Short Tandem Repeats (STRs) are defined as short lengths of 2-7 base pairs spreading through human genome which due to their highly diverse individually distribution are widely applied for identity detection and other forensic medicine purposes. Burdening considerable costs by the conventional methods such as capillary electrophoresis, we aimed to compare concomitant usage of multiplex PCR and denaturing high-performance liquid chromatography (DHPLC) as cheap, fast, highly accurate, and more accessible methods, with capillary electrophoresis (CE) to evaluate their potential for early screening of STRs.The present study randomly included 20 blood samples from the subjects referred to forensic medicine of Semnan, Iran. According to the size and allele frequency, we selected 8 major STR loci including CSF1PO, VWA, D18S51, TPOX, Amelogenin, FGA, SE33, and Penta D. A quad-STR multiplex PCR was performed for each locus and the PCR products were then analyzed using DHPLC machine and compared with the basic genetic properties obtained by capillary electrophoresis.By optimizing the PCR and DHPLC conditions, our findings suggest this strategy as an effective method for STR detection. The genotypes were determined using size of loci which led to comparable results with capillary electrophoresis confirming an insignificant variation in the detection of TOPX, Amelogenin, CSF1PO, and D18S5 (p = 0.331), but discrepant results for FGA and VWA loci (p = 0.002).Our study proposed DHPLC method as an effective screening method to characterize TOPX, Amelogenin, CSF1PO, and D18S51 as frequently used STR loci during identity detection in forensic medicine.
In the present work, we have studied a new allotrope of graphene, denoted as T-graphene (TG) flake as a versatile material in hydrogen storage. Recently, the metallic character of TG has been revealed. Our results show that the Li-decoration has a significant effect on the electronic properties of TG flake. Our density functional theory (DFT) calculations exhibit that the energy band gap of TG flake is decreased by decorating of the Li atom. Hydrogen adsorption on Li-decorated TG flake (Li/TG) under the influence of different external electric fields (EFs) is also explored by DFT calculations. We found that the hydrogen adsorption on the Li/TG increases when the positive EF is applied. Our results also show that the adsorption energy of the hydrogen on the Li/TG can be gradually enhanced by increasing the applied positive external EF along with the charge transfer direction. Moreover, Li atom in the Li/TG shows the high hydrogen capacity up to six H
The emergence of antibiotic resistance has attracted the attention of scientists and scientific circles over the decades. β-Lactam antibiotics resistance is a worldwide therapeutic challenge in bacterial infections, mediated through several mechanisms of which mutations in Penicillin Binding Proteins (PBPs) are an important issue, making critical therapeutic problems in the human population. Accordingly, investigating the dynamic structures of mutant variants could result in a profound understanding of such a specific resistance. Therefore, this work investigated structural properties sampled by all-atom molecular dynamics (MD) simulations, umbrella sampling, and binding free energy calculations for both a wild-type and a cefotaxime-resistant T to S mutant of PBP1A. The T to S mutation significantly reduces the binding affinity of cefotaxime (a frequently clinically-administrated β-lactam antibiotic) as the PBP1A inhibitor. In the conventional MD simulations presented here, more fluctuations of the mutant's active site cleft margins were detected. The cleft of the mutant protein also opened remarkably more than the wild-type's cleft and displayed more flexibility. Thus, our findings have shown that flexibility of cleft margins of the active site in the mutant PBP1A immediately results in the catalytic cleft opening. In addition, binding free energy calculation suggests that reducing hydrophobic contacts and increasing the polar contribution in the binding energy may play an important role in cefotaxime resistance.
This study reports a colorimetric sensor with excellent sensitivity to detect Cefixime base on gold nanoparticles. Cefixime is an antibiotic which has a wide range of applications in medicine. Cefixime did not change the surface plasmon resonance bond in gold nanoparticles solution; therefore, there was no change in the color solution of gold nanoparticles. The presence of Alizarin Red S in the system was necessary for the degradation of Cefixime, resulting in the aggregation of gold nanoparticles and a color change from red to blue. As a result of aggregation, the localized surface plasmon resonance band of gold nanoparticles decreased to around 525 nm and a new red-shifted band at 640 nm appeared which increases gradually as the function of Cefixime concentration. A unique detection limit (2.5 ng mL
Curcuma longa L., its derived extracts and even its major compound curcumin has a long history of use and doubtless effectiveness, reported through increasingly detailed in vitro, ex vivo, in vivo and even clinical trials. Regarding its biological effects, multiple health-promoting, disease-preventing and even treatment attributes has been remarkably highlighted. Clinical trials, although have increased in a progressive manner, significant disproportionalities have been stated in terms of biological effects assessment. In this sense, the present report aims to provide an extensive overview to curcumin therapeutic effects in human subjects. For that, clinical trials assessing the curcumin effect on inflammation, skin, eye, central nervous system, respiratory, cardiovascular, gastrointestinal, urogenital and metabolic disorders are here presented and discussed. A special emphasis was also given to curcumin activity on intoxications and multiple malignant diseases.
