Evaluation of the effectiveness of natural extract as a substituent for synthetic preservatives and antioxidants in pharmaceutical preparations.

Background: Despite the fact that synthetic preservatives and antioxidants have strong antibacterial and antioxidant activity, they are frequently associated with negative health consequences. Currently, there is an increasing interest in pharmaceutical products that are excellent in quality and free of synthetic preservatives. Methods: As a result, the purpose of this research is to assess the antibacterial and antioxidant activities of olive leaf extract, oleuropein, and thymol in various pharmaceutical products. Furthermore, the efficacy of these natural extracts to substitute synthetic preservatives (methyl-propylparaben and benzalkonium chloride) and antioxidants (butylhydroxytoluene) will be investigated. Results: The results revealed that oleuropein, olive leaf extract, and a blend of oleuropein and thyme oil may be utilized as preservatives at concentrations of (0.6 % w/v), (0.4 % w/v), and (0.4 %/0.1 % v/v), respectively. The results demonstrated that thyme oil and oleuropein have synergistic efficacy against the studied microorganisms. By assessing antibacterial activity, and physical properties, the results demonstrated that pharmaceutical formulations containing natural preservatives were stable and effective for three months under accelerated settings (40 °C/75 % RH). Conclusion: Natural compounds such as oleuropein, olive leaf extract, and thyme oil have shown antibacterial effectiveness equivalent to synthetic preservatives in selected pharmaceutical products. Furthermore, there was synergy in antimicrobial activity between thyme oil and oleuropein and this facilitates the use of these compounds at different levels.

Multi-biological activity assessment and phytochemical characterization of an aqueous extract of the Cymbopogon citratus grown in Palestine.

BACKGROUND: Plants have historically been a rich source of medicinal compounds, with many modern pharmaceuticals derived from botanical origins. In contemporary healthcare, there is a resurgence in utilizing botanical substances as recognized medicinal agents. This study delved into understanding the phytochemical makeup and the multifaceted biological activities of an aqueous extract from Cymbopogon citratus (C. citratus). The investigated activities were its effect on AMPA receptors, antioxidant capacity, anti-lipase, anti-α-amylase actions, cytotoxicity, and antimicrobial properties. METHODS: The extract of C. citratus received a comprehensive investigation, which included the study of its phytochemical composition, assessment of its antioxidant and anti-lipase properties, evaluation of its capacity to inhibit α-amylase, analysis of its impact on cell viability, and assessment of its antimicrobial activity. The approaches are used to clarify the complex physiological and biochemical characteristics. RESULTS: The results were compelling; receptor kinetics had a marked impact, notably on the GluA2 subunit. Regarding its medicinal potential, the extract demonstrated potent antioxidant and anti-diabetic activities with IC50 values of 15.13 and 101.14 µg/mL, respectively. Additionally, it displayed significant inhibitory effects on the lipase enzyme and showed cytotoxicity against the Hep3B cancer cell line, with IC50 values of 144.35 and 148.37 µg/mL. In contrast, its effects on the normal LX-2 cell line were minimal, indicating selectivity. CONCLUSION: The aqueous extract of C. citratus shows promising therapeutic properties. The findings advocate for further research into its compounds for potential isolation, purification, and in-depth pharmacological studies, especially in areas like nervous system disorders, diabetes, obesity, and combating oxidative stress.

Effects of Waterpipe Tobacco Smoking on the Spirometric Profile of University Students in Palestine: A Cross-Sectional Study.

Background: Waterpipe smoking in young individuals is increasing with limited studies addressing its respiratory health effects. The aim of the study was to determine the effect of waterpipe smoking on young adults' lung functions. Spirometric parameters were compared between waterpipe smokers and nonsmokers. Methods: A comparative cross-sectional study of university students, including males and females, was conducted. An interviewer-administered questionnaire was used to record students' characteristics. The spirometry test was performed to assess students' lung functions; we recorded the forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, peak expiratory flow (PEF), and forced expiratory flow between 25 and 75% of FVC (FEF25-75%). Results: A total of 300 apparently healthy students (150 waterpipe smokers and 150 nonsmokers) were included in the study. Waterpipe smokers showed significantly lower values in FEV1, FEV1/FVC ratio, PEF, and FEF25-75% compared to the nonsmoker group (P < 0.05 to P < 0.001). The subgroup analysis on female students (50 WP smokers and 50 nonsmokers) showed a significant decrease in FEV1/FVC ratio, PEF, and FEF25-75% parameters (P < 0.001). Conclusion: Waterpipe smoking is associated with reduced spirometric parameters in healthy young adults with relatively limited smoking years.

TGF-ß Signaling Regulates Development of Midbrain Dopaminergic and Hindbrain Serotonergic Neuron Subgroups.

