Serum prealbumin level as a biomarker of survival outcomes in patients with gastric cancer: a meta-analysis.

BACKGROUND: Previous studies have reported inconsistent results on the association between serum prealbumin level and survival outcomes in patients with gastric cancer. This meta-analysis aimed to determine the serum prealbumin level as a biomarker of survival outcomes in gastric cancer patients. METHODS: Two independent reviewers conducted a thorough search of PubMed, Embase, and Web of Science databases until April 17, 2024. Studies reporting the association between serum prealbumin level and survival outcomes and presented the multivariable-adjusted relative risks for gastric cancer patients were included. The pooled HR and 95% CI were used to assess the strength of the association. RESULTS: Twelve studies, with a total of 9,351 patients were included in the meta-analysis. The combined data showed that low serum prealbumin level was associated with shorter overall survival (HR 1.65; 95% CI 1.42-1.91) and disease-free survival (HR 1.39; 95% CI 1.14-1.70). Subgroup analysis showed that low serum prealbumin level significantly predicted poorer overall survival, regardless of patients' age, sample sizes, cutoff value for prealbumin level, and follow-up time. CONCLUSIONS: Low serum prealbumin level is an independent prognostic biomarker for shorter survival outcomes in patients with gastric cancer. Assessing serum prealbumin levels could potentially improve risk stratification for this disease.

Behavior, attitude, perception, and knowledge regarding fertility preservation among Chinese pediatric oncologists: a survey in China.

PURPOSE: Clinical specialists are supposed to inform childhood cancer patients of infertility risk and conduct fertility preservation (FP). However, little is known about whether doctors in China are fully prepared. This study aimed to investigate behavior, attitude, perception, and knowledge regarding FP among pediatric oncological specialists in a nation wide survey, to set the stage for improvements in current clinical practice patterns. METHODS: This study was conducted on physicians and surgeons specialized in pediatric oncology using a questionnaire through the WeChat platform. The behavior, attitude, perception, and knowledge were assessed by Likert questions and results were quantified to obtain scores. Data were then described and analyzed using R and GraphPad. RESULTS: Totally 373 specialists in pediatric tumors were included in the analysis. Hematologists, oncological surgeons, and reproductive medicine specialists won most trusts to be responsible for FP job. Most respondents did not have habits of delivering FP information or cooperating with FP specialists during treatment though they were well equipped with FP knowledge and desired for uniform national guideline for FP procedures. The severity of illness was regarded as the primary barrier of FP delivery. When a doctor was more educated and experienced, he was more likely to have better performance in FP. The total score, the knowledge score, and the single score concerning frequency of patients' inquiry showed aggregational trend on geographic distribution. CONCLUSION: Chinese pediatric oncologists demonstrated unsatisfactory practice behaviors based upon this self-reporting survey, although their attitude towards FP was generally positive.

Cachexia Index as a Predictor of Reduced Survival in Patients with Gastrointestinal Cancer: A Systematic Review and Meta-Analysis.

The cachexia index is a novel indicator of cachexia, but its prognostic implications for survival outcomes have not been systematically assessed in patients with gastrointestinal cancer. This systematic review and meta-analysis aimed to examine the association between the cachexia index and survival outcomes in gastrointestinal cancer patients. Two independent reviewers searched PubMed, Embase, and Web of Science to identify studies that evaluated the prognostic significance of the cachexia index in patients with gastrointestinal cancer. The prognostic value of the cachexia index was determined by combining the adjusted hazard ratios (HR) and 95% confidence intervals (CI). Thirteen studies were identified, including a total of 4207 patients. Meta-analysis indicated that a lower cachexia index was associated with shorter overall survival (HR 2.18; 95% CI 1.78-2.66) and disease-free survival (HR 1.72; 95% CI 1.50-1.97) in gastrointestinal cancer patients. Further stratified analysis confirmed the significant association between a lower cachexia index and shorter overall survival in different study designs, regions, patients' age, sample sizes, gastrointestinal cancer subtypes, tumor stages, and follow-up duration subgroups. The cachexia index could be utilized as a predictor of overall survival and disease-free survival in patients with gastrointestinal cancer. However, future prospective studies are required to confirm these findings.

