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Endothelin-1 (ET-1) is implicated in the development of atherosclerosis and mediates glycosaminoglycan (GAG) chain hyperelongation on proteoglycans. Our aim was to identify the ET-1-mediated signalling pathway involving NADPH oxidase (NOX), p38 MAP kinsae and Smad2 linker region phosphorylation (phospho-Smad2L) regulate GAG synthesising enzymes mRNA expression (C4ST-1 and ChSy1) involved in GAG chains hyperelongation in human vascular smooth muscle cells (VSMCs). Signalling intermediates were detected and quantified by Western blotting and the mRNA levels of GAG synthesising enzymes were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). ET-1 treatment of human VSMCs resulted in an increase in phospho-Smad2L level. The TGF-β receptor antagonist, SB431542 and the mixed ET

Few studies had been conducted on the phytochemical profile and the biological activities of Brachychiton rupestris. The antioxidant activity of 85% methanolic extract of B. rupestris leaves and its derived fractions was assessed using five different in-vitro assays which are DPPH• assay, phosphomolybdenum assay (TAC), hydroxyl radical (•OH) scavenging assay, nitric oxide radical (NO•) scavenging assay and permanganate reducing antioxidant capacity (PRAC). The total phenolic, flavonoid and flavonol contents were also determined for the different plant samples using Folin-Ciocalteu, aluminum chloride and aluminum chloride/ sodium acetate methods, respectively. In-vitro cytotoxic activity of the crude extract and its fractions against HepG2 cell line was also evaluated via SRB assay. The ethyl acetate fraction obtained from the aqueous methanolic extract of the plant leaves possessed the most potent antioxidant potential according to the different applied assays (DPPH• SC50 = 25.50±0.76 µg/mL, TAC= 311.98±1.19 mg AAE/g ext., •OH SA= 68.42±0.15%, NO• SA= 33.68±1.98% & PRAC = 62.88±0.27%). It also owed the highest amount of phenolics (TPC= 342.10±2.08 mg GAE/ g ext.) whose majority were flavonoids (TFC= 309.82±3.64 mg QE/ g ext.). A strong positive correlation was found between the total phenolic contents of various plant samples and their antioxidant activity. The butanol derived fraction exhibited the most potent cytotoxic activity (IC50 = 8.60 µg/mL). To the best of our knowledge, it is the first study reporting the antioxidant and the cytotoxic activities of B. rupestris leaves. The study revealed that the B. rupestris leaves could be a good source of natural antioxidants which may be applied in food and pharmaceutical industries. They could also be a new opportunity of discovering anti-mutagenic agents.

Background: Seroma is an abnormal collection of serous fluid in the dead space of post-mastectomy skin flaps and axilla or following breast-conserving surgery. Seroma is one of the most common early post-operative complications following surgery for breast cancer. Various studies report an incidence ranging from 10% to 85% following modified radical mastectomy (MRM) or axillary lymph node dissection (ALND). Objective: Evaluation of different modalities in the prevention of seroma formation post modified radical mastectomy. Patients and methods: This was a prospective comparative study carried out in the General Surgery Department, Faculty of Medicine, Aswan University, Aswan, Egypt. in the period between December 2017 and June 2018. Patients scheduled for modified radical mastectomy during the period of study were randomly divided into three groups, mastectomy flap fixation group (10 cases), ipsilateral shoulder immobilization group (10 cases) & (pre & post) operative tranexamic acid usage group (10 cases). Results: Hypertension, obesity, blood transfusion, and bloody field are at high risk of developing seroma after MRM; while DM, cancer stage, number of LN infiltrated and removed don’t affect on seroma formation after MRM. Flap fixation was found to be the best modality in the prevention of seroma formation with a low incidence in developed seroma and other complications. On the other hand, tranexamic acid usage pre- and post-operative found that no role in the prevention of seroma formation after MRM. Conclusion: The mastectomy flap fixation technique is a valuable procedure that significantly decreases the incidence of seroma formation, and reduces the duration and amount of drained fluid.

