Biocompatible scaffolds based on collagen and oxidized dextran for endothelial cell survival and function in tissue engineering.

Angiogenesis is a vital step in tissue regeneration. Hence, the current study aimed to prepare oxidized dextran (Odex)/collagen (Col)-hydrogels with laminin (LMN), as an angiogenic extracellular matrix (ECM) component, for promoting human umbilical vein endothelial cell (HUVEC) proliferation and function. Odex/Col scaffolds were constructed at various concentrations and temperatures. Using oscillatory rheometry, scanning electron microscopy (SEM), and cell viability testing, the scaffolds were characterized, and then HUVEC proliferation and function was compared with or without LMN. The gelation time could be modified by altering the Odex/Col mass ratio as well as the temperature. SEM showed that Odex/Col hydrogels had a more regular three-dimensional (3D) porous structure than the Col hydrogels. Moreover, HUVECs grew faster in the Col scaffold (12 mg/mL), whereas the Odex (30 mg/mL)/Col (6 mg/mL) scaffold exhibited the lowest apoptosis index. Furthermore, the expression level of vascular endothelial growth factor (VEGF) mRNA in the group without LMN was higher than that with LMN, and the Odex (30 mg/mL)/Col (6 mg/mL) scaffold without LMN had the highest VEGF protein secretion, allowing the cells to survive and function effectively. Odex/Col scaffolds, with or without LMN, are proposed as a tissue engineering construct to improve HUVEC survival and function for angiogenesis.

Indirect co-culture of islet cells in 3D biocompatible collagen/laminin scaffold with angiomiRs transfected mesenchymal stem cells.

Diabetes is an autoimmune disease in which the pancreatic islets produce insufficient insulin. One of the treatment strategies is islet isolation, which may damage these cells as they lack vasculature. Biocompatible scaffolds are one of the efficient techniques for dealing with this issue. The current study is aimed to determine the effect of transfected BM-MSCS with angiomiR-126 and -210 on the survival and functionality of islets loaded into a 3D scaffold via laminin (LMN). AngiomiRs/Poly Ethylenimine polyplexes were transfected into bone marrow-mesenchymal stem cells (BM-MSCs), followed by 3-day indirect co-culturing with islets laden in collagen (Col)-based hydrogel scaffolds containing LMN. Islet proliferation and viability were significantly increased in LMN-containing scaffolds, particularly in the miRNA-126 treated group. Insulin gene expression was superior in Col scaffolds, especially, in the BM-MSCs/miRNA-126 treated group. VEGF was upregulated in the LMN-containing scaffolds in both miRNA-treated groups, specifically in the miRNA-210, leading to VEGF secretion. MiRNAs' target genes showed no downregulation in LMN-free scaffolds; while a drastic downregulation was seen in the LMN-containing scaffolds. The highest insulin secretion was recorded in the Oxidized dextran (Odex)/ColLMN+ group with miRNA-126. LMN-containing biocompatible scaffolds, once combined with angiomiRs and their downstream effectors, promote islets survival and restore function, leading to enhanced angiogenesis and glycemic status.

Magnetic chitosan nanoparticles loaded with Amphotericin B: Synthesis, properties and potentiation of antifungal activity against common human pathogenic fungal strains.

Amphotericin B has long been regarded as the gold standard for treating invasive fungal infections despite its toxic potential. The main objective of this research was to develop a novel IONPs@CS-AmB formulation in a cost-effective manner in order to enhance AmB delivery performance, with lowering the drug's dose and adverse effects. The chitosan-coated iron oxide nanoparticles (IONPs@CS) were synthesized afterward, AmB-loaded IONPs@CS (IONPs@CS-AmB) prepared and characterized by AFM, FT-IR, SEM, EDX, and XRD. Biological activity of the synthesized NPs determined and the cytotoxicity of IONPs@CS-AmB evaluated using the MTT and in vitro hemolysis tests. The IONPs@CS-AmB was synthesized using the coprecipitation method with core-shell structure in size range of 27.70 to ∼70 nm. The FT-IR, XRD and EDX pattern confirmed the successful synthesis of IONPs @CS-AmB. The IONPs@CS-AmB exhibited significant antifungal activity and inhibited the metabolic activity of Candida albicans biofilms. The hemolysis and MTT assays showed that IONPs@CS-AmB is biocompatible with high cell viability when compared to plain AmB and fungizone. The IONPs@CS-AmB is more effective, less toxic and may be a suitable alternative to conventional drug delivery. IONPs@CS-AmB may be a viable candidate for use as a microbial-resistant coating on the surfaces of biomedical devices.

