Cellular patterning and cyto-architectural organization of the skin of electric catfish (Malapterurus electricus, Siluriformes) with a particular emphasis on its ampullary electroreceptor.

The functional morphology of the skin of Malapteruridae is presumably evolved to cope with a diversified range of ambient physiological, environmental, and behavioral conditions. Herein, we firstly characterized the microstructures and intriguing patterning of the skin of twelve adult electric catfish (Malapterurus electricus, Malapteruridae) using histological, histochemical, immunofluorescent, and ELISA standard methodology. The skin comprises three sequentially-oriented layers: the epidermis, dermis, and hypodermis with a significantly increased thickness of the former. The epidermis contains four types of cells: the surface epithelial cells, mucous cells, granular cells, and club cells. We defined distinctive ampullary electroreceptors in the outer epidermis that possess flask-shaped sensory crypt containing electroreceptor cells together with vertical collagen rods. Dermis and hypodermis are composed of connective tissue; however, the former is much more coarse and dense with comparable reactivity for Masson-Goldner trichrome (MT). Placing our data in the context of the limited body of previous work, we showed subtle changes in the expression of mucin subunits together with cytoskeletal fractions of collagens, myosin, F-actin, keratins, and tubulins. Taken as a whole, our results convincingly showed that the skin of M. electricus shares some structural similarities to other Siluriformes, however, it has some functional modifications that are implicated in protection, defense, and foraging behavior.

Silver Nanoparticles Decorated with Curcumin Enhance the Efficacy of Metformin in Diabetic Rats via Suppression of Hepatotoxicity.

Hepatotoxicity is one of the significant side effects of chronic diabetes mellitus (DM) besides nephrotoxicity and pancreatitis. The management of this disease is much dependent on the restoration of the liver to its maximum functionality, as it is the central metabolic organ that gets severely affected during chronic diabetes. The present study investigates if the silver nanoparticles decorated with curcumin (AgNP-Cur) can enhance the efficacy of metformin (a conventional antidiabetic drug) by countering the drug-induced hepatoxicity. Swiss albino rats were categorized into six treatment groups (n = 6): control (group I without any treatment), the remaining five groups (group II, IV, V, VI) were DM-induced by streptozocin. Group II was untreated diabetic positive control, whereas groups III was administered with AgNP-cur (5 mg/kg). Diabetic group IV treated with metformin while V and VI were treated with metformin in a combination of the two doses of NPs (5 and 10 mg/kg) according to the treatment schedule. Biochemical and histological analysis of blood and liver samples were conducted after the treatment. The groups V and VI treated with the combination exhibited remarkable improvement in fasting glucose, lipid profile (HDL and cholesterol), liver function tests (AST, ALT), toxicity markers (GGT, GST and LDH), and redox markers (GSH, MDA and CAT) in comparison to group II in most of the parameters. Histological evaluation and comet assay further consolidate these biochemical results, pleading the restoration of the cellular structure of the target tissues and their nuclear DNA. Therefore, the present study shows that the NPs can enhance the anti-diabetic action by suppression of the drug-mediated hepatoxicity via relieving from oxidative stress, toxic burden and inflammation.

Repeated sessions of PACK-CXL WA for the treatment of resistant bacterial keratitis: a retrospective study.

