According to reports, obesity has a significant impact on bone health. And the weight-adjusted-waist index (WWI), superior to BMI and waist circumference (WC), is a new obesity indicator arising in recent years. This research investigated the relationship between WWI and total bone mineral density (BMD) for adults aged 20 to 59.Using data from the 2011–2018 NHANES, we looked into the independent link between WWI and total BMD as well as its nonlinearity using weighted multiple linear regression and smooth curve fitting. Two-stage linear regression models were employed to calculate the threshold effects. There were additional subgroup analyses and testing for interactions.Multiple linear regression studies on a total of 10,372 individuals showed a significant inverse link between WWI and total BMD in adults between 20 and 59 [β = -0.04, 95% CI: (-0.04, -0.03), P<0.0001]. And smoking, race, and chronic kidney disease (CKD) had no significant effect on this negative connection (P for interaction >0.05). In addition, we found a nonlinear relationship between WWI and total BMD in diabetic and CKD patients, for which the saturation point was 11.38 cm/√kg in the CKD patient group and 10.29 cm/√kg in the diabetic patient group.Our analysis demonstrated a significant inverse association between WWI and total BMD in adults aged 20-59.

The relationship between weight-adjusted-waist index and total bone mineral density in adults aged 20-59

The growing interest in oleanolic acid (OA) as a triterpenoid with remarkable health benefits prompts an emphasis on its efficient use in pharmaceutical research. OA exhibits a range of pharmacological effects, including antidiabetic, anti-inflammatory, immune-enhancing, gastroprotective, hepatoprotective, antitumor, and antiviral properties. While OA demonstrates diverse pharmacological effects, optimizing its therapeutic potential requires overcoming significant challenges. In the field of pharmaceutical research, the exploration of efficient drug delivery systems is essential to maximizing the therapeutic potential of bioactive compounds. Efficiently delivering OA faces challenges, such as poor aqueous solubility and restricted bioavailability, and to unlock its full therapeutic efficacy, novel formulation strategies are imperative. This discussion thoroughly investigates different approaches and advancements in OA drug delivery systems with the aim of enhancing the biopharmaceutical features and overall efficacy in diverse therapeutic contexts.

Unlocking the Potential of Oleanolic Acid: Integrating Pharmacological Insights and Advancements in Delivery Systems

Nonalcoholic fatty liver disease (NAFLD) may contribute to osteoporosis. Berberine is a traditional Chinese medicine and was recently shown to be beneficial in NAFLD. However, little is known about its impact on bone loss induced by NAFLD. 

Berberine ameliorates nonalcoholic fatty liver disease-induced bone loss by inhibiting ferroptosis.

Skin wounds are susceptible to microbial infections which commonly lead to the delayed wound healing. Rapid clearance of pathogens from the wound is of great significance and importance for efficient healing of the infected wounds. Herein, we report a multifunctional hybrid dressing, which simply combines sodium bicarbonate (NaHCO3) and hyaluronic acid (HA) for the synergistic wound healing. Addition of NaHCO3 allows the hybrid dressing to have the great antibacterial and antioxidant activity, while maintaining the intrinsic skin repair function of HA. As a result, NaHCO3/HA hybrid dressing showed the great antibacterial activity against both Gram-positive (S. aureus) and Gram-negative (E. coli) pathogens, the ability to improve the fibroblasts proliferation and migration, the cell-protection capacity under H2O2-induced oxidative stress, and most importantly, the great healing efficacy for the mice wound infected by S. aureus. We further found that the epidermal regeneration, the collagen deposition and the angiogenesis were enhanced by NaHCO3/HA hybrid dressing. All these effects were NaHCO3 concentration-dependent. Since the NaHCO3/HA hybrid dressing is drug-free, easily fabricated, biocompatible, and efficient for wound healing, it may have great potentials for clinical management of infected wounds. 

Drug-free and multifunctional sodium bicarbonate/hyaluronic acid hybrid dressing for synergistic healing of infected wounds.

