Targeting STAT3 potentiates CDK4/6 inhibitors therapy in head and neck squamous cell carcinoma.

Anti-CDK4/6 therapy has been employed for the treatment for head and neck squamous cell carcinoma (HNSCC) with CDK4/6 hyperactivation, but the response rate is relatively low. In this study, we first showed that CDK4 and CDK6 was over-expressed and conferred poor prognosis in HNSCC. Moreover, in RB-positive HNSCC, STAT3 signaling was activated induced by CDK4/6 inhibition and STAT3 promotes RB deficiency by upregulation of MYC. Thirdly, the combination of Stattic and CDK4/6 inhibitor results in striking anti-tumor effect in vitro and in Cal27 derived animal models. Additionally, phospho-STAT3 level negatively correlates with RB expression and predicts poor prognosis in patients with HNSCC. Taken together, our findings suggest an unrecognized function of STAT3 confers to CDK4/6 inhibitors resistance and presenting a promising combination strategy for patients with HNSCC.

Are children with IgA nephropathy different from adult patients?

BACKGROUND: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN. METHODS: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN. RESULTS: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m2, p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids. CONCLUSIONS: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children.

Adaptation process of decellularized vascular grafts as hemodialysis access in vivo.

Arteriovenous grafts (AVGs) have emerged as the preferred option for constructing hemodialysis access in numerous patients. Clinical trials have demonstrated that decellularized vascular graft exhibits superior patency and excellent biocompatibility compared to polymer materials; however, it still faces challenges such as intimal hyperplasia and luminal dilation. The absence of suitable animal models hinders our ability to describe and explain the pathological phenomena above and in vivo adaptation process of decellularized vascular graft at the molecular level. In this study, we first collected clinical samples from patients who underwent the construction of dialysis access using allogeneic decellularized vascular graft, and evaluated their histological features and immune cell infiltration status 5 years post-transplantation. Prior to the surgery, we assessed the patency and intimal hyperplasia of the decellularized vascular graft using non-invasive ultrasound. Subsequently, in order to investigate the in vivo adaptation of decellularized vascular grafts in an animal model, we attempted to construct an AVG model using decellularized vascular grafts in a small animal model. We employed a physical-chemical-biological approach to decellularize the rat carotid artery, and histological evaluation demonstrated the successful removal of cellular and antigenic components while preserving extracellular matrix constituents such as elastic fibers and collagen fibers. Based on these results, we designed and constructed the first allogeneic decellularized rat carotid artery AVG model, which exhibited excellent patency and closely resembled clinical characteristics. Using this animal model, we provided a preliminary description of the histological features and partial immune cell infiltration in decellularized vascular grafts at various time points, including Day 7, Day 21, Day 42, and up to one-year post-implantation. These findings establish a foundation for further investigation into the in vivo adaptation process of decellularized vascular grafts in small animal model.

Antitumor Effect of Platinum-Modified STING Agonist MSA-2.

The stimulator of interferon genes (STING)-activated innate immune pathway is strong and durable for tumor immunotherapy. MSA-2 is an available non-nucleotide human STING agonist that promotes the tumor immunotherapy of STING activation. However, strategies for remolding and improving the immunotherapy effects of MSA-2 are of value for clinical applications. Here, we synthesized the platinum salt-modified MSA-2 (MSA-2-Pt) due to platinum salt being a classic chemotherapeutic drug. We found that MSA-2-Pt could achieve double-effect antitumor immunotherapy, including inducing cell death by platinum and activating the STING pathway by MSA-2. In the colon carcinoma MC38 model (sensitive to immune checkpoint immunotherapy tumor) and melanoma B16F10 model (poorly immunogenic and highly aggressive tumor), the MSA-2-Pt had a good antitumor effect, which was a little better than MSA-2 with intratumor injections. The results present a promising strategy for STING activation in tumor immunotherapy and broadening platinum-based drugs.

Peptide-drug conjugates: A new paradigm for targeted cancer therapy.

