Documented to exhibit cytotoxicity and poor oral bioavailability, alpha-mangostin was encapsulated into PLGA microspheres with optimization of formulation using response surface methodology. Mixed levels of four factors Face central composite design was employed to evaluate critical formulation variables. With 30 runs, optimized formula was 1% w/v polyvinyl alcohol, 1:10 ratio of oil to aqueous and sonicated at 2 and 5 min time for primary and secondary emulsion, respectively. Optimized responses for encapsulation efficiency, particle size and polydispersity index were found to be 39.12 ± 0.01%, 2.06 ± 0.017 µm and 0.95 ± 0.009, respectively, which matched values predicted by mathematical models. About 44.4% of the encapsulated alpha-mangostin was released over 4 weeks. Thermal analysis of the microspheres showed physical conversion of alpha-mangostin from crystallinity to amorphous with encapsulated one had lower in vitro cytotoxicity than free alpha-mangostin. Aerodynamic diameter (784.3 ± 7.5 nm) of this alpha-mangostin microsphere suggests suitability for peripheral pulmonary delivery.
The WSE is a highly polar, gummy and mucilaginous bioactive content of the Nigella sativa (L.) seeds. This study reports the anxiolytic and anti-inflammatory effects of WSE investigated using Elevated Plus Maze (EPM) and Hole-Board Test (HBT) in adult mice and human RBCs haemolysis inhibition and protein denaturation respectively. The oral WSE treatment (100 & 200 mg/kg b.w/day) for 72 hours has exhibited slightly better anxiolytic effect (p
Raloxifene hydrochloride, a highly effective drug for the treatment of invasive breast cancer and osteoporosis in post-menopausal women, shows poor oral bioavailability of 2%. The aim of this study was to develop, statistically optimize, and characterize raloxifene hydrochloride-loaded transfersomes for transdermal delivery, in order to overcome the poor bioavailability issue with the drug. A response surface methodology experimental design was applied for the optimization of transfersomes, using Box-Behnken experimental design. Phospholipon(®) 90G, sodium deoxycholate, and sonication time, each at three levels, were selected as independent variables, while entrapment efficiency, vesicle size, and transdermal flux were identified as dependent variables. The formulation was characterized by surface morphology and shape, particle size, and zeta potential. Ex vivo transdermal flux was determined using a Hanson diffusion cell assembly, with rat skin as a barrier medium. Transfersomes from the optimized formulation were found to have spherical, unilamellar structures, with a homogeneous distribution and low polydispersity index (0.08). They had a particle size of 134±9 nM, with an entrapment efficiency of 91.00%±4.90%, and transdermal flux of 6.5±1.1 μg/cm(2)/hour. Raloxifene hydrochloride-loaded transfersomes proved significantly superior in terms of amount of drug permeated and deposited in the skin, with enhancement ratios of 6.25±1.50 and 9.25±2.40, respectively, when compared with drug-loaded conventional liposomes, and an ethanolic phosphate buffer saline. Differential scanning calorimetry study revealed a greater change in skin structure, compared with a control sample, during the ex vivo drug diffusion study. Further, confocal laser scanning microscopy proved an enhanced permeation of coumarin-6-loaded transfersomes, to a depth of approximately160 μM, as compared with rigid liposomes. These ex vivo findings proved that a raloxifene hydrochloride-loaded transfersome formulation could be a superior alternative to oral delivery of the drug.
In the contemporary medical model world, the proniosomal system has been serving as a new drug delivery system that is considered to significantly enhance the bioavailability of drugs with low water solubility. The application of this system can improve the bioavailability of aceclofenac that is used for the relief of pain and inflammation in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. The present study is intended to develop an optimized proniosomal aceclofenac formula by the use of different carriers. Aceclofenac proniosomes have been prepared by slurry method, and different carriers such as maltodextrin, mannitol, and glucose were tried. Prepared proniosomes characterized by differential scanning calorimetry (DSC) analysis and Fourier transform infrared (FTIR) analysis revealed the compatibility of the drug chosen with the ingredient added, powder X-ray diffractometry (XRD) confirmed the amorphous phase of the prepared proniosomes, and finally, the surfactant layer was observed by scanning electron microscopy (SEM). Aceclofenac physical state transformations were confirmed with all formulas but maltodextrin proniosomes exhibited solubility more than other formulations. HPLC method has been used to analyze the niosomes derived from proniosomes in terms of their entrapment capability and drug content. The obtained results revealed that aceclofenac proniosomes can be successfully prepared by using different carriers.
