Signalling pathways underlying pulsed electromagnetic fields in bone repair.

Pulsed electromagnetic field (PEMF) stimulation is a prospective non-invasive and safe physical therapy strategy for accelerating bone repair. PEMFs can activate signalling pathways, modulate ion channels, and regulate the expression of bone-related genes to enhance osteoblast activity and promote the regeneration of neural and vascular tissues, thereby accelerating bone formation during bone repair. Although their mechanisms of action remain unclear, recent studies provide ample evidence of the effects of PEMF on bone repair. In this review, we present the progress of research exploring the effects of PEMF on bone repair and systematically elucidate the mechanisms involved in PEMF-induced bone repair. Additionally, the potential clinical significance of PEMF therapy in fracture healing is underscored. Thus, this review seeks to provide a sufficient theoretical basis for the application of PEMFs in bone repair.

Investigation of the active ingredients of Shuangshen Ningxin Fomula and the mechanism underlying their protective effects against myocardial ischemia-reperfusion injury by mass spectrometric imaging.

BACKGROUND: Traditional Chinese medicine, particularly Shuangshen Ningxin Capsule (SSNX), has been studied intensely. SSNX includes total ginseng saponins (from Panax ginseng Meyer), total phenolic acids from Salvia miltiorrhiza Bunge, and total alkaloids from Corydalis yanhusuo W. T. Wang. It has been suggested to protect against myocardial ischemia by a mechanism that has not been fully elucidated. METHODS: The composition and content of SSNX were determined by UHPLC-Q-TOFQ-TOF / MS. Then, a rat model of myocardial ischemia-reperfusion injury was established, and the protective effect of SSNX was measured. The protective mechanism was investigated using spatial metabolomics. RESULTS: We found that SSNX significantly improved left ventricular function and ameliorated pathological damages in rats with myocardial ischemia-reperfusion injury. Using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), the protective mechanism of SSNX was examined by comparing the monomer components of drugs targeted in myocardial tissue with the distribution of myocardial energy metabolism-related molecules and phospholipids. Interestingly, some lipids display inconsistent content distribution in the myocardial ischemia risk and non-risk zones. These discrepancies reflect the degree of myocardial injury in different regions. CONCLUSION: These findings suggest that SSNX protects against myocardial ischemia-reperfusion injury by correcting abnormal myocardial energy metabolism, changing the levels and distribution patterns of phospholipids, and stabilizing the structure of the myocardial cell membrane. MALDI-TOF MS can detect the spatial distribution of small molecule metabolites in the myocardium and can be used in pharmacological research.

Nkx2.5: a crucial regulator of cardiac development, regeneration and diseases.

Cardiomyocytes fail to regenerate after birth and respond to mitotic signals through cellular hypertrophy rather than cellular proliferation. Necrotic cardiomyocytes in the infarcted ventricular tissue are eventually replaced by fibroblasts, generating scar tissue. Cardiomyocyte loss causes localized systolic dysfunction. Therefore, achieving the regeneration of cardiomyocytes is of great significance for cardiac function and development. Heart development is a complex biological process. An integral cardiac developmental network plays a decisive role in the regeneration of cardiomyocytes. During this process, genetic epigenetic factors, transcription factors, signaling pathways and small RNAs are involved in regulating the developmental process of the heart. Cardiomyocyte-specific genes largely promote myocardial regeneration, among which the Nkx2.5 transcription factor is one of the earliest markers of cardiac progenitor cells, and the loss or overexpression of Nkx2.5 affects cardiac development and is a promising candidate factor. Nkx2.5 affects the development and function of the heart through its multiple functional domains. However, until now, the specific mechanism of Nkx2.5 in cardiac development and regeneration is not been fully understood. Therefore, this article will review the molecular structure, function and interaction regulation of Nkx2.5 to provide a new direction for cardiac development and the treatment of heart regeneration.

Nacre-Inspired MXene Nanocomposite-based Strain Sensor with Ultrahigh Sensitivity in a Small Strain Range for Parkinson's Disease Diagnosis.

Nowadays, chronic diseases are the primary threat to public health and are getting younger. By taking the advantages of continuousness, convenience, and real-time response, wearable strain sensors have been given great attention to diagnose chronic diseases via analyzing the patient's health state. However, most physiological signals, such as limb tremor of Parkinson's disease, microexpression, and slight joint movement, are tiny and difficult to be detected. Therefore, the development of strain sensors characterized with ultrahigh sensitivity in a small strain range (ε < 10%) is urgent. Inspired by nacre's hierarchical structure, we have fabricated nacre-mimetic nanocomposites with "brick-and-mortar" architecture by employing polyacrylamide (PAM) and Ti3C2Tx MXene nanosheets through a layer-by-layer (LBL) spin-coating technique. The resultant nanocomposite-based strain sensor exhibits ultrahigh sensitivity in a small strain range (GF = 296.8, ε < 10%), attributed to the bioinspired hierarchical structure and hydrogen bond-enhanced interfacial interactions. In addition, a high reliability, broad working sensing range (453%), short response time (183 ms), skin-like tensile stress (7.2 MPa), and excellent durability (2000 cycles) are also achieved. Due to the ultrahigh sensitivity within a small strain, the reported strain sensor can accurately diagnose and distinguish Parkinson's disease symptoms, including thumb pill-rolling tremor, masked face (microexpression), intermittent shaking of the head, and limb cogwheel motion. This work provides new insights to design strain sensors with high sensitivity for monitoring tiny signals and for disease diagnosis.

