The potential of marine natural Products: Recent Advances in the discovery of Anti-Tuberculosis agents.

Tuberculosis (TB) is an infectious airborne disease caused by Mycobacterium tuberculosis. Since the 1990 s, many countries have made significant progress in reducing the incidence of TB and associated mortality by improving health services and strengthening surveillance systems. Nevertheless, due to the emergence of multidrug-resistant TB (MDR-TB), alongside extensively drug-resistant TB (XDR-TB) and TB-HIV co-infection, TB remains one of the lead causes of death arising from infectious disease worldwide, especially in developing countries and disadvantaged populations. Marine natural products (MNPs) have received a large amount of attention in recent years as a source of pharmaceutical constituents and lead compounds, and are expected to offer significant resources and potential in the fields of drug development and biotechnology in the years to come. This review summarizes 169 marine natural products and their synthetic derivatives displaying anti-TB activity from 2013 to the present, including their structures, sources and functions. Partial synthetic information and structure-activity relationships (SARs) are also included.

Thiourea derivatives inhibit key diabetes-associated enzymes and advanced glycation end-product formation as a treatment for diabetes mellitus.

This study was designed to screen novel thiourea derivatives against different enzymes, such as α-amylase, α-glucosidase, protein tyrosine phosphatase 1 B, and advanced glycated end product (AGEs). A cytotoxicity analysis was performed using rat L6 myotubes and molecular docking analysis was performed to map the binding interactions between the active compounds and α-amylase and α-glucosidase. The data revealed the potency of five compounds, including E (1-(2,4-difluorophenyl)-3-(3,4-dimethyl phenyl) thiourea), AG (1-(2-methoxy-5-(trifluoromethyl) phenyl)-3-(3-methoxy phenyl) thiourea), AF (1-(2,4-dichlorophenyl)-3-(4-ethylphenyl) thiourea), AD (1-(2,4-dichlorophenyl)-3-(4-ethylphenyl) thiourea), and AH (1-(2,4-difluorophenyl)-3-(2-iodophenyl) thiourea), showed activity against α-amylase. The corresponding percentage inhibitions were found to be 85 ± 1.9, 82 ± 0.7, 75 ± 1.2, 72 ± 0.4, and 65 ± 1.1%, respectively. These compounds were then screened using in vitro assays. Among them, AH showed the highest activity against α-glucosidase, AGEs, and PTP1B, with percentage inhibitions of 86 ± 0.4% (IC50  = 47.9 µM), 85 ± 0.7% (IC50  = 49.51 µM), and 85 ± 0.5% (IC50  = 79.74 µM), respectively. Compound AH showed an increased glucose uptake at a concentration of 100 µM. Finally, an in vivo study was conducted using a streptozotocin-induced diabetic mouse model and PTP1B expression was assessed using real-time PCR. Additionally, we examined the hypoglycemic effect of compound AH in diabetic rats compared to the standard drug glibenclamide.

Fluorescence imaging approaches for eco-friendly determination of perampanel in human plasma and application for therapeutic drug monitoring.

Antiepileptic drugs are among the most common medications that require therapeutic drug monitoring (TDM). Indeed, TDM provides a realistic approach to adjust drug doses for epilepsy based on plasma concentrations to optimize its clinical outcome. The most common technique for TDM is high-performance liquid chromatography, which has a very low green profile among analytical techniques. Perampanel (PER) is an inherently fluorescent compound that its fluorophore readily allows sensitive and quantitative measurements. This paper describes the development and validation of a sensitive, specific, and eco-friendly spectrofluorimetric method for the determination of PER. Experimental parameters affecting fluorescence intensity of the compound, including solvent dilution, temperature, and excitation wavelength, were studied and optimized. The developed spectrofluorimetric method was established in acetonitrile at λex  = 295 nm and λem  = 431 nm over a concentration range of 5-60 ng/ml. The adopted method was applied for the determination of PER in human plasma; it was effective in the range of 15-50 ng/ml. The proposed method was found to be sensitive and specific for PER and can be applied successfully in TDM of PER and in quality control laboratories.

