Consequences of dietary cinnamon and ginger oils supplementation on blood biochemical parameters, oxidative status, and tissue histomorphology of growing Japanese quails.

The present study aimed to investigate the impact of various concentrations of ginger and cinnamon oils as antibiotic substitutes on some blood biochemical parameters, antioxidant capacity, and histopathological profile of the liver and gut of growing Japanese. A total of 900 Japanese quails were randomly allotted into 6 treatment groups. Each group had 5 replicates (30 chicks each). The first group received a basal diet and served as the control, while the second received a basal diet plus 0.5 g of colistin antibiotic/kg diet. The third and fourth groups were supplemented with 0.5 mL and 1.0 mL of ginger oil (GO)/kg diet, respectively. While the fifth and sixth groups received basal diet with 0.5 and 1.0 mL of cinnamon oil (CO)/kg diet, respectively. Results showed that adding herbal oils significantly (P < 0.05) decreased the aspartate aminotransferase (AST) and urea levels compared to control and colistin groups. Various levels of GO and CO significantly (P < 0.05) reduced cholesterol levels compared to control birds. Compared to the control and antibiotic groups, Japanese quails supplemented with various levels of herbal oils (GO and CO) had more extraordinarily significant (P < 0.05) values for total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPX), and glutathione reductase (GSR). Regarding histopathologic examination, the jejunum displayed a nearly empty lumen, a few fusions, and mild goblet cell metaplasia. On the other hand, the duodenum looked tall and had a few fusions of villi and remnants of removal in its lumina. It could be concluded that cinnamon and GO improved birds' blood biochemical parameters, electorate oxidative stress, and enhanced intestinal and hepatic histology of the treated quails. Also, the levels of 0.5 mL CO and 0.5 mL GO may be an acceptable substitute for antibiotics (colistin) in the diets of growing Japanese quail.

In-vitro and in-vivo assessment of pH-responsive core-shell nanocarrier system for sequential delivery of methotrexate and 5-fluorouracil for the treatment of breast cancer.

Breast cancer (BC) is one of the leading fatal diseases affecting females worldwide. Despite the presence of tremendous chemotherapeutic agents, the resistance emergence directs the recent research towards synergistic drugs' combination along with encapsulation inside biocompatible smart nanocarriers. Methotrexate (MTX) and 5-fluorouracil (Fu) are effective against BC and have sequential synergistic activity. In this study, a core-shell nanocarrier composed of mesoporous silica nanoparticles (MSN) as the core and zeolitic imidazolate framework-8 nano metal organic frameworks (ZIF-8 NMOF) as the shell was developed and loaded with Fu and MTX, respectively. The developed nanostructure; Fu-MSN@MTX-NMOF was validated by several characterization techniques and conferred high drugs' entrapment efficiency (EE%). In-vitro assessment revealed a pH-responsive drug release pattern in the acidic pH where MTX was released followed by Fu. The cytotoxicity evaluation indicated enhanced anticancer effect of the Fu-MSN@MTX-NMOF relative to the free drugs in addition to time-dependent fortified cytotoxic effect due to the sequential drugs' release. The in-vivo anticancer efficiency was examined using Ehrlich ascites carcinoma (EAC) animal model where the anticancer effect of the developed Fu-MSN@MTX-NMOF was compared to the sequentially administrated free drugs. The results revealed enhanced anti-tumor effect while maintaining the normal functions of the vital organs as the heart, kidney and liver.

Core-Shell Nanostructured Drug Delivery Platform Based on Biocompatible Metal-Organic Framework-Ligated Polyethyleneimine for Targeted Hepatocellular Carcinoma Therapy.

