A positive feedback loop between miR-574-3p and HIF-1α in promoting angiogenesis under hypoxia.

In our previous report, we presented evidence supporting the role of miR-574-3p in downregulating the expression of cullin 2 (CUL2) in gastric cancer (GC) cells. Expanding on those findings, the present study aims to confirm the direct interaction between miR-574-3p and the 3' untranslated region (3'UTR) of CUL2, which leads to the suppression of CUL2 expression and destabilization of the VCBCR complex. Based on these discoveries, we propose a novel pathway involving miR-574-3p, HIF-1α, and VEGF that contributes to angiogenesis. Through a series of meticulous experiments, we successfully validate this hypothesis. Specifically, our observations indicate that overexpression of miR-574-3p in GC cells induces an upregulation of HIF-1α and VEGF, resulting in enhanced proliferation, migration, invasion, and tube formation of HUVEC cells. Furthermore, employing a mouse model, we demonstrate that miR-574-3p facilitates the recruitment of endothelial cells towards matrigel xenografts. Additionally, we note a parallel increase in miR-574-3p and HIF-1α levels across multiple cell lines (including AGS, SGC-7901, Hela, and 293T cells) subjected to hypoxic conditions (2 % O2 or CoCl2 treatment), as well as in the myocardial muscles of sodium nitrite-induced hypoxic mice. Further investigations reveal that HIF-1α upregulates miR-574-3p expression by directly binding to the miR-574 promoter. Collectively, these findings strongly support the existence of a positive feedback loop between miR-574-3p and HIF-1α, which facilitates angiogenesis under hypoxic conditions.

Application of Extracellular Vesicles in Gynecologic Cancer Treatment.

Ovarian, cervical, and endometrial cancer are the three most common gynecological malignancies that seriously threaten women's health. With the development of molecular biology technology, immunotherapy and targeted therapy for gynecologic tumors are being carried out in clinical treatment. Extracellular vesicles are nanosized; they exist in various body fluids and play an essential role in intercellular communication and in the regulation of various biological process. Several studies have shown that extracellular vesicles are important targets in gynecologic cancer treatment as they promote tumor growth, progression, angiogenesis, metastasis, chemoresistance, and immune system escape. This article reviews the progress of research into extracellular vesicles in common gynecologic tumors and discusses the role of extracellular vesicles in gynecologic tumor treatment.

Tumor Microenvironments-Adaptive Apoptotic Effects of Cytidine 5'-monophosphate-Capped Gold Nanoclusters.

In the present work, cytidine 5'-monophosphate capped gold nanoclusters (AuNCs@CMP) are reported as a catalyst for redox reactions, which show both oxidase- and excellent peroxidase-like activity. When employing 3,3',5,5'-tetramethylbenzidine (TMB) as a substrate in the presence of hydrogen peroxide (H2O2), the maximum velocity (Vmax) was 175 × 10-8 M s-1in vitro. Besides, the AuNCs@CMP exhibited high catalytic activity for reactive oxygen species (ROS) generation with H2O2. Particularly, they also displayed excellent catalytic activity for ROS generation in tumor cells, being activated and promoted by the tumor microenvironment (TME). Consequently, the AuNCs@CMP show an excellent antitumor effect on HeLa and SW480 cells as assayed by flow cytometry. The antitumor mechanism of AuNCs@CMP was attributed to the high ROS generation based on the specific environments of the TME. Therefore, the present study provides TME-adaptive AuNCs@CMP with excellent mimetic peroxidase activity, producing significant ROS to kill the tumor cells in TME.

Spinal cord injury target-immunotherapy with TNF-α autoregulated and feedback-controlled human umbilical cord mesenchymal stem cell derived exosomes remodelled by CRISPR/Cas9 plasmid.

