Citrus flavonoids-loaded chitosan derivatives-route nanofilm as drug delivery systems for cutaneous wound healing.

This study focuses on creating new forms of biomimetic nanofiber composites by combining copolymerizing and electrospinning approaches in the field of nanomedicine. The process involved utilizing the melt polymerization of proline (Pr) and hydroxyl proline (Hyp) to synthesize polymers based on Pr (PPE) and Hyp (PHPE). These polymers were then used in a grafting copolymerization process with chitosan (CS) to produce PHPC (1560 ± 81.08 KDa). A novel electrospun nanofiber scaffold was then produced using PHPC and/or CS, hyaluronic acid, polyvinyl alcohol, and naringenin (NR) as a loading drug. Finally, Mouse Dermal Fibroblast (MDF) cells were introduced to the wound dressing and assessed their therapeutic potential for wound healing in rats. The scaffolds were characterized by FTIR, NMR, DSC, and SEM analysis, which confirmed the amino acid grafting, loading drug, and porous and nanofibrous structures (>225 nm). The results showed that the PHPC-based scaffolds were more effective for swelling/absorption of wound secretions, had more elasticity/elongation, faster drug release, more MDF-cytocompatibility, and antibacterial activity against multidrug-resistant S. aureus compared to CS-based scaffolds. The in vivo studies showed that NR in combination with MDF can accelerate cell migration/proliferation, and remodeling phases of wound healing in both PHPC/CS-based scaffolds. Moreover, PHPC-based scaffolds promote collagen content, and better wound contraction, epithelialization, and neovascularization than CS-based, showing potential as wound-dressing.

Multi-target bioactivity of summer quinones production in the Persian Gulf burrowing black-type sea urchin.

After harvesting the sea urchin gonads for Japanese food "uni" echinoculture systems, the remaining shells and spines are considered waste. However, the material of shells and spines is thought to be rich in natural bioactive molecules. The current study used liquid chromatography-electrospray mass spectrometry to extract summer quinones pigment present in spines and shells of the burrowing sea urchin 'black' type Echinometra mathaei from the natural Qeshm Island echinoculture. Then, the biochemical, antioxidant, anti-inflammatory, antidiabetic, antibacterial, and cytotoxic activities of sea urchin quinones pigment were investigated. In terms of bioactivity, both shell and spine pigments demonstrated strong radical scavenging activity (antioxidant). The shell pigment exhibited maximum albumin denaturation inhibition (IC50 = 9.62 µg/ml) (anti-inflammatory), as well as α-amylase inhibition (92.28 percent 4.77) (antidiabetic). Pigments were discovered to have a low antibacterial effect against positive gramme bacteria, as well as low cytotoxic and embryotoxic effects when compared to Artemia salina and zebrafish (Danio rerio). For identification and quantification of pigment extracts, both the photodiode array detector and LC-ESI-MS were used. Spinochrome A, B, and C, as well as echinochrome A, were identified as bioactive quinonoid pigments. This chemical defence is discussed in relation to its algal diet and environmental conditions. In conclusion, the isolated pigments obtained from the shell and spines of E. mathaei sea urchins found to have potent bio-activity and can be used for various biomedical and pharmaceutical applications.

Coelomic fluid of Echinometra mathaei: The new prospects for medicinal antioxidants.

Echinoid pigments have various biological properties such as antioxidant, cytotoxic, and antibacterial activities. We aimed to evaluate the extraction of cell-free coelomic fluid (CFCF) and coelomocyte lysate (CL) as well as qualitatively and quantitatively identify the coelomic fluid of Echinometra mathaei as a new source of polyhydroxylatednaphthoquinone (PHNQ) antioxidant pigments. Based on the High Performance liquid chromatography-electrospray mass spectrometry (HPLC-MS) analysis in negative mode, the main quinonoid (PHNQ) pigments were identified and quantified. This study also illustrated the total ion current chromatograms and related mass spectra of Spinochrome A, Spinochrome B, Spinochrome C, and Echinochrome A in CL and SpinochromeC in CFCF samples. The ions at 221, 279, 265 and 263 m/z correspond to the pseudo-molecular [M - H] ions of Spinochrome B, Spinochrome C, Echinochrome A, and Spinochrome A, respectively. These components have previously been noted from the shells and spines of sea urchins but identification of PHNQs pigments in CL and CFCF of E. mathaei using LC-MS was introduced for the first time. The results also showed that, the highest DPPH radical scavenging activity of CFCF (88.12 DPPH% scavenging at 70 µg/mL, IC50 = <10 µg/mL). The findings clearly suggest that the coelomic fluid of E. mathaei could be served as the promising as well as potential natural antioxidants in the medical and pharmaceutical industries and could replace the increasing prices of the commercial antioxidants products.

