A plant-derived natural photosynthetic system for improving cell anabolism.

Insufficient intracellular anabolism is a crucial factor involved in many pathological processes in the body1,2. The anabolism of intracellular substances requires the consumption of sufficient intracellular energy and the production of reducing equivalents. ATP acts as an 'energy currency' for biological processes in cells3,4, and the reduced form of NADPH is a key electron donor that provides reducing power for anabolism5. Under pathological conditions, it is difficult to correct impaired anabolism and to increase insufficient levels of ATP and NADPH to optimum concentrations1,4,6-8. Here we develop an independent and controllable nanosized plant-derived photosynthetic system based on nanothylakoid units (NTUs). To enable cross-species applications, we use a specific mature cell membrane (the chondrocyte membrane (CM)) for camouflage encapsulation. As proof of concept, we demonstrate that these CM-NTUs enter chondrocytes through membrane fusion, avoid lysosome degradation and achieve rapid penetration. Moreover, the CM-NTUs increase intracellular ATP and NADPH levels in situ following exposure to light and improve anabolism in degenerated chondrocytes. They can also systemically correct energy imbalance and restore cellular metabolism to improve cartilage homeostasis and protect against pathological progression of osteoarthritis. Our therapeutic strategy for degenerative diseases is based on a natural photosynthetic system that can controllably enhance cell anabolism by independently providing key energy and metabolic carriers. This study also provides an enhanced understanding of the preparation and application of bioorganisms and composite biomaterials for the treatment of disease.

Neutralization of Intracellular pH Homeostasis to Inhibit Osteoclasts Based on a Spatiotemporally Selective Delivery System.

Osteoporosis is a global disease caused by abnormal overactivation of osteoclasts. The acidic environment in sealing zone of osteoclasts with H+ pumped from cytoplasm is critical to the maturation of osteoclasts. Therefore, reducing the intracellular H+ concentration can reduce the H+ secretion of osteoclasts from the source. In our study, we developed a novel nanovesicle which encapsulates Na2HPO4 with a liposome hybridizes with preosteoclast membrane (Na2HPO4@Lipo-pOCm). These nanovesicles release Na2HPO4 into the preosteoclast by targeting preosteoclasts and membrane fusion, reducing the intracellular H+ concentration, and achieve biological cascade regulation of osteoclasts through simple pH regulation. In vitro and in vivo experiments confirmed that these nanovesicles reduce mitochondrial membrane potential by decreasing intracellular H+ concentration, thereby reducing the ROS in osteoclasts as well as the expression of the upstream transcription factor FOXM1 of Acp5. In short, this nanovesicle can significantly inhibit the osteoclasts and ameliorate osteoporosis caused by OVX.

Relationship between sarcopenia/paravertebral muscles and the incidence of vertebral refractures following percutaneous kyphoplasty: a retrospective study.

BACKGROUND: This study aimed to reveal the associations of osteoporotic vertebral compression refracture (OVCRF) incidence with sarcopenia and paravertebral muscles (PVM). METHODS: A total of 214 elderly patients who underwent percutaneous kyphoplasty in our hospital between January 2017 and December 2019 were analyzed. Data on possible risk factors, including sex, age, weight, height, diabetes, treated vertebral levels (thoracolumbar junction [(T10-L2]), vacuum clefts, and body mass index (BMI), were collected. Preoperative bone mineral density (BMD) and appendicular muscle mass were evaluated using dual-energy X-ray absorptiometry. Nutritional status was evaluated using the Mini Nutritional Assessment. Magnetic resonance imaging was performed to evaluate the physiological cross-sectional area of the PVM. RESULTS: Overall, 74 (15 men and 59 women) and 60 (55 women and 14 men) patients developed OVCRF and sarcopenia, respectively. Sarcopenia is related to advanced age, ower BMD and BMI values. Sarcopenia-related indicators (PVM fat rate, appendicular muscle mass index, grip strength) were significantly lower in the sarcopenia group. Univariate analysis showed a correlation between OVCRF and BMD, BMI, diabetes, sarcopenia, and age. Multivariate analysis suggested that fatty infiltration of the PVM, BMD, sarcopenia, diabetes, BMI, and treated vertebral level remained as the independent predictors of OVCRF (p < 0.05). CONCLUSIONS: The association between sarcopenia and PVM as independent risk factors for OVCRF was established in this study; therefore, sarcopenia should be greatly considered in OVCRF prevention.

Bibliometric and visualized analysis of scientific publications on subglottic stenosis based on web of science core collection.

