GRAS1 non-coding RNA protects against DNA damage and cell death by binding and stabilizing NKAP.

Non-coding RNA (ncRNA) gene products are involved in diverse biological processes including splicing, epigenetic regulation, gene expression, proliferation, and metabolism. The biological mechanisms by which ncRNAs contribute to cell survival remain poorly understood. We found that the Growth Regulator Antisense 1 (GRAS1) long non-coding RNA (lncRNA) transcript promotes growth in multiple human cell types by protecting against DNA damage. Knockdown of GRAS1 induced DNA damage and cell death, along with significant expression changes in DNA damage response, intrinsic apoptotic signaling, and cellular response to environmental stimulus genes. Extensive DNA damage occurred after GRAS1 knockdown, with numerous double strand breaks occurring in each cell. The number of cells undergoing apoptosis and with fragmented nuclei increased significantly after GRAS1 knockdown. We used RNA antisense purification and mass spectrometry (RAP-MS) to identify the NF-κB activating protein (NKAP) as a direct protein interaction partner of GRAS1 lncRNA. NKAP protein was degraded after GRAS1 knockdown, in a proteasome-dependent manner. Overexpression of GRAS1 or NKAP mitigated the DNA damage effects of GRAS1 knockdown. In summary, GRAS1 and NKAP directly interact to protect against DNA damage and cell death in multiple human cell lines.

The Therapeutic Potential of Melatonin in Alzheimer's Disease: A Comprehensive Review.

Alzheimer's Disease (AD) is the most common cause of dementia, afflicting over 5 million people in the United States. There remains a lack of effective disease-- modifying treatments for AD beyond a few approved drugs that provide temporary symptomatic relief. Melatonin is an endogenous hormone mainly produced by the pineal gland that regulates circadian rhythms and possesses antioxidant and anti-inflammatory properties. An expansive body of research over the past few decades has investigated melatonin as a promising therapeutic agent for AD based on its ability to target multiple pathophysiological processes implicated in AD progression. In this comprehensive review, we summarize extensive evidence from cellular and animal models that has uncovered the diverse mechanisms underpinning melatonin's neuroprotective efficacy against AD pathology. We also synthesize clinical studies examining melatonin's effects on AD progression and symptoms. Additionally, we discuss how melatonin's multimodal mechanisms, favorable safety profile, and ability to synergize with conventional therapies heighten its potential as an effective therapeutic strategy for AD. Rigorously designed clinical trials incorporating physiological biomarkers are warranted to definitively establish melatonin's disease-modifying effects. Nevertheless, the considerable preclinical data support further exploration of melatonin as a therapeutic agent for AD.

Registration study for the prevention and treatment of cerebral hemorrhage using naoxueshu oral liquid: Protocol for a research study.

BACKGROUND: Naoxueshu oral liquid is the only approved drug for acute treatment of cerebral hemorrhage in China. It has been used widely for the treatment of acute ischemic stroke and acute hemorrhagic stroke. However, safety and efficacy data on the early use of Naoxueshu oral liquid are lacking. The main purpose of this study is to observe the benefit and safety of early use of Naoxueshu oral liquid (< 72 h of cerebral hemorrhage) and offer evidence into the potential superiority of Naoxueshu oral liquid in patients with hemorrhagic stroke, and its healthcare costs. METHODS: This registration study for the prevention and treatment of cerebral hemorrhage using Naoxueshu oral liquid will be a quantitative, prospective, multicenter, observational clinical registry study. We aim to register 2000 patients with cerebral hemorrhage within 7 days of disease onset. This study will be an observational study and not interfere with the medication regimen of participants. Hence, we will not allocate patients. The main observation indicators will be the hematoma volume and the proportion of reduction 14 days post-cerebral hemorrhage (or at hospital discharge), onset of new stroke (ischemic stroke, hemorrhagic stroke) within 12 months of disease onset, independence in everyday life activities (modified Rankin Scale score ≤ 2), total cost during hospitalization, and treatment costs. CONCLUSION: This registration study will offer strong evidence for the efficacy and safety of Naoxueshu oral liquid for the prevention and treatment of cerebral hemorrhage, particularly with regard to early use (72 h after onset). It will offer evidence into the potential advantages of Naoxueshu oral liquid in patients with hemorrhagic stroke, including healthcare costs.

