As the important source of bone cells, osteoblasts are involved in bone formation and repair, and play a key role in maintaining bone balance. If the osteogenic differentiation process in vivo is disrupted, a variety of bone-related diseases may occur. Natural products, which have a wide range of sources, a wide variety of physiological activities, and few toxic side-effects, have been found in recent years to be able to regulate osteoblast differentiation. Based on the sources of natural products, this paper reviews the intervention of natural products from plant, animal and microbial sources on osteogenic differentiation, aiming to provide a theoretical basis for natural products in the treatment of bone diseases.

This study explores the role and underlying molecular mechanisms of fucoidan sulfate(FPS) in regulating heme oxygenase-1(Hmox1)-mediated ferroptosis to ameliorate myocardial injury in diabetic cardiomyopathy(DCM) through in vivo and in vitro experiments and network pharmacology analysis. In vivo, a DCM rat model was established using a combination of "high-fat diet feeding + two low-dose streptozotocin(STZ) intraperitoneal injections". The rats were randomly divided into four groups: normal, model, FPS, and dapagliflozin(Dapa) groups. In vitro, a cellular model was created by inducing rat cardiomyocytes(H9c2 cells) with high glucose(HG), using zinc protoporphyrin(ZnPP), an Hmox1 inhibitor, as the positive control. An automatic biochemical analyzer was used to measure blood glucose(BG), serum aspartate aminotransferase(AST), serum lactate dehydrogenase(LDH), and serum creatine kinase-MB(CK-MB) levels. Echocardiography was used to assess rat cardiac function, including ejection fraction(EF) and fractional shortening(FS). Pathological staining was performed to observe myocardial morphology and fibrotic characteristics. DCFH-DA fluorescence probe was used to detect reactive oxygen species(ROS) levels in myocardial tissue. Specific assay kits were used to measure serum brain natriuretic peptide(BNP), myocardial Fe~(2+), and malondialdehyde(MDA) levels. Western blot(WB) was used to detect the expression levels of myosin heavy chain 7B(MYH7B), natriuretic peptide A(NPPA), collagens type Ⅰ(Col-Ⅰ), α-smooth muscle actin(α-SMA), ferritin heavy chain 1(FTH1), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), 4-hydroxy-2-nonenal(4-HNE), and Hmox1. Immunohistochemistry(IHC) was used to examine Hmox1 protein expression patterns. FerroOrange and Highly Sensitive DCFH-DA fluorescence probes were used to detect intracellular Fe~(2+) and ROS levels. Transmission electron microscopy was used to observe changes in mitochondrial morphology. In network pharmacology, FPS targets were identified through the PubChem database and PharmMapper platform. DCM-related targets were integrated from OMIM, GeneCards, and DisGeNET databases, while ferroptosis-related targets were obtained from the FerrDb database. A protein-protein interaction(PPI) network was constructed for the intersection of these targets using STRING 11.0, and core targets were screened with Cytoscape 3.9.0. Molecular docking analysis was conducted using AutoDock and PyMOL 2.5. In vivo results showed that FPS significantly reduced AST, LDH, CK-MB, and BNP levels in DCM model rats, improved cardiac function, decreased the expression of myocardial injury proteins(MYH7B, NPPA, Col-Ⅰ, and α-SMA), alleviated myocardial hypertrophy and fibrosis, and reduced Fe~(2+), ROS, and MDA levels in myocardial tissue. Furthermore, FPS regulated the expression of ferroptosis-related markers(Hmox1, FTH1, SLC7A11, GPX4, and 4-HNE) to varying degrees. Network pharmacology results revealed 313 potential targets for FPS, 1 125 targets for DCM, and 14 common targets among FPS, DCM, and FerrDb. Hmox1 was identified as a key target, with FPS showing high docking activity with Hmox1. In vitro results demonstrated that FPS restored the expression levels of ferroptosis-related proteins, reduced intracellular Fe~(2+) and ROS levels, and alleviated mitochondrial structural damage in cardiomyocytes. In conclusion, FPS improves myocardial injury in DCM, with its underlying mechanism potentially involving the regulation of Hmox1 to inhibit ferroptosis. This study provides pharmacological evidence supporting the therapeutic potential of FPS for DCM-induced myocardial injury.
Animals ; Ferroptosis/drug effects* ; Rats ; Diabetic Cardiomyopathies/physiopathology* ; Male ; Rats, Sprague-Dawley ; Polysaccharides/pharmacology* ; Heme Oxygenase-1/genetics* ; Myocytes, Cardiac/metabolism* ; Myocardium/pathology* ; Humans ; Cell Line ; Heme Oxygenase (Decyclizing)