Research progress and future perspectives on electromagnetic wave absorption of fibrous materials.

Electromagnetic waves have caused great harm to military safety, high-frequency electronic components, and precision instruments, and so forth, which urgently requires the development of lightweight, high-efficiency, broadband electromagnetic waves (EMW) absorbing materials for protection. As the basic fibrous materials, carbon fibers (CFs) and SiC fibers (SiCf) have been widely applied in EMW absorption due to their intrinsic characteristics of low density, high mechanical properties, high conductivity, and dielectric loss mechanism. Nevertheless, it has remained a great challenge to develop lightweight EMW-absorbing fibrous materials with strong absorption capability and broad frequency range. In this review, the fundamental electromagnetic attenuation mechanisms are firstly introduced. Furthermore, the preparation, structure, morphology, and absorbing performance of CFs and SiCf-based EMW absorbing composites are summarized. In addition, prospective research opportunities are highlighted toward the development of fibrous absorbing materials with the excellent absorption performance.

Huoxin Pill Reduces Myocardial Ischemia Reperfusion Injury in Rats via TLR4/NFκB/NLRP3 Signaling Pathway.

OBJECTIVE: To explore the protective effect of Huoxin Pill (HXP) on acute myocardial ischemia-reperfusion (MIRI) injury in rats. METHODS: Seventy-five adult SD rats were divided into the sham-operated group, model group, positive drug group (diltiazem hydrochloride, DH), high dose group (24 mg/kg, HXP-H) and low dose group (12 mg/kg, HXP-L) of Huoxin Pill (n=15 for every group) according to the complete randomization method. After 1 week of intragastric administration, the left anterior descending coronary artery of the rat's heart was ligated for 45 min and reperfused for 3 h. Serum was separated and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA), hypersensitive C-reactive protein (hs-CRP) and interleukin-1ß (IL-1ß) were measured. Myocardial ischemia rate, myocardial infarction rate and myocardial no-reflow rate were determined by staining with Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC). Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN) databases were used to screen for possible active compounds of HXP and their potential therapeutic targets; the results of anti-inflammatory genes associated with MIRI were obtained from GeneCards, Drugbank, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Datebase (TTD) databases was performed; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the intersected targets; molecular docking was performed using AutoDock Tools. Western blot was used to detect the protein expression of Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NFκB)/NOD-like receptor protein 3 (NLRP3). RESULTS: Compared with the model group, all doses of HXP significantly reduced the levels of LDH, CK and CK-MB (P<0.05, P<0.01); HXP significantly increased serum activity of SOD (P<0.05, P<0.01); all doses of HXP significantly reduced the levels of hs-CRP and IL-1ß (P<0.05, P<0.01) and the myocardial infarction rate and myocardial no-reflow rate (P<0.01). GO enrichment analysis mainly involved positive regulation of gene expression, extracellular space and identical protein binding, KEGG pathway enrichment mainly involved PI3K-Akt signaling pathway and lipid and atherosclerosis. Molecular docking results showed that kaempferol and luteolin had a better affinity with TLR4, NFκB and NLRP3 molecules. The protein expressions of TLR4, NFκB and NLRP3 were reduced in the HXP group (P<0.01). CONCLUSIONS: HXP has a significant protective effect on myocardial ischemia-reperfusion injury in rats, and its effect may be related to the inhibition of redox response and reduction of the inflammatory response by inhibiting the TLR4NFκB/NLRP3 signaling pathway.

Effect of local application of bone morphogenetic protein -2 on experimental tooth movement and biological remodeling in rats.