Myeloid zinc finger 1 knockdown promotes osteoclastogenesis and bone loss in part by regulating RANKL-induced ferroptosis of osteoclasts through Nrf2/GPX4 signaling pathway.

The overactivation of the osteoclasts is a crucial pathological factor in the development of osteoporosis. MZF1, belonging to the scan-zinc finger family, plays a significant role in various processes associated with tumor malignant progression and acts as an essential transcription factor regulating osteoblast expression. However, the exact role of MZF1 in osteoclasts has not been determined. In this study, the purpose of our study was to elucidate the role of MZF1 in osteoclastogenesis. First, we established MZF1-deficient female mice and evaluated the femur bone phenotype by micro-computed tomography and histological staining. Our findings indicate that MZF1-/- mice exhibited a low bone mass osteoporosis phenotype. RANKL could independently induce the differentiation of RAW264.7 cells into osteoclasts, and we found that the expression level of MZF1 protein decreased gradually. Then, the CRISPR/Cas 9 gene-editing technique was used to build a RAW264.7 cell model with MZF1 knockout, and RANKL was used to independently induce MZF1-/- and wild-type cells to differentiate into mature osteoclasts. Tartrate-resistant acid phosphatase staining and F-actin fluorescence results showed that the MZF1-/- group produced more tartrate-resistant acid phosphatase-positive mature osteoclasts and larger actin rings. The expression of osteoclast-associated genes (including tartrate-resistant acid phosphatase, CTSK, c-Fos, and NFATc1) was evaluated by reverse transcription quantitative polymerase chain reaction and Western blot. The expression of key genes of osteoclast differentiation in the MZF1-/- group was significantly increased. Furthermore, we found that cell viability was increased in the early stages of RANKL-induced cell differentiation in the MZF1-/- group cells. We examined some prevalent ferroptosis markers, including malondialdehyde, glutathione, and intracellular Fe, the active form of iron in the cytoplasm during the early stages of osteoclastogenesis. The results suggest that MZF1 may be involved in osteoclast differentiation by regulating RANKL-induced ferroptosis of osteoclasts. Collectively, our findings shed light on the essential involvement of MZF1 in the regulation of osteoclastogenesis in osteoporosis and provide insights into its potential underlying mechanism.

Intensification of moisture separation in the pulp convective drying process with ultrasound-assisted method.

Traditional pulp convective drying (CD) is time-consuming and energy-intensive. This study aimed to assess the drying performance of pulp using ultrasound-assisted drying (UAD) and compared it with CD to intensify moisture separation. UAD was found to be fast and efficient with high effective moisture diffusivity of 2.77 × 10-10 âˆ¼ 3.20 × 10-10 m2/s, low activation energy of 20.2 kJ/mol, and short drying time of 21.0 âˆ¼ 16.5 min. It demonstrated that applying ultrasound could promote moisture separation with 26 %∼42 % reductions in drying time and 42 %∼22 % savings in energy consumption. The constant rate period was not presented and no significant differences in drying rates were observed when the moisture ratio was below 0.43 under the investigated conditions. The kinetics modeling results indicated that the Page model was the best to predict the pulp drying kinetics for both methods. It may lead to an alternative efficient approach for decarbonizing the drying process in pulp and paper production.

[Research progress in mechanism of puerarin in treating vascular dementia].