PLGA-graphene quantum dot nanocomposites targeted against αvß3 integrin receptor for sorafenib delivery in angiogenesis.

Angiogenesis is a vital step in many severe diseases such as cancer, diabetic retinopathy, and rheumatoid arthritis. Sorafenib (SFB), a multi-tyrosine kinase inhibitor, has recently been shown to inhibit tumor progression and suppress angiogenesis. Its narrow therapeutic window, however, has limited its clinical application and therapeutic efficacy. Accordingly, in this study, a nanocomposite formulation comprising of graphene quantum dots (GQDs) and poly (D, l-lactide-co-glycolide) (PLGA) nanoparticles was functionalized with an integrin-targeting ligand (RGD peptide) to improve SFB delivery for the treatment of angiogenesis. Physicochemical and biological properties of the targeted nanocomposite were evaluated in terms of chemical structure, morphology, particle size, zeta potential, photoluminescence, and cell toxicity. The loading capacity of the nanocomposite was optimized at different drug-to-PLGA ratios. Drug release behavior was also investigated at 37 °C in pH = 7.4. The SFB-to-PLGA ratio of 1:3 was selected as the optimum condition which resulted in the encapsulation efficiency and encapsulation capacity of 68.93 ± 1.39 and 18.77 ± 0.46, respectively. Photoluminescence properties of GQD in nanocomposite were used to track the delivery system. The results indicated that conjugating targeting ligand could enhance cellular uptake of nanocomposite in cells overexpressing integrin receptors. In vivo anti-angiogenesis activity of targeted nanocomposite was investigated in chick chorioallantoic membrane (CAM). The findings showed that SFB loaded in the targeted nanocomposite reduced VEGF secretion in vitro and its anti-angiogenic effect surpass free SFB. Thanks to its unique therapeutic and bioimaging properties, the developed nanocomposite could be an effective drug delivery system for poorly water-soluble therapeutic agents.

Synthesis of Pore-Size-Tunable Mesoporous Silica Nanoparticles by Simultaneous Sol-Gel and Radical Polymerization to Enhance Silibinin Dissolution.

Background: Silibinin (SBN), a major active constituent of milk thistle seeds, exhibits numerous pharmacological activities. However, its oral bioavailability is low due to poor water solubility. This study aimed to develop a new synthetic approach for tuning the pore characteristics of mesoporous silica nanoparticles (MSNs) intended for the oral delivery of SBN. In addition, the effects of the pore diameter of MSNs on the loading capacity and the release profile of SBN were investigated. Methods: The present study was performed at Shiraz University of Medical Sciences, Shiraz, Iran, in 2019. This synthesis method shares the features of the simultaneous free-radical polymerization of methyl methacrylate and the sol-gel reaction of the silica precursor at the n-heptane/water interface. SBN was loaded onto MSNs, the in vitro release was determined, and the radical scavenging activities were compared between various pH values using the analysis of variance. Results: According to the Brunauer-Emmett-Teller protocol, the pore sizes were well-tuned in the range of 2 to 7 nm with a large specific surface area (600-1200 m2/g). Dynamic light scattering results showed that different volume ratios of n-heptane/water resulted in different sizes, ranging from 25 to 100 nm. Interestingly, high SBN loading (13% w/w) and the sustained release of the total drug over 12 hours were achieved in the phosphate buffer (pH=6.8). Moreover, the antioxidant activity of SBN was well preserved in acidic gastric pH. Conclusion: Well-tuned pores of MSNs provided a proper substrate, and thus, enhanced SBN loading and oral dissolution and preserved its antioxidant activity. Nevertheless, further in vitro and in vivo investigations are needed.

