Immobilization of collagenase in inorganic hybrid nanoflowers with enhanced stability, proteolytic activity, and their anti-amyloid potential.

Organic-inorganic hybrid nanomaterials are considered as promising immobilization matrix for enzymes owing to their markedly enhanced stability and reusability. Herein, collagenase was chosen as a model enzyme to synthesize collagenase hybrid nanoflowers (Col-hNFs). Maximum collagenase activity (155.58 µmol min-1 L-1) and encapsulation yield (90 %) were observed in presence of Zn(II) ions at 0.05 mg/mL collagenase, 120 mM zinc chloride and PBS (pH 7.5). Synthesized Col-Zn-hNFs were extensively characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDX), X-ray diffraction (XRD), Fourier transform infrared (FTIR), circular dichroism (CD), fluorescence spectroscopy, dynamic light scattering (DLS) and zeta potential measurements. SEM images showed flower-like morphology with average size of 5.1 µm and zeta potential of -14.3 mV. Col-Zn-hNFs demonstrated superior relative activity across wide pH and temperature ranges, presence of organic solvents and surfactants as compared to its free form. Moreover, Col-Zn-hNFs exhibited excellent shelf life stability and favorable reusability. Col-Zn-hNFs showed the ability to suppress and eradicate fully developed insulin fibrils in vitro (IC50 = 2.8 and 6.2 µg/mL, respectively). This indicates a promising inhibitory potential of Col-Zn-hNFs against insulin amyloid fibrillation. The findings suggest that the utilization of Col-Zn-hNFs as a carrier matrix holds immense potential for immobilizing collagenase with improved catalytic properties and biomedical applications.

Phloroglucinol ameliorated methylglyoxal induced harmful effects in rats.

Glycation is among the underlying mechanisms attributed to ageing and associated morbidities. There is no drug available to combat this deleterious phenomenon. The present study aimed to explore phloroglucinol (PHL) for its anti-glycation potential at preclinical level. The rats were treated with methylglyoxal (MGO, 17.25 mg/kg, i.p. for 14 days) to induce glvcative stress. The treatment groups received additional administration of test drug (PHL; 0.25mg/kg, 0.5mg/kg, and 1mg/kg) or standard aminoguanidine (AG, 50 mg/kg) or saline (control, 5ml/kg). During 14 days, the weight and food intake was noted. Afterwards, the cognitive function was evaluated using Morris Water Maze (MWM) while hepatic and renal functions were assessed through liver function test (bilirubin, alkaline phosphatase, SGPT, and SGOT) and creatinine respectively, using chemical analyzer. The carboxymethyllysine (CML) levels were quantified in the blood using ELISA technique. Histopathological study was performed on the brain, liver, and kidney using H&E staining. Additionally, the qPCR was used to quantify the expression of TNF-α, RAGE and BACE-1 (brain), RAGE, TNF-α, and glyoxalase-I (liver) and RAGE, TNF-α, and VEGF (kidney), while glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a reference housekeeping gene. The data regarding weight and food intake did not reveal significant alterations. In MWM, the MGO treatment caused significant increase in the time to reach target quadrant, while decrease in the time spent in target quadrant and number of crossings through platform position. All these effects were inhibited by both AG and PHL. The navigation maps also exhibit that the retention of spatial memory. Additionally, the MGO-induced alteration in hepatic and renal function indicators was ameliorated by both AG and PHL treatments. The plasma CML levels were found to be elevated following MGO treatment, while the concomitant administration of AG and PHL has resisted this raise. Histopathological assessment revealed no specific pathology in liver kidney and brain tissues. The qPCR data revealed enhanced expression of all genes, especially TNF-α and BACE, which were found to be reduced following both AG and PHL treatments. PHL prevented the brain, hepatic, and renal impairments caused by MGO induced glycative stress. Hence, the PHL, a clinically used anti-spasmodic drug, presents itself as a potential candidate to be repurposed as anti-glycation drug.

Molecular Assessments of Antimicrobial Protein Enterocins and Quorum Sensing Genes and Their Role in Virulence of the Genus Enterococcus.

