (2mg/kg) led to a significant decrease in tumor uptake compared with the control group., Conclusion: These results suggest that the culture supernatants of L. acidophilus ATCC4356 at suitable concentrations can be considered as a good alternative nutraceutical with promising therapeutic indexes for breast cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Tyrosinases are copper-containing enzymes that initiate the melanin synthesis. They catalyze the direct oxidation of L-tyrosine or L-DOPA into L-DOPAquinone., Objectives: In present study, we aimed to obtain a recombinant tyrosinase with enhanced catecholase activity through site-directed mutagenesis., Materials and Methods: The coding sequence of human tyrosinase along with native signal sequence was cloned into pET-28a (+). BL-21 was used as expression host and recombinant protein was purified by Ni-NTA resins. Site-directed mutagenesis was performed on M374 residue to achieve four mutants: M374D, M374T, M374K and M374R. Chloride ions (Cl - ) were removed from all solutions, and an extra amount of Cu 2+ ions was added to recombinant tyrosinases by a novel technique during the purification process. Removal of Cl - ions and addition of extra Cu 2+ ions tripled catecholase activity of the recombinant protein. Therefore, all mutants were obtained under similar conditions., Results: Although all the mutants presented higher catecholase activity in comparison to the wild-type enzyme, a significant increase in catecholase activity of the M374D mutant was observed ‒ 13.2-fold. In silico modeling suggested that a de novo hydrogen bond occurs between side chain carboxyl oxygens of D374 and H367 in M374D. In the wild-type tyrosinase, the peptide oxygen atom of M374 is responsible for hydrogen bonding with H367., Conclusions: Our data suggests that M374D mutational variant has applications in different areas such as agriculture, industry, and medicine., (Copyright: © 2020 The Author(s); Published by Iranian Journal of Biotechnology.)

Background: Pre-eclampsia (PE) is a pregnancy complication and one of the leading causes of maternal and neonatal morbidity and mortality in the world. PE is characterized by high blood pressure and signs of damage to the other organs, most often the liver and kidneys. Given the importance of mutation in the vascular endothelial growth factor ( VEGF ) gene and its correlation with the incidence of PE, the relationship of VEGF encoding gene polymorphisms rs922583280, rs3025040 and rs10434 with the incidence of PE in the population of Iranian women was studied, in this research., Materials and Methods: In this case-control study, 100 pregnant women with PE diagnosis and 50 healthy pregnant women were evaluated using Sanger sequencing method to determine genotypes rs922583280, rs3025040 and rs10434., Results: There was no significant difference in the allele frequency of rs922583280 and rs3025040 polymorphisms between case and control groups (P>0.05), while frequency of the recessive allele (G) for rs10434 polymorphism was significantly higher in the case group compared to the control group (P=0.014, case=24%, control=12%). Frequency of the allele A in the control group was higher than the patient group (case=76%, control=88%). Frequency of AG genotype in the patient group was also higher than the control group. In addition, frequency of AA genotype in the control group was higher than the patient group (case=57%, control=78)., Conclusion: The results of this study demonstrated a significant difference between patient and control groups for the VEGF coding gene polymorphism rs10434 and it can affect the incidence of PE among Iranian women., Competing Interests: The authors declare no conflicts of interest., (Copyright© by Royan Institute. All rights reserved.)

