Destruction of cariogenic biofilms by antimicrobial photodynamic therapy mediated by phycocyanin and toluidine blue along with sodium fluoride varnish or titanium tetrafluoride.

OBJECTIVE: Evaluation of the effect of phycocyanin (PC) and toluidine blue (TBO) along with sodium fluoride varnish (FV) or titanium tetrafluoride (TiF4) under the conditions of antimicrobial photodynamic therapy (PDT) on a dual-species cariogenic biofilm and on remineralization process. DESIGN: After the development of Streptococcus mutansStreptococcus mutans and Lactobacillus acidophilus dual-species biofilms on the human enamel disks, they were divided into 11 groups (n = 9): Control (0.9 % saline), PC, TBO, FV, and TiF4 alone, PC and TBO in combination with a 635 nm diode laser (PDT treatment), PC-PDT+ (PC + FV or TiF4 + 635 nm diode laser), and TBO-PDT+ (TBO + FV or TiF4 + 635 nm diode laser). After the treatment, crystal violet assay was performed to determine the reduction of cariogenic biofilms. Enamel remineralization changes were analyzed using energy dispersive X-ray spectroscopy (EDX) and field emission scanning electron microscopy (FESEM) for the calcium and phosphorus (Ca/P) ratio. RESULTS: Only TBO-PDT+ showed superior antibiofilm activity when TiF4 was applied. Furthermore, the highest Ca/P ratio was found after treatment of enamel surfaces with TiF4-TBO-PDT+. The FESEM images showed that the enamel disks treated with TiF4 plus TBO-mediated PDT exhibited surface coating. However, TiF4 plus PC-mediated PDT cannot repair demineralized enamel. CONCLUSIONS: These data suggest that TBO-PDT along with TiF4 can effectively reduce cariogenic biofilms and significantly remineralize enamel disks, opening new avenues in caries prevention.

Green synthesis of degradable conductive thermosensitive oligopyrrole/chitosan hydrogel intended for cartilage tissue engineering.

Electroactive scaffolds containing conductive polymers can promote tissue repair and regeneration. However, these polymers are non-degradable and cannot be removed from body. To overcome this limitation of conductive polymers, we developed a novel injectable electroactive hydrogel containing pyrrole oligomers which possessed the unique properties of being both electrically conductive and biodegradable. First, pyrrole oligomers were synthesized via chemical polymerization and were found to be amorphous with a non-globular morphology. Then, three different compositions of injectable chitosan/beta glycerophosphate hydrogels containing different concentrations of pyrrole oligomers were synthesized and characterized for chemical structure, morphology, conductivity, swelling ratio, In vitro biodegradation and gelation time. An increase in oligopyrrole content resulted in decreased pore size, and increased gelation time, swelling ratio, conductivity and degradation time. Among all the hydrogel compositions, the sample with pyrrole oligomer:chitosan ratio of 0.1 (w/w) showed the most prominent biodegradability, biocompatibility, electro-activity, swelling ratio and pore size values and was chosen as the optimal electroactive hydrogel composition in this work.

Ultrasonic nanotherapy of breast cancer using novel ultrasound-responsive alginate-shelled perfluorohexane nanodroplets: In vitro and in vivo evaluation.

Development of a new class of multifunctional ultrasound-responsive smart nanocarriers that combine therapeutic properties with diagnostic imaging has gained great attention in recent years. Here, we describe the results of ultrasonic nanotherapy of breast cancer using novel alginate-stabilized perfluorohexane nanodroplets. Doxorubicin (Dox)-loaded multifunctional nanodroplets (Dox-NDs) were synthesized via nanoemulsion process and evaluated in vitro and in vivo with focus on cytotoxicity, hemolytic activity, biodistribution, biosafety, and antitumor activity. Echogenic property of nanodroplets was confirmed by B-mode ultrasound imaging. Tumor therapy using Dox-NDs combined with sonication (Dox-ND-US) resulted in strong in vivo antitumor activity characterized by tumor regression which could be because of on demand efficient ultrasound-aided drug release from nanodroplets in tumor tissue under the action of ultrasound. Dox concentration in tumor area for Dox-ND-US treated group reached 10.9µg/g after sonication for 4min (28kHz, 0.034W/cm2), which was 5.2-fold higher compared to non-sonicated Dox-NDs group. The cardiotoxicity of Dox-NDs was much lower than that of free Dox and no hemolytic activity was observed for Dox-NDs. Strong therapeutic effect of these multifunctional nanodroplets combined with their ultrasound-contrast property indicated that this drug delivery system has a great potential in smart cancer-therapy.