Background: This study attempts to detect the potential effects of local bone morphogenetic protein -2 (BMP-2) on orthodontic tooth movement and periodontal tissue remodeling. Methods: Forty adult SD rats were randomly divided into four groups: blank control group, unilateral injection of BMP-2 on the pressure side or tension side of orthodontic teeth and bilateral injection of BMP-2. Their maxillary first molar was moved by a 30 g constant force closed coil spring. 60 µL of BMP-2 with a concentration of 0.5 µg/mL was injected into each part at a time. In addition, three rats were selected as healthy control rats without any intervention. Fluorescent labeled BMP-2 was used to observe the distribution of exogenous BMP-2 in tissues. Micro-CT was used to measure the microscopic parameters of tooth displacement, trabecular bone and root absorption volume. Three different histological methods were used to observe the changes of tissue remodeling, and then the number of osteoclasts and the content of collagen fibers were calculated. Results: Compared with the blank control group, BMP-2 injection reduced the movement distance and increased the collagen fiber content and bone mass (p < 0.01). There was no significant difference in tooth movement distance, BV/TV ratio and BMD between injection sites in unilateral injection group (p > 0.05). In the case of bilateral injection of BMP-2, the osteogenesis is enhanced. Unilateral injection of BMP-2 did not promote root resorption, but double injection showed root resorption (p < 0.01). Conclusion: Our study does show that the osteogenesis of BMP-2 is dose-dependent rather than site-dependent when a certain amount of BMP-2 is applied around orthodontic teeth. Local application of BMP-2 around orthodontic teeth in an appropriate way can enhance bone mass and tooth anchorage without increasing the risk of root absorption volume. However, high levels of BMP-2 may cause aggressive root resorption. These findings are of great significance, that is, BMP-2 is an effective target for regulating orthodontic tooth movement.

Proteomic analysis revealed the pharmacological mechanism of Xueshuantong injection in preventing early acute myocardial infarction injury.

Background: Acute myocardial infarction (AMI) is a common and life-threatening cardiovascular disease. However, there is a lack of pathology and drug studies on AMI within 20 min. Xueshuantong injection (XST) is mainly composed of Panax notoginseng saponins, which can dilate blood vessels and improve blood circulation, and is clinically used in the treatment of cardiovascular and cerebrovascular diseases. Purpose: The study aimed to investigate the protective mechanism of Xueshuantong injection against acute myocardial infarction within 20 min in rats by proteomic methods and molecular docking. Method: The male Sprague-Dawley rat acute myocardial infarction model was established by LAD ligation, and Xueshuantong injection (38 mg/kg) was injected into the caudal vein 15 min before surgery. Cardiac function evaluation, morphological observation, label-free quantitative proteomics, Western blotting analysis, molecular docking, and affinity measurement were applied in this study. Results: In a span of 20 min after acute myocardial infarction, the model group showed significant cardiac function impairment. Xueshuantong injection can significantly improve cardiac function and prevent pathological injury of myocardial tissue. A total of 117 vital differentially expressed proteins were identified by proteomic analysis, including 80 differentially expressed proteins (DEPs) in the sham group compared with model rats (Sham: model) and 43 DEPs in model rats compared with the Xueshuantong injection group (Model: XST). The treatment of Xueshuantong injection mainly involves "poly(A) RNA binding" and "cadherin binding involved in cell-cell adhesion." The differentially expressed levels of the pathways related to proteins Echdc2, Gcdh, Dlst, and Nampt, as well as 14-3-3 family proteins Ywhaz and Ywhab, could be quantitatively confirmed by WB. Molecular docking analysis and SPR analysis revealed that Ywhaz has a generally stable binding with five Xueshuantong injection components. Conclusion: Xueshuantong injection (XST) could protect rat myocardial function injury against AMI in 20 min. Echdc2, Ywhaz, Gcdh, Ywhab, Nampt, and Dlst play an essential role in this protective effect. In particular, Ywhaz might be the core target of Xueshuantong injection when treating acute myocardial infarction in the early stage. This study promoted the understanding of the protective mechanism of Xueshuantong injection in 20 min injury of acute myocardial infarction and contributed to the identification of possible targets of Xueshuantong injection.

[Research progress on Chinese medicinal material-derived active polypeptides against ischemic cardiovascular and cerebrovascular diseases].

Ischemic cardiovascular and cerebrovascular diseases threatening human health and survival have high morbidity and mortality. The common cause of them is reduced blood supply caused by vascular stenosis, atherosclerosis, and infarction. However,the pathological processes of ischemic cardiovascular and cerebrovascular diseases are complex, involving oxidative stress, calcium overload, inflammation, apoptosis, autophagy and other mechanisms. Protein drugs such as recombinant tissue plasminogen activator(rt-PA) and urokinase have been proved with excellent therapeutic effects and huge economic and social benefits in the clinical treatment and interventional therapy. Among them, peptide drugs have shown unique advantages and potential prospects owing to their strong biological activity, high target specificity, biochemical diversity, and low toxicity. Chinese medicinal materials, characterized by multi-component and multi-target therapy, have also shown excellent clinical efficacy against ischemic cardiovascular and cerebrovascular diseases. However, the research and development of related peptides in Chinese medicinal materials is at the initial stage. Therefore, this paper reviewed the targets and action mechanisms of a variety of Chinese medicinal material-derived polypeptides with activities against ischemic cardiovascular and cerebrovascular diseases, aiming to provide support for the in-depth research as well as the clinical development and application of these polypeptides.