Histomorphological, Histochemical and Ultrastructural Studies on the Healthy Liver of Yemen Veiled Chameleon (Chamaeleo calyptratus) in Southern Saudi Arabia / Estudios Histomorfológicos, Histoquímicos y Ultraestructurales en el Hígado Sano del Camaleón Velado de Yemen (Chamaeleo calyptratus) en el Sur de Arabia Saudita

SUMMARY: The livers of reptiles are being studied as a model for the link between the environment and hepatic tissue. There have been few investigations on the histology of reptile livers, and very few or no studies have examined the histology of liver of veiled chameleon (Chamaeleo calyptratus). This paper describes the histomorphological, histochemical and ultrastructural characterization of the liver of veiled chameleons in southern Saudi Arabia. Seven Chamaeleo calyptratus were captured in the summer season in Abha City, Aseer region, southern Saudi Arabia. Chamaeleon liver samples were processed for histomorphology, histochemistry and ultrastructure analyses. Morphologically liver of Chamaeleo calyptratus was observed as a large dark brown organ with lighter speckles, which represent melanin deposits. It located at the ventral part of abdominal cavity forward of the stomach. Its dimensions approximately were 3.7 x 2 cm. The liver was a bilobed organ divided into two lobes, right and left lobes. The right one was bigger than the others. The gallbladder was well developed and had an elongated shape, situated between the two lobes and contained the bile for the digestion. Microscopically, the liver was found to be covered by a thick layer of connective tissue, which formed the hepatic capsule. Hepatic parenchyma probably appeared in cross sections as hepatic glandular-like alveoli "acini" or follicular structures with various diameters, each acinus contains approximately four to six hepatocytes, surrounded by sinusoidal capillaries filled with abundant melanomacrophages, which are absent in birds and mammals. Melanomacrophages are common in the hepatic parenchyma's perisinusoidal areas, particularly near portal spaces. Hepatocytes are polyhedral or pyramidal with and mostly contained large, rounded nuclei mostly peripherally located, with prominent dark oval nucleoli. Some of nuclei are eccentric or central position. The cytoplasm appeared spongy or vacuolated and more eosinophilic when stained by hematoxylin-eosin and strongly reactive to PAS staining technique, indicating abundant glycogen content. The reticular fibers that surround hepatocytes, blood arteries, and sinusoids supported the hepatic parenchyma. The blood sinusoids are seen interspersed among hepatocytes of varying sizes. The sinusoidal lumen was bordered by flattened endothelial cells and includes elliptical nucleated erythrocytes and liver macrophages as phagocytes, which are also known as Kupffer cells. Branches of the portal vein, hepatic artery, small bile duct, and lymph vessels were detected in the hepatic portal area "tract" or triad which made up of connective. Hematopoietic tissue was observed in subcapsular region and portal triads. Ultrastructurally, the hepatocyte appeared polyhedric containing a single large rounded basal or eccentric vesicular nucleus with prominent nucleolus. Extensive network of rough endoplasmic reticulum (RER) often arranged in an array parallel to the nuclear membrane with many mitochondria, and Golgi apparatus were described. The cytoplasm contained glycogen granules, vesicles or vacuoles scattered throughout the cytoplasm especially at the apical region were reported. The bile canaliculi and the hepatic "Kupffer" cells were also discussed. This is the first study on the histological characterization of the healthy liver of Yemen veiled chameleon in southern Saudi Arabia. The findings reported here should be used as a reference to compare with the pathological abnormalities of the liver in this animal.

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Effect of Vegetable Waste on Growth Performance and Hematology of Broiler Chicks.

