Antinociceptive effect of [Met5]enkephalin semicarbazide is not affected by dipeptidyl carboxypeptidase‐I

Dipeptidyl carboxypeptidase‐I is an enzyme involved in the biological degradation of enkephalins. It has been suggested that C‐terminal amidation of enkephalins enhances their resistance to dipeptidyl carboxypeptidase‐I‐mediated biodegradation. In this study, a novel [Met5]enkephalin amide (MEA) analogue [Met5]enkephalin (ME)‐semicarbazide synthesized by another laboratory in our group was assessed for its antinociceptive effects compared with ME‐ethylamide, MEA and ME, using tail flick test. To protect the administered drugs from biodegradation, rats were pretreated with peptidase inhibitors including amastatin, phosphoramidon and captopril. Then captopril (dipeptidyl carboxypeptidase‐I inhibitor) was deleted from the peptidase inhibitors' combination for evaluating in vivo resistance of the synthetic drugs to dipeptidyl carboxypeptidase‐I. According to the results, ME‐semicarbazide and MEA were resistant enough to dipeptidyl carboxypeptidase‐I to exert their strong antinociception following intrathecal administration even in the absence of captopril, whereas the antinociceptive effects produced by ME‐ethylamide (10 nmol) were abolished in rats not pretreated with captopril, indicating that significant amounts of the ME‐ethylamide were degraded by dipeptidyl carboxypeptidase‐I. Replacement of the amide moiety of MEA with semicarbazide provides a new ME derivative, with high analgesic effects as well as more resistance to dipeptidyl carboxypeptidase‐I‐mediated biodegradation. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.     

Semicarbazide Substitution Enhances Enkephalins Resistance to Ace Induced Hydrolysis

In our previous study on [Met5]-enkephalin analogues, [Met5]-enkephalin semicarbazide was found as a new enkephalin amide that produces antinociception even in ACE (Angiotensin Converting Enzyme) exposure in vivo. In the present work we examined the corresponding [Leu5]-enkephalin derivatives to confirm the influence of semicarbazide substitution. To prevent the enkephalins biodegradation animals were pretreated with a mixture of peptidase inhibitors. As assessed by tail-flick test no significant difference was detected between the produced antinociception by the [Leu5]-enkephalin derivatives. Based on our results both semicarbazide and ethylamide groups could preserve the provided analgesia after captopril (ACE inhibitor) omission from the peptidase inhibitors mixture. This work confirms that semicarbazide substitution on enkephalins yields ACE resistance antinociceptive peptides, nevertheless it may necessarily not enhance the peptides analgesic potencies.     

Dietary Intake of Magnesium May Modulate Depression

Depressive symptoms are frequent in students and may lead to countless problems. Several hypotheses associate magnesium with depression because of the presence of this mineral in several enzymes, hormones, and neurotransmitters, which may play a key role in the pathological pathways of depression. The aim of this study was to assess whether magnesium intake could modulate depressive symptoms. A cross-sectional study was conducted on a convenience sample of 402 Iranian postgraduate students studying in Malaysia to assess the relationship between magnesium intake and depressive symptoms. The mean age of the participants was 32.54?±?6.22 years. The results of the study demonstrated an inverse relationship between magnesium intake and depressive symptoms, which persisted even after adjustments for sex, age, body mass index, monthly expenses, close friends, living on campus, smoking (current and former), education, physical activity, and marital status.     

The Absence of CD47 Promotes Nerve Fiber Growth from Cultured Ventral Mesencephalic Dopamine Neurons