Background: There has been considerable interest in the potential health benefits of borage. Little information is available regarding the safety of this plant. The purpose of this study was to evaluate the impact of borage on the mouse heart., Methods: Different amounts of borage extract were injected in mice. The mice were randomly divided into 4 groups including group1 (Control group without injection), group2, 3 and 4 that received 12.5 mg/kg, 25 mg/kg and 50 mg/kg respectively for 28 days. Oxidative stress parameters (lipid peroxidation, total glutathione groups assay and cupric assay) and biochemical (Creatine kinase activity and total cholesterol) and hematology parameters were evaluated. Furthermore, histopathology study was carried out on heart tissues., Results: We found that there was no significant difference in oxidative stress parameters and biochemical parameters between the control group and the groups that received different amounts of borage extract. There were also no changes in histopathology study. In blood parameters, the level of erythrocytes, hematocrit and hemoglobin decreased to 50mg/kg, whereas the level of MCH and MCV decreased in high doses., Conclusion: This article suggested that borage did not cause significant damage to the heart tissue in mice model. In hematology factors, significant changes were observed in erythrocytes and related parameters. Therefore, hematotoxicity of consumption this plant should be considered at high doses., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Objective: Doxorubicin (DOX), despite having antitumor properties, also exhibits cardiotoxicity. Resveratrol has antitumor property for breast cancer cells. 99m Tc-MIBI has higher absorption rate in human breast cancer cell line MCF-7. In the present study, the authors intend to investigate the effect of DOX and resveratrol on the absorption of 99m Tc-MIBI in breast cancer cell xenografts in mice., Materials and Methods: Sixteen xenograft models in nude mice were divided into four groups. Group I (S, control) received 2% DMSO in 0.9% saline, group II (D) 2.5 mg/kg DOX, group III (D + R) 20 mg/kg/d resveratrol with 2.5 mg/kg DOX (total dose of 15 mg/kg in six injections), and group IV (R) 20 mg/kg/d resveratrol for 2 weeks. Single-photon emission computed tomography (SPECT) images were taken for the determination of 99m Tc-MIBI absorption. Mice were sacrificed, and the percentage of injected dose per gram (%ID/g) of the heart, liver, tumor, and muscle was measured using a gamma counter. Hematoxylin-eosin staining and Masson's trichrome staining were used for investigation of histopathological changes., Results: The %ID/g of tumor was lowest in group D + R. The severity of tumor necrosis or apoptosis was highest in group D + R, but there is no significant difference in pathological injuries and %ID/g of tumor between the group D + R and group D. In addition to the results of the %ID/g, the severity of pathological injuries to the liver and heart cells in group D + R was higher compared with group D. There is a significant difference in the %ID/g of the liver between the group D + R and group D. SPECT images showed that the lowest amount of %ID/g was observed in the tumor of group D + R., Conclusions: According to the results of pathology, biodistribution study, and imaging, the combination of DOX and resveratrol has shown higher antitumor effect; hence, 99m Tc-MIBI can be used to evaluate their antitumor effect.

Gastric cancer (GC) is the third and fifth cause of cancer-associated mortality for men and women throughout the world, respectively. Despite the use of surgery and chemotherapy for GC therapy, there are no efficient therapeutic protocols for it to date. Cancer stem cells (CSCs) due to their pivotal role in tumor initiation, growth, progression, invasion, distant metastasis, recurrence and resistance to anticancer drugs are very appealing targets for cancer therapies. Here, we isolated and identified CSCs from a chemotherapy-treated patient. Small subpopulation of dissociated cells after tissue digestion formed spheroid colonies in serum-free media under the non-adherent condition. These spheroid colonies differentiated into epithelial like cells in serum-containing medium. Few sphere-forming cells carried CD44 and CD54 markers overexpressed DLL4 that is responsible for tumor growth and angiogenesis. Subcutaneous injections of sphere-forming cells in different passages conferred tumorigenicity in nude mice. Sphere-forming cells upregulated CD44 polymorphisms CD44v3, -v6, and -v8 -10, stemness factors OCT4, SOX2, SALL4 and Cripto-1, self-renewal molecules IHh, Wnt, β-catenin and BMI1, and epithelial mesenchymal transition (EMT) markers Twist1 and Snail1 in vitro and in vivo. Moreover, these cells similar to sphere-forming cells isolated from a chemotherapy-free patient expressed Oct-4 and β-catenin proteins. However, the Twist1 protein was only expressed by sphere-forming cells derived from the chemotherapy-treated patient. Thus, these cells have all the characteristics of stationary and migratory CSCs, including tumorigenicity, self-renewal, pluripotency, invasion and metastasis. Taken together, targeting chemotherapy-enriched CSCs as chemo-resistance cells observed in GC patients can provide more effective therapeutic strategies compared to untreated patients., (© 2018 Wiley Periodicals, Inc.)