Enterococcus has emerged as an opportunistic pathogen because of its antibiotic resistance and virulence profile, which makes it a causative agent of several diseases like endocarditis, surgical site, and urinary tract infections. Currently, species of this genus are the 2nd most frequently isolated microorganisms from hospital-acquired infections. Significant association with hospitals and unhygienic conditions of the environments has made them resistant to a wide range of antibiotics. On the brighter side, enterococci have the ability to produce antimicrobial proteins (i.e., enterocins) that exhibit wide antagonistic activity, thus making them useful microbes in the food and pharmaceutical industries. Enterocins are also involved in niche control in gut microbiota which is regulated by the quorum sensing (QS) system. A bacterial communication system that is controlled by the fsr operon in enterococci consists of FsrABDC, ef1097, and GelE/SprE genes. Hence, the present study was conducted for molecular assessment of enterocins and quorum sensing genes, inter-environmental correlation, and species prevalence of enterococci isolated from different environmental niches of Karachi, Pakistan. Obtained results revealed the highest prevalence of E. faecium and E. faecalis in all environments. Bacterial antagonism and enterocin genes were observed significantly high in poultry environments. The inter-environmental correlation indicated a strong positive correlation of freshwater with sewage and soil environments. Similarly, the fsr regulatory system was mostly identified in poultry-related environments, and a significant correlation between QS system and biofilm formation was established. In conclusion, this study confirmed the high prevalence of E. faecium in all tested sources, high enterocin production in non-clinical environments, and more fsr regulatory genes in poultry-related environments.

Diagnostic challenge: Secondary omental torsion misdiagnosed as acute appendicitis-A case report.

This case presents a diagnostic challenge in a 28-year-old male initially evaluated for severe abdominal pain, vomiting, and constipation, leading to the presumption of post-appendectomy complications. Clinical examination revealed abdominal distension, tenderness, and signs of peritonism, along with a reducible inguinal hernia. On subsequent CT scan, a large, inflamed area of omentum localized to the right abdomen extending up to the defect in the inguinal region with mild ascites was revealed. Upon exploration, it was discovered that the patient's initial surgery had focused solely on an appendix deemed mildly inflamed by the operating surgeon, while a concurrent diagnosis of secondary omental torsion was missed. This oversight underscores the challenges in diagnosing abdominal pathologies, with the initial misdiagnosis leading to ongoing patient distress. Meticulous adhesiolysis and omentectomy were performed, resulting in the resolution of the patient's symptoms.

Inhibiting Intracellular α2C-Adrenoceptor Surface Translocation Using Decoy Peptides: Identification of an Essential Role of the C-Terminus in Receptor Trafficking.

The G protein-coupled α2-adrenoceptor subtype C (abbreviated α2C-AR) has been implicated in peripheral vascular conditions and diseases such as cold feet-hands, Raynaud's phenomenon, and scleroderma, contributing to morbidity and mortality. Microvascular α2C-adrenoceptors are expressed in specialized smooth muscle cells and mediate constriction under physiological conditions and the occlusion of blood supply involving vasospastic episodes and tissue damage under pathological conditions. A crucial step for receptor biological activity is the cell surface trafficking of intracellular receptors, triggered by cAMP-Epac-Rap1A GTPase signaling, which involves protein-protein association with the actin-binding protein filamin-2, mediated by critical amino acid residues in the last 14 amino acids of the receptor carboxyl (C)-terminus. This study assessed the role of the C-terminus in Rap1A GTPase coupled receptor trafficking by domain-swapping studies using recombinant tagged receptors in transient co-transfections and compared with wild-type receptors using immunofluorescence microscopy. We further tested the biological relevance of the α2C-AR C-terminus, when introduced as competitor peptides, to selectively inhibit intracellular α2C-AR surface translocation in transfected as well as in microvascular smooth muscle cells expressing endogenous receptors. These studies contribute to establishing proof of principle to target intracellular α2C-adrenoceptors to reduce biological activity, which in clinical conditions can be a target for therapy.

Molecular Assessment and Validation of the Selected Enterococcal Strains as Probiotics.