Human umbilical cord mesenchymal stem cell (hucMSC) derived exosomes (EXOs) have been investigated as a new treatment for spinal cord injury (SCI) because of their anti-inflammatory, anti-apoptotic, angiogenesis-promoting, and axonal regeneration properties. The CAQK peptide found in the brains of mice and humans after trauma has recently been found to specifically bind to the injured site after SCI. Thus, we developed a nanocarrier system called EXO-C@P based on hucMSC exosomes remodelled by the CRISPR/Cas9 plasmid to control inflammation and modified by the CAQK peptide. EXO-C@P was shown to effectively accumulate at the injury site and saturate the macrophages to significantly reduce the expression of inflammatory cytokines in a mouse model of SCI. Moreover, EXO-C@P treatment improved the performance of mice in behavioural assessments and upregulated soluble tumour necrosis factor receptor-1 (sTNFR1) in serum and at the trauma site after SCI surgery, but lowered the proportion of iNOS+ cells and the concentration of proinflammatory factors. In conclusion, EXO-C@P provides an effective alternative to multiple topical administration and drug delivery approaches for the treatment of SCI. STATEMENT OF SIGNIFICANCE: SCI is a serious disease characterised by a high incidence, high disability rate, and high medical costs, and has become a global medical problem. Several studies have shown that the inflammatory response is the critical inducer of secondary injury after SCI. The inflammatory cytokine TNF-α is considered to be one of the most significant therapeutic targets for autoimmune diseases. Antibodies targeting TNF-α and sTNFR1 are capable of neutralising free TNF-α. In this study, exosomes in the CRISPR/Cas9 system were used to establish stem cells with an autoregulated and feedback-controlled TNF-α response, with these cells secreting sTNFR1, which neutralised TNF-α and antagonised the inflammation stimulated by TNF-α. Moreover, the plasmid was combined with CAQK, which targeted the injury site and promoted the recovery of SCI function.

Exposure to neonicotinoid insecticides and their characteristic metabolites: Association with human liver cancer.

Neonicotinoid insecticides (NEOs) are commonly applied for pest control in China and around the world. Previous studies reported that NEOs are hepatotoxic to mammals. However, limited studies have explored the associations between NEOs exposure and liver disease. In the present study, we detected six parent NEOs (p-NEOs), including acetamiprid, thiacloprid, dinotefuran, clothianidin, imidacloprid, and thiamethoxam, and five characteristic metabolites (m-NEOs), including 5-hydroxy-imidacloprid, olefin-imidacloprid, N-desmethyl-acetamiprid, 1-methyl-3-(tetrahydro-3-furylmethyl) guanidine and 1-methyl-3-(tetrahydro-3-furyl methyl) urea, in blood samples collected from healthy donors (n = 100; females vs. males: 45 vs. 55; age: 22-91 years) and liver cancer patients (n = 274; females vs. males: 118 vs. 156; age: 11-88 years) in one hospital from Guangzhou city, South China. NEOs were frequently detected (61%-94%) in blood samples, with median concentrations ranging from 0.19 ng/mL to 1.28 ng/mL and 0.20 ng/mL to 2.03 ng/mL for healthy and liver cancer populations, respectively. olefin-imidacloprid was the most abundant NEOs in healthy and liver cancer populations, accounting for 23.4% and 20.7%, respectively. Significant positive correlations among most m-NEOs concentrations were found, and associations between m-NEOs and their corresponding p-NEOs were positively correlated. These findings indicated that the sources of m-NEOs were both endogenous and exogeneous. Females had higher median concentrations of NEOs and their metabolites than males. Moreover, the α-fetoprotein values and blood concentrations of target analytes (r = 0.428-0.601, p < 0.05) were positively correlated. Meanwhile, associations between the concentrations of p-NEOs and m-NEOs and liver cancer were found (odds ratio = 2.33-9.02, 95% confidence interval = 0.31-22.7, p < 0.05), indicating that human exposure to NEOs and their metabolites might increase the odds of liver cancer prevalence. Our work provided a new insight into the hepatotoxicity of NEOs and their metabolites, and human health risks of exposure to these pollutants warranted further studies.