This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

Following the core outcome set standards for development(COS-STAD), this study aims to construct core outcome set(COS) for clinical research on traditional Chinese medicine(TCM) treatment of simple obesity. Firstly, a comprehensive review was conducted on the randomized controlled trial(RCT) and systematic review(SR) about TCM treatment of simple obesity that were published in Chinese and English databases to collect reported outcomes. Additional outcomes were obtained through semi-structured interviews with patients and open-ended questionnaire surveys for clinicians. All the collected outcomes were then merged and organized as an initial outcome pool, and then a preliminary list of outcomes was formed after discussion by the working group. Subsequently, two rounds of Delphi surveys were conducted with clinicians, methodology experts, and patients to score the importance of outcomes in the list. Finally, a consensus meeting was held to establish the COS for clinical research on TCM treatment of simple obesity. A total of 221 RCTs and 12 SRs were included, and after integration of supplementary outcomes, an initial outcome pool of 141 outcomes were formed. Following discussions in the steering advisory group meeting, a preliminary list of 33 outcomes was finalized, encompassing 9 domains. Through two rounds of Delphi surveys and a consensus meeting, the final COS for clinical research on TCM treatment of simple obesity was determined to include 8 outcomes: TCM symptom scores, body mass index(BMI), waist-hip ratio, waist circumference, visceral fat index, body fat rate, quality of life, and safety, which were classified into 4 domains: TCM-related outcomes, anthropometric measurements, quality of life, and safety. This study has preliminarily established a COS for clinical research on TCM treatment of simple obesity. It helps reduce the heterogeneity in the selection and reporting of outcomes in similar clinical studies, thereby improving the comparability of research results and the feasibility of meta-analysis and providing higher-level evidence support for clinical practice.
Humans ; Obesity/therapy* ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Drugs, Chinese Herbal/therapeutic use*

Insulin-like growth factor 2 (IGF2) is a critical endocrine mediator implicated in male reproductive physiology. To investigate the correlation between IGF2 protein levels and various aspects of male infertility, specifically focusing on sperm quality, inflammation, and DNA damage, a cohort of 320 male participants was recruited from the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between 1 st January 2024 and 1 st March 2024. The relationship between IGF2 protein concentrations and sperm parameters was assessed, and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility. Enzyme-linked immunosorbent assay (ELISA) was used to measure IGF2 protein levels in seminal plasma, alongside markers of inflammation (tumor necrosis factor-alpha [TNF-α] and interleukin-1β [IL-1β]). The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX (γ-H2AX) was also explored. Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia. Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters, and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm. The observed correlations between IGF2 protein levels and specific sperm parameters, along with its connection to inflammation and DNA damage, underscore the importance of IGF2 in the broader context of male reproductive health. These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility.
Humans ; Male ; Insulin-Like Growth Factor II/metabolism* ; Infertility, Male/genetics* ; DNA Damage ; Adult ; Inflammation/metabolism* ; Spermatozoa/metabolism* ; Semen Analysis ; Semen/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Histones/metabolism* ; Interleukin-1beta/metabolism*