Novel ultrasound-responsive chitosan/perfluorohexane nanodroplets for image-guided smart delivery of an anticancer agent: Curcumin.

Ultrasound-responsive nanodroplets are a class of new emerging smart drug delivery systems which provide image-guided nano-therapy of various diseases, especially cancers. Here, we developed multifunctional smart curcumin-loaded chitosan/perfluorohexane nanodroplets for contrast-ultrasound imaging and on-demand drug delivery. The nanodroplets were synthesized via nanoemulsion process. The optimal formulation with the size of 101.2nm and 77.8% curcumin entrapment was chosen for release study and cytotoxicity evaluation. Sonication at the frequency of 1MHz, 2W/cm2 for 4min triggered the release of 63.5% of curcumin from optimal formulation (Cur-NDs-2). Ultrasound aided release study indicated that the concentration of perfluorohexane and the degree of acoustic droplet vaporization play important role in ultrasound-active drug release. B-mode ultrasound imaging confirmed strong ultrasound contrast of chitosan nanodroplets even at low concentrations via droplet to bubble transition. Finally, cytotoxicity of the ultrasound-responsive nanodroplets in the presence of ultrasound was evaluated in-vitro on 4T1 human breast cancer cells. Cell growth inhibitory effects of curcumin-loaded nanodroplets significantly increased by ultrasound exposure. According to the obtained results, these ultrasound responsive curcumin-loaded chitosan/perfluorohexane nanodroplets have a great potential for imaged-guided cancer therapy.

Bypassing multidrug resistant ovarian cancer using ultrasound responsive doxorubicin/curcumin co-deliver alginate nanodroplets.

Ultrasound-responsive perfluorocarbon nanoemulsions are a class of new multifunctional smart nanocarriers which combine diagnostic properties with therapeutic properties and release their drug payload in a controlled manner in response to ultrasound. Therefore, combination therapy using chemotherapeutic and chemosensitizing agents co-entrapped in these nanocarriers seems beneficial for cancer treatment. In the present study, multifunctional smart alginate/perfluorohexane nanodroplets were developed for co-delivery of doxorubicin and curcumin (a strong chemosensitizer). The nanodroplets with the average particle size of 55.1nm were synthesized via nanoemulsion process. The entrapment efficiency of doxorubicin was 92.3%. To improve curcumin entrapment into the alginate shell, Span 60 was added to the formulation as a co-surfactant and finally curcumin entrapment of about 40% was achieved. Ultrasound-mediated drug release kinetic was evaluated at two different frequencies of 28kHz (low frequency) and 1MHz (high frequency). Low frequency ultrasound resulted in higher triggered drug release from nanodroplets. The nanodroplets showed strong ultrasound contrast via droplet to bubble transition as confirmed via B-mode ultrasound imaging. Enhanced cytotoxicity in adriamycin-resistant A2780 ovarian cancer cells was observed for Dox-Cur-NDs compared to Dox-NDs because of the synergistic effects of doxorubicin and curcumin. However, ultrasound irradiation significantly increased the cytotoxicity of Dox-Cur-NDs. Finally, in vivo ovarian cancer treatment using Dox/Cur-NDs combined with ultrasound irradiation resulted in efficient tumor regression. According to the present study, nanotherapy of multidrug resistant human ovarian cancer using ultrasound responsive doxorubicin/curcumin co-loaded alginate-shelled nanodroplets combined with ultrasound irradiation could be a promising modality for the future of cancer treatment.

Preparation and characterization of novel functionalized multiwalled carbon nanotubes/chitosan/ß-Glycerophosphate scaffolds for bone tissue engineering.