Microneedle Arrays Combined with Nanomedicine Approaches for Transdermal Delivery of Therapeutics.

Organic and inorganic nanoparticles (NPs) have shown promising outcomes in transdermal drug delivery. NPs can not only enhance the skin penetration of small/biomacromolecule therapeutic agents but can also impart control over drug release or target impaired tissue. Thanks to their unique optical, photothermal, and superparamagnetic features, NPs have been also utilized for the treatment of skin disorders, imaging, and biosensing applications. Despite the widespread transdermal applications of NPs, their delivery across the stratum corneum, which is the main skin barrier, has remained challenging. Microneedle array (MN) technology has recently revealed promising outcomes in the delivery of various formulations, especially NPs to deliver both hydrophilic and hydrophobic therapeutic agents. The present work reviews the advancements in the application of MNs and NPs for an effective transdermal delivery of a wide range of therapeutics in cancer chemotherapy and immunotherapy, photothermal and photodynamic therapy, peptide/protein vaccination, and the gene therapy of various diseases. In addition, this paper provides an overall insight on MNs' challenges and summarizes the recent achievements in clinical trials with future outlooks on the transdermal delivery of a wide range of nanomedicines.

Paclitaxel-loaded polypeptide-polyacrylamide nanomicelles overcome drug-resistance by enhancing lysosomal membrane permeability and inducing apoptosis.

The aim of the current project was to investigate the in vitro properties of Paclitaxel (PTX)-loaded pHPMA5kD -pHis5kD -pLeu3kD nanomicelles (NMs) on multidrug resistance cell line. Circular dichroism analysis was done to investigate the effect of pH on the secondary structure of the copolymer. Cytotoxicity assay together with fluorescence imaging and flow cytometry were performed to get an insight about toxicity and cellular uptake mechanism of NMs. Acridine orange assay, rhodamine 123 (Rh123) accumulation assay, and apoptosis analysis were conducted for further investigation. It was found that the secondary structure of the copolymer changed in response to pH, PTX-loaded NMs had higher cytotoxicity on both drug-sensitive (MES-SA and MCF-7) and multidrug resistant cells (MES-SA/DX5) compared to free PTX, and interestinly free copolymer inhibited the growth of MES-SA/DX5 cells while it was nontoxic on drug-sensitive cells. Moreover, the copolymer was able to induce lysosome membrane permeation and increase Rh123 accumulation inside cells indicating inhibition of the P-gp efflux pumps. Finally, apoptosis was strongly induced in MES-SA/DX5 cells upon treatment with PTX-loaded NMs. It can be concluded that the designed hybrid copolymer is a good candidate for in vivo assay and developing a powerful system against multidrug resistance tumors.

microRNAs in liver and kidney ischemia reperfusion injury: insight to improve transplantation outcome.

Ischemia reperfusion injury (IRI) is a condition that occurs wherever blood flow and oxygen is reduced or absent, such as trauma, vascular disease, stroke, and solid organ transplantation. This condition can lead to tissue damage, especially during organ transplantation. Under such circumstances, some signaling pathways are activated, leading to up- or down- regulation of several genes such as microRNAs (miRNAs) that might attenuate or ameliorate this status. Therefore, by manipulating miRNAs level, they can be used as a biomarker for early diagnosis of IRI or suggestive to be therapeutic agents in clinical situation in future.

A DNA Based Biosensor Amplified With ZIF-8/Ionic Liquid Composite for Determination of Mitoxantrone Anticancer Drug: An Experimental/Docking Investigation.