Introduction Mesenchymal stem cells (MSCs) are considered to be the most promising stem cell type for cell-based therapies in regenerative medicine. Based on their potential to home to diseased body sites following a therapeutically application, these cells could (i) differentiate then into organ-specific cell types to locally restore injured cells or, most prominently, (ii) foster tissue regeneration including immune modulations more indirectly by secretion of protective growth factors and cytokines. As tissue-resident stem cells of mesenchymal origin, these cells are morphologically and even molecularly- at least concerning the classical marker genes- indistinguishable from similar lineage cells, particularly fibroblasts. Methods Here we used microarray-based gene expression and global DNA methylation analyses as well as accompanying computational tools in order to specify differences between MSCs and fibroblasts, to further unravel potential identity genes and to highlight MSC signaling pathways with regard to their trophic and immunosuppressive action. Results We identified 1352 differentially expressed genes, of which in the MSCs there is a strong signature for e.g., KRAS signaling, known to play essential role in stemness maintenance, regulation of coagulation and complement being decisive for resolving inflammatory processes, as well as of wound healing particularly important for their regenerative capacity. Genes upregulated in fibroblasts addressed predominately transcription and biosynthetic processes and mapped morphological features of the tissue. Concerning the cellular identity, we specified the already known HOX code for MSCs, established a potential HOX code for fibroblasts, and linked certain HOX genes to functional cell-type-specific properties. Accompanied methylation profiles revealed numerous regions, especially in HOX genes, being differentially methylated, which might provide additional biomarker potential. Discussion Conclusively, transcriptomic together with epigenetic signatures can be successfully be used for the definition (cellular identity) of MSCs versus fibroblasts as well as for the determination of the superior functional properties of MSCs, such as their immunomodulatory potential.

Comparative computational analysis to distinguish mesenchymal stem cells from fibroblasts

Since inflammatory cytokines cause stress to chondrocytes and the failure of cartilage defects repair with cartilage tissue engineering, it is necessary to develop a scaffold to maintain cartilage regeneration under inflammatory factors caused stress. Following a berberine-oleanolic acid (OA) complex salt (BOA) was grafted to hyaluronic acid (HA) to obtain water soluble BOA-g-HA, it mixed with silk fibroin (SF) to prepared 4 solutions, which contained 30 mg/mL SF and 0.75, 1.5, 2.25, and 3.0 mg/mL BOA-g-HA respectively. They were lyophilized to fabricate BOA-g-HA/SF-1, BOA-g-HA/SF-2, BOA-g-HA/SF-3, and BOA-g-HA/SF-4 composite scaffolds respectively. All prepared scaffolds displayed porous network structure and exhibited promising mechanical properties for tissue engineering applications. Among them, the BOA-g-HA/SF-3 composite scaffold showed the highest influence on maintaining chondrocytic phenotype of chondrocytes under IL-1β induced stress. Following SF, HA/SF, and BOA-g-HA/SF-3 composite scaffolds with seeded chondrocytes were treated with IL-1β induction for 1 week, specimens were incubated with cell culture medium for 3 week or were subcutaneously implanted into nude mice for 4 weeks. The results demonstrated that the BOA-g-HA/SF-3 composite scaffold promotes cartilage tissue regeneration in vitro and in vivo under IL-1β caused stress, suggesting that it can be potential applied for repairing cartilage defects in osteoarthritis patients. 

Berberine oleanolic acid complex salt grafted hyaluronic acid/silk fibroin (BOA-g-HA/SF) composite scaffold promotes cartilage tissue regeneration under IL-1β caused stress.

ABSTRACT Bariatric surgery (BS) is an effective treatment for obesity. Adipose tissue, liver tissue and skeletal muscle are important metabolic tissues. This study investigated hub genes and their association with immune infiltration in these metabolic tissues of obese patients after BS by bioinformatic analysis with Gene Expression Omnibus datasets. Differentially expressed genes (DEGs) were identified, and a protein–protein interaction network was constructed to identify hub genes. As a result, 121 common DEGs were identified and mainly enriched in cytokine–cytokine receptor interactions, chemokine signaling pathway, neutrophil activation and immune responses. Immune cell infiltration analysis showed that the abundance of M1 macrophages was significantly lower in adipose and liver tissue after BS (p<0.05). Ten hub genes (TYROBP, TLR8, FGR, NCF2, HCK, CCL2, LAPTM5, MNDA and S100A9) that were all downregulated after BS were also associated with immune cells. Consistently, results in the validated dataset showed that the expression levels of these hub genes were increased in obese patients and mice, and decreased after BS. In conclusion, this study analysed the potential immune and inflammatory mechanisms of BS in three key metabolic tissues of obese patients, and revealed hub genes associated with immune cell infiltration, thus providing potential targets for obesity treatment.

https://www.tandfonline.com/doi/pdf/10.1080/21623945.2022.2060059?needAccess=true

