Effect of peptide length on the conjugation to the gold nanoparticle surface: a molecular dynamic study

Background

Gold nanoparticles now command a great deal of attention for medical applications. Despite the importance of nano-bio interfaces, interaction between peptides and proteins with gold surfaces is not still fully understood, especially in a molecular level.

Methods

In the present study computational simulation of adsorption of 20 amino acids, in three forms of mono-amino acid, homo di-peptide and homo tri-peptide, on the gold nanoparticles was performed by Gromacs using OPLSAA force field. The flexibility, stability, and size effect of the peptides on the gold nanoparticles were studied as well as the molecular structure of them.

Results

According to our results, adsorbed homo tri-peptides on the gold surface had more flexibility, more gyration, and the farthest distance from the GNP in comparison with homo di-peptides and mono-amino acids.

Conclusion

Our findings provide new insights into the precise control of interactions between amino acids anchored on the GNPs.

     

Phenotypic Assays to Determine Virulence Factors of Uropathogenic Escherichia coli (UPEC) Isolates and their Correlation with Antibiotic Resistance Pattern

Objectives

Urinary tract infection caused by uropathogenic Escherichia coli (UPEC) strains is one of the most important infections in the world. UPEC encode widespread virulence factors closely related with pathogenesis of the bacteria. The purpose of this study was to evaluate the presence of different phenotypic virulence markers in UPEC isolates and determine their correlation with antibiotic resistance pattern.

Methods

UPEC isolates from patients with different clinical symptoms of UTI were collected and screened for biofilm and hemolysin production, mannose resistant, and mannose sensitive hemagglutination (MRHA and MSHA, respectively). In addition, antimicrobial resistance pattern and ESBL-producing isolates were recorded.

Results

Of the 156 UPEC isolates, biofilm and hemolysin formation was seen in 133 (85.3%) and 53 (34%) isolates, respectively. Moreover, 98 (62.8%) and 58 (37.2%) isolates showed the presence of Types 1 fimbriae (MSHA) and P fimbriae (MRHA), respectively. Our results also showed a relationship between biofilm formation in UPEC isolated from acute cystitis patients and recurrent UTI cases. Occurrence of UTI was dramatically correlated with the patients'' profiles. We observed that the difference in antimicrobial susceptibilities of the biofilm and nonbiofilm former isolates was statistically significant. The UPEC isolates showed the highest resistance to ampicillin, tetracycline, amoxicillin, and cotrimoxazole. Moreover, 26.9% of isolates were ESBL producers.

Conclusion

This study indicated that there is a relationship between the phenotypic virulence traits of the UPEC isolates, patients'' profiles, and antibiotic resistance. Detection of the phenotypic virulence factors could help to improve understanding of pathogenesis of UPEC isolates and better medical intervention.     

Development of a mono‐specific anti‐VEGF bivalent nanobody with extended plasma half‐life for treatment of pathologic neovascularization

Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis within solid cancers. Thus, targeting VEGF might be part of a feasible therapy for treating pathological neovascularization, and nanobodies ? derived from heavy chain‐only antibodies occurring within Camelidae ? are a novel class of nanometer‐sized antibodies possessing unique properties that could be developed into a promising therapeutic. However, nanobodies have a very short half‐life in vivo due to their small size. Development of a bivalent nanobody is one way to remediate the half‐life problem of nanobodies. Two identical anti‐VEGF nanobodies were connected using the hinge region of llama IgG2c. The recombinant plasmid (pHEN6c‐bivalent nanobody) was transformed into E.coli WK6 cells and expression of the bivalent nanobody construct was induced with 1mM Isopropyl β‐D‐1‐thiogalactopyranoside (IPTG). Recombinant bivalent nanobody was purified using nickel affinity chromatography and its activity on human endothelial cells was assessed using 3‐(4,5‐Dimethylthiazol‐2‐yr)‐2,5‐diphenyltetrazolium bromide (MTT), tube formation, and cell migration assays. The pharmacokinetic study was performed after intravenous (i.v.) injection of recombinant bivalent nanobody into six‐week‐old C57BL/6 mice. Recombinant bivalent nanobody performed significantly better than monovalent nanobody in inhibiting proliferation, tube formation, and migration of human endothelial cells. Pharmacokinetic results showed a 1.8‐fold longer half‐life of bivalent nanobody in comparison with the monovalent nanobody. These results underscore the potential of recombinant anti‐VEGF bivalent nanobody as a promising tool for development of a novel therapeutic with an extended plasma half‐life for VEGF‐related diseases.     

