Antibacterial Efficacy of Walnut Green Husk (WGH) Extract with Zinc Oxide Nanoparticles on Streptococcus Mutans

Background:Chemical agents, such as Chlorhexidine are used as one of dental plaque control strategy. Researchers are looking for a natural and economic substitute with same antibacterial efficacy and less complications. The aim of this study was to evaluate the antimicrobial efficacy of the Khorasan Razavi walnut green husk (WGH) extract with and without adding ZnO nanoparticles (nZnO) on Streptococcus mutans (S. mutans).Methods:In this in vitro study, antimicrobial effect of the Hydro-ethanolic extract of WGH, was evaluated against S. mutans. Broth Dilution and Agar diffusion methods were used with 90 tubes containing different dilutions of WGH extract (100 to 0.006 mg/ml). ZnO nanoparticles (nZnO) were added to 45 tubes. Streptococcus mutans was exposed to 15 different serial concentrations of study extracts, from 100 mg/ml to 0.006 mg/ml. Minimum inhibitory concentration (MIC) of the study extracts were determined and zone of inhibition diameter was compared to positive controls (chlorhexidine 0.2%, nZnO), and negative control (sterile distilled water). The differences between the mean diameters, were analyzed by independent sample T- teS.Results:Minimum inhibitory concentration (MIC) of study extract was found to be 50mg/mL, with adding nZnO, MIC was reduced to 3.12mg/mL. Mean diameter of inhibition zone at 3.12 mg/ml with and without adding ZnO nanoparticles were 17.67±0.57 mm and 8±0.001 mm, respectively, (p-value< 0.001).DiscussionAdding nZnO could be enhanced antimicrobial efficacy of the WGH extract against S. mutants, while it was still less effective than chlorhexidine.Key Words: Dental decay, Nanoparticles, Streptococcus mutans, Walnut green husk, Zinc oxide     

The IGSF1, Wnt5a,FGF14, and ITPR1 Gene Expression and Prognosis Hallmark of Prostate Cancer

Background:Prostate cancer is considered as the second leading cause of cancer related death in men worldwide and the third frequent cancer among Iranian men. Despite the use of PSA as the only biomarker for early diagnosis of prostate cancer, its application in clinical settings is under debate. Therefore, the introduction of new molecular markers for early detection of prostate cancer is needed. Methods:In the present study we intended to evaluate the expression of IGSF1, Wnt5a, FGF14, and ITPR1 in prostate cancer specimens by real time PCR. Biopsy samples of 40 prostate cancer cases and 41 healthy Iranian men were compared to determine the relative gene expression of IGSF1, Wnt5a, FGF14, and ITPR1 by real time PCR. Results:Our results showed that Wnt5a, FGF14, and IGSF1 were significantly overexpressed in the prostate cancer patients while the mean relative expression of ITPR1 showed a significant decrease in PCa samples compared to healthy controls. Conclusion:According to results of the present study, the combination panel of IGSF1, Wnt5a, FGF14, and ITPR1 genes could be considered as potential genetic markers for prostate cancer diagnosis. However further studies on larger populations and investigating the clinicopathological relevance of these genes is needed.Key Words: FGF14, IGSF1, ITPR1, Prostate Cancer, Wnt5a     

Successful treatment of lupoid cutaneous leishmaniasis with glucantime and topical trichloroacetic acid (a case report)

Lupoid leishmaniasis is a unique form of cutaneous leishmaniasis characterized by unusual clinical features and a chronic relapsing course, mostly caused by infection with Leishmania tropica. In this clinical form, 1-2 yr after healing of the acute lesion, new papules and nodules appear at the margin of the remaining scar. Herein, we describe a case of this clinical form that was resistant to 2 courses of treatments: systemic glucantime and then a combination therapy with allopurinol and systemic glucantime. However, marked improvement was seen after a combination therapy with topical trichloroacetic acid solution (50%) and systemic glucantime, and there were no signs of recurrence after 1 yr of follow-up.     