BACKGROUND: Subglottic Stenosis (SGS), with increasing numbers of studies, is the most specific and common clinical type of Laryngotracheal Stenosis (LTS). There is rapid publication turnover with newer management introduced and expanding research field. To our knowledge, there is no bibliometric analysis of SGS yet. METHODS: In August 2022, we performed a thorough search in the Web of Science Core Collection database using the word "subglottic stenosis," and "SGS." The 580 articles were arranged based on correlation. The collected articles were then analyzed with an assessment of relevant factors. Meanwhile, we analyzed the top 100 most-cited articles on SGS. RESULTS: The frequency of publication on SGS has increased substantially over time. The USA has contributed the most articles (n = 301). Vanderbilt University published most of the articles among other institutions (n = 18). Laryngoscope topped the list of journals and has published 89 SGS-related articles. Research hotspots shift from surgical treatment to conservative management. CONCLUSIONS: The SGS-related literature has grown rapidly in recent years. This study represents the first bibliometric analysis of scientific articles on SGS. Areas to improve in SGS research can be identified after this analysis of the most impactful articles on this topic.

Biological functions and biomedical applications of extracellular vesicles derived from blood cells.

There is a growing interest in using extracellular vesicles (EVs) for therapeutic applications. EVs are composed of cytoplasmic proteins and nucleic acids and an external lipid bilayer containing transmembrane proteins on their surfaces. EVs can alter the state of the target cells by interacting with the receptor ligand of the target cell or by being internalised by the target cell. Blood cells are the primary source of EVs, and 1 µL of plasma contains approximately 1.5 × 107 EVs. Owing to their easy acquisition and the avoidance of cell amplification in vitro, using blood cells as a source of therapeutic EVs has promising clinical application prospects. This review summarises the characteristics and biological functions of EVs derived from different blood cell types (platelets, erythrocytes, and leukocytes) and analyses the prospects and challenges of using them for clinical therapeutic applications. In summary, blood cell-derived EVs can regulate different cell types such as immune cells (macrophages, T cells, and dendritic cells), stem cells, and somatic cells, and play a role in intercellular communication, immune regulation, and cell proliferation. Overall, blood cell-derived EVs have the potential for use in vascular diseases, inflammatory diseases, degenerative diseases, and injuries. To promote the clinical translation of blood cell-derived EVs, researchers need to perform further studies on EVs in terms of scalable and reproducible isolation technology, quality control, safety, stability and storage, regulatory issues, cost-effectiveness, and long-term efficacy.

Publication Trends and Hot Spots in Cauda Equina Syndrome: A Bibliometric Analysis and Visualization of Current Research.

BACKGROUND: Cauda Equina Syndrome (CES) is a relatively uncommon and complex disorder. Recently, there has been a surge in research on CES. Although the research directions are multifarious, the overall research trends are unclear at present. We aimed to identify the 100 most cited articles on CES and analyze the hot spots trends regarding CES related research by bibliometric analysis. METHODS: Articles were obtained by conducting an English language search of the Web of Science Core Collection Databases with the keywords "cauda equina syndrome." The initial 390 articles returned from the search were analyzed by VOSviewer. Next, the top 100 most cited articles were further analyzed by title, authors, journal, year of publication, total citations, country of origin, institution, and keywords. RESULTS: A total of 390 publications were identified. The top 100 most cited articles were listed in descending order of total citations (range: 196-11). These articles originated from 24 countries; among these countries, the United Kingdom contributed the most publications (n = 29). The most prolific journal was Spine (n = 27), and the University of Edinburgh was the most productive institution (n = 9). CONCLUSIONS: The number of publications on CES increased steadily, with a stable rise in recent years. Some publications have been cited more than 100 times, indicating that these findings are widely accepted by relevant clinicians and contribute significantly to the knowledge of CES. This study represents the first bibliometric analysis and visualization of hot spots analysis and research trends on CES. We believe that this will aid clinical researchers in targeting future areas of research.

Determining the learning curve for percutaneous endoscopic lumbar interbody fusion for lumbar degenerative diseases.

