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The present study aimed to explore the associations between the expression pattern of molecules in the Notch pathway in the cumulus cells of polycystic ovary syndrome (PCOS) patients and the quality of zygotes and embryos. A total of 200 cumulus complexes surrounding mature oocytes were obtained from 40 patients with and without PCOS undergoing intracytoplasmic sperm injection (ICSI). The expressions of Notch-1, Notch-2, and Notch-3 genes were examined by Reverse Transcription Q-PCR assay. Moreover, immunocytochemistry was performed for the expressions of Jagged-1 and Jagged-2 proteins. The correlations between the Notch receptors and their ligand expressions and the qualities of the zygote and embryo were investigated. The expression levels of Notch-2, Notch-3, Jagged-1, and Jagged-2 were significantly lower in patients with PCOS than in normal women (p

Efficacy of chemotherapy is limited by the resistance of cancer cells. Phytochemicals especially Essential Oils (EOs) provide an alternative mode of cancer therapy. However, EOs utilization is restricted because of low bioavailability, and high degradation. Nanoemulsification is a method developed to overcome these obstacles. Accordingly, Citrus-Pectin nanoemulsion of Zataria Essential Oil (CP/ZEONE) was prepared to evaluate the anticancer activity and the mechanisms responsible for the caused cytotoxicity. Physical properties and FTIR spectra of CP/ZEONE were characterized. CP/ZEONE progressively improves the suppression of viability of drug-resistant MCF-7, MDA-MB-231 breast cancer cells, and spheroids. It triggers apoptosis by increasing Reactive Oxygen Species (ROS), mitochondrial membrane potential (MMP) loss, DNA damage, G2 and S-phase arrest in MDA-MB-231 cells and spheroids respectively. Additionally, spectroscopy techniques revealed the interaction of CP/ZEONE with DNA via the formation of a groove binding/partial intercalative complex. Thus, ZEO-loaded CP Nano-particles can be further explored as a promising antiproliferative and therapeutic candidate against cancer.

Senile lentigines (SLs) are hyperpigmented macules that predominantly affect the elderly. We aimed to compare the efficacy and safety of hydrogen peroxide35% solution with cryotherapy in the treatment of SLs.This clinical trial included 33 patients with SLs referred to our center. Lesions of each side of the body were randomly allocated to receive 3 sessions of treatment with hydrogen peroxide or cryotherapy at a three-week interval. All patients were followed up 1 week after each round of treatment for the evaluation of side effects, the general effect of the treatment, and the general assessment of response to treatment.Thirty-three patients were included in this study with the mean age of 61.79 ± 4.59 years. Average and excellent effects were significantly higher with cryotherapy after the 2Cryotherapy appears to be more efficacious for the treatment of SLs compared to hydrogen peroxide 35% solution; however, hydrogen peroxide seems to have fewer side effects.

Background: Sore throat, cough and hoarseness after tracheal extubation are common complications after surgery. Due to the proven effect of dexamethasone on reducing these complications, in this study, we compared the prophylactic effect of intravenous dexamethasone and dexamethasone gargle on sore throat and cough after extubation. Methods: In this clinical trial study, 96 patients between the ages of 18-64 years who underwent elective surgery and intubation under general anesthesia were randomly divided into three groups, respectively, the first group received 6 mg dexamethasone gargle. The second group received 6 mg intravenous dexamethasone and the third group received normal saline. The frequency of cough and sore throat were assessed and compared in these three groups. Results: There was no significant difference between the three groups based on hemodynamic variables and demographic data (P> 0.05). The frequency of cough in the first (1.54± 2.82) and second (1.57±2.73) groups was less than the third group (1.79±3.14), but this difference was not statistically significant (P>0.66). The mean severity of sore throat in the second group and then in the first group was lower at the time of entry into recovery and 2 hours after surgery, than the third group. (P

