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Over time, repeated mouse-dragging manipulation may cause discomfort in the upper extremities. This study compared biomechanical parameters, mouse movement data, and the discomfort perception index between 2-min mouse dragging and moving manipulation tasks with higher or normal target objectives. We recruited 20 non-symptomatic graphic design students who frequently engage in intensive mouse-dragging manipulation. We assessed the impact of continued dragging versus non-dragging manipulation using electromyographic data, mouse fingertip pressure data, and mouse trajectory velocity data. We also performed a temporal correlation analysis between EMG, mouse velocity, and fingertip pressure to investigate the relationship between physiological data and mouse movement performance. The study revealed significant differences between the dragging and moving tasks regarding muscle activity, mouse velocity, and fingertip pressure. In particular, the percentage of muscle activation on the right side of the extensor carpi radialis longus (ECR) and the lateral head of the triceps brachii (TB) differed significantly between the two tasks, with higher muscle activation levels during the dragging task. Moreover, the average muscle activation of ECR and TB was significantly higher at high target operation levels. In addition, the study revealed that the horizontal, vertical, and mean mouse velocities were significantly higher for the dragging manipulation in the high target task than for the mouse moving manipulation. In the temporal correlation analysis, the correlation coefficients of muscle activation, fingertip pressure, and mouse mean velocity differed between the two mouse manipulation behaviors, with a higher correlation between muscle activation levels and pressure values during the dragging manipulation. [ABSTRACT FROM AUTHOR]

Congenital myopathies (CMs) are a kind of non-progressive or slow-progressive muscle diseases caused by genetic mutations, which are currently defined and categorized mainly according to their clinicopathological features. CMs exhibit pleiotropy and genetic heterogeneity. Currently, supportive treatment and pharmacological remission are the mainstay of treatment, with no cure available. Some adeno-associated viruses show promising prospects in the treatment of MTM1 and BIN1-associated myopathies; however, such gene-level therapeutic interventions target only specific mutation types and are not generalizable. Thus, it is particularly crucial to identify the specific causative genes. Here, we outline the pathogenic mechanisms based on the classification of causative genes: excitation-contraction coupling and triadic assembly (RYR1, MTM1, DNM2, BIN1), actin-myosin interaction and production of myofibril forces (NEB, ACTA1, TNNT1, TPM2, TPM3), as well as other biological processes. Furthermore, we provide a comprehensive overview of recent therapeutic advancements and potential treatment modalities of CMs. Despite ongoing research endeavors, targeted strategies and collaboration are imperative to address diagnostic uncertainties and explore potential treatments. [ABSTRACT FROM AUTHOR]

Monogalactosyldiacylglycerol (MGDG), a predominant photosynthetic membrane lipid derived from plants and microalgae, has important applications in feed additives, medicine, and other fields. The low content and various structural stereoselectivity differences of MGDG in plants limited the biological extraction or chemical synthesis of MGDG, resulting in a supply shortage of monogalactosyldiacylglycerol with a growing demand. Herein, we established Saccharomyces cerevisiae as a cell factory for efficient de novo production of monogalactosyldiacylglycerol for the first time. Heterologous production of monogalactosyldiacylglycerol was achieved by overexpression of codon-optimized monogalactosyldiacylglycerol synthase gene MGD1, the key Kennedy pathway genes (i.e. GAT1, ICT1, and PAH1), and multi-copy integration of the MGD1 expression cassette. The final engineered strain (MG-8) was capable of producing monogalactosyldiacylglycerol with titers as high as 16.58 nmol/mg DCW in a shake flask and 103.2 nmol/mg DCW in a 5 L fed-batch fermenter, respectively. This is the first report of heterologous biosynthesis of monogalactosyldiacylglycerol in microorganisms, which will provide a favorable reference for study on heterologous production of monogalactosyldiacylglycerol in yeasts. [ABSTRACT FROM AUTHOR]

Microfibers from natural products are endowed with remarkable biocompatibility, biodegradability, sustainable utilization as well as environmental protection characteristics etc. Benefitting from these advantages, microfibers have demonstrated their prominent values in biomedical applications. This review comprehensively summarizes the relevant research progress of sustainable microfibers from natural products and their biomedical applications. To begin, common natural elements are introduced for the microfiber fabrication. After that, the focus is on the specific fabrication technology and process. Subsequently, biomedical applications of sustainable microfibers are discussed in detail. Last but not least, the main challenges during the development process are summarized, followed by a vision for future development opportunities. [ABSTRACT FROM AUTHOR]