Multifunctional nanosized metal-organic frameworks (NMOFs) have advanced rapidly over the past decade to develop drug delivery systems (DDSs). These material systems still lack precise and selective cellular targeting, as well as the fast release of the quantity of drugs that are simply adsorbed within and on the external surface of nanocarriers, which hinders their application in the drug delivery. Herein, we designed a biocompatible Zr-based NMOF with an engineered core and the hepatic tumor-targeting ligand, glycyrrhetinic acid grafted to polyethyleneimine (PEI) as the shell. The improved core-shell serves as a superior nanoplatform for efficient controlled and active delivery of the anticancer drug doxorubicin (DOX) against hepatic cancer cells (HepG2 cells). In addition to their high loading capacity of 23%, the developed nanostructure DOX@NMOF-PEI-GA showed an acidic pH-stimulated response and extended the drug release time to 9 days as well as enhanced the selectivity toward the tumor cells. Interestingly, the DOX-free nanostructures showed a minimal toxic effect on both normal human skin fibroblast (HSF) and hepatic cancer cell line (HepG2), but the DOX-loaded nanostructures exhibited a superior killing effect toward the hepatic tumor, thus opening the way for the active drug delivery and achieving efficient cancer therapy applications.

Compounds from myrtle flowers as antibacterial agents and SARS-CoV-2 inhibitors: In-vitro and molecular docking studies.

Plants and their related phytochemicals play a key role in the treatment of bacterial and viral infections, which inspire scientists to design and develop more efficient drugs starting from the phytochemical active scaffold. This work aims to characterize the chemical compounds of Myrtus communis essential oil (EO) from Algeria and to evaluate its in vitro antibacterial effect, as well as the in silico anti-SARS-CoV-2 activity. The chemical profile of hydrodistilled EO from myrtle flowers was determined using GC/MS analysis. The results showed qualitative and quantitative fluctuations and 54 compounds were identified including the main components: α-pinene (48.94%) and 1,8-cineole (28.3%) whereas other minor compounds were detected. The in vitro antibacterial activity of myrtle EO against Gram-negative bacteria was carried out by using the disc diffusion method. The best inhibition zone values ranged between 11 and 25 mm. The results revealed that Escherichia coli (25 mm), Klebsiella oxytoca (20 mm) and Serratia marcescens (20 mm) are the most susceptible strains to the EO which is endowed with a bactericidal effect. Furthermore, the antibacterial and anti-SARS-CoV-2 activities were investigated by the means of molecular docking (MD) study, in addition to ADME(Tox) analysis. The phytochemicals were docked against four targets: E. coli topoisomerase II DNA gyrase B (PDB: 1KZN), SARS-CoV-2 Main protease (PDB: 6LU7), Spike (PDB: 6ZLG) and angiotensin-converting enzyme II ACE2 (PDB: 1R42). The MD investigation revealed that 1,8-cineole could be the main phytochemical associated with the antibacterial activity of EO; s-cbz-cysteine, mayurone and methylxanthine were found the most promising phytochemicals against SARS-CoV-2; The ADME(Tox) analysis has shown their good druggability with no Lipinski's rule violation.

Correction: Mansour et al. Dual-Enhanced Pluronic Nanoformulated Methotrexate-Based Treatment Approach for Breast Cancer: Development and Evaluation of In Vitro and In Vivo Efficiency. Pharmaceutics 2022, 14, 2668.

In the original publication [...].

Fortified anti-proliferative activity of niclosamide for breast cancer treatment: In-vitro and in-vivo assessment.

