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High expression of nuclear factor interleukin-3 (NFIL3) and integrin Alpha M (ITGAM) was found in serum samples from Kawasaki disease (KD) patients through bioinformatics analysis. Hence, this study aimed to explore the biological functions of NFIL3 and ITGAM in KD serum-stimulated human coronary artery endothelial cells (HCAECs). The differentially-expressed genes in KD were analyzed through bioinformatics analysis. Serum samples were obtained from 18 KD patients and 18 healthy volunteers, followed by detection of NFIL3 and ITGAM levels in KD serum. After HCAECs were transfected with sh-NFIL3, sh-ITGAM, or sh-NFIL3 + oe-ITGAM and underwent 24-h KD serum stimulation, cell viability and apoptosis and the levels of inflammation-related factors were measured. The binding between NFIL3 and ITGAM was validated by dual-luciferase and chromatin immunoprecipitation (ChIP) assays. NFIL3 and ITGAM were up-regulated in serum from KD patients and KD serum-stimulated HCAECs. Down-regulation of NFIL3 or ITGAM inhibited KD serum-induced cell apoptosis and inflammatory response of HCAECs and promoted cell viability. Mechanistically, NFIL3 promoted ITGAM transcription level. Up-regulation of ITGAM reversed the improvement of NFIL3 down-regulation on KD serum-induced HCAEC injury. NFIL3 aggravated KD serum-induced HCAEC injury by promoting ITGAM transcription, which provided new insights into the treatment of KD. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by autoimmunity, synovial inflammation and joint destruction. Pannus formation in the synovial cavity can cause irreversible damage to the joint and cartilage and eventually permanent disability. Current conventional treatments for RA have limitations regarding efficacy, safety and cost. microRNA (miRNA) is a type of non-coding RNA (ncRNA) that regulates gene expression at the post-transcriptional level. The dysregulation of miRNA has been observed in RA patients and implicated in the pathogenesis of RA. miRNAs have emerged as potential biomarkers or therapeutic agents. In this review, we explore the role of miRNAs in various aspects of RA pathophysiology, including immune cell imbalance, the proliferation and invasion of fibroblast-like synovial (FLS) cell, the dysregulation of inflammatory signaling and disturbance in angiogenesis. We delve into the regulatory effects of miRNAs on Treg/Th17 and M1/M2 polarization, the activation of the NF-κB/NLRP3 signaling pathway, neovascular formation, energy metabolism induced by FLS-cell-induced energy metabolism, apoptosis, osteogenesis and mobility. These findings shed light on the potential applications of miRNAs as diagnostic or therapeutic biomarkers for RA management. Furthermore, there are some strategies to regulate miRNA expression levels by utilizing miRNA mimics or exosomes and to hinder miRNA activity via competitive endogenous RNA (ceRNA) network-based antagonists. We conclude that miRNAs offer a promising avenue for RA therapy with unlimited potential. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most common and lethal central nervous system cancer and is associated with a poor prognosis. Simvastatin, a kind of widely used hypolipidemic agent, has been investigated for its beneficial effects on various types of cancers. The main purpose of this paper is to investigate the potential inhibitory effects of simvastatin on GBM and the underlying mechanism. Cell viability and cell cycle of simvastatin-treated U87 and U251 cells were determined by CCK8 assay and flow cytometry, respectively. Additionally, we assessed cell migration and invasion abilities using a wound-healing assay and transwell assay. mRNA and protein expression patterns of caspase-1 and its markers nucleotide-binding oligomerization domain-like receptor pyrin domain–containing 3 (NLRP3) and IL-1β in different conditions were detected by real-time polymerase chain reaction, immunofluorescence staining, and Western blot. Simvastatin decreased the viability of GBM cells and inhibited cell migration and invasion in a dose-dependent manner. Moreover, suppression of pyroptosis, as characterized by decreased expression of caspase-1, NLRP3, and IL-1β, was observed. However, use of an miR-214 inhibitor reversed the simvastatin suppressive effect on GBM cells. Simvastatin inhibits GBM progression by suppressing caspase-1–dependent pyroptosis, regulated by miR-214. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis, a chronic autoimmune disease with complex etiology, is characterized by excessive proliferation of synovial cells, massive production of inflammatory cells and cartilage destruction. Studies have shown that mitochondrial dysfunction plays an important role in promoting the occurrence of RA. Mitochondria with normal structure and function are essential for the normal survival of chondrocytes and synovial cells. Once mitochondrial function is destroyed, it will affect the survival, activation and differentiation of immune cells and non-immune cells involved in the pathogenesis of RA, thus leading to the occurrence of RA. However, the mechanism of mitochondrial dysfunction in RA remains unclear. This article reviews the method of mitochondrial dysfunction leading to RA, the effects of mitochondrial dysfunction on immune cells, the etiology of mitochondrial dysfunction in RA, and the pathology of mitochondrial dysfunction in RA. We also outline some drugs that can exert therapeutic effects on RA which are associated with modulating mitochondrial activity. The understanding and summary of mitochondrial dysfunction in RA may provide new research directions for pathological intervention and prevention of RA. [ABSTRACT FROM AUTHOR]

