Aptasensors as a new sensing technology developed for the detection of MUC1 mucin: A review.

Mucin 1 protein (MUC1) is a membrane-associated glycoprotein overexpressed in the majority of human malignancies and considered as a predominant protein biomarker in cancers. Owing to the crucial role of MUC1 in cancer dissemination and metastasis, detection and quantification of this biomarker is of great importance in clinical diagnostics. Today, there exist a wide variety of strategies for the determination of various types of disease biomarkers, especially MUC1. In this regard, aptamers, as artificial single-stranded DNA or RNA oligonucleotides with catalytic and receptor properties, have drawn lots of attention for the development of biosensing platforms. So far, various sensitivity-enhancement techniques in combination with a broad range of smart nanomaterials have integrated into the design of novel aptamer-based biosensors (aptasensors) to improve detection limit and sensitivity of analyte determination. This review article provides a brief classification and description of the research progresses of aptamer-based biosensors and nanobiosensors for the detection and quantitative determination of MUC1 based on optical and electrochemical platforms.

The Effect of Estrogen Replacement Therapy on Visceral Fat, Serum Glucose, Lipid Profiles and Apelin Level in Ovariectomized Rats.

OBJECTIVES: Ovarian hormones have been shown to regulate body weight, intra-abdominal fat accumulation and plasma level of cytokines. The aim of this study was to investigate the effect of estrogen replacement therapy on visceral adipose tissue, plasma level of apelin, lipid profiles, and glucose in ovariectomized (OVX) rats. METHODS: Thirty female Wistar rats were divided into OVX (n = 20) and sham (n = 10) groups. OVX rats were subdivided into estrogen replacement therapy (OVX+est; n = 10) receiving 17 ß-estradiol valerates (30 µg/kg, s.c., 5 day/week, for eight weeks), and vehicle control group receiving sesame oil same as experiment group (OVX+ses oil; n = 10). After the treatments, all groups were sacrificed and blood samples were collected, visceral fats were taken from the abdominal cavity and weighed immediately. Apelin were measured using enzyme-linked immunosorbent assay kits. Lipid profiles and glucose were measured using the enzymatic colorimetric method. Data were analyzed with one-way analysis of variance and (P < 0.05) determined as the statistical significance level. RESULTS: After eight weeks, body weight, body mass index (BMI), visceral fat, apelin and lipid profiles (P < 0.01) were increased significantly in OVX rats compared to sham group. Treatment with estrogen leads to significant reduction in body weight and BMI (P < 0.05), there was no significant change in serum apelin level in OVX+est rats compared to OVX+ses. CONCLUSIONS: These results suggest that estradiol replacement therapy successfully attenuated some of the metabolic syndrome components, and apelin does not probably stand as a mediator of these physiological functions.

Generation and characterization of nanobodies targeting PSMA for molecular imaging of prostate cancer.

Nanobodies show attractive characteristics for tumor targeting in cancer diagnosis and therapy. A radiolabeled nanobody binding the prostate-specific membrane antigen (PSMA) could offer a noninvasive strategy to select prostate cancer patients eligible for PSMA-targeted therapies. We here describe the generation, production and in vivo evaluation of anti-PSMA nanobodies. Nanobodies were derived from heavy-chain-only antibodies, raised in immunized dromedaries. Binding characteristics were evaluated through ELISA and flow cytometry. Selected nanobodies were radiolabeled with (99m) Tc at their hexahistidine tail, after which cell binding capacity and internalization were evaluated on PSMA(pos) LNCaP and PSMA(neg) PC3 cell lines. In vivo tumor targeting was analyzed in both LNCaP and PC3 xenografted mice through SPECT/microCT and tissue sampling. A panel of 72 generated clones scored positive on ELISA, all contributing to three nanobody groups, of which group 3 dominated with 70 clones. ELISA and FACS analysis led to the selection of two dominant nanobodies. (99m) Tc-labeled PSMA6 and PSMA30 both showed specific binding on LNCAP cells, but not on PC3 cells. (99m) Tc-PSMA30 internalized significantly more in LNCaP cells compared to (99m) Tc-PSMA6. Higher absolute tumor uptake and tumor-to-normal organ ratios were observed for (99m) Tc-PSMA30 compared with (99m) Tc-PSMA6 and a (99m) Tc-control nanobody in LNCaP but not in PC3 tumor-bearing mice. PSMA30 nanobody has improved targeting characteristics both in vitro as well as in vivo compared with PSMA6 and the control nanobody, and was therefore selected as our in-house-developed lead compound for PSMA targeting.

Influence of aerobic training and detraining on serum BDNF, insulin resistance, and metabolic risk factors in middle-aged men diagnosed with metabolic syndrome.