Vascular dementia(VD) is a condition of cognitive impairment due to acute and chronic cerebral hypoperfusion. The available therapies for VD mainly focus on mitigating cerebral ischemia, improving cognitive function, and controlling mental behavior. Achievements have been made in the basic and clinical research on the treatment of VD with traditional Chinese medicine(TCM) active components, including Ginkgo leaf extract, puerarin, epimedium, tanshinone, and ginsenoside. Most of these components have anti-inflammatory, anti-apoptotic, anti-oxidant, and neuroprotective effects, and puerarin demonstrates excellent performance in mitigating cholinergic nervous system disorders and improving synaptic plasticity. Puerarin, ginkgetin, and epimedium are all flavonoids, while tanshinone is a diterpenoid. Puerariae Lobatae Radix, pungent in nature, can induce clear Yang to reach the cerebral orifices and has the wind medicine functions of ascending, dispersing, moving, and scurrying. Puerariae Lobatae Radix entering collaterals will dredge blood vessels to promote blood flow, and that entering the sweat pore will open the mind, which is in line with the TCM pathogenesis characteristics of VD. This study reviews the progress in the mechanism of puerarin, the main active component of Puerariae Lobatae Radix, in treating VD. Puerarin can ameliorate cholinergic nervous system disorders, reduce excitotoxicity, anti-inflammation, inhibit apoptosis, alleviate oxidative stress injury, enhance synaptic plasticity, up-regulate neuroprotective factor expression, promote cerebral circulation metabolism, and mitigate Aß injury. The pathways of action include activating nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE), vascular endothelial growth factor(VEGF), extracellular regulated protein kinases(ERK), phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt), Janus-activating kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3), AMP-activated protein kinase(AMPK), as well as inhibiting the tumor necrosis factor α(TNF-α), transient receptor potential melastatin 2(TRPM2)/N-methyl-D-aspartate receptor(NMDAR), p38 mitogen-activated protein kinase(p38 MAPK), Toll-like receptor 4(TLR4)/nuclear factor-kappaB(NF-κB), early growth response 1(Egr-1), and matrix metalloproteinase 9(MMP-9). By reviewing the papers about the treatment of VD by puerarin published by CNKI, Wanfang, VIP, PubMed, and Web of Science in the last 10 years, this study aims to support the treatment and drug development for VD.

Biomechanical analysis of a novel bone cement bridging screw system combined with percutaneous vertebroplasty for treating Kummell's disease.

Kummell's Disease (KD) was originally proposed by Dr. Hermann Kummell in 1891 as a type of delayed posttraumatic vertebral collapse, which is a clinical phenomenon. The purpose of this experiment is to compare the strength of bone cement and the novel bone cement bridging screw in the treatment of thoracolumbar Kummell disease (KD) with other treatment methods. Thirty sheep spine specimens were selected. T12 to L2 segments were selected, and a KD intravertebral vacuum cleft model was made at the L1 segment. According to the ways of cement filling, the specimens were divided into percutaneous vertebroplasty (PVP), PVP combined with unilateral percutaneous pediculoplasty (PPP), PVP combined with bilateral PPP, unilateral novel bone cement bridging screw system combined with PVP, and bilateral cement bridging screw system combined with PVP groups. There were two experiments: three-dimensional biomechanical strength test and axial compression test. In the three-dimensional biomechanical strength test, we measured the strength of bone cement in specimens under six motion states, including flexion, extension, left bending, right bending, and left and right axial rotations. In the axial compression test, we detected the maximum axial pressure that the bone cement could withstand when it was under pressure until the bone cement was displaced. The unilateral or bilateral novel bone cement bridging screw with PVP groups had the best strength under flexion, extension, left bending, right bending, and had better biomechanical strength, with a significant difference from the other three groups (p < 0.05). There was no significant difference between the unilateral or bilateral novel bone cement bridging screw with PVP groups (p > 0.05). Unilateral and bilateral novel bone cement bridging screw could achieve similar bone cement strength. Compared with the other three groups, the unilateral or bilateral novel bone cement bridging screw with PVP groups are higher 136.35%, 152.43%; 41.93%, 51.58%; 34.37%, 43.50% respectively. The bilateral novel bone cement bridging screw with PVP could bear the largest pressure under vertical force. To conclude, the novel bone cement bridging screw can increase the strength of bone cement and avoid the loosening and displacement of bone cement in the treatment of KD of the thoracolumbar spine.

Plasma exosome proteomics reveals the pathogenesis mechanism of post-stroke cognitive impairment.