Vegetable waste (spinach, potato, and cauliflower) is a rich and natural source of nutrients, potentially good for supplying minerals, essential amino acids, and antioxidants to the birds. Relatively, its cost very low, easily to accessible, easily process & pose little risk of illness. The aim of present study was to evaluate the effect of vegetable waste (VW) as feed supplement on growth performance and hematology of broiler chicks. For this purpose, a total of 200 (4 days old) vaccinated chicks were acquired from a commercial hatchery Multan which was acclimated for three weeks (21 days) on basal starter feed after that 25-day-old chicks with uniform body weight were allocated according to a CRD (completely randomized design) into four dietary treatments with three replicates of each contained 15 chicks in 12 pens. In dietary treatments, chicks were feed with basal feed (BF) and supplemented feed with vegetable waste (VW) of spinach, potato, and cauliflower. For this purpose, the dietary treatments included control treatment (T 1) (100% BF+0% VW) and other dietary treatments (T 2) (75% BF+25% VW), (T 3) (50% BF+50% VW), and (T 4) (25% BF+75% VW). The body weight, feed intake, food conversion ratio (FCR), and mortality were checked on weekly and daily basis. For hematology analysis, after the 1st experimental week (25-day-old chicks) and the last 5th experimental week (56-day-old chicks), the samples of blood were gathered from the wing's veins of two birds from each treatment in random way. At the end of five weeks (35 days), birds with uniform average body weight were selected per treatment with three replicates (2 bird/replicate) and then were manually slaughtered according to the Halal method to analyze the weight of internal body organs of broilers by physical and statistical analysis (ANOVA). There was no significant effect (P > 0.05) on feed intake and FCR among all the dietary treatments. But in average, body weight and BWG were higher in treatment (T 2) (P < 0.01) than all other dietary treatments (T 3) and (T 4) and control treatment (T 1). The blood constituents in this study showed that broilers in control treatment (T 1) and other dietary treatments (T 2), (T 3), and (T 4) fed on different doses were significantly (P < 0.01) different from each other. The week 5 (W 5) shows higher values of blood constituents (P < 0.01) than week 1 (W 1). The carcass yield of the chicks fed on different doses showed that they were significantly different (P < 0.01) among the dietary treatments. The VW inclusion 0%, 25%, 50%, and 75% had positive effect on blood constituents and carcass yield of the broiler chicks; they were significantly (P < 0.01) different among the treatments.

Larval cestodes infecting commercial fish of Alexandria coast along the Mediterranean Sea: morphology and phylogeny.

Members of the order Trypanorhyncha are cestode parasites that are frequently found infecting the muscles of several marine fish species, affecting fish health and resulting in consumers' rejection. Seventy-five specimens of marine fish were freshly caught from boat landing sites at the Alexandria coast along the Mediterranean Sea in Egypt, including two Carangids, the greater amberjack Seriola dumerili and the gulley jack Pseudocarans dentex; two Serranids, the Haifa grouper Epinephelus haifensis and the mottled grouper Mycteroperca rubra. Forty-five fish were infected; the infection was recorded as blastocysts embedded in fish flesh. Blastocysts were isolated and ruptured; the generated plerocerci were described morphologically, where, four different species were recovered; Callitetrarhynchus gracilis, Callitetrarhynchus speciosus, Protogrillotia zerbiae, and Grillotia brayi. The taxonomic position of these parasites was justified by multiple-sequence alignment and a phylogenetic tree was constructed following maximum likelihood analysis of the 18s rRNA sequences of the recovered worms. The accession numbers MN625168, MN625169, MN611431and MN611432 were respectively assigned to the recovered parasites. The results obtained from the molecular analyses confirmed the morphological records of the recovered parasites. Since metacestodes are found in the musculature of infected fish specimens, it is necessary to remove these areas in the commercialization of fish.

Behavioural alterations induced by chronic exposure to 10 nm silicon dioxide nanoparticles.

Silicon dioxide nanoparticles (SiO2 NPs) are widely invested in medicine, industry, agriculture, consuming products, optical imaging agents, cosmetics, and drug delivery. However, the toxicity of these NPs on human health and the ecosystem have not been extensively studied and little information is available about their behavioural toxicities. The current study aimed to find out the behavioural alterations that might be induced by chronic exposure to 10 nm SiO2 NPs. BALB/C mice were subjected to 36 injections of SiO2 NPs (2 mg/kg Bw) and subjected to 11 neurobehavioural tests: elevated plus-maze test, elevated zero-maze test, multiradial maze test, open field test, hole-board test, light-dark box test, forced swimming test, tail-suspension test, Morris water-maze test, Y-maze test and multiple T-maze test. Treated mice demonstrated anxiety-like effect, depression tendency, behavioural despair stress, exploration and locomotors activity reduction with error induction in both reference and working memories. The findings may suggest that silica NPs are anxiogenic and could aggravate depression affecting memory, learning, overall activity and exploratory behaviour. Moreover, the findings may indicate that these nanomaterials (NMs) may induce potential oxidative stress in the body leading to neurobehavioural alterations with possible changes in the vital organ including the central nervous system.