An International Consensus Survey among Pediatric Surgeons on the Role of Appendectomy in Malrotation.

Introduction: Ladd's procedure, originally described in 1936 for the treatment of malrotation, does not traditionally include appendectomy as a standard step. We conducted a multinational survey to investigate the current consensus on the role of appendectomy in Ladd's procedure. Methodology: An anonymous online survey was distributed to pediatric surgeons worldwide. The survey collected demographic data and explored surgical preferences related to the management of malrotation. Open-ended questions were used to assess the opinions regarding the necessity of appendectomy, decision-making factors, and complications associated with appendectomy during Ladd's procedure. Results: A total of 343 responses were received from 46 countries. Of the respondents, 319 (93%) were consultants and 24 (7%) were residents/trainees. When asked about the choice between open and laparoscopic Ladd's procedure, 292 (85%) preferred open surgery. Overall, 184 (53%) respondents favored appendectomy in both open and laparoscopic Ladd's procedure. Furthermore, 172 (50%) surgeons advocated for appendectomy in all malrotation cases, citing concerns about potential future appendicitis. While differences existed between all comparisons, none of them reached statistical significance. The factors influencing the decision to preserve the appendix included the risk of postoperative complications and the potential future use of the appendix as a surgical conduit. The surgical complications following appendectomy included surgical site infections in 14 (33%) patients, adhesive obstruction in 13 (31%) patients, intrabdominal abscesses in 10 (24%) patients, and fecal fistulas in 5 (12%) patients. Conclusion: The majority of surgeons aim to perform appendectomy in all malrotation cases, considering the potential risks and benefits of this approach. These findings offer valuable insights for clinical practice and may inform future guidelines and decision-making algorithms.

Enzyme-Mediated Bioorthogonal Cascade Catalytic Reaction for Metabolism Intervention and Enhanced Ferroptosis on Neuroblastoma.

It remains a tremendous challenge to explore effective therapeutic modalities against neuroblastoma, a lethal cancer of the sympathetic nervous system with poor prognosis and disappointing treatment outcomes. Considering the limitations of conventional treatment modalities and the intrinsic vulnerability of neuroblastoma, we herein develop a pioneering sequential catalytic therapeutic system that utilizes lactate oxidase (LOx)/horseradish peroxidase (HRP)-loaded amorphous zinc metal-organic framework, named LOx/HRP-aZIF, in combination with a 3-indole-acetic acid (IAA) prodrug. On the basis of abnormal lactate accumulation that occurs in the tumor microenvironment, the cascade reaction of LOx and HRP consumes endogenous glutathione and a reduced form of nicotinamide adenine dinucleotide to achieve the first stage of killing cancer cells via antioxidative incapacitation and electron transport chain interference. Furthermore, the generation of reactive oxygen species induced by HRP and IAA through bioorthogonal catalysis promotes ferritin degradation and lipid peroxidation, ultimately provoking self-enhanced ferroptosis with positive feedback by initiating an endogenous Fenton reaction. This work highlights the superiority of the natural enzyme-dependent cascade and bioorthogonal catalytic reaction, offering a paradigm for synergistically enzyme-based metabolism-ferroptosis anticancer therapy.

Cells in the liver microenvironment regulate the process of liver metastasis.

The research of liver metastasis is a developing field. The ability of tumor cells to invade the liver depends on the complicated interactions between metastatic cells and local subpopulations in the liver (including Kupffer cells, hepatic stellate cells, liver sinusoidal endothelial cells, and immune-related cells). These interactions are mainly mediated by intercellular adhesion and the release of cytokines. Cell populations in the liver microenvironment can play a dual role in the progression of liver metastasis through different mechanisms. At the same time, we can see the participation of liver parenchymal cells and nonparenchymal cells in the process of liver metastasis of different tumors. Therefore, the purpose of this article is to summarize the relationship between cellular components of liver microenvironment and metastasis and emphasize the importance of different cells in the occurrence or potential regression of liver metastasis.

