The effect of negative pressure wound therapy on the outcome of diabetic foot ulcers: A meta-analysis.

Negative pressure injury is one of the auxiliary methods of treating diabetes foot ulcers. It has been shown to be superior to conventional techniques in randomized controlled trials (RCTs). Nevertheless, the results of observational research are still scarce. A systematic review of RCTs and observations was carried out to evaluate the effectiveness and security of negative pressure wound therapy (NPWT) treatment for diabetes foot ulcers. Three English e-databases have been found for NPWT research. The meta-analyses of the comparative studies provided point estimates of results. Intermediate results were given as median and binary values were given in the form of odds ratios (OR). Seventeen trials, 13 RCTs and four randomized, controlled trials were found in the survey. Of these, 831 were treated with NPWT, 834 were treated with standard therapy. A total of 14 studies have been conducted to investigate the influence of NPWT on the healing of diabetic foot ulcers(DFU). In the study, NPWT was shown to speed up the healing of the wound in DFU patients(OR, 2.57; 95% CI, 1.72, 3.85 p < 0.0001). A subgroup analysis showed that NPWT was associated with an acceleration of the wound healing rate in 10 RCT trials (OR, 2.48; 95% CI, 1.58, 3.89 p < 0.001). In the four nRCT trials, NPWT was also shown to speed up the healing of the wound(OR, 2.95; 95% CI, 1.03, 8.42 p = 0.04). In 11 studies, the influence of NPWT on amputations of diabetes mellitus (DM) foot ulcers was investigated. The results showed that NPWT was associated with a reduction in amputations (OR, 0.53; 95% CI, 0.37, 0.74 p = 0.0002).In a subgroup of RCT trials, nine RCT trials showed a reduction in amputations(OR, 0.61; 95% CI, 0.43, 0.87 p = 0.007). In both nRCT trials, NPWT also showed a reduction in amputations (OR, 0.03; 95% CI, 0.00, 0.24 p = 0.001). Generally speaking, NPWT can help to heal the wound and lower the risk of amputations in people with diabetes. The subgroup analysis showed similar results for the RCT and non-RCT trials. NPWT can be used to treat diabetes foot ulcers caused by diabetes.

A critical review on intestinal mucosal barrier protection effects of dietary polysaccharides.

Studies have shown that dietary polysaccharides, which are widely present in natural foods, have an important impact on the intestinal mucosal barrier. Dietary polysaccharides can maintain the intestinal barrier function through multiple mechanisms. The intestinal barrier is composed of mechanical, chemical, immune, and biological barriers, and dietary polysaccharides, as a bioactive component, can promote and regulate these four barriers. Dietary polysaccharides can enhance the expression of tight junction proteins and mucins such as occludin-1 and zonula occludens-1 (ZO-1) between intestinal epithelial cells, inhibit inflammatory response and oxidative stress, increase the growth of beneficial bacteria, produce beneficial metabolites such as short chain fatty acids (SCFAs), and promote the proliferation and metabolism of immune cells. Given the critical role of the intestinal mucosal system in health and disease, the protective effects of dietary polysaccharides may be potentially valuable for the prevention and treatment of gut-related diseases. Therefore, it is of great significance to further study the mechanism and application prospects of the intestinal mucosal barrier derived from plant, animal, fungal and bacterial sources.

Enhancing supply chain management in the physical internet: a hybrid SAGA approach.

This paper introduces an advanced inventory replenishment optimization approach tailored for the Physical Internet (PI), addressing the dynamic and complex nature of this environment. We propose a hybrid Simulated Annealing-Genetic Algorithm (SA-GA), engineered to optimize the balance between exploration and exploitation, ensuring adaptability and efficiency in a variety of PI contexts. The study also presents an enriched mathematical model integrating dynamic demand, and multi-objective optimization. The SA-GA algorithm emerges as a novel contribution, characterized by its computational efficiency and adaptability, marking an advancement in PI inventory management. The incorporation of real-time data analytics in our dynamic inventory replenishment strategy enhances adaptability and responsiveness, while the robust mathematical model offers a versatile tool for both theoretical analysis and practical application. Collectively, these innovations help bridge existing gaps in PI inventory management and serve as a reference for other similar studies.