Cardiac and testicular alterations induced by acute exposure to titanium dioxide nanoparticles: Histopathological study.

Titanium dioxide nanoparticles (TiO2 NPs) have novel application and are used in many household application, nanomedicine, agriculture, industries and pharmaceutical products. These applications may be accompanied with potential risk in human health and the ecosystems. The current study was carried out to find out the acute damage that might be induced by TiO2 NPs in the heart and testis. Three groups of Wistar albino rats (Rattus norvegicus) were subjected to a single dose TiO2 NPs (126, 252, 378 mg/kg bw). Cardiac and testicular biopsies from each animal under study were handled for histological and histochemical examination. Rats exposed to TiO2 NPs demonstrated the following cardiac alterations: myofibres wavy appearance, myofibre disarray, partial cross striation, cardiomyocytes hydropic degeneration together with vacuolation and nuclear alterations. Moreover, acute exposure to TiO2 NPs induced the following testicular alterations: spermatocytes degeneration, spermatids sloughing and interstitial edema. The presented cardiac and testicular alterations were dose dependent. From the findings of the present study, it might be concluded that TiO2 nanomaterials are capable of inducing acute cardiac and testicular damage that is dose dependent and could adversely affect the function of the vital organs.

Molecular evidence and morphological aspects of Transversotrema licinum, Phyllodistomum hoggettae, and re-description of Gyliauchen volubilis (Digenea) from the Red Sea.

During a recent survey on digenean parasites infecting marine fish captured from water located along the Red Sea off Gizan Coasts, Saudi Arabia, thirty-two (29.09%) out of 110 fish were naturally infected with three different species of digenean parasites. The taxonomical status of the recovered worms was confirmed by light microscopy and molecular analysis. Transversotrema licinum infecting the Haffara seabream Rhabdosargus haffara possessed a transversely elongated body with eyespots and the anterior body margin with delineated velum along with its entire breadth. Oral sucker was absent, and eyespots were paired anterior to or at the level of ventral sucker. Phyllodistomum hoggettae from the urinary bladder of the Arabian Nagil Plectropomus areolatus was differentiated by its elongated body, narrow anterior end widened as going posteriorly with prominent marginal undulations in the hindbody. Gyliauchen volubilis infecting the marbled spinefoot Siganus rivulatus, was with fleshy body, conical, tapered anteriorly, convex dorsally, and concave ventrally. Prepharynx was very long and convoluted and had occupied the greater part of the anterior half of the body. Multiple sequence alignment and phylogeny were based on maximum likelihood analysis for the ITS-2 and 28S rDNA for Transversotrema licinum and Phyllodistomum hoggettae were constructed, respectively. They were compared to species within their families and further deposited into the Genebank under accession numbers MG 722711 and MG722710, respectively.

Abundance, distribution, and growth characteristics of three keystone Vachellia trees in Gebel Elba National Park, south-eastern Egypt.

This study was conducted to evaluate the abundance and distribution pattern of three keystone Vachellia taxa in wadi Khoda and wadi Rahaba, Gebel Elba National Park, a protected area in south-eastern Egypt. These taxa included Vachellia tortilis subsp. tortilis, Vachellia tortilis subsp. raddiana, and Vachellia ehrenbergiana. In wadi Khoda, only two of these taxa were detected (V. tortilis subsp. raddiana and V. tortilis subsp. tortilis), while all three taxa were encountered in wadi Rahaba. The density of trees in wadi Khoda was 34.3 plant ha-1 compared to 26.3 plant ha-1 in wadi Rahaba. Vachellia tortilis subsp. raddiana was the most frequently observed tree, with an average of 47.93% and 68.25% in wadi Rahaba and wadi Khoda, respectively. Crown depth and tree height were mainly associated with elevation, indicating that elevation plays a key role in the growth of these Vachellia taxa. Our results suggest that human activities have had limited effect on the distribution of these three keystone taxa. Thus, management in Gebel Elba National Park should continue to limit the impact of human activities on these three keystone species.