MicroRNA-574-5p in gastric cancer cells promotes angiogenesis by targeting protein tyrosine phosphatase non-receptor type 3 (PTPN3).

We elucidate in this study that up-regulation of miR-574-5p in gastric cancer cells under hypoxic conditions contributed to angiogenesis. We found that miR-574-5p and HIF-1α were up-regulated in gastric cancer cells cultured under 2% O2 or in medium containing CoCl2, and in muscle tissues of mice injected with NaNO2, indicating up-regulation of miR-574-5p in vitro or in vivo in response to hypoxic conditions. We hypothesized that up-regulation of miR-574-5p could promote angiogenesis. Transfection of gastric cancer cells with miR-574-5p mimics or inhibitor resulted in increase or decrease in the expression of VEGFA. Viability, migration, invasion and tube formation of HUVECs cultured with conditioned medium from SGC/574 cells transfected with miR-574-5p inhibitor were reduced. Tube formation of HUVECs cultured with conditioned medium from SGC-7901 cells transfected with miR-574-5p mimics was increased. An in vivo study demonstrated that inhibition of miR-574-5p in the tumor xenografts of mice reduced the expression of CD31 one of the endothelial cell markers. We identified PTPN3 a tyrosine phosphatase as a target of miR-574-5p that bound to the 3'UTR of PTPN3 mRNA to inhibit the expression of PTPN3. Furthermore, the data in this study demonstrated that inhibition of PTPN3 in gastric cancer cells enhanced phosphorylation of p44/42 MAPKs and promoted angiogenesis. We conclude that miR-574-5p in gastric cancer cells promoted angiogenesis via enhancing phosphorylation of p44/42 MAPKs by miR-574-5p inhibition of PTPN3 expression.

Histone H2A-peptide-hybrided upconversion mesoporous silica nanoparticles for bortezomib/p53 delivery and apoptosis induction.

The design and development of advanced gene/drug codelivery nanocarrier with good biocompatibility for cancer gene therapy is desirable. Herein, we reported a gene delivery nanoplatform to synergized bortezomib (BTZ) for cancer treatment with histone H2A-hybrided, upconversion luminescence (UCL)-guided mesoporous silica nanoparticles [UCNPs(BTZ)@mSiO2-H2A]. The functionalization of H2A on the surface of UCNPs(BTZ)@mSiO2 nanoparticles realized the improvement of biocompatibility and enhancement of gene encapsulation and transfection efficiency. More importantly, then UCNPs(BTZ)@mSiO2-H2A/p53 induced specific and efficient apoptotic cell death in p53-null cancer cells and restored the functional activity of tumor suppressor p53 by the success of co-delivery of BTZ/p53. Moreover, the transfection with UCNPs(BTZ)@mSiO2-H2A/p53 in p53-deficient non-small cell lung cancer cells changed the status of p53 and substantially enhanced the p53-mediated sensitivity of encapsulated BTZ inside the UCNPs(BTZ)@mSiO2/p53. Meanwhile, core-shell structured mesoporous silica nanoparticles UCNPs@mSiO2 as an UCL agent can detect the real-time interaction of nanoparticles with cells and uptake/penetration processes. The results here suggested that the as-developed UCNPs(BTZ)@mSiO2-H2A/p53 nanoplatform with coordinating biocompatibility, UCL image, and sustained release manner might be desirable gene/drug codelivery nanocarrier for clinical cancer therapy.

Risk factors and etiology of repeat infection in kidney transplant recipients.