Cancer is a second leading disease-causing death worldwide that will continuously grow as much as 70% in the next 20 years. Chemotherapy is still becoming a choice for cancer treatment despite its severity of side effects and low success rate due to ineffective delivery of the chemodrugs. Since it was introduced in 1960, significant progress has been achieved in the use of liposomes in drug delivery. The study aims to review relevant literatures on role of PEGylated liposome in enhancing cytotoxic activity of several agents. A systematic literature on the use of PEGylated liposomes in anticancer research via Scopus, Google scholar and PubMed databases was conducted for studies published from 2000 to 2022. A total of 15 articles were selected and reviewed from 312 articles identified covering a variety of anticancer treatments by using PEGylated liposomes. PEGylated liposome which is purposed to achieve steric equilibrium is one of enhanced strategies to deliver anticancer drugs. It has been shown that some improvement of delivery and protection form a harsh gastric environment of several anticancer drugs when they are formulated in a PEGylated liposome. One of the successful drugs that has been clinically used is Doxil®, followed by some other drugs in the pipeline Various drugs (compounds) had been used to enhance the efficacy of PEGylated liposomes for targeted cancer cells in vitro and in vivo. In conclusion, PEGylated liposomes enhance drug activities and have great potential to become efficient anticancer delivery to follow Doxil® in the clinical setting.
The genus Alocasia (Schott) G. Don consists of 113 species distributed across Asia, Southeast Asia, and Australia. Alocasia plants grow in tropical and subtropical forests with humid lowlands. Featuring their large green heart-shaped or arrow-shaped ear leaves and occasionally red-orange fruit, they are very popular ornamental plants and are widely used as traditional medicines to treat various diseases such as jaundice, snake bite, boils, and diabetes. This manuscript critically analysed the distribution, traditional uses, and phytochemical contents of 96 species of Alocasia. The numerous biological activities of Alocasia species were also presented, which include anti-cancer, antidiabetic and antihyperglycaemic, antioxidant, antidiarrhoea, antimicrobial and antifungal, antiparasitic (antiprotozoal and anthelminthic), antinociceptive and anti-inflammatory, brine shrimp lethality, hepatoprotective, anti-hemagglutinin, anti-constipation and diuretic, and radioprotective activities as well as acute toxicity studies. Research articles were acquired by the accessing three scientific databases comprising PubMed, Scopus, and Google Scholar. For this review, specific information was obtained using the general search term "Alocasia", followed by the "plant species names" and "phytochemical" or "bioactivity" or "pharmacological activity". The accepted authority of the plant species was referred from theplantlist.org. Scientific studies have revealed that the genus is mainly scattered throughout Asia. It has broad traditional benefits, which have been associated with various biological properties such as cytotoxic, antihyperglycaemic, antimicrobial, and anti-inflammatory. Alocasia species exhibit diverse biological activities that are very useful for medical treatment. The genus Alocasia was reported to be able to produce a strong and high-quality anti-cancer compound, namely alocasgenoside B, although information on this compound is currently limited. Therefore, it is strongly recommended to further explore the relevant use of natural compounds present in the genus Alocasia, particularly as an anti-cancer agent. With only a few Alocasia species that have been scientifically studied so far, more attention and effort is required to establish the link between traditional uses, active compounds, and pharmacological activities of various species of this genus.
Road surface defects are crucial problems for safe and smooth traffic flow. Due to climate changes, low quality of construction material, large flow of traffic, and heavy vehicles, road surface anomalies are increasing rapidly. Detection and repairing of these defects are necessary for the safety of drivers, passengers, and vehicles from mechanical faults. In this modern era, autonomous vehicles are an active research area that controls itself with the help of in-vehicle sensors without human commands, especially after the emergence of deep learning (DNN) techniques. A combination of sensors and DNN techniques can be useful for unmanned vehicles for the perception of their surroundings for the detection of tracks and obstacles for smooth traveling based on the deployment of artificial intelligence in vehicles. One of the biggest challenges for autonomous vehicles is to avoid the critical road defects that may lead to dangerous situations. To solve the accident issues and share emergency information, the Intelligent Transportation System (ITS) introduced the concept of vehicular network termed as vehicular ad hoc network (VANET) for achieving security and safety in a traffic flow. A novel mechanism is proposed for the automatic detection of road anomalies by autonomous vehicles and providing road information to upcoming vehicles based on Edge AI and VANET. Road images captured via camera and deployment of the trained model for road anomaly detection in a vehicle could help to reduce the accident rate and risk of hazards on poor road conditions. The techniques Residual Convolutional Neural Network (ResNet-18) and Visual Geometry Group (VGG-11) are applied for the automatic detection and classification of the road with anomalies such as a pothole, bump, crack, and plain roads without anomalies using the dataset from different online sources. The results show that the applied models performed well than other techniques used for road anomalies identification.