Exploring the Therapeutic Properties of Alga-Based Silver Nanoparticles: Anticancer, Antibacterial, and Free Radical Scavenging Capabilities.

The current study was designed to evaluate the antioxidant, anticancer and antimicrobial activities of silver nanoparticles (AgNPs) biosynthesized by Spirulina platensis extract. The biosynthesized silver nanoparticles were characterized using Fourier transform infrared (FT-IR) analysis, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD) analysis. The antioxidant activity of the biosynthesized AgNPs were determined via DPPH radical scavenging assay while its anticancer activity was determined using the MTT assay. The antimicrobial activity of the biosynthesized AgNPs were analyzed by disc diffusion method. Spirulina platensis acts as a reducing and capping agent. The efficacy of silver nanoparticles (AgNPs) in inhibiting the growth of Gram-negative bacteria, specifically Acetobacter, Klebsiella, Proteus vulgaris, and Pseudomonas aeruginosa, was assessed by the utilisation of the diffusion method. The study aimed to evaluate the efficacy of biosynthesized silver nanoparticles (AgNPs) against many strains of Pseudomonas aeruginosa bacteria. The findings of the study revealed that when administered in doses of 50 µl, 75 µl, and 100 µl, the largest observed zone of inhibition corresponded to measurements of 10.5 mm, 14 mm, and 16 mm, respectively. A zone of inhibition with dimensions of 8 mm, 10.5 mm, and 12 mm was detected during testing against Acetobacter at concentrations of 50 µl, 75 µl, and 100 µl, respectively. The findings also indicate that there is a positive correlation between the concentration of AgNP and the DPPH scavenging ability of silver nanoparticles. The percentage of inhibition observed at concentrations of 500 µg/ml, 400 µg/ml, 300 µg/ml, 200 µg/ml, and 100 µg/ml were recorded as 80±1.98, 61±1.98, 52±1.5, 42±1.99, and 36±1.97, respectively. In addition, it was observed that the silver nanoparticles exhibited the greatest antioxidant activity at a concentration of 500 g/ml, with a measured value of 80.89±1.99. The IC-50 values, representing the inhibitory concentration required to achieve 50 % inhibition, were found to be 8.16, 19.15, 30.14, 41.13, and 63.11 at inhibition levels of 36±1.97, 42±1.99, 52±1.5, 61±1.98, and 80±1.98, respectively.

Effect of the Prenatal Exposure of Khat on the Skeleton of Developing Rabbit Embryo: Morphometric and Gross Anatomical Study.

Background: Khat leaves are chewed by many people worldwide, mainly in Africa and the southwest Arabian peninsula. Materials and methods: 27 apparently healthy adult New Zealand rabbits (3 males & 24 females) of 2.5 ± 0.5 kg body weight were used in this work. The animals were divided into 4 groups (control, low, medium and high doses groups). The khat extract was administered orally during (8th -18th) day of gestation. The mothers were sacrificed on the 29th day of gestation. The skeletons of the fetuses were stained with Alizarin Red S and Alcian Blue. Results: Skeletal examination of the fetuses of treated dams showed several types of malformations and variations in all treated groups such as unossified phalanges, deformed sternum, completely unossified vertebral lamina and opened anterior and posterior fontanelles, and reduced length of limb long bones. Conclusion: These findings support the teratogenic effect of the khat on the developing rabbit fetus.

Heavy metals bioaccumulation and subsequent multiple biomarkers based appraisal of toxicity in the critically endangered Tor putitora.