Kidney transplantation (KT) is the best therapy available for patients with end-stage renal disease, but postoperative infections are a significant cause of mortality.In this retrospective study the frequency, risk factors, causative pathogens, and clinical manifestations of infection in KT recipients from Beijing Chao-Yang Hospital, Capital Medical University were investigated. Ninety-seven KT recipients who were hospitalized with infection between January 2010 and December 2016 were included. Clinical characteristics, surgery details, laboratory results, and etiology were compared in patients who developed single infection and patients who developed repeated infection (2 or more) after KT.A total of 161 infections were adequately documented in a total of 97 patients, of which 57 patients (58.8%) had 1 infection, 24 (24.7%) had 2, 11 (11.3%) had 3; 3 (3.1%) had 4, and 2 (2.1%) had 5 or more. The most common infection site was the urinary tract (90 infections; 56%), both overall and in the repeated infection group. The most frequently isolated pathogen was Pseudomonas aeruginosa. In the repeated infection patients, in most cases of P. aeruginosa infection (54%) it was cultured from urine. For first infections, a time between KT and infection of ≤ 21 days (area under receiver operating characteristic curve [AUC] 0.636) and a tacrolimus level ≥ 8 ng/mL (AUC 0.663) independently predicted repeat infection. The combination of these two predictive factors yielded an AUC of 0.716, which did not differ statistically significantly from either predictor alone.With regard to first infections after KT, a time between KT and infection of ≤ 21 days, and a tacrolimus level ≥ 8 ng/mL each independently predicted repeated infection in KT recipients.

Provider perspectives on the integration of patient-reported outcomes in an electronic health record.

OBJECTIVE: Integrating patient-reported outcomes (PROs) into electronic health records (EHRs) can improve patient-provider communication and delivery of care. However, new system implementation in health-care institutions is often accompanied by a change in clinical workflow and organizational culture. This study examines how well an EHR-integrated PRO system fits clinical workflows and individual needs of different provider groups within 2 clinics. MATERIALS AND METHODS: Northwestern Medicine developed and implemented an EHR-integrated PRO system within the orthopedics and oncology departments. We conducted interviews with 11 providers who had interacted with the system. Through thematic analysis, we synthesized themes regarding provider perspectives on clinical workflow, individual needs, and system features. RESULTS: Our findings show that EHR-integrated PROs facilitate targeted conversation with patients and automated triage for psychosocial care. However, physicians, psychosocial providers, and medical assistants faced different challenges in their use of the PRO system. Barriers mainly stemmed from a lack of actionable data, workflow disruption, technical issues, and a lack of incentives. DISCUSSION: This study sheds light on the ecosystem around EHR-integrated PRO systems (such as user needs and organizational factors). We present recommendations to address challenges facing PRO implementation, such as optimizing data collection and auto-referral processes, improving data visualizations, designing effective educational materials, and prioritizing the primary user group. CONCLUSION: PRO integration into routine care can be beneficial but also require effective technology design and workflow configuration to reach full potential use. This study provides insights into how patient-generated health data can be better integrated into clinical practice and care delivery processes.

MicroRNA-574-3p regulates epithelial mesenchymal transition and cisplatin resistance via targeting ZEB1 in human gastric carcinoma cells.

MicroRNA-574-3p (miR-574-3p) has different roles in different cancer types. However, the exact regulation mechanism of miR-574-3p in gastric cancer (GC) progression remains unclear. Thus, we aimed to evaluate the role of miR-574-3p in GC metastasis. We investigated the mechanism via which miR-574-3p regulated cancer cell migration and invasion to determine the relationship between epithelial mesenchymal transition (EMT) and drug resistance. Our results indicated that human GC cell line SGC7901 cells were more sensitive to cisplatin (DDP), but SGC7901 cisplatin-resistant cells (SGC7901/DDP) were more resistant to DDP and had mesenchymal characteristics. In addition, miR-574-3p overexpression up-regulated E-cadherin expression, and concomitantly down-regulated the expression of vimentin. We also identified zinc finger E-box binding homeobox transcription factor 1 (ZEB1), a crucial EMT inducer gene, as a new target of miR-574-3p. In fact, miR-574-3p bound the 3' untranslated region (3'-UTR) of ZEB1, regulating expression of this transcription factor at both the mRNA and protein levels. Furthermore, miR-574-3p overexpression reduced the migratory and invasive properties of the SGC7901/DDP cells and inhibited cisplatin (DDP) resistance in vitro and in vivo. In conclusion, the results indicated that miR-574-3p inhibited the EMT and enhanced cisplatin sensitivity in GC cells by suppressing ZEB1. These results provide further evidence for the critical roles of miR-574-3p and ZEB1 in invasion and migration regulation characteristics of GC cells.