Ecotoxico Linking of Phthalates and Flame-Retardant Combustion Byproducts with Coral Solar Bleaching.

Persian Gulf coral reefs are unique biota communities in the global sunbelts in being able to survive in multiple stressful fields during summertime (>36 °C). Despite the high-growth emerging health-hazard microplastic additive type of contaminants, its biological interactions with coral-algal symbiosis and/or its synergistic effects linked to solar-bleaching events remain unknown. This study investigated the bioaccumulation patterns of polybrominated diphenyl ether (PBDE) and phthalate ester (PAE) pollutants in six genera of living/bleached corals in Larak Island, Persian Gulf, and their ambient abiotic matrixes. Results showed that the levels of ∑18PBDEs and ∑13PAEs in abiotic matrixes followed the order of SPMs > surface sediments > seawater, and the cnidarian POP-uptake patterns (soft corals > hard corals) were as follows: coral mucus (138.49 ± 59.98 and 71.57 ± 47.39 ng g-1 dw) > zooxanthellae (82.05 ± 28.27 and 20.14 ± 12.65 ng g-1 dw) ≥ coral tissue (66.26 ± 21.42 and 34.97 ± 26.10 ng g-1 dw) > bleached corals (45.19 ± 8.73 and 13.83 ± 7.05 ng g-1 dw) > coral skeleton (35.66 ± 9.58 and 6.47 ± 6.47 ng g-1 dw, respectively). Overall, findings suggest that mucus checking is a key/facile diagnostic approach for fast detection of POP bioaccumulation (PB) in tropical corals. Although studied corals exhibited no consensus concerning hazardous levels of PB (log BSAF < 3.7), our bleaching evidence showed soft corals as the ultimate "summer winners" due to their flexibility/recovering ability.

Emerging POPs-type cocktail signatures in Pusa caspica in quantitative structure-activity relationship of Caspian Sea.

The Caspian seal Pusa caspica is the only endemic mammalian species throughout the Caspian Sea. This is the first report on risk assessment of persistent organic pollutants (POPs) in Caspian seals by age-sex and tissue-specific uptake, and their surrounding environment (seawater, surface sediments, and suspended particulate matters, SPMs) in the Gorgan Bay (Caspian Sea, Iran). Among the quantified 70 POPs (∑35PCBs, ∑3HCHs, ∑6CHLs, ∑6DDTs, ∑17PCDD/Fs, HCB, dieldrin, and aldrin), ∑35PCBs were dominant in abiotic matrices (48.80% of ∑70POPs), followed by HCHs > CHLs > DDTs > PCDD/Fs > other POPs in surface sediments > SPMs > seawater, while the toxic equivalent quantity (TEQWHO) exceeded the safe value (possible risk in this area). In biota, the highest levels of ∑70POPs were found in males (756.3 ng g-1 dw, p < 0.05), followed by females (419.0 ng g-1 dw) and pups (191.6 ng g-1 dw) in liver > kidney > muscle > blubber > intestine > fur > heart > spleen > brain. The positive age-related POPs declining correlation between mother-pup pairs suggested the possible maternal transfer of POPs to offspring. The cocktail toxicity assessment revealed that Caspian seals can pose a low risk based on their mixed-TEQ values. Self-organizing map (SOM) indicated the non-coplanar PCB-93 as the most over-represented functional congener in tissue-specific POPs bioaccumulation. Quantitative toxicant tissue-profiling is valuable for predicting the state of mixture toxicity in pinniped species.

Dietary intake of polycyclic aromatic hydrocarbons (PAHs) from coral reef fish in the Persian Gulf - Human health risk assessment.

