Cytotoxic and epigenetic effects of berberine-loaded chitosan/pectin nanoparticles on AGS gastric cancer cells: Role of the miR-185-5p/KLF7 axis, DNMTs, and global DNA methylation.

Poor bioavailability, solubility, and absorption of berberine (Ber) limit its widespread application. Here, we formulated novel chitosan/pectin nanoparticles (NPs) loaded with Ber to address delivery problems and promote the anticancer properties of Ber in AGS gastric cancer cells. The ionic gelification method was used to synthesize NPs-Ber. Physicochemical characterization of NPs-Ber was performed using FE-SEM, DLS, PDI, ζ potential, and FTIR. The cytotoxic effects of NPs-Ber on AGS cells were evaluated using the MTT assay. Apoptosis and cell cycle arrest were examined by flow cytometry. The gene expression levels of miR-185-5p, KLF7, caspase-3, and DNMTs were determined using RT-qPCR. In addition, the 5-methylcytosine level in the genomic DNA was quantified using ELISA. FE-SEM images revealed a denser and more packed matrix for NPs-Ber, and FTIR analysis confirmed the formation of NPs-Ber. The size (550.39 nm), PDI (0.134), and ζ potential (-16.52 mV) confirmed the stability of the prepared NPs-Ber. NPs-Ber showed a continuous release pattern following the Korsmeyer-Peppas model such that 81.36 % of Ber was released from the formulation after 240 min. Compared to NPs and free Ber, NPs-Ber was found to possess higher anticancer activity in AGS cells. This result was indicated by the viability test and further clarified by augmented apoptosis and cell cycle arrest at the G0/G1 phase. The IC50 value of NP-Ber against AGS cells was significantly lower than those of free Ber and NPs. Interestingly, our results showed that NPs-Ber considerably changed the expression levels of miR-185-5p, KLF7, caspase-3, and DNMTs (DNMT1, 3A, and 3B) compared with unloaded NPs and free Ber. Additionally, 5-methylated cytosine (5-mC) levels in cells treated with NPs-Ber were significantly higher than those in cells treated with unloaded NPs or free Ber. In summary, the present study demonstrated that Ber encapsulation in NPs enhances its cytotoxic and epigenetic effects on AGS cells, suggesting the promising potential of NPs-Ber in GC therapy.

Loaded paraquaton polymeric nanocapsules and evaluation for cardiotoxicity in Wistar rats.

Present work was conducted to prepare and evaluate, loaded paraquat nano-hydrogels using chitosan, sodium polytriphosphate, and xanthan via ionic gelification method. The fabricated L-PQ formulations were analyzed for surface morphology and functional groups using SEM and FTIR, respectively. The stability of the synthesized nanoparticle was, also, analyzed in terms of diameter size, zeta potential, dispersion index, and pH. Furthermore, the cardiotoxicity effects of the synthesized nanogels were investigated on Wistar rats in terms of enzymatic activity, echocardiographic, and histological analysis. The proper stability of the prepared formulation was also confirmed by diameter size, zeta potential, dispersion index, and pH. The efficiency of encapsulation was about 90±3.2% and the release of PQ in the loaded nanogel was about 90±2.3%. A decrease in ST (shortening time) segment by formulated PQ, either in peritoneal or gavage exposure pathway, indicates the effectiveness of the capsule layer against the penetration of toxin into the body.

A self-healable and bioadhesive acacia gum polysaccharide-based injectable hydrogel for wound healing acceleration.

The present study aimed at developing an injectable hydrogel based on acacia gum (AG) for wound healing acceleration. The hydrogels were synthetized through metal-ligand coordination mediated by Fe3+ and characterized in terms of gelation time, gel content, initial water content, swelling capacity, water retention ratio, and porosity. Moreover, FTIR, XRD and TGA analyses were performed for the hydrogels and allantoin (Alla) loaded ones. Furthermore, bioadhessiveness, and self-healing as well as antibacterial, toxicity and wound healing potentials of the hydrogels were evaluated. The hydrogels displayed fast gelation time, high swelling, porosity, and bioadhessiveness, as well as antioxidant, self-healing, antibacterial, blood clotting, and injectability properties. FTIR, XRD and TGA analyses confirmed hydrogel synthesis and drug loading. The Alla-loaded hydrogels accelerated wound healing by decreasing the inflammation and increasing the cell proliferation as well as collagen deposition. Hemocompatibility, cell cytotoxicity, and in vivo toxicity experiments were indicative of a high biocompatibility level for the hydrogels. Given the advantages of fast gelation, injectability and beneficial biological properties, the use of Alla-loaded hydrogels could be considered a new remedy for efficient wound healing.