Exploration and utilization of exosome biomarkers and their related functions provide the possibility for the diagnosis and treatment of post-stroke cognitive impairment (PSCI). To identify the new diagnostic and prognostic biomarkers of plasma exosome were uzed label-free quantitative proteomics and biological information analysis in PSCI patients. Behavioral assessments were performed, including the Mini-Mental Status Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Barthel index, the Morse Fall Seale (MFS) between control group (n = 10) and PSCI group (n = 10). The blood samples were collected to analyse the biomarker and differentially expressed proteins of plasma exosome using label-free quantitative proteomics and biological information. The exosomes marker proteins were determined by Western blot. The exosome morphology was observed by transmission electron microscopy. The scores of MMSE and MoCA were significantly decreased in the PSCI group. The PT% and high-density lipoprotein decreased and the INR ratio increased in PSCI group. The mean size of exosome was approximately 71.6 nm and the concentration was approximately 6.8E+7 particles/mL. Exosome proteomics identified 259 differentially expressed proteins. The mechanisms of cognitive impairment are related to regulate the degradation of ubiquitinated proteins, calcium dependent protein binding, cell adhesive protein binding, formation of fibrin clot, lipid metabolism and ATP-dependent degradation of ubiquitinated proteins in plasma exosome of PSCI patients. Plasma levels of YWHAZ and BAIAP2 were significantly increased while that of IGHD, ABCB6 and HSPD1 were significantly decreased in PSCI patients. These proteins might be target-related proteins and provide global insights into pathogenesis mechanisms of PSCI at plasma exosome proteins level.

Inhibiting leukocyte-endothelial cell interactions by Chinese medicine Tongxinluo capsule alleviates no-reflow after arterial recanalization in ischemic stroke.

AIMS: Despite successful vascular recanalization in stroke, one-fourth of patients have an unfavorable outcome due to no-reflow. The pathogenesis of no-reflow is fully unclear, and therapeutic strategies are lacking. Upon traditional Chinese medicine, Tongxinluo capsule (TXL) is a potential therapeutic agent for no-reflow. Thus, this study is aimed to investigate the pathogenesis of no-reflow in stroke, and whether TXL could alleviate no-reflow as well as its potential mechanisms of action. METHODS: Mice were orally administered with TXL (3.0 g/kg/d) after transient middle cerebral artery occlusion. We examined the following parameters: neurological function, no-reflow, leukocyte-endothelial cell interactions, HE staining, leukocyte subtypes, adhesion molecules, and chemokines. RESULTS: Our results showed stroke caused neurological deficits, neuron death, and no-reflow. Adherent and aggregated leukocytes obstructed microvessels as well as leukocyte infiltration in ischemic brain. Leukocyte subtypes changed after stroke mainly including neutrophils, lymphocytes, regulatory T cells, suppressor T cells, helper T type 1 (Th1) cells, Th2 cells, B cells, macrophages, natural killer cells, and dendritic cells. Stroke resulted in upregulated expression of adhesion molecules (P-selectin, E-selectin, and ICAM-1) and chemokines (CC-chemokine ligand (CCL)-2, CCL-3, CCL-4, CCL-5, and chemokine C-X-C ligand 1 (CXCL-1)). Notably, TXL improved neurological deficits, protected neurons, alleviated no-reflow and leukocyte-endothelial cell interactions, regulated multiple leukocyte subtypes, and inhibited the expression of various inflammatory mediators. CONCLUSION: Leukocyte-endothelial cell interactions mediated by multiple inflammatory factors are an important cause of no-reflow in stroke. Accordingly, TXL could alleviate no-reflow via suppressing the interactions through modulating various leukocyte subtypes and inhibiting the expression of multiple inflammatory mediators.

Single-Posterior Revision Surgery for Recurrent Thoracic/Thoracolumbar Spinal Tuberculosis With Kyphosis.

