Yttrium oxide nanoparticles ameliorates calcium hydroxide and calcium titanate nanoparticles induced genomic DNA and mitochondrial damage, ROS generation and inflammation.

Calcium hydroxide (Ca(OH)2NPs), calcium titanate (CaTiO3NPs) and yttrium oxide (Y2O3NPs) nanoparticles are prevalent in many industries, including food and medicine, but their small size raises concerns about potential cellular damage and genotoxic effects. However, there are very limited studies available on their genotoxic effects. Hence, this was done to investigate the effects of multiple administration of Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs on genomic DNA stability, mitochondrial membrane potential integrity and inflammation induction in mouse brain tissues. Mice were orally administered Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs at a dose level of 50 mg/kg b.w three times a week for 2 weeks. Genomic DNA integrity was studied using Comet assay and the level of reactive oxygen species (ROS) within brain cells was analyzed using 2,7 dichlorofluorescein diacetate dye. The expression level of Presenilin-1, tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) genes and the integrity of the mitochondrial membrane potential were also detected. Oral administration of Ca(OH)2NPs caused the highest damage to genomic DNA and mitochondrial membrane potential, less genomic DNA and mitochondrial damage was induced by CaTiO3NPs administration while administration of Y2O3NPs did not cause any remarkable change in the integrity of genomic DNA and mitochondrial membrane potential. Highest ROS generation and upregulation of presenilin-1, TNF-α and IL-6 genes were also observed within the brain cells of mice administrated Ca(OH)2NPs but Y2O3NPs administration almost caused no changes in ROS generation and genes expression compared to the negative control. Administration of CaTiO3NPs alone slightly increased ROS generation and the expression level of TNF-α and IL-6 genes. Moreover, no remarkable changes in the integrity of genomic DNA and mitochondrial DNA potential, ROS level and the expression level of presenilin-1, TNF-α and IL-6 genes were noticed after simultaneous coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs. Coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs mitigated Ca(OH)2NPs and CaTiO3NPs induced ROS generation, genomic DNA damage and inflammation along with restoring the integrity of mitochondrial membrane potential through Y2O3NPs scavenging free radicals ability. Therefore, further studies are recommended to study the possibility of using Y2O3NPs to alleviate Ca(OH)2NPs and CaTiO3NPs induced genotoxic effects.

Desert date seed extract-loaded chitosan nanoparticles ameliorate hyperglycemia and insulin deficiency through the reduction in oxidative stress and inflammation.

Plants represents a huge source of bioactive materials that have been used since the old times in the treatment of many diseases. Balanites aegyptiaca, known as desert date, has been used in treatment of fever, diabetes and bacterial infection. Desert dates contains a hard seed that resembles 50-60% of the fruit. The seed extract contains many fatty acids, amino acids and other bioactive materials that gives the extract its antioxidant and anti-inflammatory properties. The study aimed to use Balanites seed extract-loaded chitosan nanoparticles (SeEx-C NPs) for the treatment of streptozotocin (STZ)-induced diabetes in male Sprague Dawley rats. Animals were divided into two main divisions (healthy and diabetic rats). Each division contained seven groups (5 rats/group): control untreated group I, SeEx treated group II and group III (10 and 20 mg/kg b.w., respectively), C NPs treated group IV and group V (10 and 20 mg/kg b.w., respectively) and SeEx-C NPs treated group VI and group VII (10 and 20 mg/kg b.w., respectively). The therapeutical effects of SeEx-C NPs were evaluated through biochemical and immunological assessments in rats' pancreases. The results showed that SeEx-C NPs (10 and 20 mg/kg b.w.) reduced the oxidative stress and inflammation in rats' pancreases allowing the islets neogenesis. The loading of SeEx on C NPs allowed the delivery of fatty acids (oleic, lauric and myristic acid), amino acids (lysine, leucine, phenylalanine and valine) and minerals to pancreatic beta-cells in a sustainable manner. SeEx-C NPs administration successfully increased insulin secretion, allowed pancreatic islets neogenesis and reduced oxidative stress and inflammation.

Role of gamma-irradiated sodium alginate on growth, physiological and active components of iceberg lettuce (Lactuca sativa) plant.