Peptide-drug conjugates (PDCs) are the new hope for targeted therapy after antibody-drug conjugates (ADCs). Compared with ADCs, the core advantages of PDCs are enhanced tissue penetration, easier chemical synthesis, and lower production costs. Two PDCs have been approved by the US Food and Drug Administration (FDA) for the treatment of cancer. The therapeutic effects of PDCs are remarkable, but PDCs also encounter problems when used as targeted therapeutics, such as poor stability, a short blood circulation time, a long research and development time frame, and a slow clinical development process. Therefore, it is very urgent and important to understand the latest research progress of cancer cells targeting PDC, the solution to its stability problem, the scheme of computer technology to assist its research and development, and the direction of its future development. In this manuscript, based on the structure and function of PDCs, the latest research progress on PDCs from the aspects of cancer cell-targeting peptide (CTP) selection, pharmacokinetic characteristics, stability regulation and so on were systematically reviewed, hoping to highlight the current problems and future development directions of PDCs.

Mapping trends in hemifacial spasm research: bibliometric and visualization-based analyses of the Web of Science Core Collection.

Hemifacial spasm (HFS) is a common cranial nerve disease. In HFS research, we conducted a bibliometric analysis to examine the development and research trends. A retrieval of HFS studies published between 2011 and 2022 was performed from the Web of Science Core Collection in September 2022. Two scientometric tools were used to perform bibliometric and visualization-based analyses: VOSviewer and CiteSpace. Bibliometric analysis of 1461 studies published between 2011 and 2022 was carried out using data from 444 journals, 6021 authors, 1732 institutions, and 76 countries/regions. China, the USA, Japan, and South Korea were four key contributors to this study. Shanghai Jiaotong University was the major institution with the larger number of publications. Li Shiting was the most prolific author. Jannetta PJ was the most co-cited author. World Neurosurgery was the top prolific journal. Journal of Neurosurgery was the top co-cited journal. The top five keywords were hemifacial spasm, microvascular decompression, trigeminal neuralgia, surgery, and neurovascular compression. This study examines the research trends in global scientific research on HFS over the last decade. Researchers interested in learning more about current trends and novel research frontiers in this area can benefit from the study.

Bursicon regulates wing expansion via PKA in the oriental fruit fly, Bactrocera dorsalis.

BACKGROUND: Bursicon is a heterodimeric neuropeptide that is involved in many physiological activities such as cuticle tanning, wing expansion, reproduction and immunity in insects. In this study, the role of bursicon in the wing expansion was investigated in Bactrocera dorsalis, an important invasive insect pest in agriculture. RESULTS: The cDNA sequences and deduced amino acids of bursicon genes (named BdBurs-α and BdBurs-ß) were determined, and two proteins typically contained 11 cysteine residues in conserved positions that were highly conserved in other insect species. The spatiotemporal expressions of bursicon genes showed that higher expression occurred at the pupal, early adult stage and ovaries, and lower expression at the late larval stage and in wing tissue (8-day-old pupae). Dysfunction of bursicon genes by dsRNA microinjection into 5-day-old pupae reduced PKA (a downstream component of the bursicon pathway) activity and resulted in malformed adult wings. PKA inhibitor injection into 5-day-old pupae also resulted in similar phenotypes. Hematoxylin & eosin staining of the adult wing showed that RNAi and PKA inhibitor treatment reduced the thickness of the wing cuticle, which wing cuticle thickness were ≈50% thinner than in the control. Furthermore, the expression of hedgehog (Bdhh) (one of 10 tested genes related to wing development) was significantly upregulated after RNAi and PKA inhibitor application. CONCLUSION: The results indicate that bursicon plays a crucial role in the wing expansion of B. dorsalis, suggesting bursicon genes have potential to be the targets for B. dorsalis control. © 2023 Society of Chemical Industry.

Porous Titanium Scaffolds with Mechanoelectrical Conversion and Photothermal Function: A Win-Win Strategy for Bone Reconstruction of Tumor-Resected Defects.

Bone metastases severely threaten the lives of patients. Although surgical treatment combined with adjuvant chemotherapy significantly improves the survival rate of patients, tumor recurrence, or metastasis after surgical resection and bone defects caused by surgical treatment remain major challenges for clinicians. Given the abovementioned clinical requirements, barium titanate-containing iron-coated porous titanium alloy scaffolds have been proposed to promote bone defect repair and inhibit tumor recurrence. Fortunately, in vitro and in vivo experimental research confirms that barium titanate containing iron-coated porous titanium alloy scaffolds promote osteogenesis and bone reconstruction in defect repair via mechanoelectric conversion and inhibit tumor recurrence via photothermal effects. Furthermore, the underlying and intricate mechanisms of bone defect repair and tumor recurrence prevention of barium titanate-containing iron-coated porous titanium alloy scaffolds are explored. A win-win strategy for mechanoelectrical conversion and photothermal functionalization provides promising insights into bone reconstruction of tumor-resected defects.