Cryptosporidium parvum (C. parvum) is a worldwide zoonotic protozoan parasite infects most mammalian hosts causing a major health problem. The present study investigated the efficacy of ginger (Zingiber officinale), ginseng (Panax ginseng) and sage (Salvia officinalis) methanolic extracts on the progression of cryptosporidiosis in the experimental mice.Forty five mice experimentally infected with C. parvum were treated with medicinal plants extracts (ginger, ginseng and sage) as compared to the reference drug, Nitazoxanide (NTZ). Mice fecal smears were examined daily for 4 weeks post infection (PI). The results interpreted by oocysts count and histological examination of mice intestinal mucosa.The obtained results recorded that there was a statistically significant reduction in oocyst shedding in high dose ginger, ginseng and NTZ treated groups till no oocysts were found at days 21 and 23 PI, respectively. The infected non-treated, NTZ and low dose of both, ginseng and sage treated mice groups returned to excrete oocysts at low levels at day 27 PI while the other animal groups’ feces were still negative for C. parvum oocysts. The histopathological examination showed that NTZ, high dose ginger and ginseng treated mice had more protective and curative effect on infected mice intestinal epithelium in comparison with other treatments used.In conclusion, these results proved the therapeutic efficacy of ginger, ginseng and sage medicinal plants against the C. parvum in experimentally infected mice, and that theginger extract had an obvious effect on infected mice than other treatments and such results could be adapted in similar infections in susceptible animals and man.

Transforming growth factor (TGF)-β signalling commences with the engagement of TGF-β ligand to cell surface TGF-β receptors (TGFBR) stimulating Smad2 carboxyl-terminal phosphorylation (phospho-Smad2C) and downstream biological responses. In several cell models, G protein-coupled receptors (GPCRs) transactivate the TGF-β receptors type-1 (TGFBR1) leading to phospho-Smad2C, however, we have recently published that in keratinocytes thrombin did not transactivate the TGFBR1. The bulk of TGFBRs reside in the cytosol and in response to protein kinase B (Akt phosphorylation) can translocate to the cell surface increasing the cell's responsiveness to TGF-β. In this study, we investigate the role of Akt in GPCR transactivation of the TGFBR1. We demonstrate that angiotensin II and thrombin do not phosphorylate Smad2C in human vascular smooth muscle cells and in keratinocytes respectively. We used Akt agonist, SC79 to sensitise the cells to Akt and observed that Ang II and thrombin phosphorylate Smad2C via Akt/AS160-dependent pathways. We show that SC79 rapidly translocates TGFBRs to the cell surface thus increasing the cell's response to the GPCR agonist. These findings highlight novel mechanistic insight for the role of Akt in GPCR transactivation of the TGFBR1.

Toll-like receptors (TLRs) recognise pathogen‑associated molecular patterns, which allow the detection of microbial infection by host cells. Bacterial-derived toxin lipopolysaccharide activates TLR4 and leads to the activation of the Smad2 transcription factor. The phosphorylation of the Smad2 transcription factor is the result of the activation of the transforming growth factor-β receptor 1 (TGFBR1). Therefore, we sought to investigate LPS via TLR4-mediated Smad2 carboxy terminal phosphorylation dependent on the transactivation of the TGFBR1. The in vitro model used human aortic vascular smooth muscle cells to assess the implications of TLR4 transactivation of the TGFBR1 in vascular pathophysiology. We show that LPS-mediated Smad2 carboxy terminal phosphorylation is inhibited in the presence of TGFBR1 inhibitor, SB431542. Treatment with MyD88 and TRIF pathway antagonists does not affect LPS-mediated phosphorylation of Smad2 carboxy terminal; however, LPS-mediated Smad2 phosphorylation was inhibited in the presence of MMP inhibitor, GM6001, and unaffected in the presence of ROCK inhibitor Y27632 or ROS/NOX inhibitor DPI. LPS via transactivation of the TGFBR1 stimulates PAI-1 mRNA expression. TLRs are first in line to respond to exogenous invading substances and endogenous molecules; our findings characterise a novel signalling pathway in the context of cell biology. Identifying TLR transactivation of the TGFBR1 may provide future insight into the detrimental implications of pathogens in pathophysiology.