Chitosan oligosaccharide suppresses osteosarcoma malignancy by inhibiting CEMIP via the PI3K/AKT/mTOR pathway.

Osteosarcoma is a malignant bone tumor that is prone to metastasize early and primarily affects children and adolescents. Cell migration-inducing protein (CEMIP) plays a crucial role in the progression and malignancy of various tumor diseases, including osteosarcoma. Chitosan oligosaccharide (COS), an oligomer isolated from chitin, has been found to have significant anti-tumor activity in various cancers. This study investigates the effects of COS on CEMIP expression in osteosarcoma and explores the underlying mechanism. In present study, in vitro experiments were conducted to confirm the inhibitory activity of COS on human osteosarcoma cells. Our results demonstrate that COS possesses inhibitory effects against human osteosarcoma cells and significantly suppresses CEMIP expression in vitro. Next, we studied the inhibition of the expression of CEMIP by COS and then performed bioinformatics analysis to explore the potential inhibitory mechanism of COS against signaling pathways involved in regulating CEMIP expression. Bioinformatics analysis predicted a close association between the PI3K signaling pathway and CEMIP expression and that the inhibitory effect of COS on CEMIP expression may be related to PI3K signaling pathway regulation. The results of this study show that COS treatment significantly inhibits CEMIP expression and the PI3K/AKT/mTOR signaling pathway, as observed both in vitro and in vivo. This study demonstrates that COS could inhibit the expression of CEMIP, which is closely related to osteosarcoma malignancy. This inhibitory effect may be attributed to the inhibition of the PI3K/AKT/mTOR signaling pathway in vitro and in vivo.

Study on DNA Storage Encoding Based IAOA under Innovation Constraints.

With the informationization of social processes, the amount of related data has greatly increased, making traditional storage media unable to meet the current requirements for data storage. Due to its advantages of a high storage capacity and persistence, deoxyribonucleic acid (DNA) has been considered the most prospective storage media to solve the data storage problem. Synthesis is an important process for DNA storage, and low-quality DNA coding can increase errors during sequencing, which can affect the storage efficiency. To reduce errors caused by the poor stability of DNA sequences during storage, this paper proposes a method that uses the double-matching and error-pairing constraints to improve the quality of the DNA coding set. First, the double-matching and error-pairing constraints are defined to solve problems of sequences with self-complementary reactions in the solution that are prone to mismatch at the 3' end. In addition, two strategies are introduced in the arithmetic optimization algorithm, including a random perturbation of the elementary function and a double adaptive weighting strategy. An improved arithmetic optimization algorithm (IAOA) is proposed to construct DNA coding sets. The experimental results of the IAOA on 13 benchmark functions show a significant improvement in its exploration and development capabilities over the existing algorithms. Moreover, the IAOA is used in the DNA encoding design under both traditional and new constraints. The DNA coding sets are tested to estimate their quality regarding the number of hairpins and melting temperature. The DNA storage coding sets constructed in this study are improved by 77.7% at the lower boundary compared to existing algorithms. The DNA sequences in the storage sets show a reduction of 9.7-84.1% in the melting temperature variance, and the hairpin structure ratio is reduced by 2.1-80%. The results indicate that the stability of the DNA coding sets is improved under the two proposed constraints compared to traditional constraints.

Increased emergency cases for out-of-hospital cardiac arrest due to cold spells in Shenzhen, China.

Cold spells have been associated with specific diseases. However, there is insufficient scientific evidence on the effects of cold spells on out-of-hospital cardiac arrest (OHCA). Data on OHCA cases and on meteorological factors and air pollutants were collected between 2013 and 2020. We adopted a quasi-Poisson generalized additive model with a distributed lag nonlinear model (DLNM) to estimate the effect of cold spells on daily OHCA incidence. Backward attributable risk within the DLNM framework was calculated to quantify the disease burden. We compared the effects and OHCA burden of cold spells using nine definitions. The risks of different cold spells on OHCA increased at higher intensities and longer durations. Based on Akaike's information criterion for the quasi-Poisson regression model and the attributable risk, the optimal cold spell was defined as a period in the cold month when the daily mean temperature was below the 10th percentile of the temperature distribution in the study period for at least 2 days. The single-day effect of the optimal cold spell on OHCA occurred immediately and lasted for approximately 1 week. The maximum single-day effect was 1.052 (95% CI: 1.018-1.087) at lag0, while the maximum cumulative effect was 1.433 (95% CI:1.148-1.788) after a 14-day lag. Men were more susceptible to cold spells. Young and middle-aged people were affected by cold spells similar to the elderly. Cold spells can increase the risk of OHCA with an approximately 1-week lag effect. Health regulators should take more targeted measures to protect susceptible populations during cold weather.