Cancer remains a major health problem around the world. A Shiga toxin is a bacterial toxin often produced by Shigella dysenteriae and Escherichia coli. A subunit of the Shiga toxin (StxA) is a cytotoxic agent which could be used to induce death in cancer cells. StxA expressed from baculovirus was evaluated in a pTriEx™ expression vector. The baculovirus vector was used for the A subunit delivery of StxA. StxA cell cytotoxicity was induced by the virus and assessed in the MCF7 and HeLa cell lines. In addition, the breast cancer cytotoxicity of the expressed StxA was also assessed in a cancer induced in mice. The cytotoxicity of the recombinant StxA baculovirus with different multiplicities of infection (MOI) was measured. The results showed that significant cytotoxicity can be induced on the mammalian epithelial breast cancer cell lines, MCF7 and HeLa cells with MOI ≥ 2. The results also showed that a malignant tumor induced by MCF7 could be inhibited in a mouse cancer model. Therefore, it can be concluded that StxA, expressed by baculovirus, could be used for in vitro and in vivo gene delivery. In this study StxA, delivered by the baculovirus inhibited cell proliferation, and eliminated HeLa and MCF7 cells, in vitro. In conclusion, this method can be used as a safe alternative for anticancer drug delivery inside cancer cells., (Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Induction of selective thrombosis and infarction in tumor-feeding vessels represents an attractive strategy to combat cancer. Here we took advantage of the unique coagulation properties of staphylocoagulase and genetically engineered it to generate a new fusion protein with novel anti-cancer properties. This novel bi-functional protein consists of truncated coagulase (tCoa) and an NGR (GNGRAHA) motif that recognizes CD13 and α v β 3 integrin receptors, targeting it to tumor endothelial cells. Herein, we report that tCoa coupled by its C-terminus to an NGR sequence retained its normal binding activity with prothrombin and a v β 3 integrins, as confirmed in silico and in vitro. Moreover, in vivo biodistribution studies demonstrated selective accumulation of FITC-labeled tCoa-NGR fusion proteins at the site of subcutaneously implanted PC3 tumor xenografts in nude mice. Notably, systemic administration of tCoa-NGR to mice bearing 4T1 mouse mammary xenografts or PC3 human prostate tumors resulted in a significant reduction in tumor growth. These anti-tumor effects were accompanied by massive thrombotic occlusion of small and large tumor vessels, tumor infarction and tumor cell death. From these findings, we propose tCoa-NGR mediated tumor infarction as a novel and promising anti-cancer strategy targeting both CD13 and integrin α v β 3 positive tumor neovasculature.

Objective: Ovarian cancer is still a major cause of morbidity and mortality. Docetaxel (DTX) is one of the most notable cytotoxic agents for treatment of ovarian cancer. However, its side effects proposed considerable problems to the patients., Significance: Polymeric nanoparticles (NPs) of poly (butylene adipate-co-butylene terephthalate) (Ecoflex ® ), a biodegradable and biocompatible polymer, were prepared for the first time by the upgradeable electrospraying technique., Methods: The formulation and procedure variables were optimized using Design Expert software, and effect of each variable on particle size, particle size distribution, drug entrapment efficiency, and drug release of the NPs were evaluated. Then, in vitro cytotoxicity, cellular uptake, X-ray diffraction pattern, and morphological characteristics of the optimized NPs were evaluated. Finally, in vivo efficacy of the DTX-loaded NPs was evaluated on tumor bearing nude mice., Results: The optimum condition for production of NPs included voltage of 20 kV, 12 cm distance between electrodes, feeding rate of 1 mL/hr, polymer to drug ratio of 3:1, 1 w/v% of Pluronic-F127 and dichloromethane to dimethyl formamide ratio of 2.7:1. Fluorescent microscopy test showed the NPs were successfully up-taken by ovarian cancer cells. In vitro cytotoxicity test confirmed no cytotoxic effect caused by blank NPs, while cell viability of the DTX loaded NPs was significantly lower than the free DTX (p < .05). The NPs significantly enhanced anti-tumor efficacy of the drug in nude mice (p < .05)., Conclusion: The Ecoflex ® NPs could potentially provide a suitable alternative for currently available formulations of DTX.