Virtual reality has gained more attention in the physical training field, but few studies focus on the effects of VR on older adults. Based on existing study we suggest that VR-based upper limb training might be more effective for older adults and used functional near inferred spectrum and movement analysis to evaluate the effects of VR-based training on older adults. 20 older and 20 youth adults were recruited to perform VR training by extending their upper limb to reaching the objects, and non-VR training as a contrast. Both age-related and task-related differences were found in cortical activation, showing that the VR training has aroused more cortical activation. The older groups have more intensive movement but perform worse in terms of task completion. Both groups performed better in VR, and the difference in the older group was higher. [ABSTRACT FROM AUTHOR]

Background: Vascular adhesion protein-1 (VAP-1), an inflammation-inducible endothelial cell molecule, was reported to be implicated in a variety of cardiovascular diseases. However, the clinical significance of circulating VAP-1 levels in patients with coronary heart disease (CHD) remains less studied. Patients and Methods: We retrospectively analyzed clinical data of 336 hospitalized patients in the Second Affiliated Hospital of Soochow University from May 2020 to September 2022, 174 of which were diagnosed with CHD. Serum VAP-1 was measured by enzyme-linked immunosorbent assay at enrollment. The primary end point of this study was the occurrence of major adverse cardiovascular events (MACE). The coronary stenosis and clinical manifestations of CHD were assessed and recorded from medical records or follow-up calls. The relevant results were obtained, and the reliability of the conclusions was verified through regression analysis, curve fitting, and survival curve. Results: After adjusting for potential confounders, higher serum VAP-1 level was associated with increased risk of MACE in patients with CHD [(HR = 5.11, 95% CI = 1.02– 25.59), (HR = 5.81, 95% CI = 1.16– 29.11)]. The results of curve fitting and survival analysis were consistent with those of regression analysis. However, no significant association was observed between VAP-1 and MACE in the entire study population [(HR = 5.11, 95% CI = 0.41– 1.93), (HR = 1.17, 95% CI = 0.52– 2.62)]. Furthermore, the level of VAP-1 did not show a significant correlation with coronary stenosis and the clinical manifestations of CHD. Conclusion: These findings suggested that CHD patients with higher serum levels of VAP-1 are at a higher risk of adverse cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Preserving the functionality of hepatocytes in vitro poses a significant challenge in liver tissue engineering and bioartificial liver, as these cells rapidly lose their metabolic and functional characteristics after isolation. Inspired by the macroporous structures found in native liver tissues, here we develop synthetic hydrogel scaffolds that closely mimic the liver's structural organization through the phase separation between polyethylene glycol (PEG) and polysaccharides. Our hydrogels exhibit interconnected macroporous structures and appropriate mechanical properties, providing an optimal microenvironment conducive to hepatocyte adhesion and the formation of sizable aggregates. Compared to two-dimensional hepatocyte cultures, enhanced functionalities of hepatocytes cultured in our macroporous hydrogels were observed for 14 days, as evidenced by quantitative reverse-transcription–polymerase chain reactions (qRT-PCR), immunofluorescence, and enzyme linked immunosorbent assay (ELISA) analyses. Protein sequencing data further confirmed the establishment of cell-cell interactions among hepatocytes when cultured in our hydrogels. Notably, these hepatocytes maintained a protein expression lineage that closely resembled freshly isolated hepatocytes, particularly in the Notch and tumor necrosis factor (TNF) signaling pathways. These results suggest that the macroporous hydrogels are attractive scaffolds for liver tissue engineering. [ABSTRACT FROM AUTHOR]

Transcription factors are essential for the development and regeneration of the nervous system. The current study investigated key regulatory transcription factors in rat spinal cord development via RNA sequencing. The hub gene Ets1 was highly expressed in the spinal cord during the embryonic period, and then its expression decreased during spinal cord development. Knockdown of Ets1 significantly increased the axonal growth of cultured spinal cord neurons. Luciferase reporter assays and chromatin immunoprecipitation assays indicated that Ets1 could directly bind to the Lcn2 promoter and positively regulate Lcn2 transcription. In conclusion, these findings provide the first direct evidence that Ets1 regulates axon growth by controlling Lcn2 expression, and Ets1 may be a novel therapeutic target for axon regeneration in the central nervous system. [ABSTRACT FROM AUTHOR]