To evaluate the effect of double stimulations during the follicular and luteal phases in women with poor ovarian response (POR) in in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles.This prospective clinical study was performed in Royan Institute from October 2014 to January 2016. 121 patients were diagnosed as POR on the basis of Bologna criteria were included. Double stimulations were performed during the follicular and luteal phases by Letrozole, Clomid, hMG and GnRH-agonist. The patients' present cycle outcomes were compared with those of the previous cycle results using appropriate statistical tests.The total of 104 (85.9%) patients completed the stimulation stages. The analysis revealed the number of retrieved oocytes after the first and second stimulations did not differ (P = 0.2); however, the fertilization rate and the number of frozen embryos after the first stimulation were significantly higher than those of in the second stimulation (P < 0.001 and P = 0.03), indicating the better quality of retrieved oocytes after the first stimulation. The mean number of MII oocytes and the fertilization rate after Shanghai protocol were higher than those of the previous antagonist protocol with a substantial trend toward significance (P = 0.06), which can be clinically important. The cancellation rate (33%) due to no ovarian response and no embryo formation was still high in these patients.Since the intensity of stimulation in both stages was mild, this protocol can be considered a time-efficient and patient friendly regime; however, more studies are required with emphasis on its cost-effectiveness.
Given the multifactorial state of autoimmune complex diseases such as multiple sclerosis (MS), it is not clear if different risk factors act jointly or independently. Despite intensive studies investigating multi aspects of MS risk factors, findings with regards to potential biomarkers that may link these risk factors remained largely inconclusive. System biology or data integration utilizes different validated datasets to extract meaningful information and map the plausible biological pathways and networks. As such, we integrated eight transcriptome datasets to find the differentially expressed miRNAs in peripheral blood (PB) between relapsing remitting MS patients (RRMS) and normal group. After identification the targeted genes of miRNAs, the hub genes were used to construct the underlying protein-protein interaction network and signaling pathways. As results, 9 miRNAs were best exemplified by significant dysregulation including hsa-mir-15a, hsa-mir-484, hsa-mir-30d, hsa-mir-145, hsa-mir-363, has-let-7e, hsa-mir-30a, hsa-let-7b, and hsa-mir-146a. System biology analysis of miRNAs in PB of RRMS patients clearly indicates the involvement of miRNAs in many vital pathways and highlighted the possibility of an association between miRNAs with EBV and vitamin D in MS pathogenesis. Described novel pathways and genes related to miRNAs such as Transient receptor potential channels and Acid sphingomyelinase may provide a potential target for therapeutic approaches although further functional studies are warranted to test these candidates.
Fat-tailed sheep breeds can tolerate periods of negative energy balance without suffering from elevated concentration of plasma non-esterified fatty acid (NEFA). This ability was attributed to unique metabolism of fat-tailed adipose depot, whereas role of liver as an influential organ in fatty acid metabolism was not evaluated yet. Hence, current study was conducted to evaluate the effects of negative and positive energy balances on liver expression of genes related to fatty acid metabolism in fat-tailed and thin-tailed lambs. Lambs experienced negative (21 days) and positive (21 days) energy balances and were slaughtered at the beginning and end of negative energy balance and at the end of positive energy balance. Real-time quantitative polymerase chain reaction (RT-Q-PCR) was conducted to evaluate changes in gene expression. Expression of diglyceride acyltransferase 1 (DGAT1), 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) and apolipoprotein B (APOB) was not affected by genotype, energy balance and their interaction. Expression of carnitine palmitoyltransferase 1 (CPT1) was significantly higher in liver of fat-tailed comparing to thin-tailed lambs regardless of energy balance (p < 0.02). Catalase mRNA abundance was increased in response to negative energy balance (p < 0.02), and severity of this enhancement was higher in fat-tailed lambs (p < 0.06). Expression of CPT1 was positively correlated with expression of HMGCS2 in both fat-tailed (p < 0.05) and thin-tailed lambs (p < 0.002); however, the correlation was weaker in fat-tailed lambs (0.72 vs. 0.57, respectively, for thin-tailed and fat-tailed lambs). There was a positive correlation between DGAT1 and APOB genes expression in fat-tailed lambs (0.94; p < 0.001), whereas this correlation was not observed in thin-tailed lambs. Results demonstrate that liver of fat-tailed lambs has higher capacity for metabolism of mobilized NEFA exposed to liver during negative energy balance.