In ventral mesencephalic organotypic tissue cultures, two timely separated sequences of nerve fiber growth have been observed. The first appearing nerve fiber pattern is a long-distance outgrowth that occurs before astrocytes start to proliferate and migrate to form an astrocytic monolayer that finally surrounds the tissue slice. These long-distance growing nerve fibers are retracted as the astrocytes migrate, and are followed by a secondary outgrowth. The secondary outgrowth is persistent in time but reaches short distances, comparable with outgrowth seen from a dopaminergic graft implanted to the brain. The present study was focused on the interaction between the astrocytes and the long-distance growing non-glial associated nerve fibers. Cross talk between astroglia and neurite formation might occur through the integrin-associated protein CD47. CD47 serves as a ligand for signal regulatory protein (SIRP) α and as a receptor for the extracellular matrix protein thrombospondin-1 (TSP-1). Embryonic day 14 ventral mesencephalic tissue from CD47^+/+ and CD47^−/− mice was used to investigate astrocytic migration and the tyrosine hydroxylase (TH) –positive outgrowth that occurred remote from the astrocytes. TH-immunohistochemistry demonstrated that the non-glial-associated nerve fiber outgrowth in CD47^−/− cultures reached significantly longer distances and higher density compared to nerve fibers formed in CD47^+/+ cultures at 14 days in vitro. These nerve fibers often had a dotted appearance in CD47^+/+ cultures. No difference in the astrocytic migration was observed. Further investigations revealed that the presence of CD47 in control culture did neither hamper non-glial-associated growth through SIRPα nor through TSP-1 since similar outgrowth was found in SIRPα mutant cultures and in CD47^+/+ cultures treated with blocking antibodies against the TSP-1, respectively, as in the control cultures. In conclusion, long-distance growing nerve fiber formation is promoted by the absence of CD47, even though the presence of astrocytes is not inhibited.     

Prediction of HCV load using genotype,liver biomarkers,and clinical symptoms by a mathematical model in patients with HCV infection

Hepatitis C virus (HCV) infection is a major public health problem with about 1.75 million new HCV cases and 71 million chronic HCV infections worldwide. The study aimed to evaluate clinical, serological, molecular, and liver markers to develop a mathematical predictive model for the quantification of the HCV viral load in chronic HCV infected patients. In this cross‐sectional study, blood samples were taken from 249 recently diagnosed HCV‐infected subjects and were tested for liver condition, viral genotype, and HCV RNA load. Receiver operating characteristics (ROC) curves and multiple linear regression analysis were used to predict the HCV‐RNA load. Genotype 3 followed by genotype 1 were the most prevalent genotypes in Mashhad, Northeastern Iran. The maximum levels of viral load were detected in the mixed genotype group, and the lowest levels in the undetectable genotype group. The log of the HCV viral load was significantly associated with thrombocytopenia and higher serum levels of alanine transaminase (ALT). In addition, the log HCV RNA was significantly higher in patients with arthralgia, fatigue, fever, vomiting, or dizziness. Moreover, genotype 3 was significantly associated with icterus. A ROC curve analysis revealed that the best cut‐off points for serum levels of aspartate aminotransferase (AST), ALT, and alkaline phosphatase (ALP) were >31, >34, and ≤246 IU/L, respectively. Sensitivity, specificity, and positive predictive values for AST were 87.7%, 84.36%, and 44.6%, for ALT they were 83.51%, 81.11%, and 36%, and for ALP were 72.06%, 42.81%, and 8.3%, respectively. A mathematical regression model was developed that could estimate the HCV‐RNA load. Regression model: log viral load = 7.69 ? 1.01 × G3 ? 0.7 × G1 + 0.002 × ALT ? 0.86 × fatigue.     

Deep and intermediate complex morphophysiological dormancy in seeds of Ferula gummosa (Apiaceae)

We tested the hypothesis that seeds of the monocarpic perennial Ferula gummosa from the Mediterranean area and central Asia have deep complex morphophysiological dormancy. We determined the water permeability of seeds, embryo morphology, temperature requirements for embryo growth and seed germination and responses of seeds to warm and cold stratification and to different concentrations of GA₃. The embryo has differentiated organs, but it is small (underdeveloped) and must grow inside the seed, reaching a critical embryo length, seed length ratio of 0.65–0.7, before the seed can germinate. Seeds required 9 weeks of cold stratification at <10°C for embryo growth, dormancy break and germination to occur. Thus, seeds have morphophysiological dormancy (MPD). Furthermore, GA₃ improved the germination percentage and rate at 5°C and promoted 20 and 5% germination of seeds incubated at 15 and 20°C, respectively. Thus, about 20% of the seeds had intermediate complex MPD. For the other seeds in the seed lot, cold stratification (5°C) was the only requirement for dormancy break and germination and GA₃ could not substitute for cold stratification. Thus, about 80% of the seeds had deep complex MPD.     