The construction of hydropower projects discharges effluents to aquatic bodies. The effluents consist of different chemicals including heavy metals. The current study assessed the effects of effluents discharged from an under-construction hydropower project on the bioaccumulation of heavy metals in the tissues of critically endangered Tor putitora (Hamilton, 1822) in the river Panjkora. The subsequent toxic impacts of higher bioaccumulation of heavy metals on different biochemical, hematological, and serum biochemical profiles were also studied. Different biochemical changes were observed in the tissues of T. putitora including stress biomarkers such as reactive oxygen species, lipid peroxidation, total protein contents, antioxidant enzymes (peroxidase, superoxide dismutase, catalase, reduced glutathione, glutathione reductase, and glutathione-s-transferase), acetylcholinesterase, and whole-body cortisol. The hematotoxic effects were also observed as the count of red blood cells, hematocrit, and hemoglobin decreased whereas the count of white blood cells increased. Serum biochemical analysis revealed that cholesterol, urea, total bilirubin, and glucose concentration increased, whereas total proteins and albumin decreased with an increase in the concentration of heavy metals across the sampling sites. The fish from the river was found to be under severe stress as compared to the fish from the reference site. To mitigate the current scenario, stocking fish in an appropriate amount is suggested. The fish diversity and water quality should be assessed at regular intervals to avoid further deterioration and diversity loss. The safety and conservation of wild fisheries should be ensured by implementing strict environmental protection and fishing laws.

Optimization of localized surface plasmon resonance hot spots in surface-enhanced infrared absorption spectroscopy aluminum substrate as an optical sensor coupled to chemometric tools for the purity assay of quinary mixtures.

Surface-enhanced infrared absorption spectroscopy offers an alternative to conventional IR spectroscopy and utilizes the signal enhancement exerted by the plasmon resonance of nanostructured metal thin films. Citrate-capped silver nanoparticles were prepared in a single-step method, and their morphology was identified using transmission electron microscopy, scanning electron microscopy, ultraviolet/visible spectrophotometry, and Zetasizer. The nanoparticles generated were deposited on the surface of cheap aluminum slides for different durations aiming for the selection of the best time producing a thin film, suitable to act as a lab-on-a-chip SEIRA substrate. These substrates were coupled to partial least squares regression tools for simultaneous resolving of the quinary mixture in commercial dosage forms of bisoprolol, perindopril, bisoprolol acid degradation product, bisoprolol alkali degradation product, and perindoprilat in concentration ranges of 15-75, 60-300, 15-55, 12-60, and 20-80 µg/mL with limits of detection values of 0.69, 3.43, 0.97, 1.25, and 1.09 µg/mL, respectively. Overall, we could demostrate that the localized surface plasmon resonance sensor coupled to chemometrics provides cheap, simple, selective, multiplex, rapid, and molecular specific procedures for impurity detection, which would be beneficial in many applications for quality control and quality accuracy of active pharmaceutical ingredients.

Spectrofluorimetric study on fluorescence quenching of tyrosine and l-tryptophan by the aniracetam cognition enhancer drug: quenching mechanism using Stern-Volmer and double-log plots.

A novel approach on fluorescence quenching of tyrosine and l-tryptophan is presented for spectrofluorimetric determination of aniracetam in drug substances and products. The quenching mechanism was investigated using Stern-Volmer plots and ultraviolet spectra figures of quencher-fluorophore mixtures. Binding constant and stoichiometry were calculated using double-log plots. The spectrofluorimetric method was optimized for the experimental conditions affecting fluorescence quenching including fluorophore concentration, diluent, and reaction time. Moreover, the pH-rate profile of aniracetam was studied using simple kinetics and found to be stable within the pH range 5-8. Fluorescence quenching of tyrosine and l-tryptophan were observed on addition of aniracetam in aqueous medium at pH 5.5-6.5. Aniracetam quenched the fluorescence of tyrosine and l-tryptophan in the concentration range 1-20 µg/ml and 0.3-20 µg/ml, respectively, with binomial relationships between quenching values (ΔF) and aniracetam concentration. Limits of detection were found to be 0.10 µg/ml for tyrosine-aniracetam and 0.14 µg/ml for l-tryptophan-aniracetam. Method validation was performed as per ICH guidelines and demonstrated that the developed spectrofluorimetric method was accurate, precise, specific, and suitable for analysis of aniracetam in routine quality control laboratories. All experimental materials and solvents used are eco-friendly, indicating that the cited spectrofluorimetric procedure is an excellent green method.

Point-of-care diagnostics for drugs of abuse in biological fluids: application of a microfabricated disposable copper potentiometric sensor.

