Proteomic analysis of the venom of Conus flavidus from Red Sea reveals potential pharmacological applications.

BACKGROUND: Venomous marine cone snails produce unique neurotoxins called conopeptides or conotoxins, which are valuable for research and drug discovery. Characterizing Conus venom is important, especially for poorly studied species, as these tiny and steady molecules have considerable potential as research tools for detecting new pharmacological applications. In this study, a worm-hunting cone snail, Conus flavidus inhabiting the Red Sea coast were collected, dissected and the venom gland extraction was subjected to proteomic analysis to define the venom composition, and confirm the functional structure of conopeptides. RESULTS: Analysis of C. flavidus venom identified 117 peptide fragments and assorted them to conotoxin precursors and non-conotoxin proteins. In this procedure, 65 conotoxin precursors were classified and identified to 16 conotoxin precursors and hormone superfamilies. In the venom of C. flavidus, the four conotoxin superfamilies T, A, O2, and M were the most abundant peptides, accounting for 75.8% of the total conotoxin diversity. Additionally, 19 non-conotoxin proteins were specified in the venom, as well as several potentially biologically active peptides with putative applications. CONCLUSION: Our research displayed that the structure of the C. flavidus-derived proteome is similar to other Conus species and includes toxins, ionic channel inhibitors, insulin-like peptides, and hyaluronidase. This study provides a foundation for discovering new conopeptides from C. flavidus venom for pharmaceutical use.

A transmission electron microscopy investigation suggests that telocytes, skeletal muscles, myoblasts, and stem cells in common carp (Cyprinus carpio) respond to salinity challenges.

BACKGROUND: Telocytes are modified interstitial cells that communicate with other types of cells, including stem cells. Stemness properties render them more susceptible to environmental conditions. The current morphological investigation examined the reactions of telocytes to salt stress in relation to stem cells and myoblasts. The common carp are subjected to salinity levels of 0.2, 6, and 10 ppt. The gill samples were preserved and prepared for TEM. RESULTS: The present study observed that telocytes undergo morphological change and exhibit enhanced secretory activities in response to changes in salinity. TEM can identify typical telocytes. This research gives evidence for the communication of telocytes with stem cells, myoblasts, and skeletal muscles. Telocytes surround stem cells. Telopodes made planar contact with the cell membrane of the stem cell. Telocytes and their telopodes surrounded the skeletal myoblast. These findings show that telocytes may act as nurse cells for skeletal stem cells and myoblasts, which undergo fibrillogenesis. Not only telocytes undergo morphological alternations, but also skeletal muscles become hypertrophied, which receive telocyte secretory vesicles in intercellular compartments. CONCLUSION: In conclusion, the activation of telocytes is what causes stress adaptation. They might act as important players in intercellular communication between cells. It is also possible that reciprocal interaction occurs between telocytes and other cells to adapt to changing environmental conditions.

Tongue microarchitecture and functional characterization of the lingual papillae in the desert hedgehog (Paraechinus aethiopicus).

The present work attempted to provide a comprehensive description of the morphoanatomical, histological, and ultrastructural characteristics of the tongue in the desert hedgehog (Paraechinus aethiopicus), and to correlate lingual modifications to the feeding lifestyle. Five adult male hedgehogs were utilized in our investigation. The macroscopic observations revealed elongated, with a moderately pointed apex, tongue and the tongue dorsum lacks both lingual prominence and median sulcus. The main subdivisions of the tongue are radix linguae (root), corpus linguae (body), and apex linguae (apex). The tongue dorsum carries two types of mechanical (conical and filiform) and gustatory (fungiform and circumvallate) papillae. The lingual apex is characterized by the existence of a unique encapsulated muscular structure. Additionally, the lingual glands were interposed between the muscular strands and no lingual glands were detected on the lingual apex. The dorsal surface of the lingual apex exhibited the highest level of keratinization as revealed by histochemical staining while the root showed moderate staining. The topography of the tongue was investigated by scanning electron microscopy (SEM). The obtained results are important to provide basic knowledge that can contribute to better understanding of the nourishment, feeding habits and behavior in this species. Furthermore, the addition of the newly investigated species may help us to determine the evolutionary relationships among species.