The role of miR-34 in cancer drug resistance

Resistance to conventional chemotherapy remains a major cause of cancer relapse and cancer-related deaths. Therefore, there is an urgent need to overcome resistance barriers. To improve cancer treatment approaches, it is critical to elucidate the basic mechanisms underlying drug resistance. Increasingly, the mechanisms involving micro-RNAs (miRNAs) are studied because miRNAs are also considered practical therapeutic options due to high degrees of specificity, efficacy, and accuracy, as well as their ability to target multiple genes at the same time. Years of research have firmly established miR-34 as a key tumor suppressor miRNA whose target genes are involved in drug resistance mechanisms. Indeed, numerous articles show that low levels of circulating miR-34 or tumor-specific miR-34 expression are associated with poor response to chemotherapy. In addition, elevation of inherently low miR-34 levels in resistant cancer cells effectively restores sensitivity to chemotherapeutic agents. Here, we review this literature, also highlighting some contradictory observations. In addition, we discuss the potential utility of miR-34 expression as a predictive biomarker for chemotherapeutic drug response. Although caution needs to be exercised, miR-34 is emerging as a biomarker that could improve cancer precision medicine.     

Immobilization of <Emphasis Type="Italic">Pseudomonas putida</Emphasis> PT in resistant matrices to environmental stresses: a strategy for continuous removal of heavy metals under extreme conditions

The purpose of this study was to investigate the potential of immobilized lead- and cadmium-resistant Pseudomonas putida strain PT to remove heavy metals from aqueous medium under extreme conditions. The tolerance and accumulation of cadmium and lead ions by strain PT were investigated by minimal inhibitory concentration (MIC) determination and polymerase chain reaction (PCR) of cadA gene, respectively. The surface chemical functional groups of P. putida PT involved in the metal biosorption were identified by Fourier transform infrared (FTIR). Pseudomonas putida PT was immobilized in three matrices include carboxy-methyl cellulose (CMC), rice bran, and a new composite made of alginate, polyvinyl alcohol (PVA), and CaCO₃ to prepare heavy metal adsorbent. The biosorbents were analyzed by SEM, and their metal removal capability was assayed in two consecutive cycles by atomic absorption spectroscopy. The viability of immobilized bacterial cells was determined by flow cytometry during storage at 4 °C and exposure to the environmental stresses (pH and temperature). The results showed that PT strain was resistant up to 10 mM Pb²⁺ and 8 mM Cd²⁺. FTIR analysis revealed that alcohol, sulfur, phosphate, esters, and amide groups played important roles in metal biosorption process and, also change in metabolic reactions like hydration and polyesters accumulation was observed after metal biosorption. The presence of cadA gene, a heavy metal translocating pump-coding gene, indicated the ability of metals bioaccumulation by the PT strain. Immobilized cells in alginate–PVA–CaCO₃ and rice bran showed the highest metal removal efficiency for Pb²⁺ as 75% and Cd²⁺ as 96.7%, respectively. Metal adsorbents were reusable, and the highest removal efficiency in the second cycle was observed in inoculated alginate–PVA–CaCO₃ (79.5% Pb²⁺ and 45% Cd²⁺). Flow cytometric analysis represented that the immobilized cell viability was retained (<?97%) after 4 weeks storage at 4 °C. Viability under two environmental stresses in all matrices was as follows: <?96% at 25 °C, <?87% at 45 °C, <?85% at pH 4,?<?96% at pH 7, and?<?89% at pH 11. The results signify that these metal adsorbents are efficient technological tools for bioremediation even in harsh environmental conditions.     

Carbon Quantum Dots as Multi-Purpose Nanomaterial in Stem Cell Therapy

During stem cell therapy, some issues, such as obscure fate of stem cells or their low survival rate in the body, should be addressed to boost their therapeutic efficiency. Nanotechnology offers a suitable solution to combat such limitations. Carbon quantum dots (CQDs) are carbon-based nanomaterials and may be used as multi-purpose compounds in stem cell therapy. CQDs are excellent choices for stem cell labeling thanks to their special features such as optical properties and good biocompatibility. Besides, they can modulate the biological function of stem cells, such as their proliferation, homing ability, and differentiation properties. Considering the charismatic feature of CQDs and their broad unique effect on stem cells, the current review aims to summarize the most advancements in this field. Hence, we first focused on CQDs synthesis and their applications. In the next section, the stem cell categories will be discussed, and the final part is dedicated to the recent research evaluating the impact of CQDs on stem cell therapy.