Immunotherapy is one of the fastest developing areas in the field of oncology. Many immunological treatment strategies for refractory tumors have been approved and marketed. Nevertheless, much clinical and preclinical experimental evidence has shown that the efficacy of immunotherapy in tumor treatment varies markedly among individuals. The commensal microbiome mainly colonizes the intestinal lumen in humans, is affected by a variety of factors and exhibits individual variation. Moreover, the gut is considered the largest immune organ of the body due to its influence on the immune system. In the last few decades, with the development of next-generation sequencing (NGS) techniques and in-depth research, the view that the gut microbiota intervenes in antitumor immunotherapy through the immune system has been gradually confirmed. Here, we review important studies published in recent years focusing on the influences of microbiota on immune system and the progression of malignancy. Furthermore, we discuss the mechanism by which microbiota affect tumor immunotherapy, including immune checkpoint blockade (ICB) and adoptive T-cell therapy (ACT), and strategies for modulating the microbial composition to facilitate the antitumor immune response. Finally, opportunity and some challenges are mentioned to enable a more systematic understanding of tumor treatment in the future and promote basic research and clinical application in related fields. [ABSTRACT FROM AUTHOR]

The transplantation of mesenchymal stem cells-derived secretome, particularly extracellular vesicles is a promising therapy to suppress spinal cord injury-triggered neuroinflammation. However, efficient delivery of extracellular vesicles to the injured spinal cord, with minimal damage, remains a challenge. Here we present a device for the delivery of extracellular vesicles to treat spinal cord injury. We show that the device incorporating mesenchymal stem cells and porous microneedles enables the delivery of extracellular vesicles. We demonstrate that topical application to the spinal cord lesion beneath the spinal dura, does not damage the lesion. We evaluate the efficacy of our device in a contusive spinal cord injury model and find that it reduces the cavity and scar tissue formation, promotes angiogenesis, and improves survival of nearby tissues and axons. Importantly, the sustained delivery of extracellular vesicles for at least 7 days results in significant functional recovery. Thus, our device provides an efficient and sustained extracellular vesicles delivery platform for spinal cord injury treatment. Efficient delivery of extracellular vesicles to the injured spinal cord, with minimal damage, remains challenging. Here, the authors fabricate a minimally invasive microneedle device, which provides efficient and sustained extracellular vesicle delivery for spinal cord injury treatment. [ABSTRACT FROM AUTHOR]

The transplantation of mesenchymal stem cells-derived secretome, particularly extracellular vesicles is a promising therapy to suppress spinal cord injury-triggered neuroinflammation. However, efficient delivery of extracellular vesicles to the injured spinal cord, with minimal damage, remains a challenge. Here we present a device for the delivery of extracellular vesicles to treat spinal cord injury. We show that the device incorporating mesenchymal stem cells and porous microneedles enables the delivery of extracellular vesicles. We demonstrate that topical application to the spinal cord lesion beneath the spinal dura, does not damage the lesion. We evaluate the efficacy of our device in a contusive spinal cord injury model and find that it reduces the cavity and scar tissue formation, promotes angiogenesis, and improves survival of nearby tissues and axons. Importantly, the sustained delivery of extracellular vesicles for at least 7 days results in significant functional recovery. Thus, our device provides an efficient and sustained extracellular vesicles delivery platform for spinal cord injury treatment. Efficient delivery of extracellular vesicles to the injured spinal cord, with minimal damage, remains challenging. Here, the authors fabricate a minimally invasive microneedle device, which provides efficient and sustained extracellular vesicle delivery for spinal cord injury treatment. [ABSTRACT FROM AUTHOR]

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors – the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood–brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury. [ABSTRACT FROM AUTHOR]

Hypoxia is a persistent physiological feature of many different solid tumors and a key driver of malignancy, and in recent years, it has been recognized as an important target for cancer therapy. Hypoxia occurs in the majority of solid tumors due to a poor vascular oxygen supply that is not sufficient to meet the needs of rapidly proliferating cancer cells. A hypoxic tumor microenvironment (TME) can reduce the effectiveness of other tumor therapies, such as radiotherapy, chemotherapy, and immunotherapy. In this review, we discuss the critical role of hypoxia in tumor development, including tumor metabolism, tumor immunity, and tumor angiogenesis. The treatment methods for hypoxic TME are summarized, including hypoxia‐targeted therapy and improving oxygenation by alleviating tumor hypoxia itself. Hyperoxia therapy can be used to improve tissue oxygen partial pressure and relieve tumor hypoxia. We focus on the underlying mechanisms of hyperoxia and their impact on current cancer therapies and discuss the prospects of hyperoxia therapy in cancer treatment. [ABSTRACT FROM AUTHOR]