OBJECTIVE: The aim of this work is to evaluate the safety and efficacy of repeated sessions of photo-activated chromophore for keratitis-cross linking (PACK-CXL) window absorption (WA) for the treatment of resistant bacterial keratitis (BK). PATIENTS AND METHODS: This is a retrospective clinical cohort study. Thirty eyes with clinically suspected and lab-confirmed bacterial keratitis, resistant to appropriate antibiotic therapy- which was modified by sensitivity reports- for 2 weeks with failure of epithelialization for 4 weeks after the standard anti-microbial therapy (SAT) together with one setting of PACK-CXL WA were included. If after the first session of PACK-CXL, there is a start of improvement in the form of reduction of the size of corneal ulcer and stromal infiltrates together with the start of epithelialization on clinical examination and AS-OCT, another session of PACK-CXL WA was performed after one week, and so on, till the complete healing and resolution of bacterial keratitis and confirmation by negative bacterial culture. Identification of the micro-organisms was done by lab study before and after treatment. Corneal healing was evaluated by corneal examination and anterior segment OCT (AS-OCT). RESULTS: Thirty eyes of 30 patients were recruited in this study. They were 16 males and 14 females, their mean age was 44.3 ± 5.38 years. The mean ulcer size was 3.96 ± 1.87 (mm3), while the mean size of stromal infiltrates was 4.52 ± 2.24 (mm3). PACK-CXL WA treatment was performed an average of 2.87 times for the 30 eyes. Complete healing and resolution (Successful treatment) was observed in 27 eyes (90%) of cases and failure of epithelialization was observed only in 3 eyes (10%). Complete corneal healing was reported in the second month postoperatively in 90% of eyes. CONCLUSION AND RECOMMENDATION: PACK-CXL WA may be a promising, non-invasive treatment option for resistant bacterial keratitis. It may have a synergistic effect with standard antimicrobial treatment (SAT). Also, it can overcome the antibiotics resistance that has become rapidly spreading worldwide. Repeated sessions of PACK-CXL WA may be more effective for the treatment of resistant bacterial keratitis till complete epithelialization and resolution of BK than a single session with few complications. However, further prospective and comparative studies to support the results are needed.

Disulfiram Enhances the Antineoplastic Activity and Sensitivity of Murine Hepatocellular Carcinoma to 5-FU via Redox Management.

The efficacy of anticancer drug 5-FU is suppressed due to various factors, including severe side effects and decreased insensitivity during prolonged chemotherapy. Elevated endogenous copper (Cu) levels are one of the prominent hallmark features of cancer cells. In the present investigation, this feature was targeted in diethyl nitrosamine-phenobarbital-induced hepatocellular carcinoma (HCC) in a rat model system by an established anticancer drug, 5-FU, co-administered with copper and its chelating agent, disulfiram. After treatment with the test chemicals in HCC-induced rats, blood and liver samples were subjected to biochemical, molecular, and histopathological analyses. The analysis revealed that reactive oxygen species-mediated oxidative stress is the crucial etiological reason for the pathogenesis of HCC in rats, as evidenced by the significantly compromised activity of major antioxidant enzymes and elevated levels of oxidative damaged products with major histological alterations compared to the control. However, the combination of 5-FU with DSF demonstrated a significant improvement in most of the parameters, followed by 5-FU-Cu in the combination-treated groups. The combination treatment improved the histological details and triggered apoptosis in the cancer cells to a remarkable extent, as the levels of cleaved PARP and caspase-3 were significantly higher than those in the HCC rats treated with the drug alone. The present study envisages that manipulating the Cu-level greatly enhances the antineoplastic activity of 5-FU and sensitizes cancer cells to the increased efficacy of the drug.

SMILE lenticule versus amniotic membrane graft (AMG) augmented with platelet-rich plasma (PRP) for the treatment of perforated corneal ulcer.

PURPOSE: To evaluate the safety and efficacy of stromal lenticule obtained from small-incision lenticule extraction (SMILE) surgery versus amniotic membrane graft (AMG) augmented with platelet-rich plasma (PRP) for the treatment of perforated corneal ulcers and compare the results between the two groups. PATIENTS AND METHODS: This is a comparative retrospective study that included 40 eyes with medium-sized corneal perforations, which were classified into two equal groups of 20 eyes each; group (A) was treated with SMILE lenticule graft and group (B) was treated with AMG augmented with PRP. Pre- and postoperative evaluations were carried out using both slit-lamp (SL) examination and anterior segment optical coherence tomography (AS-OCT), including closure of perforation, complete healing, and best corrected visual acuity (BCVA). RESULTS: Complete closure of the perforation was achieved in both groups. However, healing was faster in the SMILE lenticule group than in the AMG with PRP group (P < 0.05). Complete healing was achieved in both groups: 100% in SMILE lenticule group and 95% in AMG with PRP group (P > 0.05). Both groups had few insignificant complications (30% in each), which were managed. CONCLUSION: Both methods achieved adequate healing of corneal perforations within few weeks without significant complications. However, the stromal lenticule obtained from small-incision lenticule extraction (SMILE) surgery tended to be safer with faster healing than AMG with PRP.

Biological Aspects of the Tongue and Oropharyngeal Cavity of the Eurasian Collared Dove (Streptopelia decaocto, Columbiformes, Columbidae): Anatomical, Histochemical, and Ultrastructure Study.