Suppression of viral RNA polymerase activity is necessary for persistent infection during the transformation of measles virus into SSPE virus.

Subacute sclerosing panencephalitis (SSPE) is a fatal neurodegenerative disease caused by measles virus (MV), which typically develops 7 to 10 years after acute measles. During the incubation period, MV establishes a persistent infection in the brain and accumulates mutations that generate neuropathogenic SSPE virus. The neuropathogenicity is closely associated with enhanced propagation mediated by cell-to-cell fusion in the brain, which is principally regulated by hyperfusogenic mutations of the viral F protein. The molecular mechanisms underlying establishment and maintenance of persistent infection are unclear because it is impractical to isolate viruses before the appearance of clinical signs. In this study, we found that the L and P proteins, components of viral RNA-dependent RNA polymerase (RdRp), of an SSPE virus Kobe-1 strain did not promote but rather attenuated viral neuropathogenicity. Viral RdRp activity corresponded to F protein expression; the suppression of RdRp activity in the Kobe-1 strain because of mutations in the L and P proteins led to restriction of the F protein level, thereby reducing cell-to-cell fusion mediated propagation in neuronal cells and decreasing neuropathogenicity. Therefore, the L and P proteins of Kobe-1 did not contribute to progression of SSPE. Three mutations in the L protein strongly suppressed RdRp activity. Recombinant MV harboring the three mutations limited viral spread in neuronal cells while preventing the release of infectious progeny particles; these changes could support persistent infection by enabling host immune escape and preventing host cell lysis. Therefore, the suppression of RdRp activity is necessary for the persistent infection of the parental MV on the way to transform into Kobe-1 SSPE virus. Because mutations in the genome of an SSPE virus reflect the process of SSPE development, mutation analysis will provide insight into the mechanisms underlying persistent infection.

Ferroptosis Inducers Kill Mesenchymal Stem Cells Affected by Neuroblastoma.

Bone marrow (BM) is the most common site of neuroblastoma (NB) metastasis, and its involvement represents poor patient prognosis. In accordance with the "seed and soil" theory of tumor metastasis, BM provides a favorable environment for NB metastasis while bone marrow mesenchymal stem cells (BMSCs) have been recognized as a central part of tumor stroma formation. Yet, there is currently no effective method for intervening these BMSCs. We found that BMSCs affected by NB (NB-BMSCs) could significantly promote NB growth and migration. Additionally, tumor cell-endowed BMSCs showed stronger resistance to several chemotherapeutic agents. Surprisingly, NB-BMSCs were more sensitive to ferroptosis than normal BMSCs. NB-BMSCs had lower levels of intracellular free iron while synthesizing more iron-sulfur clusters and heme. Moreover, the Xc-/glutathione/glutathione peroxidase 4 (Xc-/GSH/GPX4) pathway of the anti-ferroptosis system was significantly downregulated. Accordingly, ferroptosis inducers erastin and RAS-selective lethal 3 (RSL3) could significantly kill NB-BMSCs with limited effects on normal BMSCs. BMSCs from NB patients with BM metastasis also showed poor anti-ferroptosis ability compared with those from NB patients without BM metastasis. In vivo studies suggested that co-injection of mice with BMSCs and NB cells could significantly promote the growth of tumor tissues compared with injecting NB cells alone. However, treatment with erastin or RSL3 resulted in the opposite effect to some extent. Our results revealed that NB-BMSCs were vulnerable to ferroptosis from downregulation of the Xc-/GSH/GPX4 pathway. Ferroptosis inducers could effectively kill NB-BMSCs, but not normal BMSCs. This study provides possible new ideas for the treatment of tumor-associated BMSCs in NB patients.

Quercetin inhibits the amphiregulin/EGFR signaling-mediated renal tubular epithelial-mesenchymal transition and renal fibrosis in obstructive nephropathy.