The present study investigated accumulation of petrogenic polycyclic aromatic hydrocarbons (∑39PAHs) in the livers and muscles of three coral-reef fish (50 specimens) from the Persian Gulf, Kharg Island (Iran), specifically Lethrinus microdon (n = 18), Lutjanus argentimaculatus (n = 17), and Scomberomorus guttatus (n = 15). For all fish, PAHs originated mostly from petroleum and combustion sources. Concentrations of ∑39PAHs were 1004 ngg-1 freeze-dried weight (fdw) and 1390 ngg-1 fdw for liver and muscle, respectively. The biota-sediment accumulation factor of 20,181 and equivalent concentrations of ∑PAHs (liver) were highest for L. argentimaculatus. Most of the abundant PAHs identified were low molecular weight (LMW-PAH) (liver > muscle) with 2-3 aromatic ring. Results for the human health risk assessment concluded the probability of PAHs intake via fish consumption was considerable in this area (lifetime cancer risk (ILCR) > 1 × 10-5; hazard quotients (HQs) > 1; hazard index (HI) ≈6; the excess cancer risk (ECR) > 1 × 10-6) and, therefore, comprehensive management and long-term monitoring is needed.

Steroid Fingerprint Analysis of Endangered Caspian Seal (Pusa caspica) through the Gorgan Bay (Caspian Sea).

The profile of steroid congeners was evaluated in Caspian seals Pusa caspica by age, sex, and tissue-specific bioaccumulation, and compared with that of abiotic matrices (seawater, surface sediment, and suspended particulate materials, SPMs) from Miankaleh Wildlife/Gorgan Bay, (Caspian Sea, Iran). To identify the level of human fecal contamination, ∑25 sterol congeners were measured in all abiotic/biotic samples, revealing coprostanol, a proxy for human feces, as the most abundant sterol (seawater: 45.1-20.3 ng L-1; surface sediment: 90.2-70.3 ng g-1 dw; SPMs: 187.7-157.6 ng g-1 dw). The quantification of ∑25 sterols in seals followed the order of brain > liver > kidney > heart > blood > spleen > muscle > intestine > blubber > fur, and in both sexes coprostanol level (8.95-21.01% of ∑25s) was higher in blubber and fur, followed by cholesterol in brain, liver, kidney, heart, and blood, cholestanone in intestine and muscle, and ß-sitosterol in spleen. Though no age/sex differentiation was observed, the mean concentration of ∑25s was higher in male than females and pup. Different diagnostic ratios revealed sterols originating from human and nonhuman sewage sources. Findings pinpoint the urgent necessity to investigate the ecotoxicity of fecal sterols in mammals, and consequent implications for human health.

Phyco-linked vs chemogenic magnetite nanoparticles: Route selectivity in nano-synthesis, antibacterial and acute zooplanktonic responses.

Despite the fact that magnetic iron oxide nanoparticles (Fe3O4-MNPs) considered as the most promising nanoparticles (NPs) in biomedicine and environmental biotechnology, their safety and ecotoxicological impacts of biogenic and chemogenic routes of Fe3O4-MNPs in the marine aquatic system is scarcely studied. In this work, we report the optimized and suitable phyco-synthesis route for nano-Fe3O4 based on the six selected species of the Persian Gulf seaweeds: Ulva prolifera, U. flexuosa, U. linza, U. intestinalis, U. clathrata, and Sargassum boveanum. Moreover, antibacterial activities and acute zooplanktonic responses in Artemia salina and acorn barnacle Amphibalanus amphitrite to chemogenic and biogenic Fe3O4-MNPs, were evaluated. Although all the seaweeds extract showed reducing potential for Fe3O4-MNPs green synthesis - mainly on the basis of characterization results- the algal route selectivity has been demonstrated to be important for the biosynthesis of magnetite NPs. Herein, the cubo-spherical and polydisperse U. prolifera-derived Fe3O4-MNPs with particles sizes of 9.59 nm were the best ones. The comparative zooplanktonic cytotoxicity of chemo- and bio-route of Fe3O4-MNPs exhibited no acute toxicity in nauplii and adults of A. salina (96-h EC50 ≥ 1000 mg/L) and the potential of toxicity in A. amphitrite nauplii (48-h EC50 = 466.5 and 842.3 mg/L for chemo- and bio-route of Fe3O4-MNPs, respectively). The in vitro antimicrobial activity of both chemo- and bio-route of magnetite NPs to selective human pathogenic bacteria and fungi (i.e. n = 11) showed strong antagonistic activity against Staphylococcus epidermidis, Bacillus subtilis, B. pumulis, and Saccharomyces cerevisiae. In conclusion, these findings demonstrate the optimized phyco-fabrication of Fe3O4-MNPs as promising nontoxic approach in ecobiotechnology, the new insight about the potential adverse effects of chemosynthesized Fe3O4-MNPs to crustacean zoo-organisms after their possible entrance into the marine environments, and bio/chemo-route Fe3O4-MNPs as pivotal agent for nanoantimicrobials.