Probiotics are live microorganisms which confer health benefits to the host. Lactic acid bacteria (LAB) are used as probiotics since decades. Enterococci being the member of LAB have proven probiotic strains; therefore, this study was aimed at finding out the potential probiotic candidates from the pool of locally isolated strains. For initial screening, one hundred and twenty-two strains were selected and subjected to different confirmatory and phenotypic tests to choose the best strains that have potential probiotic criteria, i.e., no potential virulence traits, antibiotic resistance, and having tolerance properties. Keeping this criterion, only eleven strains (n = 11) were selected for further assessment. All virulence traits such as production of hemolysin, gelatinase, biofilm, and DNase were performed and not found in the tested strains. The molecular assessment indicates the presence of few virulence-associated genes in Enterococcus faecalis strains with variable frequency. The phenotypic and genotypic assessments of antibiotic resistance profile indicate that the selected strain was susceptible to ten commonly used antibiotics, and there were no transferrable antibiotic resistance genes. The presence of CRISPR-Cas genes also confirmed the absence of antibiotic resistance genes. Various enterocin-producing genes like EntP, EntB, EntA, and EntQ were also identified in the selected strains which make them promising probiotic lead strains. Different tolerance assays like acid, NaCl, and gastric juice tolerance that mimic host conditions was also evaluated by providing artificial conditions. Cellular adhesion and aggregation properties like auto- and co-aggregation were also checked and their results reflect all in the favor of lead probiotic strains.

Fenugreek seed ethanolic extract inhibited formation of advanced glycation end products via scavenging reactive carbonyl intermediates.

Senescence is a natural phenomenon of growing old. It accelerates under certain conditions like diabetes mellitus resulting in early decline of bodily functions, which can be avoided by many claimed functional foods. The present study aims to investigate the anti-aging ability of Fenugreek seeds (Trigonellafoenum-graecum); a common ingredient of Indo-Pak cuisines. Briefly, the Fenugreek seeds extract (FgSE) in concentrationsof0.1, 0.5 and 1 mg/ml inhibited the formation of Advanced Glycation End products (AGEs) and fructosamine adducts in Bovine serum albumin (BSA)/fructose model in vitro. The BSA conformational analysis via Circular Dichorism and Congo red assays showed that it preserves secondary structure of BSA in aforementioned model. Although mechanistic studies revealed insignificant lysine blocking ability of Fenugreek by OPA assay, however carbonyl entrapping was found to be 24%, 34% and 42% at 0.1, 0.5 and 1 mg/ml, respectively. In vivo model of High Fructose diet (HFD) induced glycation, FgSE treatment in doses of 10, 25 & 50 mg/kg markedly improved Escape latency (p < 0.01) and preserved cognition in Morris Water Maze. Our data further exhibits significant decrease of CML (Nε-carboxymethyl lysine) levels in serum and hippocampus byFgSE treatment in comparison with HFD group. Therefore, we deduced that FgSE prevents glycation-induced memory decline via entrapping the reactive carbonyl intermediates, formed during production of AGEs. Hence, as a promising functional food it slows down the harmful process of glycation and aging associated morbidities.

Naturally Isolated Sesquiterpene Lactone and Hydroxyanthraquinone Induce Apoptosis in Oral Squamous Cell Carcinoma Cell Line.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide, especially in Asian countries. The emergence of its drug resistance and its side effects demands alternatives, to improve prognosis. Since the majority of cancer drugs are derived from natural sources, it provides a window to look for more biocompatible alternatives. In this study, two natural compounds, costunolide (CE) and aloe emodin (AE), were isolated from the stem of Lycium shawii. The compounds were examined for their anticancer and apoptotic potentials against OSCC (CAL 27) cells, using an in vitro analysis, such as a MTT assay, scratch assay, gene, and protein expressions. Both compounds, CE and AE, were found to be cytotoxic against the cancer cells with an IC50 value of 32 and 38 µM, respectively. Moreover, the compounds were found to be non-toxic against normal NIH-3T3 cells and comparable with the standard drug i.e., 5-fluorouracil (IC50 = 97.76 µM). These compounds were active against normal cells at higher concentrations. Nuclear staining displayed the presence of apoptosis-associated morphological changes, i.e., karyopyknosis and karyorrhexis in the treated cancer cells. Flow cytometry results further confirmed that these compounds induce apoptosis rather than necrosis, as the majority of the cells were found in the late apoptotic phase. Gene and protein expression analyses showed an increased expression of apoptotic genes, i.e., BAK, caspase 3, 6, and 9. Moreover, the compounds significantly downregulated the expression of the anti-apoptotic (BCL-2 L1), metastatic (MMP-2), and pro-inflammatory (COX-2) genes. Both compounds have shown promising anticancer, apoptotic, and anti-migratory activities against the OSCC cell line (i.e., CAL-27). However, further in vivo studies are required to explore these compounds as anticancer agents.