Peritoneal regeneration and repair can alleviate postoperative intraperitoneal adhesions, and mesenchymal stem cells (MSCs) have demonstrated the potential for peritoneal repair and regeneration. However, extracellular vesicles (EVs) are the main carriers for the MSC activity. Thus far, the roles of MSC-derived EVs on peritoneal repair are not well understood. To investigate the therapeutic effect of adipose-derived mesenchymal stem cell-derived EVs (ADSC-EVs) in peritoneal injuries, ADSC-EVs were injected in vivo via the tail vein of rats. The antiadhesion effects were evaluated following abdominal surgery. In addition, the levels of the peritoneal fibrinolysis system were determined via enzyme-linked immunosorbent assay. Expression differences in inflammatory and apoptotic markers were detected using immunofluorescence. The expression of extracellular matrix-related indexes and peritoneal healing were observed using immunohistochemistry. In vitro, rat peritoneal mesothelial cell proliferation was assessed via a 5-ethynyl-2-deoxyuridine assay. Cell migration was determined using scratch wound and transwell assays. Related signaling networks were estimated based on sequencing and bioinformatics analyses. The roles of the MAPK–ERK1/2 and PI3K–Akt signaling networks were analyzed using immunoblotting. This is the first report of the effectiveness of ADSC-EVs in the treatment of postoperative adhesions. ADSC-EVs were incorporated in vitro and induced rat peritoneal mesothelial cell proliferation and migration. This was mediated by stimulation of the MAPK–ERK1/2 and PI3K–Akt axes. ADSC-EVs promote the healing of the injured peritoneum, suggesting a promising therapeutic approach for peritoneal adhesions. [ABSTRACT FROM AUTHOR]

Brain ischemia and reperfusion (I/R) is one of the most severe clinical manifestations of ischemic stroke, placing a significant burden on both individuals and society. The only FDA-approved clinical treatment for ischemic stroke is tissue plasminogen activator (t-PA), which rapidly restores cerebral blood flow but can have severe side effects. The complex pathological process of brain I/R has been well-established in the past few years, including energy metabolism disorders, cellular acidosis, doubling of the synthesis or release of excitotoxic amino acids, intracellular calcium homeostasis, free radical production, and activation of apoptotic genes. Recently, accumulating evidence has shown that NO may be strongly related to brain I/R and involved in complex pathological processes. This review focuses on the role of endogenous NO in pathological processes in brain I/R, including neuronal cell death and blood brain barrier disruption, to explore how NO impacts specific signaling cascades and contributes to brain I/R injury. Moreover, NO can rapidly react with superoxide to produce peroxynitrite, which may also mediate brain I/R injury, which is discussed here. Finally, we reveal several therapeutic approaches strongly associated with NO and discuss their potential as a clinical treatment for ischemic stroke. [ABSTRACT FROM AUTHOR]

Wilms tumor (WT) commonly occurs in infants and children. We evaluated clinical factors and the expression of multiple RNAs in WT samples in the TARGET database. Eight long non-coding RNAs (lncRNAs; AC079310.1, MYCNOS, LINC00271, AL445228.3, Z84485.1, AC091180.5, AP002518.2, and AC007879.3), two microRNAs (miRNAs; hsa-mir-152 andhsa-mir-181a), and nine messenger RNAs (mRNAs; TCTEX1D4, RNF133, VRK1, CCNE1, HEY1, C10orf71, SPRY1, SPAG11A, and MAGEB18) were screened from differentially expressed RNAs and used to construct predictive survival models. These models showed good prognostic ability and were highly correlated with tumor stage and histological classification. Additionally, survival-related ceRNA network was constructed using 35 RNAs (15 lncRNAs, eight miRNAs, and 12 mRNAs). KEGG pathway analysis suggested the "Wnt signaling pathway" and "Cellular senescence" as the main pathways. In conclusion, we established a multinomial predictive survival model and a survival-related ceRNA network, which provide new potential biomarkers that may improve the prognosis and treatment of WT patients. [ABSTRACT FROM AUTHOR]