The present study aimed to explore the associations between the expression pattern of molecules in the Notch pathway in the cumulus cells of polycystic ovary syndrome (PCOS) patients and the quality of zygotes and embryos.A total of 200 cumulus complexes surrounding mature oocytes were obtained from 40 patients with and without PCOS undergoing intracytoplasmic sperm injection (ICSI). The expressions of Notch-1, Notch-2, and Notch-3 genes were examined by Reverse Transcription Q-PCR assay. Moreover, immunocytochemistry was performed for the expressions of Jagged-1 and Jagged-2 proteins. The correlations between the Notch receptors and their ligand expressions and the qualities of the zygote and embryo were investigated.The expression levels of Notch-2, Notch-3, Jagged-1, and Jagged-2 were significantly lower in patients with PCOS than in normal women (p 0.05), while Notch-1 showed no meaningful difference between the groups. A positive correlation was found between Notch-1 and embryo quality. Furthermore, only Notch-2 and Jagged-2 marginally correlated with zygote quality.The data of the present study indicated that evaluating the molecules in the Notch pathway in PCOS patients' cumulus cells provides a novel approach to predict the zygote and embryo quality. However, further studies on a larger population are needed to validate this finding.

Theranostics with the ability to simultaneous monitoring of treatment progress and controlled delivery of therapeutic agents has become as an emerging therapeutic paradigm in cancer therapy. In this study, we have developed a novel surface functionalized iron oxide nanoparticle using polyethyleneimine and glutathione for targeted curcumin (CUR) delivery and acceptable pH sensitive character. The developed magnetic nanoparticles (MNPs) were physicochemically characterized by FT-IR, XRD, FE-SEM and TEM. The MNPs was obtained in spherical shape with diameter of 50 nm. CUR was efficiently loaded into the MNPs and then in vitro release analyses were evaluated and showed that the prepared MNPs could release higher amount of CUR in acidic medium compared to neutral medium due to the pH sensitive property of the coated polymer. MTT assay confirmed the superior toxicity of CUR loaded MNPs compared to the control nanoparticles. Higher cellular uptake of the MNPs than negative control cells was demonstrated in SK-N-MC cell line. In vitro assessment of MRI properties showed that synthesized MNPs could be used as MRI imaging agent. Furthermore, according to hemolysis assay, the developed formulation exhibited suitable hemocompatibility. In vivo blood circulation analysis of the MNPs also exhibited enhanced serum bioavailability up to 2.5 fold for CUR loaded MNPs compared with free CUR.

Chitosan (CS) is a semi-synthetic bio-based polysaccharide with promising biological and antitumor properties. However, its possible underlying anticancer mechanisms and molecular interactions have remained largely unknown. Herein, we have shown that CS exerts an inhibitory effect on the proliferation of MDA-MB-231, MCF-7 and T47D breast cancer cells in a dose and time-dependent manner while being non-toxic to fibroblast L929 normal cells. Exposure of MDA-MB-231 cells to CS led to depolarization of the mitochondrial membrane, increase in ROS, DNA oxidation, and S phase cell cycle arrest. Furthermore, EB/AO staining, Annexin–PI staining, TUNEL assay, and altered expression of caspase 3 in MDA-MB-231 cells all indicated that cancer cells progressively became apoptotic upon CS exposure. S phase arrest in MDA-MB-231 cells suggests possible CS–DNA interaction. UV-visible spectroscopy confirmed CS interaction with DNA, and competitive displacement fluorescence assay revealed a binding constant of 7.6 × 105 M−1 for CS. In addition, its binding modes with DNA were established by CD analysis. These results clearly indicate that along with being a safe biopolymer to normal cells, CS can be considered as an effectual anticancer agent.

Mashhad plain is an area with a dry-to-semi-dry climate in Razavi Khorasan Province, Iran. About 60% of 6 million population of the province live in this plain, and mainly in Mashhad city. Overexploitation of ground water during the past decades has led to a severe drop in groundwater table and land subsidence. In this respect, some parts of the plain show an annual groundwater-level decline of 1.5 m. The surface subsidence features such as rising of the well casing, well collapse, and tension cracks observed in different parts of the area. Studying of ENVISAT ASAR images in a period of 2003/06/30 to 2010/05/24 shows the maximum subsidence rate of 32 cm/year in the north-west of the Mashhad city, but there was a mismatch between groundwater drop and ground subsidence in some parts of the plain. The evaluation of geological characteristics of subsidence area reveals, in addition to the groundwater decline, tectonic condition and active faults which change the bedrock depth have a key role in the pattern and rate of subsidence. Also, consolidation of the Pleistocene marl bedrock located in the central part of the plain is effective in the increased subsidence rate of the study area.