An ultrasensitive DNA electrochemical biosensor based on the carbon paste electrode (CPE) amplified with ZIF-8 and 1-butyl-3-methylimidazolium methanesulfonate (BMIMS) was fabricated in this research. The DNA/BMIMS/ZIF-8/CPE was used for the selective determination of a mitoxantrone anticancer drug in aqueous solution, resulting in a good catalytic effect and a powerful ability for determining mitoxantrone. Also, the interaction of the mitoxantrone anticancer drug with guanine bases of ds-DNA was used as a powerful strategy in the suggested biosensor, which was confirmed with docking investigation. Docking study of mitoxantrone into the ds-DNA sequence showed the intercalative binding mode of mitoxantrone into the nitrogenous-based pairs of ds-DNA. The effective factors such as ds-DNA concentration, temperature, buffer types, and incubation time were also optimized for the fabricated mitoxantrone biosensor. The results showed that, under optimum conditions (T = 25°C; incubation time=12 min; pH= 4.8 acetate buffer solution and [DNA] = 50 mg/L), the DNA/BMIMS/ZIF-8/CPE could be used in mitoxantrone assay in a concentration ranging from 8.0 nM to 110 µM with a detection limit of 3.0 nM. In addition, recovery data between 99.18 and 102.08% were obtained for the determination of mitoxantrone in the injection samples using DNA/ZIF-8/BMIMF/CPE as powerful biosensors.

Evaluation of the efficacy of albendazole sulfoxide (ABZ-SO)-loaded chitosan-PLGA nanoparticles in the treatment of cystic echinococcosis in laboratory mice.

Albendazole is known as the drug of choice for medical treatment of cystic echinococcosis (CE). Albendazole sulfoxide (ABZ-SO), as the main active metabolite of albendazole, has low efficacy in the disease due to low water solubility and poor absorptivity. PLGA nanoparticles (NPs) enhance the dissolution of poorly soluble drugs, and chitosan (CS) coating enhances oral drug delivery of NPs. In this study, the efficacy of ABZ-SO-loaded CS-PGLA NPs in the treatment of CE was evaluated in laboratory mice. ABZ-SO-loaded CS-PGLA NPs were prepared by nanoprecipitation and characterized by dynamic light scattering method and scanning electron microscopy. Thirty mice were intraperitoneally infected by 1000 protoscoleces of Echinococcus granulosus. Ten months later, the mice were allocated into 3 groups: groups 1 and 2 were treated with ABZ-SO and ABZ-SO-loaded CS-PGLA NPs, respectively, and the mice in group 3 remained untreated as the control group. The drugs were administered by gavage for 45 days at a daily dose of 10 mg/kg. Finally, all mice were opened and the cysts were collected, counted, weighed, and measured separately. The therapeutic effect of ABZ-SO in the number, weight, and volume of the cysts were not statistically significant compared with those in ABZ-SO-loaded CS-PGLA NPs and the control group. However, the therapeutic effect of ABZ-SO-loaded CS-PGLA NPs in the weight and volume of cysts were statistically significant when compared with that in the control group (p ˂ 0.05). In conclusions, this study revealed that ABZ-SO-loaded CS-PGLA NPs could enhance the therapeutic efficacy of ABZ-SO in the treatment of CE in laboratory mice.

Evaluation of Pt,Pd-Doped, NiO-Decorated, Single-Wall Carbon Nanotube-Ionic Liquid Carbon Paste Chemically Modified Electrode: An Ultrasensitive Anticancer Drug Sensor for the Determination of Daunorubicin in the Presence of Tamoxifen.