Breast cancer represents one of the top lethal cancer types among the females worldwide. Several factors manipulate the clinical outcome of the treatment as the stage of the cancer upon detection, genetic and hormonal factors, drug resistance and metastasis. Accordingly, drug's repositioning, enhancing the bioavailability and encapsulation into nanoparticles (NPs) are among the predilected pathways for enhanced therapeutic outcome. Niclosamide (NIC) is an anthelmintic drug and has been repositioned as anticancer agent after revealing its anti-neoplastic activity. Piperine (PIP) was used as food spice until its anticancer activity was discovered. However, their hydrophobicity constrains their therapeutic efficiency. The cytotoxicity of both drugs in the free form was tested on MCF-7 cells, and the results indicated a NIC cytotoxicity enhancement by PIP. Then, NIC and PIP were encapsulated successfully into F127-NPs with entrapment efficiency of 97 % and 82 %, respectively. Particle size, zeta potential, TEM and FTIR confirmed the micellization process and drug encapsulation. The developed NIC-NPs and PIP-NPs exerted potent anticancer effect as compared to the free forms. Accordingly, the mixture; NIC-NPs/PIP-NPs was tested and its cytotoxicity exceeded the individually encapsulated drugs. Flowcytometry assessment was performed and demonstrated an induced cell death through the apoptotic stage. Additionally, in-vivo therapeutic efficiency of NIC-NPs/PIP-NPs was assessed through Ehrlich ascites tumor and the nanocombination therapy exerted superior additive anticancer effect when compared to NIC-NPs which is attributed to the PIP-NPs induced bioavailability. The study can be considered the first one investigating the PIP role in bioenhancing the anti-proliferative activity of NIC to combat breast cancer.

Influence of tomato processing by-product extract as dietary supplementation on growth performance, carcass characteristics and antioxidant status of growing rabbits under high ambient temperature.

This study evaluated the effects of dietary supplementation of tomato processing by-product extract (TPBE) on growth performance, carcass characteristics and antioxidant status of growing rabbits under high ambient temperature. A total of eighty weaned New Zealand White (NZW) male rabbits (6-weeks-old; initial body weight, 730.28 ± 36.05 g) were randomly assigned to 4 groups. The first group was the control without supplementation; while the other groups were fed diets supplemented with 100, 200 and 250 mg TPBE/kg. The results showed that TPBE contained 211.85 mg/100g as total phenols and total flavones of 303.36 mg/100g. Rabbits fed a 250 mg TPBE-supplemented diet showed the heaviest body weight, the lowest feed intake and the best feed conversion ratio. TPBE diets reduced mortality percentage. Dietary supplementation of 250 mg TPBE had the highest dressing percentage. Plasma total protein, globulin, catalase and glutathione peroxidase of rabbits fed diets supplemented with 200 and 250 mg TPBE were high. Plasma total cholesterol, triglycerides, plasma hydrogen peroxide and malondialdehyde concentrations were decreased with dietary levels of TPBE. Rabbits fed 250 mg TPBE had higher T-AOC than the other groups. TPBE supplemented diets improved net revenue and economic efficiency. Conclusively, TPBE is containing appreciable content of polyphenols and flavonoids and the dietary supplementation of TPBE (250 mg/kg diet) had a positive impact on growth performance, reducing mortality and enhancing the antioxidant status of rabbits reared under high ambient temperature.

Role of Oxytocin in Different Neuropsychiatric, Neurodegenerative, and Neurodevelopmental Disorders.

Oxytocin has recently gained significant attention because of its role in the pathophysiology and management of dominant neuropsychiatric disorders. Oxytocin, a peptide hormone synthesized in the hypothalamus, is released into different brain regions, acting as a neurotransmitter. Receptors for oxytocin are present in many areas of the brain, including the hypothalamus, amygdala, and nucleus accumbens, which have been involved in the pathophysiology of depression, anxiety, schizophrenia, autism, Alzheimer's disease, Parkinson's disease, and attention deficit hyperactivity disorder. Animal studies have spotlighted the role of oxytocin in social, behavioral, pair bonding, and mother-infant bonding. Furthermore, oxytocin protects fetal neurons against injury during childbirth and affects various behaviors, assuming its possible neuroprotective characteristics. In this review, we discuss some of the concepts and mechanisms related to the role of oxytocin in the pathophysiology and management of some neuropsychiatric, neurodegenerative, and neurodevelopmental disorders.

Rice gluten meal as a substitute for soybean meal in the diets for growing rabbits.