BACKGROUND: One of the most widely recognized biostimulators of plant development; is oligoalginate, which regulates the biological processes of plants and was used in horticultural fields as a plant growth regulator. The plan of the current research was to study, however, the foliar application of un-irradiated and irradiated Na-alginate (UISA and ISA) to improve the growth, physiological activity, and other active components of the Egyptian iceberg lettuce plant. Degraded Na-alginate is equipped with exposure of sodium alginate in its solid state to gamma-rays at different dose levels (0.0, 25, 50, 75, and 100 kGy). The characterization of the oligo-alginates achieved by γ-radiation deprivation at different dose levels was performed by FTIR, XRD, TGA, SEM, and TEM. Different concentrations of irradiated sodium alginate at dose levels of 100 kGy (200, 400, 600, and 800 ppm, as well as deionized water used as a control) were sprayed with a hand sprayer every week after transplanting the iceberg lettuce seedlings in the field until the harvest stage. Morphological traits were evaluated, as well as pigments, ascorbic acid, phenols, flavonoids, soluble proteins, and antioxidant activity. RESULTS: Irradiated Na-alginate resulted in the depolymerization of Na-alginate into small molecular-weight oligosaccharides, and the best dose to use was 100 kGy. Certain chemical modifications in the general structure were observed by FTIR analysis. Two absorbed bands at 3329 cm-1 and 1599 cm-1, were recognized that are assigned to O-H and C-O stretching, respectively, and peaks achieved at 1411 cm-1 represent the COO-stretching group connected to the sodium ion. The peak obtained at 1028 cm-1 was owing to the stretching vibration of C-O. The results of TGA provided that the minimum weight reminder was in the ISA at 100 kGy (28.12%) compared to the UISA (43.39%). The images of TEM pointed out that the Na-alginate was globular in shape, with the particle distribution between 12.8 and 21.7 nm in ISA at 100 kGy. Irradiated sodium alginate caused a noteworthy enhancement in the vegetative growth traits (leaf area, stem length, head weight, and leaf number). By spraying 400 ppm, ISA showed a maximum increase in total pigments (2.209 mg/g FW), ascorbic acid (3.13 mg/g fresh weight), phenols (1.399 mg/g FW), flavonoids (0.775 mg/g FW), and antioxidant activities (82.14. %). Also, there were correlation coefficients (R values) between leaf area, stem length, head weight, and leaf number values with total pigment content, antioxidant activity, total soluble proteins, and ascorbic acid. CONCLUSIONS: The outcomes of the recent investigation demonstrated that the application of spraying irradiated Na-alginate (100 kGy) resulted in an improvement of the considered characters.

Elevated expression patterns of P-element Induced Wimpy Testis (PIWI) transcripts are potential candidate markers for Hepatocellular Carcinoma.

BACKGROUND: P-Element-induced wimpy testis (PIWI) proteins, when in combination with PIWI-interacting RNA (piRNA), are engaged in the epigenetic regulation of gene expression in germline cells. Different types of tumour cells have been found to exhibit abnormal expression of piRNA, PIWIL-mRNAs, and proteins. We aimed to determine the mRNA expression profiles of PIWIL1, PIWIL2, PIWIL3, & PIWIL4, in hepatocellular carcinoma patients, and to associate their expression patterns with clinicopathological features. METHODS: The expression patterns of PIWIL1, PIWIL2, PIWIL3, PIWIL4 mRNA, was assessed via real-time quantitative polymerase chain reaction (RT-QPCR), on tissue and serum samples from HCC patients, their impact for diagnosis was evaluated by ROC curves, prognostic utility was determined, and In Silico analysis was conducted for predicted variant detection, association with HCC microRNAs and Network Analysis. RESULTS: Expression levels were significantly higher in both HCC tissue and serum samples than in their respective controls (p< 0.001). Additionally, the diagnostic performance was assessed, Risk determination was found to be statistically significant. CONCLUSION: PIWIL mRNAs are overexpressed in HCC tissue and serum samples, the expression patterns could be valuable molecular markers for HCC, due to their association with age, tumour grade and pattern. To the best of our knowledge, our study is the first to report the expression levels of all PIWIL mRNA and to suggest their remarkable values as diagnostic and prognostic biomarkers, in addition to their correlation to HCC development. Additionally, a therapeutic opportunity might be also suggested through in silico miRNA prediction for HCC and PIWIL genes through DDX4 and miR-124-3p.

Alleviation of calcium hydroxide nanoparticles induced genotoxicity and gastritis by coadministration of calcium titanate and yttrium oxide nanoparticles in mice.