Characterization of the Small Intestine in the Southern White-breasted Hedgehog (Erinaceus concolor) Using Histological, Histochemical, Immunohistochemical, and Scanning Electron Microscopic Techniques.

The present study was designed to investigate the microscopic features of the small intestine in the southern white-breasted hedgehog (Erinaceus concolor). The histochemical profile of the small intestine was investigated using periodic acid Schiff (PAS), alcian blue (AB, pH 2.5), and aldehyde fuchsin. The expression of SOX9 was also evaluated immunohistochemically, and the detailed morphology of intestinal mucosa was studied by using a scanning electron microscope. The intestinal wall was composed of the tunica mucosa, tunica submucosa, tunica muscularis, and tunica serosa. Plica circulares and muscularis mucosa were present only in the duodenum. The jejunal villi were the tallest and the ileal villi were the shortest. From the duodenum to the ileum, the population density of goblet cells decreased significantly. The goblet cells throughout the small intestine reacted positively with PAS and AB. The expression rate of SOX9 was not statistically different between the three parts of the small intestine (p > 0.05). In conclusion, despite the general characteristics of the small intestine in this species of hedgehog, there were some differences when compared with other mammalian and rodent species. These findings provide a baseline for future detailed research on the digestive system of the hedgehog species and other mammalian species.

Advanced implications of nanotechnology in disease control and environmental perspectives.

Nanotechnology encompasses a wide range of devices derived from biology, engineering, chemistry, and physics, and this scientific field is composed of great collaboration among researchers from several fields. It has diverse implications notably smart sensing technologies, effective disease diagnosis, and sometimes used in treatment. In medical science, the implications of nanotechnology include the development of elements and devices that interact with the body at subcellular (i.e., molecular) levels exhibiting high sensitivity and specificity. There is a plethora of new chances for medical science and disease treatment to be discovered and exploited in the rapidly developing field of nanotechnology. In different sectors, nanomaterials are used just because of their special characteristics. Their large surface area of them enables higher reactivity with greater efficiency. Furthermore, special surface chemistry is displayed by nanomaterials which compare to conventional materials and facilitate the nanomaterials to decrease pollutants efficiently. Recently, nanomaterials are used in some countries to reduce the levels of contaminants in water, air, and soil. Moreover, nanomaterials are used in the cosmetics and medical industry, and it develops the drug discovery (DD) system. Among a huge number of nanomaterials, Cu, Ag, TiO2, ZnO, Fe3O4, and carbon nanotubes (CNTs) are extensively used in different industries for various purposes. This extensive review study has introduced the major scientific and technical features of nanotechnology, as well as some possible clinical applications and positive feedback in environmental waste management and drug delivery systems.

Topical application of Aloe gel and/or olive oil combination promotes the wound healing properties of streptozotocin-induced diabetic rats.

Diabetic wounds are characterized by a delayed closure rate due to the excess inflammation and the inhibition of angiogenesis. Natural products derived from Aloe vera have shown great promise due to their healing magnificent properties. Olive oil is another natural product with anti-microbial and anti-inflammatory properties that may contribute to the healing process. In the present investigation, we tried to evaluate the efficacy of topical application of Aloe gel and/or olive oil in the enhancement of diabetic wounds using histological and immunohistochemical analysis. Excisional wounds were created on the back skin of streptozotocin-induced diabetic rats. Topical treatments of Aloe gel and/or olive oil were applied separately and in a combination (AVO) daily for experimental groups. Macroscopic and microscopic observations of the excision wounds were monitored at time intervals (3, 6, 9, 14 days) post-wounding. Macroscopic observations of the AVO group exhibited almost complete healing at day 14, while other groups were still in progress. Similarly, immunohistochemical analysis of the AVO group showed a mild expression pattern of NF-κB.. While, the cell proliferation (Ki-67), and angiogenesis (CD34) markers were upregulated. Conclusively, the obtained results showed that the AVO combination effectively improved the healing process in diabetic excisional wounds with significant differences in the healing kinetics compared to wounds that received Aloe gel or olive oil separately.

Spirulina platensis protects against microcystin-LR-induced toxicity in rats.