BACKGROUND AND OBJECTIVES: The treatment of thoracic/thoracolumbar spinal tuberculosis (STB) remains challenging. The spinal deformity, long disease history, heterogeneous lesion, and poor drug response make the treatment of recurrent and kyphosis cases even more difficult. This study aims to investigate the efficacy and safety of single-posterior revision surgery in patients with recurrent thoracic/thoracolumbar STB and kyphosis. METHODS: Patients with recurrent thoracic/thoracolumbar STB with kyphosis and treated with single-posterior debridement, osteotomy, correction, bone graft, and fusion in our center from 2009 to 2019 were enrolled. The clinical data, radiographs, and erythrocyte sedimentation rate (ESR) at different stages were collected. ESR, kyphotic angle, Visual Analog Scale, and neurological functions were analyzed. RESULTS: A total of 27 patients (16 male, 11 female) with an average age of 48.4 ± 13.0 years were included. The average surgery time was 320.6 ± 46.4 minutes, and the average estimated blood loss was 1470.6 ± 367.4 mL. From admittance to the latest follow-up, the average Visual Analog Scale significantly reduced from 5.6 ± 1.3 to 0.5 ± 0.7, the average ESR was improved from 69.4 ± 15.8 mm/h to normal, and the average kyphotic angle was corrected from 66.6° ± 11.7° to 34.5° ± 6.6°. For patients with preoperative neurological deficits, their neurological functions were improved to normal. In drug susceptibility tests, 70.5% (11/17) of specimens had bacteria resistant to at least 1 first-line drug. CONCLUSION: Single-posterior debridement, osteotomy, correction, bone graft, and fusion are effective and safe in the treatment of recurrent thoracic/thoracolumbar spinal tuberculosis with kyphosis. The drug treatment of recurrent spinal tuberculosis should be carefully tailored.

Supramolecular Hydrogel Microspheres of Platelet-Derived Growth Factor Mimetic Peptide Promote Recovery from Spinal Cord Injury.

Neural stem cells (NSCs) are considered to be prospective replacements for neuronal cell loss as a result of spinal cord injury (SCI). However, the survival and neuronal differentiation of NSCs are strongly affected by the unfavorable microenvironment induced by SCI, which critically impairs their therapeutic ability to treat SCI. Herein, a strategy to fabricate PDGF-MP hydrogel (PDGF-MPH) microspheres (PDGF-MPHM) instead of bulk hydrogels is proposed to dramatically enhance the efficiency of platelet-derived growth factor mimetic peptide (PDGF-MP) in activating its receptor. PDGF-MPHM were fabricated by a piezoelectric ceramic-driven thermal electrospray device, had an average size of 9 µm, and also had the ability to activate the PDGFRß of NSCs more effectively than PDGF-MPH. In vitro, PDGF-MPHM exerted strong neuroprotective effects by maintaining the proliferation and inhibiting the apoptosis of NSCs in the presence of myelin extracts. In vivo, PDGF-MPHM inhibited M1 macrophage infiltration and extrinsic or intrinsic cells apoptosis on the seventh day after SCI. Eight weeks after SCI, the T10 SCI treatment results showed that PDGF-MPHM + NSCs significantly promoted the survival of NSCs and neuronal differentiation, reduced lesion size, and considerably improved motor function recovery in SCI rats by stimulating axonal regeneration, synapse formation, and angiogenesis in comparison with the NSCs graft group. Therefore, our findings provide insights into the ability of PDGF-MPHM to be a promising therapeutic agent for SCI repair.

CRISPR/Cas9 knockout of MTA1 enhanced RANKL-induced osteoclastogenesis in RAW264.7 cells partly via increasing ROS activities.

Metastasis-associated protein 1 (MTA1), belonging to metastasis-associated proteins (MTA) family, which are integral parts of nucleosome remodelling and histone deacetylation (NuRD) complexes. However, the effect of MTA1 on osteoclastogenesis is unknown. Currently, the regulation of MTA1 in osteoclastogenesis was reported for the first time. MTA1 knockout cells (KO) were established by CRISPR/Cas9 genome editing. RAW264.7 cells with WT and KO group were stimulated independently by RANKL to differentiate into mature osteoclasts. Further, western blotting and quantitative qRT-PCR were used to explore the effect of MTA1 on the expression of osteoclast-associated genes (including CTSK, MMP9, c-Fos and NFATc1) during osteoclastogenesis. Moreover, the effects of MTA1 on the expression of reactive oxygen species (ROS) in osteoclastogenesis was determined by 2', 7' -dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Nuclear translocation of Nrf2 was assessed by immunofluorescence staining and western blotting. Our results indicated that the MTA1 deletion group could differentiate into osteoclasts with larger volume and more TRAP positive. In addition, compared with WT group, KO group cells generated more actin rings. Mechanistically, the loss of MTA1 increased the expression of osteoclast-specific markers, including c-Fos, NFATc1, CTSK and MMP-9. Furthermore, the results of qRT-PCR and western blotting showed that MTA1 deficiency reduced basal Nrf2 expression and inhibited Nrf2-mediated expression of related antioxidant enzymes. Immunofluorescence staining demonstrated that MTA1 deficiency inhibited Nrf2 nuclear translocation. Taken together, the above increased basal and RANKL-induced intracellular ROS levels, leading to enhanced osteoclast formation.