Early Hereditary Diffuse Gastric Cancer (eHDGC) is Characterized by Subtle Genomic Instability and Active DNA Damage Response.

Diffuse gastric cancer (DGC) is one of the two primary types of stomach cancer. Carriers of germline mutations in the gene encoding E-cadherin are predisposed to DGC. The primary aim of the present study was to determine if genomic instability is an early event in DGC and how it may lead to disease progression. Chromosomal aberrations in early intramucosal hereditary diffuse gastric cancer (eHDGC) were assessed using array comparative genomic hybridization (array CGH). Notably, no aneuploidy or other large-scale chromosomal rearrangements were detected. Instead, all aberrations affected small regions (< 4.8 Mb) and were predominantly deletions. Analysis of DNA sequence patterns revealed that essentially all aberrations possessed the characteristics of common fragile sites. These results and the results of subsequent immunohistochemical examinations demonstrated that unlike advanced DGC, eHDGCs is characterized by low levels of genomic instability at fragile sites. Furthermore, they express an active DNA damage response, providing a molecular basis for the observed indolence of eHDGC. This finding is an important step to understanding the pathology underlying natural history of DGC and supports a revision of the current definition of eHDGC as a malignant disease.

Mutational screening of the negative regulatory region of astrocyte elevated gene-1 promoter in hepatocellular carcinoma patients / Triagem mutacional da região reguladora negativa do promotor do gene-1 elevado em astrocito em pacientes com carcinoma hepatocelular

Astrocyte elevated gene-1 (AEG-1) is a positive regulator of tumorigenesis in human cancer cells. Human AEG-1 gene is located in chromosome 8q22 having 12 exons/11 introns. Chromosome 8q22 is known to be a hot spot for genomic alterations in several cancerous cells involving HCC. The aim of the study was assess association between the negative regulatory region of AEG-1 promoter mutations and genetic susceptibility to hepatocellular carcinoma. The negative regulatory region of the human AEG-1 promoter was evaluated in a total of 50 Iranian hepatocellular carcinomas (HCC) patients. For investigating AEG-1 promoter polymorphisms the PCR-sequencing method was used. In this study was found two new mutation C>T (-633) and G>C (-660) in the patient group. But it was not revealed the statistically significant association between any mutations in this region of the AEG-1 promoter with HCC susceptibility. According to presented data, we can say that the negative regulatory region of the AEG-1 promoter mutations did not exihibit significant relevance with hepatocellular carcinoma. We recommend further studies on the efficacy of the AEG-1 promoter in therapeutic targeting of the HCC.

Resumo: O gene AEG-1 é um regulador positivo da tumorigênese em células cancerígenas humanas. O gene humano AEG-1 está localizado no cromossomo 8q22 com 12 exons/11 introns. O cromossomo 8q22 é conhecido por ser um hotspot para alterações genômicas em várias células cancerígenas que envolvem o CHC. O objetivo do estudo foi avaliar a associação entre a região reguladora negativa das mutações do promotor AEG-1 e a suscetibilidade genética ao carcinoma hepatocelular. A região reguladora negativa do promotor humano AEG-1 foi avaliada em um total de 50 pacientes iranianos com carcinomas hepatocelulares (CHC). Para investigar os polimorfismos do promotor AEG-1, utilizou-se o método de sequenciação por PCR. Neste estudo foram encontradas duas novas mutações C>T (-633) e G>C (-660) no grupo de pacientes. Mas não foi revelada a associação estatisticamente significante entre quaisquer mutações nessa região do promotor AEG-1 com suscetibilidade ao CHC. De acordo com os dados apresentados, podemos dizer que a região reguladora negativa das mutações do promotor AEG-1 não demonstrou relevância significativa com o carcinoma hepatocelular. Recomendamos estudos adicionais sobre a eficácia do promotor AEG-1 no direcionamento terapêutico do CHC.