The major objective of this work was to develop a portable, disposable, cost-effective, and reliable POC solid-state electrochemical sensor based on potentiometric transduction to detect benzodiazepine abuse, mainly diazepam (DZP), in biological fluids. To achieve that, microfabricated Cu electrodes on a printed circuit board modified with the conducting polymer poly(3-octylthiophene) (POT) have been employed as a substrate. This polymer was introduced to enhance the stability of the potential drift (0.9 mV/h) and improve the limit of detection (0.126 nmol mL-1). Nernstian potentiometric response was achieved for DZP over the concentration range 1.0 × 10-2 to 5.0 × 10-7 mol L-1 with a slope of 55.0 ± 0.4 mV/decade and E0 ~ 478.9 ± 0.9. Intrinsic merits of the proposed sensor include rapid response time (11 ± 2 s) and long life time (3 months). In order to enhance the selectivity of the potentiometric sensor towards the target drug and minimize any false positive results, calix[4]arene (CX4) was impregnated as an ionophore within the PVC plastic ion-sensing membrane. The performance of the POC sensors was assessed using electrochemical methods of analysis and electrochemical impedance spectroscopy as a surface characterization tool. The studied sensors were applied to the potentiometric determination of DZP in different biological fluids (plasma, urine, saliva, and human milk) in the presence of its metabolite with an average recovery of 100.9 ± 1.3%, 99.4 ± 1.0%, 101.8 ± 1.2%, and 99.0 ± 2.0%, respectively. Graphical abstract.

Quantitative Particle Uptake by Cells as Analyzed by Different Methods.

There is a large number of two-dimensional static in vitro studies about the uptake of colloidal nano- and microparticles, which has been published in the last decade. In this Minireview, different methods used for such studies are summarized and critically discussed. Supplementary experimental data allow for a direct comparison of the different techniques. Emphasis is given on how quantitative parameters can be extracted from studies in which different experimental techniques have been used, with the goal of allowing better comparison.

Protective role of Monotheca buxifolia and Bosea amherstiana against H2O2 -induced DNA damage in human lymphocytes and its effect on oxidative enzymes.

Experimental based evidence suggests that most of the medicinal plants possess a wide-ranging pharmacological and biological activity that may possibly protect tissues against O2-induced damages. The objectives of the current study are: first, to investigate the effects of Monotheca buxifolia and Bosea amherstiana on H2O2 induced DNA damage in human lymphocytes and second, to determine its effect on oxidative enzymes. Cells were treated at concentration of 100µg/mL with both plants. Alkaline Single Cell Gel Electrophoresis/comet assay were used for DNA damage analysis. Activities of antioxidant enzymes TBARS, SOD, CAT and POD were assayed on treatment with the extracts. Both plants species possess the protective role against H2O2-induced lymphocytes DNA. Dichloromethane (DCM) fraction of Monotheca buxifolia (H DNA 94.79±0.29%) and methanolic fraction of Bosea amherstiana (H DNA 93.63±2.23%) possess high protection Significantly decrease occur in status of antioxidant enzymes. This study indicates that both plants have potential in preventing oxidative damages/stress related diseases and would be suitably used as supplements in combination with conventional drug for the treatment of cancer like diseases.

Transmission electron microscopic evaluation of neuronal changes in methylmercury-exposed zebrafish embryos (Danio rerio).

Our work aimed to elucidate the ultrastructural changes associated with brain neurons in wild-type zebrafish embryos exposed to different concentrations of methylmercury. Zebrafish embryos were exposed to one of five concentrations of methylmercury (0 [negative control], 5, 10, 50, and 80 parts per billion) starting at six hours post fertilization (hpf). At 96 hpf, cells in the zebrafish embryo brains were examined using transmission electron microscopy. The developing neurons of the control embryos sowed normal cellular ultrastructure. Few alterations were observed among the neurons of zebrafish embryos exposed to 5 ppb methylmercury. The cells of the embryos exposed to 10 ppb methylmercury showed slight cellular degeneration as demonstrated by the accumulation of electron dens bodies which were presumably lysosomes in different stages of formation. In embryos exposed to 50 ppb methylmercury, the neuronal cytoplasm conained large electron dense lysosomes and the rough endoplasmic reticulum appeared to be reduced and irregular in shape. Furthermore, the embryonic brain neurons exposed to 80 ppb methylmercury showed the most severe ultrastructural changes, including some that were consistent with different stages of the cell death process. Obvious cellular changes were observed in this highest exposure group included: disrupted or degenerating nuclei; fragmentation or vacuolization of mitochondrial cristae; and loss of mitochondrial matrix density. Based on these observations, we conclude that these different morphological patterns of cellular changes may reflect either different stages of the cell death process or different types of cell death due to 24 hours of exposure to 80 ppb methylmercury.