(+)-Strebloside, a significant bioactive compound isolated from the roots of Streblus asper Lour., demonstrates inhibitory effects against multiple malignancies. However, its specific function and underlying mechanistic pathways in Non-Hodgkin lymphoma (NHL) remain unexplored. This investigation sought to elucidate the role and potential mechanisms of (+)-strebloside-induced NHL cell death. The results demonstrated that (+)-strebloside significantly induced apoptosis and ferroptosis in NHL cells, including those from Raji cell-derived xenograft models. Mechanistic analyses revealed that (+)-strebloside enhanced six-transmembrane epithelial antigen of prostate 3 (STEAP3)-induced ferroptosis in NHL, and STEAP3 inhibition reduced the proliferation-inhibitory effects of (+)-strebloside. Furthermore, (+)-strebloside suppressed NHL proliferation through the mitogen-activated protein kinase (MAPK) pathway, and extracellular signal-regulated kinase (ERK) inhibition diminished the proliferation-inhibitory activity induced by (+)-strebloside. These findings indicate that (+)-strebloside presents promising therapeutic potential for NHL treatment.
Humans ; Ferroptosis/drug effects* ; Lymphoma, Non-Hodgkin/physiopathology* ; Cell Line, Tumor ; MAP Kinase Signaling System/drug effects* ; Animals ; Cell Proliferation/drug effects* ; Mice ; Apoptosis/drug effects* ; Membrane Proteins/genetics* ; Xenograft Model Antitumor Assays ; Male ; Mice, Nude

In recent years, the rapid development of transportation and sports industries, coupled with the accelerated population aging in China, has led to a steady increase in the incidence of articular cartilage injuries, wear, and degenerative changes. Currently, the clinical treatment options for cartilage defects primarily include conservative therapies and surgical interventions, both of which have certain limitations. Cartilage tissue engineering (CTE), as a novel technology, provides an infinite prospect for cartilage regeneration and repair. Because of the abilities of scaffolds to mimic the natural cartilage structure, exhibit excellent biocompatibility and biomimetic mechanical properties, and promote cell adhesion and proliferation, scaffolds are considered effective delivery systems for growth factors, genes, and drugs. This review summarizes the clinical treatments for cartilage defects and their limitations, discusses the materials and preparation techniques of scaffolds used in CTE, with a particular focus on drug-loaded scaffold delivery systems in cartilage repair and regeneration, and offers a perspective on the future application of drug-loaded CTE. The aim is to provide theoretical guidance and new approaches for the repair of cartilage defects.
Tissue Engineering/methods* ; Humans ; Tissue Scaffolds ; Drug Delivery Systems/methods* ; Regeneration ; Cartilage, Articular/physiology* ; Animals ; Biocompatible Materials

Objective:To investigate the influence of computer tomography (CT) examination bony parameters and surgical methods on difficult pelvis and perioperative efficacy of mid-low rectal cancer.Methods:The retrospective case-control study was conducted. The clinicopathological data of 191 patients who underwent robotic or laparoscopic total mesorectal excision (TME) for mid-low rectal cancer in the First Affiliated Hospital of Nanchang University from January 2021 to December 2022 were collected. There were 123 males and 68 females, aged (60±11)years. According to the surgical difficulty score, 191 patients were divided into the difficult pelvis group of 41 patients and the non-difficult pelvic group of 150 patients. Thirteen pelvic parameters were obtained on CT images of the 191 patients. Observation indicators: (1) comparison of intraoperative and postoperative conditions of patients in the difficult pelvis group and the non-difficult pelvis group; (2) analysis of factors affecting difficult pelvis in patients with mid-low rectal cancer; (3) stratified analysis of different surgical methods for patients with difficult pelvis. Measurement data with normal distribu-tion were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. Univariate and multivariate analyses were conducted using the Logistic regression model. Results:(1) Com-parison of intraoperative and postoperative conditions of patients in the difficult pelvis group and the non-difficult pelvis group. There were significant differences in operation time, volume of intra-operative blood loss, sum of the product of the longest diameters (SPD) of tumor lesions, postopera-tive complications, duration of postoperative hospital stay, and hospitalization expenses between the two groups ( t=-4.853, -5.816, Z=2.838, χ2=81.498, t=-5.897, -2.770, P<0.05). (2) Analysis of factors affecting difficult pelvis in patients with mid-low rectal cancer. Results of multivariate analysis showed that gender, age, pelvic inlet, distance between the sacral promontory and the coccyx, depth of the pelvis, line AB, angle A, and angle B were independent factors affecting difficult pelvis in patients with mid-low rectal cancer ( odds ratio=0.080, 1.067, 3.065, 0.004, 10 165.062, 0.019, 0.476, 0.662, 95% confidence interval as 0.016-0.409, 1.008-1.130, 1.388-6.767, 0.001-0.024, 477.574-216 361.071, 0.003-0.131, 0.358-0.632, 0.551-0.794, P<0.05). (3) Stratified analysis of different surgical methods for patients with difficult pelvis. ① Comparison of general preoperative data of patients with difficult pelvis receiving different surgical methods. Of the 41 mid-low rectal cancer patients with difficult pelvis, 15 underwent robotic TME, and 26 underwent laparoscopic TME. There was a significant difference in the body mass index between patients receiving the two surgical methods ( t=-2.055, P<0.05). ② Comparison of intraoperative and postoperative conditions of patients with difficult pelvis receiving different surgical methods. There was no significant difference in operation time, volume of intraoperative blood loss, SPD of tumor lesions, number of lymph nodes dissected, number of lymph node metastases, distance between tumor and anal verge, combined organ resection, postoperative complications, duration of postoperative hospital stay, hospitalization costs, T staging, N staging, M staging, vascular tumor thrombus, and nerve invasion ( P>0.05). Conclusions:Gender, age, pelvic inlet, distance between the sacral promontory and the coccyx, pelvic depth, AB line, angle A, and angle B are independent factors affecting difficult pelvis in patients with mid-low rectal cancer. There is no difference in perioperative outcomes between mid-low rectal cancer patients of difficult pelvis who received robotic surgery and laparoscopic surgery.