CountShoots: Automatic Detection and Counting of Slash Pine New Shoots Using UAV Imagery.

The density of new shoots on pine trees is an important indicator of their growth and photosynthetic capacity. However, traditional methods to monitor new shoot density rely on manual and destructive measurements, which are labor-intensive and have led to fewer studies on new shoot density. Therefore, in this study, we present user-friendly software called CountShoots, which extracts new shoot density in an easy and convenient way using unmanned aerial vehicles based on the YOLOX and Slash Pine Shoot Counting Network (SPSC-net) models. This software mainly consists of 2 steps. Firstly, we deployed a modified YOLOX model to identify the tree species and location from complex RGB background images, which yielded a high recognition accuracy of 99.15% and 95.47%. These results showed that our model produced higher detection accuracy compared to YOLOv5, Efficientnet, and Faster-RCNN models. Secondly, we constructed an SPSC-net. This methodology is based on the CCTrans network, which outperformed DM-Count, CSR-net, and MCNN models, with the lowest mean squared error and mean absolute error results among other models (i.e., 2.18 and 1.47, respectively). To our best knowledge, our work is the first research contribution to identify tree crowns and count new shoots automatically in slash pine. Our research outcome provides a highly efficient and rapid user-interactive pine tree new shoot detection and counting system for tree breeding and genetic use purposes.

An enhanced whale optimization algorithm for DNA storage encoding.

Metaheuristic algorithms have the drawback that local optimal solutions are prone to precocious convergence. In order to overcome the disadvantages of the whale optimization algorithm, we propose an improved selective opposition whale optimization algorithm (ISOWOA) in this paper. Firstly, the enhanced quasi-opposition learning (EQOBL) is applied to selectively update the position of the predator, calculate the fitness of the population before and after, and retain optimal individuals as the food source position; Secondly, an improved time-varying update strategy for inertia weight predator position is proposed, and the position update of the food source is completed by this strategy. The performance of the algorithm is analyzed by 23 benchmark functions of CEC 2005 and 15 benchmark functions of CEC 2015 in various dimensions. The superior results are further shown by Wilcoxon's rank sum test and Friedman's nonparametric rank test. Finally, its applicability is demonstrated through applications to the field of biological computing. In this paper, our aim is to achieve access to DNA files and designs high-quantity DNA code sets by ISOWOA. The experimental results show that the lower bounds of the multi-constraint storage coding sets implemented in this paper equals or surpasses that of previous optimal constructions. The data show that the amount of the DNA storage cods filtered by ISOWOA increased 2-18%, which demonstrates the algorithm's reliability in practical optimization tasks.

Aloin induced apoptosis by enhancing autophagic flux through the PI3K/AKT axis in osteosarcoma.