Advanced chemometric methods for simultaneous quantitation of caffeine, codeine, paracetamol, and p-aminophenol in their quaternary mixture.

Two different multivariate techniques have been applied for the quantitative analysis of caffeine, codeine, paracetamol and p-aminophenol (PAP) in quaternary mixture, namely, Partial Least Squares (PLS-1) and Artificial Neural Networks (ANN). For suitable analysis, a calibration set of 25 mixtures with various ratios of the drugs and PAP impurity were established using a 4-factor 5-level experimental design. The most meaningful wavelengths for the chemometric models were chosen using Genetic Algorithm (GA) as a variable selection technique. By using an independent validation set, the validity of the proposed methods was evaluated. A comparative study was established between the three multivariate models (PLS-1, GA-PLS and GA-ANN). The comparison between the various models revealed that the GA-ANN model was superior at resolving the highly overlapped spectra of this quaternary combination. The drugs were successfully quantified in their pharmaceutical dosage form utilizing the GA-ANN models.

Production of Single Cell Protein (SCP) from the Peel Waste of Pea, Potato, and Banana by Aspergillus Flavus NRRL 21882 as an Efficient Organic Poultry Supplement.

Food protein deficit has become a major issue worldwide, particularly in underdeveloped countries. Scientists are searching for a variety of less expensive solutions to this issue. One of these less expensive methods is to create single cell protein as a substrate from leftover fruit and vegetable waste, which is typically thrown away. In this regard, the fungal strain Aspergillus flavus (NRRL 21882) was used for the synthesis of SCP (single cell protein) from the waste of banana, potato, and pea. In this manner, 30 samples were collected from the whole substrate with a share of 10 samples each from banana, potato, and pea peels, which were in turn dried and powdered finely. The fermentation process was done by the process of solid state fermentation. Aspergillus flavus (NRRL 21882) generated the highest percentage, i.e. 60.67%, of crude protein from the pea peels. The composition of amino acids in crude proteins was also investigated. The findings demonstrated that the highest percentage of aspartic acid (13.34 ± 0.80%) and glutamic acid (14.92 ± 0.69%) was found in A. flavus single cell protein produced from pea peels. Soybean was supplemented with single cell protein in the boilers' diet. Compared to all treated groups, there was a substantial (p ≤ 0.05) increase in the level of antibody titer against the Newcastle disease vaccine. The supplementation of single cell protein with soybean meal had no effect on the levels of liver enzymes. The liver enzymes found in all four groups (A, B, C, and D) were within normal limits. None of the examined groups experienced any change in the feed conversion ratio, with all groups exhibiting an average FCR of 1.6. The current study concludes that broiler health and immunity is increased by supplementing poultry feed with single cell protein.

Continuous wavelet transform for solving the problem of minor components in quantitation of pharmaceuticals: a case study on the mixture of ibuprofen and phenylephrine with its degradation products.

The presence of minor components represents a challenging problem in spectrophotometric analysis of pharmaceuticals. If one component has a low absorptivity or present in a low concentration compared to the other components, this will hinder its quantitation by spectrophotometric methods. Continuous Wavelet Transform (CWT) as a signal processing technique was utilized to figure out a solution to such a problem. A comparative study was established between traditional derivative spectrophotometry (Numerical Differentiation, ND) and CWT to indicate the advantages and limitations of each technique and possibility of solving the problem of minor components. A mixture of ibuprofen (IBU) and phenylephrine (PHE) with its degradation products forming a ternary mixture was used for comparing the two techniques. The two techniques were applied on raw spectral data and on ratio spectra data resulting in four methods, namely ND, CWT, Derivative Ratio-Zero Crossing (DRZC) and Continuous Wavelet Transform Ratio-Zero Crossing (CWTR-ZC) methods. By comparing the results in laboratory prepared mixtures, CWT technique showed advantages in analysis of mixtures with minor components than ND. The proposed methods were validated according to the ICH guideline Q2(R1), where their linearity was established with correlation coefficient ranging from 0.9995 to 0.9999. The linearity was in the range 3-40 µg/mL for PHE in all methods, while for IBU it was 20-180 and 30-180 µg/mL in CWT and ND methods, respectively. The CWT methods were applied for quantitative determination of the drugs in their dosage form showing the ability of the methods to quantitate minor components in pharmaceutical formulations.