Background: Measurement of glomerular filtration rate (GFR) and monitoring of it in any patient on nephrotoxic drugs is very important. Recently, cystatin C (cys-C) has been introduced as a better marker for determining and monitoring renal function than creatinine especially in a mild decrease of GFR. This study was done to assess the change of GFR measurement based on serum Cys-C and creatinine and their comparison in children with acute pyelonephritis on amikacin., Methods: All children with acute pyelonephritis who were admitted in Nephrology ward were enrolled in this study. Serum creatinine, serum cys-C and the GFR calculation based on them were measured in patients on the day of admission (day zero) and then on days 3 and 7 after the start of treatment with amikacin and p-value less than 0.05 was considered significant., Results: Among the 70 children, 61 patients were females and the others were males. Mean age was 42.66±41.53 months. Estimated GFR based on creatinine on day 0 (before amikacin administration), 3 and 7 were 72.41±20.89 ml/min/1.73 m 2 , 78.42±21.15 ml/min/1.73 m 2 and 80.5±22.43 ml/min/1.73 m 2 , respectively. Moreover, GFR based on cys-C during these days were 116.23±58.9 ml/min/1.73 m 2 , 116.49±53.31 ml/min/1.73 m 2 and 108.37±51.02 ml/min/1.73 m 2 , respectively (p<0.05)., Conclusions: According to this study, decrease of GFR calculation based on Cys-C was seen and estimated GFR was not changed according to creatinine. So, we recommend the use of cys-C for the monitoring of renal function in any patient treated with nephrotoxic drugs such as amikacin., Competing Interests: There was no conflict of interest.

Background: Human fibronectin extra-domain B (EDB) is particularly expressed during angiogenesis progression. It is, thus, a promising marker of tumour growth. Aptides are a novel class of peptides with high-affinity binding to specific protein targets. APTEDB is an antagonist-like ligand that especially interacts with human fibronectin EDB., Objective: This study was the first attempt in which the hydrazinonicotinamide (HYNIC)-conjugated APTEDB was labelled with technetium-99m (99mTc) as an appropriate radiotracer and tricine/EDDA exchange labeling., Methods: Radiochemical purity, normal saline, and serum stability were evaluated by HPLC and radio-isotope TLC scanner. Other examinations, such as protein-binding calculation, dissociation radioligand binding assay, and partition coefficient constant determination, were also carried out. The cellular-specific binding of 99mTc- HYNIC-conjugated APTEDB was assessed in two EDB-positive (U87MG) and EDB-negative (U373MG) cell lines. Bio-distribution was investigated in normal mice as well as in U87MG and U373MG tumour-bearing mice. Eventually, the radiolabelled APTEDB was used for tumour imaging using planar SPECT., Results: Radiolabelling was achieved with high purity (up to 97%) and accompanied by high solution (over 90% after overnight) and serum (80% after 2 hours) stability. The obtained cellular-specific binding ratio was greater than nine-fold. In-vivo experiments showed rapid blood clearance with mainly renal excretion and tumour uptake specificity (0.48±0.03% ID/g after 1h). The results of the imaging also confirmed considerable tumour uptake for EDB-positive cell line compared with the EDB-negative one., Conclusion: Aptides are considered to be a potent candidate for biopharmaceutical applications. They can be modified with imaging or therapeutic agents. This report shows the capability of 99mTc-HYNIC-APTEDB for human EDB-expressing tumours detection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Due to the high rate of drug resistance among malignant melanoma cases, it seems necessary to introduce an efficient pharmaceutical approach to melanoma treatment. For this purpose, Curcumin (Cur) and Chrysin (Chr), two natural anti-cancers, were co-encapsulated in PLGA-PEG nanoparticles (NPs), characterized by DLS, FTIR and FE-SEM and investigated for their effects on MMPs, TIMPs and TERT genes expression in C57B16 mice bearing B16F10 melanoma tumours. The results showed that the expression of MMP-9, MMP-2 and TERT genes were significantly decreased in all treated groups compared to the control. This reduction had the highest amount in CurChr NPs group and then CurChr group for each three genes. Likewise, the expression of TIMP-1 and TIMP-2 genes was significantly increased in all treated groups, compared to the control. Combination groups showed the highest rise in expression of these two genes and the observed increase was greater in nano groups. Moreover, the highest melanoma tumour growth inhibition was detected for CurChr NPs, followed by CurChr = Cur NPs > Cur > Chr NP > Chr. Overall, it is speculated that the nano-combination of Cur and Chr into polymeric NPs with a one-step fabricated co-delivery system may be a promising and convenient approach to improve their efficiency in melanoma cancer therapy.

