A natural agent, 5-deoxycajanin, mitigates estrogen-deficiency bone loss via modulating osteoclast-osteoblast homeostasis.

Hyperactive osteoclasts and hypoactive osteoblasts usually result in osteolytic conditions such as estrogen-deficiency bone loss. Few natural compounds that both attenuating bone resorption and enhancing bone formation could exert effects on this imbalance. 5-Deoxycajanin (5-D), an isoflavonoid extracted from Cajan leaf with estrogen-like properties, were found to have beneficial pharmacological effects on rebalancing the activities of osteoclasts and osteoblasts. This study revealed that 5-D at the same concentration could inhibit osteoclastogenesis of BMMs and promoted osteoblast differentiation of BMSCs. 5-D not only attenuated the fluorescent formation of RANKL-induced F-actin belts and NFATc1, but also activated ALP and RUNX2 expressions. As to downstream factor expressions, 5-D could block osteoclast-specific genes and proteins including NFATc1 and CTSK, while increased osteogenic genes and proteins including OPG and OCN, as confirmed by Real-time PCR and Western Blotting. Additionally, the network pharmacology and molecular docking identified the involvement of 5-D in the MIF and MAPK signaling pathways and the stable binding between 5-D and MAPK2K1. Further Western blot studies showed that 5-D decreased the phosphorylation of p38 and ERK in osteoclasts, but promoted these phosphorylations in osteoblasts. In a female C57BL/6J mouse model of estrogen deficiency-induced bone loss, 5-D demonstrated efficacy in enhancing BMD through attenuating osteoclast activities and promoting osteogenesis. These results underscore the potential application of 5-D on treating osteolysis resulting from hyperactive osteoclasts and hypoactive osteoblasts, shedding light on modulating osteoclast-osteoblast homeostasis.

Tanshinone I attenuates estrogen-deficiency bone loss via inhibiting RANKL-induced MAPK and NF-κB signaling pathways.

AIM OF THE STUDY: This study aims to reveal the role of Tanshinone I (TI) in inhibiting osteoclast activity and bone loss in vitro and in vivo, as well as elucidate its underlying molecular mechanism. MATERIALS AND METHODS: A mouse model of estrogen deficiency was used to assess the inhibitory effect of TI on osteoclast activity and subsequent bone loss. To validate the impact of TI on osteoclast formation, TRAcP staining and pseudopodia belt staining were conducted. The expressions of osteoclast-specific genes and proteins were evaluated using RT-PCR and Western Blot analyses. Additionally, immunofluorescence staining was employed to examine the effect of TI on p65 nuclear translocation and the expression level of reactive oxygen species (ROS). RESULTS: TI demonstrated significant efficacy in alleviating bone mass loss and suppressing osteoclast activity and function in ovariectomized mice. This outcome was predominantly ascribed to a decrease in ROS levels, thereby impeding the NF-κB signaling pathway and the translocation of p65 to the nucleus. Additionally, TI hindered the RANKL-induced phosphorylation of the MAPK signaling pathway. Moreover, TI played a role in the reduction of osteoclast-specific genes and proteins. CONCLUSIONS: To summarize, this study sheds light on TI's capacity to modulate various signaling pathways triggered by RANKL, effectively impeding osteoclast formation and mitigating bone loss resulting from estrogen deficiency. Consequently, TI emerges as a promising therapeutic option for estrogen-deficiency bone loss.

Dihydrotanshinone I attenuates estrogen-deficiency bone loss through RANKL-stimulated NF-κB, ERK and NFATc1 signaling pathways.