microRNAs (miRNAs) as a group of short noncoding RNAs are crucial molecules in transcriptional and translational regulation of oncogenes and tumor suppressor genes. Evidence showed there was an association between the miRNA polymorphisms and various cancers, including papillary thyroid carcinoma (PTC). The present study aims to evaluate the possible effects of let7a-2 rs1143770 and pri-mir-34b/c rs4938723 polymorphisms on PTC susceptibility. A total of 120 patients with PTC and 130 age, sex, and race matched controls were enrolled in the case-control study. The polymerase chain reaction-restriction fragment length polymorphism method was used for genotyping of let7a-2 rs1143770 and pri-mir-34b/c rs4938723 polymorphisms. The let7a-2 rs1143770 CT and TT genotypes were associated with a 1.9-fold and 2.2-fold higher risk of PTC, respectively (P = 0.027 and P = 0.041). Moreover, the let7a-2 rs1143770 polymorphism was associated with increased PTC risk in both dominant (2-fold, P = 0.015) and the allelic model (1.5-fold, P = 0.03). The frequency of pri-mir-34b/c rs4938723TC genotype was significantly higher in patients with PTC and associated with a two-fold higher risk of PTC (P = 0.013). In addition, this polymorphism was associated with a 1.8-fold increased risk of PTC in dominant model (P = 0.021). The let7a-2 rs1143770CT genotype was associated with a 3.5-fold increased risk of N1 stage in PTC patients (P = 0.04), however, pri-mir-34b/c rs4938723TC genotype was associated with a 3.4-fold and 5.1-fold increased risk of III-IV stage and vascular invasion in PTC group, respectively (P = 0.04 and P = 0.04). In conclusion, the present study shows that let7a-2 rs1143770 and pri-mir-34b/c rs4938723 polymorphisms could be susceptible factors for PTC and some clinical features.
The most important cause of developing hereditary breast cancer is germline mutations occurring in breast cancer (BCs) susceptibility genes, for example, BRCA1, BRCA2, TP53, CHEK2, PTEN, ATM, and PPM1D. Many BC susceptibility genes can be grouped into two classes, high- and low-penetrance genes, each of which interact with multiple genes and environmental factors. However, the penetrance of genes can also be represented by a spectrum, which ranges between high and low. Two of the most common susceptibility genes are BRCA1 and BRCA2, which perform vital cellular functions for repair of homologous DNA. Loss of heterozygosity accompanied by hereditary mutations in BRCA1 or BRCA2 increases chromosomal instability and the likelihood of cancer, as well as playing a key role in stimulating malignant transformation. With regard to pathological features, familial breast cancers caused by BRCA1 mutations usually differ from those caused by BRCA2 mutations and nonfamilial BCs. It is essential to acquire an understanding of these pathological features along with the genetic history of the patient to offer an individualized treatment. Germline mutations in BRCA1 and BRCA2 genes are the main genetic and inherited factors for breast and ovarian cancer. In fact, these mutations are very important in developing early onset and increasing the risk of familial breast and ovarian cancer and responsible for 90% of hereditary BC cases. Therefore, according to the conducted studies, screening of BRCA1 and BRCA2 genes is recommended as an important marker for early detection of all patients with breast or ovarian cancer risk with family history of the disease. In this review, we summarize the role of hereditary genes, mainly BRCA1 and BRCA1, in BC.
Esophageal squamous cell carcinoma (ESCC) is the seventh most common cause of cancer death in worldwide. LncRNA-BANCR is a long non-coding RNA (lncRNA), which has made new windows in cancer investigations. The aim of this survey was to determine the lncRNA-BANCR gene expression changes in patients with ESCC. In case-control investigation was performed on 150 formalin fixed-paraffin embedded tissues (75 cancerous and 75 non-cancerous tissues) of ESCC patients. The lncRNA-BANCR gene expression alteration was assessed by Real-Time PCR technique. Our findings revealed that lncRNA-BANCR gene expression was increased significantly in tumor tissues compared with the non-cancerous tissues (p = 0.0025). In addition, lncRNA-BANCR gene expression changes was positively associated with the lymph node metastasis (p = 0.013), tumor differentiation (p = 0.019) and tumor stage (p = 0.017). Our results suggest a possible role of lncRNA-BANCR in proliferation of esophageal tissues and may be considered as a potential prognostic value for ESCC metastasis.