Diverse applications of nanoparticles due to their unique properties has rapidly increased human exposure to numerous nanoparticles such as calcium hydroxide (Ca(OH)2), calcium titanate (CaTiO3), and yttrium oxide (Y2O3) nanoparticles almost in all aspect of daily life. However, very limited data are available on the effect of these nanoparticles on genomic DNA integrity and inflammation induction in the gastric tissues. Hence, this study estimated the effect of Ca(OH)2, CaTiO3, or/and Y2O3 nanoparticles multiple oral administration on the genomic DNA damage and inflammation induction in the mice gastric tissues. A suspension containing 50 mg/kg b.w of Ca(OH)2, CaTiO3, or Y2O3 nanoparticles were given orally to male mice separately or together simultaneously three times a week for two consecutive weeks. Multiple oral administration of Ca(OH)2 nanoparticles led to significant elevations in DNA damage induction and ROS generation, in contrast to the non-significant changes observed in the level of induced DNA damage and generated ROS after administration of CaTiO3 or Y2O3 nanoparticles separately or in combination with Ca(OH)2 nanoparticles. Oral administration of Ca(OH)2 nanoparticles alone also highly upregulated INOS and COX-2 genes expression and extremely decreased eNOS gene expression. However, high elevations in eNOS gene expression were detected after multiple administration of CaTiO3 and Y2O3 nanoparticles separately or together simultaneously with Ca(OH)2 nanoparticles. Meanwhile, non-remarkable changes were noticed in the expression level of INOS and COX-2 genes after administration of CaTiO3 and Y2O3 nanoparticles separately or simultaneously together with Ca(OH)2 nanoparticles. In conclusion: genomic DNA damage and inflammation induced by administration of Ca(OH)2 nanoparticles alone at a dose of 50 mg/kg were mitigated by about 100% when CaTiO3 and Y2O3 nanoparticles were coadministered with Ca(OH)2 nanoparticles until they reached the negative control level through altering the expression level of eNOS, INOS and COX-2 genes and scavenging gastric ROS. Therefore, further studies are recommended to investigate the toxicological properties of Ca(OH)2, CaTiO3 and Y2O3 nanoparticles and possibility of using CaTiO3 and Y2O3 nanoparticles to mitigate genotoxicity and inflammation induction by Ca(OH)2 nanoparticles.

Anti-Cryptosporidium oocysts polyclonal antibodies for cryptosporidiosis diagnosis and protection.

Cryptosporidiosis is an intestinal infection that is triggered by the protozoan parasite Cryptosporidium spp. Cryptosporidium oocysts can spread from one host to another either through direct contact with infected hosts' faeces or through indirect means (consumption of contaminated water or food). Significant numbers of oocysts are produced as a result of the rapid growth of the parasite within the infected hosts. For proper care of cryptosporidiosis, a laboratory diagnosis is necessary. Therefore, this study aimed to produce anti-Cryptosporidium parvum (C. parvum) oocyst immunoglobulin (Ig)G polyclonal antibodies (pAbs). The produced pAbs were used in the detection of C. parvum oocysts antigens in stool and serum samples of infected calves. Moreover, pAbs were tested in protection of balb-c male mice from cryptosporidiosis infection. C. parvum oocysts were used in the preparation of antigens to be used in the immunization of New Zealand white rabbits. pAb was purified by ammonium sulphate precipitation method, caprylic acid purification method and diethylaminoethyl (DEAE) anion exchange chromatographic method. Sandwich enzyme-linked immunosorbent assay (ELISA) (using prepared pAb) scored higher sensitivity (85% and 95% for serum and stool samples) than that (80%) of microscopic examination of stool samples. Moreover, pAb significantly reduced the oocysts shedding, decreased inflammatory cytokines and enhanced the loss in the body weight of protected animals. The prepared pAb succeeded in the diagnosis of cryptosporidiosis in calves with high sensitivity either in the serum or stool samples. Our results indicated the usefulness of using the prepared pAb in protection against cryptosporidiosis.

Genotoxicity and oxidative stress induction by calcium hydroxide, calcium titanate or/and yttrium oxide nanoparticles in mice.

Intensive uses of Calcium hydroxide (Ca(OH)2NPs), calcium titanate (CaTiO3NPs) and yttrium oxide (Y2O3NPs) nanoparticles increase their environmental release and human exposure separately or together through contaminated air, water and food. However, too limited data are available on their genotoxicity. Therefore, this study explored the effect of Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs administration on the genotoxicityand oxidative stress induction in mice hepatic tissue. Mice were orally administered Ca(OH)2NPs, CaTiO3NPs and Y2O3NPs separately or simultaneously together at a dose level of 50 mg/kg b.w. for two successive weeks (3 days per week). Marked induction of DNA damage noticed after oral administration of Ca(OH)2NPs or CaTiO3NPs alone together with high Ca(OH)2NPs induced reactive oxygen species (ROS) generation and a slight CaTiO3NPs induced ROS production were highly decreased after simultaneous coadministration of administration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs up to the negative control level. Oral administration of Y2O3NPs alone also did not cause observable changes in the genomic DNA integrity and the ROS generation level compared to the negative control levels. Similarly, significant elevations in P53 gene expression and high reductions in Kras and HSP-70 genes expression were observed only after administration of Ca(OH)2NPs alone, while, remarkable increases in the Kras and HSP-70 genes expression and non-significant changes in p53 gene expression were noticed after administration of CaTiO3NPs and Y2O3NPs separately or simultaneously together with Ca(OH)2NPs. Conclusion: Ca(OH)2NPs exhibited the highest genotoxic effect through oxidative stress induction and disruption of apoptotic (p53 and Kras) and protective (HSP-70) genes expression. Slight DNA damage was noticed after CaTiO3NPs administration. However, administration of Y2O3NPs alone was non-genotoxic and coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs restored genomic DNA integrity and normal expression of apoptotic p53 and protective HSP-70 genes disrupted by Ca(OH)2NPs and CaTiO3NPs. Thus co-administration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs is recommended to counter Ca(OH)2NPs and CaTiO3NPs induced genotoxicity and oxidative stress.