A major limitation in current tissue engineering scaffolds is that some of the most important characteristics of the intended tissue are ignored. As piezoelectricity and high mechanical strength are two of the most important characteristics of the bone tissue, carbon nanotubes are getting a lot of attention as a bone tissue scaffold component in recent years. In the present study, composite scaffolds comprised of functionalized Multiwalled Carbon Nanotubes (f-MWCNT), medium molecular weight chitosan and ß-Glycerophosphate were fabricated and characterized. Biodegradability and mechanical tests indicate that while increasing f-MWCNT content can improve electrical conductivity and mechanical properties, there are some limitations for these increases, such as a decrease in mechanical properties and biodegradability in 1w/v% content of f-MWCNTs. Also, MTT cytotoxicity assay was conducted for the scaffolds and no significant cytotoxicity was observed. Increasing f-MWCNT content led to higher alkaline Phosphatase activity. The overall results show that composites with f-MWCNT content between 0.1w/v% and 0.5w/v% are the most suitable for bone tissue engineering application. Additionally, Preliminary cell electrical tests proved the efficiency of the prepared scaffolds for cell electrical applications.

Novel alginate-stabilized doxorubicin-loaded nanodroplets for ultrasounic theranosis of breast cancer.

Perfluorocarbon nanoemulsions are a new class of multifunctional stimuli-responsive nanocarriers which combine the properties of passive-targeted drug carriers, ultrasound imaging contrast agents, and ultrasound-responsive drug delivery systems. Doxorubicin-loaded alginate stabilized perflourohexane (PFH) nanodroplets were synthesized via nanoemulsion preparation method and their ultrasound responsivity, imaging, and therapeutic properties were studied. Doxorubicin was loaded into the nanodroplets (39.2nm) with encapsulation efficiency of 92.2%. In vitro release profile of doxorubicin from nanodroplets was an apparently biphasic release process and 12.6% of drug released from nanodroplets after 24h incubation in PBS, pH=7.4. Sonication with 28kHz therapeutic ultrasound for 10min triggered droplet-to-bubble transition in PFH nanodroplets which resulted in the release of 85.95% of doxorubicin from nanodroplets. Microbubbles formed by acoustic vaporization of the nanodroplets underwent inertial cavitation. In the breast cancer mice models, ultrasound-mediated therapy with doxorubicin-loaded PFH nanodroplets showed excellent anti-cancer effects characterized by tumor regression. Complete tumor regression was observed for the group in which doxorubicin-loaded nanodroplets were combined with ultrasound, whereas the tumor growth inhibition of doxorubicin -loaded nanodroplets was 89.6%. These multifunctional nanodroplets, with excellent therapeutic and ultrasound properties, could be promising drug delivery systems for chemotherapeutic application.

Dynamic Postural Control in Female Athletes and Nonathletes After a Whole-Body Fatigue Protocol.

Baghbani, F, Woodhouse, LJ, and Gaeini, AA. Dynamic postural control in female athletes and nonathletes after a whole-body fatigue protocol. J Strength Cond Res 30(7): 1942-1947, 2016-Postural control is a crucial element in regular training of athletes, development of complex technical movement, and injury prevention; however, distributing factor of the postural control such as fatigue has been neglected by athletic trainers in novice and inexperienced athletes. The objective of this study was to compare changes in dynamic postural control of young female athletes and nonathletes after a fatigue protocol. Thirty females (15 athletes and 15 nonathletes) with no orthopedic problems were recruited to participate in this study. All participants completed the pre-SEBT (star excursion balance test) in 8 directions at baseline; then, they performed a 20-minute fatigue protocol after which post-SEBT was measured. Rating of perceived exertion was measured using the Borg scale immediately before, mid-way through (i.e., after the third station), and after performing the fatigue protocol (i.e., immediately before the post-SEBT). Female nonathlete groups had significant differences in dynamic balance performance after fatigue in the medial, posteromedial, and posterior directions (p < 0.01) measured by SEBT. Athletes, however, showed no significant changes after the fatigue protocol. Our results indicates the importance of evaluation and monitoring of dynamic postural control of the novice with progressing the exercise time. Our findings could also help coaches to develop trainings focused on the 3 directions of medial, posteromedial, and posterior directions and aimed at exercises increasing fatigue resistance.

Formulation design, preparation and characterization of multifunctional alginate stabilized nanodroplets.