Nanosponges-based Drug Delivery System for the Cosmeceutical Applications of Stabilized Ascorbic Acid.

BACKGROUND: L-Ascorbic acid (AA) is a highly unstable compound, thus, limiting its use in pharmaceutical and cosmetic products, particularly at higher concentrations. OBJECTIVE: This study aimed to stabilize the highly sensitive molecule (AA) by encapsulating it in ß- cyclodextrin nanosponges (ß-CD NS) that can be used further in preparing cosmeceuticals products with higher AA concentrations and enhanced stability. METHODS: The NS has been synthesized by the melting method. The AA was encapsulated in ß-CD NS by the freeze-drying process. The prepared NS were characterized by FTIR spectrometry, SEM, Atomic Force Microscopy (AFM), zeta sizer, Differential Scanning Calorimetry (DSC), and the physical flow characteristics were also studied. The in vitro drug release was carried out on the Franz apparatus using a combination of two methods: sample & separate and dialysis membrane. The assay was performed using a validated spectrometric method. RESULTS: The entrapment efficiency of AA in ß-CD NS indicated a good loading capacity (83.57±6.35%). The FTIR, SEM, AFM, and DSC results confirmed the encapsulation of AA in ß-CD NS. The particle size, polydispersity index, and zeta potential results ascertained the formation of stabilized monodisperse nanoparticles. The physical flow characteristics showed good flow properties. Around 84% AA has been released from the NS in 4 h following the Korsmeyer-Peppas model. The AA-loaded NS remained stable for nine months when stored at 30±2°C/65±5% RH. CONCLUSION: It is concluded that the prepared NS can protect the highly sensitive AA from degradation and provide an extended-release of the vitamin. The prepared AA-loaded ß-CD NS can be used to formulate other cosmeceutical dosage forms with better stability and effect.

Enoxacin-based derivatives: antimicrobial and antibiofilm agent: a biology-oriented drug synthesis (BIODS) approach.

Background: To find alternative molecules against Klebsiella pneumonia, Proteus mirabilis and methicillin-resistant Staphylococcus aureus, new enoxacin derivatives were synthesized and screened. Methods: All derivatives exhibited promising antibacterial activities as compared to standard enoxacin (2 µg/ml) and standard cefixime (82 µg/ml). Compounds 2, 3 and 5 significantly downregulated the gene expression of biofilm-forming genes. Conclusion: Based on our results, these molecules may serve as potential drug candidates to cure several bacterial infections in the future.

Comparative Study to Characterise the Pharmaceutical Potential of Synthesised Snake Venom Bradykinin-Potentiating Peptides In Vivo.

BACKGROUND: Bradykinin-potentiating peptides (BPPs) are snake venom peptides inhibiting the angiotensin-converting enzyme (ACE). ACE plays an important role in the regulation of blood pressure. BPPs lead to the development of ACE inhibitors for the treatment of hypertension. OBJECTIVE: The objective of the present work was to carry out a comprehensive comparative study of four synthesised snake venom BPPs in vivo. METHODS: Four synthesised snake venom BPPs were administered to rats via the intraperitoneal route for 15 days at a fixed dose. Lisinopril was used as a comparative standard. Thirty male albino rats were divided into six groups: A, B, C, D, E (lisinopril), and F (control). Group F was maintained as the control group and given only saline. After 15 days, blood samples and tissues were removed for the study of selective biochemical parameters and histomorphometric analysis. Statistical evaluation of all results was also performed. RESULTS: The results indicated that peptide I, with the sequence ZSAPGNEAIPP, was highly toxic and adversely affected all the biochemical and histological parameters studied in this work. Peptide II (ZNWPHPQIPP) and peptide IV (ZQWAQGRAPHPP) showed lower toxicity. None of the BPPs raised the serum creatinine level and exhibited nephroprotective effects. Although lisinopril raised the creatinine level, it showed a protective role towards the pancreas and lungs in parallel. CONCLUSION: The present work shows that although there is a high sequence similarity between the four BPPs, their in vivo activity varies. The sequences of peptide II and peptide IV can be used to improve the design of current ACE inhibitors used for hypertension treatment.