Novel grape seed extract nanoparticles attenuate amikacin-induced nephrotoxicity in rats.

Amikacin (AMK), an antibiotic, is prescribed for treating various bacterial diseases like urinary tract infections, encephalitis, asthma and joint infections. The most significant side effects, which affect 1 to 10% of consumers, are kidney injury and ototoxicity. Several studies discussed the role of grape seed extract (GSE) in renoprotection against AMK. The current study aimed to extract Muscat of Alexandria grape seeds followed by its characterization to determine its bioactive components and elements. GSE nanoparticles was prepared and tested, in vitro, to determine its safety for the in vivo experiment. Experimental groups were control group I, AMK group II, GSE (50 mg/kg)-AMK group III, GSE (100 mg/kg)-AMK group IV, GSE NPs (25 mg/kg)-AMK group V and GSE NPs (50 mg/kg)-AMK group VI. Groups 2-6 received 100 mg/kg/day of AMK by intramuscular injection for two weeks for the induction of experimental nephrotoxicity. Groups 3-6 received daily doses of GSE or GSE NPs by oral gavage, concurrently, with AMK for two weeks. GSE was rich in polyphenol compounds like proanthocyanidins, phenolic acids like gallic and egallic acids, catechine and epicatechine. GSE NPs have a smooth surface and a size that ranged from 40 to 70 nm; and have an anti-oxidant, anti-inflammatory, anti-cytotoxic and anti-microbial in vitro effects. It reduced oxidative stress and inflammation that followed AMK administration; and attenuated the AMK-induced nephrotoxicity. GSE NPs were safe to be used in vivo as a renoprotective agent against AMK; where, it reduced the oxidative stress and inflammation.

miRNAs: novel noninvasive biomarkers as diagnostic and prognostic tools in neonatal sepsis.

The study aimed to assess the diagnostic and prognostic value of 3 specific microRNAs (miRNAs) in early-onset neonatal sepsis (NS). We examined miR-1, miR-124, and miR-34a in 70 NS patients upon admission and compared them to 70 healthy controls by RT-PCR. The main finding of the study was the difference in miRNA expression levels between NS patients and controls. Higher expression levels of miR-1 and miR-124 were significantly associated with NS, while miR-34a expression was reduced. Among the studied miRNAs, miR-34a exhibited the highest specificity (97%) as a confirmatory test for NS. In the multivariate model, miR-1 and miR-124 were found to be significant predictors of disease progression or mortality. Overall, the study suggests that miR-1, miR-124, and miR-34a could serve as potential biomarkers for diagnosing and predicting outcomes in early-onset NS.

Melatonin loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles reduce inflammation, inhibit apoptosis and protect rat's liver from the hazardous effects of CCL4.

Liver is an important organ that carries out major important functions including the detoxification of harmful chemicals. Numerous studies have lately focused on the impact of various substances, such as chemical pollutants and pharmaceutical drugs, on the liver. Melatonin (Mel) has been reported for the protection against liver injury. In order to enhance Mel therapeutic benefits and prevent any potential negative effects, Mel has to be delivered to the injured liver. Therefore, the goal of the current investigation was to create Mel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Mel-PLGA NPs) to alleviate carbon tetrachloride (CCL4)-induced liver damage in male Sprague Dawley rats. The prepared Mel-PLGA NPs were physically characterized to determine its size and charge. Moreover, Mel-PLGA NPs were examined, in vitro, to determine its antioxidant, anticoagulant, anti-inflammatory and cytotoxicity effects before being used in vivo. The effect of NPs on liver injury was evaluated through biochemical, immunological, histopathological examination and flow cytometry technique. Mel-PLGA NPs were smooth and spherical with no signs of aggregation and have in vitro antioxidant, anti-inflammatory and anticoagulant effects. NPs varied in size from 87 to 96 nm in transmission electron microscope images, while their hydrodynamic diameter was 41 nm and their zeta potential was -6 mV. Mel-PLGA NPs had encapsulation efficiency (EE%) and drug loading (DL%) of 59.9 and 12.5%, respectively. Treatment with Mel-PLGA NPs ameliorated all histopathological changes, in liver sections, that resulted from CCL4 administration; where, liver sections of treated groups were similar to those of healthy control GI. NPs administration were superior to free Mel and reversed the elevated levels of liver function enzymes, inflammatory cytokines and matrix metalloproteinases to their normal levels. Moreover, liver sections of groups treated with NPs showed negative immunostaining for nuclear factor-κB (NF-κB) and C-reactive protein indicating their anti-inflammatory behavior. Mel-PLGA NPs significantly protected liver from the toxicity of CCL4. The effective dose of NPs was 5 mg/kg indicating a reduction in the required Mel dose and its associated adverse effects.