PURPOSE: Percutaneous endoscopic lumbar interbody fusion (PELIF) is one of the least invasive procedures for lumbar degenerative disorders (LDD). There is limited knowledge of the learning curve for PELIF. METHODS: A total of 93 consecutive patients who underwent PELIF performed by a single spine surgeon for LDD failed with conservative treatment were retrospectively reviewed. The case series was split into three groups based on timing: A (earliest third of patients); B (middle third of patients); and C (latest third of patients). The following were also recorded: operating time, X-ray exposure time, complications, radiologic fusion rates, pre- and postoperative patient-reported outcome measures (PROMs) scores (visual analogue scale (VAS) for back pain, VAS for leg pain, Japanese Orthopaedic Association, Oswestry Disability Index and MacNab criteria), length of hospital stay, and need for revision surgeries. A learning curve was then developed by a logarithmic curve-fit regression analysis. RESULTS: The operative time gradually decreased over time, and an asymptote was reached after about 25 cases. Compared with group B or C, group A had significantly longer operative time, significantly longer length of hospital stay, needed significantly more x-ray exposure time. Though not significantly different, there are fewer complications and revision surgeries over time. There is no significant difference over time in PROMs scores except for the VAS back scores. CONCLUSIONS: PELIF is an alternative for minimal invasive surgery for LDD, PELIF presents a learning curve to the practicing spine surgeon with regard to operative time, x-ray exposure time, length of hospital stay, clinical PROMs and radiographic outcomes and complications. The presented PELIF learning curve provided valuable insight to surgeons interested in performing this surgery.

Platelet-derived extracellular vesicles ameliorate intervertebral disc degeneration by alleviating mitochondrial dysfunction.

Mitochondrial dysfunction causes the production of reactive oxygen species (ROS) and oxidative damage, and oxidative stress and inflammation are considered key factors causing intervertebral disc degeneration (IVDD). Thus, restoring the mitochondrial dysfunction is an attractive strategy for treating IVDD. Platelet-derived extracellular vesicles (PEVs) are nanoparticles that target inflammation. Moreover, the vesicles produced by platelets (PLTs) have considerable anti-inflammatory effects. We investigate the use of PEVs as a therapeutic strategy for IVDD in this study. We extract PEVs and evaluate their properties; test their effects on H2O2-induced oxidative damage of nucleus pulposus (NP) cells; verify the role of PEVs in repairing H2O2-induced cellular mitochondrial dysfunction; and demonstrate the therapeutic effects of PEVs in a rat IVDD model. The results confirm that PEVs can restore impaired mitochondrial function, reduce oxidative stress, and restore cell metabolism by regulating the sirtuin 1 (SIRT1)-peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α)-mitochondrial transcription factor A (TFAM) pathway; in rat models, PEVs retard the progression of IVDD. Our results demonstrate that the injection of PEVs can be a promising strategy for treating patients with IVDD.

Platelets and platelet extracellular vesicles in drug delivery therapy: A review of the current status and future prospects.

Platelets are blood cells that are primarily produced by the shedding of megakaryocytes in the bone marrow. Platelets participate in a variety of physiological and pathological processes in vivo, including hemostasis, thrombosis, immune-inflammation, tumor progression, and metastasis. Platelets have been widely used for targeted drug delivery therapies for treating various inflammatory and tumor-related diseases. Compared to other drug-loaded treatments, drug-loaded platelets have better targeting, superior biocompatibility, and lower immunogenicity. Drug-loaded platelet therapies include platelet membrane coating, platelet engineering, and biomimetic platelets. Recent studies have indicated that platelet extracellular vesicles (PEVs) may have more advantages compared with traditional drug-loaded platelets. PEVs are the most abundant vesicles in the blood and exhibit many of the functional characteristics of platelets. Notably, PEVs have excellent biological efficacy, which facilitates the therapeutic benefits of targeted drug delivery. This article provides a summary of platelet and PEVs biology and discusses their relationships with diseases. In addition, we describe the preparation, drug-loaded methods, and specific advantages of platelets and PEVs targeted drug delivery therapies for treating inflammation and tumors. We summarize the hot spots analysis of scientific articles on PEVs and provide a research trend, which aims to give a unique insight into the development of PEVs research focus.

Suppression of osteoclast multinucleation via a posttranscriptional regulation-based spatiotemporally selective delivery system.