Electrospun Nanofibrous Biocomposite of Royal Jelly/Chitosan/Polyvinyl Alcohol (RJ/CS/PVA) Gel as a Biological Dressing for P. aeruginosa-Infected Burn Wound.

Burn wounds are vulnerable to various infections due to damage to the tissue and changes in immune responses. Pseudomonas aeruginosa is a critical bacterium that can cause burn wound infections, which can be life-threatening and delay wound healing. Therefore, it is essential to develop an efficient strategy to prevent the spread of infection in burn wounds. The present study aims to investigate the effectiveness of electrospun nanofibers of royal jelly on a chitosan/polyvinyl alcohol polymer scaffold in repairing burn wounds infected with Pseudomonas aeruginosa. To achieve this, the researchers analyzed the morphology and physicochemical properties of the synthesized nanofibers using SEM, FTIR, BET, and TGA analyses. They also examined the antibacterial properties of the nanofibers using agar diffusion and spread plate techniques. In addition, hemolysis tests were carried out to assess biocompatibility. Finally, the ability of the nanofibers to repair burn wounds infected with Pseudomonas aeruginosa was evaluated using a laboratory mouse model. The study results showed that the synthesized nanofibers had desirable morphology and physicochemical properties and significant antibacterial effects in both in vitro and in vivo conditions. Also, loading RJ into the polymer scaffold significantly reduced erythrocyte lysis. The wound healing and contraction rates were significantly higher than the control groups, and tissue repair, re-epithelialization, and collagen synthesis occurred faster, preventing the spread of infection to deeper tissue areas. Based on these findings, the synthesized system has the potential to serve as a suitable substitute for some invasive treatments and chemical drugs to improve chronic wounds and manage infection control in burn injuries.

Green Synthesis, Characterization, and Antiparasitic Effects of Gold Nanoparticles against Echinococcus granulosus Protoscoleces.

Echinococcosis, or hydatidosis, is one of the most important zoonotic diseases, which is initiated by the larval stage in the clasts of Echinococcus granulosus. For the treatment of hydatidosis, surgery is still the preferred method and the first line of treatment for symptomatic patients. Unfortunately, most of the scolicidal agents that are injected inside cysts during hydatid cyst surgery have side effects, including leaking out of the cyst and adverse effects on the living tissue of the host, such as necrosis of liver cells, which limits their use. This work was carried out to study the lethal effect of green synthesized gold nanoparticles (Au-NCs) against hydatid cyst protoscoleces. Au-NCs were green synthesized using the Saturja khuzestanica extract. Au-NCs were characterized by UV-visible absorbance assay, electron microscopy analysis, X-ray diffraction (XRD), and Fourier transform infrared (FTIR) spectroscopy. Scolicidal properties of Au-NCs (1-5 mg/mL) were studied against protoscoleces for 10-60 min. The effect of Au-NCs on the expression level of the caspase-3 gene as well as the ultrastructural examination was studied by real-time PCR and scanning electron microscopy (SEM). The cytotoxicity of Au-NCs on hepatocellular carcinoma (HepG2) and normal embryonic kidney (HEK293) cell lines was also studied by the cell viability assay. The obtained Au-NCs are cubes and have an average size of 20-30 nm. The highest scolicidal efficacy was observed at 5 mg/mL with 100% mortality after 20 min of treatment for hydatid cyst protoscoleces. In ex vivo, Au-NCs required more incubation time, indicating more protoscolicidal effects. Au-NCs markedly upregulated the gene level of caspase-3 in protoscoleces; whereas they changed the ultra-structure of protoscoleces by weakening and disintegrating the cell wall, wrinkles, and protrusions due to the formation of blebs. We showed the effective in vitro and ex vivo scolicidal effects of Au-NCs against hydatid cyst protoscoleces by provoking the apoptosis process of caspase-3 activation and changing the ultrastructure of protoscoleces with no significant cytotoxicity against human normal cells. However, additional studies should be conducted to determine the possible harmful side effects and accurate efficacy.