Measuring the concentration of anticancer drugs in pharmacological and biological samples is a very useful solution to investigate the effectiveness of these drugs in the chemotherapy process. A Pt,Pd-doped, NiO-decorated SWCNTs (Pt,Pd-NiO/SWCNTs) nanocomposite was synthesized using a one-pot procedure and combining chemical precipitation and ultrasonic sonochemical methods and subsequently characterized by TEM and EDS analysis methods. The analyses results showed the high purity and good distribution of elements and the ~10-nm diameter of the Pt,Pd-NiO nanoparticle decorated on the surface of the SWCNTs with a diameter of about 20-30 nm. Using a combination of Pt,Pd-NiO/SWCNTs and 1-butyl-2,3-dimethylimidazolium tetrafluoroborate (1B23DTFB) in a carbon paste (CP) matrix, Pt,Pd-NiO/SWCNTs/1B23DTFB/CP was fabricated as a highly sensitive analytical tool for the electrochemical determination of daunorubicin in the concentration range of 0.008-350 µM with a detection limit of 3.0 nM. Compared to unmodified CP electrodes, the electro-oxidation process of daunorubicin has undergone significant improvements in current (about 9.8 times increasing in current) and potential (about 110 mV) decreasing in potential). It is noteworthy that the designed sensor can well measure daunorubicin in the presence of tamoxifen (two breast anticancer drugs with a ΔE = 315 mV. According to the real sample analysis data, the Pt,Pd-NiO/SWCNTs/1B23DTFB/CP has proved to be a promising methodology for the analysis and measuring of daunorubicin and tamoxifen in real (e.g., pharmaceutical) samples.

Facile synthesis and characterization of magnetic nanocomposite ZnO/CoFe2O4 hetero-structure for rapid photocatalytic degradation of imidacloprid.

This work has attempted to investigate the potential of ZnO/CoFe2O4 magnetic nanocomposite to mineralize imidacloprid completely to have sustainable pollutant free and safe water supply. The co-precipitation method was performed to prepare the composites; was performed to characterize composites, scanning electron microscope (SEM), transmission electron microscopy (TEM), energy dispersive x-ray crystallography (EDX), x-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, and vibrating sample magnetometer (VSM). It was attempted to explore and enhance parameters influencing the process and the percentage of imidacloprid degradation, including photocatalyst amount, pesticide concentration, pH, radiation time, and temperature. UV-Vis spectrophotometer was used for the degradation percent of organochlorine pesticides. Parameters affecting the process, including photocatalyst amount, pesticide concentration, pH, radiation time, and temperature effect on the percentage of imidacloprid degradation were Investigated and optimized. 0.05 g of photocatalyst, with a concentration of 5 ppm for 45 min under light exposure was obtained at pH 10 at room temperature.

Nanoparticulate delivery of irinotecan active metabolite (SN38) in murine colorectal carcinoma through conjugation to poly (2-ethyl 2-oxazoline)-b-poly (L-glutamic acid) double hydrophilic copolymer.

SN-38 is the active metabolite of irinotecan, an FDA-approved chemotherapeutic agent indicated for colorectal carcinoma, which would not be clinically applicable due to its very poorly soluble and hydrolytic degradation properties. To overcome these limitations, it was proposed to conjugate SN38 to residing carboxylic acid residues in poly (2-ethyl 2-oxazoline) block poly (L-glutamic acid), inducing nano-assembly in aqueous medium. Following a series of reactions including poly (2-ethyl oxazoline) macro-initiated ring opening polymerization of N-carboxyanhydride, deprotection of benzyl group and chemical conjugation of SN38 via biodegradable ester linkage, the as-synthesized product was characterized by dynamic light scattering, ζ potential and transmission electron microscopy. The resulting particles presented about 90% loading efficiency with a mean size of 90 nm. Upon incubation with colorectal carcinoma CT26 cell line, higher association of SN-38 fluorescence and significantly more specific cytotoxicity was noticed for the SN38 conjugated particles than free drug. Therapeutic applicability of the as-synthesized product was evaluated in CT26 allograft tumor model in BALB/c mice, showing superior efficiency of the SN38 conjugated particles particularly in tumors with sizes larger than 200 mm3 than parent irinotecan and reduced mortality rate by 2.5 times. Conclusively, the poly (2-ethyl 2-oxazoline) decorated nano-conjugates of poly (L-glutamic acid) and SN38 can be regarded as a novel and potentially efficient drug delivery system for advanced colorectal carcinoma.

Generation and characterization of a specific single-chain antibody against DSPP as a prostate cancer biomarker: Involvement of bioinformatics-based design of novel epitopes.