We characterized the morphological and anatomical adaptations of the lingual microstructures of the Eurasian collared dove and discussed their implications for its dietary niche. We analyzed tongues of nine S. decaocto using histological, histochemical, stereomicroscopic, and scanning electron microscopic techniques. Our findings showed that the tongue is relatively short with a tapered apex that carries a terminal lingual nail. However, the lingual body has median scales and is bordered laterally by filiform papillae. Further, the tongue body bears a distinctive papillary crest. The tongue root is nonpapillate and infiltered with orifices of the posterior salivary glands. The bulky laryngeal mound has a circular glottic fissure, carrying a single row of papillae at the rear edge. Concurrently, our histological and histochemical findings demonstrate that the tongue has taste buds, anterior and posterior salivary glands, along with an elongated entoglossum that extends from lingual apex to root. Besides, ovoid and globular mucous glands displayed intense alcianophilic reactions. More substantially, the palate is made up of three palatine ridges with a caudal choanal cleft that was bounded by two rows of palatine papillae. Our data indicate multiple and novel structural variations for the lingual and palatal sculptures coopted for their feeding style.

Macro- and microstructures of the digestive tract in the Eurasian collared dove, Streptopelia decaocto (Frivaldszky 1838): Adaptive interplay between structure and dietary niche.

We describe the functional morphology of the digestive tract of the Eurasian collared dove, Streptopelia decaocto using anatomical, morphometric, histological, histochemical, and ultrastructure techniques, and relate our findings to the species' dietary niche. Our results revealed that the esophagus is displaced on both sides of the neck and has highly folded tunica mucosa, which confer greater elasticity for efficient swallowing and passage of food to the crop. The proventriculus is delicate and its mucosal layer contains polymorphic glands with dense profound and superficial secretory units that open to the luminal surface by gastric pores. The ventriculus is biconvex and lined with a keratinized koilin membrane. The tubular glands within the mucosal lining include the isthmus, the neck, and the basal segment that comprise chief and basal cells with prominent nuclei. At the cuticle-mucosal interface, pyramidal vertical rodlets of the cuticle are secreted and superficially covered by a thin film of a horizontal matrix. The mucosa of the ileum form pyramidal villi that are oriented perpendicularly to the central lumen. Enterocytes infiltrated with goblet cells make up the epithelial lining of the villi. There are subtle differences in the thicknesses of corresponding tunics together with histochemical reactions of alcian blue (AB) and Masson-Goldner trichrome (MT) for their microstructures. Overall, our findings reveal remarkable convergence of both macro-and microstructures in S. decaocto to other granivorous species, and offer further evidence of the close association between functional morphology and feeding style relative to food swallowing, digestion, and absorption.

Vitamin A and Daucus carota root extract mitigate STZ-induced diabetic retinal degeneration in Wistar albino rats by modulating neurotransmission and downregulation of apoptotic pathways.

The objective of our study was to explore the deleterious effects of diabetes on the visual functions of the retina and to address whether the administration of vitamin A and carrot root extract (CE) confer retinal protection in hyperglycemic rats via modulation of oxidative stress, biochemical alternations, and retinal neurotransmission. Fifty male Wistar albino rats weighing 180 ± 12.41 g were randomized into five groups (n = 10): controls, diabetic group (injected with 40 mg/kg dissolved in 0.1 sodium citrate buffer), diabetic group treated with vitamin A (2,500 IU/kg, low dose), diabetic group treated with vitamin (5,000 IU/kg, high dose), and diabetic groups administered CE (200 mg/kg/every other day). Our findings showed that, compared to controls, diabetic rats showed a significant decrease in their retinal thickness, increased apoptotic ganglion cells, and a noticeable degeneration of their synaptic layers. The inner retina displayed increased activity of neovascularization; however, the outer retina exhibited vacuolar degeneration of the photoreceptor cell layer. Our biochemical assessments showed reduced levels of CAT, SOD, and GST along with increased lipid peroxidation. Concurrently, cellular angiogenic and stress markers were significantly elevated associated with increased apoptotic activities as evidenced by increased expressions of annexin-V and PARP. Furthermore, the neurotransmitter content of the retina was altered in diabetic rats compared to controls and diabetic-treated groups. Paradoxically, vitamin A and CE supplementation attenuate these retinal insults in diabetic animals and normalized aforementioned assayed parameters; evidencing that both treatments exerted ameliorative impacts and restored visual functions by diminishing oxidative stress and neuronal degeneration. PRACTICAL APPLICATIONS: Diabetes is a complex disease that involves various physiological perturbations especially visual functions. In our study, we showed that vitamin A and carrot root extract (CE) confer remarkable protection against retinal degeneration in STZ-induced diabetic rats. Our findings showed that the chemical and phytochemical ingredients of the vitamin A and CE substantially attenuated the histopathological changes, oxidative stress, inflammatory reactions, and cellular death in diabetic rats. These favorable changes are attributable to the high content of retinoic acid, carotenoids, and phenolic compounds that effectively regulates the production of visual pigments, increases the antioxidant defense system, and diminishes the pro-inflammatory and apoptotic pathways. Thus, the nutritional values of vitamin A and CE represent promising therapeutic choices to mitigate the retinal-induced diabetic insults.