Microcystis aeruginosa produces an abundant cyanotoxin (microcystins (MCs) in freshwater supplies. MCs have adverse health hazards to animals and humans. Microcystin-leucine-arginine (microcystin-LR or MC-LR) is the most studied among these MCs due to their high toxicity. So, this study was designed to evaluate the possible therapeutic role of the natural algal food supplement, Spirulina platensis (SP), against MC-LR-induced toxic effects in male Wistar rats. Forty rats were randomly divided into five groups. Control and SP groups orally administered distilled water and SP (1000 mg/kg/daily), respectively, for 21 days. MC-LR group was intraperitoneally injected with MC-LR (10 µg/kg/day) for 14 days. MC-LR-SP500 and MC-LR-SP1000 groups were orally treated with SP (500 and 1000 mg/kg, respectively) for 7 days and concomitantly with MC-LR for 14 days. MC-LR induced oxidative hepatorenal damage, cardiotoxicity, and neurotoxicity greatly, which was represented by reduction of reduced glutathione content and the activities of glutathione peroxidase, catalase, and superoxide dismutase and elevation of concentrations of nitric oxide and malondialdehyde in renal, hepatic, brain, and heart tissues. In addition, it increased serum levels of urea, creatinine, tumor necrosis factor-alfa, interleukin-1beta and interleukin-6 and serum activities of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase, and creatine kinase-MB. However, S. platensis restored normal levels of measured serum parameters, ameliorated MC-LR-induced oxidative damage, and normalized tissue antioxidant biomarkers. In conclusion, SP alleviated MC-induced organ toxicities by mitigating oxidative and nitrosative stress and lipid peroxidation.

Aloe vera and wound healing: a brief review

Abstract Aloe vera possesses a great therapeutic importance in traditional medicine. It has attracted the attention of modern medical fields due to its wide pharmacological applications. The bioactive substances in Aloe vera proved to have antioxidant, anti-inflammatory, antibacterial, and antiviral properties. Taken into our consideration the long history of clinical applications of Aloe vera in traditional medicine, especially for promoting the healing of cutaneous wounds with rare adverse effects, it provides a cheap alternative to many expensive synthetic drugs. Recent techniques in tissue engineering created novel scaffolds based on Aloe gel extracts for wound healing applications. Nonetheless, further guided researche is required to foster the development of Aloe vera based scaffolds for the benefit of worldwide populations. Here, I systemically summarize the main events following wounding and the mechanism of action of Aloe vera in promoting the healing process. I hope to provide a solid piece of information that might be helpful for designing new research studies into this topic.

Proteomic analysis of Red Sea Conus taeniatus venom reveals potential biological applications.

BACKGROUND: Diverse and unique bioactive neurotoxins known as conopeptides or conotoxins are produced by venomous marine cone snails. Currently, these small and stable molecules are of great importance as research tools and platforms for discovering new drugs and therapeutics. Therefore, the characterization of Conus venom is of great significance, especially for poorly studied species. METHODS: In this study, we used bioanalytical techniques to determine the venom profile and emphasize the functional composition of conopeptides in Conus taeniatus, a neglected worm-hunting cone snail. RESULTS: The proteomic analysis revealed that 84.0% of the venom proteins were between 500 and 4,000 Da, and 16.0% were > 4,000 Da. In C. taeniatus venom, 234 peptide fragments were identified and classified as conotoxin precursors or non-conotoxin proteins. In this process, 153 conotoxin precursors were identified and matched to 23 conotoxin precursors and hormone superfamilies. Notably, the four conotoxin superfamilies T (22.87%), O1 (17.65%), M (13.1%) and O2 (9.8%) were the most abundant peptides in C. taeniatus venom, accounting for 63.40% of the total conotoxin diversity. On the other hand, 48 non-conotoxin proteins were identified in the venom of C. taeniatus. Moreover, several possibly biologically active peptide matches were identified, and putative applications of the peptides were assigned. CONCLUSION: Our study showed that the composition of the C. taeniatus-derived proteome is comparable to that of other Conus species and contains an effective mix of toxins, ionic channel inhibitors and antimicrobials. Additionally, it provides a guidepost for identifying novel conopeptides from the venom of C. taeniatus and discovering conopeptides of potential pharmaceutical importance.