Anti-obesity effects of aerobic exercise along with Rosa canina seed extract supplementation in rats: The role of irisin and adipolin.

Aerobic exercise and some bioactive compounds in medicinal plants have anti-obesity effects and can suppress body weight. The aim of this study was to determine the anti-obesity effects of 6 weeks of aerobic exercise (AE) and supplementation of the hydroalcoholic extract of Rosa canina fruit seed (RC) in obese male rats. In this experimental study, 24 high-fat diet (HFD) obese male Wistar rats were used. The animals were randomly divided into 4 groups (6 rat in group), including 1. HFD (the control group), 2. HFD + AE, 3. HFD + RC and 4. HFD + AE + RC. An obesity protocol was implemented for 12 weeks with the consumption of HFD along with the consumption of water containing 1 % fructose. Afterwards, the animals were given access only to HFD food until the end of the study in all the groups. After the obesity protocol, 6 weeks of exercise (50-70 % VO2 max) and access to the extract (1 % of the consumed food) were given. Bodyweight, subcutaneous adipose tissue mass, and some serum lipid profiles were measured in the experimental groups. The serum levels of irisin and adipolin were evaluated by the ELISA method. Expression of FNDC5 and CTRP12 in adipose tissue were determined by real-time PCR. The findings of this study showed that body weight (P = 0.001), subcutaneous adipose tissue mass (P = 0.001), and lipid profile were significantly reduced in HFD + AE and HFD + AE + RC groups compared with the HFD group. Irisin was significantly increased in the HFD + AE and HFD + AE + RC groups compared with the HFD group (P = 0.019 and P = 0.001; respectively) and in the HFD + AE + RC group compared with the HFD + RC group (P = 0.004). Moreover, adipolin, expression of FNDC5 and CTRP12 were significantly increased in the HFD + AE + RC group compared with the HFD group (P = 0.004, P = 0.023, and P = 0.001; respectively). Altogether, HFD + AE with HFD + RC diet supplementation could reduce weight and the risks of obesity, at least, through the up-regulation of irisin and adipolin.

Evaluation of scolicidal potential of salicylate coated zinc nanoparticles against Echinococcus granulosus protoscoleces.

Echinococcosis is a zoonotic disease caused by larval stages of the Echinococcus genus (metastasis). In this study, salicylate-coated Zinc oxide nanoparticles (SA-ZnO-NPs) were fabricated and characterized by SEM, FTIR and XRD analytical techniques. After that, different doses of SA-ZnO-NPs, SA and ZnO-NPs were taken to assess scolicidal potency. Scanning electron microscopy (SEM) micrographs were also used to evaluate the morphological deformities of treated protoscoleces. Furthermore, Caspase-3&7 inductions were examined in protoscoleces cysts treated with all formulations. Based on SEM and DLS analyses, the size of SA-ZnO-NPs was between 30 and 40 nm, with a spherical shape. The FTIR spectrum verified the presence of SA functional groups on the ZnO coating. At 20 min, SA-ZnO-NPs at 2000 µg/ml exhibited the greatest activity on protoscolices with 100% mortality, followed by ZnO-NPs at 1500 µg/ml at 10 min and SA alone at 2000 µg/ml at 30 min. The activation of Caspase-3&7 apoptotic enzyme was determined for 2000 µg/ml of SA-ZnO-NPs, ZnO-NPs and SA to be 16.4, 31.4, and 35.7%, respectively. The SEM image revealed apoptogenic alterations and the induction of tegument surface wrinkles, as well as abnormalities in rostellum protoscolices. According to the current study, SA-ZnO-NPs have a high mortality rate against hydatid cyst protoscolices. As a result, further studies on the qualitative assessment of these nanoformulations in vivo and preclinical animal trials seem to be required. Furthermore, the adoption of nano-drugs potentially offers alternative therapeutic approaches to combat hydatid cysts.