In the present study the effect of process (homogenization speed) and formulation (polymer-alginate-concentration, surfactant concentration, drug amount, perfluorohexane volume fraction and co-surfactant inclusion) variables on particle size, entrapment efficiency, and drug release kinetics of doxorubicin-loaded alginate stabilized perfluorohexane nanodroplets were evaluated. Particle size and doxorubicin entrapment efficiency were highly affected by formulation and process variables. Increase in homogenization speed resulted in significant decrease in particle size and increase in entrapment efficiency. Polymer concentration and perfluorohexane amount both had similar effect on particle size. Particle size increased by an increase in the amount of both. Entrapment efficiency increased by increasing polymer concentration. In case of surfactant concentration and drug amount, particle size and entrapment efficiency had optimum values and an increase in concentration of both of them behind a certain limit resulted in increase in particle size and decrease in doxorubicin entrapment. In vitro release profile of doxorubicin was an apparently biphasic release process and 7%-13% of drug released after 24h incubation in PBS, pH=7.4, depending on the nanodroplets composition but ultrasound exposure for 10min resulted in triggered release of 85.95% of doxorubicin from optimal formulation (formulation E1 with 39.2nm diameter size and 92.2% entrapment efficiency).

Effects of probiotic Lactobacillus acidophilus and Lactobacillus casei on colorectal tumor cells activity (CaCo-2).

BACKGROUND: The probiotic microorganisms are live normal flora that provide nutritional benefits. When probiotic administered in adequate amounts, they also confer a health benefit on the host. Different mechanisms of probiotic effects include the following: stimulating the immune system, modifying the composition of normal intestinal flora and preventing the carcinogenic activity of fecal enzymes. In this study, direct effects of probiotic lactobacilli on tumor cells were investigated. METHODS: Supernatants and bacterial extracts of two standard Lactobacillus species (L. acidophilus and L. casei) were prepared and CaCo-2 cells were treated with them. Probiotic effects on cell proliferation, necrosis, apoptosis, migration and invasion were assessed. RESULTS: The supernatants of Lactobacilli decreased cell proliferation and increased cell apoptosis, however, no significant effect on cell necrosis was reported. In contrast, Lactobacilli extract, reduced cell proliferation and increased cell apoptosis. Lactobacilli extract also led to cell necrosis. Furthermore, both supernatants and cell extracts of the probiotic agents resulted in decreased cells' migration and invasion. CONCLUSION: In this study, it was shown that Lactobacilli probiotics useful effects are not confined to the enhancement of the immune system; however, they effectively suppress the malignant phenotypes of colorectal cancer cells.

Robertsonian translocation between chromosomes (no.21/14) in relation to the history of spontaneous abortion in a family.

BACKGROUND: Approximately 205 million pregnancies occur each year in the worldwide. On the other hand, Spontaneous abortion has been reported in 15-20% of all diagnosed pregnancies. The most common cause of spontaneous abortion is chromosomal abnormalities of the embryo. Robertsonian translocation carriers specially 21-14 are the most common balanced rearrangement among the carrier couples with the history of spontaneous abortion. In order to search for balanced chromosomal rearrangement and cytogenetic disorders, 10 members of related family with consanguinity marriage with the history of recurrent miscarriage were assessed. CASE: Cytogenetic evaluation on the basis G-banding technique at high resolution was performed in 3 couples and their related family with the history of idiopathic RSA in order to postulate any balanced chromosomal rearrangement. CONCLUSION: six members of them appeared with robertsonian balanced translocation between chromosome No.21 to No. 14 with the karyotype of 45, XX, t (14, 21) and 45, XY, t (14, 21), which this results are in agreement with several similar works which claimed that the risk of spontaneous abortion in couples with balanced chromosomal rearrangements is higher compared with general population. Considering to results of present study, it seems as if the cytogenetic analysis of couples with the history of recurrent abortions should be suggested compulsory to estimate the probable presence of any chromosomal rearrangement. This offer wills valuable information for genetic consulting.

Association of heteromorphism of chromosome 9 and recurrent abortion (ultrasound diagnosed blighted ovum): A case report.

