Anti-Mucin1 aptamer-conjugated chitosan nanoparticles for targeted co-delivery of docetaxel and IGF-1R siRNA to SKBR3 metastatic breast cancer cells

Background: Targeted co-delivery of siRNA and a chemotherapeutic drug is an attractive approach to cancer drug design and treatment. This study was carried out to design an anti-Mucin1 aptamer [Apt]-conjugated chitosan nanoparticle [NP] for targeted co-delivery of insulin-like growth factor receptor 1 [IGF-1R] Silencer siRNA and docetaxel [DTX] to SKBR3 cells

Methods: Characterization of nano-drugs, cellular uptake of NPs, cell viability, and gene expression studies were evaluated based on metastatic breast cancer cells

Results:The results of this study showed that NPs had spherical and smooth morphology with 110-118 nm in size and had positive zeta potential [12-14 mV]. siRNA and DTX were considerably loaded into NPs. The appropriate conjugation of the Apt to the NPs was affirmed by gel electrophoresis. The Apt-conjugated NPs were observed to enhance the cellular uptake of NPs into the SKBR3 cells. Although the combination treatment significantly decreased the cell viability of SKBR3 cells, the augmentative effect was observed when Apt was conjugated to NPs. Furthermore, Apt-conjugated NPs dramatically reduced the genetic expression of IGF-1R, signal transducers and activators of transcription 3 [STAT3], matrix metalloproteinases [MMP9], and vascular growth factor [VEGF]

Conclusion: The targeted NPs may augment the targeting of pathways involved in tumorigenesis and metastasis of breast cancer. Therefore, more animal model experiments are needed to further clarify the efficacy and safety of this functionalized nanodrug

Effects of hypoxia on biology of human leukemia T-cell line [MOLT-4 cells] Co-cultured with bone marrow mesenchymal stem cells

Background: One of the most significant problems in the treatment of leukemia is the expansion of resistance to chemotherapeutic agents. Therefore, assessing the drug resistance and especially the drug resistance genes of leukemic cells is important in any treatment. The impact of Mesenchymal Stem Cells [MSCs] and hypoxic condition have been observed in the biological performance of majority of leukemic cells

Methods: MOLT-4 cells were co-cultured with MSCs in the hypoxic condition induced by Cobalt Chloride [CoCl2] for 6 and 24 hr. Then, apoptosis of cells was analyzed using annexin-V/PI staining and expression of the drug resistance genes including MDR1, MRP, and BCRP along with apoptotic and anti-apoptotic genes, including BAX and BCL2, was evaluated by real-time PCR

Results: The hypoxic condition for MOLT-4 cells co-cultured with MSCs could significantly increase the expression of MDR1 and BCRP genes [p<0.05] which are involved in drug resistance. Also, the results indicated that this condition significantly increases the expression of BCL2 [p<0.05] and reduces the apoptosis in MOLT- 4 cells co-cultured with MSCs in the hypoxic condition

Conclusions: These effects can demonstrate the important role of hypoxia and MSCs on the biological behavior of Acute Lymphoblastic Leukemia [ALL] cells that may lead to particular treatment outcomes

role of M2000 as an anti-inflammatory agent in toll-like receptor 2/microRNA-155 pathway

Background: M2000 is a newly designed and safe Non-Steroidal Anti-Inflammatory Drug [NSAID]. The aim of this study was to assess the effects of M2000 on expression levels of Suppressor of Cytokine Signaling-1 [SOCS-1] and Src Homology-2 domain containing inositol-5'-phosphatase 1 [SHIP1] proteins via Toll-Like Receptor [TLR] 2/microRNA-155 pathway

Methods: HEK293 TLR2 cell line and Peripheral Blood Mononuclear Cells [PBMCs] were treated by different concentrations of M2000 in MTT assay. RNA was extracted by miRN easy Mini kit. Then, cDNA was synthesized and the expression levels of SOCS1, SHIP1 and miRNA155 were evaluated by Quantitative Real time PCR

Results: Our results showed that M2000 significantly increased the expression levels of SOCS1 and SHIP-1 in Lipopolysachride [LPS]-treated and non-treated cells. Moreover, M2000 decreased expression level of miR-155 in LPS treated PBMCs

Conclusion: M2000 can be used as NSAID in LPS induced inflammation and decrease inflammatory cytokines production by targeting SOCS1, SHIP1 and miR-155 in autoimmune and inflammatory diseases

Pulmonary Tuberculosis Diagnosis: Where We Are? / 결핵및호흡기질환

In recent years, in spite of medical advancement, tuberculosis (TB) remains a worldwide health problem. Although many laboratory methods have been developed to expedite the diagnosis of TB, delays in diagnosis remain a major problem in the clinical practice. Because of the slow growth rate of the causative agent Mycobacterium tuberculosis, isolation, identification, and drug susceptibility testing of this organism and other clinically important mycobacteria can take several weeks or longer. During the past several years, many methods have been developed for direct detection, species identification, and drug susceptibility testing of TB. A good understanding of the effectiveness and practical limitations of these methods is important to improve diagnosis. This review summarizes the currently-used advances in nonmolecular and molecular diagnostics.