Toxicity of green synthesized TiO2 nanoparticles (TiO2 NPs) on zebra fish.

Nanoparticles (NPs) is usually fabricated by physical and chemical methods which, consequently, may have adverse effects for human and environment. Therefore, novel environmentally friendly synthesis methods for are essential and preferred. The purpose of this study was to synthesize TiO2 NPs using Echinophora cinerea extract and evaluate its toxicity on zebra fish. In the work, extraction phase was performed using a water as solvent. FTIR, XRD, SEM, and DLS analyzes were performed to determine the characteristics of synthesized TiO2 NPs. The effect of different parameters such as pH, extract concentration, TiO2 concentration, and temperature were investigated on TiO2 NP and optimized. Then, the acute toxicity of synthesized TiO2 NPs at different concentrations was investigated for 96 h on zebra fish. The bioassay data was analyzed via probit regression technique. Based on the obtained results, the optimal conditions for the synthesized TiO2 NPs were 9, 20 g/L, 0.4 g/L, and 25 °C for pH, extract concentration, TiO2 concentration and temperature, respectively. Both FTIR and XRD analysis confirmed the stability and structure of the synthesized NPs. According to SEM and DLS analysis, the synthesized NPs were spherical in shape and about 244.7 nm in diameter. Based on bioassay, LC50 for green synthesized TiO2 NPs with Echinophora cinerea extract at 48 h was 300 mg/L, which revealed a less hazardous material.

Native Iranian Medicinal Plants with Anti-Vaginal Infection Properties: A Systematic Review.

BACKGROUND: The use of herbs has recently been considered an effective method in the treatment of infections. The purpose of this study was to introduce Iranian medicinal plants with an effect on vaginal infections. METHODS: In our systematic review study, keywords including 'medicinal plants', 'Iranian medicinal plants', 'vaginal infection', 'essential oils', and 'extracts' were searched in PubMed, Web of Science Direct, Scopus, Scientific Information Database, and Google Scholar. This study focused on the articles published from 2000 to 2019. RESULTS AND DISCUSSION: According to our investigation, Stachys lavandulifolia, Thymus vulgaris L., Origanum vulgare L., Allium jesdianum, Cichorium intybus, Trigonella foenum-graecum, Azadirachta Indica, Stachys lavandulifolia, Coriandrum sativum L., Rosmarinus officinalis, Ferula gummosa L., Origanum syriacum, Eucalyptus globulus, Myrtus communis, Zingiber officinale, Punica granatum, Vitex agnus-castus, Mentha suaveolens, Quercus Brantii Lindl, Zataria multiflora, Berberis vulgaris, Thymus vulgaris L., Echinophora platyloba, Stachys lavandulifolia, Viola odorata, Menthe piperita, Eucalyptus camaldulensis, Ziziphus mauritiana, Quercus infectoria, Hypericum perforatum, Glycyrrhiza glabra L., Calendula officinalis, Origanum vulgare, Ziziphus nummularia, Satureja Bachtiarica, Foeniculum vulgare, Nigella sativa, Anethum graveolens, Salvia officinalis, and Calendula officinalis are used to treat vaginal infections. CONCLUSION: Therefore, native plants of Iran have been reported to have antimicrobial properties for the treatment of vaginal infections and can be used as a suitable and effective alternative to antibiotics in future research.

Genome-wide evaluation of transcriptomic responses of human tissues to smoke: A systems biology study.

The harmful compounds in various sources of smoke threaten human health. So far, many studies have investigated the effects of compounds of smoke on transcriptome changes in different human tissues. However, no study has been conducted on the effects of these compounds on transcriptome changes in different human tissues simultaneously. Hence, the present study was conducted to identify smoke-related genes (SRGs) and their response mechanisms to smoke in various human cells and tissues using systems biology based methods. A total of 6,484 SRGs were identified in the studied tissues, among which 4,095 SRGs were up-regulated and 2,389 SRGs were down-regulated. Totally, 459 SRGs were smoke-related transcription factors (SRTFs). Gene regulatory network analysis showed that the studied cells and tissues have different gene regulation and responses to compounds of smoke. The comparison of different tissues revealed no common SRG among the all studied tissues. However, the CYP1B1 gene was common among seven cells and tissues, and had the same expression trend. Network analysis showed that the CYP1B1 is a hub gene among SRGs in various cells and tissues. To the best of our knowledge, for the first time, our results showed that compounds of smoke induce and increase the expression of CYP1B1 key gene in all target and non-target tissues of human. Moreover, despite the specific characteristics of CYP1B1 gene and its identical expression trend in target and non-target tissues, it can be used as a biomarker for diagnosis and prognosis.