Natural products based crown ethers: synthesis and their anticancer potential.

Natural products based novel crown ethers have been prepared by employing biologically active natural structures including tetrahydroisoquinoline, chrysin and biochanin-A as the side arms. The resulting crown scaffolds were evaluated for their anticancer potential against two cancer cell lines i.e. NCI-H460 (non-small lung carcinoma), MCF-7 (breast adenocarcinoma). The comparative study showed that the addition of crown scaffold put marked effects on antiproliferative profile of parent natural precursors and is significant for lung carcinoma in particular. Biochanin-A derived crown ether showed three (03) folds higher antiproliferative activity (IC50 = 6.08 ± 0.07 µM) against lung carcinoma as compared to standard drug cisplatin (IC50 = 19.00 ± 1.24 µM). Cytotoxic trends for NIH-3T3 cell lines were also examined and found reduced as compared to parent natural structures. Hence, these findings could open a new pathway towards developing effective carcinostatic drugs.HIGHLIGHTSFour natural products based novel crown ethers have been developed.Comparative antiproliferative screening of crown ethers and natural precursors.Addition of crown showed marked effects on anticancer profile of natural products.Crown formation is significant for lung carcinoma potential in particular.Biochanin-A derived crown ether found three folds more active than standard drug.

A Genus-Wide Bioactivity Analysis of Daboia (Viperinae: Viperidae) Viper Venoms Reveals Widespread Variation in Haemotoxic Properties.

The snake genus Daboia (Viperidae: Viperinae; Oppel, 1811) contains five species: D. deserti, D. mauritanica, and D. palaestinae, found in Afro-Arabia, and the Russell's vipers D. russelii and D. siamensis, found in Asia. Russell's vipers are responsible for a major proportion of the medically important snakebites that occur in the regions they inhabit, and their venoms are notorious for their coagulopathic effects. While widely documented, the extent of venom variation within the Russell's vipers is poorly characterised, as is the venom activity of other species within the genus. In this study we investigated variation in the haemotoxic activity of Daboia using twelve venoms from all five species, including multiple variants of D. russelii, D. siamensis, and D. palaestinae. We tested the venoms on human plasma using thromboelastography, dose-response coagulometry analyses, and calibrated automated thrombography, and on human fibrinogen by thromboelastography and fibrinogen gels. We assessed activation of blood factors X and prothrombin by the venoms using fluorometry. Variation in venom activity was evident in all experiments. The Asian species D. russelii and D. siamensis and the African species D. mauritanica possessed procoagulant venom, while D. deserti and D. palaestinae were net-anticoagulant. Of the Russell's vipers, the venom of D. siamensis from Myanmar was most toxic and D. russelli of Sri Lanka the least. Activation of both factor X and prothrombin was evident by all venoms, though at differential levels. Fibrinogenolytic activity varied extensively throughout the genus and followed no phylogenetic trends. This venom variability underpins one of the many challenges facing treatment of Daboia snakebite envenoming. Comprehensive analyses of available antivenoms in neutralising these variable venom activities are therefore of utmost importance.

Pharmacological Characterisation of Pseudocerastes and Eristicophis Viper Venoms Reveal Anticancer (Melanoma) Properties and a Potentially Novel Mode of Fibrinogenolysis.

