Potential application of nanotechnology in the treatment, diagnosis, and prevention of schistosomiasis

Schistosomiasis is one of the neglected tropical diseases that affect millions of people worldwide. Globally, it affects economically poor countries, typically due to a lack of proper sanitation systems, and poor hygiene conditions. Currently, no vaccine is available against schistosomiasis, and the preferred treatment is chemotherapy with the use of praziquantel. It is a common anti-schistosomal drug used against all known species of Schistosoma. To date, current treatment primarily the drug praziquantel has not been effective in treating Schistosoma species in their early stages. The drug of choice offers low bioavailability, water solubility, and fast metabolism. Globally drug resistance has been documented due to overuse of praziquantel, Parasite mutations, poor treatment compliance, co-infection with other strains of parasites, and overall parasitic load. The existing diagnostic methods have very little acceptability and are not readily applied for quick diagnosis. This review aims to summarize the use of nanotechnology in the treatment, diagnosis, and prevention. It also explored safe and effective substitute approaches against parasitosis. At this stage, various nanomaterials are being used in drug delivery systems, diagnostic kits, and vaccine production. Nanotechnology is one of the modern and innovative methods to treat and diagnose several human diseases, particularly those caused by parasite infections. Herein we highlight the current advancement and application of nanotechnological approaches regarding the treatment, diagnosis, and prevention of schistosomiasis

Hyperglycemia-induced oxidative stress and epigenetic regulation of ET-1 gene in endothelial cells

Introduction: Hyperglycemia-induced endothelial dysfunction and the subsequent increase of oxidative stress could lead to aberrant regulation of various genes which are responsible for a range of functions. This study aims to find out how hyperglycemia affect oxidative stress and then the expression and methylation of endothelin 1 (ET-1) gene in in human umbilical vein endothelial cells (HUVEC).Methods: Cells were cultured in growth medium and exposed to low and high glucose concentrations to mimic normal and diabetic condition respectively. Computational analysis were performed using UCSC genome browser and eukaryotic promoter database (EPD). The expression of ET-1 gene was investigated by real time PCR. Cytotoxicity and oxidative stress were determined by MTT and DCFH-DA assays respectively. Promoter methylation was assessed by the bisulfite sequencing method.Results: DCFH-DA assay showed that hyperglycemia can significantly increase the regulation of reactive oxygen species synthesis. The relative expression of ET-1 gene was increased due to exposure to high glucose concentration. MTT assay revealed reduced viability of cells due to the glucose induced damage. Methylation analysis revealed hypomethylation of the promoter of ET-1 however the difference was not significant. Out of 175 CpGs at 25 CpG sites, only 36 CpGs were methylated (20.5% methylation) in cell treated with normal glucose. Upon exposure to high glucose only 30 CpGs were methylated in 175 CpGs at 25 CpG sites (17.1% methylation).Discussion: Our study concludes a significantly high expression of ET-1 gene in response to high glucose exposure in HUVECs. It also reports that hyperglycemic condition leads to elevated oxidative stress. No significant change was found in methylation when cells were treated with high and low glucose concentrations

Surface engineered mesoporous silica carriers for the controlled delivery of anticancer drug 5-fluorouracil: Computational approach for the drug-carrier interactions using density functional theory

Introduction: Drug delivery systems are the topmost priority to increase drug safety and efficacy. In this study, hybrid porous silicates SBA-15 and its derivatives SBA@N and SBA@3N were synthesized and loaded with an anticancer drug, 5-fluorouracil. The drug release was studied in a simulated physiological environment.Method: These materials were characterized for their textural and physio-chemical properties by scanning electron microscopy (SEM), nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), small-angle X-ray diffraction (SAX), and nitrogen adsorption/desorption techniques. The surface electrostatics of the materials was measured by zeta potential.Results: The drug loading efficiency of the prepared hybrid materials was about 10%. In vitro drug release profiles were obtained in simulated fluids. Slow drug release kinetics was observed for SBA@3N, which released 7.5% of the entrapped drug in simulated intestinal fluid (SIF, pH 7.2) and 33% in simulated body fluid (SBF, pH 7.2) for 72 h. The material SBA@N presented an initial burst release of 13% in simulated intestinal fluid and 32.6% in simulated gastric fluid (SGF, pH 1.2), while about 70% of the drug was released within the next 72 h. Density functional theory (DFT) calculations have also supported the slow drug release from the SBA@3N material. The release mechanism of the drug from the prepared carriers was studied by first-order, second-order, Korsmeyer–Peppas, Hixson–Crowell, and Higuchi kinetic models. The drug release from these carriers follows Fickian diffusion and zero-order kinetics in SGF and SBF, whereas first-order, non-Fickian diffusion, and case-II transport were observed in SIF.Discussion: Based on these findings, the proposed synthesized hybrid materials may be suggested as a potential drug delivery system for anti-cancer drugs such as 5-fluorouracil

Effect of Gelam Honey on the Oxidative Stress-Induced Signaling Pathways in Pancreatic Hamster Cells