Exercise therapy versus surgery for lumbar spinal stenosis: A systematic review and meta-analysis.

OBJECTIVE: To compare the effectiveness of exercise therapy with surgery for lumbar spinal stenosis. METHODS: Five English databases PubMed, the Cochrane Library, Web of science, OVID and PEDro database were searched for randomized controlled trials comparing surgical procedures with exercise therapy for lumbar spinal stenosis. Information on patients, study design, inclusion criteria, intervention and follow-up, outcomes, treatment details and adverse events were extracted. Meta-analysis was performed using Review Manager Version 5.3. RESULTS: Two randomized controlled trials and one mixed design trial with a total of 897 patients were included. The pooled results showed a significant difference between exercise and surgery in Oswestry Disability Index at two years (MD= 3.85, 95%CI: 0.48 to 7.22; P=0.03), but no significant difference at six months (MD= 2.18, 95%CI: -2.80 to 7.17; P=0.39) and one year (MD= 4.26, 95%CI: -1.79 to 10.32; P=0.17). In terms of physical function of 36 Items Short Form Health Survey, there were no significant differences between exercise and surgery at six months (MD= -2.23, 95% CI: -7.46 to 2.99; P=0.40), one year (MD= -2.17, 95% CI: -7.44 to 3.10; P=0.42) and two years (MD= -0.67, 95% CI: -6.16 to 4.82; P=0.81). CONCLUSION: In brief, the current evidence demonstrated a trend that exercise therapy had a similar effect for lumbar spinal stenosis compared with decompressive laminectomies. However, for the small sample size and low methodology quality of the included trials, some rigorously designed and large-scaled RCTs need to be performed to confirm the conclusion.

hucMSC derived exosomes promote functional recovery in spinal cord injury mice via attenuating inflammation.

The exploration of effective spinal cord injury (SCI) healing still remain a great challenge due to the high morbidity, complex pathology and unclear targets. Human umbilical cord mesenchymal stem cells (hucMSC) play an important role in tissue regeneration. However, transplanting stem cells has a potential risk of teratogenicity. Recent studies have suggested that exosomes secreted by stem cells may contribute to tissue injury repair. We hypothesized that the application of hucMSC derived exosomes may be a potential way for SCI treatment. Our studies showed the hucMSC derived exosomes with a mean particle size of 70 nm could effectively trigger the bone marrow derived macrophage (BMDM) polarization from M1 to a M2 phenotype. In vivo studies demonstrated that the hucMSC derived exosomes could improve the functional recovery after SCI through down-regulation of the inflammatory cytokines, such as TNF-α, MIP-1α, IL-6 and IFN-γ. Collectively, our findings indicated that hucMSC derived exosomes could facilitate spinal cord injury healing via attenuating the inflammation of the injury region. Our results provided a new perspective and therapeutic strategy for the use of hucMSC derived exosomes in soft tissue repair.

MicroRNA-27a contributes to the malignant behavior of gastric cancer cells by directly targeting PH domain and leucine-rich repeat protein phosphatase 2.