The impacts of different dietary levels of rice gluten meal (RGM) on growth performance, digestibility, carcass characteristics, and blood traits of growing New Zealand White (NZW) rabbits were studied. One hundred and twenty, 6 weeks old weaned male rabbits (body weight; 682 [g] ± 23) were randomly allotted into four groups. The control diet contained 160 [g/kg] soybean meal (SBM), while the other three diets were obtained by replacing 40, 80, and 120 [g/kg] SBM with RGM (RGM40, RGM80, and RGM120, respectively). The results showed that RGM contained higher levels of dry matter (DM), crude protein (CP), ether extract (EE), ash, and gross energy than SBM. RGM contained a high level of arginine followed by leucine and valine as essential amino acids and high levels of glutamic, aspartic acid, and alanine as non-essential amino acids. The obtained results showed that the final body weight of rabbits fed diets containing 40, 80, and 120 [g/kg] RGM was higher than those fed the control diet. The daily weight gain of rabbits fed RGM diets increased (p < 0.05) by 10.50%, 6.50%, and 10.00%, respectively, compared to the control group. Rabbits fed RGM80 showed the highest (p < 0.05) digestibility of DM, organic matter (OM), EE, neutral detergent fibre (NDF), and acid detergent fibre (ADF) compared to the other tested levels. Rabbits fed RGM120 had the highest (p < 0.05) digestible energy (DE) and digestible crude protein (DCP) values. RGM inclusion levels of 40 and 80 [g/kg] increased (p < 0.05) plasma total protein and albumin compared to the control group. Rabbits fed a diet containing RGM40 had the highest (p < 0.05) globulin level. The highest (p < 0.05) plasma urea concentration level was measured in the rabbit group fed the RGM120 diet. Conclusively, RGM could be a valuable ingredient for growing rabbits, as at all the tested levels improved growth performance, digestibility, and nutritional values.

Dual-Enhanced Pluronic Nanoformulated Methotrexate-Based Treatment Approach for Breast Cancer: Development and Evaluation of In Vitro and In Vivo Efficiency.

Breast cancer is a prevalent tumor and causes deadly metastatic complications. Myriad cancer types, including breast cancer, are effectively treated by methotrexate (MTX). However, MTX hydrophobicity, adverse effects and the development of resistance have inspired a search for new effective strategies to overcome these challenges. These may include the addition of a bioenhancer and/or encapsulation into appropriate nano-based carriers. In the present study, the anticancer effect of MTX was fortified through dual approaches. First, the concomitant use of piperine (PIP) as a bioenhancer with MTX, which was investigated in the MCF-7 cell line. The results depicted significantly lower IC50 values for the combination (PIP/MTX) than for MTX. Second, PIP and MTX were individually nanoformulated into F-127 pluronic nanomicelles (PIP-NMs) and F-127/P-105 mixed pluronic nanomicelles (MTX-MNMs), respectively, validated by several characterization techniques, and the re-investigated cytotoxicity of PIP-NMs and MTX-MNMs was fortified. Besides, the PIP-NMs/MTX-MNMs demonstrated further cytotoxicity enhancement. The PIP-NMs/MTX-MNMs combination was analyzed by flow cytometry to understand the cell death mechanism. Moreover, the in vivo assessment of PIP-NMs/MTX-MNMs was adopted through the Ehrlich ascites model, which revealed a significant reduction of the tumor weight. However, some results of the tumor markers showed that the addition of PIP-NMs to MTX-MNMs did not significantly enhance the antitumor effect.

Intranasal Oxytocin Attenuates Cognitive Impairment, ß-Amyloid Burden and Tau Deposition in Female Rats with Alzheimer's Disease: Interplay of ERK1/2/GSK3ß/Caspase-3.