Renal Alterations Induced by Chronic Exposure to Therapeutic Doses of Antihypercholestremic Atorvastatin.

BACKGROUND: Atorvastatin (ATOR) is widely used for the treatment and prevention of hypercholesterolemia and various diseases, such as cardiovascular complications, with little data about the histopathological and ultrastructural renal alterations that might be induced by this drug. OBJECTIVES: The present study was undertaken to investigate the potential toxicity of therapeutic doses of atorvastatin on the microanatomy and ultrastructure of renal tissues from Wistar albino rats. METHODS: Adult male Wistar albino rats received an oral daily dose of 5 mg/kg bodyweight for 90 consecutive days. Biopsies from both kidneys of each study rat were taken for histopathological and ultrastructural examination. RESULTS: ATOR-treated rats exhibited glomerular, tubular, and interstitial histological alterations, including degeneration, necrosis, hyaline droplets, edema, cortical hemorrhages, mesangial hypercellularity, and blood capillary dilation and congestion. In addition, ATOR exposure increased the activity of glucose-6-phosphate dehydrogenase and alkaline phosphatase with a concurrent reduction in proteins and neutral mucosubstances content of the glomeruli and renal cells. Moreover, ATOR-treated animals demonstrated glomerular ultrastructural alterations, consisting mainly of capillary tuft dilatation, glomerular basement membrane thickening, and mesangial cell proliferation. The renal cells of the proximal tubules demonstrated damaged mitochondria, degenerative cellular changes, endoplasmic reticulum dilatation, lysosomal and autophagosome activation, nuclear alteration, myelin figure formation, and microvilli disorganization. CONCLUSION: The findings of the present work may indicate that ATOR can induce renal histological, histochemical, and ultrastructural alterations that may affect kidney and other vital organ functions.

Silver/chitosan nanocomposites induce physiological and histological changes in freshwater bivalve.

BACKGROUND: Bivalves can accumulate and concentrate most pollutants, even if they are present in somewhat low concentrations. The present study aimed to use freshwater bivalveas for the first time as vital indicator for silver/chitosan nanocomposites (Ag-CS NCs) in the freshwater environment. METHODS: Following the preparation and characterization of Ag-CS NCs by using UV-vis spectrophotometer, X-ray diffraction, transmission electron microscopy, and acute toxicity study, the animals exposed to three different dose of nano chitosan (CS), AgNPs, and Ag-CS NCs (12.5, 25 and 50 mg/L) for consecutive 6 days. RESULTS: Ag-CS particles were in size range of 8-19 nm. The nominal concentrations for Ag-CS NCs were 12.5, 25 and 50 mg Ag L-1 were corresponding to measured concentration of AgNPs 0.37, 0.81, and 1.65 mg Ag L-1, respectively. All concentrations of Ag-CS NCs caused a significant increase in MDA and NO, while GSH and CAT levels decreased significantly in all organs. Histological investigation of the gills, labial palp and foot tissues showed alternation after exposure to Ag-CS NCs, especially at dose 50 mg/L. CONCLUSION: The present study showed that exposure to Ag-CS NCs caused oxidative stress responses in Coelatura aegyptiaca and histological changes in the organs. These physiological and histological changes observed after exposure to Ag-CS NCs were most likely the result of the action of AgNPs themselves while the effect of chitosan on these changes was negligible. We concluded that Coelatura aegyptiaca was a sensitive bio-indicator for monitoring of the past and the present water pollution by nanoparticles.

Combined Supplementation of Nano-Zinc Oxide and Thyme Oil Improves the Nutrient Digestibility and Reproductive Fertility in the Male Californian Rabbits.