G protein-coupled receptor (GPCR) agonist endothelin-1 (ET-1) through transactivation of the transforming growth factor (TGF) β receptor (TGFBR1) stimulates glycosaminoglycan (GAG) elongation on proteoglycans. GPCR agonists thrombin and lysophosphatidic acid (LPA) via respective receptors transactivate the TGFBR1 via Rho/ROCK dependent pathways however mechanistic insight for ET-1 transactivation of the TGFBR1 remains unknown. NADPH oxidase (NOX) generates reactive oxygen species (ROS) and is a signalling entity implicated in the pathogenesis of many diseases including atherosclerosis. If implicated in this pathway, NOX/ROS would be a potential therapeutic target. In this study, we investigated the involvement of NOX in ET-1/ET receptor-mediated transactivation of TGFBR1 to stimulate mRNA expression of GAG chain synthesizing enzymes chondroitin 4-O-sulfotransferase 1 (C4ST-1) and chondroitin sulfate synthase 1 (ChSy-1). The invitro model used vascular smooth muscle cells that were treated with pharmacological antagonists in the presence and absence of ET-1 or TGF-β. Proteins and phosphoproteins isolated from treated cells were quantified by western blotting and quantitative real-time PCR was used to assess mRNA expression of GAG synthesizing enzymes. In the presence of diphenyliodonium (DPI) (NOX inhibitor), ET-1 stimulated phospho-Smad2C levels were inhibited. ET-1 mediated mRNA expression of GAG synthesizing enzymes C4ST-1 and ChSy-1 was also blocked by TGBFR1 antagonists, SB431542, broad spectrum ET receptor antagonist bosentan, DPI and ROS scavenger N-acetyl-L-cysteine. This work shows that NOX and ROS play an important role in ET-1 mediated transactivation of the TGFBR1 and downstream gene targets associated with GAG chain elongation. As ROS is involved in GPCR to protein tyrosine kinase receptor transactivation, the NOX/ROS axis presents as the first common biochemical target in all GPCR to kinase receptor transactivation signalling.

Purpose. To determine the effect of laser puncture on arterial blood gases for mechanically ventilated patients. Design. Single blind randomized controlled trial. Methods. Forty patients participated in the study, they were recruited from the critical care unit in Cairo University hospitals Kasr el Einy hospitals, Cairo, Egypt; their ages ranged from 50-70 years old, through a period of 33 months (from May 2016 to February 2019). Confidentiality was assured. They were assigned randomly into two groups equally in number; 20 patients each: Group (A) patients received both Laser puncture with an output of 5–20 mW, wavelength of 905 nm and frequency of 5000 Hz. laser probe stimulated on each point for 1 min, once daily for 10 days and routine intensive care physical therapy program twice per day. Group (B) patients received a routine intensive care physical therapy program (modified postural drainage, airway clearance techniques, lung expansion techniques and circulatory exercises for lower limbs) twice per day for 10 days. Pre and post Blood gas analysis for assessment of arterial blood gases (PaO2, PaCO2, O2%, and PaO2/FiO2) for all patients. Results. This study revealed improvement in PaO2/FiO2 in group (A), non significant change in PaO2, PaCO2 level, O2% after 10 days in both groups. Conclusion. Laser puncture had a significant effect in PaO2/FiO2, so this study supports the value of laser puncture on arterial blood gases for mechanically ventilated patients.

The present study describes air-drying, which is an alternative method to study and teach gross anatomy to undergraduate and postgraduate students. In order to preserve the hollow organs of different animals, an air-drying pump (compressor) was used; then, the preserved specimens were expanded through the injection of foam into their lumen followed by the application of varnish on their external surface to protect them from insect damage. This method of preservation is suitable for developing countries because it is cheap to prepare, simple to perform, and can be performed at room temperature (37°-40°C) without special equipment. The produced specimens have many advantages: their normal anatomical form remains durable, very light in weight, non- toxic regarding handling, and resistant to improper handling and deterioration by fungi or bacteria, with all structures very clear. These preserved specimens last for many years without any changes.