BACKGROUND: Osteosarcoma is a malignant tumor of bone and soft tissue in adolescents. Due to its tumor biological behavior pattern, osteosarcoma usually generates poor prognosis. Autophagy is an important self-defense mechanism in osteosarcoma. METHODS: Cell viability in IC50 testing and reverse assays was examined by the MTT assay. Cell apoptosis conditions were examined by flow cytometry, Hoechst 33,342 staining and apoptosis-related protein immunoblotting. Autophagy conditions were tested by autophagy-related protein immunoblotting, transmission electron microscopic observation and dual fluorescence autophagy flux detection. The possible targets of aloin were screened out by network pharmacology and bioinformatic methods. Osteosarcoma xenografts in nude BALB/c mice were the model for in vivo research on tumor suppression, autophagy induction, pathway signaling and toxicity tests. In vivo bioluminescence imaging systems, immunohistochemical assays, and gross tumor volume comparisons were applied as the main research methods in vivo. RESULTS: Aloin induced osteosarcoma apoptosis in a dose-dependent manner. Its possible effects on the PI3K/AKT pathway were screened out by network pharmacology methods. Aloin increased autophagic flux in osteosarcoma by downregulating the PI3K/AKT pathway. Aloin promoted autophagic flux in the osteosarcoma cell lines HOS and MG63 in a dose-dependent manner by promoting autophagosome formation. Chloroquine reversed the apoptosis-promoting and autophagy-enhancing effects of aloin. Autophagy induced by starvation and rapamycin significantly enhanced the autophagic flux and apoptosis induced by aloin, which verified the role of the PI3K/AKT axis in the pharmacological action of aloin. Therapeutic effects, autophagy enhancement and regulatory effects on the PI3K/AKT/mTOR pathway were demonstrated in a nude mouse xenogeneic osteosarcoma transplantation model. CONCLUSIONS: Aloin inhibited the proliferation of osteosarcoma by inhibiting the PI3K/AKT/mTOR pathway, increasing autophagic flux and promoting the apoptosis of osteosarcoma cells.

Blockage of Extracellular Signal-Regulated Kinase Exerts an Antitumor Effect via Regulating Energy Metabolism and Enhances the Efficacy of Autophagy Inhibitors by Regulating Transcription Factor EB Nuclear Translocation in Osteosarcoma.

Accumulating evidence suggests that extracellular signal-regulated kinase (ERK) is a valuable target molecule for cancer. However, antitumor drugs targeting ERK are still in their clinical phase and no FDA-approved medications exist. In this study, we identified an ERK inhibitor (ERKi; Vx-11e) with potential antitumor activities, which was reflected by the inhibition in the survival and proliferation of Osteosarcoma (OS) cells. Mechanistically, the ERKi regulated autophagic flux by promoting the translocation of transcription factor EB (TFEB) in OS cells, thereby increasing the dependence of OS cells on autophagy and sensitivity to treatment with autophagy inhibitors in OS. Besides, we also found that the ERKi could regulate mitochondrial apoptosis through the ROS/mitochondria pathway and aerobic glycolysis in OS, which also increases the dependence of OS cells on autophagy to clear metabolites to a certain extent. These results may provide a reference for the clinically improved efficacy of ERKis in combination with autophagy inhibitors in the treatment of OS and indicate its potential as a therapeutic agent.

Hydrogen Sulfide Improves Functional Recovery in Rat Traumatic Spinal Cord Injury Model by Inducing Nuclear Translocation of NF-E2-Related Factor 2.

Hydrogen sulfide (H2S), an important gaseous messenger, is known to have neuroprotective effects in many neurological disorders. This study examined the neuroprotective effects and the associated mechanisms of H2S in the model Sprague-Dawley (SD) rats with spinal cord injury (SCI). We found that H2S showed neuroprotective effects in SCI model rats, improved the symptoms of neurological impairment, reduced the secretion of inflammatory factors, nerve cell apoptosis, and endoplasmic reticulum (ER), and oxidative stresses. Moreover, these effects were produced by activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) protein. Our results suggest that H2S supplementation could be a potential therapeutic strategy to promote SCI recovery.

A colloidal gold-based immunochromatographic strip for rapid detection of SARS-CoV-2 antibodies after vaccination.

Vaccination interventions is consideredan important preventive measure to block the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and protect the organism from pathogen infection effectively. However, a quick and accurate technique to evaluate the immune efficacy of the SARS-CoV-2 inactivated vaccine remains scarce. In this paper, an IgM-IgG antibody combined detection colloidal gold immunochromatography assay kit was optimized and developed, which can assess the efficacy of the inactivated SARS-CoV-2 vaccine. We collected fingertip blood samples from 3 vaccinees and 1 unvaccinated sample. The results showed that the proportion of antibody was high after the second shots immunization. The colloidal gold-based immunochromatographic strip is rapid, convenient and easy to operate. It can be used as an auxiliary method for preliminary evaluation of the antibody effect of vaccine recipients, and provide a reference index for the potential clinical application value of the vaccine.

Non-destructive Measurements of Toona sinensis Chlorophyll and Nitrogen Content Under Drought Stress Using Near Infrared Spectroscopy.