Rodent dorsal root ganglion (DRG) is widely used for studying axonal injury. Extensive studies have explored genome-wide profiles on rodent DRGs under peripheral nerve insults. However, systematic integration and exploration of these data still be limited. Herein, we re-analyzed 21 RNA-seq datasets and presented a web-based resource (DRGProfile). We identified 53 evolutionarily conserved injury response genes, including well-known injury genes (Atf3, Npy and Gal) and less-studied transcriptional factors (Arid5a, Csrnp1, Zfp367). Notably, we identified species-preference injury response candidates (e.g. Gpr151, Lipn, Anxa10 in mice; Crisp3, Csrp3, Vip, Hamp in rats). Temporal profile analysis reveals expression patterns of genes related to pre-regenerative and regenerating states. Finally, we found a large sex difference in response to sciatic nerve injury, and identified four male-specific markers (Uty, Eif2s3y, Kdm5d, Ddx3y) expressed in DRG. Our study provides a comprehensive integrated landscape for expression change in DRG upon injury which will greatly contribute to the neuroscience community. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have shown chondroprotective effects in cartilage repair. However, side effects caused by MSC treatment limit their application in clinic. As a cell-free therapy, MSC-derived exosomes (EXOs) have attracted much more attention in recent years. In the present study, we prepared EXOs from human bone marrow mesenchymal stem cells (hBMSCs) and examined their therapeutic potentials in cartilage repair. Our results showed that the prepared extracellular vesicles exhibit classical features of EXOs, such as cup-like shape, around 100 nm diameter, positive protein markers (CD81, TSG101, and Flotillin 1), and ability of internalization. In primary chondrocytes, the treatment of hBMSC-EXOs markedly increases cell viability and proliferation in a dose-dependent manner. Moreover, wound healing assay showed that hBMSC-EXOs accelerate cell migration in primary chondrocytes. JC-1 staining revealed that the mitochondrial membrane potential was enhanced by hBMSC-EXOs, indicating cell apoptosis was decreased in the presence of hBMSC-EXOs. In rabbits with articular cartilage defects, local administration with hBMSC-EXOs facilitates cartilage regeneration as evidenced by gross view and hematoxylin-eosin (H&E) and Saf-O/Fast Green staining. In addition, the International Cartilage Repair Society (ICRS) score was increased by the application of hBMSC-EXOs. Overall, our data indicate that the treatment with hBMSC-EXOs is a suitable cell-free therapy for treating cartilage defects, and these benefits are likely due to improved cell proliferation and migration in chondrocytes. [ABSTRACT FROM AUTHOR]

Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity and unique brain functions in rodents1,2 and are dysregulated in multiple human neurological disorders3–5. Little is known about the molecular characteristics of adult human hippocampal imGCs, and even their existence is under debate1,6–8. Here we performed single-nucleus RNA sequencing aided by a validated machine learning-based analytic approach to identify imGCs and quantify their abundance in the human hippocampus at different stages across the lifespan. We identified common molecular hallmarks of human imGCs across the lifespan and observed age-dependent transcriptional dynamics in human imGCs that suggest changes in cellular functionality, niche interactions and disease relevance, that differ from those in mice9. We also found a decreased number of imGCs with altered gene expression in Alzheimer's disease. Finally, we demonstrated the capacity for neurogenesis in the adult human hippocampus with the presence of rare dentate granule cell fate-specific proliferating neural progenitors and with cultured surgical specimens. Together, our findings suggest the presence of a substantial number of imGCs in the adult human hippocampus via low-frequency de novo generation and protracted maturation, and our study reveals their molecular properties across the lifespan and in Alzheimer's disease.Single-nucleus RNA-sequencing analysis supports the presence of immature dentate granule cells throughout the human lifespan and shows that these cells are reduced in number and dysregulated in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: Circular RNA (circRNA) tubulin gamma complex associated protein 3 (circTUBGCP3) has been reported to play an oncogenic role in colorectal cancer and osteosarcoma. Aims: We further assessed the role and working mechanism of circTUBGCP3 in rectal cancer progression. Methods: Colony formation assay and transwell assays were performed to analyze cell colony formation ability and motility. Flow cytometry was utilized to assess cell cycle progression and cell apoptosis. The production of lactate and the consumption of glucose were evaluated by fluorescence-based glucose/lactate assay kit to analyze cell glycolysis. The intermolecular interaction was verified by dual-luciferase reporter assay. In vivo experiments were carried out to analyze the role of circTUBGCP3 in tumor growth using xenograft tumor model. Results: CircTUBGCP3 was significantly up-regulated in rectal cancer tissues and cell lines. CircTUBGCP3 interference inhibited the colony formation ability, migration, invasion, cell cycle progression, and glycolysis and promoted the apoptosis in rectal cancer cells. CircTUBGCP3 negative regulated microRNA-375 (miR-375) expression through interacting with it and circTUBGCP3 silencing-mediated effects in rectal cancer cells were largely based on the up-regulation of miR-375. Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) was a target of miR-375, and ROCK1 was regulated by circTUBGCP3/miR-375 axis in rectal cancer cells. MiR-375 overexpression suppressed the malignant behaviors of rectal cancer cells partly through down-regulating ROCK1. CircTUBGCP3 interference restrained rectal cancer progression in vivo. Conclusion: CircTUBGCP3 acted as an oncogene to promote the malignant phenotypes of rectal cancer cells by modulating miR-375/ROCK1 axis. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury is common, and can lead to skeletal muscle atrophy and dysfunction. However, the underlying molecular mechanisms are not fully understood. The transcription factors have been proved to play a key role in denervated muscle atrophy. In order to systematically analyze transcription factors and obtain more comprehensive information of the molecular regulatory mechanisms in denervated muscle atrophy, a new transcriptome survey focused on transcription factors are warranted. In the current study, we used microarray to identify and analyze differentially expressed genes encoding transcription factors in denervated muscle atrophy in a rat model of sciatic nerve dissection. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to explore the biological functions of differentially expressed transcription factors and their target genes related to skeletal muscle pathophysiology. We found that the differentially expressed transcription factors were mainly involved in the immune response. Based on correlation analysis and the expression trends of transcription factors, 18 differentially expressed transcription factors were identified. Stat3, Myod1, Runx1, Atf3, Junb, Runx2, Myf6, Stat5a, Tead4, Klf5, Myog, Mef2a, and Hes6 were upregulated. Ppargc1a, Nr4a1, Lhx2, Ppara, and Rxrg were downregulated. Functional network mapping revealed that these transcription factors are mainly involved in inflammation, development, aging, proteolysis, differentiation, regeneration, autophagy, oxidative stress, atrophy, and ubiquitination. These findings may help understand the regulatory mechanisms of denervated muscle atrophy and provide potential targets for future therapeutic interventions for muscle atrophy following peripheral nerve injury. [ABSTRACT FROM AUTHOR]