Quercetin is a widely distributed, bioactive flavonoid compound, which displays potential to inhibit fibrosis in several diseases. The purpose of our study was to determine the effect of quercetin treatment on renal fibrosis and investigate the mechanism. Human proximal tubular epithelial cells (HK-2) stimulated by transforming growth factor-ß1 (TGF-ß1) and a rat model of unilateral ureter obstruction (UUO) that contributes to fibrosis were used to investigate the role and molecular mechanism of quercetin. PD153035 (N-[3-Bromophenyl]-6,7-dimethoxyquinazolin-4-amine) was used to inactivate EGFR (epidermal growth factor receptor). The level of fibrosis, proliferation, apoptosis, and oxidative stress in HK-2 were measured. All data are presented as means ± standard deviation (SD). p-value < .05 was considered statistically significant. In UUO rats, quercetin reduced the area of fibrosis as well as inflammation, oxidative stress, and cell apoptosis. In cultured HK-2 cells, quercetin significantly ameliorated the EMT induced by TGF-ß1, which was accompanied by increased amphiregulin (AREG) expression. Moreover, quercetin inhibited AREG binding to the EGFR receptor, thereby further affecting other downstream pathways. Quercetin may alleviate fibrosis in vitro and in vivo by inhibiting the activation of AREG/EGFR signaling indicating a potential therapeutic effect of quercetin in renal fibrosis.

Optimizing bowel preparation for colonoscopy: A cross-sectional study of the Chinese population.

Background: The quality of bowel preparation is an important factor in the success of colonoscopy. However, the quality of bowel preparation is often affected by multiple factors. The main objective of this study was to explore the specific factors that affect the quality of bowel preparation. Methods: Patients were consecutively recruited from the gastroenterology department in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan from May 2018 to December 2018. All patients were undergoing colonoscopy. Bowel preparation was evaluated by the Ottawa Bowel preparation Scale (OBPS) and all patients were categorized into 2 groups according to the OBPS. Multivariate analysis was conducted to identify the factors associated with bowel preparation quality. Results: A total of 910 patients were included in the analysis with an average age of 48.62 ± 13.57 years. Patient source (P < 0.001) and the preparation method (P = 0.029) were correlated with OBPS adequacy. In addition, after stratified by age, preparation method (P = 0.022) was a significant factor among patients under 50 years old; whereas waiting time (P = 0.005) was a significant factor among patients over 50 years old. Conclusion: Bowel preparation should be tailored based on the age of the patients to determine the most appropriate plan, including the most appropriate waiting time and the most appropriate purgative combination. Doctors should also focus more on the quality of bowel preparation in inpatients, who are more likely than outpatients to have an inadequate bowel preparation.

Eugenol-Preconditioned Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Antioxidant Capacity of Tendon Stem Cells In Vitro and In Vivo.

Tendon stem cells (TSCs) are often exposed to oxidative stress at tendon injury sites, which impairs their physiological effect as well as therapeutic application. Recently, extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (BMSCs) were shown to mediate cell protection and survival under stress conditions. The function of BMSC-EVs may be affected by pretreatment with various factors such as eugenol (EUG)-a powerful antioxidant. In our previous study, we found that H2O2 significantly impaired TSC proliferation and tenogenic differentiation capabilities. Apoptosis and intracellular ROS accumulation in TSCs were induced by H2O2. However, such H2O2-induced damage was prevented by treatment with EUG-BMSC-EVs. Furthermore, EUG-BMSC-EVs activated the Nrf2/HO-1 pathway to counteract H2O2-induced damage in TSCs. In a rat patellar tendon injury model, the ROS level was significantly higher than that in the normal tendon and TSCs not pretreated showed a poor therapeutic effect. However, EUG-BMSC-EV-pretreated TSCs significantly improved tenogenesis and matrix regeneration during tendon healing. Additionally, the EUG-BMSC-EV group had a significantly improved fiber arrangement. Overall, EUG-BMSC-EVs protected TSCs against oxidative stress and enhanced their functions in tendon injury. These findings provide a basis for potential clinical use of EUG-BMSC-EVs as a new therapeutic vehicle to facilitate TSC therapies for tendon regeneration.