Cell-type-specific molecular characterization of cells from circulation and kidney in IgA nephropathy with nephrotic syndrome.

Nephrotic syndrome (NS) is a relatively rare and serious presentation of IgA nephropathy (IgAN) (NS-IgAN). Previous research has suggested that the pathogenesis of NS-IgAN may involve circulating immune imbalance and kidney injury; however, this has yet to be fully elucidated. To investigate the cellular and molecular status of NS-IgAN, we performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) and kidney cells from pediatric patients diagnosed with NS-IgAN by renal biopsy. Consistently, the proportion of intermediate monocytes (IMs) in NS-IgAN patients was higher than in healthy controls. Furthermore, flow cytometry confirmed that IMs were significantly increased in pediatric patients with NS. The characteristic expression of VSIG4 and MHC class II molecules and an increase in oxidative phosphorylation may be important features of IMs in NS-IgAN. Notably, we found that the expression level of CCR2 was significantly increased in the CMs, IMs, and NCMs of patients with NS-IgAN. This may be related to kidney injury. Regulatory T cells (Tregs) are classified into two subsets of cells: Treg1 (CCR7 high, TCF7 high, and HLA-DR low) and Treg2 (CCR7 low, TCF7 low, and HLA-DR high). We found that the levels of Treg2 cells expressed significant levels of CCR4 and GATA3, which may be related to the recovery of kidney injury. The state of NS in patients was closely related to podocyte injury. The expression levels of CCL2, PRSS23, and genes related to epithelial-mesenchymal transition were significantly increased in podocytes from NS-IgAN patients. These represent key features of podocyte injury. Our analysis suggests that PTGDS is significantly downregulated following injury and may represent a new marker for podocytes. In this study, we systematically analyzed molecular events in the circulatory system and kidney tissue of pediatric patients with NS-IgAN, which provides new insights for targeted therapy in the future.

Klotho inhibits renal ox-LDL deposition via IGF-1R/RAC1/OLR1 signaling to ameliorate podocyte injury in diabetic kidney disease.

OBJECTIVE: Diabetic kidney disease (DKD) is characterized by the abnormal deposition of oxidized low-density lipoprotein (ox-LDL), which contributes to podocyte damage. Klotho, an aging suppressor that plays a critical role in protecting podocytes in DKD, is mainly expressed in kidney tubular epithelium and secreted in the blood. However, it has not been established whether Klotho can alleviate podocyte injury by inhibiting renal ox-LDL deposition, and the potential molecular mechanisms require further investigation. METHODS: We conducted a comprehensive analysis of serum and kidney biopsy samples obtained from patients diagnosed with DKD. Additionally, to explore the underlying mechanism of Klotho in the deposition of ox-LDL in the kidneys, we employed a mouse model of DKD with the Klotho genotype induced by streptozotocin (STZ). Furthermore, we conducted meticulous in vitro experiments on podocytes to gain further insights into the specific role of Klotho in the deposition of ox-LDL within the kidney. RESULTS: Our groundbreaking study unveiled the remarkable ability of the soluble form of Klotho to effectively inhibit high glucose-induced ox-LDL deposition in podocytes affected by DKD. Subsequent investigations elucidated that Klotho achieved this inhibition by reducing the expression of the insulin/insulin-like growth factor 1 receptor (IGF-1R), consequently leading to a decrease in the expression of Ras-related C3 botulinum toxin substrate 1 (RAC1) and an enhancement of mitochondrial function. Ultimately, this series of events culminated in a significant reduction in the expression of the oxidized low-density lipoprotein receptor (OLR1), thereby resulting in a notable decrease in renal ox-LDL deposition in DKD. CONCLUSION: Our findings suggested that Klotho had the potential to mitigate podocyte injury and reduced high glucose-induced ox-LDL deposition in glomerulus by modulating the IGF-1R/RAC1/OLR1 signaling. These results provided valuable insights that could inform the development of novel strategies for diagnosing and treating DKD.

Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis: a nationwide retrospective study in China.