An analytical method based on ultra high performance liquid chromatography-high resolution tandem mass spectrometry(UHPLC-HRMS/MS)and high performance liquid chromatography-triple quadrupole mass spectrometry(HPLC-TQ MS)was established to reveal the characteristics of various sulfur mustard analogs with different active thiol molecules in CWC Schedule 1.A.04.Firstly,the toxic agents were prepared by micro-directed synthesis,and then the differences of the reactivity and abundance of formed adducts between different sulfur mustards and glutathione(GSH),cysteine(Cys)and N-acetylcysteine(NAC)in incubation solution,plasma and cell were investigated,respectively.The results indicated that all target sulfur mustards could react with three kinds of thiol molecules.The content of Cys and sulfur mustard adducts in plasma was higher than that of GSH and sulfur mustard adducts,while NAC and sulfur mustard adducts might have fewer types of adducts due to low content or poor mass spectrometry response.Additionally,the content of GSH and sulfur mustard adducts in exposed cells was higher than that of Cys,which should be due to the significant difference in the content of thiol molecules in plasma and cells.

Objective:To determine the motion detection uncertainty of the real-time CybeRay ? imaging system and patient intrafractional motion with thermoplastic mask-based immobilization. Methods:Real-time CybeRay ? imaging system was used for irradiation and treatment for head phantom and patients with brain tumors. All patients were immobilized with thermoplastic masks. Real-time imaging was delivered using kilovoltage projection images during radiotherapy. The detected patient motion data was collected from 5 head phantom measurements and 27 treatment fractions of 9 brain tumor patients admitted to Kaifeng Cancer Hospital. The accuracy and uncertainty of the motion monitoring system were determined. Results:The mean and standard deviation (SD) of the detected motion in the X, Y, and Z directions for phantom were (-0.02±0.41) mm, (-0.05±0.22) mm and (0.01±0.35) mm, respectively. The detected motion in the X, Y and Z directions for patents were (-0.13±0.48) mm, (-0.05±0.48) mm and (0.11±0.36) mm, respectively. After removing the motion detection uncertainty, the actual intrafractional motion of patients were (-0.11±0.25) mm, (0±0.43) mm and (0.10±0.08) mm in three directions, respectively. Conclusions:The uncertainty of real-time imaging-based motion monitoring system of CybeRay ? is less than 0.5 mm. It is feasible to apply thermoplastic masks for brain tumor patients in clinical practice, which can provide steady immobilization and limit the SD of patient intrafractional motion within 0.5 mm. Real-time imaging-based motion monitoring system of CybeRay ? is accurate for patient motion monitoring during frameless stereotactic radiosurgery/radiotherapy.