Heterotopic ossification is common in tendon healing after trauma, but the detailed mechanisms remain unknown. Tendon‐derived stem cells (TDSCs) are a type of progenitor cell found in the tendon niche, and their incorrect differentiation after trauma may lead to tendon calcification. The expression of hepatocyte growth factor (HGF) presents drastic fluctuations in serum/tissue after trauma and was found to activate quiescent stellate cells and contribute to wound healing; however, its potential role in TDSCs remains elusive. In this study, TDSCs isolated from rats were cultured in media containing HGF with or without a signaling inhibitor, and the proliferation, migration, and differentiation ability of TDSCs were measured to determine the role and mechanism of HGF in TDSCs. We showed that HGF promotes TDSC proliferation and migration but inhibits TDSC osteogenic differentiation ability. HGF activated‐HGF/c‐Met, mitogen‐activated protein kinase (MAPK)/extracellular signal‐regulated protein kinases 1 and 2 (ERK1/2), and phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT) signaling, which was positively correlated with TDSCs proliferation and migration but negatively related to TDSC osteogenic differentiation ability. The phosphorylation of Smad1/5/8 was also negatively related to HGF/c‐Met, MAPK/ERK1/2, and PI3K/AKT signaling, which demonstrated that the inhibition of osteogenic differentiation was dependent on BMP/Smad1/5/8 signaling. Overall, we showed that HGF could promote TDSCs proliferation and migration and inhibit osteogenic differentiation in vitro, suggesting a potential role for HGF as a cytokine treatment of tendon trauma. [ABSTRACT FROM AUTHOR]

Background These experiments were employed to explore the mechanisms underlying baicalin action on Candida albicans . Methodology and principal findings We detected the baicalin inhibition effects on three isotope-labeled precursors of 3 H-UdR, 3 H-TdR and 3 H-leucine incorporation into C. albicans using the isotope incorporation technology. The activities of Succinate Dehydrogenase (SDH), cytochrome oxidase (CCO) and Ca 2 + –Mg 2+ ATPase, cytosolic Ca 2+ concentration, the cell cycle and apoptosis, as well as the ultrastructure of C. albicans were also tested. We found that baicalin inhibited 3 H-UdR, 3 H-TdR and 3 H-leucine incorporation into C. albicans ( P < 0.005). The activities of the SDH and Ca 2 + –Mg 2+ ATPase of C. albicans in baicalin groups were lower than those in control group ( P < 0.05). Ca 2+ concentrations of C. albicans in baicalin groups were much higher than those in control group ( P < 0.05). The ratio of C. albicans at the G0/G1 stage increased in baicalin groups in dose dependent manner ( P < 0.01). There were a significant differences in the apoptosis rate of C. albicans between baicalin and control groups ( P < 0.01). After 12–48 h incubation with baicalin (1 mg/ml), C. albicans shown to be markedly damaged under transmission electron micrographs. Innovation and significance Baicalin can increase the apoptosis rate of C. albicans . These effects of Baicalin may involved in its inhibiting the activities of the SDH and Ca 2 + –Mg 2+ ATPase, increasing cytosolic Ca 2+ content and damaging the ultrastructure of C. albicans . [ABSTRACT FROM AUTHOR]

