Recently Published Documents
Early IGF-1 Gene Therapy Prevented Oxidative Stress and Cognitive Deficits Induced by Traumatic Brain Injury
Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality in adults under 40 years old. Once primary injury occurs after TBI, neuroinflammation and oxidative stress (OS) are triggered, contributing to the development of many TBI-induced neurological deficits, and reducing the probability of critical trauma patients´ survival. Regardless the research investment on the development of anti-inflammatory and neuroprotective treatments, most pre-clinical studies have failed to report significant effects, probably because of the limited blood brain barrier permeability of no-steroidal or steroidal anti-inflammatory drugs. Lately, neurotrophic factors, such as the insulin-like growth factor 1 (IGF-1), are considered attractive therapeutic alternatives for diverse neurological pathologies, as they are neuromodulators linked to neuroprotection and anti-inflammatory effects. Considering this background, the aim of the present investigation is to test early IGF-1 gene therapy in both OS markers and cognitive deficits induced by TBI. Male Wistar rats were injected via Cisterna Magna with recombinant adenoviral vectors containing the IGF-1 gene cDNA 15 min post-TBI. Animals were sacrificed after 60 min, 24 h or 7 days to study the advanced oxidation protein products (AOPP) and malondialdehyde (MDA) levels, to recognize the protein oxidation damage and lipid peroxidation respectively, in the TBI neighboring brain areas. Cognitive deficits were assessed by evaluating working memory 7 days after TBI. The results reported significant increases of AOPP and MDA levels at 60 min, 24 h, and 7 days after TBI in the prefrontal cortex, motor cortex and hippocampus. In addition, at day 7, TBI also reduced working memory performance. Interestingly, AOPP, and MDA levels in the studied brain areas were significantly reduced after IGF-1 gene therapy that in turn prevented cognitive deficits, restoring TBI-animals working memory performance to similar values regarding control. In conclusion, early IGF-1 gene therapy could be considered a novel therapeutic approach to targeting neuroinflammation as well as to preventing some behavioral deficits related to TBI.
Neutrophilic Asthma Is Associated With Smoking, High Numbers of IRF5+, and Low Numbers of IL10+ Macrophages
Asthma is a heterogenous disease with different inflammatory subgroups that differ in disease severity. This disease variation is hampering treatment and development of new treatment strategies. Macrophages may contribute to asthma phenotypes by their ability to activate in different ways, i.e., T helper cell 1 (Th1)-associated, Th2-associated, or anti-inflammatory activation. It is currently unknown if these different types of activation correspond with specific inflammatory subgroups of asthma. We hypothesized that eosinophilic asthma would be characterized by having Th2-associated macrophages, whereas neutrophilic asthma would have Th1-associated macrophages and both having few anti-inflammatory macrophages. We quantified macrophage subsets in bronchial biopsies of asthma patients using interferon regulatory factor 5 (IRF5)/CD68 for Th1-associated macrophages, CD206/CD68 for Th2-associated macrophages and interleukin 10 (IL10)/CD68 for anti-inflammatory macrophages. Macrophage subset percentages were investigated in subgroups of asthma as defined by unsupervised clustering using neutrophil/eosinophil counts in sputum and tissue and forced expiratory volume in 1 s (FEV1). Asthma patients clustered into four subgroups: mixed-eosinophilic/neutrophilic, paucigranulocytic, neutrophilic with normal FEV1, and neutrophilic with low FEV1, the latter group consisting mainly of smokers. No differences were found for CD206+ macrophages within asthma subgroups. In contrast, IRF5+ macrophages were significantly higher and IL10+ macrophages lower in neutrophilic asthmatics with low FEV1 as compared to those with neutrophilic asthma and normal FEV1 or mixed-eosinophilic asthma. This study shows that neutrophilic asthma with low FEV1 is associated with high numbers of IRF5+, and low numbers of IL10+ macrophages, which may be the result of combined effects of smoking and having asthma.
The Synergistic Anti-Apoptosis Effects of Amniotic Epithelial Stem Cell Conditioned Medium and Ponesimod on the Oligodendrocyte Cells
Multiple sclerosis is a chronic inflammatory and neurodegenerative disease of the central nervous system. The current treatment of Multiple sclerosis is based on anti-inflammatory disease-modifying treatments, which can not regenerate myelin and eventually neurons. So, we need new approaches for axonal protection and remyelination. Amniotic epithelial stem cells amniotic epithelial cells, as a neuroprotective and neurogenic agent, are a proper source in tissue engineering and regenerative medicine. Due to differentiation capability and secretion of growth factors, AECs can be a candidate for the treatment of MS. Moreover, sphingosine-1-phosphate (S1P) receptor modulators were recently approved by FDA for MS. Ponesimod is an S1P receptor-1 modulator that acts selectively as an anti-inflammatory agent and provides a suitable microenvironment for the function of the other neuroprotective agents. In this study, due to the characteristics of AECs, they are considered a treatment option in MS. The conditioned medium of AECs concurrently with ponesimod was used to evaluate the viability of the oligodendrocyte cell line after induction of cell death by cuprizone. Cell viability after treatment by conditioned medium and ponesimod was increased compared to untreated groups. Also, the results showed that combination therapy with CM and ponesimod had a synergistic anti-apoptotic effect on oligodendrocyte cells. The combination treatment with CM and ponesimod reduced the expression of caspase-3, caspase-8, Bax, and Annexin V proteins and increased the relative BCL-2/Bax ratio, indicating inhibition of apoptosis as a possible mechanism of action. Based on these promising results, combination therapy with amniotic stem cells and ponesimode could be a proper alternative for multiple sclerosis treatment.