The present study aimed to determine the effects of zinc oxide nanoparticles (ZnO-NPs), thyme oil (THO), or their combination on the nutrient digestibility coefficients, reproductive parameters, and some blood metabolites of male Californian rabbits. One hundred rabbits, 29-weeks of age (initial body weight 3.48 ± 0.08 kg) were randomly distributed into four groups, 25 rabbits each. Treatment groups were fed a control diet, a control diet supplemented with ZnO-NPs (100 mg/kg), THO (500 mg/kg), or combination of ZnO-NPs (100 mg/kg) and THO (500 mg/kg). The feeding trial lasted for 35 days. Results showed improvements in dry matter, crude protein, ether extract, and crude fiber in ZnO-NPs, THO, and their combination treated groups compared to those of control. Furthermore, semen volume, sperm motility, vitality, and morphology were significantly improved (p < 0.01) in ZnO-NPs and THO groups rather than the control. Both ZnO-NPs and THO, as either individual or combined treatments significantly improved the serum alanine amino-transferase (ALT), aspartate amino-transferase (AST), urea, and creatinine compared to the control. Moreover, serum concentrations of testosterone were significantly increased in rabbits supplemented with ZnO-NPs, THO, or their combination compared to those of control (p < 0.05). In conclusion, ZnO-NPs, THO, or their combination improved the digestibility of nutrients, liver/ kidney functions, semen characteristics, and testosterone concentration in male rabbits.

Prosopis juliflora leave extracts induce cell death of MCF-7, HepG2, and LS-174T cancer cell lines.

Prosopis juliflora (P. juliflora) is a widespread phreatophytic tree, which belongs to the Fabaceae family. The goal of the present study is to investigate the potential anti-cancer effect of P. juliflora leave extracts and to identify its chemical composition. For this purpose, MCF-7 (breast), HepG2 (liver), and LS-174T (colorectal) cancer cell lines were cultivated and incubated with various concentrations of P. juliflora leave extracts, and its impact on cell viability, proliferation, and cell cycle stages was investigated. P. juliflora leave extracts induced concentration-dependent cytotoxicity against all tested cancer cell lines. The calculated IC50 was 18.17, 33.1 and 41.9 µg/ml for MCF-7, HePG2 and LS-174T, respectively. Detailed analysis revealed that the cytotoxic action of P. juliflora extracts was mainly via necrosis but not apoptosis. Moreover, DNA content flow cytometry analysis showed cell-specific anti-proliferative action and cell cycle stages arrest. In order to identify the anti-cancer constituents of P. juliflora, the ethyl extracts were analyzed by liquid chromatography-mass spectrometry. The major constituents identified in the ethyl extracts of P. juliflora leaves were hydroxymethyl-pyridine, nicotinamide, adenine, and poly-(methyl methacrylate) (PMMA). In conclusion, P. juliflora ethyl acetate extracts have a potential anti-cancer effect against breast adenocarcinoma, hepatocellular carcinoma, and colorectal adenocarcinoma, and is enriched with anti-cancer constituents. See also Figure 1(Fig. 1).

Freshwater Clam as a Potential Bioindicator for Silver/Saponin Nanocomposites Toxicity.

Despite the progress in using silver nano products in many fields, including medicine, food, and industry, their effects on the environment need more attention. Therefore, the current study aimed to assess the effect of silver/saponin nanocomposites (Ag/S NCs) for the first time on the aquatic environment by using freshwater clam, Caelatura aegyptiaca, as a fundamental bioindicator in the freshwater system. Following the preparation and characterization of Ag/S NCs by using atomic absorption spectrophotometer, UV-Vis spectrophotometer, X-ray diffraction, transmission electron microscopy, and acute toxicity study, we exposed the clam to three different doses of Ag/S NCs (12.5, 25 and 50 mg L-1) for consecutive 6 days. All Ag/S NCs concentrations caused a significant increase in malondialdehyde and nitric oxide while induced a notable decrease in glutathione and catalase levels in all studied organs. Moreover, the histological alternations were observed in gills, labial palp, and foot tissues, particularly at dose 50 mg L-1. From the results of our work, we concluded that toxicity of Ag/S NCs on freshwater clam leads to an oxidative stress response as well as histopathological changes. Besides, we assumed that Coelatura aegyptiaca could be used as a sensitive bioindicator for monitoring water pollution caused by different nanoparticles. Therefore, we do recommend performing further studies by using fresh clam to provide a better assessment for our aquatic environment to prevent water pollution locally and globally.

Black tea and curcumin synergistically mitigate the hepatotoxicity and nephropathic changes induced by chronic exposure to aflatoxin-B1 in Sprague-Dawley rats.