Associations Between Serum Soluble Toll-like Receptors 4 and 9 and Breast Cancer in Egyptian Patients.

BACKGROUND: Toll-like receptors (TLRs) play an important role in regulation of immune cells and are vital in tumorigenesis due to its crucial role in inflammatory microenvironment regulation, as they promote the synthesis and release of inflammatory cytokines and chemokines. Toll-like receptors 4 and TLRs 9 were found to be highly expressed in breast cancer. The aim of this study is to investigate the soluble toll-like receptors 4 and 9 (sTLR4 and sTLR9) as potential biomarkers for diagnosis and prognosis of breast cancer and their association with the clinicopathological parameters of breast cancer. PATIENTS AND METHOD: In this retrospective case-control study, 186 female subjects were recruited and divided into three groups, Group I: 62 healthy control, Group II: 62 subjects diagnosed with non-metastatic breast cancer, and Group III: 62 subjects diagnosed with metastatic breast cancer. Enzyme-linked immunosorbent assay (ELISA) technique was used to quantify the levels of sTLR4 and sTLR9 in serum. RESULTS: Both non-metastatic and metastatic groups showed significant higher levels of both serum sTLR4 and sTLR9 expression compared to healthy controls. Only sTLR9 was significantly increased among metastatic patients compared to non-metastatic group. Serum levels of sTLR9 and sTLR4 were still significantly associated with breast cancer in a multiple logistic regression model (P = <.001). ROC curves showed that both sTLR4 and sTLR9 can be a significant parameter to discriminate between normal females and breast cancer patients. CONCLUSION: Soluble toll-like receptors 4 and sTLR9 are over-expressed in patients with metastatic and non-metastatic BC than in benign cases. The expression levels of sTLR4 and TLR9 have clinical interest as indicators of tumor aggressiveness suggested to be prognostic biomarkers. Toll-like receptors may represent therapeutic targets in breast cancer.

Immunohistochemical Expression of CD90, CD133, and TPM1 in Relation to Gastric Cancer and H. pylori Association.

BACKGROUND: Gastric cancer (GC) is the second most common cause of cancer-related death worldwide. Multiple malignancies overexpress CD90, making it a helpful diagnostic and prognostic marker. CD133 is suggested to be related to poor prognosis in GC. Tropomyosin-1 (TPM1) tumor-suppressor gene low expression may predict poor survival in GC. Our study aimed to investigate CD90, CD133, and TPM1 immunohistochemical expression in GC in relation to diagnosis, prognosis, and Helicobacter pylori (H. pylori) infection. METHODS: 144 paraffin blocks containing gastric cancerous (108 cases), and non-cancerous (36 cases) tissue were analyzed histopathologically for the type of lesion, grade, and stage of malignancy and by using an immunohistochemical assay for studying the expression of CD90, CD133, and TPM1. Data analysis was carried out using the Statistical Package for the Social Sciences (SPSS) version 20.0. RESULTS: The obtained results showed a significantly higher expression of CD90 and CD133 while showing a significantly lower expression of TPM1 in malignant samples compared to benign ones. CD90 was significantly higher in grade-3, stage-3, and N3 (p<0.05), with no significant difference concerning positive and negative H. pylori samples. CD133 percentage and H-score were significantly higher in grade-2 and stage-4 tumors than in other grades and stages, while being insignificantly higher in N3 and H. pylori-positive cases. TPM1 expression levels were significantly downregulated in GC and H. pylori-positive cases (p<0.05). TPM1 downregulation was associated with grade progression, increased depth of invasion, and tumor node metastasis. CONCLUSION: CD90, CD133, and TPM1 immunohistochemical expression in the gastric biopsy are related firmly to grades and stages of GC as well as H. pylori infection, so they could be of prognostic value. Further studies on a larger sample size are recommended.

Changes in morphological traits, anatomical and molecular alterations caused by gamma-rays and zinc oxide nanoparticles in spinach (Spinacia oleracea L.) plant.