A solvent-free HPLC method for the simultaneous determination of Favipiravir and its hydrolytic degradation product.

During COVID-19 pandemic, Favipiravir (FPV) showed a great efficacy against COVID-19 virus, it produced noticeable improvements in recovery of the patients. The aim of this study was to develop a new, green and simple method for the simultaneous determination of FPV and its acid-induced degradation product (ADP) in its pure and pharmaceutical dosage forms. This method will be key for the inevitable development of FPV solution and inhaler formulations. A green micellar RP-HPLC method was developed using an RP-VDSPHERE PUR 100 column (5 µm, 250 × 4.6 mm) and an isocratic mixed micellar mobile phase composed of 0.02 M Brij-35, 0.1 M SDS and 0.01 M potassium dihydrogen orthophosphate anhydrous and adjusted to pH 3.0 with 1.0 mL min-1 flow rate. The detection was performed at 280 nm with a run time of less than six min. Under the optimized chromatographic conditions, linear relationship has been established between peak area and concentration of FPV and its ADP in the range of 5-100 and 10-100 µg mL-1 with elution time of 3.8 and 5.7 min, respectively. The developed method was validated according to the ICH guidelines and applied successfully for determination of FPV in its pharmaceutical dosage form.

Development of an eco-friendly HPLC method for the stability indicating assay of binary mixture of ibuprofen and phenylephrine.

The development and validation of the stability indicating HPLC technique has contributed to the understanding of the stability profile of ibuprofen (IBU) and phenylephrine (PHE). Stability profile was achieved for PHE; the drug was found to be liable to be influenced by stress oxidative conditions; two oxidative degradants (Deg1 & Deg2) were formed and their structures were confirmed using IR and mass spectrometry. The drugs and degradation products were successfully separated using a gradient elution method on YMC-C8 column with 0.1% hexanesulfonic acid and acetonitrile as a mobile phase at pH 6.6. The flow rate was 1.0 mL/min, and a diode array detector operating at 220 nm was used for UV detection. The retention times of degradants Deg1, Deg2, ibuprofen (IBU), and phenylephrine hydrochloride (PHE) were 2.0, 2.2, 3.2 and 7.0 min, respectively. The proposed method was validated with respect to linearity, accuracy, precision, specificity, and robustness using ICH guidelines. The linearities of ibuprofen and phenylephrine hydrochloride were in the range of 10-100 µg/mL and 0.3-10 µg/mL, respectively. The % recoveries of the two drugs were found to be 100.75 ± 1.44%, 99.67% ± 1.67, and the LOD was found to be 2.75/mL and 0.09/mL for IBU, and PHE, respectively. The method was successfully applied to the estimation of ibuprofen and phenylephrine hydrochloride combination in pharmaceutical dosage form. The proposed technique was validated using ICH guidelines and its greenness was assessed according to Analytical Eco Scale metric (AES). Molecular docking was used to assess the two drugs and PHE oxidative degradants interaction with the stationary phase and to confirm the outcomes of the proposed method with regard to the order of elution of the two drugs and PHE degradation products. Eco-friendly and environmental safety were assessed through the application of one of the most applicable greenness assessment tool; Analytical Eco Scale metric (AES).

Predictive Factors for Magnetic Resonance Imaging Changes Suggestive of Demyelination in Adult Patients with Uveitis Scanned Prior to Commencing Adalimumab Therapy.