In contrast to the adult mammalian central nervous system (CNS), the neurons in the peripheral nervous system (PNS) can regenerate their axons. However, the underlying mechanism dictating the regeneration program after PNS injuries remains poorly understood. Combining chemical inhibitor screening with gain- and loss-of-function analyses, we identified p90 ribosomal S6 kinase 1 (RSK1) as a crucial regulator of axon regeneration in dorsal root ganglion (DRG) neurons after sciatic nerve injury (SNI). Mechanistically, RSK1 was found to preferentially regulate the synthesis of regeneration-related proteins using ribosomal profiling. Interestingly, RSK1 expression was up-regulated in injured DRG neurons, but not retinal ganglion cells (RGCs). Additionally, RSK1 overexpression enhanced phosphatase and tensin homolog (PTEN) deletion-induced axon regeneration in RGCs in the adult CNS. Our findings reveal a critical mechanism in inducing protein synthesis that promotes axon regeneration and further suggest RSK1 as a possible therapeutic target for neuronal injury repair. This study shows that p90 ribosomal S6 kinase 1 (RSK1) responds differentially to nerve injury in the peripheral and central nervous systems, and identifies it as a crucial regulator of axonal regeneration; mechanistically, RSK1 preferentially induces the synthesis of regeneration-related proteins via the RSK1-eEF2K-eEF2 axis. [ABSTRACT FROM AUTHOR]

Prior research generally confirms that there are no neuronal cell bodies in the adult sciatic nerve. However, we occasionally find some neuronal cells in adult rat sciatic nerves, either intact or crush-injured. By whole-mount staining and optical imaging of the hyalinized sciatic nerves for Stmn2 (a specific marker for neuronal cells), we found those neuronal cells with irregular distribution in the sciatic nerves in both crushed model and normal rats. We investigated the identity of those cells and established a cultured sciatic nerve model. Immunohistochemistry evidence both in vivo and in vitro illustrated that some of those cells are mature neurons in sciatic nerves. With single-cell sequencing of neuronal cells in adeno-associated virus (AAV)-infected sciatic nerves, we identified that some of those cells are a kind of neuronal stem-like cells. Then we constructed a Nestin-CreERT 2 rat line and traced those cells with fluorescence labeling which was induced by tamoxifen. Interesting, we proved that neuronal stem-like cells could proliferate by combination of EdU incorporation with staining in the sciatic nerves of transgenic rats. Together, the discovery of neuronal cells in adult sciatic nerves will make us aware of the distribution of neurons in the peripheral nervous system. Especially our data suggest that neuronal stem-like cells could proliferate in the sciatic nerves of adult rats. [ABSTRACT FROM AUTHOR]