BACKGROUND: Pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children. METHODS: Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored. RESULTS: Renal involvement was the most typical manifestation (95.5%), and the crescent was the predominant pathological lesion (84.9%). The estimated glomerular filtration rate (eGFR) was evaluated in 114 patients, of whom 59.6% developed ESRD, and the median time to ESRD was 3.20 months. The eGFR [P = 0.006, odds ratio (OR) = 0.955, 95% confidence interval (CI) = 0.924-0.987] and the percentages of global glomerulosclerosis (pGGS; P = 0.018, OR = 1.060, 95% CI = 1.010-1.112) were independent risk factors for ESRD of renal biopsy. Based on the pGGS and eGFR at renal biopsy, we developed three risk grades of ESRD and one predictive model. The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades (P < 0.001). Compared with serum creatinine at baseline, the predictive model had higher accuracy (0.86 versus 0.58, P < 0.001) and a lower coefficient of variation (0.07 versus 0.92) in external validation. CONCLUSIONS: Renal involvement is the most common manifestation of pediatric AAV in China, of which more than half deteriorates into ESRD. The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children. Supplementary file 2 (MP4 18937 KB).

Designing nanohesives for rapid, universal, and robust hydrogel adhesion.

Nanoparticles-based glues have recently been shown with substantial potential for hydrogel adhesion. Nevertheless, the transformative advance in hydrogel-based application places great challenges on the rapidity, robustness, and universality of achieving hydrogel adhesion, which are rarely accommodated by existing nanoparticles-based glues. Herein, we design a type of nanohesives based on the modulation of hydrogel mechanics and the surface chemical activation of nanoparticles. The nanohesives can form robust hydrogel adhesion in seconds, to the surface of arbitrary engineering solids and biological tissues without any surface pre-treatments. A representative application of hydrogel machine demonstrates the tough and compliant adhesion between dynamic tissues and sensors via nanohesives, guaranteeing accurate and stable blood flow monitoring in vivo. Combined with their biocompatibility and inherent antimicrobial properties, the nanohesives provide a promising strategy in the field of hydrogel based engineering.

Nuclear receptor RXRα binds the precursor of miR-103 to inhibit its maturation.

BACKGROUND: The maturation of microRNAs (miRNAs) successively undergoes Drosha, Dicer, and Argonaute -mediated processing, however, the intricate regulations of the individual miRNA maturation are largely unknown. Retinoid x receptor alpha (RXRα) belongs to nuclear receptors that regulate gene transcription by binding to DNA elements, however, whether RXRα binds to miRNAs to exert physiological functions is not known. RESULTS: In this work, we found that RXRα directly binds to the precursor of miR-103 (pre-miR-103a-2) via its DNA-binding domain with a preferred binding sequence of AGGUCA. The binding of RXRα inhibits the processing of miR-103 maturation from pre-miR-103a-2. Mechanistically, RXRα prevents the nuclear export of pre-miR-103a-2 for further processing by inhibiting the association of exportin-5 with pre-miR-103a-2. Pathophysiologically, the negative effect of RXRα on miR-103 maturation correlates to the positive effects of RXRα on the expression of Dicer, a target of miR-103, and on the inhibition of breast cancer. CONCLUSIONS: Our findings unravel an unexpected role of transcription factor RXRα in specific miRNA maturation at post-transcriptional level through pre-miRNA binding, and present a mechanistic insight regarding RXRα role in breast cancer progression.

Simultaneous quantitation of multiple myeloma related dietary metabolites in serum using HILIC-LC-MS/MS.

Background: Recent studies from targeted and untargeted metabolomics have consistently revealed that diet-related metabolites, including carnitine (C0), several species of acylcarnitines (AcyCNs), amino acids, ceramides, and lysophosphatidylcholines (LPCs) may serve as potential multiple myeloma (MM) biomarkers. However, most of these approaches had some intrinsic limitations, namely low reproducibility and compromising the accuracy of the results. Objective: This study developed and validated a precise, efficient, and reliable liquid chromatography tandem mass spectrometric (LC-MS/MS) method for measuring these 28 metabolic risk factors in human serum. Design: This method employed isopropanol to extract the metabolites from serum, gradient elution on a hydrophilic interaction liquid chromatographic column (HILIC) for chromatographic separation, and multiple reaction monitor (MRM) mode with positive electrospray ionization (ESI) for mass spectrometric detection. Results: The correlation coefficients of linear response for this method were more than 0.9984. Analytical recoveries ranged from 91.3 to 106.3%, averaging 99.5%. The intra-run and total coefficients of variation were 1.1-5.9% and 2.0-9.6%, respectively. We have simultaneously determined the serological levels of C0, several subclasses of AcyCNs, amino acids, ceramides, and LPCs within 15 min for the first time. Conclusion: The established LC-MS/MS method was accurate, sensitive, efficient, and could be valuable in providing insights into the association between diet patterns and MM disease and added value in further clinical research.