Background. Oxidative stress induced by reactive oxygen and nitrogen species is critically involved in the impairment of β-cell function during the development of diabetes. Methods. HIT-T15 cells were cultured in 5% CO2 and then preincubated with Gelam honey extracts (20, 40, 60, and 80 µg/mL) as well as quercetin (20, 40, 60, and 80 µM), prior to stimulation by 20 and 50 mM of glucose. Cell lysate was collected to determine the effect of honey extracts and quercetin on the stress activated NF-κB, MAPK pathways, and the Akt (ser473) activated insulin signaling pathway. Results. HIT-T15 cells cultured under hyperglycemic conditions demonstrated insulin resistance with a significant increase in the levels of MAPK, NF-κB, and IRS-1 serine phosphorylation (ser307); however, Akt expression and insulin contents are significantly decreased. Pretreatment with quercetin and Gelam honey extract improved insulin resistance and insulin content by reducing the expression of MAPK, NF-κB, and IRS-1 serine phosphorylation (ser307) and increasing the expression of Akt significantly. Conclusion. Gelam honey-induced differential expression of MAPK, NF-κB, IRS-1 (ser307), and Akt in HIT-T15 cells shows that Gelam honey exerts protective effects against diabetes- and hyperglycemia-induced oxidative stress by improving insulin content and insulin resistance

Preparation of cellulosic Ag-nanocomposites using an ionic liquid

© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Cellulose-based nanocomposites have gained much attention due to their remarkable biological properties such as biodegradability, biocompatibility, and low toxicity. In this research work, 1-h-3-methylimidazolium hydrogen sulfate ionic liquid was employed as an efficient solvent for preparation of cellulosic Ag-nanocomposites (CRC/AgNPs composite) from Neem plant. Ionic liquid plays a dual role in obtaining cellulose-rich compound (CRC; removing lignin and hemicellulose components) and plant’s extract (phenolic compounds such as flavonoids, tannins, etc.) that reduces the AgNO 3 into AgNPs for preparation of CRC/AgNPs composite. The prepared CRC/AgNPs composite was characterized using XRD, FTIR and SEM techniques. The XRD and FTIR spectral analysis showed the characteristic peaks assigned to cellulosic constituent and AgNPs. SEM analysis revealed the particles in the range from 26 to 56 nm. The CRC/AgNPs composite was evaluated for its antibacterial and mechanical properties. The antibacterial activity against S. aureus and E. coli for CRC/AgNPs composite was observed in comparison to CRC. Cell viability and morphology were performed on MC3T3-E1 cells which showed no as such toxicity for the prepared CRC/AgNPs composite. Moreover, the addition of CRC/AgNPs composite as a filler increased the compression strength of polymeric materials

Low genetic polymorphism in the immunogenic sequences of Rhipicephalus microplus clade C

Rhipicephalus microplus tick highly affects the veterinary sector throughout the world. Different tick control methods have been adopted, and the identification of tick-derived highly immunogenic sequences for the development of an anti-tick vaccine has emerged as a successful alternate. This study aimed to characterize immunogenic sequences from R. microplus ticks prevalent in Pakistan. Ticks collected in the field were morphologically identified and subjected to DNA and RNA extraction. Ticks were molecularly identified based on the partial mitochondrial cytochrome C oxidase subunit (cox) sequence and screened for piroplasms (Theileria/Babesia spp.), Rickettsia spp., and Anaplasma spp. PCR-based pathogens-free R. microplus-derived cDNA was used for the amplification of full-length cysteine protease inhibitor (cystatin 2b), cathepsin L-like cysteine proteinase (cathepsin-L), glutathione S-transferase (GST), ferritin 1, 60S acidic ribosomal protein (P0), aquaporin 2, ATAQ, and R. microplus 05 antigen (Rm05Uy) coding sequences. The cox sequence revealed 100% identity with the nucleotide sequences of Pakistan’s formerly reported R. microplus, and full-length immunogenic sequences revealed maximum identities to the most similar sequences reported from India, China, Cuba, USA, Brazil, Egypt, Mexico, Israel, and Uruguay. Low nonsynonymous polymorphisms were observed in ATAQ (1.5%), cathepsin-L (0.6%), and aquaporin 2 (0.4%) sequences compared to the homologous sequences from Mexico, India, and the USA, respectively. Based on the cox sequence, R. microplus was phylogenetically assembled in clade C, which includes R. microplus from Pakistan, Myanmar, Malaysia, Thailand, Bangladesh, and India. In the phylogenetic trees, the cystatin 2b, cathepsin-L, ferritin 1, and aquaporin 2 sequences were clustered with the most similar available sequences of R. microplus, P0 with R. microplus, R. sanguineus and R. haemaphysaloides, and GST, ATAQ, and Rm05Uy with R. microplus and R. annulatus. This is the first report on the molecular characterization of clade C R. microplus-derived immunogenic sequences

Glutamine treatment attenuates hyperglycemia-induced mitochondrial stress and apoptosis in umbilical vein endothelial cells