Molecular and functional diversity within midbrain dopaminergic (mDA) and hindbrain serotonergic (5-HT) neurons has emerged as a relevant feature that could underlie selective vulnerability of neurons in clinical disorders. We have investigated the role of transforming growth factor beta (TGF-ß) during development of mDA and 5-HT subgroups. We have generated TßRIIflox/flox::En1cre/+ mice where type II TGF-ß receptor is conditionally deleted from engrailed 1-expressing cells and have investigated the hindbrain serotonergic system of these mice together with Tgf-ß2-/- mice. The results show a significant decrease in the number of 5-HT neurons in TGF-ß2-deficient mice at embryonic day (E) 12 and a selective significant decrease in the hindbrain paramedian raphe 5-HT neurons at E18, compared to wild type. Moreover, conditional deletion of TGF-ß signaling from midbrain and rhombomere 1 leads to inactive TGF-ß signaling in cre-expressing cells, impaired development of mouse mDA neuron subgroups and of dorsal raphe 5-HT neuron subgroups in a temporal manner. These results highlight a selective growth factor dependency of individual rostral hindbrain serotonergic subpopulations, emphasize the impact of TGF-ß signaling during development of mDA and 5-HT subgroups, and suggest TGF-ßs as potent candidates to establish diversity within the hindbrain serotonergic system. Thus, the data contribute to a better understanding of development and degeneration of mDA neurons and 5-HT-associated clinical disorders.

TGFß-facilitated optic fissure fusion and the role of bone morphogenetic protein antagonism.

The optic fissure is a transient gap in the developing vertebrate eye, which must be closed as development proceeds. A persisting optic fissure, coloboma, is a major cause for blindness in children. Although many genes have been linked to coloboma, the process of optic fissure fusion is still little appreciated, especially on a molecular level. We identified a coloboma in mice with a targeted inactivation of transforming growth factor ß2 (TGFß2). Notably, here the optic fissure margins must have touched, however failed to fuse. Transcriptomic analyses indicated an effect on remodelling of the extracellular matrix (ECM) as an underlying mechanism. TGFß signalling is well known for its effect on ECM remodelling, but it is at the same time often inhibited by bone morphogenetic protein (BMP) signalling. Notably, we also identified two BMP antagonists among the downregulated genes. For further functional analyses we made use of zebrafish, in which we found TGFß ligands expressed in the developing eye, and the ligand binding receptor in the optic fissure margins where we also found active TGFß signalling and, notably, also gremlin 2b (grem2b) and follistatin a (fsta), homologues of the regulated BMP antagonists. We hypothesized that TGFß is locally inducing expression of BMP antagonists within the margins to relieve the inhibition from its regulatory capacity regarding ECM remodelling. We tested our hypothesis and found that induced BMP expression is sufficient to inhibit optic fissure fusion, resulting in coloboma. Our findings can likely be applied also to other fusion processes, especially when TGFß signalling or BMP antagonism is involved, as in fusion processes during orofacial development.

The effect of inhalation of Citrus sinensis flowers and Mentha spicata leave essential oils on lung function and exercise performance: a quasi-experimental uncontrolled before-and-after study.

BACKGROUND: Recently, there has been an increased interest in the effects of essential oils on athletic performances and other physiological effects. This study aimed to assess the effects of Citrus sinensis flower and Mentha spicata leaves essential oils inhalation in two different groups of athlete male students on their exercise performance and lung function. METHODS: Twenty physical education students volunteered to participate in the study. The subjects were randomly assigned into two groups: Mentha spicata and Citrus sinensis (ten participants each). One group was nebulized by Citrus sinensis flower oil and the other by Mentha spicata leaves oil in a concentration of (0.02 ml/kg of body mass) which was mixed with 2 ml of normal saline for 5 min before a 1500 m running tests. Lung function tests were measured using a spirometer for each student pre and post nebulization giving the same running distance pre and post oils inhalation. RESULTS: A lung function tests showed an improvement on the lung status for the students after inhaling of the oils. Interestingly, there was a significant increase in Forced Expiratory Volume in the first second and Forced Vital Capacity after inhalation for the both oils. Moreover significant reductions in the means of the running time were observed among these two groups. The normal spirometry results were 50 %, while after inhalation with M. spicata oil the ratio were 60 %. CONCLUSION: Our findings support the effectiveness of M. spicata and C. sinensis essential oils on the exercise performance and respiratory function parameters. However, our conclusion and generalisability of our results should be interpreted with caution due to small sample size and lack of control groups, randomization or masking. We recommend further investigations to explain the mechanism of actions for these two essential oils on exercise performance and respiratory parameters. TRIAL REGISTRATION: ISRCTN10133422, Registered: May 3, 2016.

Assessing worldwide research activity on probiotics in pediatrics using Scopus database: 1994-2014.