Isolation of specific single chain antibodies (scFvs) against key epitopes of cancer markers are applied for cancer immunotherapy and diagnosis. In this study following the prediction of the 3D structure of the DSP part of Dentin sialophosphoprotein (DSPP), the epitope was chosen using in silico programs. Panning process was applied to isolate specific human scFv against the epitope. PCR and DNA fingerprinting differentiated the specific clones, which were evaluated by phage ELISA. Following DNA sequencing, the 3D structure of isolated scFv was modeled and Docked on DSP. Results demonstrated the selection of a specific anti-DSPP scFv with 40% frequency, which reacted significantly with the predicted epitope and PCa patients' urines in ELISA tests (P-value < 0.05). The VH and VL of the isolated scFv were from VH1 and VL3 gene families with several amino acid changes in CDRs and FRs domains. The scFv tightly bound to the DSP epitope with the lowest energy level by hydrogen bonds, cation-pi, hydrophobic and ionic interactions demonstrating the specificity of Ag-Ab interactions. The anti-DSPP scFv selected in this study with significant specificity to DSPP antigen offers a promising new agent for both PCa early detection and treatment of cancers with DSPP expression.

Reversing multi-drug tumor resistance to Paclitaxel by well-defined pH-sensitive amphiphilic polypeptide block copolymers via induction of lysosomal membrane permeabilization.

A series of hybrid di-block copolymers of poly(l- glutamic acid-b-l- leucine) (PGA-PLeu), methoxy poly (ethylene glycol)-b-poly(l-leucine) (PEG-PLeu), methoxy poly(ethylene glycol)-b-poly(γ-benzyl-l-glutamic acid) (PEG-PBLG) and tri-block copolymers of poly(ethylene glycol)-b-poly(l-glutamic acid-co-null-leucine) (PEG-PGA-PLeu) were synthesized through sequential HMDS-mediated ring-opening polymerization (ROP). Chemical structure of copolymers was studied by FTIR and 1H-NMR and their molecular weight was determined by 1H-NMR and gel permeation chromatography (GPC). Copolymers self-assembled into nanomicelles with particle size (PS) of 65 to 139 nm. Higher fraction of polyleucine (% fPLeu) led to significantly larger PS, lower critical aggregation concentration (CAC) and higher drug loading content (DLC%). In addition, introducing PEG segment led to significant decrease in PS, increase of CAC and DLC%. Apart from copolymer composition, DLC% changed by the method with significantly higher loading for solid dispersion. Remarkably, the release of PTX from PEG-PGA-PLeu tri-block copolymers was highly dependent on pH, revealing a relatively two-fold faster release at pH 5 than pH 7.4. CD spectroscopy showed transition to α-helix secondary structure at acidic pH. Hemocompatibility assay confirmed that copolymers were absolutely hemocompatible at physiological pH. MTT assays demonstrated that unlike MCF7 and 4T1 cells that PTX-loaded nanoparticles (PTX-NPs) exhibited similar antitumor activity, ten-fold higher toxicity was recognized in multidrug-resistant uterine sarcoma cells (MES-SA/DX5). Fluorescent imaging and flow cytometric analysis of cellular uptake showed that nanoparticles' uptake was time-dependent. It was also revealed that higher toxicity of the PTX-NPs could be due to ability of copolymer to inhibit P-gp pumps and induce lysosomal membrane permeabilization (LMP).

Effect of PEGylation on assembly morphology and cellular uptake of poly ethyleneimine-cholesterol conjugates for delivery of sorafenib tosylate in hepatocellular carcinoma.