Olive Oil/Pluronic Oleogels for Skin Delivery of Quercetin: In Vitro Characterization and Ex Vivo Skin Permeability.

The main objective of this study was to prepare and characterize oleogel as potential carrier for quercetin skin delivery. The formulations were prepared by adding olive oil (5-30%) to Pluronic F127 hydrogel and were evaluated for particle size, zeta potential, viscosity in vitro quercetin release and stability, and were compared with that of Pluronic F127 hydrogel. The selected formulation was characterized for its interaction possibility, ex vivo skin permeation and skin histological changes and safety. The particle sizes ranged from 345.3 ± 5.3 nm to 401.5 ± 2.8 nm, and possessed negative charges. The viscosities of the formulations were found in the range of 6367-4823 cps with inverse proportionality to olive oil percentage while the higher percentages showed higher quercetin release. Percentages of 25% and 30% olive oil showed instability pattern under the conditions of accelerated stability studies. Differential scanning calorimetry verified the existence of quercetin in micellar aggregation and the network in the case of hydrogel and oleogel respectively. Ex vivo skin permeation showed an improved skin permeation of quercetin when 20% olive oil containing oleogel was used. Skin histology after 10 days of application showed stratum corneum disruption and good safety profile. Based on these findings, the proposed oleogel containing 20% olive oil denotes a potential carrier for topical delivery of quercetin.

Potential protective effects of Spirulina platensis on liver, kidney, and brain acrylamide toxicity in rats.

Acrylamide (AA) is a hazardous chemical that is widely used in industrial practices. Spirulina platensis (SP) is a blue green alga that is rich in bioactive compounds with many medicinal benefits. The aim of the present study was to evaluate the ameliorative effect of SP against AA toxicity in rats. Animals were divided into six groups: Group (1) was normal rats, groups (2) and (3) received SP at 500 and 1000 mg/kg BW orally respectively for 21 days, group (4) was administered 20 mg/kg BW AA daily for 14 days, while groups (5) and (6) were given orally SP at the same doses of groups (2) and (3), then AA at similar dose of group (4). Rats that received AA alone displayed markedly increased serum levels of liver enzymes (ALT, AST, and ALP), kidney function parameters (urea and creatinine), DNA damage marker (8-OHdG), and proinflammatory cytokines (IL-1ß, IL-6, and TNF-α), compared to control rats. Furthermore, tissue analysis revealed marked increases in hepatic, renal, and brain MDA and NO, as well as marked reductions in the antioxidant biomarkers (GSH, GSH-Px, SOD, and CAT) in acrylamide-intoxicated rats. Spirulina ameliorated the alterations in serum biochemical parameters and reduced MDA and NO, as well as improved antioxidant biomarkers in AA-intoxicated rats in a dose-dependent manner. Our results show that SP has a powerful protective effect on serum biochemistry and liver, kidney, and brain antioxidant machinery in AA-intoxicated rats.

Proteomic analysis of Red Sea Conus taeniatus venom reveals potential biological applications

Diverse and unique bioactive neurotoxins known as conopeptides or conotoxins are produced by venomous marine cone snails. Currently, these small and stable molecules are of great importance as research tools and platforms for discovering new drugs and therapeutics. Therefore, the characterization of Conus venom is of great significance, especially for poorly studied species. Methods: In this study, we used bioanalytical techniques to determine the venom profile and emphasize the functional composition of conopeptides in Conus taeniatus, a neglected worm-hunting cone snail. Results: The proteomic analysis revealed that 84.0% of the venom proteins were between 500 and 4,000 Da, and 16.0% were > 4,000 Da. In C. taeniatus venom, 234 peptide fragments were identified and classified as conotoxin precursors or non-conotoxin proteins. In this process, 153 conotoxin precursors were identified and matched to 23 conotoxin precursors and hormone superfamilies. Notably, the four conotoxin superfamilies T (22.87%), O1 (17.65%), M (13.1%) and O2 (9.8%) were the most abundant peptides in C. taeniatus venom, accounting for 63.40% of the total conotoxin diversity. On the other hand, 48 non-conotoxin proteins were identified in the venom of C. taeniatus. Moreover, several possibly biologically active peptide matches were identified, and putative applications of the peptides were assigned. Conclusion: Our study showed that the composition of the C. taeniatus-derived proteome is comparable to that of other Conus species and contains an effective mix of toxins, ionic channel inhibitors and antimicrobials. Additionally, it provides a guidepost for identifying novel conopeptides from the venom of C. taeniatus and discovering conopeptides of potential pharmaceutical importance.(AU)