DNA targeting anticancer agents have been very successful in clinic, especially, when used in combinatorial therapy. But unfortunately, they often exhibit high levels of toxicity towards normal cells. Hence, much effort has been put into finding agents with more selectivity, and less toxicity. Pectins are natural polysaccharides, and beneficial nutritional fibers that have attracted attentions due to their antitumor properties. However, their molecular targets, and mechanism of action are widely unknown. Here, we have reported that citrus pectin (CP) and apple pectin (AP) selectively suppress viability in MDA-MB-231, MCF-7 and T47D human Breast cancer cells, while non-toxic to L929 normal cells. Upon CP, and AP treatments, cancer cells’ ROS content increased rapidly, and led to the collapse of the mitochondrial transmembrane potential which functions upstream of the caspase-dependent apoptosis. CP and AP treated cancer cells were also arrested at the S and G1 or G2/M phases of the cell cycle, respectively. Furthermore, mRNA expression of Galectin-3 (a multi-functional lectin involved in cell adhesion, cell cycle, and apoptosis) reduced in both CP and AP treated cells. Growth inhibition of MDA-MB-231 cells by CP, and AP was concomitant with DNA damage (oxidation, and strand breaks). In this context, in an effort to clarify the mechanism of action, we showed that CP, and AP are able to interact with DNA. The strength and mode of DNA binding were established by spectroscopy techniques. We demonstrated that CP, and AP bind to dsDNA by intercalation, and groove binding/partial intercalation, respectively. In conclusion, our findings suggest that CP, and AP induce apoptosis in MDA-MB-231 cells by increasing the release of ROS, which may be related to the mitochondrial apoptosis pathway, and direct interactions with DNA. Our data indicate that these compounds may be potentially useful in cancer treatment.

Theranostics with the ability to simultaneous monitoring of treatment progress and controlled delivery of therapeutic agents has become as an emerging therapeutic paradigm in cancer therapy. In this study, we have developed a novel surface functionalized iron oxide nanoparticle using polyethyleneimine and glutathione for targeted curcumin (CUR) delivery and acceptable pH sensitive character. The developed magnetic nanoparticles (MNPs) were physicochemically characterized by FT-IR, XRD, FE-SEM and TEM. The MNPs was obtained in spherical shape with diameter of 50 nm. CUR was efficiently loaded into the MNPs and then in vitro release analyses were evaluated and showed that the prepared MNPs could release higher amount of CUR in acidic medium compared to neutral medium due to the pH sensitive property of the coated polymer. MTT assay confirmed the superior toxicity of CUR loaded MNPs compared to the control nanoparticles. Higher cellular uptake of the MNPs than negative control cells was demonstrated in SK-N-MC cell line. In vitro assessment of MRI properties showed that synthesized MNPs could be used as MRI imaging agent. Furthermore, according to hemolysis assay, the developed formulation exhibited suitable hemocompatibility. In vivo blood circulation analysis of the MNPs also exhibited enhanced serum bioavailability up to 2.5 fold for CUR loaded MNPs compared with free CUR.

Brucellosis is still one of the most common causes of fever of unknown origin (FUO) in endemic areas and is associated with several complications. Here, we report a patient with a diagnosis of brucellosis and FUO who developed a rare complication of vestibulopathy in the course of treatment and follow-up. We treated the vestibulopathy with acupuncture, and during 10 days of treatment, the irreversible complication of vestibulopathy disappeared. To the best of our knowledge, this is the first case report of brucellosis with vestibulopathy treated with traditional medicine that achieved complete improvement within 10 days.