The morbidity and mortality of cardiovascular diseases (CVDs) have been increasing year by year all over the world and expanding greatly to the younger population, which becomes the leading causes of death globally that threatens human life safety. Prediction of the occurrence of diseases by using risk related adverse events is crucial for screening and early detection of CVDs. Thus, the discovery of new biomarkers that related to risks of CVDs are of urgent in the field. Retinol-binding protein 4 (RBP4) is a 21-kDa adipokine, mainly secreted by adipocytes. Besides its well-established function in the induction of insulin resistance, it has also been found in recent years to be closely associated with CVDs and other risk factors, such as hypertension, coronary heart disease, heart failure, obesity, and hyperlipidemia. In this review, we mainly focus on the progress of research that establishes the correlation between RBP4 and CVDs and the corresponding major risk factors in recent years. [ABSTRACT FROM AUTHOR]

Background: Inflammation may trigger skeletal muscle atrophy induced by cancer cachexia. As a pro-inflammatory factor, interleukin-6 may cause skeletal muscle atrophy, but the underlying molecular mechanisms have not been explored. Methods: In this experimental study, we used adult male ICR mice, weighing 25 ± 2 g, and the continuous infusion of interleukin-6 into the tibialis anterior muscle to construct a skeletal muscle atrophy model (experimental group). A control group received a saline infusion. RNA-sequencing was used to analyze the differentially expressed genes in tissue samples after one and three days. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis were applied to define the function of these genes, and protein-protein interaction analysis was performed to identify potential transcription factors. Fluorescence microscopy was used to determine the muscle fiber cross-sectional area after 14 days. Results: Continuous infusion of interleukin-6 for 14 days caused significant muscle atrophy. RNA-sequencing found 359 differentially expressed genes in the 1- and 3-day tissue samples and 1748 differentially expressed genes only in the 3-day samples. Functional analysis showed that the differentially expressed genes found in both the 1- and 3-day samples were associated with immune receptor activation, whereas the differentially expressed genes found only in the 3-day sample were associated with reduced energy metabolism. The expression of multiple genes in the oxidative phosphorylation and tricarboxylic acid cycle pathways was down-regulated. Furthermore, differentially expressed transcription factors were identified, and their interaction with interleukin-6 and the differentially expressed genes was predicted, which indicated that STAT3, NF-κB, TP53 and MyoG may play an important role in the process of interleukin-6-induced muscle atrophy. Conclusions: This study found that interleukin-6 caused skeletal muscle atrophy through immune receptor activation and a reduction of the energy metabolism. Several transcription factors downstream of IL-6 have the potential to become new regulators of skeletal muscle atrophy. This study not only enriches the molecular regulation mechanism of muscle atrophy, but also provides a potential target for targeted therapy of muscle atrophy. [ABSTRACT FROM AUTHOR]

Background: The tumor microenvironment (TME) has significantly correlation with tumor occurrence and prognosis. Our study aimed to identify the prognostic immune-related genes (IRGs)in the tumor microenvironment of colorectal cancer (CRC).Methods: Transcriptome and clinical data of CRC cases were downloaded from TCGA and GEO databases. Stromal score, immune score, and tumor purity were calculated by the ESTIMATE algorithm. Based on the scores, we divided CRC patients from the TCGA database into low and high groups, and the differentially expressed genes (DEGs) were identified. Immune-related genes (IRGs) were selected by venn plots. To explore underlying pathways, protein-protein interaction (PPI) networks and functional enrichment analysis were used. After utilizing LASSO Cox regression analysis, we finally established a multi-IRGs signature for predicting the prognosis of CRC patients. A nomogram consists of the thirteen-IRGs signature and clinical parameters was developed to predict the overall survival (OS). We investigated the association between prognostic validated IRGs and immune infiltrates by TIMER database.Results: Gene expression profiles and clinical information of 1635 CRC patients were collected from the TCGA and GEO databases. Higher stromal score, immune score and lower tumor purity were observed positive correlation with tumor stage and poor OS. Based on stromal score, immune score and tumor purity, 1517 DEGs, 1296 DEGs, and 1892 DEGs were identified respectively. The 948 IRGs were screened by venn plots. A thirteen-IRGs signature was constructed for predicting survival of CRC patients. Nomogram with a C-index of 0.769 (95%CI, 0.717-0.821) was developed to predict survival of CRC patients by integrating clinical parameters and thirteen-IRGs signature. The AUC for 1-, 3-, and 5-year OS were 0.789, 0.783 and 0.790, respectively. Results from TIMER database revealed that CD1B, GPX3 and IDO1 were significantly related with immune infiltrates.Conclusions: In this study, we established a novel thirteen immune-related genes signature that may serve as a validated prognostic predictor for CRC patients, thus will be conducive to individualized treatment decisions. [ABSTRACT FROM AUTHOR]