The study aimed to clarify the characteristics of black tea (BTE) and/or curcumin (CMN) against aflatoxin-B1 (AFB1). Forty eight adult male Sprague-Dawley rats were divided into eight groups. G1 was non-treated control. G2, G3, and G4 were olive oil, BTE, and CMN, respectively. G5 was olive oil-dissolved AFB1 (25 µg/kg b.w). G6, G7, and G8 were AFB1 along with BTE (2%), CMN (200 mg/kg b.w.), and BTE plus CMN, respectively. All treatments were orally given for consecutive 90 days. After treatment period, rats were sacrificed. Serobiochemical analysis and histopathology showed hepatorenal dysfunction in response to AFB1. Glutathione-antioxidants were significantly decreased versus increased lipid peroxides (p < .05-.001). AFB1 significantly increased the expression of the antitumor p53, but decreased that of antiapoptotic Bcl2 in liver or kidney tissue, either (p < .05). BTE or CMN ameliorated those changes induced by AFB1 in both liver and kidney with highly pronounced improvement when combined BTE/CMN was used. PRACTICAL APPLICATIONS: Black tea (BTE) and curcumin (CMN) were known for their antioxidant effects, and several studies reported their independent effects against different toxicities including aflatoxicosis. The current study clarifies the ameliorative characteristics of both agents; BTE and/or CMN, against the toxicity resulted from the chronic exposure to aflatoxin-B1 (AFB1) (25 µg/kg b.w. for consecutive 90 days). The dose of either agents, BTE or CMN, was 200 mg/kg b.w. along with AFB1. The pathologic changes, serobiochemical parameters, oxidative stress, histological changes, and the molecular disruption, induced by AFB1 in both liver and kidney were obviously and significantly ameliorated after BTE and/or CMN treatments in variable potencies where both agents showed the most effective antitoxic capacities.

The influence of five metallic nanoparticles on the expression of major drug-metabolizing enzyme genes with correlation of inflammation in mouse livers.

Metallic nanoparticles (NPs) are widely used in medical preparations. The present study aims to find out the influence of widely used five metallic NPs on the expression of major hepatic drug-metabolizing enzyme (DME) genes. Six groups of BALB/C mice, 7 mice each, were exposed to: Gold NPs, silver NPs, copper oxide NPs, silicon dioxide NPs and zinc oxide NPs, for 21 days. Liver biopsies from all mice were subjected to mouse cyp3a11, cyp2c29, ugt2b1 and interleukin-6 (il6) gene expression quantification using real-time polymerase chain reaction, in addition to inflammatory cell infiltration examination. All tested NPs caused a sharp and significant (ANOVA, p value <0.05) downregulation in the expression of DME genes, with the highest influence was observed in mice exposed to copper oxide NPs. Additionally, all NPs induced hepatic inflammation and upregulated the expression of il6 gene, which were inversely correlated with the expression of DMEs. It is concluded that all tested NPs downregulated the expression of DME genes, with the highest influence exhibited by copper oxide NPs, in correlation with inflammation and il6 gene induction in the liver. Further studies are needed to find out the effect of anti-inflammatory compounds against the alterations induced by metallic NPs exposure on hepatic DMEs.

Curcumin phytosome modulates aluminum-induced hepatotoxicity via regulation of antioxidant, Bcl-2, and caspase-3 in rats.

Increasing entrance of aluminum chloride (AlCl3) in many fields exposes human beings to its biotoxicity. Thereby, the present study assesses the potential ameliorative role of curcumin phytosome (CP) on AlCl3-induced hepatotoxicity. Rats were divided into four groups (n = 6): group 1 served as control; group 2 received CP (200 mg CP/kg b.wt) for 21 days; group 3 injected three doses of AlCl3 (30 mg/kg/body weight) every 5 days intraperitoneally; group 4 received CP for 7 days prior to AlCl3 and then received CP concurrently with AlCl3 for another 14 days. AlCl3 markedly increased (P < 0.05) the concentrations of AST, ALT, ALP, LDH, total bilirubin, and LPO as well as depleted (P < 0.05) albumin, GSH, SOD, and GPx stores in comparison to the control group. These biochemical alterations supported by the lesion observed in histological sections, increasing the expression of caspase-3 and decreasing the expression of Bcl-2. Treatment with CP modulates the hepatic dysfunction, boosting the endogenous antioxidant status, downregulating the expression of caspase-3, and upregulating the expression of Bcl-2. This hepatic ameliorative effect may be mediated by the ability of CP to repair the oxidant/antioxidant equilibrium rather than its ability to suppress apoptosis.