Drought is a climatic event that considerably impacts plant growth, reproduction and productivity. Toona sinensis is a tree species with high economic, edible and medicinal value, and has drought resistance. Thus, the objective of this study was to dynamically monitor the physiological indicators of T. sinensis in real time to ensure the selection of drought-resistant varieties of T. sinensis. In this study, we used near-infrared spectroscopy as a high-throughput method along with five preprocessing methods combined with four variable selection approaches to establish a cross-validated partial least squares regression model to establish the relationship between the near infrared reflectance spectroscopy (NIRS) spectrum and physiological characteristics (i.e., chlorophyll content and nitrogen content) of T. sinensis leaves. We also tested optimal model prediction for the dynamic changes in T. sinensis chlorophyll and nitrogen content under five separate watering regimes to mimic non-destructive and dynamic detection of plant leaf physiological changes. Among them, the accuracy of the chlorophyll content prediction model was as high as 72%, with root mean square error (RMSE) of 0.25, and the RPD index above 2.26. Ideal nitrogen content prediction model should have R 2 of 0.63, with RMSE of 0.87, and the RPD index of 1.12. The results showed that the PLSR model has a good prediction effect. Overall, under diverse drought stress treatments, the chlorophyll content of T. sinensis leaves showed a decreasing trend over time. Furthermore, the chlorophyll content was the most stable under the 75% field capacity treatment. However, the nitrogen content of the plant leaves was found to have a different and variable trend, with the greatest drop in content under the 10% field capacity treatment. This study showed that NIRS has great potential for analyzing chlorophyll nitrogen and other elements in plant leaf tissues in non-destructive dynamic monitoring.

The Mevalonate Pathway Is Important for Growth, Spore Production, and the Virulence of Phytophthora sojae.

The mevalonate (MVA) pathway in eukaryotic organisms produces isoprenoids, sterols, ubiquinone, and dolichols. These molecules are vital for diverse cellular functions, ranging from signaling to membrane integrity, and from post-translational modification to energy homeostasis. However, information on the MVA pathway in Phytophthora species is limited. In this study, we identified the MVA pathway genes and reconstructed the complete pathway in Phytophthora sojae in silico. We characterized the function of the MVA pathway of P. sojae by treatment with enzyme inhibitor lovastatin, deletion of the geranylgeranyl diphosphate synthase gene (PsBTS1), and transcriptome profiling analysis. The MVA pathway is ubiquitously conserved in Phytophthora species. Under lovastatin treatment, mycelial growth, spore production, and virulence of P. sojae were inhibited but the zoospore encystment rate increased. Heterozygous mutants of PsBTS1 showed slow growth, abnormal colony characteristics, and mycelial morphology. Mutants showed decreased numbers of sporangia and oospores as well as reduced virulence. RNA sequencing analysis identified the essential genes in sporangia formation were influenced by the enzyme inhibitor lovastatin. Our findings elucidate the role of the MVA pathway in P. sojae and provide new insights into the molecular mechanisms underlying the development, reproduction, and virulence of P. sojae and possibly other oomycetes. Our results also provide potential chemical targets for management of plant Phytophthora diseases.

Water extract of sporoderm-broken spores of Ganoderma lucidum enhanced pd-l1 antibody efficiency through downregulation and relieved complications of pd-l1 monoclonal antibody.