Resveratrol attenuates chronic social isolation stress-induced affective disorders: Involvement of NF-κB/NLRP3 axis

Social isolation stress (SIS) is associated with affective disorders (i.e., anxiety and depression) in adults. In a preclinical study, we aimed to investigate the effects of resveratrol (RV) on the mood swings of rats exposed to SIS. Animals were randomized into six different groups, including control: healthy animals received normal saline (NS) as a vehicle; SIS + NS: SIS animals received NS; SIS + FL: SIS animals received fluoxetine (10 mg/kg/i.p.); SIS + RV20, SIS + RV40, and SIS + RV80: SIS animals received RV (20, 40, and 80 mg/kg/i.p). SIS was induced for 4 weeks, then animals were treated with NS, FL, and RV for 4 weeks. Rats were evaluated by the behavioral tests, including the elevated plus-maze, tail suspension test, the open field test, and forced-swimming test, for mood alterations and nuclear factor kappa B (NF-κB) levels, along with NLRP3, apoptosis-associated speck-like (ASC), and proCaspase-1 were determined in the hippocampus. Behavioral tests confirmed that exposing the animals to SIS caused anxiety and depression. The highest concentrations of NLRP3, proCaspase-1, ASC, and NF-κB, were confirmed in the SIS + NS group. Compared to FL, RV showed antidepressant potential according to the behavioral tests. In particular, the administration of RV (20, 40, and 80 mg/kg) revered the NF-κB/NLRP3 axis cascade in rats exposed to chronic SIS. Our findings revealed that RV attenuated anxiety and depression of SIS-exposed rats via regulation of NF-κB/NLRP3 signaling pathways. RV can be used as a potential anxiolytic agent and antidepressant.     

Common gene polymorphism in ATP-binding cassette transporter A1 and coronary artery disease: A genetic association study and a structural analysis

ATP-binding cassette transporter A1 (ABCA1) has a crucial role in removing intracellular cholesterol and plays a protective role against atherosclerosis. Therefore, genetic polymorphisms in this gene may alter the susceptibility to coronary artery disease (CAD). This study was aimed to examine the association of rs2230806 (c.1051 G > A; p.R219K) variation in the ABCA1 gene with CAD in a case-control design which was followed by a meta-analysis and in silico approach. In the case-control study, 300 subjects including 150 individuals with CAD and 150 healthy controls were recruited. The c.1051 G > A genotyping was done by polymerase chain reaction-restriction fragment length polymorphism method. In the meta-analysis, eligible studies were collected from PubMed, Google Scholar, and ScienceDirect databases and pooled odds ratio, heterogeneity, publication bias, and sensitivity analyses were carried. Finally, some bioinformatics tools were employed to assess the impacts of p.R219K variation on ABCA1 protein structure. Our case-control examination showed a statistically significant association between c.1051 G > A genetic polymorphism and CAD risk. In addition, the meta-analysis showed reliable significant associations between c.1051 G > A transition and risk of CAD in the Caucasian population. In silico analysis showed that the p.R219K substitution could alter the secondary structure, hydrophobicity pattern, and Ramachandran plot of ABCA1. These findings elucidate that the c.1051 G > A variation could be a genetic risk factor for CAD and it could be considered as a prognostic and predictive biomarker for susceptible individuals.     

Modeling the interaction between anti-cancer drug penicillamine and pristine and functionalized carbon nanotubes for medical applications: density functional theory investigation and a molecular dynamics simulation

Abstract

The present study focuses on the prediction and investigation of binding properties of penicillamine with pure (5,5) single-walled carbon nanotube (SWCNT) and functionalized SWCNT (f-SWCNT) through the B3LYP and M06-2X functionals using the 6-31G** basis set. The electronic and structural properties, adsorption energy and frontier molecular orbitals of various configurations are examined. Our theoretical results indicated that the interaction of the nanotubes with penicillamine molecule is weak so that the drug adsorption process is typically physisorption. Also, results of theoretical calculations show that the adsorption of the drug molecule on f-SWCNT is stronger with shorter intermolecular distances in comparison to pure SWCNT. The natural bond orbital (NBO) analysis of studied systems demonstrates that the charge is transferred from penicillamine molecule to the nanotubes. Furthermore, molecular dynamics (MD) simulation is employed to evaluate the dynamic and diffusion behavior of drug molecule on SWCNT and f-SWCNT. Energy results show that drug molecule spontaneously moves toward the carriers, and the van der Waals energy contributions in drug adsorption are more than electrostatic interaction. The obtained results from MD simulation confirm that the functionalization of SWCNT leads to increase in the solubility of the carrier in aqueous solution.