Spinach seeds were irradiated with gamma-rays after that soaked in zinc oxide nanoparticles (ZnO-NPs) at 0.0, 50, 100 and 200 ppm for twenty-four hours at room temperature. Vegetative plant growth, photosynthetic pigments, and proline contents were investigated. Also, anatomical studies and the polymorphism by the SCoT technique were conducted. The present results revealed that the germination percentage was at the maximum values for the treatment of 100 ppm ZnO-NPs (92%), followed by 100 ppm ZnO-NPs + 60 Gy (90%). The application of ZnO-NPs resulted in an enhancement in the plant length. The maximum of chlorophylls and carotenoids content was recorded in the treatment, 100 ppm ZnO-NPs + 60 Gy. Meanwhile, the irradiation dose level (60 Gy) with all ZnO-NPs treatments increased proline content and reached its maximum increase to 1.069 mg/g FW for the treatment 60 Gy combined with 200 ppm ZnO-NPs. Also, the anatomical studies declared that there were variations between the treatments; un-irradiated and irradiated combined with ZnO-NPs plants which reveal that the leave epidermal tissue increased with 200 ppm ZnO-NPs in both the upper and lower epidermis. While irradiated plants with 60 Gy combined with 100 ppm ZnO-NPs gave more thickness of upper epidermis. As well as SCoT molecular marker technique effectively induced molecular alterations between the treatments. Where, SCoT primers targeted many new and missing amplicons that are expected to be associated with the lowly and highly expressed genes with 18.2 and 81.8%, respectively. Also, showed that the soaking in ZnO-NPs was helped for reducing molecular alteration rate, both spontaneous and induced by gamma irradiation. This nominates ZnO-NPs as potential nano-protective agents that can reduce irradiation-induced genetic damage.

Estimation of Calcium Titanate or Erbium Oxide Nanoparticles Induced Cytotoxicity and Genotoxicity in Normal HSF Cells.

Extensive uses of calcium titanate nanoparticles (CaTiO3-NPs) and erbium oxide nanoparticles (Er2O3-NPs) increase their release into the environment and human exposure, particularly through skin contact. However, there are almost no studies available on the effect of these nanoparticles on skin integrity. Therefore, this study was undertaken to estimate CaTiO3-NP- or Er2O3-NP-induced cytotoxicity and genotoxicity in normal human skin fibroblast (HSF) cells. Cell viability was measured using sulforhodamine B (SRB) assay, while the level of DNA damage was detected using the alkaline comet assay. The intracellular levels of reactive oxygen species (ROS) as well as the expression level of p53, Bax, and Bcl2 genes were detected. Although the viability of HSF cells was non-markedly changed after 24 h, prolonged treatment with CaTiO3-NPs or Er2O3-NPs for 72 h induced concentration-dependent death of HSF cells. Treatment of normal HSF cells with IC50/72 h of CaTiO3-NPs or Er2O3-NPs did not cause marked changes in the intracellular level of ROS, DNA damage parameters, and expression levels of apoptosis genes compared to their values in the untreated HSF cells. We thus concluded that CaTiO3-NPs or Er2O3-NPs cause time- and concentration-dependent cytotoxicity toward normal HSF cells. However, safe and non-genotoxic effects were demonstrated by the apparent non-significant changes in intracellular ROS level, DNA integrity, and apoptotic genes' expression after exposure of normal HSF cells to nanoparticles. Thus, it is recommended that further studies be conducted to further understand the toxic and biological effects of CaTiO3-NPs and Er2O3-NPs.

Co-treatment with grape seed extract and mesenchymal stem cells in vivo regenerated beta cells of islets of Langerhans in pancreas of type I-induced diabetic rats.

BACKGROUND: Nowadays, diabetes mellitus is known as a silent killer because individual is not aware that he has the disease till the development of its complications. Many researchers have studied the use of stem cells in treatment of both types of diabetes. Mesenchymal stem cells (MSCs) hold a lot of potential for regenerative therapy. MSCs migrate and home at the damaged site, where they can aid in the repair of damaged tissues and restoring their function. Oxidative stress and inflammation represent a huge obstacle during MSCs transplantation. Therefore, the present study aimed to evaluate the role of grape seed extract (GSE) administration during MSCs transplantation in streptozotocin (STZ)-induced type I diabetes. Furthermore, testing some of GSE components [procyanidins(P)-B1 and P-C1] in conjunction with MSCs, in vivo, was performed to determine if one of them was more effective in relieving the measured attributes of diabetes more than the whole GSE. METHODS: Firstly, GSE was prepared from the seeds of Muscat of Alexandria grapes and characterized to identify its phytochemical components. Experimental design was composed of control group I, untreated diabetic group II, GSE (300 mg/kg)-treated diabetic group III, MSCs (2 × 106 cells/rat)-treated diabetic group IV and GSE (300 mg/kg)/MSCs (2 × 106 cells/rat)-treated diabetic group V. Type I diabetes was induced in rats by intravenous injection with 65 mg/kg of STZ. Treatment started when fasting blood glucose (FBG) level was more than 200 mg/dl; GSE oral administration started in the same day after MSCs intravenous injection and continued daily for 30 consecutive days. RESULTS: The results showed that GSE/MSCs therapy in type I-induced diabetic rats has dramatically managed homeostasis of glucose and insulin secretion; together with, improvement in levels of inflammatory markers and oxidative stress. CONCLUSION: Co-treatment with GSE and MSCs in vivo regenerates beta cells in type I-induced diabetic rats.

Estimation of genotoxicity, apoptosis and oxidative stress induction by TiO2 nanoparticles and acrylamide subacute oral coadministration in mice.