Proteomic analysis of Red Sea Conus taeniatus venom reveals potential biological applications

Abstract Background: Diverse and unique bioactive neurotoxins known as conopeptides or conotoxins are produced by venomous marine cone snails. Currently, these small and stable molecules are of great importance as research tools and platforms for discovering new drugs and therapeutics. Therefore, the characterization of Conus venom is of great significance, especially for poorly studied species. Methods: In this study, we used bioanalytical techniques to determine the venom profile and emphasize the functional composition of conopeptides in Conus taeniatus, a neglected worm-hunting cone snail. Results: The proteomic analysis revealed that 84.0% of the venom proteins were between 500 and 4,000 Da, and 16.0% were > 4,000 Da. In C. taeniatus venom, 234 peptide fragments were identified and classified as conotoxin precursors or non-conotoxin proteins. In this process, 153 conotoxin precursors were identified and matched to 23 conotoxin precursors and hormone superfamilies. Notably, the four conotoxin superfamilies T (22.87%), O1 (17.65%), M (13.1%) and O2 (9.8%) were the most abundant peptides in C. taeniatus venom, accounting for 63.40% of the total conotoxin diversity. On the other hand, 48 non-conotoxin proteins were identified in the venom of C. taeniatus. Moreover, several possibly biologically active peptide matches were identified, and putative applications of the peptides were assigned. Conclusion: Our study showed that the composition of the C. taeniatus-derived proteome is comparable to that of other Conus species and contains an effective mix of toxins, ionic channel inhibitors and antimicrobials. Additionally, it provides a guidepost for identifying novel conopeptides from the venom of C. taeniatus and discovering conopeptides of potential pharmaceutical importance.

Protective effects of hesperidin and diosmin against acrylamide-induced liver, kidney, and brain oxidative damage in rats.

Acrylamide (AA) is a heat-induced toxin formed during thermal processing of many commonly consumed foods, including meat products, French fries, potato crisps, bread, cereals, cookies, and coffee. There is thus potentially high dietary exposure of humans to AA, which can induce significant oxidative stress. Hesperidin (HS) and diosmin (DS) are flavone glycosides that have antioxidant properties. The aim of this study was to investigate the protective effects of HS and DS against AA toxicity. Fifty-six adult male Wistar albino rats were divided into seven groups. The first group was orally administered 0.5% (w/v) dimethyl sulfoxide (DMSO) and considered as the control group. The second and third groups were orally administered 10 mg/kg/day of HS or DS, respectively. The fourth group received 20 mg/kg/day of AA orally for 14 days. The fifth and sixth groups were given 10 mg/kg/day of HS or DS, respectively, followed by AA. The seventh group was given both HS and DS after AA administration. AA intoxication significantly (p ≤ 0.05) increased serum levels of liver function enzymes (ALT, AST, and ALP), kidney function products (urea and creatinine), oxidative DNA damage marker (OHdG), proinflammatory markers (TNF-α, IL-1ß, and IL-6), lipid peroxidation marker (malondialdehyde), and nitric oxide (NO). On the other hand, it significantly (p ≤ 0.05) decreased levels of reduced glutathione (GSH) in the liver, kidney, and brain. The activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) in the liver, kidney, and brain tissues were also reduced. HS and DS supplementation prevented lipid peroxidation, normalized the serum parameters altered by AA, and enhanced the tissue concentrations and activities of antioxidant biomarkers. It could be concluded that HS and DS have potent protective effects against oxidative stress, lipid peroxidation, and DNA damage induced by AA toxicity in rats.

Isolation, structural identification and biological characterization of two conopeptides from the Conus pennaceus venom.

A novel anti-mollusk conopeptide pn4c was isolated from the Conus pennaceus venom by repeated HPLC fractionation based on the activity against freshwater snails. The primary structure of pn4c was determined by the mass spectrometric de novo sequencing analysis. In addition, pn3a was isolated from the same fraction containing pn4c, as a peptide with unknown functions.