M protein of subacute sclerosing panencephalitis virus, synergistically with the F protein, plays a crucial role in viral neuropathogenicity.

Subacute sclerosing panencephalitis (SSPE) is a rare fatal neurodegenerative disease caused by a measles virus (MV) variant, SSPE virus, that accumulates mutations during long-term persistent infection of the central nervous system (CNS). Clusters of mutations identified around the matrix (M) protein in many SSPE viruses suppress productive infectious particle release and accelerate cell-cell fusion, which are features of SSPE viruses. It was reported, however, that these defects of M protein function might not be correlated directly with promotion of neurovirulence, although they might enable establishment of persistent infection. Neuropathogenicity is closely related to the character of the viral fusion (F) protein, and amino acid substitution(s) in the F protein of some SSPE viruses confers F protein hyperfusogenicity, facilitating viral propagation in the CNS through cell-cell fusion and leading to neurovirulence. The F protein of an SSPE virus Kobe-1 strain, however, displayed only moderately enhanced fusion activity and required additional mutations in the M protein for neuropathogenicity in mice. We demonstrated here the mechanism for the M protein of the Kobe-1 strain supporting the fusion activity of the F protein and cooperatively inducing neurovirulence, even though each protein, independently, has no effect on virulence. The occurrence of SSPE has been estimated recently as one in several thousand in children who acquired measles under the age of 5 years, markedly higher than reported previously. The probability of a specific mutation (or mutations) occurring in the F protein conferring hyperfusogenicity and neuropathogenicity might not be sufficient to explain the high frequency of SSPE. The induction of neurovirulence by M protein synergistically with moderately fusogenic F protein could account for the high frequency of SSPE.

Ascorbic acid mitigates the deleterious effects of nicotine on tendon stem cells.

Purpose: Nicotine causes tendon degeneration, whereas ascorbic acid imparts beneficial effects on tendon cells. Tendon stem cells (TSCs) play a vital role in maintaining tissue integrity and promoting restoration of structure and function after tendon injury. In the present study, cell culture experiments were performed to determine the effects of nicotine on TSCs and whether ascorbic acid supplementation could antagonize the action of high concentration nicotine. Methods: After treatment with nicotine and ascorbic acid, TSC proliferation, migration, stemness, apoptosis, and differentiation were analyzed. Results: TSC proliferation and expression of stem cell markers were significantly impaired by a high concentration of nicotine (1000 ng/mL), but a lower concentration (100 ng/mL) induced proliferative effects in TSCs. Moreover, the highest concentration of nicotine tested (1000 ng/mL) significantly inhibited the migratory ability of TSCs, while relatively high concentrations (100 and 1000 ng/mL) significantly (p < 0.05) up-regulated non-tenocyte genes. When ascorbic acid was added, the inhibitory effects of nicotine on the proliferation, migration, and stemness of TSCs were reversed. In addition, flow cytometry analysis showed that these nicotine concentrations could induce cell apoptosis, while the addition of ascorbic acid inhibited apoptosis. Conclusion: Addition of ascorbic acid partially reversed the inhibitory effect of a high concentration of nicotine. These findings indicate that while nicotine impairs the biological characteristics of TSCs, ascorbic acid can mitigate these deleterious effects and, therefore, may be useful for decreasing nicotine-induced tendon degeneration.

The preventative effect of bone marrow-derived mesenchymal stem cell exosomes on urethral stricture in rats.

