Biological Assessment of the NO-Dependent Endothelial Function

Nitric oxide (NO) is implicated in numerous physiological processes, including vascular homeostasis. Reduced NO bioavailability is a hallmark of endothelial dysfunction, a prequel to many cardiovascular diseases. Biomarkers of an early NO-dependent endothelial dysfunction obtained from routine venous blood sampling would be of great interest but are currently lacking. The direct measurement of circulating NO remains a challenge due by its high reactivity and short half-life. The current techniques measure stable products from the NO signaling pathway or metabolic end products of NO that do not accurately represent its bioavailability and, therefore, endothelial function per se. In this review, we will concentrate on an original technique of low temperature electron paramagnetic resonance spectroscopy capable to directly measure the 5-α-coordinated heme nitrosyl-hemoglobin in the T (tense) state (5-α-nitrosyl-hemoglobin or HbNO) obtained from fresh venous human erythrocytes. In humans, HbNO reflects the bioavailability of NO formed in the vasculature from vascular endothelial NOS or exogenous NO donors with minor contribution from erythrocyte NOS. The HbNO signal is directly correlated with the vascular endothelial function and inversely correlated with vascular oxidative stress. Pilot studies support the validity of HbNO measurements both for the detection of endothelial dysfunction in asymptomatic subjects and for the monitoring of such dysfunction in patients with known cardiovascular disease. The impact of therapies or the severity of diseases such as COVID-19 infection involving the endothelium could also be monitored and their incumbent risk of complications better predicted through serial measurements of HbNO.     

Effect of Cordyceps spp. and Cordycepin on Functions of Bones and Teeth and Related Processes: A Review

Cordyceps spp. (belonging to the Ascomycota group) are entomopathogenic mushrooms that have traditionally been used in ethnomedicine in Asian countries such as China, Japan, Korea, and India. They are unique parasites of larvae of selected species of moths. Cordyceps militaris is one of the best sources of cordycepin. Worldwide, osteoporosis is one of the most common bone diseases, whose pharmacotherapy includes various medical interventions; however, the research and development of new molecules and new drugs is required. The impact of adenosine receptors (ARs) on the purinergic signaling pathway may regulate proliferation, differentiate dental pulp stem cells and bone marrow, and modulate osteogenesis and bone repair. The aim of the review was to collect and analyze the available data on the effects of Cordyceps spp. or cordycepin on bone function and related processes. To the best of our knowledge, this is the first systematic review in this perspective, not necessarily using mushroom raw material or even the isolated parent compound cordycepin, but new molecules that are analogs of nucleosides, such as those from C. militaris. This review found that Cordyceps spp. or isolated cordycepin interacts via the AR, 5′ adenosine monophosphate-activated protein kinase (AMPK), and adenosine-5′-triphosphate (ATP) signaling pathway and evaluated their impact on bones, teeth, and dental pulp. Cordyceps spp. was found to have the potential to develop regenerative medicines, thus providing an opportunity to expand the treatment or intervention methods in the recovery after traumatic injuries, convalescence, and terminal-stage or devastating diseases.     

Inosine in Neurodegenerative Diseases: From the Bench to the Bedside

Neurodegenerative diseases, such as Alzheimer′s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), currently represent major unmet medical needs. Therefore, novel therapeutic strategies are needed in order to improve patients’ quality of life and prognosis. Since oxidative stress can be strongly involved in neurodegenerative diseases, the potential use of inosine, known for its antioxidant properties, in this context deserves particular attention. The protective action of inosine treatment could be mediated by its metabolite urate. Here, we review the current preclinical and clinical studies investigating the use of inosine in AD, PD, ALS, and MS. The most important properties of inosine seem to be its antioxidant action and its ability to raise urate levels and to increase energetic resources by improving ATP availability. Inosine appears to be generally safe and well tolerated; however, the possible formation of kidney stones should be monitored, and data on its effectiveness should be further explored since, so far, they have been controversial. Overall, inosine could be a promising potential strategy in the management of neurodegenerative diseases, and additional studies are needed in order to further investigate its safety and efficacy and its use as a complementary therapy along with other approved drugs.     

治疗呼吸系统疾病中草药微量元素含量测定

微量元素与人体健康有密切的关系,各微量元素之间按一定比例存在,以维护各自的生理功能,如果比例平衡失调,疾病就可能发生或发展,中草药中含微量元素丰实。选取了16种临床上常用的治疗呼吸系统疾病的中草药百合、鱼腥草、甘草、板兰根、五味子、黄芩、贝母、何首乌、紫草、石菖蒲、半夏、银杏、金银花、葛根、柴胡和川芎,采用HNO3-HClO4湿法消化,用原子吸收分光光度计测定其Fe,Ni,Mn,Cr,Cu和Zn六种微量元素的含量,通过药物中微量元素含量的测定,观察不同药物中微量元素的含量差别。测定结果显示,16种中草药中微量元素含量丰富,含量较多的微量元素有Fe,Zn和Mn,不同药物中含量有所差别,含微量元素较丰富的是何首乌、银杏叶、柴胡、五味子、半夏和紫草;含量较少的葛根、石菖蒲和板兰根。分析结果为研究中药理论、药理药效等方面的深入研究提供了有效的参考数据。     

Identification and Evaluation of Traditional Chinese Medicine Natural Compounds as Potential Myostatin Inhibitors: An In Silico Approach