Bioaccumulation of lead nitrate in tissues and its effects on hematological and biochemical parameters of Clarias gariepinus.

Clarias gariepinus, weighing 119.18 ± 5.21 g, were exposed to 0%, 20%, 40%, and 60% of the LC50 lead nitrate, Pb(NO3)2, which represents the following treatments 0 (control), 16, 32, and 48 mg/l, respectively, for a period of 10 and 20 days. The results showed that the bioaccumulation of Pb(NO3)2 in gills were significantly increased (p < 0.05) after 10 days having 0.17 ± 0.07, 5.05 ± 1.04, 6.01 ± 0.82, and 9.61 ± 1.76 mg/100 g wet weight, respectively, for the treatments. However, after 20 days these values increased ((0.17 ± 0.07, 4.34 ± 1.27, 10.83 ± 0.97, and 19.18 ± 2.40 mg/100 g) for 0%, 20%, 40%, and 60% of LC50 Pb(NO3)2 respectively. There was an increase with each increasing concentration level of Pb(NO3)2 as compared with that of the control group. The accumulation of Pb(NO3)2 in the liver, showed a significant increase (p < 0.05) with the increasing period of exposed and Pb concentration with LC50 values ranging between 3.32 ± 0.91 and 4.42 ± 0.78 after 10 days as compared with that of the control group 0.08 ± 0.02 mg/100 g wet weight. Although white muscles and skin displayed lower values of bioaccumulation than gills and liver after 10 days, after 20 days the results were slightly more increased in the white muscles than in the skin. However, the observed pattern of increase was the same compared to that of the control group. Therefore, hematological parameters, such as red blood cells (RBCs), hemoglobin (Hb), and hematocrit (Hct) showed significant (p < 0.05) concentration-dependent decreases in fish exposed to Pb(NO3)2 during both periods. However, the values of white blood cells (WBCs) showed a significant reduction when levels of Pb concentration increased. Hepatic enzyme activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) displayed a significant increase with increasing concentrations and exposure time.

Thymoquinone ameliorates Pachycondyla sennaarensis venom-induced acute toxic shock in male rats.

BACKGROUND: For many decades, the sting of Samsun ant (Pachycondyla sennaarensis) has been a serious clinical challenge for the people living in some of the major Middle East and Asian countries. In the present study, the therapeutic potential of Nigella sativa derived plant extract component, thymoquinone (TQ) has been tested against the Samsun ant venom (SAV) at the toxic dose in the rats. METHODS: The adult male rats were divided into four groups (n = 10): control, SAV treated, SAV + TQ treated and TQ alone treated. It was found that the sub-lethal dose of SAV alters not only many of the kidney and liver function markers but also induces oxidative stress in the animals. Moreover, the SAV also disturbs various immunological parameters including expression of PMNs, CD-80, CD-86, interleukins and other cytokines compromising the affected organism towards mild to severe allergic reactions including life-risking anaphylaxis. RESULTS: The plant extract, TQ, effectively restores many of the biochemical and oxidative stress parameters comparable to the normal concomitant with improving the immunological aspects that might attributive in relieving from SAV-induced toxicity and allergic reactions in the affected organism to a greater extent. CONCLUSION: Hence, TQ has an excellent antidote property against SAV-induced toxicities in vivo. Although the study is a vivid indication of the potential therapeutic potential of TQ against the SAV induced in vivo toxicity, yet the actual mechanism of interaction translating the toxicity amelioration warrants further investigations.