BACKGROUND: Urethral stricture (US) is a major challenge in urology and there is an urgent need for effective therapies for its treatment. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exos) have been shown to be effective in preventing scar and fibrosis formation after tissue injury. However, the potential utility of BMSCs-Exos in the prevention of US remains unknown. We hypothesized that local administration of BMSCs-Exos may influence urethral healing and scar formation in a rat model of US. METHODS: A previously established model of rat US was used in this study. Sprague Dawley rats were randomly assigned into sham, US, and US + BMSCs-Exos groups. Micro-ultrasound assessment, histopathology, immunohistochemistry, and gene expression analysis were performed at four weeks post-surgery. RESULTS: US rats exhibited thick urethral walls with a narrowed lumen, when compared with sham rats. However, these changes were suppressed in the US + BMSCs-Exos group. The preventative effects of BMSCs-Exos on US formation were also apparent histologically. US + BMSCs-Exos rats demonstrated decreased expression of several fibrosis-related genes in urethral tissues, including Col I, fibronectin, and elastin, when compared with US rats. BMSCs-Exos treatment also led to an increase in the expression of angiogenesis-related genes in these tissues, including VEGF, eNOS, and bFGF. CONCLUSIONS: Our findings therefore demonstrate that the local administration of BMSCs-Exos prevents urethral stricture formation by regulating fibrosis and angiogenesis. These findings provide a basis for an innovative strategy involving the clinical application of exosomes to counteract US formation.

"Watch and Wait" Strategy for Multicystic Dysplastic Kidney (MCDK): Status Survey of Perceptions, Attitudes, and Treatment Selection in Chinese Pediatric Urologists and Pediatric Surgeons.

To investigate the perceptions, attitudes, and treatment selection of Chinese pediatric urologists and pediatric surgeons regarding a "watch and wait" strategy for multicystic dysplastic kidney (MCDK). We used a cross-sectional survey in this study. We sent the questionnaire to pediatric urologists and pediatric surgeons to capture their views via the "Questionnaire Star" online survey platform between November and December 2019. The questionnaire contained the basic information and surgical experiences of the respondent, respondents' awareness regarding the counseling of prenatally-diagnosed MCDK and the treatment of MCDK, and respondents' knowledge regarding the imaging modalities, frequency, and duration of follow-up. Of the 200 questionnaires we sent, we received 151 responses. Of those 151 complete responses, most respondents were women (n = 104, 68.9%), pediatric urologists (n = 78, 51.6%), and practicing with at least 5 years of surgical experience (n = 112, 74.2%); 11.9% reported >20 years' experience. Eighty-two surgeons (54.3%) provided positive counseling for prenatally-diagnosed MCDK. Ninety-nine surgeons (65.6%) advocated conservative management for MCDK, and only 14.8% of respondents suggested limiting the use of radiographic evaluation for MCDK. Surgeons working in academic teaching facilities and those from East China were more likely to select a "watch and wait" strategy. Chinese pediatric urologists and pediatric surgeons have inadequate knowledge of the "watch and wait" strategy for MCDK. An expert consensus on the strategy of "watch and wait" for MCDK in China is urgently needed to promote the application of this non-surgical treatment mode in clinical practice. A larger sample size is required to fully identify the current opinion of Chinese pediatric urologists and pediatric surgeons regarding the management of MCDK.

Extracellular vesicles produced by bone marrow mesenchymal stem cells attenuate renal fibrosis, in part by inhibiting the RhoA/ROCK pathway, in a UUO rat model.