The development of hydrogel films as wound healing dressings is of a great interest owing to their biological tissue-like nature. Polyvinyl alcohol/polyethylene glycol (PVA/PEG) hydrogels loaded with asiaticoside, a standardized rich fraction of Centella asiatica, were successfully developed using the freeze-thaw method. Response surface methodology with Box-Behnken experimental design was employed to optimize the hydrogels. The hydrogels were characterized and optimized by gel fraction, swelling behavior, water vapor transmission rate and mechanical strength. The formulation with 8% PVA, 5% PEG 400 and five consecutive freeze-thaw cycles was selected as the optimized formulation and was further characterized by its drug release, rheological study, morphology, cytotoxicity and microbial studies. The optimized formulation showed more than 90% drug release at 12 hours. The rheological properties exhibited that the formulation has viscoelastic behavior and remains stable upon storage. Cell culture studies confirmed the biocompatible nature of the optimized hydrogel formulation. In the microbial limit tests, the optimized hydrogel showed no microbial growth. The developed optimized PVA/PEG hydrogel using freeze-thaw method was swellable, elastic, safe, and it can be considered as a promising new wound dressing formulation.
Thymoquinone (TQ) is the main constituent of black seed (Nigella sativa, spp) essential oil which shows promising in vitro and in vivo anti-neoplastic activities in different tumor cell lines. However, to date there are only a few reports regarding the apoptotic effects of TQ on cervical cancer cells. Here, we report that TQ stimulated distinct apoptotic pathways in two human cervical cell lines, Siha and C33A. TQ markedly induced apoptosis as demonstrated by cell cycle analysis in both cell lines. Moreover, quantitative PCR revealed that TQ induced apoptosis in Siha cells through p53-dependent pathway as shown by elevated level of p53-mediated apoptosis target genes, whereas apoptosis in C33A cells was mainly associated with the activation of caspase-3. These results support previous findings on TQ as a potential therapeutic agent for human cervical cancer.
Recently there was huge increase in using of 'herbal products'. These can be defined as plants, parts of plants or extracts from plants that are used for curing disease. However, Calophyllum species is a tropical plant and it has been used in traditional medicine, the limitation in safety and effectiveness information could lead to serious health problems. Providing information for communities by evaluating the phytochemical contents, antioxidant, antimicrobial and cytotoxic activities will improve the therapeutic values. Three main Calophyllum canum fractions (none - high polar) were tested to find out the phenolic, flavonoid, flavonol content, DPPH radical scavenging, reducing power and chelating iron ions. Also were tested against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Psedomonas aeruginosa, Candida albicans, and Cryptococcus neoformans. In addition, cytotoxic activity was assayed against lung cancer A549 cell line. The methanol fraction showed no bioactivity but achieved the highest amount of phenolic, flavonol and flavonoid contents, also it showed a significant result as antioxidant, reducing power and chelating agent. The n-hexane fraction achieved the minimum inhibitory concentration (MIC) value 12.5 μg. mL(-1) against B. cereus while the MIC value for DCM fraction was 25 μg. mL(-1). The DCM fraction was more active against S. aureus where the result was 50 μg. mL(-1) while the n-hexane fraction was 100 μg. mL(-1). The three main fractions have shown no activity against gram negative bacterial and fungal. The n-hexane and DCM fractions have shown cytotoxicity against lung cancer cell line; the 50% inhibition concentration (IC(50)) was 22 ± 2.64 and 32 ± 3.78 μg. mL(-1) respectively. The results were statistically significant (P < 0.05). Among the results, C. canum fractions proved to be effective against gram positive bacterial and anti-proliferation activity. Also it showed antioxidant activity as well. The results provided beneficial information for communities as well as can help to search for alternative drugs, and will contribute to establish safe and effective use of phytomedicines in the treatment of diseases.