Oxytocin is a neuropeptide hormone that plays an important role in social bonding and behavior. Recent studies indicate that oxytocin could be involved in the regulation of neurological disorders. However, its role in modulating cognition in Alzheimer's disease (AD) has never been explored. Hence, the present study aims to investigate the potential of chronic intranasal oxytocin in halting memory impairment & AD pathology in aluminum chloride-induced AD in female rats. Morris water maze was used to assess cognitive dysfunction in two-time points throughout the treatment period. In addition, neuroprotective effects of oxytocin were examined by assessing hippocampal acetylcholinesterase activity, ß-amyloid 1-42 protein, and Tau levels. In addition, ERK1/2, GSK3ß, and caspase-3 levels were assessed as chief neurobiochemical mediators in AD. Hippocampi histopathological changes were also evaluated. These findings were compared to the standard drug galantamine alone and combined with oxytocin. Results showed that oxytocin restored cognitive functions and improved animals' behavior in the Morris test. This was accompanied by a significant decline in acetylcholinesterase activity, 1-42 ß-amyloid and Tau proteins levels. Hippocampal ERK1/2 and GSK3ß were also reduced, exceeding galantamine effects, thus attenuating AD pathological hallmarks formation. Determination of caspase-3 revealed low cytoplasmic positivity, indicating the ceasing of neuronal death. Histopathological examination confirmed these findings, showing restored hippocampal cells structure. Combined galantamine and oxytocin treatment showed even better biochemical and histopathological profiles. It can be thus concluded that oxytocin possesses promising neuroprotective potential in AD mediated via restoring cognition and suppressing ß-amyloid, Tau accumulation, and neuronal death.

Neuroinflammation and Behavioral Deficit in Rotenone-Induced Neurotoxicity in Rats and the Possible Effects of Butanolic Extract of Centaurea africana.

BACKGROUND: Many studies have used rotenone (ROT) to create an experimental animal model of Parkinson's disease (PD) because of its ability to induce similar behavioral and motor deficits. PD is the most common age-related motoric neurodegenerative disorder. Neuroinflammation and apoptosis play an important role in the pathogenesis of this disease. OBJECTIVE: This study investigated the effect of butanolic (n-BuOH) extract of Centaurea africana (200 mg/kg, 16 days) on a ROT-induced neurotoxicity model in male Wistar albino rats. METHODS: Estimation of Tumor Necrosis Factor (TNF-α) and Nitric Oxide (NO) levels along with the myeloperoxidase (MPO) activity in brains was carried out in order to evaluate neuro-inflammation. Oxidative stress, Caspase 3 activity (apoptosis), and behavioral alterations were also evaluated. RESULTS: In behavior assessment, using Ludolph Movement Analysis Scale, all ROT treated animals showed a decreased locomotor activity. The mitochondrial dysfunction induced by ROT was expressed by a decreased activity of complex I of the mitochondrial respiratory chain and increased lipid peroxidation and caspase 3. Co-treatment with the n-BuOH extract significantly restored the activity of complex I (65.41 %) compared to treatment with ROT alone. The n-BuOH extract also reduced the neuroinflammation in rat brains by reducing MPO activity (75.12 %), NO levels (77.43 %), and TNF-α (71.48 %) compared to the group treated with ROT. CONCLUSION: The obtained results indicated that C. africana n-BuOH extract exhibited a protective effect in rats.

pH-responsive aminolipid nanocarriers for antimicrobial peptide delivery.