Hypoxia-inducible factor 1α enhances RANKL-induced osteoclast differentiation by upregulating the MAPK pathway.

Background: Hypoxia (low-oxygen tension) and excessive osteoclast activation are common conditions in many bone loss diseases, such as osteoporosis, rheumatoid arthritis (RA), and pathologic fractures. Hypoxia-inducible factor 1 alpha (HIF1α) regulates cellular responses to hypoxic conditions. However, it is not yet known how HIF1α directly affects osteoclast differentiation and activation. This study sought to. explore the effects of HIF1α on osteoclast differentiation and it's molecular mechanisms. Methods: L-mimosine, a prolyl hydroxylase (PHDs) domain inhibitor, was used to stabilize HIF1α in normoxia. In the presence of receptor activator of nuclear factor-kB (NF-kB) ligand (RANKL), RAW264.7 cells were cultured and stimulated by treatment with L-mimosine at several doses to maintain various levels of intracellular HIF1α. The multi-nucleated cells were assessed by a tartrate-resistant acid phosphatase (TRAP) and F-actin ring staining assays. The osteoclast-specific genes, such as Cathepsin K, ß3-Integrin, TRAP, c-Fos, nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), and matrix metallo-proteinase 9 (MMP9), were analyzed by real time-polymerase chain reaction (RT-PCR). The expression of relevant proteins was analyzed by Western blot. Results: L-mimosine increased the content of intracellular HIF1α in a dose-dependent manner, which in turn promoted RANKL-induced osteoclast formation and relevant protein expression by upregulating the mitogen-activated protein kinase (MAPK) pathways. Conclusions: Our findings suggest that HIF1α directly increases the osteoclast differentiation of RANKL-mediated RAW264.7 cells in vitro by upregulating the MAPK pathways.

Thoracic Jia-Ji electro-acupuncture mitigates low skeletal muscle atrophy and improves motor function recovery following thoracic spinal cord injury in rats.

OBJECTIVES: The goal of this study was to determine whether electro-acupuncture (EA) stimulation might protect the motor endplate, minimize muscle atrophy in the hind limbs, and enhance functional recovery of rats with spinal cord injury (SCI). METHODS: Sprague-Dawley adult female rats (n = 30) were randomly assigned into Sham, SCI, and EA + SCI groups (n = 10 each). Rats in the Sham and SCI groups were bound in prone position only for 30 min, and rats in the EA + SCI group were treated with electro-acupuncture. The EA was conducted from the first day after surgery, lasted for 30 mins, once every day for 28 consecutive days. RESULTS: EA significantly prevented motor endplate degeneration, improved electrophysiological function, and ameliorated hindlimb muscle atrophy after SCI. Meanwhile, EA upregulated Tuj-1 expression, downregulated GFAP expression, and reduced glial scar formation. Additionally, after 4 weeks of EA treatment, the serum of SCI rats exhibited a reduced inflammatory response. CONCLUSION: These findings suggest that EA can preserve the motor endplate and reduce muscular atrophy. In addition, EA has been shown to improve the function of upper and lower neurons, reduce glial scar formation, suppress systemic inflammation, and improve axon regeneration.

Biomechanical analysis of a novel bone cement bridging screw system for the treatment of Kummell disease: a finite element analysis.

When bone cement is used to strengthen the vertebrae in patients with Kummell disease (KD), loosening and displacement of cement are common complications that can cause poor results. We developed a bone cement bridging screw system to avoid this complication. This three-dimensional finite element study aims to analyze the biomechanical properties of the novel bridging screw system and compare it to single vertebroplasty and vertebroplasty combined with pediculoplasty. After the effective establishment of a KD three-dimensional finite element model, the stability of the bone cement in the five treatment methods was analyzed and compared on four aspects. According to the calculation results of the maximum von Mises stress of bone cement and the relative displacement ratio of bone cement, it was determined that the stability of the bone cement was significantly improved when combined with the bridging screw system or pediculoplasty. In addition, according to the calculation results of the maximum von Mises stress of the inferior endplate of T12 and the displacement load ratio of the bone cement, we further found that after using the bridging screw system, the bone cement in the vertebral body has the best stability, and the risk of bone cement loosening or displacement is the lowest. In conclusion, for treating KD with bone cement augmentation, the bone cement bridging screw system combined with vertebroplasty has better stability and safety than ordinary single vertebroplasty and vertebroplasty combined with pediculoplasty. This treatment approach has the most robust ability to avoid loosening and displacement of bone cement.