Biocompatible multi-layer iron oxide magnetic nanoparticles (MNPs) for drug delivery applications with increased loading capacity, sustained sensitive release profile, and high inherent magnetic properties as well as improved cellular uptake were prepared. In this approach, Fe3O4 MNPs were obtained by a co-precipitation method and functionalized using hydroxyapatite (HAP) and/or polyethyleneimine (PEI). They were then modified with β-cyclodextrin (CD) to increase their loading capacity. These MNPs allowed suitable encapsulation of hydrophobic curcumin (CUR) in the CD shell and CUR adsorption into the polymeric layers. The dissolution profile of CUR showed pH sensitive release of CUR. The protein corona pattern of the MNPs by electrophoresis showed lower protein adsorption for CD modified MNPs than for other MNPs. No significant toxicity was observed for the target MNPs, whereas the CUR loaded MNPs inhibited MCF-7 breast cancer cells more efficiently than free CUR. Moreover, the negligible hemolytic activity of the target MNPs showed their excellent haemocompatibility for cancer treatment. The preferential uptake of the drug by MCF-7 cells was observed for CUR loaded MNPs in comparison with free CUR using flow cytometric analysis. As a result, the designed and prepared MNPs can be considered to be a promising CUR delivery platform.

Recognizing new anticancer compounds to improve Breast cancer treatment seems crucial. Essential oil of Zataria Multiflora (ZEO) is a secondary metabolite with some biological properties, yet underlying cellular and molecular anticancer properties of ZEO is unclear. GC/MS analysis revealed that carvacrol is the major ingredient of the essential oil. ZEO increasingly suppressed viability in MDA-MB-231, MCF-7 and T47D Breast cancer cells while nontoxic to L929 normal cells in monolayer cell cultures (2D), whereas MDA-MB-231 multicellular spheroids (3D) were more resistant to inhibition. ZEO significantly induced cell apoptosis confirmed by fluorescent staining, flow cytometry analysis and DNA fragmentation in MDA-MB-231 2D and 3D cell cultures. ZEO increased ROS generation and subsequent loss of ΔΨm, caspase 3 activation and DNA damage which consequently caused G1 and G2/M cell cycle arrest in a dose- and time-dependent manner in 2D. S phase arrest occurred in cell spheroids therefore ZEO possible DNA interaction with gDNA was investigated and revealed ZEO binds DNA via intercalation. Altogether, these data corroborate anticancer properties of ZEO and suggest that cell culture format (2D monolayer vs. 3D spheroid) plays a critical role in drug response and provides new insights into the mechanisms underlying ZEO cytotoxicity effect on Breast cancer cells.

A series of 7H-benzo[7,8]chromeno[2,3-d]pyrimidin-8-amines 6a-t were synthesized as new potential antiproliferative agents. The in vitro antiproliferative activity evaluation of title compounds using MTT assay revealed that most compounds showed significant activity against tested cancer cell lines (A549, MOLT-4, and HeLa). The 2-fluoro-aniline derivatives 6e and 6l were the most active compounds against A549 and MOLT-4 cells, respectively. The benzylamine analog 6h showed superior activity against HeLa cells. However, compound 6l with IC50 values of 5.2–6.9 μM had the best profile of activity against all tested cell lines. The morphological and flow cytometric analyses showed that compound 6l can induce apoptosis in the MOLT-4 cells.

Pro-apoptotic peptides induce intrinsic apoptosis pathway in cancer cells. However, poor cellular penetration of the peptides is often associated with limited therapeutic efficacy. In this report, a series of peptide-gold nanoparticle platforms were developed to evaluate the anticancer activity of a novel alpha-lipoic acid-peptide conjugate, LA-WKRAKLAK, with respect to size and shape of nanoparticles. Gold nanoparticles (AuNPs) were found to enhance cell internalization as well as anticancer activity of the peptide conjugates. The smaller nanospheres showed a higher cytotoxicity, morphological change and cellular uptake compared to larger nanospheres and nanorods, whereas nanorods showed more hemolytic activity compared to nanospheres. The findings suggested that the anticancer and biological effects of the peptides induced by intrinsic apoptotic pathway were tuned by peptide-functionalized gold nanoparticles (P-AuNPs) as a function of their size and shape.