Acrylamide is used in the industry and can be a by-product of high-temperature food processing which has toxic potential in various tissues, and titanium dioxide nanoparticles (TiO2NPs) are widely used in toothpaste, sweets, food perseveration, chewing gum and medicines. Consequently, humans are daily exposed to large amounts of acrylamide and TiO2NPs mainly through food intake. However, limited studies are available on the effect of simultaneously intake of acrylamide and TiO2NPs on the integrity of genomic DNA and the induction of apoptosis in brain tissues. Therefore, this study estimated the influence of acrylamide coadministration on TiO2NPs induced genomic instability and oxidative stress in the brain tissues of mice. To achieve this, mice were orally administrated acrylamide (3 mg/kg b.w) or/and TiO2NPs (5 mg/kg b.w) for two successive weeks (5 days per week). The comet assay results showed that concurrent oral administration of acrylamide and TiO2NPs strongly induced single- and double stranded DNA breaks, and that the level of reactive oxygen species (ROS) was also highly elevated within neural cells after simultaneous oral intake of acrylamide and TiO2NPs compared to those observed after administration of acrylamide or/TiO2NPs alone. Moreover, oral co-administration of acrylamide with TiO2NPs increased apoptotic DNA damage to neurons by upregulating the expression levels of P53, TNF-α, IL-6 and Presenillin-1 genes compared to groups administered TiO2NPs. Therefore, from these results, the present study concluded that coadministration of acrylamide renders TiO2NPs more genotoxic and motivates apoptotic DNA damage and oxidative stress induced by TiO2NPs in brain cells, and thus it is recommended to avoid concurrent oral acrylamide administration with TiO2NPs.

Induction of ROS mediated genomic instability, apoptosis and G0/G1 cell cycle arrest by erbium oxide nanoparticles in human hepatic Hep-G2 cancer cells.

The remarkable physical and chemical characteristics of noble metal nanoparticles, such as high surface-to-volume ratio, broad optical properties, ease of assembly, surfactant and functional chemistry, have increased scientific interest in using erbium oxide nanoparticles (Er2O3-NPs) and other noble metal nanostructures in cancer treatment. However, the therapeutic effect of Er2O3-NPs on hepatic cancer cells has not been studied. Therefore, the current study was conducted to estimate the therapeutic potential of Er2O3-NPs on human hepatocellular carcinoma (Hep-G2) cells. Exposure to Er2O3-NPs for 72 h inhibited growth and caused death of Hep-G2 cells in a concentration dependent manner. High DNA damage and extra-production of intracellular reactive oxygen species (ROS) were induced by Er2O3-NPs in Hep-G2 cells. As determined by flow cytometry, Er2O3-NPs arrested Hep-G2 cell cycle at the G0/G1 phase and markedly increased the number of Hep-G2 cells in the apoptotic and necrotic phases. Moreover, Er2O3-NPs caused simultaneous marked increases in expression levels of apoptotic (p53 and Bax) genes and decreased level of anti-apoptotic Bcl2 gene expression level in Hep-G2 cells. Thus it is concluded that Er2O3-NPs inhibit proliferation and trigger apoptosis of Hep-G2 cells through the extra ROS generation causing high DNA damage induction and alterations of apoptotic genes. Thus it is recommended that further in vitro and in vivo studies be carried out to study the possibility of using Er2O3-NPs in the treatment of cancer.

Eco-physiological response and genotoxicity induced by crude petroleum oil in the potential phytoremediator Vinca rosea L.

BACKGROUND: Phytoremediation is determined as an emerging green technology suitable for the safe remediation and restoration of polluted terrestrial and aquatic environments. In this study, the assessment of an ornamental plant, Vinca rosea L., as a phytoremediator of crude oil in polluted soils was conducted. In an open greenhouse experiment, plants were raised in sandy-clayey soils treated with 1, 3, 5, and 7% oil by weight. The experiment was conducted over 5 months. RESULTS: Total petroleum hydrocarbon (TPH) degradation percentage by V. rosea after a 5-month growth period ranged from 86.83 ± 0.44% to 59.05% ± 0.45% in soil treated with 1 and 7%, respectively. Plants raised in polluted soils demonstrated a dramatic reduction in germination rates, in addition to growth inhibition outcomes shown from decreased plant height. An increase in branching was observed with an increase in oil pollution percentages. Moreover, the phytomass allocated to the leaves was higher, while the phytomass witnessed lower values for fine roots, flowering and fruiting when compared to the controls. Apart from the apparent morphological changes, there was a decrease in chlorophyll a/b ratio, which was inversely proportional to the oil pollution level. The contents of carotenoids, tannins, phenolics, flavonoids, and antioxidant capacity were elevated directly with an increase in oil pollution level. The start codon-targeted (SCoT) polymorphisms and inter-simple sequence repeat (ISSR) primers showed the molecular variations between the control and plants raised in polluted soils. The genetic similarity and genomic DNA stability were negatively affected by increased levels of crude oil pollution. CONCLUSIONS: The ability of V. rosea to degrade TPH and balance the increased or decreased plant functional traits at the macro and micro levels of plant structure in response to crude oil pollution supports the use of the species for phytoremediation of crude oil-polluted sites. The genotoxic effects of crude oil on V. rosea still require further investigation. Further studies are required to demonstrate the mechanism of phenolic, flavonoid, and antioxidant compounds in the protection of plants against crude oil pollution stress. Testing different molecular markers and studying the differentially expressed genes will help understand the behavior of genetic polymorphism and stress-resistant genes in response to crude oil pollution.