A functionalized self-assembling peptide containing E7 and YIGSR sequences enhances neuronal differentiation of spermatogonial stem cells on aligned PCL fibers for spinal cord injury repair.

Background: Spinal cord injury (SCI) induces neuronal death and disrupts the nerve fiber bundles, which leads to partial or complete sensorimotor function loss of the limbs. Transplantation of exogenous neurons derived from stem cells to the lesion site becomes a new neurorestorative strategy for SCI treatment. Spermatogonial stem cells (SSCs) can attain pluripotency features by converting to embryonic stem-like cells in vitro. However, differentiating SSCs into lineage-specific neurons is quite difficult and low efficiency. Methods: Immunofluorescence, immunohistochemistry, Western blotting, whole-cell patch clamp, and behavioral tests were performed to verify that self-assembled hydrogels could improve the directional differentiation efficiency of SSCs and the feasibility of SSC-derived neurons in the treatment of spinal cord injury. Results: We developed a novel self-assembled peptide Nap-FFGEPLQLKMCDPGYIGSR (Nap-E7-YIGSR) coated with aligned electrospun PCL fibers to enhance neuronal differentiation of SSCs. The Nap-E7-YIGSR peptide could evenly self-assemble on the surface of PCL fibers, enhanced the materials's hydrophilicity, and improved the SSC affinity of PCL fibers through the stem cell adhesion peptide sequence EPLQLKM domain. In addition, Nap-E7-YIGSR could effectively induce SSC neuron differentiation by activating the integrin ß1/GSK3ß/ß-catenin signaling pathway. Moreover, implanting the induced neurons derived from SSCs into SCI lesion sites in rats resulted in the formation of new relay circuits, myelination, and synapse formation. Furthermore, SSC-derived neurons could survive and function in the spinal cord injury microenvironment, boosting the recovery of locomotion. Conclusion: The combination of the multifunctional peptide and aligned fibers can potentially trigger SSC differentiation to neurons, facilitating neuronal replacement therapy and promoting functional recovery after SCI.

Receptor activator of nuclear factor-κB ligand-mediated osteoclastogenesis signaling pathway and related therapeutic natural compounds.

Osteoclast is a hematopoietic precursor cell derived from the mononuclear macrophage cell line, which is the only cell with bone resorption function. Its abnormal activation can cause serious osteolysis related diseases such as rheumatoid arthritis, Paget's disease and osteoporosis. In recent years, the adverse effects caused by anabolic anti-osteolytic drugs have increased the interest of researchers in the potential therapeutic and preventive effects of natural plant derivatives and natural compounds against osteolytic diseases caused by osteoclasts. Natural plant derivatives and natural compounds have become major research hotspots for the treatment of osteolysis-related diseases due to their good safety profile and ability to improve bone. This paper provides an overview of recent advances in the molecular mechanisms of RANKL and downstream signaling pathways in osteoclast differentiation, and briefly outlines potential natural compounds with antiosteoclast activity and molecular mechanisms.

Hydrogel-based delivery system applied in the local anti-osteoporotic bone defects.

Osteoporosis is an age-related systemic skeletal disease leading to bone mass loss and microarchitectural deterioration. It affects a large number of patients, thereby economically burdening healthcare systems worldwide. The low bioavailability and complications, associated with systemic drug consumption, limit the efficacy of anti-osteoporosis drugs currently available. Thus, a combination of therapies, including local treatment and systemic intervention, may be more beneficial over a singular pharmacological treatment. Hydrogels are attractive materials as fillers for bone injuries with irregular shapes and as carriers for local therapeutic treatments. They exhibit low cytotoxicity, excellent biocompatibility, and biodegradability, and some with excellent mechanical and swelling properties, and a controlled degradation rate. This review reports the advantages of hydrogels for adjuvants loading, including nature-based, synthetic, and composite hydrogels. In addition, we discuss functional adjuvants loaded with hydrogels, primarily focusing on drugs and cells that inhibit osteoclast and promote osteoblast. Selecting appropriate hydrogels and adjuvants is the key to successful treatment. We hope this review serves as a reference for subsequent research and clinical application of hydrogel-based delivery systems in osteoporosis therapy.