The efficacy of olive leaf extract on healing herpes simplex virus labialis: A randomized double-blind study.

OBJECTIVE: Herpes simplex virus (HSV), as a common infection in healthy individuals, is treated symptomatically, but drug resistance and the side effects of drugs have drawn the attention of researchers to complementary medicine. Olive Leaf Extract (OLE) has antiviral effects that may treat HSV. The current study aimed to compare the clinical effects of OLE and Acyclovir on HSV-1. METHODS: This randomized double-blind clinical trial was conducted on 66 patients who had already been diagnosed with HSV-1. The participants were randomized into two groups, receiving 2% OLE cream or 5% acyclovir cream five times a day for six days. The symptoms were evaluated before, and three and six days after the interventions. Data were analyzed using the SPSS software through the Kolmogorov-Smirnov test, chi-squared, t-test, and repeated measures ANOVA. RESULTS: The results showed clinical symptoms decreased in both groups during the study and both medications were effective in the treatment of HSV-1. However, the OLE group experienced less bleeding (P = 0.038), itching (P = 0.002), and pain (P = 0.001) on the third day as well as less irritation (P = 0.012), itching (P = 0.003) and color change (P = 0.001) on the sixth day compared to the acyclovir group. The treatment course for participants in the OLE group was shorter than in the acyclovir group (P = 0.001). CONCLUSION: The evidence from these trials suggests the OLE cream is superior in the healing of episodes of HSV-1 over the acyclovir cream. Future studies are recommended to investigate if OLE could be an adjunct to acyclovir treatment.

Pectin/chitosan/tripolyphosphate encapsulation protects the rat lung from fibrosis and apoptosis induced by paraquat inhalation.

BACKGROUND: Paraquat poisoning leads to lung injury and pulmonary fibrosis. The effect of paraquat encapsulation by previously described Pectin/Chitosan/Tripolyphosphate nanoparticles on its pulmonary toxicity was investigated in present study in a rat model of poison inhalation. MATERIAL AND METHOD: The rats inhaled nebulized different formulation of paraquat (n = 5) for 30 min in various experimental groups. Lung injury and fibrosis scores, Lung tissue enzymatic activities, apoptosis markers were determined compared among groups. RESULTS: Encapsulation of paraquat significantly rescued both lung injury and fibrosis scores. Lung MDA level was reduced by encapsulation. Paraquat poisoning led to lung tissue apoptosis as was evidenced by higher Caspase-3 and Bax/Bcl2 expressions in rats subjected to paraquat inhalation instead of normal saline or free nanoparticles. Again, nanoencapsulation reduced these apoptosis markers significantly. Alpha-SMA expression was also reduced by encapsulation. Nanoparticles per se have no or little toxicity as was evidenced by inflammatory and apoptotic markers and histological scores. CONCLUSION: In a rat model of inhalation toxicity of paraquat, loading of this herbicide on PEC/CS/TPP nanoparticles reduced acute lung injury and fibrosis. The encapsulation also led to lower apoptosis, oxidative stress and alpha-SMA expression in the lung tissue.

Encapsulation of Satureja khuzistanica jamzad essential oil in chitosan nanoparticles with enhanced antibacterial and anticancer activities.

