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Osteoarthritis (OA) is no longer regarded as a simple wear-and-tear problem of articular cartilage. Instead, OA is a whole joint disorder involving both cartilaginous and non-cartilaginous tissues such as subchondral bone and synovium. Among them, subchondral bone undergoes constant remodeling in response to the changes of mechanical environment. Current understanding of subchondral bone disturbance in OA is limited to its link with an altered local mechanical loading as a result of ligament or meniscus injury. Very recently, hypertension, the most common vascular morbidity, has been emerged as an independent risk factor of OA. It might suggest a plausible role of systemic hemodynamic mechanical stress in subchondral bone remodeling and the pathogenesis of OA. However, their relationship remains not fully understood. Based on our preliminary clinical observation on the association of hemodynamic parameters with subchondral bone mass and microstructure in late-stage knee OA patients, we formulate a vascular etiology hypothesis of OA from a mechanobiology perspective. Noteworthily, hemodynamic stress associated with subchondral bone mineral density; yet compressive mechanical loading does not. Furthermore, hemodynamic parameters positively correlated with subchondral plate-like trabecular bone volume but negatively associated with rod-like trabecular bone volume. In contrast, compressive mechanical loading tends to increase both plate-like and rod-like trabecular bone volume. Taken together, it warrants further investigations into the distinct role of hemodynamic or compressive stress in shaping subchondral bone in the pathophysiology of OA. The Translational potential of this article: This work provides a new insight, from the angle of biomechanics, into the emerging role of vascular pathologies, such as hypertension, in the pathogenesis of OA. It might open up a new avenue for the development of a mechanism-based discovery of novel diagnostics and therapeutics.

Abstract Background Buzhongyiqi decoction (BD), Sijunzi decoction (SD), and Shenlingbaizhu decoction (SHD) have been extensively used clinically for the treatment of diseases caused by spleen-Qi deficiency and microbial fermentation has historically been utilized in traditional Chinese medicine (TCM). This study aimed to investigate the mitigative effect of TCM and fermented TCM (FTCM) with Lactobacillus plantarum (LP) on antibiotic-associated diarrhea, and to select an optimal formula and then identify its compounds. Methods Dysbacteriosis in mice was induced by ceftriaxone sodium (CS). The mice were then treated with LP, BD, SD, SHD, fermented BD, fermented SD (FSD), and fermented SHD. Diarrhea indexes, the abundances of gut bacteria, intestinal morphometrics, and mRNA expressions of genes related to intestinal barrier function were assessed. Then, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) were employed to identify and relatively quantify the compounds in the selected decoctions. Results CS significantly increased the fecal output weight, the total number of fecal output, and fecal water content, indicating the occurrence of diarrhea. Bacterial culture tests showed that the above symptoms were accompanied by the disruption of specific intestinal flora. TCM, LP, and FTCM alleviated the diarrhea index and recovered the intestinal microbiota. FTCM showed more advantageous than TCM or LP alone. The mRNA expressions of aquaporins (AQPs) and tight junctions (TJs) decreased by CS were enhanced by TCM, LP, and FTCM. In addition, through UHPLC-Q-TOF/MS, (S)-(-)-2-hydroxyisocaproic acid, L-methionine, 4-guanidinobutyric acid (4GBA), and phenyllactate (PLA) in SD and FSD were identified and relatively quantified. Conclusions TCM, LP, and TCM fermented with LP alleviated CS-induced diarrhea symptoms, and improved the intestinal flora and barrier function. Four compounds including (S)-(-)-2-hydroxyisocaproic acid, L-methionine, 4GBA, and PLA in FSD, which were identified by UHPLC-Q-TOF/MS, might function in modulating intestinal flora and improving villi structure.

This study aimed to optimize the fermentation conditions of apple juice by Lactobacillus plantarum to obtain fermented apple juice (FAJ) with high probiotic content and tannic acid content. The apple juice and FAJ compounds were identified and relatively quantified by UHPLC-ESI-Q TRAP-MS/MS. Treating mice with ceftriaxone sodium induced diarrhea. However, ingestion of FAJ helped alleviate these symptoms. Furthermore, via 16S rRNA sequencing, FAJ reduced the proportion of Bacillota to Bacteroidota at the phyla level. Moreover, at the genus level, FAJ also caused a lower relative abundance of Enterococcus and Clostridium, and a higher relative abundance of Lactobacillus and Prevotella. Additionally, FAJ improved the intestinal morphology and intestinal barrier function. Five up-regulated bioactive compounds (l-isoleucine, l-leucine, l-valine, 4-Guanidinobutyric acid, and Phenyllactate) are partly responsible for the performances of FAJ. All these findings implied that FAJ could be a dietary supplement for lessening antibiotic-associated diarrhea by regulating intestinal microbiota and barrier function.

Background/Aims: We investigated the combined toxic effect of sodium fluoride (NaF) and sulfur dioxide (SO2) on kidney morphological changes and DNA damage in male Wistar rats. Methods: In this study we selected totally 96 male Wistar rats (12-week-old) then randomly group-housed them into four cages, treated with deionized water, NaF, SO2 and co-treatment of NaF and SO2 respectively. Morphological changes of kidney were detected by hematoxylin and eosin (H&E) staining at 2, 4, 6 and 8 weeks. Correspondingly, tailing ratio and comet length were measured by BAB Bs Comet Assay System, including DNA damage special unit were calculated to evaluate the grades of kidney DNA damage at the same time. Results: Treated groups showed a body weight decrease when compared to control group. However, no significant difference in the relative weight of kidney was found in all four groups. It is noteworthy that at 2, 4, 6 and 8 weeks after exposure, the morphological alteration of renal tubules were observed in all treated groups, especially in group-IV. Also, at 4 and 6 weeks, notable DNA damage was found in all treated groups, as assessed by significantly increasing trend of comet length tailing ratio. Conclusion: The study manifests that presence of NaF and SO2 will not only induce renal tissue lesions but also impact DNA integrity. In addition, this combined exposure exhibits a synergistic effect, characterizing a dose-dependence and time correlation. These findings may provide novel insights regarding perturbations of DNA damage and its functions as a potential new mechanism, by which cautious interpretation of NaF and SO2 co-exposure evolved in both animals and human beings is necessary.

A calcium-binding peptide was successfully purified from tilapia (Oreochromis niloticus) scale protein hydrolysate by hydroxylapatite affinity (HA), gel filtration and reverse phase high-performance liquid chromatography (RP-HPLC). This peptide was sequenced as DGDDGEAGKIG (N- to C-terminal, MW = 1033 Da) based on MALDI-TOF-MS/MS. There was no significant difference in body weight gain, serum P content or alkaline phosphatase (ALP) level in Ca-deficient rats after supplementation with TSPH–Ca (tilapia scale protein hydrolysate calcium complex), CPP–Ca (casein phosphopeptide calcium complex), CaCO3 or saline (control). However, the apparent absorptivity of calcium, serum and femur Ca content, femur bone mineral density and strength in the rats fed with TSPH–Ca were significantly higher than those of rats in the control and CaCO3 groups (P 0.05), indicating that TSPH possesses the potential to serve as an alternative for CPP.