Supercritical carbon dioxide (SC-CO2) extraction of fucoxanthin is more advantageous over conventional solvent extraction as it is less toxic, less hazardous to the environment and preserves the bioactivity of fucoxanthin. A face-centered central composite design (FCCCD) based on response surface methodology (RSM) was employed for SC-CO2 extraction of oils and fucoxanthin from the brown seaweed Sargassum binderi, with ethanol as a co- solvent. Three independent parameters namely, extraction temperature (A: 40, 50, 60oC), pressure (B: 2900, 3625, 4350 psig and particle size (C: 90, 500 and 1000 µm) were investigated to optimize extraction oil yields (EOY) and fucoxanthin yields (FY). A regression model was developed, tested for quality of fit (R2) and expressed in the form of 3D response surface curve and 2D contour. The optimum extraction conditions were obtained at extraction temperature (A) 50oC, pressure (B) 3625 psig and particle size (C) 500 µm. Under these conditions, optimal EOY and FY were 10.04 mg/g and 3188.99 µg/g, respectively. The difference between the lowest and the highest response in EOY and FY were 5.44 – 10.04 mg/g and 2109.10 - 3188.90 µg/g, respectively. The lowest yields were identified at 60oC, 2900 psig and 1000 µm. The regression models generated showing interactions between the variables and EOY and FY response were significant as tested by ANOVA (p < 0.0005 and p < 0.0007, respectively) with high R2 values (0.9848 and 0.9829, respectively). Interactions between the parameters had a strong synergistic effect on EOY and FY values, as indicated by the 3D response surface curve and 2D contour. The experimental results matched the predicted results closely. This indicated the suitability of the models developed and the success of FCCCD under RSM in optimizing the S. binderi extraction conditions.
A phytochemical investigation of the stem bark of Calophyllum canum resulted in the isolation of a new xanthone dimer identified as biscaloxanthone (1), together with four compounds; trapezifoliaxanthone (2), trapezifolixanthone A (3), taraxerone (4) and taraxerol (5). The structures of these compounds were determined via spectroscopic methods of IR, UV, MS and NMR (1D and 2D). The cytotoxicity of compounds 1-3 were screened against A549, MCF-7, C33A and 3T3L1 cell lines, wherein weak cytotoxic activities were observed (IC50 > 50 μm).
Sponge-derived fungi have recently attracted attention as an important source of interesting bioactive compounds. Aspergillus nomius NC06 was isolated from the marine sponge Neopetrosia chaliniformis. This fungus was cultured on rice medium and yielded four compounds including three new oxisterigmatocystins, namely, J, K, and L (1, 2, and 3), and one known compound, aspergillicin A (4). Structures of the compounds were elucidated by 1D and 2D NMR spectroscopy and by high-resolution mass spectrometry. The isolated compounds were tested for cytotoxic activity against HT 29 colon cancer cells, where compounds 1, 2, and 4 exhibited IC50 values of 6.28, 15.14, and 1.63 µM, respectively. Under the fluorescence microscope by using a double staining method, HT 29 cells were observed to be viable, apoptotic, and necrotic after treatment with the cytotoxic compounds 1, 2, and 4. The result shows that compounds 1 and 2 were able to induce apoptosis and cell death in HT 29 cells.
The global expansion of the Visual Internet of Things (VIoT)'s deployment with multiple devices and sensor interconnections has been widespread. Frame collusion and buffering delays are the primary artifacts in the broad area of VIoT networking applications due to significant packet loss and network congestion. Numerous studies have been carried out on the impact of packet loss on Quality of Experience (QoE) for a wide range of applications. In this paper, a lossy video transmission framework for the VIoT considering the KNN classifier merged with the H.265 protocols. The performance of the proposed framework was assessed while considering the congestion of encrypted static images transmitted to the wireless sensor networks. The performance analysis of the proposed KNN-H.265 protocol is compared with the existing traditional H.265 and H.264 protocols. The analysis suggests that the traditional H.264 and H.265 protocols cause video conversation packet drops. The performance of the proposed protocol is estimated with the parameters of frame number, delay, throughput, packet loss ratio, and Peak Signal to Noise Ratio (PSNR) on MATLAB 2018a simulation software. The proposed model gives 4% and 6% better PSNR values than the existing two methods and better throughput.