Satureja khuzistanica jamzad (SKJ), which is a member of Lamiaceae, has various proven effects such as antispasmodic and anti-inflammatory, anti-diabetic, antioxidant, and antifungal properties. However, the use of essential oil of plants is limited due to their inherent instability in the environment. Encapsulation with nanoparticles in the nanogel forms is one of their stabilization methods. The aim of this study was to synthesize nano-gel based on chitosan (CS) and extracts of SKJ essential oil, and to evaluate the antibacterial and anticancer activities. SKJ essential oil was extracted using water distillation method. Then, it was loaded on CS particles using two-step process as following: droplets formation and freezing. The Dynamic Light Scattering (DLS), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), and Zeta potential determination were used to evaluate the physical and chemical properties of CS-SKJ nanogel, which its result was acceptable. After confirmation of the loaded essential oil rate and releasing amount, the antibacterial effects were evaluated on five Gram-positive bacteria and five Gram-negative bacteria using microbroth dilution method. The encapsulation efficiency, size, polydispersity index, and zeta potential of nanoparticles were characterized were 30.74%, 571.00 nm, 0.451 and -67.2 mV, respectively. The results were significant not only on Gram-positive bacteria, but also on Gram-negative bacteria. The MIC range was between 7.8 and 500 µg/ml. The CS-SKJ nanogel has acceptable anticancer activities on KB and A549 tumor cell lines. the IC50 range was between 5.6 and 6.71 µg/ml. The results indicate that both CS particles and SKJ alone, and CS-SKJ nanogel could be considered as the outlook to produce new antimicrobial and anticancer drugs.

Myrtus communis Essential Oil; Anti-Parasitic Effects and Induction of the Innate Immune System in Mice with Toxoplasma gondii Infection.

BACKGROUND: Myrtus communis (M. communis) is a wild aromatic plant used for traditional herbal medicine that can be demonstrated in insecticidal, antioxidant, anti-inflammatory, and antimicrobial activity of its essential oils (MCEO). AIM: The present study aimed to evaluate the prophylactic effects of M. communis essential oil (MCEO) against chronic toxoplasmosis induced by the Tehran strain of Toxoplasma gondii in mice. METHODS: Gas chromatography/mass spectrometry (GC/MS) analysis was performed to determine the chemical composition of MCEO. Mice were then orally administrated with MCEO at the doses of 100, 200, and 300 mg/kg/day and also atovaquone 100 mg/kg for 21 days. On the 15th day, the mice were infected with the intraperitoneal inoculation of 20-25 tissue cysts from the Tehran strain of T. gondii. The mean numbers of brain tissue cysts and the mRNA levels of IL-12 and IFN-γ in mice of each tested group were measured. RESULTS: By GC/MS, the major constituents were α-pinene (24.7%), 1,8-cineole (19.6%), and linalool (12.6%), respectively. The results demonstrated that the mean number of T. gondii tissue cysts in experimental groups Ex1 (p < 0.05), Ex2 (p < 0.001) and Ex3 (p < 0.001) was meaningfully reduced in a dose-dependent manner compared with the control group (C2). The mean diameter of tissue cyst was significantly reduced in mice of the experimental groups Ex2 (p < 0.01) and Ex3 (p < 0.001). The results demonstrated that although the mRNA levels of IFN-γ and IL-12 were elevated in all mice of experimental groups, a significant increase (p < 0.001) was observed in tested groups of Ex2 and Ex3 when compared with control groups. CONCLUSION: The findings of the present study demonstrated the potent prophylactic effects of MCEO especially in the doses 200 and 300 mg/kg in mice infected with T. gondii. Although the exceptional anti-Toxoplasma effects of MCEO and other possessions, such as improved innate immunity and low toxicity are positive topics, there is, however, a need for more proof from investigations in this field.

Preparation and characterization of loaded paraquat- polymeric chitosan/xantan/tripolyphosphate nanocapsules and evaluation for controlled release.

PURPOSE: Paraquat is an effective, non-selective, and fast-acting contact herbicide that is widely used. Its high solubility in water and adsorption in soil can easily poison the non-target organs. In this study, paraquat nano-hydrogels was synthesized using chitosan. METHODS: Sodium tripolyphosphate and xanthan via iononic gellification method. After preparation the loaded paraquat formulations, to verify the morphology and analysis the functional groups on the formulation, SEM and FTIR analysis were used, respectively. In this work, stability of the formulation was measured in terms of size distribution, surface charge, and pH values. To determine the release kinetics, a dialysis bag was used. In addition, herbicidal activity of the prepared formulation was tested on corn bushes and wild mustard. RESULTS: From the analysis, FT-IR spectra confirmed the hydrogel formation, and SEM images showed a dense structure in the synthesized hydrogel. According to the results of size distribution, surface charge, dispersion index and pH, it was proved that the prepared hydrogel was stable. The optimal values of chitosan, SPP, xanthan, and PQ were 0.3, 0.1, 0.15, and 20 mg, respectively. Based on the peppas equation, about 89.82% of the paraquat was released from the formulation with a paraquat loading of 89.1 ± 4.6%. CONCLUSIONS: The effect of loaded paraquat formulations on mustard and corn plants showed that the herbicidal properties of the encapsulated paraquat were preserved. This study reveal that the loaded paraquat L-PQ is a stable formulation with less toxicity effects.