Shear wave elastography of temporomandibular joint disc and masseter muscle stiffness in healthy children and adolescents: a preliminary study

Oral Radiology - Shear wave elastography (SWE) are promising techniques in diagnosing temporomandibular joint (TMJ) disc and masseter muscle disorders. To investigate normative stiffness values of...     

Elevated IL-38 Serum Levels in Newly Diagnosed Multiple Sclerosis and Systemic Sclerosis Patients

ObjectiveInterleukin (IL)-38 is a newly discovered member of the IL-1 cytokine family with a proposed anti-inflammatory profile. We studied the probable role of this cytokine in the pathogenesis of two autoimmune diseases: multiple sclerosis (MS) and systemic sclerosis (SSc).Subjects and MethodsA total of 87 MS patients and 86 SSc patients (40 new and recently untreated cases and 46 treated cases) were selected for this study. Eighty-seven and 80 age- and sex-matched healthy subjects were included as controls for MS and SSc, respectively. Clinical and paraclinical features of the patients were recorded at the time of sampling. Serum IL-38 was measured by ELISA.ResultsLevels of serum IL-38 did not significantly differ between the total MS or SSc patients compared to controls. However, levels of IL-38 were significantly higher in newly diagnosed patients of MS (206.43 ± 38.97 pg/mL, p < 0.0001) than in those previously treated (158.04 ± 39.45 pg/mL). Similarly, new/recently untreated cases of SSc patients showed increased IL-38 levels (185.19 ± 36.27 pg/mL, p = 0.001) compared to treated patients (166.82 ± 33.08 pg/mL). IL-38 levels in newly diagnosed MS patients (p = 0.007) and new/recently untreated SSc patients (p = 0.032) were significantly higher than those in healthy controls.ConclusionThe higher serum levels of IL-38 in new or recently untreated cases of MS and SSc patients than in treated patients and healthy controls suggest the possible role of this cytokine in the development of these diseases or as part of a feedback loop to attenuate the inflammatory conditions in early stages of these diseases.     

Seasonal effect of GnIH on gonadotrope functions in the pituitary of goldfish

Gonadotropin-inhibitory hormone (GnIH) inhibits gonadotropin release in birds and mammals. To investigate its role in teleosts, we examined the effects of synthetic goldfish (g)GnIH on pituitary LH-β and FSH-β subunit, and gGnIH receptor (gGnIH-R) mRNA levels and LH secretion in goldfish. Intraperitoneal injections of gGnIH increased pituitary LH-β and FSH-β mRNA levels at early to late gonadal recrudescence, but reduced serum LH and pituitary gGnIH-R mRNA levels, respectively, at early to mid-recrudescence and later stages of recrudescence. Static incubation with gGnIH elevated LH secretion from dispersed pituitary cell cultures from prespawning fish, but not at other recrudescent stages; suppressed LH-β mRNA levels at early recrudescence and prespawning but elevated LH-β at mid-recrudescence; and consistently attenuated FSH-β mRNA in a dose-specific manner. Results indicate that in goldfish, regulation of LH secretion and gonadotropin subunit mRNA levels are dissociated in the presence of gGnIH and dependent on maturational status and administration route.     

Asymptomatic seminal infection of herpes simplex virus:impact on male infertility

In more than half of infertile men,the cause of their infertility is unknown.Several studies revealed the role of viral infections in male infertility.The aim of the present study was to determine the prevalence of herpes simplex virus-1 (HSV-1) and HSV-2 in semen from asymptomatic infertile male patients,and its association with altered semen parameters.A total of 70 semen samples were collected from infertile men who attended the Research and Clinical Center for Infertility in Yazd,Iran.Semen analysis and diagnostic real-time PCR using specific primers and probes for HSV-1 and HSV-2 DNA were performed.Comparison of semen parameters between virally infected and non-infected samples were performed with independent t-test and Mann-Whitney test.Semen analysis showed that infertile men fell into two groups,the male factor group and the unexplained group.HSV-1 and HSV-2 DNA was detected in 16 (22.9%) and 10 (14.3%) of 70 semen samples,respectively.All HSV-positive samples had abnormal semen parameters (the male factor group).Although HSV infection was not associated with sperm motility and morphological defects,it was correlated with lower sperm count in the seminal fluid.The findings suggest that asymptomatic seminal infection of HSV plays an important role in male infertility by adversely affecting sperm count.