OBJECTIVE: To study the influence of aerobic exercise training on brain-derived neurotrophic factor (BDNF), insulin resistance, and lipid profile in middle-aged men diagnosed with metabolic syndrome (MetS). DESIGN: This is an experimental repeated measure study. SETTING: Subjects participated in aerobic training programs (18 sessions of 25-40 minutes per session) in Guilan University gymnasium and court. PARTICIPANTS: A total of 21 middle-aged men (50-65 years old) diagnosed with MetS participated. INTERVENTIONS: We randomly divided 21 middle-aged men with MetS into exercise and control groups. The exercise group followed an aerobic training program (18 sessions, 3/wk) at 50% to 60% of V[Combining Dot Above]O2 peak (25-40 minutes per session) and 6 weeks of detraining. Blood samples were collected at baseline, end of the training, and detraining. MAIN OUTCOME MEASURES: High BDNF level in patients with MetS and its reduction after chronic aerobic exercise. RESULTS: Aerobic training significantly decreased all the metabolic risk factors, including overall MetS z score, insulin resistance, and lipid profile (P < 0.05). After the detraining period, plasma triglyceride, high-density lipoprotein, and also overall MetS z score remained unchanged (P < 0.05); however, serum BDNF, which was decreased by aerobic training (P = 0.013), restored to the baseline at the end of the detraining (P = 0.018). CONCLUSIONS: Improved metabolic risk factors along with decreased serum BDNF in response to aerobic training and the opposite direction during the detraining emphasize the importance of physical activity in the treatment of MetS and prevention of related diseases.

Long term habitual exercise is associated with lower resting level of serum BDNF.

This experiment has been designed to evaluate the basal serum BDNF level and memory performance, and also the change in BDNF in response to acute aerobic and anaerobic training in athletes and sedentary groups. Nineteen middle aged elite athletes (45-65 years) who used to be competing at domestic championship for more than 10 years and 20 sedentary subjects participated in this study. Blood samples and cognitive function were assessed at rest and also after performing a single bout of acute aerobic and anaerobic exercise. Basal serum BDNF significantly was lower in the athletes group compared to the control one (475.18±45.32, 1089.30±94.92, P=0.001). Serum BDNF was inversely correlated with Vo2 max (r=-0.5, P=0.013), but positively with BMI (r=0.2, p=0.4). Pictures recall memory was better in the athlete group (9.25±1.61) compared with the control ones (8±1.15, p=0.04). Basal platelets did not show any significant differences between athletes and controls (p>0.05). Both acute aerobic and anaerobic activity elevated serum BDNF and platelets in athletes and sedentary groups compared with rest (P<0.001). This study suggests that long-term habitual exercise is associated with lower peripheral BDNF and better intermediate memory. However acute form of intensive activity either aerobic or anaerobic are capable to elevate serum BDNF level in both sedentary and athletes.

Camel heavy chain antibodies against prostate-specific membrane antigen.

Prostate-specific membrane antigen (PSMA), a type II integral membrane glycoprotein, is highly overexpressed in all forms of prostate cancer tissues. It has also been demonstrated in a wide range of neovasculature of non-prostatic solid tumors, including bladder, pancreas, lung, kidney, colorectal, and gastric cancers. Given the unique expression of PSMA, it is considered an alluring target for antibody-based imaging and therapy of cancer. In the present study, the production and characterization of camel heavy chain antibodies (HCAbs) specific for the external domain of the PSMA are reported. Due to the absence of the CH1 domain, HCAbs are smaller than their counterparts in conventional antibodies. In this study, camel antibodies were generated through immunization of Camelus dromedarius with a synthetic 28 amino acid peptide corresponding to the external surface domain of antigen and PSMA-expressing cell lines. Different binding properties to protein A and protein G affinity columns were deployed to separate three subclasses of camel IgG. The affinity purified HCAbs bound selectively to the synthetic peptide in enzyme linked immunosorbent assay (ELISA) and reacted specifically with PSMA-expressing cell line through immunocytochemistry study. Currently, we are attempting to develop recombinant variable domain of these heavy chain antibodies (VHH or nanobody) for tumor imaging and cancer therapy.

Dopaminergic activity in the medial prefrontal cortex modulates fear conditioning.

The purpose of the present study was to determine the role of medial prefrontal cortex (mPFC) dopaminergic system in fear conditioning response considering individual differences. Animals were initially counterbalanced and classified based on open field test, and then were given a single infusion of the dopamine agonist, amphetamine (AMPH) and antagonist, clozapine (CLZ) into the medial prefrontal cortex. Rats received tone-shock pairing in a classical fear conditioning test and then exposed to the tone alone. Freezing responses were measured as conditioned fear index. The results showed that both AMPH and CLZ infusion in mPFC reduced the expression of conditioned fear. This finding indicates that elevation or reduction in the dopaminergic activity is associated with the decrease of fear responses, despite preexisting individual-typological differences.