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BACKGROUND: Protein degradation is the main reason of exercise induced muscle damage (ElMO). High-intensity exercise may lead to the misfolding of proteins and fonn aggregates, which is harmful to the ultrastructure of skeleton muscle. OBJECTIVE: To determine the formation and role of protein aggregate (especially the desmin aggregate) in ElMO. METHODS: Sixty-four adult male Sprague-Dawtey rats (purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., China) were randomly divided into eight groups (control, post-exercise 0, 3, 6, 12, 24, 48, and 72 hours, eight rats in each). A damage model was established by downhill running (-160, 16m/min, 90 minutes). All rats were then killed at corresponding time points to take the soleus as specimen. Severity of damage was observed histologically under a transmission electron microscope. Expression of ubiquitin in the insoluble protein of soleus muscle was detected using western blot, and expression of desmin aggregates was observed by immunofluorescence double labeling. All experimental procedures were approved by the Beijing Sport University Institutional Review Board. RESULTS AND CONCLUSION: (1) After a large-load eccentric exercise, the sarcomere of the soleus muscle was widened, the Z-line was broken, and the myofibril was broken and distorted, all of which was most serious at 12 hours after exercise, and recovered completely at 72 hours after exercise. (2) Western blot results indicated that the expression of ubiquitin in the skeletal muscle increased first and then decreased after a large-load eccentric exercise. The expression peaked at 12 hours after exercise and returned to normal at 72 hours after exercise. (3)0verall expression of desmin aggregates significantly raised (P < 0.01) instantly when the ElMO occurred. It reached the peak at 12 hours after exercise, then reduced somewhat (P < 0.01) at 24 and 48 hours, and finally recovered at 72 hours. (4)These findings indicate that desmin aggregation may be one of the causes of ElMO. [ABSTRACT FROM AUTHOR]

Congenital cataracts caused by genetic disorders are the primary cause of child blindness across the globe. In this work, we investigated the underlying molecular mechanism of two mutations, L45P and Y46D of γC-crystallin in two Chinese families causing nuclear congenital cataracts. Spectroscopic experiments were performed to determine structural differences between the wild-type (WT) and the L45P or Y46D mutant of γC-crystallin, and the structural stabilities of the WT and mutant proteins were measured under environmental stress (ultraviolet irradiation, pH disorders, oxidative stress, or chemical denaturation). The L45P and Y46D mutants had lower protein solubility and more hydrophobic residues exposed, making them prone to aggregation under environmental stress. The dynamic molecular simulation revealed that the L45P and Y46D mutations destabilized γC-crystallin by altering the hydrogen bonds network around the Trp residues in the second Greek key motif. In summary, L45P and Y46D mutants of γC-crystallin caused more hydrophobic residues to be solvent-exposed, lowered the solubility of γC-crystallin, and increased aggregation propensity under environmental stress. These might be the pathogenesis of γC-crystallin L45P and Y46D mutants related to congenital cataract., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In China, a decoction is one of the most common clinical dosage forms. Nanometre aggregates (NAs), which often consist of circular or irregular nanoparticles, have been observed in previous research on decoctions. A Bai-Hu-Tang (BHT) decoction is an ancient clinical dosage form in China. The purpose of this work was to isolate and characterize NAs from BHT and to investigate their antipyretic effect. A BHT decoction was prepared by the traditional method. The mechanism and active components of the aggregates in BHT were investigated by high-speed centrifugation, transmission electron microscopy (TEM), and HPLC (high-performance liquid chromatography). In addition to the aggregation, therapeutic activities were evaluated through temperature measurements, enzyme-linked immunosorbent assays, cellular uptake measurements and fluorescence imaging. The majority of the NAs in BHT had diameters of 100 nm, and the spherical structures contained C, O, Mg, Al, Si, Ca, Zn et al. Antipyretic bioactive compounds, such as neomangiferin, mangiferin, glycyrrhizic acid and ammonium glycyrrhizinate, existed in the aggregates. In addition, the NAs in BHT had a better antipyretic effect than the other dispersion phases of BHT. In particular, the nanometre aggregates of Bai-Hu-Tang (N-BHT) were easily taken up by cells, and the fluorescein isothiocyanate (FITC) signals of NAs were more enriched in the lungs and brain than in other organs over time. These results revealed that the antipyretic effect was associated with the NAs in BHT. The discovery of NAs might present a new perspective for understanding BHT decoctions and even lead to the development of a new nanomedicine approach in traditional Chinese medicine (TCMs). Therefore, this topic deserves further study.