BACKGROUND: A wide variety of probiotic products has been introduced into the market in the past decade. Research trends and activity on probiotics help understand how these products were evolved and their potential future role in medicine. The objective of this study was to assess the research activity on probiotics in pediatrics using bibliometric indicators and network visualization. METHODS: Original and review articles on probiotics in pediatrics published worldwide were retrieved from SciVerse, Scopus (1994-2014) and analyzed. VOSviewer was used for network visualization. RESULTS: The total number of documents published on probiotics in pediatrics was 2817. Research activity on probiotics in pediatrics showed approximately 90- fold increase during the study period. Approximately 22 % of published articles originated from USA and has the greatest share, however, Finland ranked first when data were stratified by population or income. The most productive institution in this field was Turku University in Finland with 82 (2.91 %) articles. Half of the prolific authors were also from Finland. Most of the published research activity appeared in Journal of Pediatric Gastroenterology and Nutrition. Most frequently encountered title terms include nutrition, infant formula, necrotizing enetrocolitis, allergy, and diarrhea. The total number of citations for the retreived documents documents was 70991, and the average citation per article was 25.20. CONCLUSIONS: Interest in probiotic research and its potential benefits in pediatric ailments is relatively recent but significantly increasing. Bibliometric analysis can be used as an indicator of the importance and growth of probiotic use in pediatrics.

Intravenous Lipid Emulsion as an Antidote for the Treatment of Acute Poisoning: A Bibliometric Analysis of Human and Animal Studies.

In recent years, there has been increasing interest in the role of intravenous lipid formulations as potential antidotes in patients with severe cardiotoxicity caused by drug toxicity. The aim of this study was to conduct a comprehensive bibliometric analysis of all human and animal studies featuring lipid emulsion as an antidote for the treatment of acute poisoning. The Scopus database search was performed on 5 February 2016 to analyse the research output related to intravenous lipid emulsion as an antidote for the treatment of acute poisoning. Research indicators used for analysis included total number of articles, date (year) of publication, total citations, value of the h-index, document types, countries of publication, journal names, collaboration patterns and institutions. A total of 594 articles were retrieved from Scopus database for the period of 1955-2015. The percentage share of global intravenous lipid emulsion research output showed that research output was 85.86% in 2006-2015 with yearly average growth in this field of 51 articles per year. The USA, United Kingdom (UK), France, Canada, New Zealand, Germany, Australia, China, Turkey and Japan accounted for 449 (75.6%) of all the publications. The total number of citations for all documents was 9,333, with an average of 15.7 citations per document. The h-index of the retrieved documents for lipid emulsion research as antidote for the treatment of acute poisoning was 49. The USA and the UK achieved the highest h-indices, 34 and 14, respectively. New Zealand produced the greatest number of documents with international collaboration (51.9%) followed by Australia (50%) and Canada (41.4%) out of the total number of publications for each country. In summary, we found an increase in the number of publications in the field of lipid emulsion after 2006. The results of this study demonstrate that the majority of publications in the field of lipid emulsion were published by high-income countries. Researchers from institutions in the USA led scientific production on lipid emulsion research. There is an obvious need to promote a deeper engagement through international collaborative research projects and funding mechanisms.

Localization of reelin signaling pathway components in murine midbrain and striatum.

We investigated the distribution patterns of the extracellular matrix protein Reelin and of crucial Reelin signaling components in murine midbrain and striatum. The cellular distribution of the Reelin receptors VLDLr and ApoER2, the intracellular downstream mediator Dab1, and the alternative Reelin receptor APP were analyzed at embryonic day 16, at postnatal stage 15 (P15), and in 3-month-old mice. Reelin was expressed intracellularly and extracellularly in midbrain mesencephalic dopaminergic (mDA) neurons of newborns. In the striatum, Calbindin D-28k(+) neurons exhibited Reelin intracellularly at E16 and extracellularly at P15 and 3 months. ApoER2 and VLDLr were expressed in mDA neurons at E16 and P15 and in oligodendrocytes at 3 months, whereas Dab1 and APP immunoreactivity was observed in mDA at all stages analyzed. In the striatum, Calbindin D-28k(+)/GAD67(+) inhibitory neurons expressed VLDLr, ApoER2, and Dab1 at P15, but only Dab1 at E16 and 3 months. APP was always expressed in mouse striatum in which it colocalized with Calbindin D-28k. Our data underline the importance of Reelin signalling during embryonic development and early postnatal maturation of the mesostriatal and mesocorticolimbic system, and suggest that the striatum and not the midbrain is the primary source of Reelin for midbrain neurons. The loss of ApoER2 and VLDLr expression in the mature midbrain and striatum implies that Reelin functions are restricted to migratory events and early postnatal maturation and are dispensable for the maintenance of dopaminergic neurons.

