The Effect of Mitochondrial Damage in Chondrocytes on Osteoarthritis / 生物化学与生物物理进展

The pathogenesis of osteoarthritis (OA) is related to a variety of factors such as mechanical overload, metabolic dysfunction, aging, etc., and is a group of total joint diseases characterized by intra-articular chondrocyte apoptosis, cartilage fibrillations, synovial inflammation, and osteophyte formation. At present, the treatment methods for osteoarthritis include glucosamine, non-steroidal anti-inflammatory drugs, intra-articular injection of sodium hyaluronate, etc., which are difficult to take effect in a short period of time and require long-term treatment, so the patients struggle to adhere to doctor’s advice. Some methods can only provide temporary relief without chondrocyte protection, and some even increase the risk of cardiovascular disease and gastrointestinal disease. In the advanced stages of OA, patients often have to undergo joint replacement surgery due to pain and joint dysfunction. Mitochondrial dysfunction plays an important role in the development of OA. It is possible to improve mitochondrial biogenesis, quality control, autophagy balance, and oxidative stress levels, thereby exerting a protective effect on chondrocytes in OA. Therefore, compared to traditional treatments, improving mitochondrial function may be a potential treatment for OA. Here, we collected relevant literature on mitochondrial research in OA in recent years, summarized the potential pathogenic factors that affect the development of OA through mitochondrial pathways, and elaborated on relevant treatment methods, in order to provide new diagnostic and therapeutic ideas for the research field of osteoarthritis.

An integrated strategy for comprehensive characterization of metabolites and metabolic profiles of bufadienolides from Venenum Bufonis in rats / 药物分析学报

Comprehensive characterization of metabolites and metabolic profiles in plasma has considerable sig-nificance in determining the efficacy and safety of traditional Chinese medicine(TCM)in vivo.However,this process is usually hindered by the insufficient characteristic fragments of metabolites,ubiquitous matrix interference,and complicated screening and identification procedures for metabolites.In this study,an effective strategy was established to systematically characterize the metabolites,deduce the metabolic pathways,and describe the metabolic profiles of bufadienolides isolated from Venenum Bufonis in vivo.The strategy was divided into five steps.First,the blank and test plasma samples were injected into an ultra-high performance liquid chromatography/linear trap quadrupole-orbitrap-mass spectrometry(MS)system in the full scan mode continuously five times to screen for valid matrix compounds and metabolites.Second,an extension-mass defect filter model was established to obtain the targeted precursor ions of the list of bufadienolide metabolites,which reduced approximately 39％of the interfering ions.Third,an acquisition model was developed and used to trigger more tandem MS(MS/MS)fragments of precursor ions based on the targeted ion list.The acquisition mode enhanced the acquisition capability by approximately four times than that of the regular data-dependent acquisition mode.Fourth,the acquired data were imported into Compound Discoverer software for identification of metabolites with metabolic network prediction.The main in vivo metabolic pathways of bufadienolides were elucidated.A total of 147 metabolites were characterized,and the main biotransformation reactions of bufadienolides were hydroxylation,dihydroxylation,and isomerization.Finally,the main prototype bufadienolides in plasma at different time points were determined using LC-MS/MS,and the metabolic profiles were clearly identified.This strategy could be widely used to elucidate the metabolic profiles of TCM preparations or Chinese patent medicines in vivo and provide critical data for rational drug use.