A Systematic Approach to Agastache mexicana Research: Biology, Agronomy, Phytochemistry, and Bioactivity
Mexico is the center of origin of the species popularly known as toronjil or lemon balm (Agastache mexicana Linton & Epling). Two subspecies have been identified and are commonly called purple or red (Agastache mexicana Linton & Epling subspecies. mexicana) and white (Agastache mexicana subspecies xolocotziana Bye, E.L. Linares & Ramamoorthy). Plants from these subspecies differ in the size and form of inflorescence and leaves. They also possess differences in their chemical compositions, including volatile compounds. Traditional Mexican medicine employs both subspecies. A. mexicana exhibits a broad range of pharmacological properties, such as anti-inflammatory, anxiolytic, and antioxidant. A systematic vision of these plant’s properties is discussed in this review, exposing its significant potential as a source of valuable bioactive compounds. Furthermore, this review provides an understanding of the elements that make up the species’ holistic system to benefit from lemon balm sustainably.
Development, Characterization and Pharmacological Investigation of Umbelliferone Conjugates of NSAIDs
The present investigation developed the ester prodrugs of Non-steroidal anti inflammatory drugs (NSAIDs), Mefenamic acid and Flurbiprofen by conjugating with the natural antioxidant, 4-methyl umbelliferone that resulted the formation of Mefenamic acid-umbelliferone ester prodrug and Flurbiprofen-umbelliferone ester prodrug .The principal objective this study is the synthesis of the ester prodrugs of NSAIDs with the enhanced therapeutic activity and minimized side effects. Prodrugs were synthesized by coupling method using N,N’- dicyclohexylcarbodiimide/4-dimethylaminopyrimidine, subjected to physical, chemical characterization, spectral characterization (IR, 1H NMR, 13C NMR and Mass spectra),hydrolysis-kinetic study and pharmacological evaluation such as anti-inflammatory, ulcerogenecity as well as the effect of the NSAIDs in the central nervous system against degenerative mechanisms. The current study revealed that the umbelliferone conjugates of NSAIDs which upon administration would release the parent drug as a result of enzymatic or non-enzymatic hydrolysis in the desired site with enhanced anti inflammatory activity and reduction in the gastro intestinal toxicity. Also the synthesized pordrugs showed enhanced brain targeting efficiency with protective action against the degenerative processes.
Neutrophil Decoys with Anti‐Inflammatory and Anti‐Oxidative Properties Reduce Secondary Spinal Cord Injury and Improve Neurological Functional Recovery
Zoology, chemical composition, pharmacology, quality control and future perspective of Musk (Moschus): a review
AbstractMusk, the dried secretion from the musk sac gland which is located between the navel and genitals of mature male musk deer, is utilized as oriental medicine in east Asia. It has been utilized to treat conditions such as stroke, coma, neurasthenia, convulsions, and heart diseases in China since ancient times. This paper aims to provide a comprehensive overview of musk in zoology, chemical composition, pharmacology, clinical applications, and quality control according to the up-to-date literature. Studies found that musk mainly contains macrocyclic ketones, pyridine, steroids, fatty acids, amino acids, peptides, and proteins, whilst the main active ingredient is muscone. Modern pharmacological studies have proven that musk possesses potent anti-inflammatory effects, neuroprotective effects, anti-cancer effects, antioxidant effects, etc. Moreover, muscone, the main active ingredient, possesses anti-inflammatory, neuroprotective, antioxidant, and other pharmacological effects. In the quality control of musk, muscone is usually the main detection indicator, and the common analytical method is GC, and researchers have established novel and convenient methods such as HPLC-RI, RP-UPLC-ELSD, and Single-Sweep Polarography. In addition, quality evaluation methods based on steroids and the bioactivity of musk have been established. As for the identification of musk, due to various objective factors such as the availability of synthetic Muscone, it is not sufficient to rely on muscone alone as an identification index. To date, some novel technologies have also been introduced into the identification of musk, such as the electronic nose and DNA barcoding technology. In future research, more in vivo experiments and clinical studies are encouraged to fully explain the pharmacological effects and toxicity of musk, and more comprehensive methods are needed to evaluate and control the quality of musk.