Myostatin (MSTN), a negative regulator of muscle mass, is reported to be increased in conditions linked with muscle atrophy, sarcopenia, and other muscle-related diseases. Most pharmacologic approaches that treat muscle disorders are ineffective, emphasizing the emergence of MSTN inhibition. In this study, we used computational screening to uncover natural small bioactive inhibitors from the Traditional Chinese Medicine database (~38,000 compounds) for the MSTN protein. Potential ligands were screened, based on binding affinity (150), physicochemical (53) and ADMET properties (17). We found two hits (ZINC85592908 and ZINC85511481) with high binding affinity and specificity, and their binding patterns with MSTN protein. In addition, molecular dynamic simulations were run on each complex to better understand the interaction mechanism of MSTN with the control (curcumin) and the hit compounds (ZINC85592908 and ZINC85511481). We determined that the hits bind to the active pocket site (Helix region) and trigger conformational changes in the MSTN protein. Since the stability of the ZINC85592908 compound was greater than the MSTN control, we believe that ZINC85592908 has therapeutic potential against the MSTN protein and may hinder downstream singling by inhibiting the MSTN protein and increasing myogenesis in the skeletal muscle tissues.     

Chemical Composition Profiling and Antifungal Activity of Saffron Petal Extract

Numerous fungal plant pathogens can infect fresh fruits and vegetables during transit and storage conditions. The resulting infections were mainly controlled by synthetic fungicides, but their application has many drawbacks associated with the threatened environment and human health. Therefore, the use of natural plants with antimicrobial potential could be a promising alternative to overcome the side effects of fungicides. In this regard, this study aimed at evaluating the antifungal activity potential of saffron petal extract (SPE) against three mains important fungal pathogens: Rhizopus stolonifer, Penicillium digitatum and Botritys cinerea, which cause rot decay on the tomato, orange and apple fruits, respectively. In addition, the organic composition of SPE was characterized by attenuated total reflection Fourier transform infrared (ATR-FT-IR) spectroscopy and its biochemical, and gas chromatography-mass spectrometry (GC-MS) analyses were carried out. The obtained results highlighted an increased inhibition rate of the mycelial growth and spore germination of the three pathogenic fungi with increasing SPE concentrations. The mycelial growth and spore germination were completely inhibited at 10% of the SPE for Rhizopus stolonifer and Penicillium digitatum and at 5% for B. cinerea. Interestingly, the in vivo test showed the complete suppression of Rhizopus rot by the SPE at 10%, and a significant reduction of the severity of grey mold disease (37.19%) and green mold, when applied at 5 and 10%, respectively. The FT-IR spectra showed characteristic peaks and a variety of functional groups, which confirmed that SPE contains phenolic and flavonoid components. In addition, The average value of the total phenolic content, flavonoid content and half-maximal inhibitory concentration (IC₅₀) were 3.09 ± 0.012 mg GAE/g DW, 0.92 ± 0.004 mg QE/g DW and 235.15 ± 2.12 µg/mL, respectively. A volatile analysis showed that the most dominant component in the saffron petal is 2(5H)-Furanone (92.10%). Taken together, it was concluded that SPE could be used as an alternative to antioxidant and antifungal compounds for the control of postharvest diseases in fruits.     

The Impact of Software Used and the Type of Target Protein on Molecular Docking Accuracy

The modern development of computer technology and different in silico methods have had an increasing impact on the discovery and development of new drugs. Different molecular docking techniques most widely used in silico methods in drug discovery. Currently, the time and financial costs for the initial hit identification can be significantly reduced due to the ability to perform high-throughput virtual screening of large compound libraries in a short time. However, the selection of potential hit compounds still remains more of a random process, because there is still no consensus on what the binding energy and ligand efficiency (LE) of a potentially active compound should be. In the best cases, only 20–30% of compounds identified by molecular docking are active in biological tests. In this work, we evaluated the impact of the docking software used as well as the type of the target protein on the molecular docking results and their accuracy using an example of the three most popular programs and five target proteins related to neurodegenerative diseases. In addition, we attempted to determine the “reliable range” of the binding energy and LE that would allow selecting compounds with biological activity in the desired concentration range.     

Mechanopathology of red blood cell diseases — Why mechanics matters

During the onset of a disease a cell may experience alterations in both the composition and organization of its cellular and molecular structures. These alterations may eventually lead to changes in its geometrical and mechanical properties such as cell size and shape, deformability and adhesion. As such, knowing how diseased cells respond to mechanical forces can reveal ways by which they differ from healthy ones. Here, we will present biomechanistic insights into red blood cell related diseases that manifest mechanical property changes and how they directly contribute to the pathophysiology of diseases. By conducting cell and molecular mechanics studies, not only can we elucidate changes in the structure-property-function relationship of diseased cells, we can also exploit the new knowledge gained to develop biomechanics based devices that may better detect and diagnose these diseases as well as help identify important biomechanical targets for possible therapeutic interventions.     

Optical Coherence Tomographic Features of Macular Diseases

Optical coherence tomography (OCT) is a new diagnostic technology which allows visualization of a cross-sectional image of the anterior eye and the retina in vivo with a high resolution similar to a histological section by light microscopy. Although the fundus can be examined at the semihistologic level by a biomicroscope, histopathologic study has been difficult because of the rare opportunity for retinal biopsy or enucleation. OCT reveals the intraretinal structure of macular diseases on the histopathologic level. In this article, we review the research on various macular diseases using OCT at Gunma University School of Medicine.