Restrained management of copper level enhances the antineoplastic activity of imatinib in vitro and in vivo.

The present study was designed to investigate if elevated copper level can be targeted to enhance the efficacy of a significant anticancer drug, imatinib (ITB). The antineoplastic activity of this drug was assessed in the HepG2, HEK-293, MCF-7 and MDA-MD-231 cells targeting elevated copper level as their common drug target. The cell lines were treated with the different doses of copper chloride (Cu II) and disulfiram (DSF) alone as well as in their combinations with the drug for 24 h in standard culture medium and conditions. The treated cells were subjected to various assays including MTT, PARP, p-53, caspase-7, caspase-3, LDH and single cell electrophoresis. The study shows that DSF and Cu (II) synergizes the anticancer activity of ITB to a significant extent in a dose-specific way as evidenced by the combinations treated groups. Furthermore, the same treatment strategy was employed in cancer-induced rats in which the combinations of ITB-DSF and ITB-Cu II showed enhanced antineoplastic activity as compared to ITB alone. However, DSF was more effective than Cu (II) as an adjuvant to the drug. Hence, restrained manipulation of copper level in tumor cells can orchestrate the redox and molecular dispositions inside the cells favoring the induction of apoptosis.

Allelic variation of melanocortin-1 receptor locus in Saudi indigenous sheep exhibiting different color coats.

OBJECTIVE: This study was designed to characterize the DNA polymorphisms of the melanocortin-1 receptor (MC1R) gene in indigenous Saudi Arabian sheep breeds exhibiting different color coats, along with individuals of the Sawaknee breed, an exotic sheep imported from Sudan. METHODS: The complete coding region of MC1R gene including parts of 3' and 5' untranslated regions was amplified and sequenced from three the indigenous Saudi sheep; Najdi (generally black, n = 41), Naeimi (generally white with brown faces, n = 36) and Herri (generally white, n = 18), in addition to 13 Sawaknee sheep. RESULTS: Five single nucleotide polymorphisms (SNPs) were detected in the MC1R gene: two led to nonsynonymous mutations (c.218 T>A, p.73 Met>Lys and c.361 G>A, p.121 Asp>Asn) and three led to synonymous mutations (c.429 C>T, p.143 Tyr>Tyr; c.600 T>G, p.200 Leu>Leu, and c.735 C>T, p.245 Ile>Ile). Based on these five SNPs, eight haplotypes representing MC1R Ed and E+ alleles were identified among the studied sheep breeds. The most common haplotype (H3) of the dominant Ed allele was associated with either black or brown coat color in Najdi and Sawaknee sheep, respectively. Two other haplotypes (H6 and H7) of Ed allele, with only the nonsynonymous mutation A218T, were detected for the first time in Saudi indigenous sheep. CONCLUSION: In addition to investigating the MC1R allelic variation in Saudi indigenous sheep populations, the present study supports the assumption that the two independent nonsynonymous Met73Lys and Asp121Asn mutations in MC1R gene are associated with black or red coat colors in sheep breeds.

Neurochemical, structural and neurobehavioral evidence of neuronal protection by whey proteins in diabetic albino mice.

BACKGROUND: Diabetes Mellitus (DM) is associated with pathological changes in the central nervous system (CNS) and alterations in oxidative stress. The aim of this study was to determine whether dietary supplement with whey protein (WP) could improve neurobehavior, oxidative stress and neuronal structure in the CNS. METHODS: Animals were distributed in three groups, a control group (N), a diabetic mellitus group (DM) and a DM group orally supplemented with WP (WP). RESULTS: The DM group of animals receiving WP had reduced blood glucose, significantly decreased free radical Diphenyl-picrylhydrazyl (DPPH) and lower lipid peroxidation in brain tissue. The WP group of animals showed improvement in balancing, coordination and fore-limb strength, oxidative stress and neuronal structure. CONCLUSION: The results of this study show that dietary supplementation with WP reduced oxidative stress, protected CNS neurons and improved the neurobehavior of diabetic mice.