Venoms are a rich source of potential lead compounds for drug discovery, and descriptive studies of venom form the first phase of the biodiscovery process. In this study, we investigated the pharmacological potential of crude Pseudocerastes and Eristicophis snake venoms in haematological disorders and cancer treatment. We assessed their antithrombotic potential using fibrinogen thromboelastography, fibrinogen gels with and without protease inhibitors, and colourimetric fibrinolysis assays. These assays indicated that the anticoagulant properties of the venoms are likely induced by the hydrolysis of phospholipids and by selective fibrinogenolysis. Furthermore, while most fibrinogenolysis occurred by the direct activity of snake venom metalloproteases and serine proteases, modest evidence indicated that fibrinogenolytic activity may also be mediated by selective venom phospholipases and an inhibitory venom-derived serine protease. We also found that the Pseudocerastes venoms significantly reduced the viability of human melanoma (MM96L) cells by more than 80%, while it had almost no effect on the healthy neonatal foreskin fibroblasts (NFF) as determined by viability assays. The bioactive properties of these venoms suggest that they contain a number of toxins suitable for downstream pharmacological development as candidates for antithrombotic or anticancer agents.

Proteomic Investigations of Two Pakistani Naja Snake Venoms Species Unravel the Venom Complexity, Posttranslational Modifications, and Presence of Extracellular Vesicles.

Latest advancement of omics technologies allows in-depth characterization of venom compositions. In the present work we present a proteomic study of two snake venoms of the genus Naja i.e., Naja naja (black cobra) and Naja oxiana (brown cobra) of Pakistani origin. The present study has shown that these snake venoms consist of a highly diversified proteome. Furthermore, the data also revealed variation among closely related species. High throughput mass spectrometric analysis of the venom proteome allowed to identify for the N. naja venom 34 protein families and for the N. oxiana 24 protein families. The comparative evaluation of the two venoms showed that N. naja consists of a more complex venom proteome than N. oxiana venom. Analysis also showed N-terminal acetylation (N-ace) of a few proteins in both venoms. To the best of our knowledge, this is the first study revealing this posttranslational modification in snake venom. N-ace can shed light on the mechanism of regulation of venom proteins inside the venom gland. Furthermore, our data showed the presence of other body proteins, e.g., ankyrin repeats, leucine repeats, zinc finger, cobra serum albumin, transferrin, insulin, deoxyribonuclease-2-alpha, and other regulatory proteins in these venoms. Interestingly, our data identified Ras-GTpase type of proteins, which indicate the presence of extracellular vesicles in the venom. The data can support the production of distinct and specific anti-venoms and also allow a better understanding of the envenomation and mechanism of distribution of toxins. Data are available via ProteomeXchange with identifier PXD018726.

Synthesis and characterization of maltol capped silver nanoparticles and their potential application as an antimicrobial agent and colorimetric sensor for cysteine.

Maltol capped silver nanoparticles (McAgNPs) were synthesized using maltol (3-hydroxy-2-methyl-4-pyrone) as reducing and capping agent. McAgNPs were characterized by Visible and FTIR (Fourier transform infrared) spectroscopy, dynamic light scattering (DLS), and atomic force microscopy (AFM). Bright yellow color McAgNPs showed surface plasmon resonance (SPR) band at 436 nm, spherical shape and the average size between 35 to 50 nm. McAgNPs revealed higher stability against varying storage time, temperature, pH and salt concentrations. McAgNPs were successfully utilized for the selective and highly sensitive colorimetric detection of cysteine (Cys). Addition of Cys in a solution of McAgNPs, resulted a rapid change in color from yellow to orange because of the formation of nanoaggregates as confirmed by Visible/FTIR spectroscopy, DLS, and AFM studies. The estimated limit of detection (0.043 µM) was found to be more sensitive than previously reported other optical methods. The practical applicability of probe was also established by spiking the known concentrations of Cys in biological (blood plasma and urine) and environmental (tap and lake water) samples with significant recovery rates (92-104.6%). Despite being nontoxic to various tested cell lines, McAgNPs demonstrated potent antimicrobial, antibiofilm, and biofilm eradicating activities, thus potentially valuable in diagnostics and/or the synthesis of other nanocomposite material for broader applications.