Preliminary assessment of various additives on the specific reactivity of anti- rHBsAg monoclonal antibodies

Antibodies have a wide application in diagnosis and treatment. In order to maintain optimal stability of various functional parts of antibodies such as antigen binding sites, several approaches have been suggested. Using additives such as polysaccharides and polyols is one of the main methods in protecting antibodies against aggregation or degradation in the formulation. The aim of this study was to evaluate the protective effect of various additives on the specific reactivity of monoclonal antibodies [mAbs] against recombinant HBsAg [rHBsAg] epitopes. To estimate the protective effect of different additives on the stability of antibody against conformational epitopes [S3 antibody] and linear epitopes [S7 and S11 antibodies] of rHBsAg, heat shock at 37[degree]C was performed in liquid and solid phases. Environmental factors were considered to be constant. The specific reactivity of antibodies was evaluated using ELISA method. The data were analyzed using SPSS software by Mann-Whitney nonparametric test with the confidence interval of 95%. Our results showed that 0.25 M sucrose, 0.04 M trehalose and 0.5% BSA had the most protective effect on maintaining the reactivity of mAbs [S3] against conformational epitopes of rHBsAg. Results obtained from S7 and S11 mAbs against linear characteristics showed minor differences. The most efficient protective additives were 0.04 M trehalose and 1 M sucrose. Nowadays, application of appropriate additives is important for increasing the stability of antibodies. It was concluded that sucrose, trehalose and BSA have considerable effects on the specific reactivity of anti rHBsAg mAbs during long storage

Analysis of human B cell response to recombinant Leishmania LPG3

OBJECTIVE@#To evaluate the capability of recombinant Leishmania LPG3 and its fragments in the activation of B cells.@*METHODS@#In the present study, human B cells were purified from peripheral blood of 10 adult healthy subjects using magnetic-activated cell sorting technique. Subsequently, purified B cells were treated with recombinant LPG3, and its N-terminal and C-terminal fragments at different concentrations (2, 10 and 20 μg/mL). B cell activation was assessed through expression of CD69 molecule by flow cytometry and secretion of IL-6, TNF-α and IL-10 cytokines via enzyme-linked immunosorbent assay following treatment with recombinant antigens.@*RESULTS@#Our results showed that while the recombinant LPG-3 could significantly increase the production of IL-6 and TNF-α (P < 0.05) in B cells, it had no effect on the secretion of IL-10 by B cells.@*CONCLUSIONS@#Our study indicated that recombinant LPG-3 and especially its N-terminal fragment could stimulate B cell response as an important immune response component against leishmaniasis. Thus, it seems that it can be considered as an effective adjuvant in vaccine developments against leishmaniasis.

Analysis of human B cell response to recombinant Leishmania LPG3

Objective: To evaluate the capability of recombinant Leishmania LPG3 and its fragments in the activation of B cells. Methods: In the present study, human B cells were purified from peripheral blood of 10 adult healthy subjects using magnetic-activated cell sorting technique. Subsequently, purified B cells were treated with recombinant LPG3, and its N-terminal and C-terminal fragments at different concentrations (2, 10 and 20 μg/mL). B cell activation was assessed through expression of CD69 molecule by flow cytometry and secretion of IL-6, TNF-α and IL-10 cytokines via enzyme-linked immunosorbent assay following treatment with recombinant antigens. Results: Our results showed that while the recombinant LPG-3 could significantly increase the production of IL-6 and TNF-α (P < 0.05) in B cells, it had no effect on the secretion of IL-10 by B cells. Conclusions: Our study indicated that recombinant LPG-3 and especially its N-terminal fragment could stimulate B cell response as an important immune response component against leishmaniasis. Thus, it seems that it can be considered as an effective adjuvant in vaccine developments against leishmaniasis.

Household health costs: direct, indirect and intangible

Background: This study aimed at identifying components of the household health costs

Methods: This study was a qualitative research conducted in two main phases. The first phase consisted of interviews with sample households selected in eight provinces of Iran. They were to identify components of the household health costs. In the second phase, components were determined as direct, indirect and intangible based on a content analysis

Results: In the first phase of the study, 93 components of households' health costs were identified. According to the content analysis, 44 components were categorized as direct costs, 10 components were indirect and 39 components were categorized as intangible

Conclusion: All components of households' health costs including: direct, indirect and intangible costs, should be considered in the planning and policy-making in the health system

Is scores derived from the most internationally applied patient safety culture assessment tool correct?

Hospital Survey on Patient Safety Culture, known as HSOPS, is an internationally well known and widely used tool for measuring patient safety culture in hospitals. It includes 12 dimensions with positive and negative wording questions. The distribution of these questions in different dimensions is uneven and provides the risk of acquiescence bias. The aim of this study was to assess the questionnaire against this bias. Three hundred nurses were assigned into study and control groups randomly. Short form of HSOPS was distributed in the control group and totally reversed form of it was given to the study group. Percent positive scores and t-test were applied for data analysis. Statistical analyses were conducted using SPSS Version 16. Finally a total of 272 nurses completed the questionnaire. All dimensions with positive wording items in both groups had higher scores compared with their negative worded format. The first dimension "organizational learning and continued improvement" which had the only statistically significant difference, got 16.2% less score in the study group comparing the other group. In addition six out of 18 differences in questions were statistically significant. The popular and widely used HSOPS is subject to acquiescence bias. The bias might lead to exaggerate the status of some patient safety culture composites. Balancing the number of positive and negative worded items in each composite could mitigate the mentioned bias and provide a more valid estimation of different elements of patient safety culture