Efficacy and safety of Songling Xuemaikang capsule for essential hypertension: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Hypertension is one of the most significant public health challenges worldwide. An increasing number of patients prefer to incorporate traditional Chinese medicine into their hypertensive care. The Songling Xuemaikang capsule (SXC), a Chinese herbal formula, is widely used in China for essential hypertension. PURPOSE: To assess the efficacy and safety of SXC for essential hypertension. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We conducted a systematic literature search of seven databases to identify randomized controlled trials of SXC for hypertension. The outcome measures included blood pressure parameters and patient-reported outcomes. Potential heterogeneity between the studies was resolved by subgroup and sensitivity analyses. The quality of the results was evaluated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. RESULTS: A total of 34 trials with 4306 patients were included. The results showed that SXC plus antihypertensive drugs produced a greater effect on reducing systolic blood pressure (SBP) (MD: -7.54 mmHg; 95% CI: -8.92, -6.17; p < 0.00001), diastolic blood pressure (DBP) (MD: -6.42 mmHg; 95% CI: -7.54, -5.29; p < 0.00001), 24-hour SBP (MD: -6.88 mmHg; 95% CI: -8.36, -5.39; p < 0.00001), and 24-hour DBP (MD: -4.31 mmHg; 95% CI: -6.55, -2.07; p = 0.0002) and improving hypertensive symptoms (SMD: -1.09; 95% CI: -1.34, -0.84; p < 0.00001) than antihypertensive drugs alone. SXC monotherapy was less effective than antihypertensive drugs for 24-hour SBP reduction (MD: 2.07 mmHg; 95% CI: 0.19, 3.96; p = 0.03). No significant difference was observed in the incidence of adverse events between the SXC and control groups. CONCLUSION: SXC is beneficial for essential hypertension; it can lower BP, improve hypertensive symptoms and is well tolerated.

Trial of a prehospital intervention with traditional Chinese medicine for acute stroke (TRACE): Protocol for a mixed-methods research study.

Background: As the only traditional Chinese medicine injection approved by the China Food and Drug Administration for use as stroke first aid in ambulances, Xingnaojing Injection (XNJI) has been widely used in cases of both acute ischemic stroke (IS) and intracerebral hemorrhage (ICH). However, there is no robust clinical evidence regarding the efficacy and safety of the early use of XNJI during stroke first aid. The main purpose of this trial is to observe whether XNJI, intravenously administered within 24 h of onset in the prehospital ambulance setting, protects against early neurological deterioration (END) on the third day of onset in patients with acute stroke. Methods: The Trial of a prehospital intervention with traditional Chinese medicine for acute stroke (TRACE) is a Mixed-Methods research (MMR) study that involves a combination of quantitative and qualitative research. The quantitative research part of this project is a prospective, multicenter, observational, clinical registry study, for which we aimed to recruit 1,000 patients with acute stroke (IS and ICH). Based on our observation of whether XNJI was intravenously administered within 24 h of onset in the prehospital ambulance setting, patients with acute stroke will be divided into two groups: the exposure group comprising patients who were intravenously administered XNJI and the nonexposure group comprising patients who were not. The primary outcome is early neurological deterioration (END) on the third day of onset defined as an increase of 2 or more points in the National Institute of Health Stroke Scale score between baseline and day 3. In addition, based on the aforementioned quantitative research, qualitative research will be conducted by interviewing emergency doctors about their knowledge and attitude regarding XNJI used for stroke first aid. Discussion: The results of the TRACE study will provide preliminary evidence for the relationship between XNJI used within 24 h of onset and the presence of END on the third day after stroke onset; it will aid in improving the current knowledge regarding the early use of XNJI for stroke first aid. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04275349.