scholarly journals Metabolomics Coupled with Pathway Analysis Provides Insights into Sarco-Osteoporosis Metabolic Alterations and Estrogen Therapeutic Effects in Mice

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 41
Author(s):  
Ziheng Wei ◽  
Fei Ge ◽  
Yanting Che ◽  
Si Wu ◽  
Xin Dong ◽  
...  
Keyword(s):  
Bone Loss ◽  
Pathway Analysis ◽  
Three Dimensional ◽  
Metabolic Reprogramming ◽  
Therapeutic Effects ◽  
Sham Surgery ◽  
Polar Metabolites ◽  
Metabolic Mechanism ◽  
Histopathology Examination ◽  
Tof Ms

Postmenopausal osteoporosis (PMOP) and sarcopenia are common diseases that predominantly affect postmenopausal women. In the occurrence and development of these two diseases, they are potentially pathologically connected with each other at various molecular levels. However, the application of metabolomics in sarco-osteoporosis and the metabolic rewiring happening throughout the estrogen loss-replenish process have not been reported. To investigate the metabolic alteration of sarco-osteoporosis and the possible therapeutical effects of estradiol, 24 mice were randomly divided into sham surgery, ovariectomy (OVX), and estradiol-treated groups. Three-dimensional reconstructions and histopathology examination showed significant bone loss after ovariectomy. Estrogen can well protect against OVX-induced bone loss deterioration. UHPLC-Q-TOF/MS was preformed to profile semi- polar metabolites of skeletal muscle samples from all groups. Metabolomics analysis revealed metabolic rewiring occurred in OVX group, most of which can be reversed by estrogen supplementation. In total, 65 differential metabolites were identified, and pathway analysis revealed that sarco-osteoporosis was related to the alterations in purine metabolism, glycerophospholipid metabolism, arginine biosynthesis, tryptophan metabolism, histidine metabolism, oxidative phosphorylation, and thermogenesis, which provided possible explanations for the metabolic mechanism of sarco-osteoporosis. This study indicates that an UHPLC-Q-TOF/MS-based metabolomics approach can elucidate the metabolic reprogramming mechanisms of sarco-osteoporosis and provide biological evidence of the therapeutical effects of estrogen on sarco-osteoporosis.

Current RNA-based Therapeutics in Clinical Trials

2019 ◽  
Vol 19 (3) ◽  
pp. 172-196 ◽  
Author(s):  
Ling-Yan Zhou ◽  
Zhou Qin ◽  
Yang-Hui Zhu ◽  
Zhi-Yao He ◽  
Ting Xu
Keyword(s):  
Clinical Trials ◽  
Rapid Development ◽  
Genetic Diseases ◽  
Three Dimensional ◽  
Therapeutic Effects ◽  
Messenger Rnas ◽  
Small Interfering Rnas ◽  
Rna Modifications ◽  
Guide Rna ◽  
Endogenous Genes

Long-term research on various types of RNAs has led to further understanding of diverse mechanisms, which eventually resulted in the rapid development of RNA-based therapeutics as powerful tools in clinical disease treatment. Some of the developing RNA drugs obey the antisense mechanisms including antisense oligonucleotides, small interfering RNAs, microRNAs, small activating RNAs, and ribozymes. These types of RNAs could be utilized to inhibit/activate gene expression or change splicing to provide functional proteins. In the meantime, some others based on different mechanisms like modified messenger RNAs could replace the dysfunctional endogenous genes to manage some genetic diseases, and aptamers with special three-dimensional structures could bind to specific targets in a high-affinity manner. In addition, the recent most popular CRISPR-Cas technology, consisting of a crucial single guide RNA, could edit DNA directly to generate therapeutic effects. The desired results from recent clinical trials indicated the great potential of RNA-based drugs in the treatment of various diseases, but further studies on improving delivery materials and RNA modifications are required for the novel RNA-based drugs to translate to the clinic. This review focused on the advances and clinical studies of current RNA-based therapeutics, analyzed their challenges and prospects.

scholarly journals Metabolomic Profiles Delineate Signature Metabolic Shifts during Estrogen Deficiency-Induced Bone Loss in Rat by GC-TOF/MS

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e54965 ◽  
Author(s):  
Bo Ma ◽  
Jiannan Liu ◽  
Qi Zhang ◽  
Hanjie Ying ◽  
Jiye A ◽  
...  
Keyword(s):  
Bone Loss ◽  
Estrogen Deficiency ◽  
Tof Ms

scholarly journals How to measure a Hill–Sachs lesion: a systematic review

2019 ◽  
Vol 4 (4) ◽  
pp. 151-157 ◽  
Author(s):  
Marta Maio ◽  
Marco Sarmento ◽  
Nuno Moura ◽  
António Cartucho
Keyword(s):  
Bone Loss ◽  
Three Dimensional ◽  
Correlation Coefficients ◽  
Glenohumeral Instability ◽  
Search Terms ◽  
Simultaneous Evaluation ◽  
Length Width ◽  
Anterior Glenohumeral Instability ◽  
The Hill ◽  
Mri Measurements