Biocompatibility, Cytotoxicity, Antimicrobial and Epigenetic Effects of Novel Chitosan-Based Quercetin Nanohydrogel in Human Cancer Cells.

BACKGROUND: Previous studies have reported that quercetin (Q) has a potential antibacterial and anticancer activity. However, its application is limited by many important factors including high hydrophobicity and low absorption. METHODOLOGY: In the current study, we synthesized and characterized (Patent) a novel chitosan-based quercetin nanohydrogel (ChiNH/Q). Encapsulation efficiency was confirmed by UV/VIS spectrophotometer. Physicochemical characterization of ChiNH/Q was assessed by PDI, DLS, SEM, FTIR, and XRD. The toxicity of the ChiNH/Q against five strains of the pathogen and HepG2 cells was examined. Moreover, the quantification of ChiNH/Q on genomic global DNA methylation and expression of DNMTs (DNMT1/3A/3B) in HepG2 cancer cells were evaluated by ELISA and real-time PCR, respectively. RESULTS: Under the SEM-based images, the hydrodynamic size of the ChiNH/Q was 743.6 nm. The changes in the PDI were 0.507, and zeta potential was obtained as 12.1 mV for ChiNH/Q. The FTIR peak of ChiNH/Q showed the peak at 627 cm-1 corresponded to tensile vibrational of NH2-groups related to Q, and it is the indication of Q loading in the formulation. Moreover, XRD data have detected the encapsulation of ChiNH/Q. The ChiNH/Q showed a potent antimicrobial inhibitory effect and exerted cytotoxic effects against HepG2 cancer cells with IC50 values of 100 µg/mL. Moreover, our data have shown that ChiNH/Q effectively reduced (65%) the average expression level of all the three DNMTs (p<0.05) and significantly increased (1.01%) the 5-methylated cytosine (5-mC) levels in HepG2 cells. CONCLUSION: Our results showed for the first time the bioavailability and potentiality of ChiNH/Q as a potent antimicrobial and anticancer agent against cancer cells. Our result provided evidence that ChiNH/Q could effectively reduce cellular DNMT expression levels and increase genomic global DNA methylation in HepG2 cancer cells. Our results suggest a potential clinical application of nanoparticles as antimicrobial and anticancer agents in combination cancer therapy.

Investigation of 3T3-L1 Cell Differentiation to Adipocyte, Affected by Aqueous Seed Extract of Phoenix Dactylifera L.

BACKGROUND: Obesity, often associated with insulin resistance and type 2 diabetes, is a metabolic disease that can result in dyslipidemia and hyperglycemia. Many reports describe the hypoglycemic and hypolipidemic properties of the Phoenix dactylifera L. seed extract in STZ-induced diabetic rat models, however, its anti-diabetic effects in other diabetic models are less characterized in the literature. This study set out to determine the possible effects of the Phoenix dactylifera L. seed extract on adipogenesis and glucose homeostasis. METHODS: 3T3-L1 cells were cultured in adipocyte differentiation media with or without varying doses of Phoenix dactylifera L. extract (0.312-1 mg/ml). Assays were performed on days 5, 8, and 12 after induced differentiation. RESULTS: Our results demonstrate that the triglyceride content in treated groups was significantly lower compared to controls. Further, treating 3T3-L1 cells with Phoenix dactylifera L. seed extract reduced adipogenesis through the downregulation of PPAR-γ and CEBP-α, and adipocyte-specific genes involved in fatty acid metabolism including ap2, ACACA, and FAS. CONCLUSION: Phoenix dactylifera L. seeds have the potential to inhibit adipogenesis and obesity. Overall, this study explored the inhibitory effects of Phoenix dactylifera L. seed extract on adipogenesis in 3T3-L1 cells on the molecular level.