BACKGROUND: Accumulating evidence indicates that microRNA-27a (miR-27a) is involved in carcinogenesis and tumor progression. However, the exact function and molecular mechanism of miR-27a in gastric cancer remain unclear. METHODS: Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of miR-27a and its target gene. The function of miR-27a in gastric cancer was investigated through in vitro and in vivo assays (MTT assay, colony formation assay, flow cytometry assay, wound healing assay, migration and invasion assay, immunohistochemistry (IHC), immunofluorescence (IF) and Western blot). A luciferase reporter assay was conducted to confirm the target gene of miR-27a. RESULTS: We found that miR-27a was commonly overexpressed in gastric cancer and high expression of miR-27a was associated with distant metastasis, lymph node metastasis, advanced T stage and advanced clinical stage. Functional assays demonstrated that overexpression of miR-27a in AGS cells accelerated cell proliferation, migration and invasion and suppressed apoptosis. Meanwhile, opposite results were observed in SGC-7901 cells when miR-27a was suppressed. Consistently, down-regulation of miR-27a inhibited the growth and metastasis of engrafted tumors in vivo. Furthermore, we found PH domain and leucine-rich repeat protein phosphatase 2 (PHLPP2) to be a new target of miR-27a, and downregulation of PHLPP2 could rescue the effect of anti-miR-27a in gastric cancer cells. In addition, miR-27a-mediated suppression of PHLPP2 led to stimulation of the AKT/GSK3ß pathway. CONCLUSIONS: Our data suggest that miR-27a functions as a crucial oncogenic miRNA in gastric cancer. It can promote proliferation and metastasis of tumor cells by suppressing PHLPP2 and activating the AKT/GSK3ß pathway. Therefore, miR-27a is a potential novel therapeutic target in gastric cancer treatment.

Upregulation of microRNA-574-3p in a human gastric cancer cell line AGS by TGF-ß1.

The mechanisms that regulate miR-574-3p expression in cells remain elusive. In the present study, we used real-time PCR assay to demonstrate TGF-ß1-induced miR-574-3p upregulation in AGS cells, which was inhibited by TGF-ß receptor I inhibitor SB431542. We used a computer search to identify Smad binding sites upstream of the miR-574-3p precursor sequence. We demonstrated that silencing Smad4, but not Smad2 or Smad3, significantly inhibited the TGF-ß1-induced miR-574-3p upregulation in AGS cells. Furthermore, TGF-ß1 significantly increased the activity of a dual-luciferase reporter that contains the Smad binding sites upstream of the miR-574 precursor sequence. Silencing Smad4 significantly inhibited the TGF-ß1-induced increase in the activity of the reporter in AGS cells. ChIP assay showed that Smad4 directly bound to the promoter of miR-574-3p. MiR-574-3p inhibition was effective in eliminating the inhibition of AGS cell proliferation induced by TGF-ß1, suggesting that TGF-ß1 inducing upregulation of miR-574-3p is functionally significant.

Streptomyces luozhongensis sp. nov., a novel actinomycete with antifungal activity and antibacterial activity.

A novel actinomycete strain, designated TRM 49605T, was isolated from a desert soil sample from Lop Nur, Xinjiang, north-west China, and characterised using a polyphasic taxonomic approach. The strain exhibited antifungal activity against the following strains: Saccharomyces cerevisiae, Curvularia lunata, Aspergillus flavus, Aspergillus niger, Fusarium oxysporum, Penicillium citrinum, Candida albicans and Candida tropicalis; Antibacterial activity against Bacillus subtilis, Staphylococcus epidermidis and Micrococcus luteus; and no antibacterial activity against Escherichia coli. Phylogenetic analysis based on 16S rRNA gene sequences affiliated strain TRM 49605T to the genus Streptomyces. Strain TRM 49605T shows high sequence similarities to Streptomyces roseolilacinus NBRC 12815T (98.62 %), Streptomyces flavovariabilis NRRL B-16367T (98.45 %) and Streptomyces variegatus NRRL B-16380T (98.45 %). Whole cell hydrolysates of strain TRM 49605T were found to contain LL-diaminopimelic acid as the diagnostic diamino acid and galactose, glucose, xylose and mannose as the major whole cell sugars. The major fatty acids in strain TRM 49605T were identified as iso C16:0, anteiso C15:0, C16:0 and Summed Feature 5 as defined by MIDI. The main menaquinones were identified as MK-9(H4), MK-9(H6), MK-9(H8) and MK-10(H6). The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol and phosphatidylinositol mannoside. The G+C content of the genomic DNA was determined to be 71.2 %. The DNA-DNA relatedness between strain TRM 49605T and the phylogenetically related strain S. roseolilacinus NBRC 12815T was 60.12 ± 0.06 %, which is lower than the 70 % threshold value for delineation of genomic prokaryotic species. Based on the phenotypic, chemotaxonomic and phylogenetic data, strain TRM 49605T (=CCTCC AA2015026T = KCTC 39666T) should be designated as the type strain of a novel species of the genus Streptomyces, for which the name Streptomyces luozhongensis sp. nov. is proposed.