Postmenopausal osteoporosis, a chronic condition that predominantly affects postmenopausal women, presents a significant impediment to their overall well-being. The condition arises from estrogen deficiency, leading to enhanced osteoclast activity. Salvia miltiorrhiza, a well-established Chinese herbal medicine with a history of clinical use for osteoporosis treatment, contains diverse active constituents that have shown inhibitory effects on osteoclast formation and bone loss. Dihydrotanshinone I (DTI), a phenanthrenonequinone compound derived from the root of Salvia miltiorrhiza, has been identified as a potential therapeutic agent, although its mechanism of action on osteoclasts remains elusive. In this study, we aimed to elucidate the inhibitory potential of DTI on RANKL-induced osteoclastogenesis. We observed the ability of DTI to effectively impede the expression of key osteoclast-specific genes and proteins, as assessed by Real-time PCR and Western Blotting analyses. Mechanistically, DTI exerted its inhibitory effects on osteoclast formation by modulating critical signaling pathways including NF-κB, ERK, and calcium ion signaling. Notably, DTI intervention disrupted the nuclear translocation and subsequent transcriptional activity of the NFATc1, thus providing mechanistic insights into its inhibitory role in osteoclastogenesis. To further assess the therapeutic potential of DTI, we employed an ovariectomized osteoporosis animal model to examine its impact on bone loss. Encouragingly, DTI demonstrated efficacy in mitigating bone loss induced by estrogen deficiency. In conclusion, our investigation elucidates the ability of DTI to regulate multiple signaling pathways activated by RANKL, leading to the inhibition of osteoclast formation and prevention of estrogen-deficiency osteoporosis. Consequently, DTI emerges as a promising candidate for the treatment of osteoporosis.

Protein-folding-inspired approach for UF fouling mitigation using elevated membrane cleaning temperature and residual hydrophobic-modified flocculant after flocculation-sedimentation pre-treatment.

Hydrophobic-modified flocculants have demonstrated considerable promise in the removal of emerging contaminants by flocculation. However, there is a lack of information about the impacts of dosing such flocculants on the performance of subsequent treatment unit(s) in the overall water treatment process. In this work, inspired by the ubiquitous protein folding phenomenon, an innovative approach using an elevated membrane cleaning temperature as the means to induce residual hydrophobic-modified chitosan flocculant (TRC), after flocculation-sedimentation, to reduce membrane fouling in a subsequent ultrafiltration was proposed; this was evaluated in a continuous flocculation-sedimentation-ultrafiltration (FSUF) process treating samples of the Yangtze River. The hydrophobic chains of TRC had similar temperature-dependent hydrophobicity to those of natural proteins. In the 40-day operation of the FSUF system with combined dosing of alum and TRC, a moderately elevated cleaning water temperature (45 °C) of both backwash with air-bubbling and soaking with sponge-scrubbing cleaning, significantly reduced reversible and irreversible fouling resistance by 49.8%∼61.3% and 73.9%∼83.3%, respectively, compared to the system using cleaning water at 25 °C. Material flow analysis, statistical analysis, instrumental characterizations, and computational simulations, showed that the enhanced fouling mitigation originated from three factors: the reduced contaminant accumulation onto membranes, the strengthened membrane-surface-modification role of TRC, and the weakened structure of the fouling material containing TRC, at the elevated cleaning temperature. Other measures of the performance, these being water purification, membrane stability and economic aspects, also confirmed the potential and feasibility of the proposed approach. This work has provided new insights into the role of hydrophobic-modified flocculants in membrane fouling control, in addition to emerging contaminant removal, in a FSUF surface water treatment process.

One in five patients require conversion to arthroplasty after non-vascularized bone grafts in patients with osteonecrosis of the femoral head: a systematic review.

BACKGROUND: Non-vascularized bone grafting (NVBG) has demonstrated to treat osteonecrosis of the femoral head (ONFH). There are a number of articles updating the use of NVBG to treat the ONFH, but the percentage of patients subsequently undergoing a total hip arthroplasty (THA) is controversial. METHODS: Several electronic databases, including PubMed, Embase, Web of Science, and Cochrane databases, were searched to find studies using NVBG to treat ONFH. The pooled rate and 95% confidence interval (CI) were used to assess the conversion rate to THA after NVBG. In addition, we performed subgroup, sensitivity, and publication bias analysis. RESULTS: A total of 37 studies describing 2599 hips were included. The mean weighted follow-up time was 50.5 months and the mean age at surgery was 36.3 years. The conversion rate to THA after NVBG was 21% (95%CI: 17% to 25%), and subgroup analyzes indicated lightbulb, trapdoor and Phemister techniques incidences with THA of 15%, 19%, and 24%, respectively. CONCLUSIONS: This study preliminarily obtained the general trend of the survival rate of NVBG patients, but these results should be interpreted cautiously. Pooled results from 2599 hips and of these nearly 80% with early stage of osteonecrosis, showed that approximately 21% of patients underwent a THA following NVBG. NVBG treatment for patient with ONFH appears to defer or at least delay the need for THA.