HYPOTHESIS: pH-responsive aminolipid self-assemblies are promising platforms for the targeted delivery of antimicrobial peptides (AMPs), with the potential to improve their therapeutic efficiency and physico-chemical stability. EXPERIMENTS: pH-sensitive nanocarriers based on dispersed self-assemblies of 1,2-dioleoyl-3-dimethylammonium-propane (DODAP) with the human cathelicidin LL-37 in excess water were characterized at different pH values using small-angle X-ray scattering, cryogenic transmission electron microscopy, and dynamic light scattering. Fluorescence and electrophoretic mobility measurements were used to probe the encapsulation efficiency of LL-37 and the nanocarriers' surface potential. FINDINGS: Upon decreasing pH in the DODAP/water systems, normal oil-in-water emulsions at pH ≥ 5.0 transitioned to emulsions encapsulating inverse hexagonal and cubic structures at pH between 4.5 and 4.0, and mostly positively-charged vesicles at pH < 4.0. These colloidal transformations are driven by the protonation of DODAP upon pH decrease. The larger lipid-water interfacial area provided by the DODAP self-assemblies at pH ≤ 4.5 allowed for an adequate encapsulation efficiency of LL-37, favouring the formation of vesicles in a concentration-dependent manner. Contrary, LL-37 was found to dissociate from the emulsion droplets at pH 6.0. The knowledge on the pH-triggered self-assembly of LL-37 and DODAP, combined with the results on peptide release from the structures contribute to the fundamental understanding of lipid/peptide self-assembly. The results can guide the rational design of future pH-responsive AMP delivery systems.

Relation of asymmetric dimethylarginine with pulmonary morbidities in neonatal respiratory distress syndrome.

BACKGROUND: Asymmetric Dimethyl Arginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS) is important in different diseases characterized by decreased nitric oxide (NO) availability. We aimed to assess the serum ADMA level in preterm infants suffering from respiratory distress syndrome (RDS) and its relationship with pulmonary outcomes. METHODS: This prospective study included 50 preterm neonates suffering from RDS aging≤32 weeks and weighing≤1500  gm. Serum ADMA levels were estimated in the 1st and 28th day of life by ELISA, and its correlation with surfactant requirement, duration of ventilation, and development of BPD was assessed. RESULTS: Fifty preterm infants with RDS were included, 30 infants were treated with surfactant within 12 hours after birth, the 1stday ADMA level was higher significantly in infants who required surfactant treatment than infants without surfactant treatment, At 36 weeks postmenstrual age, 16 infants were diagnosed with BPD, the 28th day ADMA level was significantly higher in infants with BPD than others without BPD. 1st-day ADMA level was significantly correlated with days on mechanical ventilation but there were no significant correlations between 1st day ADMA and days on CPAP and days on supplemental O2. CONCLUSION: Elevated serum ADMA level in preterm neonates with RDS estimated in the 1st and 28th day of life is a good predictor for pulmonary morbidities such as surfactant requirement, duration of mechanical ventilation, and development of BPD.

Effects of ecofriendly synthesized calcium nanoparticles with biocompatible Sargassum latifolium algae extract supplementation on egg quality and scanning electron microscopy images of the eggshell of aged laying hens.

In the present study, 200 Brown commercial egg-type layers (60 wk old) were used to study the effects of different levels of ecofriendly synthesis of calcium (Ca) nanoparticles (0.0, 0.50, 1.0, and 1.5 g/kg diet) with biocompatible Sargassum latifolium algae extract (SL-CaNps) on exterior egg quality traits, electronic microscopic view of eggshells, Ca and phosphorus (P) retention, serum Ca and P concentrations, and the histology of the uterus. Hens fed with dietary SL-CaNps powder had higher egg weight and shell weight % values than those of the control group. All SL-CaNps treatment groups had the greatest values of shell weight per unit surface area and shell thickness. Dietary supplementation of SL-CaNps at graded levels up to 1.5 g/kg diet had higher serum Ca and inorganic P levels than that of the control. Laying hens fed with SL-CaNps-added diets had beneficial effects on shell ultrastructure in terms of well-developed palisade and mammillary layers. The numbers of apical cells along the branched tubular gland were greater in SL-CaNps-treated groups than those of control. Conclusively, supplementing SL-CaNps powder up to 1.5 g/kg to the diet of laying hens improved eggshell thickness, shell weight% and shell weight per unit surface and has no adverse effect on their eggshell quality or electronic microscopic view of their eggshell.