Chemical profiling of Huashi Baidu prescription, an effective anti-COVID-19 TCM formula, by UPLC-Q-TOF/MS / 中国天然药物

Huashi Baidu prescription (HSBDF), recommended in the Guideline for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Pneumonia (On Trials, the Seventh Edition), was clinically used to treat severe corona virus disease 2019 (COVID-19) with cough, blood-stained sputum, inhibited defecation, red tongue etc. symptoms. This study was aimed to elucidate and profile the knowledge on its chemical constituents and the potential anti-inflammatory effect in vitro. In the study, the chemical constituents in extract of HSBDF were characterized by UPLC-Q-TOF/MS in both negative and positive modes, and the pro-inflammatory cytokines were measured by enzyme-linked immunosorbent assays (ELISA) to determine the effects of HSBDF in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results showed that a total of 217 chemical constituents were tentativedly characterized in HSBDF. Moreover, HSBDF could alleviate the expression levels of IL-6 and TNF-α in the cell models, indicating that the antiviral effects of HSBDF might be associated with regulation of the inflammatory cytokines production in RAW264.7 cells. We hope that the results could be served as the basic data for further study of HSBDF on anti-COVID-19 effect.

Relaxant effects of Aike Mixture on isolated bladder and prostatic urethral smooth muscle of rabbits / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the relaxant effect of Aike Mixture (AKM) on isolated bladder and prostatic urethral smooth muscle of rabbits.</p><p><b>METHODS</b>The isolated bladder and prostatic urethral smooth muscle from male rabbits were placed in a Magnus bath and smooth muscle contraction was measured using a biological signal acquisition and analysis system. The effects of AKM in combination with methoxyamine, carbachol and CaCl2 on the contractile tension of muscle strips were determined by cumulative dosing.</p><p><b>RESULTS</b>AKM dose-dependently reduced contractile tension of bladder trigone smooth muscle (r=0.831, P<0.05), reduced contractile wave amplitude (r=0.837, P<0.05) and decreased contractile frequency (r=-0.917, P<0.01). AKM significantly inhibited the increases in smooth muscle contraction induced by methoxyamine, carbachol and CaCl2.</p><p><b>CONCLUSION</b>AKM dose-dependently inhibited the contraction of rabbit isolated bladder and prostatic urethral smooth muscle by antagonizing α1-adrenergic receptors and M-cholinergic receptors.</p>

Estimation of postmortem interval with single-voxel proton 1H-MR spectroscopy at different temperature / 法医学杂志

OBJECTIVE@#To find an objective method for estimation of postmortem interval (PMI) with single-voxel proton MR spectroscopy at different temperature.@*METHODS@#Changes of metabolite peak area and peak area ratio of the N-acetylaspartate (Naa), choline (Cho) and total creatine (Cr) in the brain of 24 rabbit models were measured by 1H-MR spectroscopy (1H-MRS) at 0.5, 1, 2, 4, 6, 8, 12, 16 and 24 h, respectively after death.@*RESULTS@#Naa and Cr decreased continuously with the extension of PMI, and the ratios of Naa/Cr and Cho/Cr also decreased continuously with the extension of PMI within 24 h. The quadratic polynomial regression equation is y=0.0019x2-0.803x+1.4498 (R2=0.962) (Equation 1) with the Naa/Cr used as an independent variable, while the quadratic polynomial regression equation is y=-0.0024x2+0.926x+1.1777 (R2=0.986) (Equation 2) with the Cho/Cr used as an independent variable. The average deviations were about 2.10-37.90 min and 1.69-40.87 min, respectively if the PMI was estimated by Equation 1 and Equation 2, respectively.@*CONCLUSION@#Our study indicates that there is a strong correlation between Naa/Cr, Cho/Cr and PMI, which may be used for estimation of PMI at different temperature.

Estimation of postmortem interval with multivoxel-voxel proton 1H-MR spectroscopy / 法医学杂志

OBJECTIVE@#The purpose of our study was to evaluate the postmortem interval with multi-voxel 1H-MR spectroscopy.@*METHODS@#Twelve healthy rabbits were studied and the quantities of N-acetylaspartate, total choline, phosphocreatine and creatine were measured by 1H-MR spectroscopy after death at 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 h.@*RESULTS@#The levels of Naa/Cr and Naa/Ch decreased following death, while the level of Ch/Cr increased initially and then decreased following death.@*CONCLUSION@#Multi-voxel proton MR spectroscopy for Naa/Cr and Ch/Cr metabolic ratio could be used in future postmortem interval studies.