BACKGROUND: Extracellular vesicles produced by bone marrow mesenchymal stem cells (BMSC-EVs) can play important roles in the repair of injured tissues. Though numerous studies have reported the effect of EVs on renal fibrosis, the underlying mechanisms remain unclear. We hypothesized that BMSC-EVs containing milk fat globule-epidermal growth factor-factor 8 (MFG-E8) could attenuate renal fibrosis by inhibiting the RhoA/ROCK pathway. METHODS: We investigated whether BMSC-EVs have anti-fibrotic effects in a rat model of renal fibrosis, in which rats were subjected to unilateral ureteral obstruction (UUO), as well as in cultured HK2 cells. Extracellular vesicles from BMSCs were collected and co-cultured with HK2 cells during transforming growth factor-ß1 (TGF-ß1) treatment. HK2 cells co-cultured with TGF-ß1 were also treated with the ROCK inhibitor, Y-27632. RESULTS: Compared with the Sham group, UUO rats displayed fibrotic abnormalities, accompanied by an increased expression of α-smooth muscle actin and Fibronectin and reduced expression of E-cadherin. These molecular and pathological changes suggested increased inflammation in damaged kidneys. Oxidative stress, as evidenced by an increased level of MDA and decreased levels of SOD1 and Catalase, was also observed in UUO kidneys. Additionally, activation of cleaved caspase-3 and PARP1 and increased apoptosis in the proximal tubules confirmed tubular cell apoptosis in the UUO group. All of these phenotypes exhibited by UUO rats were suppressed by treatment with BMSC-EVs. However, the protective effect of BMSC-EVs was completely abolished by the inhibition of MFG-E8. Consistent with the in vivo results, treatment with BMSC-EVs reduced inflammation, oxidative stress, apoptosis, and fibrosis in HK-2 cells stimulated with TGF-ß1 in vitro. Interestingly, treatment with Y-27632 protected HK-2 cells against inflammation and fibrosis, although oxidative stress and apoptosis were unchanged. CONCLUSIONS: Our results show that BMSC-EVs containing MFG-E8 attenuate renal fibrosis in a rat model of renal fibrosis, partly through RhoA/ROCK pathway inhibition.

MFG-E8 regulates inflammation and apoptosis in tendon healing, and promotes tendon repair: A histological and biochemical evaluation.

Several studies have identified potential roles for MFG-E8 in promoting tissue repair. However, the effects of MFG-E8 on tendon repair have not yet been investigated. Therefore, we explored the role of MFG-E8 on tendon repair using a rat model of patellar tendon injury. The patellar tendons of Sprague Dawley rats (n = 24/group) received window defects and, after modeling, three groups were randomly assigned: (a) recombinant MFG-E8 (rMFG-E8) group, implantation with MFG-E8 and fibrin glue (400 ng in 10 µl); (b) fibrin group, implantation with fibrin only; and (c) control group, without any treatment. Histopathology, immunohistochemistry, and gene expression analyses were performed at 2 and 4 weeks after healing. Administration of rMFG-E8 in injury sites significantly improved tendon healing histologically at 4 weeks after injury. In addition, numbers of M1 macrophages and M1-stimulator genes, including IFNG, Il-1B, and Il-6, were reduced in the repair sites at 2 weeks by rMFG-E8 administration. In parallel, rMFG-E8 significantly increased the number of M2 macrophages and expression of anti-inflammatory IL-10 and IL-4 at 2 weeks after injury. Treatment with rMFG-E8 markedly decreased tendon cell apoptosis. Moreover, rMFG-E8 significantly enhanced the expression of genes related to tendon matrix formation at 2 weeks after injury, including Col1a1and tenascin-C. We conclude that MFG-E8 could regulate inflammatory responses and apoptotic cell accumulation in tendon repair, and promote the healing process of injured tendon tissue. Thus, exogenous application of MFG-E8 might have therapeutic potential for repair of tendon injuries.

A nanocomposite consisting of ZnO decorated graphene oxide nanoribbons for resistive sensing of NO2 gas at room temperature.

A composite prepared from zinc oxide and graphene oxide nanoribbons (ZnO/GONR) is demonstrated to enable improved room temperature (RT) detection of nitrogen dioxide (NO2). Low-cost hydrothermal synthesis is used to construct the composite. The properties of the resistive sensor, including the sensitivity, response and recovery times, repeatability and selectivity, were investigated in the NO2 concentration range from 1 to 50 ppm at RT. The sensor, typically operated at a voltage of 5 V, exhibits a low detection limit of 1 ppm, a fast response-recovery time, and excellent repeatability which outperforms that of pure ZnO sensors. The sensing mechanism is explained in terms of a redox reaction between NO2 and oxygen anions on the surface of the ZnO/GONR composite. Graphical abstract Schematic representation of the NO2 sensing mechanisms on the surface of the ZnO/GONR composite and overall improved NO2 gas-sensing performance.