Mac-2 binding protein glycan isomer as noninvasive tool to assess liver fibrosis in children with chronic liver disease.

AIM: This study is aimed to measure the value of serum Mac-2 binding protein glycan isomer (M2BPGI) in children with chronic liver diseases in comparison with liver biopsy and serum biomarkers. METHODS: Comparative cross-sectional study included 100 children with chronic liver diseases and 50 healthy age/sex-matched control group. All subjects were evaluated via medical history, clinical, radiological and laboratory examinations. Liver biopsy was performed for studied patients and serum M2BPGI level was measured by Enzyme Linked Immune Sorbent Assay (ELISA) in all studied subjects. RESULTS: Serum M2BPGI level increased more significantly in chronic liver disease patients (6.04 ± 2.72 ng/ml) than in healthy controls (1.12 ± 0.83 ng/ml) (P < 0.001). M2BPGI level was significantly elevated with progressive fibrosis (P < 0.001), and differed significantly between high and low Child-Pugh score, pediatric end-stage liver disease score and model for end-stage liver disease score score. Serum M2BPGI was correlated with serum biomarkers and degree of fibrosis in patients. CONCLUSION: M2BPGI could be used as one of noninvasive tools for detecting and staging of hepatic fibrosis in Egyptian children with chronic liver disease.

Antioxidant, Anti-Inflammatory and Cytotoxic Properties of Centaurea africana Lamk var. [Bonnet] M].

BACKGROUND: In Algerian traditional medicine, Centaurea species are well known in traditherapy. Centaurea africana has been used in folk medicine for the treatment of several inflammatory disorders. OBJECTIVE: This study aims to examine the antioxidant, anti-inflammatory and anti-proliferative potential of both n-Butanol (BECA) and ethyl acetate (EAECA) extracts of Centaurea africana. METHODS: The phytochemical analysis of both BECA and EAECA were explored and the antioxidant activities were investigated by measuring the DPPH° scavenging effect, the reducing power and the inhibition of lipid peroxidation (LPO) induced by by Fe2+/ ascorbic acid system. The antiinflammatory properties were determined by measuring the NO° scavenging effect and by using carrageenan-induced rat paw oedema. The antiproliferative activity was studied on HT29 (human colorectal adenocarcinoma), OV2008 (human ovarian cancer) and C6 (Rattus norvegicus brain glioma) cell lines using the Sulforhodamine B assay. RESULTS: The total polyphenol contents (TPC) of EAECA and BECA are recorded at 125.24±10.14 and 53.03±2.50 mgGAE/g extract, respectively. Both extracts revealed the antioxidant activity in a concentration-dependent manner; this effect is more pronounced with EAECA. The BECA exhibited a higher anti-inflammatory activity. This anti-inflammatory activity was reflected in a reduction of swelling of carrageenan-evoked edemas (48.45 %), inhibition of nitric oxide (84.7 %), effective decrease in myeloperoxidase activity (58.82 %) and malondialdehyde level (65.58 %). The cytotoxic effect of BECA was found to be more pronounced against C6 cell lines (IC50 value: 131.93 µg/mL) while the cytotoxic activity of EAECA was more effective against HT29 and OV2008 cell lines. CONCLUSION: The obtained results indicated that EAECA exhibited a high antioxidant activity, while BECA has significant anti-inflammatory activity. Both extracts showed cytotoxic effects against cancer cell lines at certain concentrations in a cell-specific manner.

Serum Neurotensin: An Objective Mirror to Acne-induced Quality of Life and Psychological Impairment.