Dysregulation of non-coding RNAs in gastric cancer.

Gastric cancer (GC) is one of the most common cancers in the world and a significant threat to the health of patients, especially those from China and Japan. The prognosis for patients with late stage GC receiving the standard of care treatment, including surgery, chemotherapy and radiotherapy, remains poor. Developing novel treatment strategies, identifying new molecules for targeted therapy, and devising screening techniques to detect this cancer in its early stages are needed for GC patients. The discovery of non-coding RNAs (ncRNAs), primarily microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), helped to elucidate the mechanisms of tumorigenesis, diagnosis and treatment of GC. Recently, significant research has been conducted on non-coding RNAs and how the regulatory dysfunction of these RNAs impacts the tumorigenesis of GC. In this study, we review papers published in the last five years concerning the dysregulation of non-coding RNAs, especially miRNAs and lncRNAs, in GC. We summarize instances of aberrant expression of the ncRNAs in GC and their effect on survival-related events, including cell cycle regulation, AKT signaling, apoptosis and drug resistance. Additionally, we evaluate how ncRNA dysregulation affects the metastatic process, including the epithelial-mesenchymal transition, stem cells, transcription factor activity, and oncogene and tumor suppressor expression. Lastly, we determine how ncRNAs affect angiogenesis in the microenvironment of GC. We further discuss the use of ncRNAs as potential biomarkers for use in clinical screening, early diagnosis and prognosis of GC. At present, no ideal ncRNAs have been identified as targets for the treatment of GC.

Serum gp73 is also a biomarker for diagnosing cirrhosis in population with chronic HBV infection.

OBJECTIVES: To clarify the role of Golgi membrane glycoprotein 73 (gp73) in evaluating the progression of chronic hepatitis B virus (HBV) infection. DESIGN AND METHODS: Participants included 958 controls, 421 chronic hepatitis B, 944 hepatic cirrhosis, and 127 hepatocellular carcinoma (HCC) patients. All the patients, with the exception of the controls, were diagnosed HBsAg positive. Serum biomarkers, including gp73, alpha-fetoprotein (AFP), alpha-l-fucosidase, and Lens culinaris agglutinin-reactive fraction of AFP, were determined. RESULTS: The patients with Hepatic cirrhosis gp73 levels over 150 ng/mL had an odds ratio of 3.21 (95% CI: 2.07-5.00). In hepatic cirrhosis patients, serum gp73 correlated with the Child-Pugh score. gp73 is a marker for diagnosing cirrhosis in the hepatitis populations. When the cut-off was set at 75.5 ng/mL, the sensitivity, specificity, and AUC were 75.6% (95% CI: 71.30%-79.62%), 60.3% (95% CI: 56.95%-63.63%) and 0.72 (95% CI: 0.69-0.75), respectively. CONCLUSION: The variation trend of gp73 in chronic liver disease may indicate that monitoring of serum gp73 is helpful to diagnose cirrhosis in population with chronic HBV infection.

GP73 is a potential marker for evaluating AIDS progression and antiretroviral therapy efficacy.