Abstract: Background: Extensive experimental and clinical studies have shown that ischemic preconditioning (IP) can produce protective effects during hepatic ischemia reperfusion (I/R) injury. Our recent studies indicate that rat liver I/R injury is related to an abnormal increase in leukotriene (LT) C4 production. However, the mechanisms underlying IP actions on LTC4 generation during hepatic I/R injury remain to be explored. Methods: We randomly divided adult male Sprague-Dawley rats into sham (control), I/R, and IP groups (n = 6). We subjected rat liver to 60 min partial hepatic ischemia followed by 5 h reperfusion with saline administered intravenously. We detected protein expression of LTC4 synthase (LTC4S) with Western blot, and measured LTC4 synthesis enzymes'' activities and content by reverse-phase high-performance liquid chromatography. We assessed tissue injury using serum aspartate aminotransferase and aspartate aminotransferase activities and histologic changes. We examined liver tissue glutathione levels by a biochemical method. Results: Ischemic preconditioning markedly decreased LTC4 content, reduced LTC4S protein expressions, and inhibited LTC4 synthesis enzymes'' activities in rat liver compared with the I/R group (P < 0.05). We also observed a decline in serum alanine aminotransferase and aspartate aminotransferase activities (P < 0.05), together with hepatic tissue glutathione elevation (P < 0.05) in the IP groups. Positive expression of LTC4S on hepatocytes and sinusoidal endothelial cells in the IP group was significantly lower than that in the I/R group. Conclusions: These findings demonstrate that reduced LTC4 production by IP treatment during hepatic I/R injury could partially result from the down-regulation of LTC4S protein expression and the depression of LTC4 synthesis enzyme activity. They suggest that the beneficial effects of IP may be involved in repression of LTC4 generation during hepatic I/R injury. [Copyright &y& Elsevier]

The amyloid hypothesis of Alzheimer's disease has long been the predominant theory, suggesting that Alzheimer's disease is caused by the accumulation of amyloid beta protein (Aβ) in the brain, leading to neuronal toxicity in the central nervous system (CNS). Because of breakthroughs in molecular medicine, the amyloid pathway is thought to be central to the pathophysiology of Alzheimer's disease (AD). Currently, it is believed that altered biochemistry of the Aβ cycle remains a central biological feature of AD and is a promising target for treatment. This review provides an overview of the process of amyloid formation, explaining the transition from amyloid precursor protein to amyloid beta protein. Moreover, we also reveal the relationship between autophagy, cerebral blood flow, ACHE, expression of LRP1, and amyloidosis. In addition, we discuss the detailed pathogenesis of amyloidosis, including oxidative damage, tau protein, NFTs, and neuronal damage. Finally, we list some ways to treat AD in terms of decreasing the accumulation of Aβ in the brain. [ABSTRACT FROM AUTHOR]

Hepatic ischemia-reperfusion injury is a major cause of post-operative hepatic dysfunction and liver failure after transplantation. Mitochondrial pathways can be either beneficial or detrimental to hepatic cell apoptosis during hepatic ischemia/reperfusion injury, depending on multiple factors. Hepatic ischemia/reperfusion injury may be induced by opened mitochondrial permeability transition pore, released apoptosis-related proteins, up-regulated B-cell lymphoma-2 gene family proteins, unbalanced mitochondrial dynamics, and endoplasmic reticulum stress, which are integral parts of mitochondrial pathways. In this review, we discuss the role of mitochondrial pathways in apoptosis that account for the most deleterious effect of hepatic ischemia/reperfusion injury. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO), a free radical, plays a critical role in a wide range of physiological and pathological processes. Due to its pleiotropic function, it has been widely investigated in various types of cancers and is strongly associated with cancer development. Mounting pieces of evidence show that NO regulates various cancer-related events, which mainly depends on phosphorylating the key proteins in several signaling pathways. However, phosphorylation of proteins modulated by NO signaling pathway may lead to different effects in different types of cancer, which is complex and remains unclear. Therefore, in this review, we focus on the effect of protein phosphorylation modulated by NO signaling pathway in different types of cancers including breast cancer, lung cancer, prostate cancer, colon cancer, gastric cancer, pancreatic cancer, ovarian cancer, and neuroblastoma. Phosphorylation of key proteins, including p38 MAPK, ERK, PI3K, STAT3, and p53, modified by NO in various signaling pathways affects different cancer-related processes including cell apoptosis, proliferation, angiogenesis, metastasis, and several cancer therapies. Our review links the NO signaling pathway to protein phosphorylation in cancer development and provides new insight into potential targets and cancer therapy. [ABSTRACT FROM AUTHOR]