BACKGROUND: Acne is a multifactorial disorder, and stress potentially plays a role in its pathogenesis. OBJECTIVES: We aimed to assess the serum levels of neurotensin in patients with acne vulgaris (AV) and investigate the relationship of these levels to quality of life (QoL), depression, anxiety, and stress. METHODS: The study included 60 patients with AV classified into mild (n=20), moderate (n=20), and severe (n=20) groups and 20 healthy, age-matched, sex-matched, and body mass index (BMI)-matched individuals in a control group. Patient QoL was assessed using the Dermatology Life Quality Index (DLQI). Each participant completed the Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS-10). Serum levels of neurotensin were measured with enzyme-linked immunosorbent assay (ELISA). RESULTS: Neurotensin levels and scores from the three questionnaires were significantly higher among the patients with AV than the control subjects. They were also significantly elevated in patients with post-acne scars and hyperpigmentation and in those with severe acne. CONCLUSION: It is well known that acne greatly impacts QoL and might be associated with depression, anxiety, and stress. Further, serum neurotensin could be a promising marker to objectively evaluate the psychosocial impact of AV.

Selective VEGFR-2 inhibitors: Synthesis of pyridine derivatives, cytotoxicity and apoptosis induction profiling.

VEGFR-2 is a key regulator in cancer angiogenesis. This research displays the design and synthesis of novel 3-cyano-6-naphthylpyridine scaffold-based derivatives as selective VEGFR-2 inhibitors and cytotoxic agents. In vitro percent kinase activity inhibition screening against a panel of 23 kinases at a single high dose (30 nM) affirmed that VEGFR-2 was selectively the most responsive to inhibition by the investigated chemotypes. IC50 values determination demonstrated kinase inhibitory activities of the test compounds at the sub-nanomolar level. In vitro testing of the new compounds against two prostate cancer cell lines namely PC3 and DU145 and two breast cancer cell lines namely MCF-7 and MDA-MB435 confirmed their potent cytotoxic activity with IC50s at the nanomolar level. The most active compound against MCF-7 viz.11d was subjected to an in vivo examination against a xenograft mouse model and was found effective. Studying the tissue mRNA expression levels of various cell cycle controlling biomolecules in 11d-treated MCF-7 cells demonstrated (i) upregulation of p53, p21 and p27, (ii) cleavage of PARP protein, (iii) activation of caspase-3, -8 and -9, (iv) downregulation of the anti-apoptotic protein Bcl, (v) upregulation of the pro-apoptotic protein Bax, and (vi) decreased expression of Cdks 2, 4, 6 and cyclin D1. Additionally, 11d affected a cell cycle arrest at the G1 phase in treated MCF-7 cells and an S phase arrest in MCF-7 p53 knockdown cells. Additionally, molecular docking was performed to predict how 11d might bind to its biological target VEGFR-2. Finally, in-silico ADME and drug-likeness profiling of these derivatives demonstrated favorable properties thereof.

Serum levels of brain-derived neurotrophic factor in patients with acne vulgaris.

BACKGROUND: Many dermatological diseases have a great impact on the psychological state of patients, like urticaria, psoriasis, atopic dermatitis, and acne vulgaris. Finding a "gold standard" biomarker for chronic stress in acne patients is challenging because of the complex etiology of the chronic stress and its variable manifestations. AIMS: The aim of this study was to evaluate the correlation between serum levels of BDNF and the presence and severity of acne vulgaris and to assess the relationship of this biomarker to both the degree of psychological stress and the quality of patients' lives (QoL). PATIENTS AND METHODS: Sixty patients with acne vulgaris were included, together with twenty apparently healthy, age-, and sex-matched individuals as a control group. Patients filled a Dermatology Life Quality Index (DLQI) questionnaire; both patients and controls filled a Hospital Anxiety and Depression scale (HADS) and perceived stress scale-10 (PSS) questionnaires. Serum levels of BDNF were measured for patients and controls using ELISA technique. RESULTS: Patients with acne had significantly lower levels of BDNF and significantly higher HADS and PSS-10 questionnaires scores. A significant negative correlation was found between serum levels of BDNF and PSS questionnaire scores. CONCLUSION: Patients with acne are at a high risk to develop chronic stress, anxiety, and depression. BDNF is a good predictor for assessment of chronic stress in such patients.