The apoptotic effect of resveratrol in ovarian cancer cells is associated with downregulation of galectin-3 and stimulating miR-424-3p transcription.

This study investigated if the well-reported anti-tumor effects of resveratrol (RES) is mediated by modulation levels of galectin-3 (GAL-3), an anti-apoptotic lectin that is highly overexpressed in ovarian cancer cells. SKOV3 and OVCAR-3 OC cells were untreated or incubated with DMOS or increasing concentrations of RES (25, 50, 100 µM) for 72 hr. RES, in a dose-dependent manner and in both cell lines, induced cell death and inhibited cell migration and invasion It also downregulated Bcl-2 levels, increased cleaved caspase-3, and GAL-3 protein (but not mRNA) levels, suggesting increased breakdown. These effects were associated with reduced levels of p-NF-κB P65, p-IKKα/ß, and p-Akt, major targets of Gal-3. Further investigation showed that RES enhanced levels of miR-424-3p which is able to degrade GAL-3. Conclusion: Findings of this study suggest that RES induced apoptosis in cancerous cells is associated with increased levels of miR-424-3p and reduced levels of GAL-3. PRACTICAL APPLICATIONS: This study highlights a possible mechanism by which RES could enhance cell death in OC cells and enhances their sensitivity to cisplatin. RES apoptotic effect and enhancement of OC cells to chemotherapy were associated with decreased abundance of GAL-3, a common cell survival molecule that promotes tumorigenesis and increased transcription of miR-424-3p that has the ability to degrade cellular GAL-3. These findings add a possible new mechanism by which RES acts and opens a window for further research to understand its mechanism of action.

Ameliorative effect of selenium nanoparticles against aluminum chloride-induced hepatorenal toxicity in rats.

The present study evaluated the possible ameliorative efficacy of selenium nanoparticles (SeNPs) on AlCl3-induced hepatorenal injury in rats. Animals were randomly divided into four groups (n = 6): group 1, the control; group 2, received SeNPs (0.4 mg/kg b.wt) for 21 days; group 3, injected with three doses of AlCl3 intraperitoneally (30 mg/kg/body weight) every 5 days; group 4, received SeNPs for 7 days prior to AlCl3 and then received SeNPs concurrently with AlCl3 for the following 14 days. It was observed that AlCl3 increased the levels of AST, ALT, ALP, LDH, total bilirubin, creatinine, urea, uric acid, and MDA significantly; as well as the reduction in the levels of GSH, SOD, GPx stores in comparison with the control group. These biochemical alterations were accompanied and confirmed by the lesion appeared in histological sections in addition to the increase in the expression of caspase-3 and the decrease of the Bcl-2expression. Treatment with SeNPs ameliorates the hepatorenal dysfunction, replenishes the endogenous antioxidant system, downregulates the expression of caspase-3, and upregulates the expression of Bcl-2. This hepatorenal ameliorative role may be due to the ability of SeNPs to equilibrate the oxidant/antioxidant system besides its ability to attenuate apoptosis process.

Calycosin induces apoptosis in adenocarcinoma HT29 cells by inducing cytotoxic autophagy mediated by SIRT1/AMPK-induced inhibition of Akt/mTOR.

Autophagy promotes cell survival or induces apoptosis in cancer cells. While SIRT1 and AMPK induce autophagy in both normal and cancer cells, Akt and mTOR can inhibit it. Calycosin, a methoxyisoflavone, protects against several types of solid tumours including colorectal cancer. However, the mechanisms behind the antitumour effect of Calycosin remain largely unknown. This study investigates if autophagy mediates the anti-tumourigenesis effect afforded by Calycosin and examines if this effect involves activation of SIRT1 and/or AMPK. Human colorectal (HT29) carcinoma cells were cultured under normal conditions with Calycosin (50 µmol/L) in the presence or absence of chloroquine (10 µmol/L), EX-527 (100 nmol/L, SIRT1 inhibitor), or IGF-1 (100 ng/mL, Akt/mTOR activator) for 48 hours. Calycosin inhibited cell growth, proliferation and invasion and increased protein levels of Beclin-1 and LC3II, markers of autophagy. It significantly increased protein levels of cleaved caspase-3, Bax, and SIRT1, and activity of AMPK and reduced those of Bcl-2. These effects were parallel with concomitant reduction in protein levels p-src, integrin-ß1 and Cyclin-D1 and activities of Akt and mTOR. Inhibition of autophagy by CQ reversed all these effects except cell invasion. Interestingly, co-incubating the cells with either EX-527 or IGF-1 completely prevented Calycosin-induced autophagy and all other associated effects and increased cell invasion. Also, blockade of SIRT-1 prevented the activation of AMPK, Akt, and mTOR, suggesting it to be an upstream regulator of these markers. In conclusion, Calycosin stimulates CRC cell apoptosis and inhibits their invasion by acting as SIRT1 activator which induces activation of AMPK-induced inhibition of Akt/mTOR axis.