Clear cell renal carcinoma (ccRCC) is one of the most common renal carcinomas worldwide, which has worse prognosis compared with other subtypes of tumors. We propose a potential RNA regulatory mechanism associated with ccRCC progression. Accordingly, we screened out clinical factors and the expression of RNAs and miRNAs of ccRCC from the TCGA database. 9 lncRNAs (FGF12-AS2, WT1-AS, TRIM36-IT1, AC009093.1, LINC00443, TCL6, COL18A1-AS1, AC110619.1, HOTTIP), 2 miRNAs (mir-155 and mir-21), and 3 mRNAs (COL4A4, ERMP1, PRELID2) were selected from differential expression RNAs and built predictive survival models. The survival models performed very well in predicting prognosis and were found to be highly correlated with tumor stage. In addition, the survival-related lncRNA-miRNA-mRNA (ceRNA) network was constructed by 18 RNAs including 12 mRNAs, 2 miRNAs, and 4 lncRNAs. It is found that the "ECM-receptor interaction," "Pathways in cancer," and "Chemokine signaling pathway" as the main pathways in KEGG pathway analysis. Overall, we established predictive survival model and ceRNA network based on multivariate Cox regression analysis. It may open a new approach and potential biomarkers for clinical prognosis and treatment of ccRCC patients. [ABSTRACT FROM AUTHOR]

To evaluate the biomechanical stability of stand-alone (SA) oblique lateral interbody fusion (OLIF) under different bone mineral density conditions. The finite element model of L2-L5 was reconstructed and verified via computed tomography scan images (M0). The L4-L5 segment of SA OLIF was created based on the validation model. By changing bone mineral density, SA OLIF was established in the normal bone mineral density group (M1), osteopenia group (M2), and osteoporosis group (M3). A 500 N vertical axial preload was imposed on the superior surface of L2, and a 10 N-m moment was applied on the L2 superior surface along the radial direction to simulate 6 different physiological motions: flexion, extension, left and right lateral bending, left and right rotation. Compared with M0, the range of motion of the fusion segment was significantly reduced, and the maximum stress of the upper and lower end plates was significantly increased in all motion modes. Compared with M1, the maximum relative increases of range of motion, cephalic end-plate stress and tail end-plate stress of M2 in the L4-L5 segment were 39.1%, 9.9%, and 10.7%, and the maximum increases of the above parameters in M3 were 100%, 28.9%, and 31.6%. The maximum stress of the tail end plate of the M3 model during flexion was 54.617 MPa, which was very close to the yield stress of the lamellar bone (60 MPa). With the increase of the degree of osteoporosis, the maximum stress on the upper and lower end plates of the fusion segment increased significantly, thus increasing the potential risk of implant subsidence. SA OLIF could not provide sufficient stability for patients with osteoporosis. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Thromboangiitis obliterans (TAO) or Buerger''s disease is a non atherosclerotic, segmentar inflammatory vasculitis that is incurable at present. Shenfu injection (SFI), a traditional Chinese formulation, have been confirmed to produce protective influences on several organs and limb during ischemia and reperfusion (IR) injury in rats. However, the effects of SFI on TAO remain unclear. Materials and Methods: Adult male Sprague Dawley rats were randomly divided into sham operated group, TAO model group, SFI 2.5mg/kg (low dose), 5mg/kg (medium dose) and 10mg/kg (high dose) groups (n =8). Rats were intravenously administered SFI 2.5, 5 and 10mg/kg or saline once per day for 15 days. TAO model was prepared by injecting sodium laurate into the femoral artery of rats. Then we examined the changes of pathological signs, pathologic grading of thrombus, the indexes of hematology, the contents of thromboxane B2 (TXB2), 6-keto-prostaglandin F lα (6-K-PGF 1α ) in plasma following SFI or saline treatment. Results: More pathological signs of lesions, higher grades of pathological thrombosis, increased blood platelet counts, the increase in the TXB2 and TXB2/6-K-PGF1α ratio, as well as the decrease of 6-K-PGF1α in TAO model group were shown in present experiments; SFI treatment significantly improved the pathological signs of lesions induced by sodium laurate injection, reduced the numbers of thrombus formation, blood platelet counts, the TXB2 and TXB2/6-K-PGF1α ratio but increased the 6-K-PGF1α compared with TAO model group. However, there were no significant alterations in the counts of red blood cell, leucocyte and neutrophil among these groups. Conclusions: Our preliminary findings first indicated that SFI can produce significant therapeutic effects on experimental Buerger''s disease model rats in a dose independent manner. The underlying mechanisms may be due to its modifying hematology, inhibiting platelet aggregation and enhancing anti-thrombotic function of vessel endothelia. [Copyright &y& Elsevier]