Redundancy of multinucleated mature osteoclasts, which results from the excessive fusion of mononucleated preosteoclasts (pOCs), leads to osteolytic diseases such as osteoporosis. Unfortunately, the currently available clinical drugs completely inhibit osteoclasts, thus interfering with normal physiological bone turnover. pOC-specific regulation may be more suitable for maintaining bone homeostasis. Here, circBBS9, a previously unidentified circular RNA, was found to exert regulatory effects via the circBBS9/miR-423-3p/Traf6 axis in pOCs. To overcome the long-standing challenge of spatiotemporal RNA delivery to cells, we constructed biomimetic nanoparticles to achieve the pOC-specific targeted delivery of circBBS9. pOC membranes (POCMs) were extracted to camouflage cationic polymer for RNA interference with circBBS9 (POCM-NPs@siRNA/shRNAcircBBS9). POCM-NPs endowed the nanocarriers with improved stability, accurate pOC targeting, fusogenic uptake, and reactive oxygen species-responsive release. In summary, our findings may provide an alternative strategy for multinucleated cell-related diseases that involves restriction of mononucleated cell multinucleation through a spatiotemporally selective delivery system.

Emerging Antioxidant Paradigm of Mesenchymal Stem Cell-Derived Exosome Therapy.

Mesenchymal stem cell-derived exosomes have been under investigation as potential treatments for a diverse range of diseases, and many animal and clinical trials have achieved encouraging results. However, it is well known that the biological activity of the exosomes is key to their therapeutic properties; however, till date, it has not been completely understood. Previous studies have provided different explanations of therapeutic mechanisms of the exosomes, including anti-inflammatory, immunomodulatory, and anti-aging mechanisms. The pathological effects of oxidative stress often include organ damage, inflammation, and disorders of material and energy metabolism. The evidence gathered from research involving animal models indicates that exosomes have antioxidant properties, which can also explain their anti-inflammatory and cytoprotective effects. In this study, we have summarized the antioxidant effects of exosomes in in vivo and in vitro models, and have evaluated the anti-oxidant mechanisms of exosomes by demonstrating a direct reduction in excessive reactive oxygen species (ROS), promotion of intracellular defence of anti-oxidative stress, immunomodulation by inhibiting excess ROS, and alteration of mitochondrial performance. Exosomes exert their cytoprotective and anti-inflammatory properties by regulating the redox environment and oxidative stress, which explains the therapeutic effects of exosomes in a variety of diseases, mechanisms that can be well preserved among different species.

Bibliometric and Visualized Analysis of Scientific Publications on Ossification of the Posterior Longitudinal Ligament Based on Web of Science.

BACKGROUND: In recent years, there has been increasing study of ossification of the posterior longitudinal ligament (OPLL), leading to many articles on this topic. We aimed to identify trends in OPLL-related research and to analyze the most highly cited scientific articles on OPLL. METHODS: We searched the Web of Science Core Collection database for all articles on OPLL. The years of publication, countries, journals, institutions, and total citations were extracted and analyzed. Results related to countries, institutions, and keywords were subjected to co-occurrence analysis using VOSviewer software. The top 100 most-cited articles on OPLL were analyzed. RESULTS: A total of 876 articles related to OPLL were identified. The frequency of publication on OPLL has increased substantially over time. Among all countries, Japan has contributed the most articles on OPLL (n = 349). The most productive institution has been Hirosaki University (n = 57). Spine topped the list of journals and has published 120 OPLL-related articles, which received 4221 total citations. The surgical treatment of OPLL has been the most common research focus in the OPLL literature. CONCLUSIONS: The scientific literature on OPLL has rapidly expanded in recent years. This study represents the first bibliometric analysis of scientific articles on OPLL and can serve as a useful guide to clinicians and researchers in the field.

Bibliometric Analysis of the Scientific Literature on Adolescent Idiopathic Scoliosis.

BACKGROUND: In recent years, there has been increasing research on adolescent idiopathic scoliosis (AIS), leading to many publications on this topic. To our knowledge, no study has focused on the research trends in this field. METHODS: Using the Web of Science Core Collection database for all articles on AIS, the number of citations, authorship, year of publication, journal of publication, country and institution of origin, and keywords were subjected to co-occurrence analysis using VOSviewer software. The top 100 most-cited articles on AIS were analyzed. RESULTS: Between 1985 and 2020, 2266 articles related to AIS were identified. The frequency of publication on AIS has increased substantially over time. Among all countries, the United States has contributed the most articles on AIS (n = 671). The most productive institution has been Nanjing University (n = 154). Spine topped the list of journals and has published 569 AIS-related articles, which received 19,862 total citations. The clinical description of AIS has been the most common research focus in the AIS literature. CONCLUSIONS: The scientific literature on AIS has rapidly expanded in recent years. This study represents the updated bibliometric analysis of scientific articles on AIS and provides a research trend for the first time, which aims to give a unique insight into the development of AIS research focus and serve as a useful guide to clinicians and researchers in the field.