Acylated Ghrelin Renders Chemosensitive Ovarian Cancer Cells Resistant to Cisplatin Chemotherapy via Activation of the PI3K/Akt/mTOR Survival Pathway.

This study investigated the effect of acylated synthetic ghrelin (AG) on the survival and proliferation of human chemosensitive ovarian cancer cells (A2780) and explored some mechanisms of action with a focus on the p53 apoptotic pathway and PI3K/Akt and NF-κB survival pathways. Human A2780 ovarian cancer cells were cultured with or without AG treatment in the presence or absence of cisplatin. In some cases, cisplatin+AG-treated cells were pre-incubated either with [D-Lys3]-GHRP-6, a ghrelin receptor antagonist, or with LY294002, a PI3K inhibitor. mRNA of ghrelin receptors(GHS-R1a and GHS-R1b), as well as, protein levels of GHS-R1a, were expressed abundantly in A2780 cells. AG treatment did not affect the mRNA and protein levels of GHS-R1a and GHS-R1b in both control and Cis-treated cells. However, while AG treatment had no effect on control cell viability, it significantly increased cell viability and proliferation and inhibited cell death in Cis-treated cells. In both control and Cis-treated cells, AG treatment significantly increased PI3K/Akt/mTOR signaling and enhanced the nuclear accumulation of NF-κB. Concomitantly, in both control and Cis-treated cells, AG significantly lowered the protein levels of p53, p-p53 (Ser16), PUMA, cytochrome C, and cleaved caspase-3. Interestingly, pre-incubating the cells with either [D-Lys3]-GHRP-6 or LY294002 completely abolished the above-mentioned effect of AG in both control and Cis-treated cells. In conclusion, the findings of this study show that AG promotes cell survival of the OC cells and renders them resistat to Cis therapy, an effect that is mediated by the activation of PI3K/Akt/mTOR and activation of NF-κB, and requires GHS-R1a.

Taxonomic Justification of the Pathogenic Strongylid Infecting the Arabian Camel Camelus Dromedarius as Haemonchus Longistipes by Morphological and Molecular Phylogeny.

INTRODUCTION: There is still lack of morphological and phylogenetic information on the pathogenic nematode of the camel Haemonchus longistipes. In the present study, this parasite was isolated in Saudi Arabia and described. MATERIAL AND METHODS: The abomasa of two Arabian camels were collected from a slaughterhouse in Abha province and examined for nematode infection. Worms were described morphologically and morphometrically by electron microscopy. Multiple sequence alignment and the phylogenetic tree of the parasite were constructed from maximum likelihood analysis of its ITS-2 rDNA sequences. RESULTS: These nematodes had a slender body terminating anteriorly at a conspicuous dorsal lancet. A pair of lateral cervical papillae distant from the anterior end was observed. The buccal aperture was hexagonal and surrounded by two amphids, six externo-labial papillae, and four cephalic papillae. Males terminated posteriorly at a bursa supported by spicules and lateral and dorsal rays. Females were linguiform and knobbed morphotypes with distinct ovijectors and a dorsal rim covering the anal pore. The taxonomy was confirmed by the morphology and number of the longitudinal cuticular ridges in a 43-46 range. The sequence alignment and phylogeny revealed 92% homology with H. longistipes (AJ577461.1), and the sequence was deposited into GenBank. CONCLUSION: The present study describes H. longistipes morphologically and molecularly which facilitates further discrimination of this species worldwide.