Value of the modified semiquantitative classification in predicting outcomes in children with Henoch-Schönlein purpura nephritis.

BACKGROUND: The modified semiquantitative classification (SQC) is a new pathological classification for Henoch-Schönlein purpura nephritis (HSPN), and its prognostic value with regard to the outcomes of HSPN is unclear. METHODS: We performed a retrospective review of 249 patients with biopsy-proven HSPN admitted to the Children's Hospital of Chongqing Medical University. In addition to the International Study of Kidney Disease in Children (ISKDC) classification, renal biopsy specimens were also reevaluated according to the SQC. RESULTS: During the follow-up period of 2.9 (1.0-6.9) years, 14 (5.6%) patients reached the poor outcome at the end of follow-up. The SQC activity and chronicity indexes were positively correlated with the clinical manifestations, conventional pathology grades, and 24-h urinary protein (24hUP). The difference in the areas under the curve between the total biopsy SQC scores and ISKDC classification was 0.12 (p = .001, 95% CI: 0.0485-0.192). In the receiver operating characteristic (ROC) curve analysis of 1-year, 3-year, and 5-year poor outcomes and total biopsy SQC scores, a total biopsy score ≥10 was associated with a higher risk of an adverse outcome. CONCLUSION: Our study suggests that the SQC indexes are clearly correlated with the clinical and pathological findings of HSPN. The SQC is more sensitive than ISKDC classification for the prediction of the long-term outcomes of HSPN in children.

Relevant Risk Factor and Follow-Up of Lung Nodules in Physical Examination with Low-Dose CT Screening.

Background: We aimed to explore the risk factors of lung nodules and lung cancer in physical examination population with low-dose multi-slice spiral CT (LDCT) screening, to provide basis for lung cancer screening and follow-up management after CT examination. Methods: The general data, serum tumor markers and CT images of 2,274 patients underwent LDCT in the Physical Examination Center of the Fourth Hospital of Hebei Medical University, China in 2019 were retrospectively analyzed and followed up for three years. Results: The detection rate of lung nodules was 48.42%. The detection rate of lung nodules was higher in females, those over 70, those with history of smoking, passive smoking, drinking, precious history of lung diseases and family history of malignant tumors, with statistically significant differences (P<0.05). The abnormal rate of serum tumor markers (CA199, CA125 female and CYFRA211) were higher than that in the non-nodule group, with statistically significant differences (P<0.05). Multivariate logistic regression analysis showed that gender, age, history of smoking, passive smoking, family history of malignant tumors and serum tumor markers (CYFRA211 and CA199) were independent risk factors for the occurrence of lung nodules. Conclusion: Gender female, age>35, history of smoking, passive smoking, history of drinking, history of past lung disease, family history of malignant tumors, abnormal CYFRA211 tumor markers were detected and low dose multi-slice spiral CT image showed ground-glass nodules are risk factors for lung nodules and lung cancer, which should be paid close attention to during physical examination and follow-up.

Non-acid reflux and esophageal dysmotility is associated with early esophageal squamous cell carcinoma.

BACKGROUND: Studies have demonstrated that non-acid reflux (NAR) is associated with esophageal squamous cell carcinoma (ESCC). Esophageal dysmotility is associated with NAR but few studies have focused on the esophageal motility of ESCC patients. We explored the relationship between ESCC, NAR and esophageal dysmotility with the aid of multichannel intraluminal impedance and pH (MII-pH) and high-resolution manometry (HRM). METHODS: From Jan 2021 to Oct 2022, 20 patients with superficial ESCC were enrolled as the ESCC group, while 20 age and gender matched individuals without gastroesophageal reflux disease (GERD) symptoms and 20 age and gender matched patients with GERD symptoms were recruited as the control groups. Patients received 24 h MII-pH and HRM procedure before endoscopic submucosal dissection (ESD), and the data were then collected to identify the type of reflux and esophageal dysmotility. RESULTS: Prevalence of esophageal dysmotility was significantly different among the three groups, 75.0% in the ESCC group, 35.0% in the non-GERD group and 70.0% in the GERD group (P = 0.029). NAR episodes at 15 cm above the lower esophageal sphincter (LES) in the ESCC group were significantly higher than that in the non-GERD group (6.5 (3.5-9.3) vs 1.0 (0.8-4.0), P = 0.001) and were similar with that in the GERD group (6.5 (3.5-9.3) vs 5.5 (3.0-10.5), P > 0.05). NAR episodes at 5 cm above LES was significantly higher in the ESCC group than that in the non-GERD group (38.0 (27.0-60.0) vs 18.0 (11.8-25.8), P = 0.001) and was significantly higher than that in the GERD group (38.0 (27.0-60.0) vs 20.0 (9.8-30.5)), P = 0.010). Prevalence of pathologic non-acid reflux was significantly different among the three groups, 30.0% in the ESCC group, 0.0% in the non-GERD group and 10.0% in the GERD group (P < 0.001). CONCLUSION: Our study found NAR and esophageal dysfunction frequently occur in ESCC patients. NAR and esophageal dysmotility may be associated with ESCC. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2200061456.