Integrated Bioinformatic Analysis of the Shared Molecular Mechanisms Between Osteoporosis and Atherosclerosis.

Background: Osteoporosis and atherosclerosis are common in the elderly population, conferring a heavy worldwide burden. Evidence links osteoporosis and atherosclerosis but the exact underlying common mechanism of its occurrence is unclear. The purpose of this study is to further explore the molecular mechanism between osteoporosis and atherosclerosis through integrated bioinformatic analysis. Methods: The microarray data of osteoporosis and atherosclerosis in the Gene Expression Omnibus (GEO) database were downloaded. The Weighted Gene Co-Expression Network Analysis (WGCNA) and differentially expressed genes (DEGs) analysis were used to identify the co-expression genes related to osteoporosis and atherosclerosis. In addition, the common gene targets of osteoporosis and atherosclerosis were analyzed and screened through three public databases (CTD, DISEASES, and GeneCards). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Metascape. Then, the common microRNAs (miRNAs) in osteoporosis and atherosclerosis were screened out from the Human microRNA Disease Database (HMDD) and the target genes of whom were predicted through the miRTarbase. Finally, the common miRNAs-genes network was constructed by Cytoscape software. Results: The results of common genes analysis showed that immune and inflammatory response may be a common feature in the pathophysiology of osteoporosis and atherosclerosis. Six hub genes (namely, COL1A1, IBSP, CTSD, RAC2, MAF, and THBS1) were obtained via taking interaction of different analysis results. The miRNAs-genes network showed that has-let-7g might play an important role in the common mechanisms between osteoporosis and atherosclerosis. Conclusion: This study provides new sights into shared molecular mechanisms between osteoporosis and atherosclerosis. These common pathways and hub genes may offer promising clues for further experimental studies.

Influence of less invasive hip preservation surgery on subsequent hip arthroplasty for osteonecrosis of the femoral head.

The purpose of this study was to evaluate the outcomes of total hip arthroplasty (THA) following less invasive hip-preserving procedures (LIHPs) and present a critical overview of the literature to aid in better result interpretation. The search time was from the establishment of the database to September 2021, and the outcome indicators were extracted and analyzed by Cochrane Collaboration Review Manager software (RevMan version 5.4). Finally, 10 articles were included in this meta-analysis by searching Chinese databases and English databases. Three of them were published in Chinese, and the remaining studies were published in English. LIHP was further divided into the tantalum rod implantation group and the non-tantalum rod implantation group. The results showed that prior tantalum rod implantation increased the difficulty of conversion to THA, which was reflected mainly in the longer operative time [weighted mean difference (WMD) = 24.50, 95% confidence interval (CI) = 14.09-34.91, P < 0.00001] and greater intraoperative blood loss (WMD = 114.74, 95% CI = 33.52-195.96, P = 0.006), while no significant difference was found between the non-tantalum rod implantation group and the control group. Simultaneously, easier intraoperative fracture [odds ratio (OR) = 5.88, 95% CI = 0.93-37.05, P = 0.06] and stem malalignment (OR = 4.17, 95% CI = 1.18-14.71, P = 0.03) in the LIHP group tended to be observed than in the control THA group. However, there was no significant difference in cup anteversion and inclination angle, ectopic ossification, postoperative Harris Hip Score and survivorship between the LIHP group and the control group. Although LIHP increased the difficulty of the conversion to THA, it does not detrimentally affect the clinical results of subsequent THA in the mid-term follow-up.

Integrated Analysis of Crucial Genes and miRNAs Associated with Osteoporotic Fracture of Type 2 Diabetes.