Quantifying bone loss is important to decide the best treatment for patients with recurrent anterior glenohumeral instability. Currently, there is no standard method available to make a precise evaluation of the Hill–Sachs lesion and predict its engagement before the surgical procedure. This literature review was performed in order to identify existing published imaging methods quantifying humeral head bone loss in Hill–Sachs lesions. Searches were undertaken in Scopus and PubMed databases from January 2008 until February 2018. The search terms were “Hill-Sachs” and “measurement” for the initial search and “Hill–Sachs bone loss” for the second, to be present in the keywords, abstracts and title. All articles that presented a method for quantifying measurement of Hill–Sachs lesions were analysed. Several methods are currently available to evaluate Hill–Sachs lesions. The length, width and depth measurements on CT scans show strong inter and intra-observer correlation coefficients. Three-dimensional CT is helpful for evaluation of bony injuries; however, there were no significant differences between 3D CT and 3D MRI measurements. The on-track off-track method using MRI allows a simultaneous evaluation of the Hill–Sachs and glenoid bone loss and also predicts the engaging lesions with good accuracy. Cite this article: EFORT Open Rev 2019;4:151-157. DOI: 10.1302/2058-5241.4.180031

The impact of the primary canine premature extraction on the sagittal, vertical and transversal dimensions of the bone tissue

2021 ◽  
Vol 21 (1) ◽  
pp. 47-50
Author(s):  
Ad. A. Mamedov ◽  
T. V. Timoshenko ◽  
T. S. Gutnikova
Keyword(s):  
Bone Loss ◽  
Three Dimensional ◽  
Volume Measurement ◽  
Growth Spurt ◽  
Special Technique ◽  
Suggested Technique ◽  
Present Case Study ◽  
The Impact ◽  
Primary Canine

Relevance. The article studies the primary canine premature extraction as the cause of three-dimensional (sagittal, transversal, vertical) bone underdevelopment in the area of the extracted tooth. The research is relevant as there are insufficient data in the scientific literature on this topic and the prevalence of premature primary canine extraction for therapeutic and orthodontic indications is high.Materials and methods. The present case study developed a special technique for bone volume measurement in all planes by CBCT.Results. Several CBCTs of one patient over the period of three years were analyzed according to the suggested technique. The calculations demonstrated significant sagittal and vertical bone loss.Conclusions. The results of the research allowed us to conclude that premature extraction of the primary canines leads to the significant sagittal and vertical bone loss. Besides, no increase in the intercanine distance was detected despite the patient’s growth spurt.

Differential Constituents in Roots, Stems and Leaves of Polygonum multiflorum Thunb. Screened by UPLC/ESI-Q-TOF-MS and Multivariate Statistical Analysis

2019 ◽  
Vol 58 (2) ◽  
pp. 136-143 ◽  
Author(s):  
Wen Rui ◽  
Wanxia Xia ◽  
Wei Zhao ◽  
Bingling Li ◽  
Jian Li ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Multivariate Statistical Analysis ◽  
Composition Analysis ◽  
Chemical Compositions ◽  
Therapeutic Effects ◽  
Polygonum Multiflorum ◽  
Multivariate Statistical ◽  
Analytical Strategy ◽  
Relative Standard ◽  
Tof Ms

Abstract The differential constituents in leaves, stems and roots of Polygonum multiflorum Thunb. were analyzed by ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC/ESI-Q-TOF-MS) and by multivariate statistical analysis. The established extraction and analysis method showed relative standard deviations (RSDs) for intra-day precision of less than 3.40%, for repeatability of less than 4.06% and for stability of less than 5.10%. Principal component analysis and orthogonal projections to latent structures discriminant analysis of the UPLC/ESI-Q-TOF-MS data showed good ability to classify the leaves, stems and roots of P. multiflorum Thunb. The differential constituents, such as stilbenes, polygoacetophenoside, flavonoids and anthraquinones, accounting for variations between the leaves, stems and roots, were filtered through the variable importance in projection values and were further identified by elemental composition analysis, mass fragmentation data and retention times of available standards. Differences between the chemical compositions in the leaves, stems and roots of P. multiflorum Thunb. were closely related to their various therapeutic effects. This UPLC/ESI-Q-TOF-MS-based analytical strategy could be further utilized to evaluate the overall quality of traditional Chinese medicines and their differences of chemical constituents in different parts of the plant and/or in the plants of different geographical locations.

scholarly journals Decomposing the Mechanism of Qishen Granules in the Treatment of Heart Failure by a Quantitative Pathway Analysis Method

Molecules ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 1829 ◽  
Author(s):  
Weiquan Ren ◽  
Sheng Gao ◽  
Huimin Zhang ◽  
Yinglu Ren ◽  
Xue Yu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Energy Metabolism ◽  
Pathway Analysis ◽  
Ventricular Remodeling ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Therapeutic Effects ◽  
Analysis Tool ◽  
Ventricular Ejection Fraction ◽  
Pathway Analysis Tool

Qishen granules (QSG) have beneficial therapeutic effects for heart failure, but the effects of decomposed recipes, including Wenyang Yiqi Huoxue (WYH) and Qingre Jiedu (QJ), are not clear. In this study, the efficacy of WYH and QJ on heart failure is evaluated by using transverse aortic constriction (TAC) induced mice and the significantly changed genes in heart tissues were screened with a DNA array. Furthermore, a new quantitative pathway analysis tool is developed to evaluate the differences of pathways in different groups and to identify the pharmacological contributions of the decomposed recipes. Finally, the related genes in the significantly changed pathways are verified by a real-time polymerase chain reaction and a Western blot. Our data show that both QJ and WYH improve the left ventricular ejection fraction, which explain their contributions to protect against heart failure. In the energy metabolism, QJ achieves the therapeutic effects of QSG through nicotinamide nucleotide transhydrogenase (Nnt)-mediated mechanisms. In ventricular remodeling and inflammation reactions, QJ and WYH undertake the therapeutic effects through 5′-nucleotidase ecto (Nt5e)-mediated mechanisms. Together, QJ and WYH constitute the therapeutic effects of QSG and play important roles in myocardial energy metabolism and inflammation, which can exert therapeutic effects for heart failure.

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