Chemotherapeutic-caused liver toxicity hinders nanomedicine development.

Few nanomedicines are approved for clinical cancer treatment as only about 0.7% (median) of nanoparticles enter solid tumors. Nanomedicine as the second medication is usually used in cancer treatment after chemotherapy, immunotherapy surgery, or radiotherapy treatment. However, it is currently unpredictable whether the priority treatment enhances or reduces the therapeutic effect of nanomedicine. Here, by considering prior chemotherapy (5-FU or cisplatin treatment), immunotherapy (IL-2, IL-6, or IL-21-treatment), or phosphate-buffered saline (PBS treatment), we compared the biodistribution of AuNPs in the liver, spleen, kidney, and tumor. We found that the accumulation of AuNPs in the liver and spleen increased in cisplatin pretreatment compared to the PBS treatment, while there was no significant effect on the accumulation of AuNPs in the tumor due to cisplatin-induced significant liver damage while other treatments did not change the biodistribution of AuNPs in the liver, spleen, kidney, and tumor. These results indicated that cisplatin pretreatment is not suitable for subsequent nanomedical cancer therapy. Our work opens a new insight to design low-toxicity chemotherapy to be applied before nanomedicine.

[Retracted] MicroRNA­21 promotes migration and invasion of glioma cells via activation of Sox2 and ß­catenin signaling.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that there were several data panels showing the results of Transwell migration and invasion assay experiments in Figs. 1A and 2A that contained overlapping sections of data, such that these data, which were intended to have shown the results from differently performed experiments, appeared to have been derived from a smaller number of original sources. Furthermore, the data panels shown in Fig. 3A for the 'Control/U343' and 'Control/172', and the 'miR­21/ß­catenin' and 'Control/T98', experiments were also found to be unexpectedly similar, given that these were likewise intended to show the results from differently performed experiments. After having conducted an independent investigation in the Editorial Office, the Editor of Molecular Medicine Reports has determined that the above paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [Molecular Medicine Reports 15: 187­193, 2017; DOI: 10.3892/mmr.2016.5971].

A high-impact FN1 variant correlates with fibronectin-mediated glomerulopathy via decreased binding to collagen type IV.

The glomerular basement membrane (GBM) consists of laminins, collagen IV, nidogens, and fibronectin and is essential for filtration barrier integrity in the kidney. Critically, structural and functional abnormalities in the GBM are involved in chronic kidney disease (CKD) occurrence and development. Fibronectin is encoded by FN1 and is essential for podocyte-podocyte and podocyte-matrix interactions. However, disrupted or disordered fibronectin occurs in many kidney diseases. In this study, we identified a novel mutation (c.3415G>A) in FN1 that causes glomerular fibronectin-specific deposition in a gain-of-function manner, that may be associated with thin basement membrane nephropathy (TBMN) and expand the spectrum of phenotypes seen in glomerulopathy with fibronectin deposits (GFND). Our studies confirmed this variant increased fibronectin's ability to bind to integrin, thereby maintaining podocyte adhesion. Also, we hypothesised that TBMN arose as the fibronectin variant exhibited a decreased capacity to bind COL4A3/4. Our study is the first to identify and link this novel pathogenic mutation (c.3415G>A) in FN1 to GFND as well as TBMN, which may broaden the phenotype and mutation spectrums of the FN1 gene. We believe our data will positively impact genetic counselling and prenatal diagnostics for GFND with TBMN and other associated conditions that may be commonly benign conditions in humans, and may not require proteinuria-lowering treatments or renal biopsy.