Vascular adhesion protein-1 (VAP-1) is a semicarbazide-sensitive amine oxidase (SSAO), whose enzymatic activity regulates the adhesion/exudation of leukocytes in/from blood vessels. Due to its abundant expressions in vascular systems and prominent roles in inflammations, increasing attentions have been paid to the roles of VAP-1/SSAO in atherosclerosis, a chronic vascular inflammation that eventually drives clinical cardiovascular events. Clinical studies have demonstrated a potential value of soluble VAP-1 (sVAP-1) for the diagnosis and prognosis of cardiovascular diseases. Recent findings revealed that VAP-1 is expressed in atherosclerotic plaques and treatment with VAP-1 inhibitors alleviates the progression of atherosclerosis. This review will focus on the roles of VAP-1/SSAO in the progression of atherosclerotic lesions and therapeutic potentials of VAP-1 inhibitors for cardiovascular diseases. [ABSTRACT FROM AUTHOR]

In this study, we aimed to investigate the role of circORC2 in modulating miR‐19a and its downstream signalling during the pathogenesis of STC. In this study, three groups of patients, that is healthy control (HC) group, normal transit constipation (NTC) group (N = 42) and slow transit constipation (STC) group, were, respectively, recruited. RT‐PCR and Western blot analysis were exploited to investigate the changes in the expression levels of miR‐19a and circORC2 in these patients, so as to establish a circORC2/miR‐19a signalling pathway. The basic information of the patients showed no significant differences among different patient groups. Compared with the HC group, concentrations of neurotensin (NST) and motilin (MLN) were both significantly reduced in the NTC and STC groups, especially in the STC group. Also, miR‐19a level was highest, whereas circORC2 level was lowest in the STC group. Furthermore, circORC2 was validated to sponge the expression of miR‐19a, and the transfection of circORC2 reduced the expression of miR‐19a. Meanwhile, MLN and NST mRNAs were both targeted by miR‐19a, and the transfection of circORC2 dramatically up‐regulated the expression of MLN and NST. On the contrary, the transfection of circORC2 siRNA into SMCs and VSMCs exhibited the opposite effect of circORC2. Collectively, the results of this study established a regulatory relationship among circORC2, miR‐19a and neurotensin/motilin, which indicated that the overexpression of circORC2 could up‐regulate the levels of neurotensin and motilin, thus exerting a beneficial effect during the treatment of STC. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disease caused by a variety of unclear complex pathogenic factors. The 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine/probenecid (MPTP/p)-induced progressive PD mice is a well-recognized classic model for studying PD, but the molecular toxicology of this model is still unclear. Here, for the first time, we report gradual neurodegenerative processes in MPTP/p-induced progressive PD mice model using RNA-seq. Transcriptional responses are orchestrated to regulate the expression of many genes in substantia nigra, such as Ntf3, Pitx3, Th, and Drd2, leading to the degeneration of dopaminergic neurons at last. We proposed that the established model could be divided into three phases based on their molecular toxicological features: "the stress response phase" which maintained the microenvironment homeostasis, "the pre-neurodegenerative phase" which demonstrated observed MPTP/p cytotoxicity and gradual degeneration of dopaminergic neurons, and "the neurodegenerative phase" which reflected distinct damage and dopaminergic neuron apoptotic process. Glia cells exhibited a certain protective effect on dopaminergic neurons in 3rd and 6th MPTP/p-induced cytotoxicity. But in 10th MPTP/p injection, glia cells play a promoting role in PD and tissue damages caused by oxidative stress. This study also indicated that the substantia nigra of PD mice showed unique patterns of changes at each stage. Moreover, neurotrophic signaling pathway, ECM-receptor interaction, oxidative phosphorylation, apoptosis and necroptosis were enriched at 3rd and 6th MPTP/p injection, which might be associated with the PD progress. This study provided an extensive data set of molecular toxicology for elucidating of PD progression and offered comprehensive theoretical knowledge for the development of new therapy. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) is a common transcriptomic modification in cancer. Recently, it has been found to be involved in the regulation of non-small cell lung cancer (NSCLC) formation and metastasis. Interleukin 37 (IL-37) plays a crucial protective role in lung cancer. In our previous studies, we found that IL-37 is a potential novel tumor suppressor by inhibiting IL-6 expression to suppress STAT3 activation and decreasing epithelial-to-mesenchymal transition. Moreover, we found that treatment of IL-37 in lung cancer cells induced widespread and dynamic RNA m6A methylation. The effects of RNA m6A methylation of IL-37 treatment require further study. However, the functions of RNA m6A methylation of IL-37 treatment still await elucidation. Using MeRIP-seq and RNA-seq, we uncovered a unique m6A methylation profile in the treatment of IL-37 on the A549 cell line. We also showed the expression of m6A writers METTL3, METTL14, and WTAP and erasers ALKBH5 and FTO in A549 cells and lung cancer tissues after the treatment of IL-37. This study showed that IL-37 could lead to changes in m6A methylation level and related molecule expression level in A546 cells and may downregulate the proliferation by inhibiting Wnt5a/5b pathway in A549 cells. We conclude that IL-37 suppresses tumor growth through regulation of RNA m6A methylation in lung cancer cells. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a kind of malignant tumor, and the development of chemoradiotherapy resistance (CRR) increases the difficulty of its treatment. The role of circular RNAs (circRNAs) in cancer progression has been well documented. Nevertheless, the function of circ_0007031 in the growth and CRR of CRC has not been well elucidated. Methods: CRR cell lines were constructed using 5-Fu and radiation. Cell counting kit 8 (CCK8) assay was employed to measure the 5-Fu resistance and proliferation of cells. Clonogenic assay was used to evaluate the radiation resistance of cells. Also, the expression of circ_0007031 and microRNA-760 (miR-760) was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The cell cycle distribution and apoptosis of cells were assessed by flow cytometry. Besides, the levels of apoptosis-related protein and mRNA-decapping enzyme 1a (DCP1A) protein were measured by Western blot (WB) analysis. Further, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to confirm the interaction between miR-760 and circ_0007031 or DCP1A. In addition, animal experiments were performed to evaluate the function of silenced circ_0007031 on the 5-Fu and radiation resistance of CRC tumors. Results: Circ_0007031 expression was markedly increased in CRC tissues and cells, especially in CRC resistant cells. Circ_0007031 knockdown hindered proliferation, induced cell cycle arrest in the G0/G1 phase, enhanced apoptosis, and lowered the CRR of CRC resistant cells. Further, miR-760 could be targeted by circ_0007031, and its inhibitor could reverse the inhibition effect of circ_0007031 knockdown on the growth and CRR of CRC resistant cells. Moreover, DCP1A was a target of miR-760, and its overexpression could invert the suppression effect of miR-760 overexpression on the growth and CRR of CRC resistant cells. Circ_0007031 silencing could enhance the sensitivity of CRC tumors to 5-Fu and radiation to markedly reduce CRC tumor growth in vivo. Conclusion: Circ_0007031 might play a positive role in the CRR of CRC through regulating the miR-760/DCP1A axis, which might provide a new approach for treating the CRR of CRC. [ABSTRACT FROM AUTHOR]