Background: Fibrosis and inflammation due to ureteropelvic junction obstruction substantially contributes to poor renal function. Urine-derived stem-cell-derived exosomes (USC-Exos) have therapeutic effects through paracrine. Methods: In vitro, the effects of USC-Exos on the biological functions of HK-2 and human umbilical vein endothelial cells were tested. Cell inflammation and fibrosis were induced by transforming growth factor-β1 and interleukin-1β, and their anti-inflammatory and antifibrotic effects were observed after exogenous addition of USC-Exos. Through high-throughput sequencing of microRNA in USC-Exos, the pathways and key microRNAs were selected. Then, the antifibrotic and anti-inflammatory effects of exosomal miR-122-5p and target genes were verified. The role of the miR-122-5p/SOX2 axis in anti-inflammatory and antifibrotic effects was verified. In vivo, a rabbit model of partial unilateral ureteral obstruction (PUUO) was established. Magnetic resonance imaging recorded the volume of the renal pelvis after modeling, and renal tissue was pathologically analyzed. Results: We examined the role of USC-Exos and their miR-122-5p content in obstructive kidney injury. These Exos exhibit antifibrotic and anti-inflammatory activities. SOX2 is the hub gene in PUUO and negatively related to renal function. We confirmed the binding relationship between miR-122-5p and SOX2. The anti-inflammatory and antifibrotic effects of miR-122-5p were inhibited, indicating that miR-122-5p has anti-inflammatory and antifibrotic effects by inhibiting SOX2 expression. In vivo, the PUUO group showed typical obstructive kidney injury after modeling. After USC-Exo treatment, the shape of the renal pelvis shown a remarkable improvement, and inflammation and fibrosis decreased. Conclusions: We confirmed that miR-122-5p from USC-Exos targeting SOX2 is a new molecular target for postoperative recovery treatment of obstructive kidney injury., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Wenjun Lu et al.)

Background: The posterior cruciate ligament avulsion fracture (PCLAF) is a special type of PCL rupture, and arthroscopic fixation for PCLAF has been recommended currently. The bio-absorbable suture anchor is a novel internal fixation for PCLAF. This study aims to estimate and compare the safety, efficacy, and functional outcomes between the bio-absorbable anchor and the traditional suture pull-out technique for arthroscopic fixation of PCLAF. Methods: This was a prospective cohort study. PCLAF patients were included from 1 January 2020, to 31 August 2021, in our department, and randomly divided into the absorbable anchor group and control group (pull-out suture fixation). Clinical assessments included: post drawer test, gravity test, anterior-posterior laxity (KT-2000), range of motion, Lysholm and International Knee Documentation Committee (IKDC) scores, total failure rate, and returning to sports rate. The minimum follow-up was 1 year (y). Results: 31 patients had accomplished the 1 year follow-up (missing rate: 13.9%). We did not face any complications such as neurovascular injury, fever, infection, un-union, or re-rupture during the follow-up. CT scan showed that all of the patients in the two groups had a well bone union at 3 months in post-operation. At 1 year follow-up, the total failure rate of the bio-absorbable anchor group (1/17, p = 0.036) was lower than the control group (5/14), and the IKDC (86.24 ± 4.35, p = 0.008) and return to sports rate (11/17, p = 0.045) of the bio-absorbable anchor group were higher than that of the control group (81.43 ± 5.06) (4/14). Conclusion: Both the bio-absorbable anchor and suture pull-out technique for arthroscopic fixation of PCLAF have acquired a well bone union and superior safety, but the bio-absorbable anchor group had better efficacy and functional outcomes than the traditional pull-out technique., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ren, Wang, Yang, Liu, Wang, Zhang, Li and Zhang.)

Coxsackievirus B (CVB), a member of Enterovirus genus of Picornaviridae , is the leading pathogen of viral myocarditis and dilated cardiomyopathy. The pathogenesis of CVB-induced myocarditis has not been completely elucidated, and no specific antiviral measurement is available presently. Circular RNAs (circRNAs) have been reported to be able to modulate viral replication and infection through bridging over non-coding RNAs (ncRNAs) and coding messenger RNAs (mRNAs). To date, the role of circRNAs in CVB infection is largely unknown. In this study, we found that hsa&#95;circ&#95;0076631 (circ&#95;0076631) significantly promoted CVB type 3 (CVB3) replication. Further study showed that the underneath mechanism was circ&#95;0076631 indirectly interacting with CVB3 through sponging miR-214-3p, which targeted the 3D-coding region of CVB3 genome to suppress viral translation. Knocking down circ-0076631 caused a suppression of CVB3 infection; thus, circ-0076631 may be a potential target for anti-CVB therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qin, Lin, Yang, Dai, Zhang, Huang, Deng, Yue, Ren, Fei, Zhao, Wang and Zhong.)