Extracellular vesicles from bone marrow-derived multipotent mesenchymal stromal cells regulate inflammation and enhance tendon healing.

BACKGROUND: Extracellular vesicles from bone marrow-derived multipotent mesenchymal stromal cells (BMSC-EVs) can play important roles in the repair of injured tissues. However, no reports have investigated the role and underlying mechanisms of BMSCs-EVs in the tendon repair process. We hypothesized that BMSC-EVs may play a role in modulating inflammation during tendon healing and improving tendon repair in a rat model of patellar tendon injury. METHODS: First, we created window defects in the patellar tendons of Sprague-Dawley rats. Rats (n = 16) were then randomly assigned to three groups: BMSC-EVs group, Fibrin group, and control group. Rats in the BMSC-EVs group were treated with BMSC-EVs and fibrin glue (25 µg in 10 µL). Rats in the fibrin group were treated with fibrin only, and those in the control group received no treatment. Histopathology, immunohistochemistry, and gene expression analyses were performed at 2 and 4 weeks after surgery. RESULTS: At 4 weeks, tendons treated with BMSC-EVs showed regularly aligned and compact collagen fibers as compared with the disrupted scar-like healing in rats in the fibrin and control groups. The expression of genes related to tendon matrix formation and tenogenic differentiation: collagen (COL)-1a1, scleraxis (SCX), and tenomodulin (TNMD) was significantly higher in the BMSC-EVs group than in the other two groups. With histopathology, we observed significantly higher numbers of CD146+ tendon stem cells and fewer numbers of apoptotic cells and C-C chemokine receptor type 7 (CCR7)-positive proinflammatory macrophages in the BMSC-EVs group. BMSC-EVs treatment also led to an increase in the expression of anti-inflammatory mediators (IL-10 and IL-4) at 2 weeks after surgery. CONCLUSIONS: Overall, our findings show that the local administration of BMSC-EVs promotes tendon healing by suppressing inflammation and apoptotic cell accumulation and increasing the proportion of tendon-resident stem/progenitor cells. These findings provide a basis for the potential clinical use of BMSC-EVs in tendon repair.

Predictive Factors of Contralateral Operation after Initial Pyeloplasty in Children with Antenatally Detected Bilateral Hydronephrosis Due to Ureteropelvic Junction Obstruction.

OBJECTIVES: This study was performed to analyze the predictive factors of a contralateral operation after initial pyeloplasty in patients with antenatally detected bilateral ureteropelvic junction obstruction. METHODS: Patients with prenatally diagnosed bilateral ureteropelvic junction obstruction who underwent initial pyeloplasty (aged <12 months at initial pyeloplasty) were offered to participate in the study. Patients were recruited from January 2012 to December 2015. The anteroposterior renal pelvic diameter, parenchymal thickness, and calyceal dilatation were evaluated. Predictive factors of contralateral pyeloplasty after initial unilateral pyeloplasty were also examined. RESULTS: In total, 82 patients were included in the study (mean age, 2.8 months). Among all patients who underwent initial pyeloplasty, additional contralateral pyeloplasty was required in 11 patients (13.4%). The outcome of contralateral hydronephrosis was assessed as resolution, persistence, or surgery. The median anteroposterior renal pelvic diameter and calyceal dilatation were significantly different among the groups (p < 0.001). Calyceal dilatation of ≥10 mm and a calyceal dilatation/parenchymal thickness ratio of ≥5 strongly suggested the likelihood of a contralateral operation. CONCLUSIONS: In most patients with bilateral ureteropelvic junction obstruction, improvement or resolution of contralateral hydronephrosis following initial unilateral pyeloplasty can be expected. Patients with contralateral calyceal dilatation >10 mm and the calyceal dilatation/parenchymal thickness ratio >5 are at higher risk of surgery.