Background: Endoscopic carpal tunnel release (ECTR) and open carpal tunnel release (OCTR) both have advantages and disadvantages for the treatment of carpal tunnel syndrome (CTS). We compared the effectiveness and safety of ECTR and OCTR based on evidence from a high-level randomized controlled trial.Methods: We comprehensively searched PubMed, EMBASE, Cochrane Library, Web of Science, and Medline to identify relevant articles published until August 2019. Data regarding operative time, grip strength, Boston Carpal Tunnel Questionnaire scores, digital sensation, patient satisfaction, key pinch strength, return to work time, and complications were extracted and compared. All mean differences (MD) and odds ratios (OR) were expressed as ECTR relative to OCTR.Results: Our meta-analysis contained twenty-eight studies. ECTR was associated with significantly higher satisfaction rates (MD, 3.13; 95% confidence interval [CI], 1.43 to 4.82; P = 0.0003), greater key pinch strengths (MD, 0.79 kg; 95% CI, 0.27 to 1.32; P = 0.003), earlier return to work times (MD, - 7.25 days; 95% CI, - 14.31 to - 0.19; P = 0.04), higher transient nerve injury rates (OR, 4.87; 95% CI, 1.37 to 17.25; P = 0.01), and a lower incidence of scar-related complications (OR, 0.20; 95% CI, 0.07 to 0.59; P = 0.004). The permanent nerve injury showed no significant differences between the two methods (OR, 1.93; 95% CI, 0.58 to 6.40; P = 0.28).Conclusions: Overall, evidence from randomized controlled trials indicates that ECTR results in better recovery of daily life functions compared to OCTR, as revealed by higher satisfaction rates, greater key pinch strengths, earlier return to work times, and fewer scar-related complications. Our findings suggest that patients with CTS can be effectively managed with ECTR. [ABSTRACT FROM AUTHOR]