PURPOSE: Osteosarcoma is a malignant musculoskeletal tumor with early metastasis and a poor prognosis, especially in adolescents. Ganoderma lucidum (Leyss. Ex Fr.) Karst (G. lucidum), a traditional East Asian medicine, has been reported to play a critical role in antitumor and immunomodulatory activity. The aim of this study was to investigate the effects and molecular mechanisms of water extract of sporoderm-broken spores of G. lucidum (BSGWE) on osteosarcoma PD-L1 (programmed cell death-ligand 1) transcriptional regulation, efficacy enhancement, and side effect remission. METHODS: The antitumor effects on cell proliferation of BSGWE in osteosarcoma cells were detected by apoptosis flow cytometry, and the migration ability of HOS and K7M2 cells were evaluated by cell scratch assay. Potential signaling regulation of PD-L1 was detected by western blotting. To confirm the signaling pathway of BSGWE-related PD-L1 downregulation, a pho-STAT3 turnover experiment was carried out. Colivelin was administered as a pho-STAT3 activator to rescue the BSGWE-induced PD-L1 inhibition. To further study in vivo signaling, in a Balb/c osteosarcoma allograft model, tumor volume was measured using an in vivo bioluminescence imaging system. The body weight curve and tumor volume curve were analyzed to reveal the remission effects of BSGWE on PD-L1 antibody-related body weight loss and its immunomodulatory effects on the osteosarcoma and spleen. The PD-L1 expression level and expression of related transcription-factor pho-STAT3 in tumor cells and spleens were assessed by IHC analysis. RESULTS: BSGWE suppressed the proliferation and migration of osteosarcoma cells in vitro via induction of apoptosis. In addition, BSGWE downregulated PD-L1 expression and related STAT3 (signal transducers and activators of transcription) phosphorylation levels in a dose-dependent manner. Western blotting and qRT-PCR assay revealed that BSGWE downregulated PD-L1 expression by inhibiting STAT3 phosphorylation. A turnover experiment showed that colivelin administration could rescue PD-L1 inhibition via pho-STAT3 activation. BSGWE not only downregulated PD-L1 expression via the STAT3 pathway in an allograft Balb/c mouse model, but also relieved complications including weight loss and spleen atrophy in a mouse monoclonal antibody therapy model on the basis of its traditional advantages in immune enhancement. CONCLUSION: BSGWE downregulated PD-L1 expression via pho-STAT3 inhibition of protein and RNA levels. BSGWE enhanced PD-L1 antibody efficacy via phosphorylated STAT3 downregulation in vitro and in vivo. BSGWE also relieved complications of weight loss and spleen atrophy in a murine allograft osteosarcoma immune checkpoint blockade therapy model.

Antibody-Based Immunotherapeutic Strategies for the Treatment of Hematological Malignancies.

As the most common type of cancer in the world, hematological malignancies (HM) account for 10% of all annual cancer deaths and have attracted more attention. Conventional treatments, such as chemotherapy, radiotherapy, and hematopoietic stem cell transplantation (HSCT), could relieve patients suffering HM. However, serious side effects and high costs bring patients both physical complaints and mental pressure. Recently, compared with conventional therapeutic strategies for HM patients, antibody-based immunotherapies, including cancer vaccines, oncolytic virus therapies, monoclonal antibody treatments, and CAR-T cell therapies, have displayed longer survival time and fewer adverse reactions, even though specific efficacy and safety of these antibody-based immunotherapies still need to be evaluated and improved. This review summarized the advantages of antibody-based immunotherapies over conventional treatments, as well as its existing difficulties and solutions, thereby enhancing the understanding and applications of antibody-based immunotherapies in HM treatment.

Application of Chimeric Antigen Receptor T Cells in the Treatment of Hematological Malignancies.

T cell immune protection plays a pivotal role in the treatment of patients with hematological malignancies. However, T cell exhaustion might lead to the possibility of immune escape of hematological malignancies. Adoptive cell therapy (ACT) with chimeric antigen receptor T (CAR-T) cells can restore the activity of exhausted T cell through reprogramming and is widely used in the treatment of relapsed/refractory (r/r) hematological malignancies. Of note, CD19, CD20, CD30, CD33, CD123, and CD269 as ideal targets have shown extraordinary potential for CAR-T cell therapy and other targets such as CD23 and SLAMF7 have brought promising future for clinical trials. However, CAR-T cells can also produce some adverse events after treatment of hematological malignancies, such as cytokine release syndrome (CRS), neurotoxicity, and on-target/off-tumor toxicity, which may cause systemic immune stress inflammation, destruction of the blood-brain barrier, and even normal tissue damage. In this review, we aim to summarize the composition of CAR-T cell and its application in the treatment of acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL), multiple myeloma (MM), and acute myeloid leukemia (AML). Moreover, we will review the disadvantages of CAR-T cell therapy and propose several comprehensive recommendations which might guide its development.

Catalpol suppresses osteoclastogenesis and attenuates osteoclast-derived bone resorption by modulating PTEN activity.