In vivo requirement of TGF-beta/GDNF cooperativity in mouse development: focus on the neurotrophic hypothesis.

Neurotrophic factors are well-recognized extracellular signaling molecules that regulate neuron development including neurite growth, survival and maturation of neuronal phenotypes in the central and peripheral nervous system. Previous studies have suggested that TGF-beta plays a key role in the regulation of neuron survival and death and potentiates the neurotrophic activity of several neurotrophic factors, most strikingly of GDNF. To test the physiological relevance of this finding, TGF-beta2/GDNF double mutant (d-ko) mice were generated. Double mutant mice die at birth like single mutants due to kidney agenesis (GDNF-/-) and congential cyanosis (TGF-beta2-/-), respectively. To test for the in vivo relevance of TGF-beta2/GDNF cooperativity to regulate neuron survival, mesencephalic dopaminergic neurons, lumbar motoneurons, as well as neurons of the lumbar dorsal root ganglion and the superior cervical ganglion were investigated. No loss of mesencephalic dopaminergic neurons was observed in double mutant mice at E18.5. A partial reduction in neuron numbers was observed in lumbar motoneurons, sensory and sympathetic neurons in GDNF single mutants, which was further reduced in TGF-beta2/GDNF double mutant mice at E18.5. However, TGF-beta2 single mutant mice showed no loss of neurons. These data point towards a cooperative role of TGF-beta2 and GDNF with regard to promotion of survival within the peripheral motor and sensory systems investigated.

Transforming growth factor beta cooperates with persephin for dopaminergic phenotype induction.

The aim of the present study was to investigate the putative cooperative effects of transforming growth factor beta (TGF-beta) and glial cell line-derived neurotrophic factor (GDNF) family ligands in the differentiation of midbrain progenitors toward a dopaminergic phenotype. Therefore, a mouse midbrain embryonic day (E) 12 neurospheres culture was used as an experimental model. We show that neurturin and persephin (PSPN), but not GDNF, are capable of transient induction of dopaminergic neurons in vitro. This process, however, requires the presence of endogenous TGF-beta. In contrast, after 8 days in vitro GDNF rescued the TGF-beta neutralization-dependent loss of the TH-positive cells. In vivo, at E14.5, no apparent phenotype concerning dopaminergic neurons was observed in Tgf-beta2(-/-)/gdnf(-/-) double mutant mice. In vitro, combined TGF-beta/PSPN treatment achieved a yield of approximately 20% TH-positive cells that were less vulnerable against 1-methyl-4-phenyl pyridinium ion toxicity. The underlying TGF-beta/PSPN differentiation signaling is receptor-mediated, involving p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways. These results indicate that phenotype induction and survival of fully differentiated neurons are accomplished through distinct pathways and individual factor requirement. TGF-beta is required for the induction of dopaminergic neurons, whereas GDNF is required for regulating and/or maintaining a differentiated neuronal phenotype. Moreover, this study suggests that the combination of TGF-beta with PSPN is a potent inductive cocktail for the generation of dopaminergic neurons that should be considered in tissue engineering and cell replacement therapies for Parkinson's disease.

Isoform-specific role of transforming growth factor-beta2 in the regulation of proliferation and differentiation of murine adrenal chromaffin cells in vivo.

Chromaffin cells, the neuroendocrine cells of the adrenal medulla, play an important role in molecular, cellular, and developmental neurobiology. Unlike the closely related sympathetic neurons, chromaffin cells are able to proliferate throughout their whole life span. Proliferation of chromaffin cells in vivo is thought to be regulated by the interaction of neurogenic and hormonal signals. Previous studies have shown that chromaffin cells synthesize and release transforming growth factor-betas (TGF-betas). In the present study, effects of TGF-betas on proliferation and differentiation of chromaffin cells in mouse adrenal chromaffin cells were investigated in a genetic mouse model. We observed a significant increase in the total number of tyrosine hydroxylase-positive (TH(+)) cells in Tgfbeta2(-/-) knockout mouse embryos at embryonic day (E) 18.5 compared with wild-type animals (Tgfbeta2(+/+)), but no changes in the number of TH(+) cells were observed in Tgfbeta3(-/-) mouse mutants. At E15.5, but not at E18.5, there was a marked increase in the number of proliferative cell nuclear antigen-positive chromaffin cells in Tgfbeta2(-/-) knockout embryos compared with the wild-type group. On the other hand, there was a clear decrease in the ratio of total number of phenylethanolamine-N-methyltransferase-positive cells to the total TH(+) in Tgfbeta2(-/-) mice embryos at E18.5 compared with wild-type animals. This is the first documentation of the physiological significance of the TGF-beta2, an isoform that has been suggested to play a role in the regulation of chromaffin cells proliferation and differentiation based on in vitro experiments.