Correction: Acridinedione as selective flouride ion chemosensor: a detailed spectroscopic and quantum mechanical investigation.

[This corrects the article DOI: 10.1039/C7RA11974G.].

Synthesis and sensitive detection of doxycycline with sodium bis 2-ethylhexylsulfosuccinate based silver nanoparticle.

The monitoring of residual antibiotics in the environment has gained a significant importance for the effective control, because of the high risk to human health. A simple strategy was designed for the green synthesis and detection of doxycycline (Dox) by using anionic surfactant sodium bis 2-ethylhexylsulfosuccinate based silver nanoparticles (AOT-AgNPs). The chemical reduction and capping of Ag+1 ions was achieved by sulfonyl and carbonyl functional groups of AOT molecule. The AOT-AgNPs were found to have excellent stability at variable environmental parameters (i.e. temperature, storage period, salt concentration and pH) possibly due to the strong emulsifying nature of the surfactant. Mechanism of interaction between the AOT-AgNPs and Dox was established with UV/visible, Fourier transform infrared (FTIR) spectroscopy, Atomic force microscopy (AFM) and Dynamic light scattering (DLS) techniques, which suggests the interaction via aggregates formation. The synthesize probe could detect the Dox within 15 min over a wide range of concentrations from 0.1 to 140µM with limit of detection (LOD) of 0.2 µM. As proof of strategy, we have illustrated that the AOT-AgNPs also detect Dox in biological and environmental samples with negligible interference and very significant recovery rates. Moreover, non-toxic nature against various tested cell lines (i.e. normal mouse fibroblast (NIH-3 T3) and cancerous non-small lung carcinoma (NCI-H460)) and significant antimicrobial, antibiofilm and biofilm eradicating potential of AOT-AgNPs were provide ideal nanomaterial for further applications.

The Scorpion Venom Peptide Smp76 Inhibits Viral Infection by Regulating Type-I Interferon Response.

Dengue virus (DENV) and Zika virus (ZIKV) have spread throughout many countries in the developing world and infect millions of people every year, causing severe harm to human health and the economy. Unfortunately, there are few effective vaccines and therapies available against these viruses. Therefore, the discovery of new antiviral agents is critical. Herein, a scorpion venom peptide (Smp76) characterized from Scorpio maurus palmatus was successfully expressed and purified in Escherichia coli BL21(DE3). The recombinant Smp76 (rSmp76) was found to effectively inhibit DENV and ZIKV infections in a dose-dependent manner in both cultured cell lines and primary mouse macrophages. Interestingly, rSmp76 did not inactivate the viral particles directly but suppressed the established viral infection, similar to the effect of interferon (IFN)-ß. Mechanistically, rSmp76 was revealed to upregulate the expression of IFN-ß by activating interferon regulatory transcription factor 3 (IRF3) phosphorylation, enhancing the type-I IFN response and inhibiting viral infection. This mechanism is significantly different from traditional virucidal antimicrobial peptides (AMPs). Overall, the scorpion venom peptide Smp76 is a potential new antiviral agent with a unique mechanism involving type-I IFN responses, demonstrating that natural AMPs can enhance immunity by functioning as immunomodulators.

Snake Venom Peptides: Tools of Biodiscovery.

Nature endowed snakes with a lethal secretion known as venom, which has been fine-tuned over millions of years of evolution. Snakes utilize venom to subdue their prey and to survive in their natural habitat. Venom is known to be a very poisonous mixture, consisting of a variety of molecules, such as carbohydrates, nucleosides, amino acids, lipids, proteins and peptides. Proteins and peptides are the major constituents of the dry weight of snake venoms and are of main interest for scientific investigations as well as for various pharmacological applications. Snake venoms contain enzymatic and non-enzymatic proteins and peptides, which are grouped into different families based on their structure and function. Members of a single family display significant similarities in their primary, secondary and tertiary structures, but in many cases have distinct pharmacological functions and different bioactivities. The functional specificity of peptides belonging to the same family can be attributed to subtle variations in their amino acid sequences. Currently, complementary tools and techniques are utilized to isolate and characterize the peptides, and study their potential applications as molecular probes, and possible templates for drug discovery and design investigations.