Introduction: Sorafenib (SFB) is an FDA-approved chemotherapeutic agent with a high partition coefficient (log P = 4.34) for monotherapy of hepatocellular carcinoma (HCC). The oral bioavailability is low and variable, so it was aimed to study the application of the polymeric nanoassembly of cholesterol conjugates of branched polyethyleneimine (PEI) for micellar solubilization of SFB and to investigate the impact of the polymer PEGylation on the physicochemical and cellular characteristics of the lipopolymeric dispersions. Methods: Successful synthesis of cholesterol-PEI lipopolymers, either native or PEGylated, was confirmed by FTIR, 1H-NMR, pyrene assay methods. The nanoassemblies were also characterized in terms of morphology, particle size distribution and zeta-potential by TEM and dynamic light scattering (DLS). The SFB loading was optimized using general factorial design. Finally, the effect of particle characteristics on cellular uptake and specific cytotoxicity was investigated by flow cytometry and MTT assay in HepG2 cells. Results: Transmission electron microscopy (TEM) showed that PEGylation of the lipopolymers reduces the size and changes the morphology of the nanoassembly from rod-like to spherical shape. However, PEGylation of the lipopolymer increased critical micelle concentration (CMC) and reduced the drug loading. Moreover, the particle shape changes from large rods to small spheres promoted the cellular uptake and SFB-related cytotoxicity. Conclusion: The combinatory effects of enhanced cellular uptake and reduced general cytotoxicity can present PEGylated PEI-cholesterol conjugates as a potential carrier for delivery of poorly soluble chemotherapeutic agents such as SFB in HCC that certainly requires further investigations in vitro and in vivo.

Co-condensation synthesis of well-defined mesoporous silica nanoparticles: effect of surface chemical modification on plasmid DNA condensation and transfection.

Chemically modified mesoporous silica nanoparticles (MSNs) are of interest due to their chemical and thermal stability with adjustable morphology and porosity; therefore, it was aimed to develop and compare the MCM-41 MSNs functionalised with imidazole groups (MCM-41-Im) to unmodified (MCM-41-OH) and primary amine functionalised (MCM-41-NH2) MSNs for experimental gene delivery. The results show efficient transfection of the complexes of the plasmid and either MCM-41-NH2 or MCM-41-Im. Furthermore, following transfection of HeLa cells using MCM-41-Im, an enhanced GFP expression was achieved consistent with the noticeable DNase1 protection and endosomal escape properties of MCM-41-Im using carboxyfluorescein tracer.

The structural damages of lens crystallins induced by peroxynitrite and methylglyoxal, two causative players in diabetic complications and preventive role of lens antioxidant components.

Peroxynitrite (PON) and methylglyoxal (MGO), two diabetes-associated compounds, are believed to be important causative players in development of diabetic cataracts. In the current study, different spectroscopic methods, gel electrophoresis, lens culture and microscopic assessments were applied to examine the impact of individual, subsequent or simultaneous modification of lens crystallins with MGO and PON on their structure, oligomerization and aggregation. The protein modifications were confirmed with detection of the significantly increased quantity of carbonyl groups and decreased levels of sulfhydryl, tyrosine and tryptophan. Also, lens proteins modification with these chemical agents was accompanied with important structural alteration, oligomerization, disulfide/chromophore mediated protein crosslinking and important proteolytic instability. All these structural damages were more pronounced when the lens proteins were modified in the presence of both mentioned chemical agents, either in sequential or simultaneous manner. Ascorbic acid and glutathione, as the main components of lens antioxidant defense mechanism, were also capable to markedly prevent the damaging effects of PON and MGO on lens crystallins, as indicated by gel electrophoresis. The results of this study may highlight the importance of lens antioxidant defense system in protection of crystallins against the structural insults induced by PON and MGO during chronic hyperglycemia in the diabetic patients.

Effectiveness of Anise Oil for Treatment of Mild to Moderate Depression in Patients With Irritable Bowel Syndrome: A Randomized Active and Placebo-Controlled Clinical Trial.

Depression is a prevalent disorder among patients suffering from irritable bowel syndrome. The current study was performed to evaluate the effect of a traditional Persian medicine product, anise oil, in removing the symptoms of mild to moderate depression in patients with irritable bowel syndrome. In a randomized double-blinded active and placebo controlled clinical trial, 120 participants with mild to moderate depression according to the Beck Depression Inventory-II total scores were categorized into 3 equal groups and received anise oil, Colpermin, and placebo. The results at the end of trial (week 4) and follow-up (week 6) demonstrated significant priority against active and placebo groups. Although the mechanism is unknown yet, anise oil could be a promising choice of treatment for depressed patients with irritable bowel syndrome.