Identification of common key regulators in rat hepatocyte cell lines under exposure of different pesticides.

Pesticides exposure can have harmful effects on human health. The liver is the most common organ of pesticides toxicity due to its major metabolic activity. The molecular mechanism of pesticides effect is complex and is controlled by gene regulatory networks. All components of regulatory networks are controlled by transcription factors and other regulatory elements. Therefore, identification of key regulators through system biology approaches and high-throughput techniques can help to provide comprehensive insights into molecular mechanisms of the pesticide effect. In the current study, a microarray data-set was used to potentially identify molecular mechanisms that regulate gene expression profile of rat hepatocyte cell lines in response to pesticides exposure. Results showed that the number of differentially expressed genes (DEGs) and differentially expressed transcription factors (DE-TFs) were dramatically different among pesticides tested. Results also revealed 205 common DEGs and 11 DE-TFs among pesticides tested. Additionally, we found that six DE-TFs (CREB1, CTNNB1, PPARG, SP1, SRF and STAT3) had the highest number of interactions with other DEGs and acted as the key regulatory genes. The results of this study revealed regulator genes that have the key functions in response to pesticides toxicity in rat liver, which can provide the basis for future studies. Furthermore, these regulatory genes can be used as toxicity biomarkers to improve diagnosis and prognosis.

Fabrication of new generation of co-delivery systems based on graphene-g-cyclodextrin/chitosan nanofiber.

Although many techniques have been devoted to promote therapeutic purposes of drug carrier systems, however, there are still many challenges in this area. Here, we designed co-loaded delivery systems, composed of curcumin loaded cyclodextrin-graphene oxide core (Cur@CD-GO) and gallic acid loaded chitosan shell nanofibers (Cur-Ga NF), which can promote the therapeutic efficiency of drugs. The synthesized nanofibres were fabricated by electrospinning technique with the coaxial system. Results showed that co-loaded delivery systems (Cur-Ga NF) provide better performance over single drug-loaded NFs (Cur@CD-GO). It was demonstrated that the nanofibers were successfully prepared, and the drugs in the core and sell of nanofibers were released in a controlled and sustained manner. The produced Cur-Ga NF, providing improved anti-cancer activity, antimicrobial activity, antioxidant activity and anti-inflammatory outcome as compared to single drug-loaded NFs. Our investigations showed that such co-delivery fiber systems could be employed as a promising nanocarrier for therapeutic applications.

Pectin/Chitosan/Tripolyphosphate Nanoparticles: Efficient Carriers for Reducing Soil Sorption, Cytotoxicity, and Mutagenicity of Paraquat and Enhancing Its Herbicide Activity.

As a potent herbicide capable of contaminating water and soil environments, paraquat, which is still widely used worldwide, is toxic to mammals, algae, aquatic animals, etc. Paraquat was loaded on novel nanoparticles composed of pectin, chitosan, and sodium tripolyphosphate (PEC/CS/TPP). The size, polydispersity index, and ζ potential of nanoparticles were characterized. Further assessments were carried out by SEM, AFM, FT-IR, and DSC. The encapsulation was highly efficient, and there was a delayed release pattern of paraquat. The encapsulated herbicide was less toxic to alveolar and mouth cell lines. Moreover, the mutagenicity of the formulation was significantly lower than those of pure or commercial forms of paraquat in a Salmonella typhimurium strain model. The soil sorption of paraquat and the deep soil penetration of the nanoparticle-associated herbicide were also decreased. The herbicidal activity of paraquat for maize or mustard was not only preserved but also enhanced after encapsulation. It was concluded that paraquat encapsulation with PEC/CS/TPP nanoparticles is highly efficient and the formulation has significant herbicide activity. It is less toxic to human environment and cells, as was evidenced by less soil sorption, cytotoxicity, and mutagenicity. Hence, paraquat-loaded PEC/CS/TPP nanoparticles have potential advantages for future use in agriculture.