Purpose: The aim of this study is to explore pathological mechanisms of bone fragility in type 2 diabetes mellitus (T2DM) patients. Methods: Identifying common genes for T2DM and osteoporosis by taking the intersection is shared by the Comparative Toxicogenomics Database (CTD), DISEASES, and GeneCards databases. The differentially expressed genes (DEGs) and the differentially expressed miRNAs (DEMs) were identified by analyzing the Gene Expression Omnibus (GEO) datasets (GSE35958, GSE43950, and GSE70318). FunRich and miRNet were applied to predict potential upstream transcription factors and downstream target genes of candidate DEMs, respectively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore potential mechanisms using Metascape. Eventually, a miRNA-gene network was constructed by Cytoscape software. Results: 271 common targets and 35 common DEGs between T2DM and osteoporosis were screened out in the above databases, and a total of ten DEMs were obtained in the GSE70318. SP1 was predicted to potentially regulate most of the DEMs. Enrichment analysis showed the PI3K-Akt signaling pathway and AGE-RAGE signaling pathway in diabetic complications may play an important role in diabetic skeletal fragility. Two genes (NAMPT and IGFBP5) were considered as key genes involving in the development of diabetic osteoporosis. Through the construction of the miRNA-gene network, most of the hub genes were found to be potentially modulated by miR-96-5p and miR-7-5p. Conclusion: The study uncovered several important genes, miRNAs, and pathological mechanisms involved in diabetic skeletal fragility, among which the PI3K-Akt signaling pathway and AGE-RAGE signaling pathway in diabetic complications may play important roles.

Influence of DOM characteristics on the flocculation removal of trace pharmaceuticals in surface water by the successive dosing of alum and moderately hydrophobic chitosan.

Hydrophobically-modified chitosan (HC) has emerged as a promising flocculant for trace pharmaceutical removal from surface water. However, the variation in the characteristics of dissolved organic matter (DOM) in different water sources influences the efficacy of HC in removing pharmaceutical compounds. In this work, the flocculation performance of sequentially dosing alum and HC (alum+HC) for the treatment of five water types (three synthetic waters, and samples of two real waters collected from the Yangtze River and the Thames River), having different DOM and five representative pharmaceuticals (initial concentration: 100 ng/L), was assessed by bench-scale jar tests. The DOM characteristics were correlated quantitatively with the removal efficiencies (REs) of the pharmaceuticals. Density functional theory computations were performed to illuminate the interfacial interactions in the flocculation. Alum+HC exhibited a remarkably higher RE of all five pharmaceuticals (maximum RE: 73%-95%) from all waters compared to a conventional coagulant or flocculant (alum or polyacrylamide, respectively). In contrast to using HC alone, alum+HC also achieved a higher RE of pharmaceuticals with nearly half the HC dosage, thereby enhancing the cost-effectiveness of the alum+HC dosing system. Among the different key DOM characteristics, the surface charge and molecular weight of DOM had no evident correlation with RE(pharmaceutical), but the hydrophobic/hydrophilic nature and functional group composition of organic carbon of DOM were strongly correlated: Strongly hydrophobic fractions, with C-C & C=C functional groups (binding pharmaceuticals via hydrophobic association), were beneficial, while hydrophilic fractions with C-OH groups were less effective, for pharmaceutical removal. This work showed the enhanced performance of the alum+HC dosing combination in the removal of different pharmaceutical compounds from different waters, and filled the knowledge gap regarding the performance of hydrophobically-modified flocculants in the treatment of different surface water sources.

[3D printing navigation template-guided percutaneous radiofrequency thermocoagulation for V2 trigeminal neuralgia treatment].

OBJECTIVE: This paper aimed to evaluate the effectiveness of the 3D printing puncture navigation template-guided percutaneous radiofrequency thermocoagulation for V2 trigeminal neuralgia treatment. METHODS: A total of 52 patients with V2 trigeminal neuralgia were treated with radiofrequency thermocoagulation. A total of 32 patients were treated under the guidance of the 3D printing puncture navigation template (guide plate group), while 20 patients underwent puncture via pterygopalatine fossa routinely (routine treatment group). The puncture time, operation time, puncture success rate, and immediate postoperative pain were recorded. The degree of immediate postoperative pain was indicated by visual analogue scale (VAS). Barrow Neurological Institute (BNI) classification criteria were used to evaluate the efficacy, and the postoperative complications were observed. All patients were followed up for 1 year. RESULTS: The two groups showed significant decrease in VAS after the operation (P<0.05). The puncture and operation times of the guide plate group were significantly lower than those of the routine treatment group (P<0.05). The difference in terms of the clinical effects and recurrence rate between the two groups was insignificant (P>0.05). CONCLUSIONS: 3D printing puncture navigation template-guided radiofrequency thermocoagulation may increase the operation success rate and reduce complication incidence. Therefore, this technique possesses clinical promotional value.