Background: In recent years, plant extracts are considered as an important source of many drug formulations for treatment of human beings from infection diseases. The objective of this study was to evaluate the antimicrobial activity of Salix mucronata leaves extracts and isolate their bioactive phytochemicals. Methods: The dry powder of Salix mucronata was extracted with different aqueous methanol concentrations. The 85% methanolic extract was further fractionated using different organic solvents. The antimicrobial activity of different extracts and fractions was evaluated. The most bioactive fractions were submitted for chromatographic isolation and structure elucidation of their phytochemicals using chromatographic and spectroscopic methods. Results: The ethyl acetate and the butanolic fractions derived from 85% MeOH extract gave a high antimicrobial activity with inhibition zones ranging between 10 mm and 26 mm and minimum inhibitory concentration (MIC) value of 8 mg/mL. While the butanolic fraction showed zones of inhibition ranging between 10 mm and 25 mm with MIC 8 mg/mL. Six compounds were isolated from ethyl acetate fraction and their structures were elucidated as; apigenin (1), quercetin (2), quercetrin (3), rhamnazin -3-O-β-D-glucopyranoside (4), Chrysoeriol-7-O-β-D-glucuronoid- 6ʺ -methyl ester (5), and tremuloidin (6). Also, five compounds were isolated from the butanolic fraction and their structures were elucidated as; kaempferol (7), luteolin (8), luteolin-3ʹ - methoxy-4ʹ - O-β-D- glucopyranoside (9), isorhamnetin -3-O-β -D-glucopyranoside (10) and salicin (11). Conclusion: The results of the present study showed that the ethyl acetate and the butanolic fractions contain high flavonoids and salicinoids compounds which may attribute to their potential as antimicrobial agents.

Orodispersible sublingual films (OSFs) composed of hydrophilic polymers were loaded with poloxamer-188 and d-&alpha, tocopheryl polyethylene glycol succinate (TPGS-1000) mixed micelles to improve the oral bioavailability of a poorly soluble drug, ebastine (EBT). Mixed micelles formed by thin-film hydration method were incorporated into orodispersible sublingual film, consisting of HPMC and glycerol, using solvent casting technique. The mixed micelles and films were thoroughly evaluated for physicochemical characterization (size, polydispersity index, zeta potential, entrapment efficiency, thickness, weight, surface pH studies, disintegration time, swelling indices, mechanical properties, FTIR, PXRD, DSC, SEM, AFM, in vitro drug release, in vivo bioavailability, and toxicological studies). The results showed that the average particle size of mixed micelles was 73 nm. The mean zeta potential and PDI of the optimal mixed micelles formulation were &minus, 26 mV and 0.16, respectively. Furthermore, the maximum entrapment efficiency 82% was attained. The film&rsquo, s disintegration time was in the range of 28 to 102 s in aqueous media. The integrity of micelles was not affected upon incorporation in films. Importantly, the micelles-loaded films revealed rapid absorption, high permeability, and increased bioavailability of EBT as compared to the pure drug. The existence of ebastine loaded mixed micelles in the films enhanced the bioavailability about 2.18 folds as compared to pure drug. Further, the results evidently established in-vitro and in-vivo performance of bioavailability enhancement, biocompatibility, and good safety profile of micelles-loaded orodispersible EBT films. Finally, it was concluded that film loaded with poloxamer-188/TPGS-1000 mixed micelles could be an effective carrier system for enhancing the bioavailability of ebastine.

Malaria is still a severe health problem especially in developing countries which occur and young children are the most affected. The present study was designed to compare the insecticidal potential of Lantana camara leaves extract alone and its synthesized nanoparticles against Anopheles multicolor.Copper nanoparticles CuNPs were synthesized by green bio-reduction method using aqueous extract of leaves of Lantana camara plant. The CuNPs formation was confirmed by ultraviolet visible spectrophotometer (UV-VIS) and Transitional Electron Microscopy (TEM). The application of L. camara extract and its synthesized CuNPs on different stages of A. multicolor were adopted.The biosynthesized CuNPs were spherical with the average sizes of 11-17.8 nm. The highest insecticidal effect (100% of larval mortality) achieved at high dose (140 ppm) of L. camara leaves extract alone comparing with that occur at low dose (20 ppm) of CuNPs synthesized L. camara leaves. The LC50 and LC90 for the 4 instar larvae were 63.5 and 119.9 ppm for plant extract alone compared to 12.6 and 18.4 ppm for CuNPs preparation.So, this study proved that CuNPs preparation of L. camara leaves is highly efficient compared to the plant extract alone and more economic as less quantities were used. Also, awareness against invasion of Anopheles mosquito vectors with effective preventive measures to protect from malaria infection.