BACKGROUND: Chromosomal disorders are the most common cause of first trimester spontaneous abortion. Among the human chromosomes, chromosome no.9 was the most common structural chromosomal variant and it is not thought to be of any functional importance, which often considers as a normal variation in structural polymorphisms, nevertheless there are some studies which claim that there is an association between heteromorphism of chromosome no.9 and some pregnancy complication. CASE: To postulate any correlation between chromosome no. 9 heteromorphism and recurrent abortion, chromosomal analysis was performed on the basis of G-banding technique at high resolution for a couple with the history of 4 ultrasound diagnosed blighted ovum and Chromosome constitution appeared with chromosome no.9 heteromorphism in all 30 metaphases screened for both partners (9p11-q13). CONCLUSION: Observation of reproductive failure in couples with heteromorohic pattern of chromosome no.9 suggests that, although the heteromorphism of chromosome no.9 is not a rare condition which often consider as a normal variation with no evidence of any phenotypic effect of patient, nevertheless it seems as if the location of heteromorphic region maybe interfere with meiotic events like the phenomenon of crossing over or miotic segregation of fertilized egg that eventually lead to the development of fertilized eggs with chromosomal abnormalities leading to the possibility of anemberyonic pregnancy, therefore chromosomal analysis for detecting of chromosome no.9 heteromorphism for couples with the history of ultrasound diagnosed blighted ovum will be strongly suggested.

Identification of novel hypoxia response genes in human glioma cell line a172.

OBJECTIVE(S): Hypoxia is a serious challenge for treatment of solid tumors. This condition has been manifested to exert significant therapeutic effects on glioblastoma multiform or (WHO) astrocytoma grade IV. Hypoxia contributes numerous changes in cellular mechanisms such as angiogenesis, metastasis and apoptosis evasion. Furthermore, in molecular level, hypoxia can cause induction of DNA breaks in tumor cells. Identification of mechanisms responsible for these effects can lead to designing more efficient therapeutic strategies against tumor progression which results in improvement of patient prognosis. Materials and Methods : In order to identify more hypoxia regulated genes which may have a role in glioblastoma progression, cDNA-AFLP was optimized as a Differential display method which is able to identify and isolate transcripts with no prior sequence knowledge. RESULTS: Using this method, the current study identified 120 Transcription Derived Fragments (TDFs) which were completely differentially regulated in response to hypoxia. By sequence homology searching, the current study could detect 22 completely differentially regulated known genes and two unknown sequence matching with two chromosome contig and four sequence matches with some Expressed Sequence Tags (ESTs). CONCLUSION: Further characterizing of these genes may help to achieve better understanding of hypoxia mediated phenotype change in tumor cells.

Identification of Xq22.1-23 as a region linked with hereditary recurrent spontaneous abortion in a family.

BACKGROUND: Recurrent spontaneous abortion (RSA) is one of the most common health complications with a strong genetic component. Several genetic disorders were identified as etiological factors of hereditary X linked RSA. However, more genetic factors remain to be identified. OBJECTIVE: In this study we performed linkage analysis on a large X linked RSA pedigree to find a novel susceptibility locus for RSA. MATERIALS AND METHODS: A linkage scan using 11 microsatellites was performed in 27 members of a large pedigree of hereditary X-linked RSA. Two point parametric Linkage was performed using Superlink v 1.6 program. RESULTS: Evidence of linkage was observed to markers at Xq23, DXS7133 and at Xq22.1 DXS101, with LOD score of 3.12 and 1.60, respectively. CONCLUSION: Identified locus in this study may carry a responsible gene in RSA. Narrowing down of this region may leads to identification of this gene. This article extracted from M.Sc. thesis. (Sahar Shekouhi).

A Case of Autism with Ring Chromosome 14.

BACKGROUND: Autism is a complex neuropsychiatric disorder that manifests in early childhood. Although the etiology is unknown yet but, new hypothesis focused on identifying the key genes related to autism may elucidate its etiology. The main objective of the present study was to verify the value of karyotyping in autistic children and identifying association between chromosome abnormalities and autism. METHODS: We examined the peripheral blood lymphocytes cell culture for cytogenetic alterations by GTG-banding technique. The investigation was carried out on 50 autistic patients referred by Pediatric neurologist to Cytogenetic Laboratory in Khorasan-e-razavi Province, Iran. RESULTS: Using GTG-banding technique, the chromosome analysis of patients identified an unbalanced male karyotype with a r (14) in all 50 metaphaseswere examined. CONCLUSION: Since structural abnormalities may have a critical role in the etiology of autism, according to the region where is affected and number of related genes, therefore an outcome with wide spectrum of clinical manifestations could be expected. Furthermore by considering of recent study, the results indicated that there is an association between chromosome 14 with brain development and neurological disorders, but, in conclusion, it could not be suggested that in order to postulate cytogenetic testing in idiopathic autism patients, specifically screening for chromosome 14 which might has diagnostic value.