Golgi protein-73 (GP73) is upregulated in cancers and viral infections; however, its role in human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) remains undetermined. GP73 was evaluated as a biomarker of HIV progression and AIDS treatment efficacy. Forty-eight HIV patients (≤ 350 CD4 + T cells/µL) undergoing highly active antiretroviral therapy (HAART group) and 18 HIV patients expected to undergo HAART within 9 months (>350 CD4 + T cells/µL) (control group) were enrolled in a prospective, single center, cohort study from May 2009 to Jun 2012. Blood aspartate aminotransferase, alanine aminotransferase (ALT), cholesterol, triglycerides, and total bilirubin were assessed at baseline, 2 weeks, and 1, 3, 6, 9, and 12 months (HAART group) or 3 month intervals (control group). Serum HIV RNA level (viral load) was determined by reverse-transcriptase polymerase chain reaction (RT-PCR), and serum and peripheral blood mononuclear cell (PBMC) GP73 concentration were determined by chemiluminescent immunoassay kit and western blot, respectively. Significant positive and negative correlations in baseline serum GP73 concentration and HIV viral load (r = 0.39, P < 0.001) and CD4 + T cell count (r = -0.501, P < 0.001) were observed, respectively. In receiver operator characteristic (ROC) analysis, area under the curve (AUC) was 0.79 (95 % CI 0.66-0.92). The sensitivity and specificity of GP73 for correct identification of patients with ≤350 CD4 + T cells/µL were 76.09 and 75.0 %, respectively, with an ROC-derived cut-off of 100.6 ng/mL. For HIV patients undergoing antiretroviral therapy, GP73 may be a potential biomarker treatment efficacy useful in AIDS management.

Rotator cuff repair augmentation with local autogenous bone marrow via humeral cannulation in a rat model.

BACKGROUND: Growth factors have been shown to improve healing after rotator cuff repair. Bone marrow is a potential vehicle for growth factor augmentation, yet methods of delivering marrow to cuff repair sites are still under-researched. We hypothesized that a cannulated humeral implant would deliver local bone marrow and thereby improve healing in a rat model. METHODS: Twenty-eight rats underwent bilateral rotator cuff injury and repair. Each rat acted as its own control, randomized to a cannulated humeral implant in one shoulder and a solid implant in the other. Rats were euthanized at 4 and 8 weeks to create 4 time-treatment cohorts. Tendon healing was evaluated by dimensional measurements, biomechanical testing, and histology. RESULTS: Tendon thickness, all biomechanical measures, and semi-quantitative histologic scores improved over time (P < .05) but not with treatment. The most common site of biomechanical tendon failure was midsubstance in the 8-week cannulated cohort and at the tendon footprint in the other 3 cohorts. Intraluminal bone growth was evident in all cannulated implants. CONCLUSIONS: Humeral cannulation did not quantifiably improve tendon-to-bone healing in a rat model. The diminutive size of implants in rats, however, may have prevented sufficient delivery of local autogenous bone marrow; hence, further study in a larger animal is recommended.

Serum GP73, a marker for evaluating progression in patients with chronic HBV infections.

This study was designed to investigate the role of serum GP73 for diagnosing significant fibrosis in patients with chronic hepatitis B virus (HBV) infections. Two populations were enrollment. All subjects were patients with chronic HBV infections. First population included 761 patients, who received liver stiffness measurement; the second population included 633 patients, who undertaken liver biopsy, in which 472 patients with nearly normal ALT. All patients received serum GP73 test. The effect of GP73 recombinant protein to HepG2 cells and LX2 cells were observed in vitro. Results showed that serum GP73 concentration is correlated with liver stiffness (r = 0.601). The area under ROC curve is 0.76. The sensitivity and specificity of GP73 for significant fibrosis (≥F2) diagnosis were 62.81%, 80.05% respectively (cut off: 76.6 ng/ml). Serum GP73 concentration was significantly correlated with the grading of fibrosis (r = 0.32, and 0.35, in 633 and 472 patients, respectively.) GP73 had a striking performance for diagnosing S2 in patients with chronic HBV infections. In 472 patients with nearly normal ALT, the sensitivity and specificity of GP73 for S2 diagnosis were 62.5% and 80.0% respectively, where the cut-off was set at 82 ng/ml. GP73 recombinant protein may prompt LX2 cells proliferation at the concentration 10-100 ng/ml. The present results indicated that GP73 may be a marker for diagnosing significant fibrosis in patients with chronic HBV infections, and may be a new contributor to fibrogensis.