Organic and inorganic nano-Fe3O4: Alga Ulva flexuosa-based synthesis, antimicrobial effects and acute toxicity to briny water rotifer Brachionus rotundiformis.

Following the recent progress in magnetic nanotechnology, concern over the optimal benefits and potential risks of iron oxide nanoparticles (Fe NPs), has increased. Hence, to minimize the negative impacts of inorganic Fe NPs, we report the phyco-synthesis and characterization of superparamagnetic Fe3O4 NPs via reduction of ferric/ferrous chloride solution (2:1 M ratio; 88 °C) with green macroalga, Ulva flexuosa (wulfen) J.Agardh aqueous extract. The biogenic process is clean, eco-friendly, rapid, and facile to handle. These green fabricated magnetite NPs are characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), thermogravimetric analysis (TGA), particle size analysers (PSA), zeta potential (ZP) measurement, and vibrating sample magnetometry (VSM) techniques. The results confirmed that the cubo-spherical, polydisperse of biosynthesized Fe3O4 NPs with an average diameter of 12.3 nm was formed. The antagonistic effects of algal extract, chemo-route and U. flexuosa-derived Fe3O4 MgNPs on selective human pathogenic microbes (i.e. n = 11) resulted in strong antibacterial and moderate antifungal activity. The comparative toxic and reproductive effects of the chemo- and bio-routes of Fe3O4-MgNPs against rotifer B. rotundiformis exhibited low acute toxicity with a lower inducing effect of biogenic nano-magnetite on reduction rotifer reproductive rate than its chemogenic counterpart. In view of the nanoecotoxicity, though the current study covered a wide range of exposure concentrations (10-500 mg/L) of organic and inorganic nano sizes of Fe3O4 in brackish water rotifer, a biotoxicity assay at higher dosage or a comprehensive risk assessment in different aqua-organisms is recommended.

Cytotoxicity and antimicrobial activity of marine macro algae (Dictyotaceae and Ulvaceae) from the Persian Gulf.

Pharmaceutical industry now accept the worlds ocean which contains a vast array of organisms with unique biological properties, as a major frontier for medical investigation. Bioactive compounds with different modes of action, such as, antiproliferative, antioxidant, antimicrotubule, have been isolated from marine sources, specifically macro and micro algae, and cyanobacteria. The aim of this work was to investigate antimicrobial and cytotoxic activities of the extracts of marine macro algae Ulva flexuosa, Padina antillarum and Padina boergeseni from the northern coasts of the Persian Gulf, Qeshm Island, Iran, against three cell lines including MCF7, HeLa and Vero, as well as their inhibitory effects against a wide array (i.e. n = 11) of pathogenic bacteria and fungi. Antimicrobial activity of the marine macro algal extracts was assessed using a disc diffusion method; an MTT cytotoxicity assay was employed to test the effects of the extracts on each cancer cell line. The algal extracts showed considerable antimicrobial activity against the majority of the tested bacteria and fungi. Both ethyl acetate and methanol extracts at the highest concentration (100 µg/ml) caused cell death, with the IC50 values calculated for each cell type and each algal extracts. Results are exhibited a higher decrease in the viability of the cells treated at the highest concentration of marine macro algal ethyl acetate extracts compared to the methanol extracts (78.9 % death in Vero cells by ethyl acetate extracts from U. flexuosa). Despite, the ethyl acetate extracts with lower dose- response of cells, exhibited better cytotoxic activity than methanol extracts (IC50: 55.26 µg/ml in Vero cells by ethyl acetate extracts from U. flexuosa). Based on the findings, it is concluded that the marine macro algal extracts from the Persian Gulf possess antibacterial and cytotoxic potential, which could be considered for future applications in medicine and identifying novel drugs from the marine resources.