Integrative analyses of hub genes and their association with immune infiltration in adipose tissue, liver tissue and skeletal muscle of obese patients after bariatric surgery

Large bone defect reconstruction undergoes hypoxia and remains a major practical challenge. Bone tissue engineering with a more promising stem cell source facilitates the development of better therapeutic outcomes. Human dental follicle stem cells (hDFSCs) with superior multipotency, osteogenic capacity, and accessibility have been proven a promising cell source for bone regeneration. We previously identified a novel long noncoding RNA (lncRNA), HOTAIRM1, to be highly expressed in hDFSCs. Here we found that HOTAIRM1 overexpressed hDFSCs promoted bone regeneration in rat critical‐size calvarial defect model. Mechanically, HOTAIRM1 was induced in hDFSCs under hypoxic conditions and activated HIF‐1α. RNA‐sequencing analysis indicated that HOTAIRM1 upregulated oxygen‐sensing histone demethylases KDM6A/B and suppressed methyltransferase EZH2 via targeting HIF‐1α. The osteogenic differentiation of hDFSCs was accompanied with demethylation of H3K27, and HOTAIRM1 overexpression decreased the distribution of H3K27me3 in osteogenic genes, including ALP, M‐CSF, Wnt‐3a, Wnt‐5a, Wnt‐7a, and β‐catenin, thus promoted their transcription. Our study provided evidence that HOTAIRM1 upregulated KDM6A/B and inhibited EZH2 in a HIF‐1α dependent manner to enhance the osteogenesis of hDFSCs. HOTAIRM1‐mediated hDFSCs may serve as a promising therapeutic approach to promote bone regeneration in clinical practice.

LncRNA HOTAIRM1 promotes dental follicle stem cell‐mediated bone regeneration by regulating HIF‐1α/KDM6/EZH2/H3K27me3 axis

The relationship of obesity and osteoporosis has been widely studied over the past years. However, the implications of obesity for bone health remain controversial, and the underlying molecular mechanism is not yet fully understood. This study demonstrated that high‐fat diet‐induced obesity leads to significantly decreased bone volume/tissue volume (BV/TV), trabecular number (Tb.N), and cortical thickness (Ct.Th) of male rat femur after mechanical loading effects of body weight were controlled. HFD‐induced obese rats exhibited attenuated expression of ferroptosis inhibitory protein SLC7A11 and GPX4 in bone tissues, which was correlated with elevated serum TNF‐α concentration. Ferroptosis inhibitor administration could effectively rescue decreased osteogenesis‐associated type H vessels and osteoprogenitors, and downregulate serum levels of TNF‐α to ameliorate bone loss in obese rats. Since ferroptosis and TNF‐α both affect bone and vessel formation, we further investigated the interaction between ferroptosis and TNF‐α, and its impact in osteogenesis and angiogenesis in vitro. In human osteoblast‐like MG63 and umbilical vein endothelial cells (HUVEC), TNF‐α/TNFR2 signaling promoted cystine uptake and GSH biosynthesis to provide protection against low‐dose ferroptosis inducer erastin. While, TNF‐α/TNFR1 facilitated ferroptosis in the presence of high‐dose erastin through ROS accumulation. Moreover, TNF‐α regulated ferroptosis‐induced osteogenic and angiogenic dysfunctions based on its ferroptosis regulatory role. Meanwhile, ferroptosis inhibitors could reduce intracellular ROS overproduction and enhance osteogenesis and angiogenesis in TNF‐α‐treated MG63 and HUVECs. This study revealed the interaction between ferroptosis and TNF‐α and its impact in osteogenesis and angiogenesis, which provides new insights into the pathogenesis and regenerative therapy of obesity‐related osteoporosis.

Interaction between ferroptosis and TNF‐α: Impact in obesity‐related osteoporosis

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Berberine oleanolic acid complex salt grafted hyaluronic acid/silk fibroin (BOA-g-HA/SF) composite scaffold promotes cartilage tissue regeneration under IL-1β caused stress.

Integrative analyses of hub genes and their association with immune infiltration in adipose tissue, liver tissue and skeletal muscle of obese patients after bariatric surgery

LncRNA HOTAIRM1 promotes dental follicle stem cell‐mediated bone regeneration by regulating HIF‐1α/KDM6/EZH2/H3K27me3 axis

Interaction between ferroptosis and TNF‐α: Impact in obesity‐related osteoporosis