Lipid metabolism disorder plays a fundamental role in the pathogenesis of atherosclerosis. As the largest metabolic organ of the human body, the liver has a key role in lipid metabolism by influencing fat production, fat decomposition, and the intake and secretion of serum lipoproteins. Numerous clinical and experimental studies have indicated that the dysfunction of hepatic lipid metabolism is closely related to the onset of atherosclerosis. However, the identity and functional role of hepatic lipid metabolism responsible for these associations remain unknown. This review presented that cholesterol synthesis, cholesterol transport, and the metabolism of triglycerides, lipoproteins, and fatty acids are all associated with hepatic lipid metabolism and atherosclerosis. Moreover, the roles of gut microbiota, inflammatory response, and oxidative stress in the pathological association between hepatic lipid metabolism and atherosclerosis are also discussed. This significant evidence strongly supports that hepatic lipid metabolism disorders may increase the risk of atherosclerosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Wilms tumor (WT) is a widespread urologic tumor in children. Ferroptosis, on the other hand, is a novel form of cell death associated with tumor development. In this study, we aim to explore the predictability of ferroptosis-related biomarkers in estimating prognosis in WT patients., Methods: To determine a link between ferroptosis-related gene expression and WT prognosis, we first collected RNA sequencing data and clinical information, involving 124 WT and 6 healthy tissue samples, from the TARGET database. Next, we screened the collected information for ferroptosis-related long non-coding RNA using Cox regression analysis, and constructed a signature model, as well as a nomogram, related to prognosis. Finally, we explored a potential link between ferroptosis-related lncRNA and tumor immunity and screened for possible immune checkpoints., Results: We constructed a WT prognosis prediction signature containing 12 ferroptosis-related lncRNAs. The area under the curves values, from the ROC curves, predicting overall survival rates at the 1, 3-, and 5-year timepoints were 0.775, 0.867, and 0.891 respectively. Moreover, we generated a nomogram, using clinical features and risk scores, carrying a C-index value of 0.836, which suggested a high predictive value. We also demonstrated significant differences in tumor immunity between low- and high-risk WT patients, particularly in the presence of B cells, NK cells, Th1 cells, Treg cells, inflammation promoting, and type I and II IFN responses. In addition, we showed that immune checkpoints like SIRPA , ICOSLG , LAG3 , PVRIG , NECTIN1 , and SIRPB2 can serve as potential therapeutic targets for WT., Conclusions: Based on our analyses, we generated a ferroptosis-related lncRNA signature that can both estimate prognosis of WT patients and may provide basis for future WT therapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tp-21-211). ZL reports that the manuscript was supported by the National Natural Science Foundation of China (81871837 and 81572117) and the Specialized Research Fund for Doctoral Programs in Colleges and Universities of China (20132307110007). The other authors have no conflicts of interest to declare., (2021 Translational Pediatrics. All rights reserved.)