Induction of thrombosis in tumor vasculature represents an appealing strategy for combating cancer. Herein, we combined unique intrinsic coagulation properties of staphylocoagulase with new acquired functional potentials introduced by genetic engineering, to generate a novel bi-functional fusion protein consisting of truncated coagulase (tCoa) bearing an RGD motif on its C-terminus for cancer therapy. We demonstrated that free coagulase failed to elicit any significant thrombotic activity. Conversely, RGD delivery of coagulase retained coagulase activity and afforded favorable interaction of fusion proteins with prothrombin and α v β 3 endothelial cell receptors, as verified by in silico, in vitro, and in vivo experiments. Although free coagulase elicited robust coagulase activity in vitro, only targeted coagulase (tCoa-RGD) was capable of producing extensive thrombosis, and subsequent infarction and massive necrosis of CT26 mouse colon, 4T1 mouse mammary and SKOV3 human ovarian tumors in mice. Additionally, systemic injections of lower doses of tCoa-RGD produced striking tumor growth inhibition of CT26, 4T1 and SKOV3 solid tumors in animals. Altogether, the nontoxic nature, unique shortcut mechanism, minimal effective dose, wide therapeutic window, efficient induction of thrombosis, local effects and susceptibility of human blood to coagulase suggest tCoa-RGD fusion proteins as a novel and promising anticancer therapy for human trials.

Background: Acute and chronic pain is prevalent in patients with opioid dependence. Lack of knowledge concerning the complex relationship between pain, opioid use, and withdrawal syndrome can account for the barriers encountered for pain management. This study was designed to evaluate the efficacy of sublingual (SL) buprenorphine for post-operative analgesia, compared with intravenous (IV) morphine., Methods: A total of 68 patients, aged 20-60 years were randomly selected from whom had been underwent laparotomy due to acute abdomen in a University Teaching Hospital in Arak, Iran, and were also opioid (opium or heroin) abuser according to their history. After end of the surgery and patients' arousal, the patients were evaluated for abdominal pain and withdrawal syndrome by visual analog scale (VAS) and clinical opioid withdrawal score (COWS), respectively 1, 6, and 24 h after the surgery. They received either morphine 5 mg IV or buprenorphine 2 mg SL, 1 h after end of the surgery, and then every 6 h for 24 h., Findings: VAS was 4.47 ± 0.73 and 2.67 ± 0.53 at h 6 and 24 in buprenorphine group, respectively. The corresponding score was 5.88 ± 0.69 and 4.59 ± 0.74 in morphine group. At the same time, patients in buprenorphine experienced less severe withdrawal syndrome., Conclusion: The present study confirmed the efficacy of SL buprenorphine as a non-invasive, but effective method for management of post-operative pain in opioid dependent patients. Result of this study showed that physicians can rely on SL buprenorphine for post-operative analgesia.