PURPOSE: To report the predictive clinical factors for abnormal magnetic resonance imaging (MRI) scans suggestive of demyelination by analysis of MRI's performed for adult non-infectious uveitic patients prior to commencing adalimumab therapy. METHODS: Retrospective case review of 240 patients was conducted in a single tertiary institution between November 2017 and March 2020. Aetiology of underlying disease, clinical characteristics, and MRI outcomes were analysed. RESULTS: The presence of bilateral idiopathic intermediate uveitis (IIU) (p = .0048) and neurological symptoms (p = .028) were highly predictive of an abnormal MRI strongly suggestive of demyelination (MRSSD); 5 out of 64 scans (7.8%) with these clinical characteristics had MRSSD. CONCLUSIONS: Tumor necrosis factor antagonist-induced demyelination is a concern in adalimumab use. We propose an MRI screening protocol to identify those at high risk of demyelination; positive results can be maximised by screening all patients with IIU and those with neurological symptoms.

Cytotoxic Activity of Phytoconstituents Isolated from Monotheca buxifolia against Hepatocellular Carcinoma Cell Line HepG2: In Vitro and Molecular Docking Studies.

Natural products and conventional chemotherapeutic drugs are believed to enhance anticancer treatment efficacy while lowering toxicity. The current study investigates the cytotoxic and apoptogenic effects of Monotheca buxifolia bioactive compounds on HepG2 cell lines. MTT assay was used to assess the effect on the viability of HepG2 cells. Morphological changes were investigated. Annexin-V-FITC/PI was used to demonstrate apoptotic activity. A molecular dynamics simulation study was carried out to investigate the compound binding pattern in the active site of the PPRAδ protein. MTT and annexin V-FITC/PI assays revealed that the isolated compounds lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate inhibited the growth of hepatocellular cancer cells. The IC50 value for lauric acid was 56.46 ± 1.20 µg/mL, 31.94 ± 1.03 µg/mL for oleanolic acid, and 83.80 ± 2.18 µg/mL for bis(2-ethylhexyl) phthalate. Apoptosis was observed in 29.5, 52.1 and 22.4% of HepG2 cells treated with lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate, respectively, after 24 h of treatment. Morphological assays and Hoechst staining microscopy revealed that the treatment caused morphological changes in the cell membrane and nuclear condensation. The high fluctuation indicates that various interactions were highly potent and widely adopted, and vice versa. Oleanolic acid displayed high residue fluctuation, remaining stable in the active site of the PPRAδ protein and involved in various interactions while remaining locally fluctuating in the binding sites of the other two compounds. These findings concluded that lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate have a significant apoptogenic effect against HepG2 cells in inducing apoptosis. Our findings suggest that these bioactive compounds could be used as adjuvant therapies.

Anatomical, histochemical and surface ultrastructural characteristics of cavum nasi of the common quails (Coturnix coturnix. Erlangeri).

Ten normal, mature and common quails were used to study in detail the gross anatomy, histochemical and surface ultrastructural characteristics of the nasal cavity. The relationship between the structure and function of the nasal cavity also were assessed. The quail nasal cavity was divided into the vestibule, nasal cavity proper and fundus. The nasal cavity began rostrally by two slit-like external nares located laterally in the middle third of the upper beak. A previous authors stated that no rostral concha but the current study record that the rostral nasal concha was located opposite the nostrils and exhibited a C-shaped appearance in transverse section and was 5 mm long and 3 mm wide. The middle nasal concha was narrow and elongated. The caudal nasal concha was spherical, located caudodorsal to the rostral nasal concha and measured 2 mm in diameter. The infraorbital sinus was a roughly triangular cavity situated immediately rostral to the orbit. The histological and surface ultrastructural study of the nasal cavity of common quail did not studied previously. Histologically, the cavum nasi was composed of three regions: vestibule, respiratory and olfactory. The vestibule was lined with stratified squamous epithelium that was keratinized rostrally and non-keratinized caudally. The respiratory region was covered by pseudostratified columnar epithelium. Intra-epithelial mucous glands were present in the respiratory region and displayed a strong reaction with Alcian blue. The lining epithelium in the olfactory region was pseudostratified and contained olfactory, supporting and basal cells.