Sonar sound datasets are of significant importance in the domains of underwater surveillance and marine research as they enable experts to discern intricate patterns within the depths of the water. Nevertheless, the task of classifying sonar sound datasets continues to pose significant challenges. In this study, we present a novel approach aimed at enhancing the precision and efficacy of sonar sound dataset classification. The integration of deep long-short-term memory (DLSTM) and convolutional neural networks (CNNs) models is employed in order to capitalize on their respective advantages while also utilizing distinctive feature engineering techniques to achieve the most favorable outcomes. Although DLSTM networks have demonstrated effectiveness in tasks involving sequence classification, attaining their optimal performance necessitates careful adjustment of hyperparameters. While traditional methods such as grid and random search are effective, they frequently encounter challenges related to computational inefficiencies. This study aims to investigate the unexplored capabilities of the fuzzy slime mould optimizer (FUZ-SMO) in the context of LSTM hyperparameter tuning, with the objective of addressing the existing research gap in this area. Drawing inspiration from the adaptive behavior exhibited by slime moulds, the FUZ-SMO proposes a novel approach to optimization. The amalgamated model, which combines CNN, LSTM, fuzzy, and SMO, exhibits a notable improvement in classification accuracy, outperforming conventional LSTM architectures by a margin of 2.142%. This model not only demonstrates accelerated convergence milestones but also displays significant resilience against overfitting tendencies.
Therapeutic gene editing is becoming more feasible with the emergence of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) system. However, the successful implementation of CRISPR/Cas9-based therapeutics requires a safe and efficient in vivo delivery of the CRISPR components, which remains challenging. This study presents successful preparation, optimization, and characterization of alginate nanoparticles (ALG NPs), loaded with two CRISPR plasmids, using electrospray technique. The aim of this delivery system is to edit a target gene in another plasmid (green fluorescent protein (GFP)). The effect of formulation and process variables were evaluated. CRISPR ALG NPs showed mean size and zeta potential of 228 nm and -4.42 mV, respectively. Over 99.0% encapsulation efficiency was achieved while preserving payload integrity. The presence of CRISPR plasmids in the ALG NPs was confirmed by Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy. The tests revealed that the nanoparticles were cytocompatible and successfully introduced the Cas9 transgene in HepG2 cells. Nanoparticles-transfected HepG2 was able to edit its target plasmid by introducing double-strand break (DSB) in GFP gene, indicating the bioactivity of CRISPR plasmids encapsulated in alginate nanoparticles. This suggests that this method is suitable for biomedical application in vitro or ex vivo. Future investigation of theses nanoparticles might result in nanocarrier suitable for in vivo delivery of CRISPR/Cas9 system.
Acute abdominal pain in pregnancy remains a surgical conundrum. A 25-year-old primigravid at 29 weeks gestation presented with a two-week history of epigastric pain, nausea and vomiting. She had a distended abdomen consistent with a full term gravid uterus; tender at the epigastric and right hypochondrium suggestive of small bowel obstruction or acute appendicitis. Abdominal ultrasound was inconclusive but abdominal Computed Tomography (CT) suggested small bowel volvulus. An exploratory laparotomy revealed a segmental jejunal volvulus and small bowel diverticulum contributing to the volvulus. A short segmental bowel resection was performed. Histopathology confirmed a Meckel's Diverticulum. The patient recovered well but underwent premature labour 10 days later. Small bowel obstruction secondary to Meckel's diverticulum is rare in pregnancy. In an acute gestational abdomen, clinical examination is key. Radiological imaging may be helpful, whilst surgical intervention is confirmatory and therapeutic in the event of an obstructive volvulus.
Obesity has taken the 21st century by storm, posing negative effects on of the various facades of health, healthcare and global economy. With regards to pulmonary performance, numerous studies have proven the detrimental effects of obesity while reinstating the positive effects of weight loss on overall pulmonary function. However, effects of exercise on pulmonary function and correlation between changes in pulmonary function test with weight loss have yet to be described. We performed a prospective interventional study to determine the effects of regular exercise on Pulmonary Function Tests (PFT) and ascertain the relationship between weight loss and change in PFT in obese patients.