Excessive activation of osteoclast activity is responsible for many bone diseases, such as osteoporosis, rheumatoid arthritis, periprosthetic osteolysis, and periodontitis. Natural compounds that inhibit osteoclast formation and/or function have therapeutic potential for treating these diseases. Catalpol, a bioactive iridoid extracted from a traditional herbal medicine Rehmannia glutinosa, exhibits various pharmacological properties, including anti-inflammatory, antioxidant, antidiabetic, and antitumor effects. However, its effects on osteoclast formation and function remain unknown. In the present study, we showed that catalpol inhibited receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation and bone resorption, as well as the expression of osteoclast-related marker genes. The investigation of molecular mechanisms showed that catalpol upregulated phosphatase and tensin homolog (PTEN) activity by reducing its ubiquitination and degradation, subsequently suppressing RANKL-induced NF-κB and AKT signaling pathways, leading to an inhibition on NFATc1 induction. Furthermore, catalpol protected mice against inflammation- and ovariectomy-induced bone loss by inhibiting osteoclast activity in vivo. These results suggest that catalpol might be developed as a promising candidate for treating osteoclast-related bone diseases.

Stachydrine prevents LPS-induced bone loss by inhibiting osteoclastogenesis via NF-κB and Akt signalling.

Osteoclast overactivation-induced imbalance in bone remodelling leads to pathological bone destruction, which is a characteristic of many osteolytic diseases such as rheumatoid arthritis, osteoporosis, periprosthetic osteolysis and periodontitis. Natural compounds that suppress osteoclast formation and function have therapeutic potential for treating these diseases. Stachydrine (STA) is a bioactive alkaloid isolated from Leonurus heterophyllus Sweet and possesses antioxidant, anti-inflammatory, anticancer and cardioprotective properties. However, its effects on osteoclast formation and function have been rarely described. In the present study, we found that STA suppressed receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation and bone resorption, and reduced osteoclast-related gene expression in vitro. Mechanistically, STA inhibited RANKL-induced activation of NF-κB and Akt signalling, thus suppressing nuclear factor of activated T cells c1 induction and nuclear translocation. In addition, STA alleviated bone loss and reduced osteoclast number in a murine model of LPS-induced inflammatory bone loss. STA also inhibited the activities of NF-κB and NFATc1 in vivo. Together, these results suggest that STA effectively inhibits osteoclastogenesis both in vitro and in vivo and therefore is a potential option for treating osteoclast-related diseases.

Identification of key genes and pathways in Ewing's sarcoma patients associated with metastasis and poor prognosis.

Background: Ewing sarcoma (ES) is the second commonest primary malignant bone neoplasm. Metastatic status at diagnosis strongly predicted poor prognosis of Ewing sarcoma patients. Yet little was known about the underlying mechanism of ES metastasis. Purpose:This study intended to identify the relationship between key genes/pathways and metastasis/poor prognosis in Ewing's sarcoma patients by using bioinformatic method. Methods: In this study, multi-center sequencing data were obtained from the GEO database, including gene and miRNA expression profile and prognosis information of ES patients. Differentially expressed genes (DEGs) were identified between primary and metastasis ES samples by the GEO2R online tool. Gene ontology (Go) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses of DEGs were performed. And PPI network analyses were conducted. The ES patient's prognostic information was employed for survival analysis, and the potential relationship between miRNAs and key genes was analyzed. Results: The results showed that a total of 298 and 428 DEGs were screened out in metastasis samples based on GSE17618 and GSE12102 dataset compared to primary samples respectively. The most significantly enriched KEGG pathway was the mismatch repair (MMR) pathway. MSH2, MSH6, RPA2, and RFC2 that belong to the MMR pathway were identified as key genes. Moreover, the expression of key genes was increased in metastasis samples compared with primary ones and was associated with poor event-free and overall survival of ES patients. The negative correlation of the expression level of the key genes with patients prognosis also supported by TCGA sarcoma database. Furthermore, knockdown of EWSR/FLI1 fusion in ES cell line A673 down-regulates the expression of the 4 key genes was revealed by GDS4962. Conclusion: In conclusion, the present study indicated that the key genes promote our understanding of the molecular mechanisms underlying the development of ES metastasis, and might be used as molecular targets and diagnostic biomarkers for the treatment of ES.