The exposure to heavy metals and polycyclic aromatic hydrocarbons (PAHs) bound to particulate matter 2.5 (PM
Nowadays, cancer remains a major cause of death affecting millions of people. Currently, the antimicrobial peptides (AMPs) as potent anticancer therapeutic agents offer specificity and low levels of side effects in cancer therapy. In the present study, a cationic chimeric peptide (cLFchimera), derived from camel lactoferrin, was expressed as a secretory peptide using P170 expression system in L. lactis. Peptide purification was carried out using Ni-NTA agarose column from culture medium with 21 μ/mL concentration. The recombinant peptide was investigated for its activity against four tumor and one normal cell line. The cLFchimera was more active against two tumor cell lines (chondrosarcoma and colorectal cancer cells), but the activity against two other tumor cell lines (hepatoma and breast cancer cell line) and normal cells was low. Finally, to have better insight into the mode of action of the peptide on cytotoxic activity, we examined the interaction of cationic peptide with two glycosaminoglycans (GAGs), heparan sulfate (HS) and chondroitin sulfate (CS), as the two most anionic molecules on the cell surface by molecular dynamic simulation. The results of in silico analysis showed that the cLFchimera interacted with HS and CS with a totally different amino acid profile. Hydrogen bonding screening in GAGs-peptide complexes revealed K
Consumption of high fat diet (HFD) is a health concern in modern societies, which participate in wide range of diseases. One underlying mechanism in the HFD mediated pathologies is disruption of insulin signaling activity. It is believed that HFD activates several stress signaling molecules such as MAPKs signaling pathway and these molecules participate in harmful effects in different cell populations including hippocampal cells. However, the activity of MAPKs signaling molecules are time dependent, even causing some opposing effects. Given that, MAPKs activity fluctuate with time of stress, there is less cleared how different lengths of HFD consumption can affect hippocampal MAPK. To test how duration of HFD consumption affect hippocampal MAPKs and insulin signaling activity and animal's cognitive function, rats were fed with HFD for different lengths (up to 6 months) and after each point spatial memory performances of animals was tested, then the peripheral indices of insulin resistance and hippocampal MAPKs and insulin signaling activity was evaluated. Results showed that while different time courses of HFD, up to 6 months, did not bring about significant spatial memory impairment, meanwhile the peripheral insulin sensitivity as well as hippocampal insulin and MAPKs signaling showed significant fluctuations during the different time courses of high fat diet regime. These results showed that neuronal responses to HFD is not constant and differ in a time-dependent manner, it seems that in acute phase molecular responses aimed to compensate the HFD stress but in chronic states these responses failed and devastating effects of stress began.
5-Amino-pyrazoles have proven to be a class of fascinating and privileged organic tools for the construction of diverse heterocyclic or fused heterocyclic scaffolds. This review presents comprehensively the applications of 5-amino-pyrazoles as versatile synthetic building blocks in the synthesis of remarkable organic molecules with an emphasis on versatile functionalities. Following a brief introduction of synthesis methods, planning strategies to construct organic compounds, particularly diverse heterocyclic scaffolds, such as poly-substituted heterocyclic compounds and fused heterocyclic compounds via 5-amino-pyrazoles, have been summarized. Fused heterocycles are classified as bicyclic, tricyclic, tetracyclic, and spiro-fused pyrazole derivatives. These outstanding compounds synthesized via wide variety of approaches include conventional reactions, one-pot multi-component reactions, cyclocondensation, cascade/tandem protocols, and coupling reactions. 5-Amino-pyrazoles represent a class of promising functional reagents, similar to the biologically active compounds, highlighted with diverse applications especially in the field of pharmaceutics and medicinal chemistry. Notably, this critical review covers the articles published from 1981 to 2018.