Characterization of the venom of the vermivorous cone snail Conus fulgetrum.

Over 200 components with molecular mass ranging mainly from 400 to 4000 Da were characterized from the venom of the vermivorous cone snail Conus fulgetrum that inhabit Egyptian Red Sea. One major component having a molecular mass of 2946 Da was purified by HPLC, and its primary structure was determined by a combination of Edman degradation and MS/MS analysis.

Serotonin- and two putative serotonin receptors-like immunohistochemical reactivities in the ground crickets Dianemobius nigrofasciatus and Allonemobius allardi.

Serotonin (5-hydroxytryptamine; 5-HT)- and two putative serotonin receptors, 5-HT1A- and 5-HT1B-like, immunohistochemical reactivities were investigated in the cephalic ganglia of two ground crickets, Dianemobius nigrofasciatus and Allonemobius allardi. 5-HT-ir was strongly expressed in the central body, accessory medulla region of the optic lobe, frontal ganglion, posterior cortex of the protocerebrum, dorsolateral region of the protocerebrum, and the suboesphageal ganglion (SOG) in both crickets. However, 5-HT1A-ir and 5-HT1B-ir showed quite mutually distinct patterns that were also distinct from 5-HT-ir. 5-HT1A-ir was located in the pars intercerebralis, dorsolateral region of the protocerebrum, optic tract, optic lobe, and the midline of the SOG in both crickets. 5-HT1B-ir was located in the pars intercerebralis and dorsolateral region of the protocerebrum, and detected weakly in the optic lobe, tritocerebrum, and the midline of the SOG in both crickets. Interspecific differences were observed with 5-HT1A-ir. 5-HT1A-ir was expressed weakly in two neurons in the mandibular neuromere of the SOG in D. nigrofasciatus, while it was expressed strongly in the tritocerebrum, mandibular neuromere, and maxillary neuromere of the SOG in A. allardi and co-localized with CLOCK-ir (CLK-ir). 5HT-1B-ir was co-localized with CLK-ir in the tritocerebrum, mandibular neuromere, and maxillary neuromere of the SOG when double-labeling was conducted in both crickets. These results indicated that 5-HT and both types of 5-HT receptors may regulate circadian photo-entrainment or photoperiodism in A. allardi, while only 5-HT1B may be involved in circadian photo-entrainment or photoperiodism in D. nigrofasciatus.

Precursor structure, distribution and possible functions of pigment-dispersing hormone (PDH) in the terrestrial isopod Armadillidium vulgare (Latreille).

Pigment-dispersing hormone (PDH) is an 18 amino acid neuropeptide that induces pigment migration in Decapoda and serves as a circadian neurotransmitter in the locomotor activity rhythm in Drosophila. In this study, a cDNA encoding PDH was cloned from adult brains of the pill bug, Armadillidium vulgare (Av). The cDNA comprising 529 bp encodes a peptide (AvPDH) that consists of a putative 26 amino acid signal peptide, and a 34 amino acid PDH-precursor-related peptide containing an 18 amino acid mature peptide. The peptide shows a high sequence identity (55-77%) to crustacean ß-PDHs and insect PDFs. The tissue-specific expression pattern was examined by reverse transcription PCR. The transcript is expressed in the brain strongly and ventral nerve cord weakly, but the signal was not detected in the intestinal tract. A similar expression profile appeared in Western blot analyses. Western blot analyses with timed samples showed more intense expression of PDH-like antigen at night. PDH-like immunohistochemical reactivity (PDH-ir) was detected in the optic lobe, anteromedian protocerebrum, accessory lobe, tritocerebrum, and suboesophageal ganglion but the reactivity was faint or nil in the pseudofrontal organ (sinus gland). These results were substantiated by in situ hybridization. Co-localization using anti-Gryllus bimaculatus (Gb)-PDF, anti-Bombyx mori (Bm)-CLK, and anti-Bm-CYC showed a co-localization of these antigens in the optic lobe and SOG. The results provide the first structural and immunocytochemical identification of PDH neurons in terrestrial isopods, and the co-localization of PDH with CLK and CYC supports its possible involvement in circadian clock. A day/night rhythm of PDH content is also a new feature.