The therapeutic impact of stem cells is potentially largely attributable to secretion of exosomes and soluble factors. The present study evaluates the impact of hepatocyte growth factor (HGF)-expressing tendon stem cells (TSCs) on tendon healing in a rat model. Patellar tendon TSCs were isolated and underwent transfection with lentiviral vectors containing HGF or green fluorescent protein (GFP) genes. In vivo , immunohistochemistry of tendons sampled 1 week postsurgery demonstrated that all stem cell-treated groups exhibited higher numbers of CD163 + M2 monocytes and IL-10 + cells (anti-inflammatory), and lower numbers of CCR7 + M1 monocytes and IL-6 + as well as COX-2 + cells (pro-inflammatory). Effects were most pronounced in the HGF-expressing TSCs (TSCs + HGF) treated group. Histology ± immunohistochemistry of tendons sampled 4 and 8 weeks postsurgery demonstrated that all stem cell-treated groups exhibited more ordered collagen fiber arrangement and lower levels of COLIII, α-SMA, TGF-β1, and fibronectin (proteins relevant to fibroscarring). Effects were most pronounced in the TSCs + HGF-treated group. For the in vitro study, isolated tendon fibroblasts pretreated with TGF-β1 to mimic the in vivo microenvironment of tendon injury were indirectly cocultured with TSCs, TSCs + GFP, or TSCs + HGF using a transwell system. Western blotting demonstrated that all stem cell types decreased TGF-β1-induced increases in fibroblast levels of COX-2, COLIII, and α-SMA, concomitant with decreased activation of major TGF-β1 signaling pathways (p38 MAPK, ERK1/2, but not Smad2/3). This effect was most pronounced for TSCs + HGF, which also decreased the TGF-β1-induced increase in activation of the Smad2/3 signaling pathway. The presence of specific inhibitors of these pathways during fibroblast TGF-β1 stimulation also attenuated increases in levels of COX-2, COLIII, and α-SMA. In conclusion, TSCs + HGF, which exhibit HGF overexpression, may promoting tendon healing via decreasing inflammation and fibrosis, perhaps partly via inhibiting TGF-β1-induced signaling. These findings identify a novel potential therapeutic strategy for tendon injuries, warranting additional research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Liu, Shi, Zhang, Lu, Yang, Cui and Li.)

Tendon repair is a medical challenge. Our present study investigated the effectiveness of acellular therapy consisting of conditioned medium (CM) of tendon stem cells (TSCs) induced with hepatocyte growth factor (HGF) in promoting the healing of injured Achilles tendon in a rat model. Proteomic analysis of soluble substances in the CM was performed using an array chip, and bioinformatic analysis was carried out to evaluate interactions among the factors. The effects of CM on viability and migratory capacity of tendon fibroblasts derived from rats with ruptured Achilles tendon were evaluated with the Cell Counting Kit 8 and wound healing assay, respectively. The expression of extracellular matrix (ECM)-related protein was assessed by western blotting. Rats with Achilles tendon injury were treated with CM by local injection for 2 weeks, and the organization of tendon fibers at the lesion site was evaluated by hematoxylin and eosin and Masson's trichrome staining of tissue samples. The deposition and degradation of ECM proteins and the expression of inflammatory factors at the lesion site were evaluated by immunohistochemistry and immunofluorescence. Biomechanical testing was carried out on the injured tendons to assess functional recovery. There were 12 bioactive molecules in the CM, with HGF as the hub of the protein-protein interaction network. CM treatment enhanced the viability and migration of tendon fibroblasts, altered the expression of ECM proteins, promoted the organization of tendon fibers, suppressed inflammation and improved the biomechanics of the injured Achilles tendon. These results suggest that HGF stimulates the secretion of soluble secretory products by TSCs and CM promotes the repair and functional recovery of ruptured Achilles tendon. Thus, HGF-induced TSC CM has therapeutic potential for the treatment of tendinopathy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Li, Zhang, Shi, Song, Yang, Liu, Zhang, Cui and Li.)

Adult rats were implanted with sleep-wake recording electrodes in our experiments. Polygraphic signs of undisturbed sleep-wake activities were recorded for 24 h before cocaine administration, cocaine withdrawal day 1 (acute), day 8 (subacute), and day 14 (subchronic). Western blot method was performed to examine the expression levels of adenosine receptor subtypes in hypothalamus and cerebellum. Non rapid eye movement (NREM) sleep was significantly increased during nighttime (P < 0.01) and daytime (P < 0.05) on withdrawal day 8. The increase of NREM sleep was significant during nighttime (P < 0.01) and slight during daytime on withdrawal day 14, whereas both daytime and nighttime rapid eye movement (REM) sleeps were reduced markedly (P < 0.01) on withdrawal day 8 and 14. In addition, A2A receptor level was significantly enhanced on cocaine withdrawal day 8 and day 14 (P < 0.05), whereas A1 receptor level reduced markedly on withdrawal day 14 (P < 0.05). However, compared with that in the control group, no significant changes existed among adenosine A1, A2A and A2B receptors in rat cerebellum on cocaine withdrawal day 1, day 8 and day 14. Our findings suggest that sleep disorder caused by subacute and subchronic cocaine abstinence may be associated with over-expression of adenosine A2A receptor in rat hypothalamus to some extent.