Communicated by Ramaswamy H. Sarma     

Identification of an AAA ATPase VPS4B-dependent pathway that modulates epidermal growth factor receptor abundance and signaling during hypoxia

VPS4B, an AAA ATPase (ATPase associated with various cellular activities), participates in vesicular trafficking and autophagosome maturation in mammalian cells. In solid tumors, hypoxia is a common feature and an indicator of poor treatment outcome. Our studies demonstrate that exogenous or endogenous (assessed with anchorage-independent three-dimensional multicellular spheroid culture) hypoxia induces VPS4B downregulation by the ubiquitin-proteasome system. Inhibition of VPS4B function by short hairpin VPS4B (sh-VPS4B) or expression of dominant negative VPS4B(E235Q) promotes anchorage-independent breast cancer cell growth and resistance to gefitinib, U0126, and genotoxicity. Biochemically, hyperactivation of epidermal growth factor receptor (EGFR), a receptor tyrosine kinase essential for cell proliferation and survival, accompanied by increased EGFR accumulation and altered intracellular compartmentalization, is observed in cells with compromised VPS4B. Furthermore, enhanced FOS/JUN induction and AP-1 promoter activation are noted in EGF-treated cells with VPS4B knockdown. However, VPS4B depletion does not affect EGFRvIII stability or its associated signaling. An inverse correlation between VPS4B expression and EGFR abundance is observed in breast tumors, and high-grade or recurrent breast carcinomas exhibit lower VPS4B expression. Together, our findings highlight a potentially critical role of VPS4B downregulation or chronic-hypoxia-induced VPS4B degradation in promoting tumor progression, unveiling a nongenomic mechanism for EGFR overproduction in human breast cancer.     

Kinetic aspects of alkaline phosphatase refolding in the presence of alpha-cyclodextrin

To get a better understanding of the molecular aspects of protein folding, the refolding kinetic behavior of guanidine hydrochloride-denatured alkaline phosphatase (ALP) was studied in the presence of alpha-cyclodextrin (alpha-CD) through two different approaches: the dilution additive and the artificial chaperone-assisted methods. It was found that alpha-CD enhanced the recovered activity more than 50% via both approaches while decreased the refolding rate, perhaps due to engaging the hydrophobic patches of the protein in a rigid conformation. In contrast, detergents used in the artificial chaperone method increased the refolding rate significantly. A comparison of the rate constants for the refolding and the activity recovery of denatured ALP in the presence of various concentrations of CD and different kinds of detergents showed that they do not progress in a synchronized pattern. This may be attributed to continuous structural rearrangements in the protein long after the return of enzyme activity. These observations are discussed in terms of kinetic and structural aspects of the refolding pathway.     

Estradiol's salutary effects on keratinocytes following trauma-hemorrhage are mediated by estrogen receptor (ER)-alpha and ER-beta

Although administration of 17beta-estradiol (estrogen) following trauma-hemorrhage attenuates the elevation of cytokine production and mitogen-activated protein kinase (MAPK) activation in epidermal keratinocytes, whether the salutary effects of estrogen are mediated by estrogen receptor (ER)-alpha or ER-beta is not known. To determine which estrogen receptor is the mediator, we subjected C3H/HeN male mice to trauma-hemorrhage (2-cm midline laparotomy and bleeding of the animals to a mean blood pressure of 35 mmHg and maintaining that pressure for 90 min) followed by resuscitation with Ringer's lactate (four times the shed blood volume). At the middle of resuscitation we subcutaneously injected ER-alpha agonist propyl pyrazole triol (PPT; 5 microg/kg), ER-beta agonist diarylpropionitrile (DPN; 5 microg/kg), estrogen (50 microg/kg), or ER antagonist ICI 182,780 (150 microg/kg). Two hours after resuscitation, we isolated keratinocytes, stimulated them with lipopolysaccharide for 24 h (5 microg/mL for maximum cytokine production), and measured the production of interleukin (IL)-6, IL-10, IL-12, and TNF-alpha and the activation of MAPK. Keratinocyte cytokine production markedly increased and MAPK activation occurred following trauma-hemorrhage but were normalized by administration of estrogen, PPT, and DPN. PPT and DPN administration were equally effective in normalizing the inflammatory response of keratinocytes, indicating that both ER-alpha and ER-beta mediate the salutary effects of estrogen on keratinocytes after trauma-hemorrhage.