OBJECTIVE: The aim of this study was to determine the in vitro effect of glutamine and insulin on apoptosis, mitochondrial membrane potential, cell permeability, and inflammatory cytokines in hyperglycemic umbilical vein endothelial cells. MATERIALS AND METHODS: Human umbilical vein endothelial cells were grown and subjected to glutamine and insulin to examine the effects of these agents on the hyperglycemic state. Mitochondrial function and the production of inflammatory cytokines were assessed using fluorescence analysis and multiple cytotoxicity assays. Apoptosis was analyzed by the terminal deoxynucleotidyl transferase dUTP nick end-labeling assay. RESULTS: Glutamine maintains the integrity of the mitochondria by reducing the cell permeability and cytochrome c levels and increasing the mitochondrial membrane potential. The cytochrome c level was significantly (

Role of Potash Alum in Hepatitis C virus Transmission at Barber's Shop

Hepatitis C virus (HCV) is the main cause of severe liver disease, including hepatocellular carcinoma, cirrhosis and end stage liver disease. In Pakistan most of HCV positive patients have history of facial/armpit shaving from barbers. 79% of barbers are rubbing Potash Alum stone on facial shaving cuts. Dark blood spots are analyzed on Potash Alum stones being used at different barber shops. The aim of the study was to check the viability of hepatitis C virus on potash alum stone being used at barber shops. Blood samples from HCV positive patients were taken and treated with 0.1, 0.2, 0.3, 0.4 and 0.5 molar concentrations of Potash Alum for different periods of time. Blood was centrifuged to isolate the serum; HCV RNA was extracted from serum and subjected to first strand synthesis and PCR. PCR fragments were confirmed by sequencing. PCR amplification was observed in all the samples, treated with different concentrations of Potash Alum, indicated that the virus remains alive on Potash Alum stone for a long period of time. Potash Alum being used by barbers on facial shaving cuts has definite role in HCV transmission in Pakistani population. Therefore use of Potash Alum stone should be banned on facial shaving cuts at barber shops

Exploring extracellular vesicles in zoonotic helminth biology: implications for diagnosis, therapeutic and delivery

Extracellular vesicles (EVs) have emerged as key intercellular communication and pathogenesis mediators. Parasitic organisms’ helminths, cause widespread infections with significant health impacts worldwide. Recent research has shed light on the role of EVs in the lifecycle, immune evasion, and disease progression of these parasitic organisms. These tiny membrane-bound organelles including microvesicles and exosomes, facilitate the transfer of proteins, lipids, mRNAs, and microRNAs between cells. EVs have been isolated from various bodily fluids, offering a potential diagnostic and therapeutic avenue for combating infectious agents. According to recent research, EVs from helminths hold great promise in the diagnosis of parasitic infections due to their specificity, early detection capabilities, accessibility, and the potential for staging and monitoring infections, promote intercellular communication, and are a viable therapeutic tool for the treatment of infectious agents. Exploring host-parasite interactions has identified promising new targets for diagnostic, therapy, and vaccine development against helminths. This literature review delves into EVS’s origin, nature, biogenesis, and composition in these parasitic organisms. It also highlights the proteins and miRNAs involved in EV release, providing a comprehensive summary of the latest findings on the significance of EVs in the biology of helminths, promising targets for therapeutic and diagnostic biomarkers

The global fatty liver disease Sustainable Development Goal country score for 195 countries and territories

Background and aims: Fatty liver disease is highly prevalent, resulting in overarching wellbeing and economic costs. Addressing it requires comprehensive and coordinated multisectoral action. We developed a fatty liver disease Sustainable Development Goal (SDG) country score to provide insights into country-level preparedness to address fatty liver disease through a whole-of-society lens. Approach and results: We developed 2 fatty liver disease-SDG score sets. The first included 6 indicators (child wasting, child overweight, noncommunicable disease mortality, a universal health coverage service coverage index, health worker density, and education attainment), covering 195 countries and territories between 1990 and 2017. The second included the aforementioned indicators plus an urban green space indicator, covering 60 countries and territories for which 2017 data were available. To develop the fatty liver disease-SDG score, indicators were categorized as "positive" or "negative" and scaled from 0 to 100. Higher scores indicate better preparedness levels. Fatty liver disease-SDG scores varied between countries and territories (n = 195), from 14.6 (95% uncertainty interval: 8.9 to 19.4) in Niger to 93.5 (91.6 to 95.3) in Japan; 18 countries and territories scored > 85. Regionally, the high-income super-region had the highest score at 88.8 (87.3 to 90.1) in 2017, whereas south Asia had the lowest score at 44.1 (42.4 to 45.8). Between 1990 and 2017, the fatty liver disease-SDG score increased in all super-regions, with the greatest increase in south Asia, but decreased in 8 countries and territories. Conclusions: The fatty liver disease-SDG score provides a strategic advocacy tool at the national and global levels for the liver health field and noncommunicable disease advocates, highlighting the multisectoral collaborations needed to address fatty liver disease, and noncommunicable diseases overall