Melatonin relieves diabetic complications and regenerates pancreatic beta cells by the reduction in NF-kB expression in streptozotocin induced diabetic rats.

Melatonin, a pleiotropic hormone, has many regulatory effects on the circadian and seasonal rhythms, sleep and body immune system. It is used in the treatment of blind circadian rhythm sleep disorders, delayed sleep phase and insomnia. It is a potent antioxidant, anti-inflammatory, free radical scavenger, helpful in fighting infectious disease and cancer treatment. Decreased level of circulating melatonin was associated with an increased blood glucose level, losing the anti-oxidant protection and anti-inflammatory responses. We aimed to evaluate the effect of melatonin administration, in streptozotocin (STZ) induced diabetic rats, on blood glucose level and pancreatic beta (ß) cells. Diabetes mellitus was induced in Sprague dawley male rats by the intravenous (i.v) injection of 65 mg/kg of STZ. Diabetic rats received melatonin at a dose of 10 mg/kg daily for 8 weeks by oral routes. The results showed, after 8 weeks of melatonin administration, a reduction in: 1- fasting blood glucose (FBG) and fructosamine (FTA) levels, 2- kidney and liver function parameters, 3- levels of serum triglycerides, cholesterol and LDL-C, 4- malondialdehyde (MDA), 5- NF-κB expression in treated group, 6- pro-inflammatory cytokines (IL-1ß and IL-12) and immunoglobulins (IgA, IgE and IgG). Furthermore, an elevation in insulin secretion was noticed in melatonin treated group that indicated ß cells regeneration. Therefore, melatonin administration, in STZ induced diabetic rats; reduced hyperglycemia, hyperlipidemia and oxidative stress. Melatonin acted as an anti-inflammatory agent that reduced pro-inflammatory cytokines (IL-1ß and IL-12) and oxidative stress biomarkers (MDA). Melatonin succeeded in protecting ß cells under severe inflammatory situations, which was apparent by the regeneration of islets of Langerhans in treated diabetic rats. Moreover, these results can open a gate for diabetes management and treatment.

Garlic (Allium sativum Linnaeus) improved inflammation and reduced cryptosporidiosis burden in immunocompromised mice.

ETHNOPHARMACOLOGICAL RELEVANCE: For thousands of years, garlic (Allium sativum Linnaeus) has been consumed in food and health by numerous civilizations. Cryptosporidium (C.) parvum is an apicomplexan parasite that causes a gastrointestinal disease, with the most common symptoms being watery diarrhea. Although several substances have been tried for its anti-cryptosporidial action, there is no effective treatment for Cryptosporidium disease, especially in immunocompromised individuals. The present study aimed firstly to characterize the bio-active compounds in Allium sativum L. and secondly to evaluate its efficacy as a therapy for cryptosporidiosis especially in immunocompromised mice. MATERIALS AND METHODS: This was accomplished by evaluating the parasitological and histopathological parameters in the experimentally infected immunocompetent and immunocompromised mice. Also, the cytokine profile during the experimental time was recorded through the measuring of T helper (h)1, Th2 and Th17 cells cytokines. Immunosuppressed mice were given 0.25 µg/g per day of dexamethasone orally, before infection with Cryptosporidium parvum oocysts, for fourteen consecutive days. Starting 10 days post infection (PI), nitazoxanide (100 mg/kg per day) or Allium sativum (50 mg/kg per day) was given orally for fourteen consecutive days. RESULTS: Our results showed that oocyst shedding, on the 32nd day PI, in immunocompromised infected group treated with Allium sativum (354.11, 99.35% PR) showed a significant decrease when compared to its corresponding group treated with nitazoxanide (4369.14, 92.05% PR). On the 32nd day PI, all cytokines levels have been decreased to levels that were similar to those of their uninfected corresponding control groups; also, the histopathological changes and the loss in animals' body weight had been improved. Treatment with nitazoxanide did not result in infection clearance or a reduction in the increased cytokines' levels. CONCLUSION: Allium sativum L. displayed high efficacy as a potential therapeutic agent against Cryptosporidium, which supports its traditional usage in parasite diseases.