In recent years, platelet-rich plasma (PRP) has emerged as a promising autologous biological treatment modality for the use in aesthetic and regenerative medicine. PRP is a high concentration of platelets derived from whole blood which is isolated by centrifugation to separate and concentrate platelet-containing plasma from red blood cells. PRP comprises hundreds of bioactive proteins, including growth factors, peptides, and cytokines that stimulate healing of skin and soft tissues. Attractive features of PRP are the extended release of various growth and differentiation factors from activated platelets, tissue regenerative, and healing capabilities, as well as the lack of problems associated with immunogenicity. Because of the unique biological features of this whole blood-derived biological agent, multiple clinical uses for PRP exist for aesthetic and regenerative medicine.A comprehensive review of the literature regarding the use of platelet-rich plasma in aesthetic and regenerative medicine was performed.Therapeutic applications of PRP including several methods for its clinical deployment in conditions related to aesthetic and regenerative medicine including wound healing, skin and facial rejuvenation, hair restoration, hand rejuvenation, breast augmentation, and musculoskeletal regeneration were reviewed.PRP treatment has shown itself as a bright future for a safe and efficient cosmetic intervention. However, more studies are needed to better our understanding of limitations and benefits in clinical phases associated with the aesthetic use of PRP.This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
The aim of this meta-analysis of randomized placebo-controlled clinical trials was to assess the effect of ezetimibe on plasma lipoprotein(a) concentrations. Only randomized placebo-controlled trials investigating the impact of ezetimibe treatment on cholesterol lowering that include lipoprotein(a) measurement were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases (from inception to February 26
Observational studies that investigated the association between adherence to low carbohydrate diet and odds of glioma are sparse. This is particularly relevant in developing countries where dietary carbohydrate intake is very high.This study was, therefore, conducted to investigate the association between adherence to low carbohydrate dietary pattern and odds of glioma among Iranian adults.In this hospital-based case-control study, 128 newly diagnosed glioma cases were recruited and 256 age- and sex-matched subjects were enrolled as controls. Dietary intakes were examined by the use of a 126-item validated FFQ. Low carbohydrate diet (LCD) score was computed for each participant based on deciles of percentages of energy from carbohydrates, proteins, and fats. Individuals in the lowest decile of carbohydrate consumption received 10 points. Participants in second decile received 9 points and so on down to participants in the highest decile received 1 points. For fat and protein intakes, the points assigned to deciles were reversed; such that those in the highest decile received 10 points and those in the lowest decile received 1 point. We then summed all points of the three macronutrients to achieve the overall diet score, which ranged from 3 (highest carbohydrate intake and lowest fat and protein intakes) to 30 (lowest carbohydrate intake and highest fat and protein intakes). The higher the score, the greater adherence to the LCD dietary pattern.After adjustment for age and sex, we found that individuals in top tertile of LCD score were 60% less likely to have glioma compared with those in the bottom tertile (OR: 0.40; 95% CI: 0.23, 0.67). Additional controlling for other potential confounders made the association slightly attenuated (OR: 0.49; 95%CI: 0.26, 0.93). Further adjustment for dietary nutrient intakes strengthened the association (OR: 0.32; 95%CI: 0.12, 0.81). After additional controlling for BMI, we found that adherence to LCD was protectively associated with reduced odds of glioma (OR: 0.32; 95%CI: 0.12, 0.81).We found an inverse association between adherence to LCD and odds of glioma among Iranian population. Prospective cohort studies are needed to confirm these findings.
Counterforce orthoses are used to manage lateral elbow tendinopathy, and their effectiveness in improving motor function has been documented. Little is known about the impact of bracing on sensory function. The objective of this study was to investigate the immediate effectiveness of 2 counterforce orthoses in improving the sensorimotor abilities of the hand in patients with lateral elbow tendinopathy.In this crossover, randomized controlled trial, elbow proprioception, pain severity, pain-free grip strength, and finger dexterity were measured in 50 participants with a diagnosis of lateral elbow tendinopathy. Outcomes were measured in 3 randomized conditions (no brace, forearm band, or elbow sleeve). Data were analyzed using 1-way repeated-measures analysis of variance for each outcome measure.Better scores were observed with the forearm band, as compared with no orthosis, for multiple outcomes including joint position reproduction score at 70° of elbow flexion (P = .006), pain (P < .001), grip strength (P = .01), and dexterity (P < .001). The elbow sleeve yielded better scores than no orthosis for the following outcomes: joint position reproduction score at 110° (P < .001), pain (P < .001), and grip strength (P = .012). No statistically significant difference was found between the orthoses' effects on pain reduction and grip strength (P > .05). The forearm band showed better scores on joint position reproduction at 70° compared with the elbow sleeve (P = .006), whereas the elbow sleeve showed better scores at 110° (P < .001).Our results support the mechanisms occurring with the use of either of the described orthotic interventions. Future randomized trials with longer-term outcomes that include sensorimotor mechanisms might enhance our understanding of the comparative effectiveness.